# Presentation: 168588

## Data Collection of Primary Central Nervous System (CNS) Tumors

**DEPARTMENT OF HEALTH AND HUMAN SERVICES**
**CENTERS FOR DISEASE CONTROL AND PREVENTION**
**Atlanta, Georgia, USA**

## 	Portions of this presentation are based on non-malignant CNS tumor data collection rules adopted by the North American Association of Central Cancer Registries (NAACCR) Uniform Data  Standards Committee - June 2003.

**Notes:**
This presentation reflects decisions and materials concerning data collection for non-malignant CNS tumors approved by NAACCR’s Uniform Data Standards Committee on June 23, 2003.

## Part I

- Rationale
- History
- Definition of Reportable Cases
- Casefinding
- Anticipated Impact on Registries

**Notes:**
Part I will cover 
Rationale 
History
Definition of Reportable Cases
Casefinding
Anticipated Impact on Registries

## Rationale for Non-malignant CNS Tumor Surveillance and Registration

- Non-malignant CNS tumors cause disruption in normal function similar to that caused by malignant CNS tumors.
- Location of a CNS tumor is as important as tumor behavior (benign  or malignant) to morbidity and mortality.

**Notes:**
What is the rationale for collecting benign and borderline (hereafter referred to as non-malignant)  intracranial and CNS tumors (hereafter referred to as CNS tumors) for surveillance and registration? 

In the early 1900s, the neurosurgeon Harvey Cushing observed  that some brain tumors are malignant because of their histology, and some are malignant because of their location.  By this he meant that in the early 1900’s some tumors were not resectable due to their location and would result in the death of the patient because of mass effects on vital areas of the brain. 

In the past 100 years, with advances in microsurgery, radiation therapy, and earlier diagnosis, the maxim of Dr. Cushing still stands, although to a greatly diminished extent.  Brain tumors, whether benign or malignant, produce clinical effects by similar mechanisms of mass effect, hemorrhage, seizure activity, and edema. Although these tumors are individually rare, patients with benign brain tumors experience an under-appreciated financial and health burden in the United States.  These cases include those tumors arising in families with an inherited tendency to develop benign and malignant brain tumors, tumors arising from developmental abnormalities, morbidity from ruptured benign brain tumors, and eventual malignant transformation in a subgroup of patients with optic nerve gliomas. 

More than 28,000 new cases of primary malignant and benign brain tumors were diagnosed nationwide in 1995. Approximately 12,000 people died of invasive brain tumors and 947 died of benign brain tumors during that year.  Another 131 deaths were due to tumors of uncertain behavior and 2,788 deaths were due to tumors of unspecified behavior reported for those sites. (from Brain Tumor Working Group report)

## History 1992 -1996

- 1992 Central Brain Tumor Registry of the United States (CBTRUS) formed to report population-based data on primary benign, borderline, and malignant CNS tumors.
- 1996  National Coordinating Council on Cancer Surveillance (NCCCS) formed Brain Tumor Working Group (BTWG) to explore the feasibility of registering non-malignant** **CNS tumors

**Notes:**
Prior to January 1, 2004, the cancer registry data collection standard setters, including the National Program of Cancer Registries (NPCR), National Cancer Institute’s (NCI) the Surveillance, Epidemiology, and End Results (SEER) Program, and the Commission on Cancer (COC) of the American College of Surgeons required central cancer registries and COC-approved hospital cancer programs to collect data on malignant CNS tumors, but not on non-malignant CNS tumors.  The incidence of malignant, benign, and borderline CNS tumors is not great, but the clinicians treating the patients and researchers studying the diseases felt that it was as important to study the non-malignant CNS tumors as the malignant tumors.  Clinicians and researchers urged the cancer surveillance community to include non-malignant CNS tumors in cancer registries so that the data were available for research.  

In July 1992, the Central Brain Tumor Registry of the United States (CBTRUS) was established.  Its mission was to report population-based incidence data on all primary CNS tumors, regardless of tumor behavior.  At that time 15 state cancer registries collected benign, borderline, and malignant primary CNS tumors, and many shared aggregate data with CBTRUS. The need for national population-based incidence data on all CNS tumors was presented to National Coordinating Council on Cancer Surveillance (NCCCS) which is composed of stakeholders in the cancer surveillance community and provides an arena for identification of issues involved with cancer data collection and data use. 

In 1996, NCCCS formed a Brain Tumor Working Group (BTWG) to examine all issues involved in collecting data on of non-malignant CNS tumors in cancer registries.

## History 1998

- BTWG forwarded four recommendations to  the NCCCS
- NCCCS
- Accepted recommendations 1 and 2
- Deferred recommendations 3 and 4

**Notes:**
In September 1998,  BTWG forwarded a report with four recommendations to NCCCS.  The recommendations in their entirety are found in the BTWG report to the NCCS, Appendix E in the handouts. 

The Council accepted recommendations 1 and 2 and deferred recommendations 3 and 4.

## BTWG Recommendations (1)

- The following standard definition is to be used for collecting precise data for all primary intracranial and CNS tumors:
- 	Primary intracranial and CNS tumors are all primary tumors occurring in the following sites, irrespective of histologic type or behavior:

- Brain
- Spinal cord
- Pituitary gland
- Craniopharyngeal duct

- Meninges
- Cauda equina
- Pineal gland

- Cranial nerves and other parts of the CNS.

**Notes:**
The recommendations from the NCCCS Report were: 
Recommendation Number 1: We recommend that the following standard definition be used for collecting precise data for all primary intracranial and CNS tumors: 

Primary intracranial and CNS tumors are all primary tumors occurring in the following sites, irrespective of histologic type or behavior: brain, meninges, spinal cord, cauda equina, cranial nerves and other parts of the CNS, pituitary gland, pineal gland, and craniopharyngeal duct. 

## BTWG Recommendations (2)

- Develop a standard site and histology definition for tabulating estimates of CNS tumors to allow comparability of information across registries.
- All registries, both hospital- and population-based, should collect data on primary CNS tumors.

**Notes:**
Recommendation 2: Develop a standard site and histology definition for tabulating estimates of CNS tumors to allow comparability of information across registries.  Pathologists, the North American Association of Central Cancer Registries (NAACCR), the Commission on Cancer (COC), the Surveillance, Epidemiology, and End Results (SEER) Program, the National Program of Cancer Registries (NPCR), and the International Agency for Research on Cancer (IARC) need to be involved in developing this standard. 

Recommendation 3: All registries, hospital- and population-based, collect data for CNS tumors.  This effort will necessitate a change in the COC requirements and will increase costs to the hospital-based programs.  Federal funding should be allocated to supplement the additional transition and ongoing data collection costs that will be incurred by central registries.  Before additional data collection is implemented, a pilot study should be conducted in multiple states to assess the procedures and quality control functions needed, as well as the costs of collecting data on these tumors.

## BTWG Recommendations (3)

- Develop training for reporting and     tabulating primary intracranial and CNS tumors, and develop computerized edit- checking procedures.

**Notes:**
Recommendation 4: The appropriate government and professional organizations develop and implement special training programs and curricula for central registry, hospital registry, and laboratory personnel, and develop computerized edit-checking procedures.  Training for reporting and tabulating primary intracranial and CNS tumors should be offered on a regular basis.

## History 2000

- International Classification of Diseases for Oncology 3rd Edition (ICD-O-3) and World Health Organization (WHO) 2000 Brain Tumor Classification are compatible.
- November
- Consensus conference on brain tumor 	definition convened. Group agrees to:
- Site definition as in Recommendation 1.
- Need to develop a standard site and histology definition based on the SEER site and histology validation list.

**Notes:**
In November 2000 at the annual meeting of the Society for Neuro-Oncology, a consensus conference was convened.  The group agreed with the site definition in Recommendation 1 of the BTWG Report.  They also agreed to the development of a standard site and histology definition based on the SEER site and histology validation list.  They discussed differences in definition of CNS tumors between the surveillance community and the neuropathology clinical community.  For example, the clinicians wanted lymphomas of the brain included with brain tumors.  Brain lymphomas have always been collected by registries, but the incidence is tabulated with lymphoma, not brain.  All involved recognized the importance of continuing the dialogue between the clinical community and the surveillance community.

## History 2001-2002

- 2001  NCCCS
- Accepted Recommendations 1 and 2 as completed.
- Reconvened the BTWG to work on Recommendations 3 and 4.
- 2002  NAACCR established subcommittee of  Registry Operations Committee to:
- Identify changes needed in registry operations for inclusion of non-malignant CNS tumors.
- October: Benign Brain Tumor Cancer Registries Amendment Act (Public Law 107-260) signed by President Bush.

**Notes:**
In 2001 the Coordinating Council met and accepted Recommendations 1 and 2 as being completed.  They reconvened the BTWG and asked them to work on Recommendations 3 and 4. 

At the request of the BTWG in January 2003, NAACCR established a Benign Brain Tumor subcommittee of its Registry Operations Committee to develop procedure guidelines for registry operations when including data on non-malignant CNS tumors in data collection efforts.

Concurrently, the North American Brain Tumor Coalition and brain tumor activists brought the issue of collection benign brain tumors to Congress.  Representative Barbara Lee (D-CA)  introduced HR 239, the Benign Brain Tumor Bill, “to amend the Public Health Service Act to provide for the collection of data on benign brain-related tumors through the National Program of Cancer Registries”.  The Centers for Disease Control and Prevention’s (CDC) legislative staff  worked with Representative Lee and the brain tumor community to ensure that the BTWG definition in Recommendation 1 was included in the legislative language of the bill.  A senate bill was drafted by Senator Jack Reed (D-RI).  In October 2002, President Bush signed Public Law 107-260, the Benign Brain Tumor Cancer Registries Amendment Act. 

## Reportable Brain-Related Tumors (1)

- Public Law 107-260 requires reporting of brain-related tumors.
- The term “brain-related tumor” means a listed primary tumor (whether malignant or benign) occurring in any of the following sites:
- 	(I) The brain, meninges, spinal cord, cauda equina, a cranial nerve or nerves, or any other part of the CNS.
- 	(II) The pituitary gland, pineal gland, or craniopharyngeal duct.

**Notes:**
The Benign Brain Tumors Cancer Registries Amendment Act, Public Law 107-260, refers to CNS tumors as “brain-related tumors”.  Brain-related tumors are defined by Public Law 107-260 as follows

“The term ‘brain-related tumor’ means a listed primary tumor (whether malignant or benign) occurring in any of the following sites: (I) the brain, meninges, spinal cord, cauda equina, a cranial nerve or nerves, or any other part of the central nervous system,  (II) the pituitary gland, pineal gland, or craniopharyngeal duct.

Listed means listed in the ICD-O.

All cancer registry standard setters have adopted this definition for reportability of brain tumors.

The COC requires that clinically and pathologically diagnosed analytic (Class of Case 0-2) non-malignant primary intracranial and CNS tumors diagnosed on or after January 1, 2004, with an ICD-O-3 behavior code of 0 or 1 be accessioned, abstracted,  and followed for the following primary sites: meninges (C70._), brain (C71._). spinal cord, cranial nerves, and other parts of the CNS (C72._), pituitary gland (C75.1), craniopharyngeal duct (C75.2),  and pineal gland (C75.3). 

## Reportable Brain-Related Tumors (2)

- Brain
- Cerebrum (C71.0)
- Frontal lobe (C71.1)
- Temporal lobe (C71.2)
- Parietal lobe (C71.3)
- Occipital lobe (C71.4).

**Notes:**
The ICD-O-3 codes for brain are C71.0 through C71.9.  Parts of the brain are the cerebrum, frontal lobe, temporal lobe, parietal lobe, occipital lobe, 

(Continued on next slide)

## Reportable Brain-Related Tumors (3)

- Brain (continued)
- Ventricle (C71.5)
- Cerebellum (C71.6)
- Brain stem (C71.7)
- Overlapping lesion of the brain (C71.8)
- Brain NOS (C71.9)

**Notes:**

(Continued from previous slide)

and the ventricle, cerebellum,  brain stem, overlapping lesions of the brain, and Brain, NOS

## Reportable Brain-Related Tumors (4)

- Meninges
- Cerebral meninges (C70.0)
- Spinal meninges (C70.1)
- Meninges NOS (C70.9)
- Spinal cord (C72.0)
- Cauda equina (C72.1)

**Notes:**
These sites are included in the definition of CNS tumors. The ICD-O-3 codes for meninges are C70.0 through C70.9.  The ICD-O-3 code for spinal cord is C72.0, and for cauda equina is C72.1. 

## Reportable Brain-Related Tumors (5)

- Cranial nerves
- Olfactory nerve (C72.2)
- Optic nerve (C72.3)
- Acoustic nerve (C72.4)
- Cranial nerve NOS (C72.5)

**Notes:**
Tumors of cranial nerves are also included in the definition of CNS tumors.  The codes for cranial nerves are C72.2 through C72.5.

## Reportable Brain-Related Tumors (6)

- Other CNS (C72.8, C72.9)
- Pituitary gland (C75.1)
- Craniopharyngeal duct (C75.2)
- Pineal gland (C75.3)
- For the sites described, benign, borderline, and malignant tumors are reportable for cases diagnosed on or after January 1, 2004.

**Notes:**
These other sites are also included in the definition of CNS tumors. The ICD-O-3 codes for these other parts of the CNS are C72.8 and C72.9.  The ICD-O-3 code for pituitary gland is C75.1, for craniopharyngeal duct is C75.2, and for pineal gland is C75.3. 

Again, for the sites described tumors with non-malignant and malignant behavior are reportable for cases diagnosed on or after January 1, 2004.

## History 2003

- 2003  SEER-supported registries and COC-approved hospital cancer registries will also report non-malignant CNS tumors diagnosed on or after January 1, 2004.

**Notes:**
Both SEER and COC agreed to require reporting of non-malignant brain tumors beginning with cases cases diagnosed January 1, 2004 and later.

## Impact of Collecting Data on Non-malignant CNS Tumors (1)

- Annual increase in number of cases estimated by doubling the number of malignant CNS cases diagnosed in the same year
- Increase in hospital registry case load will depend on the type of hospital:
- Community hospitals with small or no neurology service will likely experience a small increase in case load.
- Hospitals with a large neurology service will likely experience a larger increase.

**Notes:**
What will the impact be of collecting non-malignant CNS tumors on registry operations?  

The BTWG report estimated that the annual increase in the number of cases expected from adding non-malignant CNS tumors can be calculated by doubling the number of cases of malignant  CNS tumors diagnosed in the same year.  So, if a registry has an average of 50 malignant CNS tumors annually, the estimated increase in case load from the addition of non-malignant CNS tumors is 50 cases annually, for a total of 100 CNS cases.  This usually equates to a one percent total increased case load for cancer registries.  For hospital programs with few malignant CNS cases, the estimated case load increase will be minimal.  For hospital programs with a large neurology service, the case load increase may be greater.  

The clinicians interested in using information on benign and malignant CNS tumors may be helpful in acquiring additional financial support for the registry. 

For CBTRUS, from 1990 to 1993,  approximately 46 percent of the tumors reported for these sites were non-malignant. Fifty-one percent of the primary CNS tumors reported by Minnesota Cancer Surveillance System (MCSS) from 1989 to 1994 were non-malignant, and National Cancer Data Bases (NCDB) reported that more than 33 percent of primary CNS tumors were non-malignant during that period.

For registries that consider making non-malignant CNS tumors reportable,
a doubling in the overall number of CNS cases could be expected. 

## Impact of Collecting Data on Non-malignant CNS Tumors (2)

- Central registry case load is estimated to increase by 1%.
- In 2002, 21 state cancer registries collected data on non-malignant CNS tumors:
- Minimal impact if registry’s definition for brain-related sites does not change.

**Notes:**
In 2002, 21 state central cancer registries collected data on all CNS tumors, regardless of behavior.  In those states, the impact of collecting all CNS primary tumors may be minimal because the cases are already part of the case load.  

The increase in case load for central cancer registries adding non-malignant CNS tumors is the same as for hospitals and is expected to be about 1% of the total annual caseload.

## Impact of Collecting Data on Non-malignant CNS Tumors (3)

- Central registries adding non-malignant CNS tumors to reportable case definition may have to change state reporting law if law does not allow for collection of data on non-malignant cases.

**Notes:**
If the central cancer registry’s definition for CNS sites is not the same as the definition in the public law, the definition must be changed.  The central registries that do not currently collect  data on non-malignant CNS  tumors must make sure that their reporting law allows them to include these cases.  If it does not, the state reporting law  may need to be changed or amended.

All cancer registries must use the same definition for brain-related tumors, implement data edits created for non-malignant CNS tumors, and report rates for these tumors.

## Impact of Collecting Data on Non-malignant CNS Tumors (4)

- All cancer registries must:
- Have the same definition for brain-related tumors.
- Implement data edits created for non-malignant CNS tumors.
- Report rates for these tumors.

**Notes:**
If the central cancer registry’s definition for CNS sites is not the same as the definition in the public law, the definition will have to be changed.  The central registries that do not currently collect  non-malignant CNS  tumors will have to make sure that their reporting law allows them to include these cases.  If it does not, the state reporting law  may have to be changed or amended.

All cancer registries will have to use the same definition for brain-related tumors, implement data edits created for non-malignant CNS tumors, and report rates.

## Case-finding (1)

- Additional or expanded case-finding mechanisms:
- Pathology
- Radiology
- Treatment facilities:
- Radiation oncology centers and departments
- Gamma or cyber knife center.

**Notes:**
Cancer registries should first examine the sources used to identify malignant CNS tumors and expand the procedures to include those needed to identify non-malignant CNS tumors. 

Since surgery is often the treatment of choice  for CNS tumors of all behaviors, pathology reports are an excellent casefinding source.  

Many patients with CNS tumors of all behaviors are treated with adjuvant or primary radiation therapy and a review of radiation oncology appointment logs can identify these cases. of primary CNS tumors.

Gamma or cyber knife is becoming a common treatment for non-malignant CNS tumors.  If the hospital has a gamma or cyber knife center, logs and schedules should be reviewed as part of casefinding.

## Case-finding (2)

- Disease indices
- Surgery logs
- Diagnostic imaging
- Radiation oncology
- Neurology clinics
- Medical oncology
- Autopsy reports.

**Notes:**
Disease indices include diagnosis codes for both inpatients and outpatients.  Cases coded with a diagnosis of non-malignant or malignant neoplasm of a CNS site should be reviewed. 

As mentioned, since surgery is often the treatment of choice  for CNS tumors of all behaviors, inpatient and outpatient surgery logs should also be reviewed.

Diagnostic imaging is often the first source of diagnosis for CNS tumors and a review of imaging reports is recommended; however, because  so many diagnostic imaging procedures are performed, the work involved in reviewing all imaging reports is often not worth the effort for the number of cases identified.  

Logs or schedules from hospital departments or clinics for radiation oncology,  neurology, and medical oncology should be reviewed.  In facilities with large neurology services, many cases may be identified through the neurology clinic schedules.  

Autopsy reports should be reviewed because occasionally a non-malignant intracranial tumor is identified only at autopsy.  

## Case-finding Sources

- Free-standing radiation therapy centers
- Free-standing Magnetic Resonance Imaging (MRI) centers
- Free-standing gamma or cyber knife centers
- Free-standing oncology centers
- Data exchange with other central registries
- Death clearance process

**Notes:**
Central cancer registries have additional casefinding sources including freestanding radiation therapy centers, freestanding MRI centers, free-standing oncology centers, and freestanding gamma or cyber knife centers which are not associated with a hospital.  

Central cancer registries should consult with the licensing board in their state or region or identify other sources to ensure that they have identified of all facilities using nuclear sources for treatment. 

Additional cases of residents diagnosed in other states are identified through case sharing agreements with other central cancer registries.

CNS cases may also be identified through data exchange with other central registries and through the death clearance process.

## ICD-9-CM Codes for Case-finding

**Notes:**
The hospital disease index is one source of casefinding utilized by cancer registrars and central registry staff.  Data are stored in the index by ICD code.  At this time, hospitals in the United States continue to assign ICD-9-CM codes to final diagnoses.  The ICD-9-CM codes shown on the slide should be added to casefinding lists to identify non-malignant CNS tumors through the hospital disease index.  A copy of the list is provided in Appendix B of the materials.

## Unusual and Ambiguous Terminology

- If the final pathologic diagnosis is a CNS “neoplasm” or “mass”, an ICD-O-3 histology code must exist for the case to be reportable.
- Hypodense mass or cystic neoplasm are _not_ reportable, even for CNS sites.
- A benign meningioma with a skull site should be coded to the cerebral meninges (C70.1).

**Notes:**
Unusual and ambiguous terminology used in the diagnosis of CNS tumors makes it difficult to determine if a case is reportable, and if it is reportable, to determine site and histology. 

If the final pathologic diagnosis is a CNS neoplasm or mass, an ICD-O-3 code must be assigned for the mass or neoplasm to be reportable.  If  no ICD-O-3 code is assigned for the mass or neoplasm, the case should not be reported. 

If the only diagnosis is “hypodense mass” or “cystic neoplasm”  this is not reportable even for CNS sites because there are no ICD-O-3 codes for this terminology.  

If the ONLY diagnosis available is CNS “tumor” or “neoplasm”,  this is reportable and is coded  8000/.1

A benign meningioma with the site listed as ”skull” should be coded to the cerebral meninges.  The meninges are between the skull and the intracranial tissues.  A meningioma originates in the meninges and can invade the skull.

## Part II

- CNS Anatomy and Function
- Histologies and Primary Sites
- Grading Systems and Coding Grade

**Notes:**
 Part II covers 
CNS Anatomy and Function
Histologies and Primary Sites
Grading Systems and Coding Grade

## CNS Functional Anatomy

**Source: URL: **_[www.solinas.com/solinas/brain.html](http://www.solinas.com/solinas/brain.html)_**  accessed 7/18/03.**

**Notes:**
Because the brain and CNS control the functions of the human body, CNS tumors are a grave concern.  As shown in this picture, the brain controls thought, feeling, and function, including knowledge and memory, as well as the senses of smell, sight, hearing, and touch.  Any abnormal growth in the CNS can affect a person’s ability to function.

## CNS Anatomy

- C71

- C71.6

- C71.7

- C72.0

- C71.0

- C75.3

- C75.1

- C71.7

**Source: URL: **_[www.universalpeace.ca/principles.htm](http://www.universalpeace.ca/principles.htm)_** accessed 7/18/03.**

**Notes:**
Shown here are the major areas of the CNS sites. The intracranial sites are the brain (C71.0-C71.9), cerebral meninges (C70.1), cranial nerves and other intracranial parts of the CNS (C72.0-C72.9), the craniopharyngeal duct (C75.2), and the pineal (C75.3) and pituitary (C75.1) glands. The brain is the largest intracranial organ. The pituitary and pineal glands and the cranial nerves are found inside of the brain tissue. The brain is attached to the spinal cord. 

The extracranial sites are the spinal cord, cauda equina, and spinal meninges. The spinal cord is part of the CNS even though it is not intracranial. The non-malignant tumors must originate in the brain and spinal cord, not in the skull or vertebrae, which are bone, to be reportable.

## Intracranial Sites

- C71.0

- C71.6

- C41.0

- C71.7

- C72.0

**Source: URL: mscenter.ucsf.edu/faq.htm  accessed 7/18/03.**

- Parietal lobe

- Frontal lobe

**Notes:**
The skull or cranium is bone that covers the brain. Non-malignant tumors of tissues inside of the cranium, in other words, those that are intracranial, are reportable. 

## Cerebrum

- C71.1

- C71.2

- C71.7

- C71.3

- C71.4

- C71.6

- C71.0

**Source: URL: **_[www.sciencebob.com/lab/bodyzone/brainprint.html](http://www.sciencebob.com/lab/bodyzone/brainprint.html)_** Accessed 7/18/03.**

**Notes:**
	The cerebrum is the largest part of the brain and contains two hemispheres.  The right hemisphere controls the left side of the body, and the left hemisphere controls the right side of the body.  Each hemisphere contains four lobes; the frontal lobe, the parietal lobe, the occipital lobe, and the temporal lobe.  

The frontal lobe controls cognitive ability, memory, behavior, and the ability to speak and write.  Symptoms caused by a frontal lobe tumor include seizures, impaired judgment, personality changes, and short-term memory loss.  

The parietal lobe controls sensory discrimination and body orientation.  Spatial disorders, seizures, language disturbances, and the inability to do arithmetic are symptoms of a parietal lobe tumor.  

The occipital lobe controls the understanding of visual images.  Symptoms of a tumor in the occipital lobe include blindness in one direction and seizures.  

The temporal lobe controls hearing and the ability to understand the spoken word, and the most common symptom of a tumor in the temporal lobe is seizure.  

## Cerebellum and Brain Stem

- C71.0

- C71.1

- C71.2

- C71.7

- C71.3

- C71.4

- C71.6

**URL: **_[www.sciencebob.com/lab/bodyzone/brain.html](http://www.sciencebob.com/lab/bodyzone/brain.html)_** 7/18/03**

**Notes:**
The cerebellum is the second largest area of the brain.  It plays a role in muscle coordination, walking, and speech.  Symptoms of a tumor in the cerebellum may include but are not limited to swaying, difficulty with coordination and walking, and difficulty with speech. 

The brain stem is at the bottom of the brain and connects the spinal cord to the cerebrum.  The pons, midbrain, medulla oblongata, and reticular formation are part of the brain stem.  The brain stem controls blood pressure, heart beat, breathing, consciousness, and eating and sleeping patterns.  Brain stem tumor symptoms may include but are not limited to vomiting, one-sided facial muscle weakness, swallowing difficulty, double vision, and headache just after waking. 

## The Ventricular System

**http://www.abta.org/primer2.htm**

**Notes:**
The ventricular system is divided into four cavities called ventricles which are connected by a series of holes (called foramen) and tubes called aqueducts or canals). The ventricles contain cerebrospinal fluid that is produced by the choroid plexus, and flows through the ventricles and the subarachnoid space of the meninges.

Two ventricles enclosed in the cerebral hemispheres are called the lateral ventricles. They are called lateral rather than first and second because they are paired, but they count as two of the four ventricles.  The third and fourth are unique so they each have their own numbered names.  The lateral ventricles  each communicate with the third ventricle through a separate opening called the Foramen of Munro. Central neurocytoma and choroid plexus papilloma are rare central nervous system tumors typically found in the lateral ventricles. The third ventricle is in the bottom center of the brain and its walls are made up of the thalamus and hypothalamus. Tumors in this location the choroid glioma. The third ventricle connects with the fourth ventricle through a long tube called the Aqueduct of Sylvius. The lateral ventricles and the third ventricle are coded to C71.5 Ventricle NOS. Most of the fourth ventricle is between the pons and cerebellum. Meduloblastomas and epedymomas commonly occur in the fourth ventricle. Tumors of the fourth ventricle are coded to C71.7 Brain stem.  

Marked expansion of the ventricles, called hydrocephalus, may occur when there is a blockage in the pathways through which the fluid normally travels. It may also arise from an overproduction of fluid or a difficulty in absorbing the fluid that is produced.  Because the brain is enclosed within the bony skull, this extra fluid within the ventricular system will produce increased pressure symptoms: headaches, vomiting, drowsiness and in some cases, confusion. Rare tumors involving the choroid plexus within the ventricles may affect the production and absorption of the fluid. A similar condition may arise in the spinal cord as tumors block the flow of fluid down the central canal of the spinal cord; this is known as syringomyelia.

## Pineal and Pituitary Glands

- C75.1

- C71.7

- C75.3

- C71.6

- C72.0

**Source: URL: training.seer.cancer.gov/module_anatomy/unit6_3_endo_gl... Accessed 7/18/03.**

**Notes:**
The pineal and pituitary glands are located deep inside the brain.  The pineal gland produces melatonin, the hormone that controls biological body rhythms.  Hydrocephalus is a symptom of pineal tumors.  A symptom of a pineal tumor in children is precocious puberty. 

The pituitary gland produces several hormones, including growth hormone.  Symptoms of pituitary tumors may include but are not limited to diabetes, headache, vision changes, and breast enlargement caused by inappropriate hormone secretion.

## Cranial Nerves

- I=C72.2, II=C72.3, VIII=C72.4, Others=C72.5

**Source: URL: faculty.washington.edu/chudler/cranial.html Accessed 7/18/03.**

**Notes:**
	The human body has 12 pairs of cranial nerves.  Cranial nerves 3 through 12 are found in the brain stem.  3 and 4 are in the mid-brain,  5 through 8 are in the pons, and 9 through 12 are in the medulla oblongata.  

The olfactory nerve  controls sense of smel; l
The optic nerve controls vision
The oculomotor nerve controls eye movement and pupil size 
The trochlear nerve controls eye movement 
The trigeminal nerve controls sensation in the face, nose, mouth, teeth, cornea, chewing, and facial expression
The abducens nerve controls eye muscles
The facial nerve controls facial expression, tears, and saliva taste
The vestibulocochlear, also known as acoustic, nerve  controls hearing and balance 
The glossopharyngeal nerve controls throat movement and sensation, and taste
The vagus nerve controls sensation and muscles in the throat and windpipe
The accessory nerve controls movement of the neck
The hypoglossal nerve controls tongue movement and swallowing.  

	Symptoms may include but are not limited to problems in the functions described above for each nerve. 

## Meninges

- C71.0

- C70.0

- C70.0

**Source: URL: **_[www.cardioliving.com/consumer/Stroke/Hemorrhagic_Stroke.sht](http://www.cardioliving.com/consumer/Stroke/Hemorrhagic_Stroke.sht)_** Accessed 7/18/03.**

**Notes:**
The meninges are three membranes that cover the brain and spinal cord, and protect the CNS.  The dura mater is the tough outer membrane.  The arachnoid is the middle web-like membrane.  The pia mater is the inner-most membrane and is delicate and highly vascular.  The subarachnoid space is between the arachnoid and pia mater and contains cerebrospinal fluid (CSF).  Symptoms of tumors of the meninges are usually caused by compression and pressure, not by growth into brain tissue.  Seizures are the most common symptom of such tumors.

## Tentorium

- C70.0

- C70.0

**Source: URL: neurosurgery.mgh.harvard.edu/abta/primer.htm Accessed 7/18/03. **

**Notes:**
The tentorium is a flap of meninges that separates the cerebral hemispheres from the posterior fossa.  The posterior fossa contains the cerebellum and brain stem.  Intracranial tumors are often described by their location in relation to the tentorium.  Supratentorial tumors are located above the tentorium in the cerebral hemispheres and include tumors in the parietal lobe.  Infratentorial tumors are located below the tentorium in the cerebellum or brain stem and include tumors in the medulla oblongata, part of the brain stem. 

## Spinal Cord

- C72.0

- C70.1

**Source: URL: **_[www.merck.com/pubs/mmanual/figures/182fig1.htm](http://www.merck.com/pubs/mmanual/figures/182fig1.htm)__ Accessed 7/18/03_

**Notes:**
The spinal cord begins in the medulla oblongata, which is part of the brain stem and is made up of nerve fibers.  Meninges cover and protect the spinal cord.  Symptoms of spinal cord tumors depend on the nerves involved and may include pain in the chest for thoracic tumors,  and pain in the neck, arm, back, or leg with lumbar or cervical tumors.

## Cellular Classification

**Neuroepithelial tumors**
- Astrocytomas
- Oligodendrogliomas
- Ependymomas
- Pineal parenchymal tumors
**Other CNS tumors**** **
- Sellar tumors
- Hematopoetic tumors
- Germ cell tumors
- Meningiomas
- Tumors of cranial nerves

**Notes:**
The WHO classification of tumors affecting the CNS divides tumors into Neuroepithelial and Other CNS neoplasms.

Neuroepithelial means derived from neurons and glia cells of the nervous system. The neuroepithelial tumors include astrocytomas, oligodendroglioma, ependymomas, pineal parenchymal tumors, and others. 

The category of “Other” includes tumors derived from non-glial cells such as sellar tumors, hematopoetic tumors, germ cell tumors, meningiomas, and tumors of cranial nerves.

## Glial Tumors (1) 

- Glial tissue: supportive tissue of brain made up of astrocytes and oligodendrocytes
- Glial tumors assigned ICD-O-3 histology codes from glioma series:
- Codes 938 through 948.

**Notes:**
Many researches divide brain tumors into two categories of glial and non-glial. 
Glia (glial tissue) is the supportive tissue of the brain made up of astrocytes and oligodendrocytes which are glial cells.  

Glial tumors develop from glial tissue and may be benign, borderline, or malignant. They assigned ICD-O-3 histology codes from the glioma series, codes 938 through 948.  

Some histologies of glial origin are glioma, subependymoma, astrocytoma, glioblastoma, and medulloblastoma. 

CNS tumors that develop in other tissues are defined as non-glial tumors and may be benign, borderline, or malignant.  Some non-glial histologies are meningioma, germ cell tumor, and pituitary adenoma.

## Glial Tumors (2)

- Astrocytic tumors
- Noninfiltrating
- Juvenile pilocytic (M9421)
- Subependymal (M9383)
- Infiltrating
- Well-differentiated mildly and moderately anaplastic astrocytomas (M9401)
- Anaplastic astrocytomas
- Glioblastoma multiforme (M9440)
- Brain stem gliomas (M9380)

**Notes:**
Astrocytic tumors are divided into non-infiltrating and infiltrating categories.

Noninfiltrting tumors include Juvenile pilocytic and subependymal astrocytomas which are often curable.

In the Infiltrating category, well-differentiated mildly and moderately anaplastic astrocytomas are less often curable. 

For anaplastic astrocytomas of higher grade, the cure rate is low with standard local treatment. 

The cure rate for glioblastoma multiforme, is very also low with standard local treatment. 

Brain stem gliomas have a relatively poor prognosis that is correlated with histology (when biopsies are performed), location, and extent of tumor. The overall median survival time of patients with brain stem gliomas in studies has been 44 to 74 weeks. The best results have been attained with hyperfractionated radiation therapy.
. 

## Glial Tumors (3)

- Ependymal tumors
- Myxopapillary and well-differentiated ependymomas (M9394)
- Anaplastic ependymomas (M9392)
- Ependymoblastomas (M9392)
- Oligodendroglial tumors
- Well-differentiated oligodendrogliomas (M9450)
- Anaplastic oligodendrogliomas (M9451)

**Notes:**
Myxopapillary and well differentiated ependymoma are often curable.  Malignant ependymomas have variable prognoses that depend on the location and extent of disease. Frequently, but not invariably, anaplastic ependymomas have a worse prognosis than well-differentiated ependymomas.  The rare ependymoblastoma has a much poorer prognosis. 

Oligodendrogliomas are more slow-growing tumors that usually occur in young adults. Adult well-differentiated Oligodendrogliomas behave very similarly to the well-differentiated mildly and moderately anaplastic astrocytomas.  They are frequently located within the frontal, temporal, or parietal lobes and cause seizures in a relatively high percentage of patients. Many oligodendrogliomas contain little specks of calcium (bone) and can easily bleed. Treatment is usually surgery, and,  in cases of a benign tumor, no additional chemotherapy or radiation therapy is recommended following surgery. Anaplastic or mixed oligodendrogiomas are more aggressive forms of this tumor. For anaplastic oligodendrogliomas of higher grade, the cure rate is low with standard local treatment. Both chemotherapy and radiation therapy are usually advised. 

## Glial Tumors (4)

- Mixed tumors
- Mixed astrocytoma-ependymomas
- Mixed astrocytoma-oligodendrogliomas
- Mixed astrocytoma-ependymoma-oligodendrogliomas
- Other gliomas
- Ganglioneuromas (M9490)
- Optic nerve gliomas

**Notes:**
The mixed glial tumors have a prognosis similar to that for anaplastic astrocytomas and can be treated as such. 

Ganglioneuromas are the rarest form of glioma.  These tumors grow relatively slowly and may occur in the brain or spinal cord. They are usually treated with surgery. 

Optic Nerve Gliomas also named for their location, are found on the optic nerve and are particularly common in individuals who have neurofibromatosis. Treatment may include surgery, radiation, or chemotherapy. Some of these tumors are slow growing and are best managed by observation alone. 

## Non-Glial Tumors (1) 

- Pineal region tumors
- Parenchymal tumors
- Pineocytomas (M9361)
- Pineoblastomas (M9362)
- Pineal astrocytomas (M9400)
- Germ cell tumors
- Germinomas (M9064)
- Embryonal carcinomas (M9070)
- Choriocarcinomas (M9100)
- Teratomas (M9080)

**Notes:**
Pineocytomas are slow growing and carry variable prognoses for cure. Pineoblastomas are more rapidly growing and have a poorer prognosis. Pineal astrocytomas vary in prognosis depending on the degree of anaplasia. Higher grades have a poorer prognosis.

Germ cell tumors include germinoma, embryonal carcinoma, choriocarcinoma, and teratoma.  The prognosis and treatment depends on the histology, location, presence  and amount of biological markers, and surgical resectability

Germinomas are the most common tumors of germ cell origin, representing approximately 0.5–2% of primary intracranial tumors. They are midline tumors and common sites include the pineal region, suprasellar cistern, and posterior third ventricle. Suprasellar germinomas may represent a primary localization or metastatic disease from pineal lesions. Synchronous occurrence in the pineal gland and suprasellar cistern is frequent.

Embryonal cell carciniomas  and choriocarcinomas are  rare, highly malignant germ cell tumors of the pineal region that are devoid of specific characteristics on imaging studies compared to other germ cell tumors. Prior to biopsy, the diagnosis may be suspected clinically on the basis of cerebral spinal fluid analysis of tumor markers. Embryonal cell carcinomas express both AFP and the beta subunit of HCG.  Choriocarcinomas express the beta subunit of -HCG but not AFP. 

Teratomas arise from multipotential cells that produce tissues consisting of a mixture of two or more embryological layers (ectoderm, mesoderm, and endoderm). They can be benign (typical, or mature or immature) or malignant (formerly called teratocarcinomas). Teratomas are the second most common pineal region tumor, accounting for 15% of pineal masses. Male predominance ranges from 2:1 to 8:1.

## Non-Glial Tumors (2)

- Meningiomas
- Meningioma: Benign (M953_)
- Malignant meningiomas
- Anaplastic meningioma
- Hemangiopericytoma (M9150)
- Papillary meningioma (M9538)
- Choroid plexus tumors
- Choroid plexus papilloma (M9390)
- Choroid plexus carcinoma
- Choroid plexus meningioma (M9538)

**Notes:**
Benign meningiomas are usually curable when they are resectable. 
The prognosis for patients with malignant meningioma is poorer than for the more well-differentiated meningiomas because complete resections are less common and the proliferative capacity is greater. 

The choroid plexus can be the site of different types of tumors, including those that are primary or secondary, and benign or malignant. The most common primary tumors are choroid plexus papilloma, choroid plexus carcinoma, and choroid plexus meningioma. Radiological diagnosis is based on location within the ventricles, mainly lateral ventricles in the trigonal region but also the fourth and, more rarely, the third ventricle. MRI shows a thin rim of cerebral spinal fluid around the tumor; sometimes, however, the tumor becomes so large that makes it is difficult to determine its primary intraventricular origin.

There is a code for "multiple meningiomas" M9530/1.  Note that this has a behavior code of "1" and SHOULD NOT be used to code multiple or sequential malignant meningiomas that have a behavior code of "3."  

Multiple meningiomas (also called meningiomatosis) are almost always benign and are strongly associated with Neurofibromatosis type 2 (NF2) and other genetic disorders.  Occasionally multiple meningiomas develop that are not associated with a genetic disorder; these may be referred to as "sporadic" meningiomas.  

Multiple malignant meningiomas are very rare and should be coded to 9530/3 (malignant meningioma) unless there is a description of a specific type of meningioma that has a different morphology code.

## Other CNS Tumors (1) 

- Craniopharyngiomas (M9350)
- Rathke pouch tumors
- Chordomas (M9370)
- Schwannomas (M9560)
- Acoustic schwannomas/neuromas

**Notes:**
Craniopharyngiomas are tumors usually located in the sellar and parasellar region, deriving from squamous epithelial resting along the involuted hypophyseal Rathke's duct. These tumors account for approximately 3–5% of all intracranial tumors and show no sex predominance. They have a bimodal age distribution; more than half occur in childhood or adolescence, with a peak incidence between 5 and 10 years of age; there is a second smaller peak in the sixth decade. These tumors are often curable. 

Chordomas are most common in people in their 20s and 30s. These tumors develop from the remains of a spine-like structure that forms and then dissolves in the fetus. Although these tumors are often slow-growing, they can metastasize or recur even after treatment. They are usually treated with a combination of surgery and radiation. 

Schwannomas come from the cells that form a protective sheath around the body's nerve fibers. They are usually benign and are surgically removed when possible.
One of the more common forms of this tumor affects the eighth cranial nerve, which contains nerve cells that are important for balance and hearing. Also known as "vestibular schwannomas" or "acoustic neuromas," these tumors may grow on one or both sides of the brain and are potentially curable with surgery or stereotactic radiosurgery. Acoustic neuromas account for about 7% of all skull tumors. Early symptoms may include loss of hearing, ringing in the ears, dizziness and vertigo. When the condition is detected early, doctors may order an MRI scan and conduct hearing tests, which may include a special technique to test nerve impulses as they travel to the brain. When tumors are small, they can be removed through microsurgical procedures, avoiding damage to the facial nerve. For larger tumors, extensive surgery many be needed. 

## Other CNS Tumors (2)

- Embryonal tumors
- Retinoblastomas (M9510)
- Primitive neuroectodermal tumors (PNETs)
- Meduloblastomas (M9470)
- Neuroblastomas (M9500)

**Notes:**
Retinoblastomas cause the growth of malignant tumors in the retinal cell layer of the eye. Although the disease is very rare, it is the third most common cancer overall in children, representing about 2% of childhood malignancies. The disease may be inherited or result from a new germinal mutation. About 10% of patients have a family history of retinoblastoma and another 20 to 30% have bilateral disease. Most of the remaining 60% of patients, with unilateral disease and no family history of retinoblastoma, have non-heritable disease. However, about 5% of these patients may also carry the gene for retinoblastoma and risk of passing the trait to their children. Tumors appear as single or multiple gray-white elevations in the retina; tumor seeds may be visible in the vitreous. In almost all tumors, calcification can be detected by CT. Untreated, retinoblastoma is almost always fatal; therefore, early diagnosis and treatment are critical in saving lives and preserving visual function. More than 90% of children with retinoblastoma can be cured by early detection and treatment of the affected eye.
Primitive neuroectodermal tumors (PNETs) can occur anywhere in the brain, although the most common site is in the back of the brain near the cerebellum. When they occur here, they are called medulloblastomas. The classification is based on both histopathological characteristics and location in the brain. Undifferentiated neuroectodermal tumors of the cerebellum have historically been referred to as medulloblastomas, while tumors of identical histology in the pineal region are referred to as pineoblastomas. The symptoms depend on their location in the brain, but typically include increased intracranial pressure. These tumors are fast growing and often malignant, with occasional spreading throughout the brain or spinal cord. They may spread contiguously to the cerebellar peduncle,  the floor of the fourth ventricle, and into the cervical spine, or above the tentorium. In addition, they may spread via the cerebrospinal fluid intracranially or to the spinal cord. The tumors often block drainage of the cerebral spinal fluid, causing symptoms associated with increased Intracranial pressure. A combination of surgery, radiation, and chemotherapy is usually necessary to control these tumors. 
Neuroblastoma  tumors  belong to the group of PNETs in which they are considered  the prototypical supratentorial manifestations. Neuroblastomas occur in young children, with over 50% found within the first 5 years of life. Clinical presentation is usually in the form of raised intracranial pressure. These tumors are large solid masses, that are frequently haemorrhagic, with calcification and cysts, typically deep seated within the frontoparietal lobes and adjacent to the lateral ventricles; they may, however, be found anywhere in the nervous system.

## Other CNS Tumors (3)

- Lymphomas (M9590)
- Arise from
- Indigenous brain** **histiocytes (microglia)
- Rare lymphocytes in meninges
- High incidence in patients with AIDS
- Vascular tumors
- Rare, non-malignant tumors
- Arise from blood vessels of brain and spinal cord
- Hemangioblastoma (M9161) most common vascular tumor

**Notes:**
Primary cerebral lymphomas are thought to arise from indigenous brain histiocytes (microglia) or from rare lymphocytes that are normally present in the meninges and around vessels. Most often, they affect immunosuppressed individuals, such as patients with AIDS, but may also develop in people with intact immune systems. Their high incidence in patients with AIDS and frequency in non immunosupressed people, have made primary cerebral lymphomas a relatively common brain tumor. The brain, especially subarachnoid space, is also a frequent site of metastasis of systemic lymphoma and leukemia. Grossly, cerebral lymphomas are single or multiple, poorly defined tumors with necrosis, similar to glioblastomas. Meningeal spread is very common, and some cerebral lymphomas arise in the subarachnoid space. Cerebral lymphomas, like their extracerebral high-grade counterparts, are highly malignant. 
Vascular tumors are rare, non-cancerous tumors that arise from the blood vessels of the brain and spinal cord. The most common vascular tumors are the hemangioblastomas, often linked in a small number of people to a genetic disorder called von Hippel-Lindau disease. Hemangioblastomas do not usually spread, and surgery can offer a cure. 

## Other CNS Tumors (4) 

- Cysts and tumor-like lesions
- Reportable
- Dermoid cysts (M9084)
- Granular cell tumors  (M9580)
- Rathke pouch tumors (M9350)
- Not reportable
- Epidermoid cysts
- Colloid cysts
- Enterogenous cysts
- Neuroglial cysts
- Plasma cell granulomas
- Nasal glial herterotopias
- Rathke cleft cysts

**Notes:**
The NPCR law defines a “brain-related tumor” as a primary tumor listed in the ICD-O.  Therefore, only tumors listed in ICD-O are reportable. The WHO lists several cysts and tumor-like conditions.  Of these, only three are reportable.

Dermoid cysts or tumors are congenital ectodermal inclusion cysts. All elements composing the tumors originate from the embryonic ectoderm. These are rare tumors, accounting for less than 0.5% of all intracranial tumors. Dermoid cysts may be found intracranially or in the spinal canal, mainly in or near the midline; some typical locations are frontobasal, parasellar, or in the posterior fossa. They are cystic masses, with a fibrous capsule lined with squamous epithelium and containing a thick fluid composed of cholesterol, keratin, and lipid metabolites, derived from decomposed epithelial cells. The cysts may rupture and fatty components of their contents may spread into the subarachnoid spaces and within the ventricles. 
Granular cell tumors (GCTs) are benign neoplasms composed of proliferations of round or polygonal cells that contain eosinophilic granular cytoplasm. The most common locations are tongue and subcutaneous tissue, but a variety of other sites may be involved, including the CNS. Most CNS GCTs arise in the pituitary gland, but rare cases involving brain and leptomeninges have been described. 
“Rathke pouch tumor” is a synonym for craniopharyngioma
All of the other listings are NOT reportable because they do not have an ICD-O code. Including Rathke's cleft cyst.  
Some controversy exists among pathologists regarding the need to include some CNS cystic lesions in the ICD-O.  A concensus conference is being planned to discuss issues pertaining to CNS ICD-O codes. Some have suggested revising to the ICD-0 in a few years.

## Childhood versus Adult Tumors

- CNS tumor histology and location are different in adult and children.
- Tumor location and extent of spread affect treatment and prognosis.
- Most common solid tumor in childhood.

**Notes:**
CNS tumors occur in both adults and children, but the histologies and location are different. 

Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis in both children and adults. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification.

Primary brain tumors are a diverse group of diseases that,  together, constitute the most common solid tumors of childhood.  CNS tumors are the most common solid tumors of childhood and occur more often in children aged 7 years and younger than in older children.  

## Childhood Brain Tumors

- Meduloblastomas are the most common CNS histology in children.
- 50% are infratentorial.
- Common infratentorial tumors:
- Cerebellar astrocytomas
- Meduloblastomas
- Ependymomas
- Brain stem gliomas
- Atypical teratoid tumors

**Notes:**
The most common histology for childhood CNS  tumors is medulloblastoma, a malignant tumor.  

Approximately 50% of brain tumors in children are infratentorial, and three-quarters of these are located in the cerebellum or fourth ventricle. Infratentorial means that the tumor originates BELOW  the tentorium, the meninges separating the cerebrum from the cerebellum and brain stem. 

Common infratentorial (posterior fossa) tumors include: cerebellar astrocytomas (usually pilocytic but also fibrillary and high-grade), medulloblastomas (primitive neuroectodermal tumors), ependymomas (low-grade or anaplastic), brain stem gliomas (high-grade or low-grade), and atypical teratoid tumors.

## Cellular Classification Childhood Brain Tumors (1)

- Supratentorial tumors in children

- Craniopharyngiomas
- Germ cell tumors
- Diencephalic and 	hypothalamic gliomas
- Low grade astrocytomas
- Mixed gliomas
- Anaplastic astrocytomas
- Oligodendrogliomas
- PNETs
- Meningiomas

- Glioblastoma multiforme
- Low-grade or anaplastic 	ependymomas
- Choroid plexus tumors
- Pineal parenchymal tumors
- Gangliogliomas
- Desmoplastic infantile 	gangliogliomas
- Dysembryoplastic 	neuroepithelial tumors

**Notes:**
Supratentorial tumors occur above the tentorium in the sellar or suprasellar region (around the sella turcica, the bone that contains the pituitary gland), in the cerebrum, or in the diencephalon (part of the cerebrum).  Approximately 20% of childhood CNS tumors are located in the sellar or suprasellar region. Supratentorial tumors in children include:
 craniopharyngiomas
 diencephalic and hypothalamic gliomas
 germ cell tumors
 low grade astrocytomas
 anaplastic astrocytomas
 glioblastoma multiforme, 
 mixed gliomas
 oligodendrogliomas
 PNETs
 low-grade or anaplastic ependymomas 
 meningiomas 
 choroid plexus tumors 
 pineal parenchymal tumors 
 gangliogliomas 
 desmoplastic infantile gangliogliomas
 dysembryoplastic neuroepithelial tumors.

## Cellular Classification Childhood Brain Tumors (2)

- The histopathology of childhood spinal tumors is the same as for childhood brain tumors.
- Primary spinal cord tumors** **comprise approximately 1% to 2% of all childhood CNS tumors.

**Notes:**
The histopathology of childhood spinal tumors is the same as for childhood brain tumors.  Primary spinal cord tumors comprise approximately 1% to 2% of all childhood CNS tumors. As is the case for primary brain tumors, such lesions are histologically heterogeneous. Approximately 70% of all intramedullary spinal cord tumors are low-grade astrocytomas or gangliogliomas. Other tumor types include ependymomas, high grade glial tumors, and (rarely) PNETs. Myxopapillary ependymomas have a proclivity to develop in the conus and caudae equina region. 

Symptoms and signs of spinal cord tumors are highly dependent on the location of the tumors and their extent.  Some low-grade spinal cord tumors are associated with large cysts that extend rostrally and caudally and have been termed “holocord astrocytomas”.  At times, it is impossible to distinguish tumors arising in the medulla from a tumor which arises in the upper cervical cord.  

No uniformly accepted staging system exists for childhood primary spinal cord tumors. These tumors are classified based on their location within the spinal cord and histology. Low-grade spinal cord tumors rarely disseminate elsewhere in the nervous system; however, higher grade tumors may disseminate. Despite this, and because of the location of the tumors and concerns about causing further neurological deterioration by cerebrospinal fluid attainment, routine lumbar spinal punctures are not indicated in the evaluation of children with spinal cord tumors. For high-grade glial spinal cord tumors, and possibly lower grade tumors and ependymomas, neuroimaging of the entire neuroaxis (brain and entire spine) is indicated at the time of diagnosis to determine extent of disease. 

## Cellular Classification Childhood CNS Tumors

- Cause of childhood CNS tumors remains unknown.
- American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of pediatric cancer patients.

**Notes:**
The cause of the vast majority of childhood brain tumors remains unknown.  More than half of children diagnosed with brain tumors survive 5 years from diagnosis. In some subgroups of patients, the survival and cure rate is higher.  Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.

## ICD-O-3 Coding Issues (1)

- Some histologies may be difficult to determine if the primary site is intracranial or the skull (C41.0).
- Non-malignant tumors of the skull are not reportable.
- Chondroma (M9220/0) must originate in a brain-related site to be reportable.
- Chordoma (M9370/3) and chondrosarcoma (M9220/3) are malignant.
- Tumors in brain-related sites are analyzed separately from those in the skull.

**Notes:**
For some histologic types, it is difficult to determine if the primary site is intracranial or the skull (C41.0).  Tumors that originate in the skull are not intracranial.  
The malignant tumors are reportable regardless of origin, but non-malignant tumors that originate in the skull are not reportable.

Chondromas (9220/0) are benign tumors of cartilage cells.  The ICD-O-3 manual shows the code for bone in parentheses next to the morphology. The record shoukd be reviewed carefully to determine if the tumor originated in bone or in an intracranial site.  Because chondroma is a benign tumor, an abstract should only be completed  if the primary tumor is in an intracranial site. A chondroma of the skull is not reportable. 

Chordomaa are  malignant tumors arising from the embryonic notochord, and chondrosarcomas (9220/3) are malignant tumors of cartilage cells. These tumor histologies are reportable, but registrars must determine if the primary site is bone or an intracranial site because intracranial tumors are analyzed separately.  

## ICD-O-3 Coding Issues (2)

- Continue to assign histology code M9421/3 to pilocytic astrocytoma.
- When the primary site for intracranial schwannoma (9560/0) is not documented in source documents, the site should be coded to cranial nerves NOS (C72.5).

**Notes:**
When ICD-O-3 was published, the code for pilocytic astrocytoma changed from malignant behavior (3) to  borderline behavior (1).  Registrars were instructed to continue to assign the code for malignant behavior.  For data consistency, the malignant behavior code (3) should still be assigned to pilocytic astrocytoma even after non-malignant CNS cases are collected.  

Intracranial schwannoma (9560/0) is reportable for cases diagnosed January 1, 2004 and later.  It is difficult to determine the intracranial site of a schwannoma.  Assign the primary site for intracranial schwannoma to cranial nerves NOS (C72.5) when the site is not documented in the health record.

## Grade for CNS Tumors

- Sixth digit of ICD-O-3 histology code
- Describes tumor differentiation or grade.
- Is not usually specified for CNS tumors.
- Is always assigned code 9 for non-malignant CNS tumors:
- Not determined, not stated, or not applicable.
- Per ICD-O-3, page 30, Rule G, paragraph 1 “Only malignant tumors are graded.”
- Not the same as WHO grade.

**Notes:**
The sixth digit of the ICD-O-3 morphology code describes the histologic grade or differentiation of the tumor.  The ICD-O-3 grade or differentiation is not always described by pathologists for CNS tumors.  When it is not described, code 9 (not determined, not stated, or not applicable) should be assigned
.  
Some histologies include differentiation in the terms. When this is the case, the differentiation can be coded.  Also, other terms for grade may be used such as with low grade astrocytomas (M9400/3).  These should be coded according to FORDS, pg. 97 and SEER Program Manual pg. 102. In this case,  low grade is coded as a grade I-II or code 2.

The ICD-O-3 grade or differentiation code for non-malignant CNS tumors is always code 9.  This is documented in ICD-O-3, pg. 30, Rule G, paragraph 1. 

Other grading systems used to describe CNS tumors are WHO grade, Kernohan grade, and St. Anne-Mayo grade.  These grades are not the same as the ICD-O-3 grade or differentiation, and are not recorded in the sixth digit histology code data field for grade. The grade is used by the clinician to plan treatment and predict prognosis.  

This is NOT the same as WHO grade.  WHO grade is recorded in the Collaborative Stage Site-specific fields for Brain

## WHO Grade (1)

- WHO grade coded in Collaborative Stage data field:
-  Site-specific factor 1 for Brain.
- Four-category tumor grading system
- Grade I
- Slow growing
- Non-malignant tumors
- Patients have long-term survival.

**Notes:**
The WHO grade is not coded as the sixth digit of the histology code.  WHO grade is coded in the collaborative stage data field, site-specific factor 1.

WHO grade is a four-category system with grade I being the least aggressive and grade IV being the most aggressive.  

Grade I tumors are slow growing and non-malignant , and are associated with  long-term survival. 

## WHO Grade (2)

- Grade II
- Relatively slow growing
- Sometimes recur as higher grade tumors
- May be non-malignant or malignant .
- Grade III
- Malignant tumors
- Often recur as higher grade tumors.
- Grade IV
- Highly malignant and aggressive.

**Notes:**
Grade II tumors are relatively slow growing but sometimes recur as higher grade tumors.  They may be non-malignant or malignant.  

Grade III tumors are malignant and often recur as higher grade tumors.  

Grade IV tumors reproduce rapidly and are very aggressive malignant tumors.  

If different WHO grades are reported,  the rule to use is  “grade up- -stage down” and the highest grade (worst prognosis) should be coded.

If the pathology report does NOT state a WHO grade but another diagnostic test such as an MRI does, the WHO grade from the diagnostic test can be used.

## Kernohan Grade

- Defines progressive malignancy for astrocytoma
- Grade 1:  benign astrocytomas
- Grade 2:  low-grade astrocytomas
- Grade 3:  anaplastic astrocytomas
- Grade 4:  glioblastoma multiforme
- No NAACCR data field for Kernohan grade.

**Notes:**
The Kernohan grade defines progressive malignancy for astrocytoma.  A grade 1 tumor is a benign astrocytoma, a grade 2 tumor is a low-grade astrocytoma, a grade 3 tumor is an anaplastic astrocytoma, and a grade 4 tumor is a glioblastoma multiforme.  No NAACCR data field is available for Kernohan grade.

## St. Anne-Mayo Grade (1)

- Used for astrocytomas.
- Uses four morphologic criteria:
- Nuclear atypia
- Mitosis
- Endothelial proliferation
- Necrosis
- No NAACCR data field for the St. Anne-Mayo grade.

**Notes:**
The St. Anne-Mayo grade is also used to grade astrocytomas.  It is a four-grade system defined by four morphologic criteria.  Nuclear atypia, mitosis, endothelial proliferation, and necrosis are the criteria used in this system. No NAACCR data field is available for the St. Anne-Mayo grade.

## St. Anne-Mayo Grade (2)

- Grade 1: No criteria
- Grade 2: One criterion, usually nuclear 			atypia
- Grade 3: Two criteria, usually nuclear 				atypia and mitosis
- Grade 4: Three or four criteria

**Notes:**
Grade 1 tumors do not have any of the criteria.  Grade 2 tumors have one criterion, usually nuclear atypia.  Grade 3 tumors have two criteria, usually nuclear atypia and mitosis.  Grade 4 tumors have three  or four of the criteria.

## Grade for CNS Tumors

- Do _not_ record WHO grade, Kernohan grade, or St. Anne/Mayo grade in the sixth digit histology code data field

**Notes:**
Other grading systems used to describe CNS tumors are WHO grade, Kernohan grade, and St. Anne/Mayo grade.  These grades are not the same as the ICD-O-3 grade or differentiation and are not recorded in the sixth digit histology code data field for grade. The grade is used by the clinician to plan treatment and predict prognosis.  

## Part III

- Laterality
- Multiple Primaries
- Malignant Transformation
- Sequence Numbers
- Date of Diagnosis

**Notes:**
Part II covers 
Multiple Primaries
Laterality
Date of Diagnosis
Sequence Numbers
Malignant Transformation

## Determining Multiple Primaries: Laterality

- Brain is not a paired organ.
- Laterality collected on both non-malignant and malignant tumors.
- Used to determine if multiple non-malignant CNS tumors are counted as multiple primary tumors.
- _Not_ used to determine if multiple malignant tumors of the same intracranial or CNS site are multiple primary tumors.

**Notes:**
The brain is not a paired organ but laterality should be collected on both non-malignant and malignant CNS tumors.

Researchers, including epidemiologists, have requested the collection of laterality, because the location of certain tumors might help in determining causation.  Certain investigations, such as those involving cell phone usage, would benefit from having this information routinely available.  Also, non-treatment-related factors, such as location of tumor by hemisphere, can be predictive factors for cognitive outcome. 

Laterality is used  to determine if multiple non-malignant CNS tumors are counted as multiple primary tumors.  Laterality is not used to determine if multiple malignant tumors of the same CNS site are multiple primary tumors.  How to code laterality for CNS sites is discussed in later slides.

## Coding Laterality (1)

- CNS sites to be coded with laterality:
- Cerebral meninges, NOS (C70.0)
- Cerebrum (C71.0)
- Frontal lobe (C71.1)
- Temporal lobe (C71.2)
- Parietal lobe (C71.3)
- Occipital lobe (C71.4).

**Notes:**
The CNS sites to be coded with laterality are cerebral meninges, NOS (C70.0), cerebrum (C71.0), frontal lobe (C71.1), temporal lobe (C71.2), parietal lobe (C71.3),and occipital lobe (C71.4). 

## Coding Laterality (2)

- CNS sites to be coded with laterality (continued):
- Olfactory nerve (C72.2)
- Optic nerve (C72.3)
- Acoustic nerve (C72.4)
- Cranial nerve, NOS (C72.5)

**Notes:**
Laterality is also assigned to olfactory nerve (C72.2), optic nerve (C72.3), acoustic nerve (C72.4), and cranial nerve, NOS (C72.5).  Laterality should be coded using codes 1 through 4 or 9 (paired site but lateral origin unknown; midline tumor).  The laterality for all other CNS sites is coded 0 (not a paired organ).

## Determining Multiple Primaries:Definitions

- Non-malignant tumor
- Tumor with ICD-O-3 behavior code
-  0 (benign) or 1 (borderline).
- CNS
- 		Includes intracranial and central 	nervous system topographic sites.

**Notes:**
A non-malignant tumor is any tumor with an ICD-O-3 behavior code of 0 (benign) or 1 (borderline).

CNS is used to describe intracranial and central nervous system tumors.

## Determining Multiple PrimariesMalignant (1)

**NO CHANGES (at this time)**
**Site **
- Rule: Each category (first three characters) as delineated in ICD-O-3 is considered to be a separate site.
- Multiple tumors are:
- Same: C7**1**.0 Cerebrum, C71.**2** Temporal lobe
- Different: C7**0**.0 Cerebral Meninges, C7**1**.0 Cerebrum

**Notes:**
The rules for determining multiple primary tumors of all CNS sites and histologies were reviewed by the NAACCR registry operations subcommittee and recommendations for changes to the rules were suggested.  The changes for the non-malignant CNS tumors were approved by the NAACCR Uniform Data Standards (UDS) committee but the suggested changes for the malignant CNS tumors were not approved. These suggested changes have been submitted to the SEER committee, which is reviewing multiple primary rules for all sites. 

At this time, the rules for determining multiple primary tumors for malignant CNS tumors will remain the same as they are now, which is the same as the  rules used for all other malignant tumors. The rule is that each category (first three characters),  as delineated in ICD-O-3, is considered a separate site. Therefore,  multiple tumors occurring in the cerebrum and the temporal lobe of the brain are considered the same tumor and only one abstract is completed. Multiple tumors occurring in the meninges and in the cerebrum are considered different tumors and separate abstracts are completed

## Determining Multiple Primaries: Malignant (2)

**Histology **
- Rule: Differences in histologic type refer to differences in the *FIRST THREE** *digits of the morphology code.
- Multiple tumors in the same site are:
- Same: Choroid plexus carcinoma (M9390),  Ependymoma (M9391)
- Different: Astrocytoma (M94**0**0), Gemistocytic astrocytoma (M94**1**1)

**Notes:**
The rule for histology is that differences in histologic type refer to differences in the FIRST THREE digits of the morphology code. Therefore, if multiple tumors occur in the same site and the first three digits of the histology code are the same, they are the considered the same tumor and one abstract is completed.  An example of this is a choroid plexus carcinoma (M9390) and an ependymoma (M9391). 

If the first three digits of the histology codes are different, the tumors are different and separate abstracts should be completed.  An example of this is an astrocytoma (M9400),  an a gemistocytic astrocytoma (M9411).

## Determining Multiple PrimariesNon-malignant (1)

**NEW RULES**
**Site **
- Rule:** **Each** ****sub-site** (fourth-digit level) as delineated in ICD-O-3 is considered a separate site.
- Same site if separate tumors with the same histology are in the same sub-site.
- Different site if separate tumors have the same histology in different sub-site
- C71.**1 **Frontal lobe,  C71.**4 **Occipital lobe
- C7**0.****0** Cerebral Meninges, C70.**1** Spinal meninges.

**Notes:**
As mentioned, the NAACCR UDS committee approved the NAACCR registry operations subcommittee’s recommendations for changes to the rules for the non-malignant CNS tumors.  

The rationale for these changes is based on the fact that the natural biology of non-malignant tumors is that of expansive, localized growth,  local recurrences are common, and metastases are uncommon. Non-malignant brain tumors confine themselves to one location, their site of origin, and thus any new non-malignant brain tumor represents a new tumor, a clinically significant event in the life of the patient worthy of capture. Therefore,  if multiple non-malignant tumors of the same histology are identified in different locations, they should be considered separate primaries. 

Non-malignant tumors of the same histology, same site, and same side recur in the same location.  If they recur, even after 20 years, they are still considered the same tumor. 

## Determining Multiple PrimariesNon-malignant (2)

**Site (cont) **
**EXCEPT** NOS (C_ _.9) with specific four-digit site code in same rubric** **
*	**	**Example:  *meninges, NOS (C70.9) with 		spinal meninges (C70.1) or cerebral 	meninges (C70.0).

**Notes:**
If the first three digits are the same and the fourth digit is a 9  or NOS (not otherwise specified) site, this is considered one site and should be coded to the more specific site.  For example if a tumor is identified as meninges, NOS and a separate tumor is identified as occurring in either the spinal or cerebral meninges, this is considered one tumor and only one abstract is completed using the more specific site code. 

## Determining Multiple PrimariesNon-malignant (3)

**Site (cont) **
- Laterality: For non-malignant cases only
- 	If multiple tumors of the same site and same histologic type are identified and _both sides_ of a site listed as lateral are involved, tumors should be counted as separate primaries.
- Different:
- Right  temporal lobe (**C71.2**) and left temporal lobe (**C71.2**)

**Notes:**
Several of the CNS site codes represent separate locations such as the right and left temporal lobes of the brain, or right and left acoustic nerves.  Therefore, laterality is considered when determining multiple primaries for non-malignant CNS tumors.

If multiple tumors of the same site and same histologic type are identified and both sides of a site listed as lateral are involved, the tumors should be counted as separate primaries and separate abstracts should be completed.

## Determining Multiple Primaries: Non-malignant (4)

**Histology**

**Notes:**
At this time, this table applies only to non-malignant histologies .  A separate table was submitted for malignant histologies. A decision regarding a separate table for malignant histologies is pending review by a SEER multiple primary committee. Originally, ICD-O histology codes were grouped into categories that were considered biologically related. Hence, the epithelial neoplasms were coded M801 to 804, the squamous cell neoplasms were coded from M805 to 808 etc. This is the origin of the multiple primary rule that differences in histologic type refer to differences in the first three digits of the morphology code.

Brain tumor histologies grouped in Table 2 do not follow the standard three-digit histology difference rule because they represent a progression, differentiation, or subtype of a single histologic category.  In a review of the ICD-O histology codes, applying the current three-digit histology rule to non-malignant tumors would combine tumors that are no longer considered to be biologically related. 

Over time and several versions of the WHO classification of brain tumors, some new codes were inserted in ICD-O where numbers were available a rather than where the code would logically fit. Thus, not all codes in a three-digit rubric may be part of the same histologic group. 

## Determining Multiple Primaries:Non-malignant (5)

**Histology **
- 	If multiple tumors are in the same site, refer to Table 2, and use the following rules in priority order:
- 	A-1: If the first three digits are the same but 	the codes are not found in Table 2, 	then the histology is considered to be the** ****	****SAME**.
- 		A-2:  If the first three digits are different 			but the codes are not found in Table 2, 			then the histology is **considered to be** 			**DIFFERENT.**

**Notes:**
To determine if the histology in multiple non-malignant CNS tumors is the same, Table 2 on the previous slide should be consulted, and the following rules should be used in priority order: 

Following the site rules just discussed, when multiple tumors are in the same site and:

If the first three digits of the histology code are the same and the codes are not found in Table 2, then the histology is considered to be THE SAME. Only one abstract should be completed.

If the first three digits are different, and the codes are not found in Table 2, then the histology is considered  to be DIFFERENT. Separate abstracts should be completed.

This follows the rule for histology,  that differences in histologic type refer to differences in the first three digits of the morphology code, and is the same rule as for malignant CNS tumors.  

Note: When multiple tumors are determined to be the same primary, but with different histology codes, existing rules for selecting which histology to code should be followed. Rule K: ICD-O pg. 34. When no single code includes all diagnostic terms, use the numerically higher  code number.

## Determining Multiple Primaries: Non-malignant (6)

**Histology (cont.)**
- 	B.  If **all** histologies are listed in the same 			histologic group in Table 2, then the 			histology is considered to be the** SAME. *******
- Example: Ependymomas:  M9394, Myxopapillary ependymoma and M9444, Chordoid glioma have the same histology
- 	*Note: If two histologies are in the same group in 	Table 2, code the first or  more specific histology.

**Notes:**
 If all histologies are in the same histologic group in Table 2, then the histology is considered to be the SAME, even though the first three digits are different.  
These two histologies represent a progression, differentiation or subtype of a single histologic category. On abstract should be prepared.

 *Note: If two histologies are in the same group in Table 2, the first (one with the earliest dx date) or  more specific histology should be coded.  

Example of using the most specific histology code:  A  patient has a diagnosis of a Choroid plexus papilloma, NOS (9390/0), which is a non-specific term, and is subsequently diagnosed with an Atypical choroid plexus papilloma (9390/1), a more specific histology, in the same site. These terms are both in the grouping of Choroid plexus neoplasms in Table 2. The  9390/0 is the first diagnosis (earliest dx date) but 9390/1 is more specific so 9390/1 should be used.  

Example of using the "first" histology code: If a patient has a subsequent tumor in the same site and both histologies are "specific" and in the same grouping on Table 2, you keep the first diagnosis. The patient has subependymoma (9383/1) (a "specific" histology) and is subsequently diagnosed with a Choroid glioma (9444/1) (also a "specific" histology) both listed in Table 2 in the Ependymomas grouping.  The first histology of subependymoma (9383/1) would be coded.

## Determining Multiple Primaries: Non-malignant (7)

**Histology (cont)**
- 	C: 	If the first three digits are the same as the 			first three digits for **any histology** in one of 			the groupings in Table 2 , then the histology 			is considered to be the **SAME.***
- 			Example: On table: Neuronal and neurol-glial 			neoplasm: M9505, ganglioglioma, Not on 			table: M9507, Pacinian tumor
- * Note: If two histologies are in the same group in Table 		2, code the first or more specific histology.

**Notes:**
If the first three digits are the same as the first three digits for any histology in one of the groupings in Table 2, then the histology is considered to be the SAME.

Example: On the  table in the category ”Neuronal and neurol-glial neoplasm”,  M9505/1 is the code for ganglioglioma. If a patient has a separate Pacinian tumor that is  coded M9507/0 and is not on the table but has the same first three digits as the ganglioglioma, the Pacinian tumor is considered the same tumor and only one abstract is completed.

*Note: If two histologies are in the same group in Table 2, the first or more specific histology should be coded.

## Determining Multiple Primaries: Non-malignant (8)

**Histology (cont)**
- 	D: If the first three digits are the same and the 	histologies are from two different groups in 	the histologic groupings table, the histologies 	are considered to be **DIFFERENT.**
- 		Example: Gliomas: M9442, Gliofibroma; 	Ependymoma: M9444, Chordoid glioma

**Notes:**
If the first three digits are the same and the histologies are from two different groups in the histologic groupings table, the histologies are considered to be DIFFERENT.

Example: In the table under Gliomas is M9442/1, the code for gliofibroma. If you had a separate chordoid glioma coded  M9444/1, listed in the category of ependymoma, these are different tumors, even thought their codes have the same first three digits.  Two abstracts would be completed.

## Determining Multiple Primaries:Timing (1)

- Primary malignant CNS tumors
**NO CHANGE**
- Malignant tumors of the same site and same histology, diagnosed within 2 months:
- Tumors are counted as the **SAME** primary.
- Malignant tumors of the same site and same histology, diagnosed more than 2 months apart:
- Tumors are counted as **DIFFERENT** primary sites.

**Notes:**
The current timing rule for determining multiple primary tumors applies to malignant CNS tumors. If two or more primary malignant CNS tumors are diagnosed in the same site with the same histology within two months of the diagnosis of the first primary, the tumors are counted as one primary.  If multiple tumors of the same site are diagnosed more than two months apart, the tumors are counted as separate primary sites.  

## Determining Multiple Primaries:Timing (2)

- Primary non-malignant CNS tumors
**NEW**
- No timing rule
- If a new non-malignant tumor of the same histology** **as an earlier tumor that had been diagnosed in the same** **site is diagnosed subsequently at *any* time, it is considered to be the SAME primary tumor.

**Notes:**
The current 2-month rule does not apply to non-malignant CNS tumors. Non-malignant tumors recur in the same location and are considered the same tumor regardless of the time frame. If a non-malignant tumor of the same histology, same site, and same side recur in the same location, even after 20 years, they are still considered the same tumor.

## General Rules for Determining Multiple Primaries of CNS Sites (1)

- Multiple lesions: all **non-malignant**
- If different sites, then **DIFFERENT** primaries.
- If different histologies, then **DIFFERENT** primaries.

**Notes:**
The general rules for determining multiple primaries for non-malignant CNS tumors  were developed by the NAACCR Registry Operations Subcommittee and approved by the NAACCR UDS Committee.  

If a patient has multiple CNS tumors that are all non-malignant, they are counted as separate previously discussed  rules for site and histology.   

## General Rules for Determining Multiple Primaries of CNS Sites (2)

- Multiple lesions: all **non-malignant ** (cont.)
- If same site and same histology:
- Laterality is same side, one side unknown or not applicable, then **SAME** primary.
- Laterality is both sides, then **DIFFERENT** primaries.

**Notes:**
If the site and histology are the same, and the laterality of one tumor is  unknown or not applicable, then it is counted as a single primary.  If the site and histology are the same and the laterality is both sides, consider these separate primary tumors.  

## General Rules for Determining Multiple Primaries of CNS Sites (3)

- Multiple tumors: **One ****non-malignant** and  **one  malignant **
- Non-malignant tumor followed by malignant tumor: **DIFFERENT** primaries, regardless of timing.
- Malignant tumor followed by a non-malignant tumor: **DIFFERENT **primaries, regardless of timing.

**Notes:**
When multiple tumors include one malignant and one non-malignant tumor, they are always considered to be separate primary tumors regardless of the time of diagnosis.

## Histologic Transformation (1)

- Histologic transformation or progression to a higher grade:
- Determined by pathological review.
- Final diagnosis made by review of previous biopsies or excisions and comparison to newly biopsied or resected brain tumor
- Non-malignant tumor transforms to malignant tumor.
- Malignant tumors transforms to higher grade tumor.

**Notes:**
Transformation or progression of CNS tumors to higher grade tumors can be determined from physician statements in patient medical records or by pathological review. Pathologists develop a final diagnosis of transformation or progression by comparing slides from previous biopsies or excisions of the original tumor, to that of newly biopsied or resected CNS tumors. Tranformation may simply be reported as a recurrence with a different behavior. This transformation or grade change may result in a difference in the morphology code of the tumor. 

Histologic transformation can change a non-malignant tumor into a malignant tumor or change the malignant tumor to a higher grade with a different histologic code.

## Histologic Transformation (2)

- If a malignant CNS tumor recurs (transforms) as a higher grade tumor,
- SAME tumor.
- Do not change the histology or grade.
- Do not abstract as new primary.
- Example: Astrocytoma (M9400) transforms to glioblastoma multiforme (M9440).

**Notes:**
Malignant CNS tumors may recur or transform to higher grade tumors. This may change the morphology code of the tumor. 

If a malignant CNS tumor recurs or progresses to a higher grade tumor, it is the SAME  tumor. The original diagnosis should not be changed and a separate abstract should not be created. 

For example if an astrocytoma (M9400) recurs as a glioblastoma multiforme (M9440), code as one primary tumor because a glioblastoma multiforme is defined as a grade 4 astrocytoma. 

## Histologic Transformation (3)

- Transformation of a non-malignant tumor to a malignant tumor is rare.
- Malignant transformations include:
- Changes from WHO grade I to WHO grade II, III, or IV.
- Changes from behavior code 0 or 1 to code 2 or 3.
- Complete two abstracts:
- One for the non-malignant tumor
- One for the malignant tumor

**Notes:**
In some patients, a diagnosed non-malignant tumor  transforms into a malignant tumor; however, this occurs rarely.

Malignant transformation includes changes in the morphology in tumors from WHO grade I to WHO grade II, III, or IV,  or changes in the behavior code from 0 or 1 to codes 2 or 3.

When this malignant transformation occurs in a previously non-malignant tumor, the tumors are considered separate primaries and two abstracts are completed because of the change from non-malignant to malignant. Recording these as separate primaries will allow researchers investigating these conditions to identify cases.  This will also allow these cases to be included  when registries report only malignant cases.

This rule is similar to the rule that if an in situ tumor recurs as an invasive tumor,  a second  abstract is completed for the invasive tumor. 

Malignant transformation and progression to malignancy are the same thing.

## Histologic Transformation (4)Sequence Numbers

- Non-malignant tumors: assigned sequence numbers from the reportable-by-agreement series.
- Malignant tumors: assigned sequence numbers from the malignant series.
- Example:  Patient has a non-malignant CNS tumor that progressed into a malignant CNS tumor:
- Non-malignant tumor is sequenced as 60.
- Malignant tumor is sequenced as 00.

**Notes:**
When histologic transfomation has occurred, the sequence number for the non-malignant tumor is assigned using the reportable-by-agreement series of sequence numbers (60 through 87) which includes other non-CNS reportable-by-agreement cases. The malignant tumor is assigned a sequence number from the malignant series of sequence numbers (00 through 35).  

For example,  if a patient had one non-malignant CNS tumor that progressed into a malignant CNS tumor, the sequence number for the non-malignant tumor would be 60, and the sequence number for the malignant tumor would be 00. 

Code 60 is used in the same way as 00 in that it represents the occurrence of only one reportable-by-agreement tumor.  If a second non-malignant tumor is diagnosed or if other reportable-by-agreement cases occur, the first tumor is coded as 61 and the second as 62.

## Histologic Transformation (5)Date of Diagnosis

- Non-malignant tumors: First date that a medical practitioner diagnosed the non-malignant tumor either clinically or histologically.
- Malignant tumors:  First date that a medical practitioner diagnosed the malignant transformation either clinically or histologically.

**Notes:**
When recording the date of diagnosis for transformation cases the date for a non-malignant tumor is the date that a medical practitioner first diagnosed the non-malignant tumor either clinically or histologically.  The date of diagnosis for the malignant tumor is also the date that the malignant transformation was first diagnosed by a medical practitioner either clinically or histologically.  

## Coding Sequence Numbers (1)

- Indicates the sequence of all reportable neoplasms over the lifetime of the person.
- Codes 00 – 35:  Malignant and in situ reportable neoplasms.
- Codes 60 – 87:  Reportable-by-agreement  including non-malignant tumors diagnosed after January1, 2004.

**Notes:**
In general, the sequence of occurrence of neoplasms throughout the lifetime of a patient is recorded in the sequence number data field. Instructions for assigning sequence numbers are found in the Facility Oncology Data Standards (FORDS), Section 2: Coding Instructions, pages 34 and 35.  

Malignant and in situ neoplasms, including malignant CNS neoplasms, are assigned codes 00 through 35.  If a patient has only one primary malignant or in situ neoplasm, the sequence number assigned is 00. If a patient has multiple malignant primary neoplasms during his or her lifetime, the sequence number for the first tumor is 01, the sequence number for the second primary tumor is 02, and so forth. 

Non-malignant tumors are coded in the reportable-by-agreement range of codes 60 to 87.  If only one reportable-by-agreement tumor occurs, it is coded as 60. If subsequent nonmalignant tumors or other reportable-by-agreement tumors are diagnosed, the first tumor would is coded as 61 and the second tumor as 62. 

## Coding Sequence Numbers (2)

- Reportable-by-agreement neoplasms are defined by each facility and/or central cancer registry:
- Non-malignant CNS tumors are assigned reportable-by-agreement sequence numbers even when they are reportable.
- Codes 60 – 87

**Notes:**
Reportable-by-agreement neoplasms are defined by each facility and central cancer registry. They are not considered reportable by the COC.  Non-malignant CNS tumors are assigned reportable-by-agreement sequence numbers in the 60 to 87 range, even though they are defined as reportable.  This allows for consistency in sequence numbers for facilities that abstracted these cases prior to implementation of Public Law 107-260.  

## Coding Sequence Numbers (3)

- Sequence numbers for non-malignant CNS tumors are assigned over the lifetime of the person.
- Example:  Patient diagnosed with a non-malignant CNS tumor in January, 2003 (not reportable by state or hospital reporting rules) and diagnosed with second non-malignant CNS tumor in 2004:
- Second is sequence number 62.
- Complete abstract for the second tumor only.

**Notes:**
Sequence numbers for both malignant cases and reportable-by-agreement cases are assigned over a lifetime.  Therefore, if a patient was diagnosed with a non-malignant CNS neoplasm before reporting was required (January 1, 2004) and was diagnosed with a second non-malignant CNS neoplasm in 2004,  the second neoplasm is assigned sequence number 62, even though an abstract is required only for the second tumor.  

## Assigning Diagnosis Date

- Rules for assigning diagnosis date are the same for malignant and non-malignant tumors.
- Review source records carefully to determine _initial_ diagnosis date, regardless of whether it is a clinical or histological diagnosis.

**Notes:**
The same rules are used to assign diagnosis date for non-malignant and malignant CNS tumors.  These rules are found in FORDS, Section 2: Coding Instructions, pages 89 and 90. 

It is not unusual for a patient with a non-malignant CNS tumor to be diagnosed in a physician’s office and treated with watchful waiting.  Several years may go by before the patient receives subsequent treatment at a health care facility in the form of surgery,  radiation therapy,  or some type of systemic therapy.  Also, non-malignant CNS tumors, especially meningiomas, often recur.  

The date of initial diagnosis, not the date of subsequent treatment or date of recurrence, should be recorded in the abstract.  Health records must be reviewed carefully to determine the initial date of diagnosis by a medical practitioner, regardless of whether the initial diagnosis was clinical or histologic.

## Part IV	

- Staging
- Risk Factors
- Genetic Syndromes
- Diagnostic Tools
- Treatment
- Edits
- Data Analysis

**Notes:**
Part four covers 
Staging
Risk factors 
Genetic syndromes
Diagnostic tests
Treatment
Edits 
Data analysis

## Collaborative Stage (CS)

- A computer algorithm uses the collaborative stage (CS) data fields to calculate site-specific American Joint Committee on Cancer (AJCC) TNM stage, SEER Summary Stage 1977, and SEER Summary Stage 2000.

**Notes:**
Collaborative stage (CS) is a set of data fields that describe the extent of the disease.  For cases diagnosed on or after January 1 , 2004 CS is collected for all tumors.  An algorithm is applied to the CS data fields to calculate TNM stage, summary stage 1977, and summary stage 2000 for specific sites. No TNM stage is available for brain tumors at this time.  

## Coding Collaborative Stage (1)

- Separate sets of extension codes for:
- Brain and cerebral meninges
- Other parts of the CNS
- Glands: pituitary gland, craniopharyngeal duct, and pineal gland.

**Notes:**
The CS date fields for extension, lymph nodes, and metastasis at diagnosis are site specific.  Three site-specific sets of extension codes exist for CNS sites.  One set for brain and cerebral meninges, one set for other parts of the CNS, and one set for glands, including the pituitary gland, craniopharyngeal duct, and pineal gland.  

## Coding Collaborative Stage (2)

- Site-specific codes for lymph nodes
- Same for the Brain, cerebral meninges and other CNS.
- Code 88: Not applicable.
- For pituitary gland, craniopharyngeal duct, and pineal gland
- Code 99: Not applicable.
- Metastasis at Diagnosis
- Same for the pituitary gland, craniopharyngeal duct, and pineal gland and other CNS.
- Different for brain and cerebral meninges.

**Notes:**
The site-specific codes for lymph nodes are the same for the brain and cerebral meninges and Other parts of the CNS. For brain and cerebral meninges,  code 88- not applicable should be used.

For the pituitary gland, craniopharyngeal duct, and pineal gland code 99: Not applicable should be used. The code description includes “For pituitary gland, craniopharyngeal duct, and pineal gland.”

The pituitary gland, craniopharyngeal duct, and pineal gland and Other parts of the CNS use the same site-specific codes for metastasis at diagnosis. 

A different set of codes is used for metastasis at diagnosis in brain and cerebral meninges.

## CS Extension: Brain and MeningesC70.0, C71.0 – C71.9 (1)

**05****	****Benign or borderline brain tumors**
- 10	Supratentorial tumor confined to CEREBRAL HEMISPHERE (cerebrum) or MENINGES of cerebral hemisphere one side: frontal lobe, occipital lobe, parietal lobe, or temporal lobe
- 11	Infratentorial tumor confined to CEREBELLUM or MENINGES of CEREBELLUM on one side: Vermis, lateral lobes, median lobe of cerebellum

**Notes:**
The first set of extension codes is for cerebral meninges (C70.0) and brain (C71.0 – C71.9). The extension code structure describes what area of the brain is involved by tumor and how far the tumor has spread.  
Code 05 is assigned to non-malignant tumors.  
All of the other codes are used for malignant tumors only.  Codes 10 through 12 are assigned when the tumor is confined to a single intracranial location and is a localized tumor.  

## CS Extension: Brain and MeningesC70.0, C71.0 – C71.9 (2) 

- 12	Infratentorial tumor confined to BRAIN 	STEM or MENINGES of BRAIN STEM on 	one side: medulla oblongata, midbrain 	(mesencephalon), pons, hypothalamus, or thalamus
- 15	Confined to brain, NOS,  Confined to 	meninges, NOS
- 20	Infratentorial tumor: Both cerebellum and 	brain stem involved with tumor on	one side
- 30	Confined to ventricles - Tumor invades or 	encroaches upon ventricular system

**Notes:**
Codes 15 through 30 are used to describe localized tumors.  

## CS Extension: Brain and MeningesC70.0, C71.0 – C71.9 (3)

- 40	Tumor crosses the midline: involves the 	contralateral hemisphere,  involves corpus 	callosum (including splenium)
- 50	Supratentorial tumor extends 	infratentorially to involve cerebellum or 	brain stem
- 51	Infratentorial tumor extends 	supratentorially 	to involve cerebrum (cerebral hemisphere)
- 60	Tumor invades bone (skull), major 	blood vessel(s), meninges (dura), nerves, NOS (cranial nerves), or spinal cord/canal

**Notes:**
Tumors assigned codes 40 through 51 have crossed the midline of the brain or extended across the tentorium, and are categorized as regional disease. 
Extension code 60 is for regional disease and represents tumor invasion into the skull, blood vessels, dural meninges, nerves, or spinal cord. 

## CS Extension: Brain and MeningesC70.0, C71.0 – C71.9 (4)

- 70	Circulating cells in cerebral spinal fluid; nasal cavity; nasopharynx; posterior pharynx; or outside CNS
- 80	Further contiguous extension
- 95	No evidence of primary tumor
- 99	Unknown extension; Primary tumor cannot be accessed;  Not documented in patient record

**Notes:**
Code 70 is used to describe distant disease due to circulating cells in the cerebral spinal fluid that circulate to the spinal cord and brain.  This code also represents direct tumor extension through the skull into the nasal cavity, posterior pharynx, or further.  
Code 80 is assigned for distant extension not described in code 70. 
Code 95 is used when intracranial malignancy is diagnosed but the tumor itself cannot be found.  
Code 99 indicates that the tumor extension is unknown. 

## CS Extension: Other CNS C70.1-9, C72.0–C72.9 (1)

- Spinal meninges, meninges NOS
- Spinal cord
- Caudia equina
- Olfactory, acoustic, cranial nerve, NOS
- Overlapping brain and CNS
- Nervous system, NOS

**Notes:**
The second set of extension codes is used to  describe tumor extension for spinal meninges (C70.1); meninges NOS (C70.9); and spinal cord, cranial nerves, and other parts of the CNS (C72._).

This is compatible with the AJCC 4th edition scheme for spinal cord, but the AJCC 6th edition does not recommend a schema for these sites.

## CS Extension: Other CNSC70.1-9, C72.0–C72.9 (2)

**05****	****Benign or borderline tumors**
- 10	Tumor confined to tissue or site of origin
- 30	Localized, NOS
- 40	Meningeal tumor infiltrates nerve; nerve tumor infiltrates meninges (dura)
- 50	Adjacent connective/soft tissue; adjacent muscle
- 60	Brain, for cranial nerve tumors; major blood vessel(s); sphenoid and frontal sinuses (skull)

**Notes:**
The descriptions in this schema are less detailed than those in the first scheme.  
Code 05 is used for non-malignant tumors, and the other codes are used for malignant tumors.  
Codes 10 and 30 are used to describe localized disease.  
Code 40 is used to define regional extension for spinal and NOS tumors of the meninges.
 Code 50 is used to describe regional extension for any of the included sites.
Code 60 is used to describe regional disease for cranial nerve tumors.

## CS Extension: Other CNS C70.1-9, C72.0–C72.9 (3)

- 70	Brain except for cranial nerve tumors; bone, other than skull; eye
- 80	Further contiguous extension
- 95	No evidence of primary tumor
- 99	Unknown extension; primary tumor cannot be assessed; not documented in patient record

**Notes:**
Codes 70 and 80 are used to describe distant disease. 
Code 95 is used when intracranial malignancy is diagnosed but the tumor itself cannot be found. 
Code 99 indicates that the tumor extension is unknown. 

## CS Extension: Other Endocrine C75.1, C75.2, C75.3

- 00	In situ; non-invasive; intraepithelial
- 05	Benign or borderline tumors
- 10	Invasive carcinoma confined to gland of origin
- 30 	Localized, NOS
- 40	Adjacent connective tissue
- 60	_Pituitary and craniopharyngeal duct_: Cavernous sinus; infundibulum; pons; sphenoid body and siunses
- 	_Pineal:_ Infratentorial and central brain
- 80	Further contiguous extension
- 95	No evidence of primary tumor
- 99	Unknown extension

**Notes:**
	The third set of extension codes is used to describe tumor extension for other endocrine glands, including the pituitary gland, the craniopharyngeal duct, and the pineal gland. 
Code 00 is used for in situ neoplasms.  
Code 05 is used for benign tumors.
Codes 10 through 30 indicate local disease.  
Codes 40 through 60 indicate regional tumor spread.  Adjacent connective tissue in code 40 indicates involvement with tissues that immediately surround the structure with primary cancer, but these are not adjacent organs.  
Code 80 is used for distant disease.
Code 95 is used when malignancy is diagnosed in the gland but the tumor itself cannot be found.  
Code 99 indicates that the tumor extension is unknown. 

## CS Lymph Nodes

- 	Describes tumor involvement of regional lymph nodes.
- Code for CS Lymph Nodes is 88 (not applicable) for meninges, brain, spinal cord, cranial nerves, and other parts of the CNS.
- Code for CS Lymph Nodes is 99 (unknown, not stated) for pituitary gland, craniopharyngeal duct, and pineal gland.

**Notes:**
The data field, CS Lymph Nodes, indicates tumor involvement of regional lymph nodes.  Because no lymph node drainage occurs for CNS sites, lymph nodes for meninges (C70.0-.9,); brain (C71.0-C71.9); and spinal cord, cranial nerves, and other parts of the CNS (C72.0-C72.9) are always coded 88 (not applicable).  

The code for CS Lymph Nodes for pituitary gland (C75.1), craniopharyngeal duct (C752.), and pineal gland (C75.3) is 99 (unknown, not stated, regional lymph nodes cannot be assessed, not documented in patient record).

## CS Metastasis at DiagnosisBrain and Meninges C70.0, C71.0-9

- 	00	No; None
- 	10	Distant metastases
- 	85	“Drop” metastases
- 	99	Unknown; distant metastasis cannot 	be assessed; not documented in patient 	record

**Notes:**
	The Metastasis at Diagnosis data field is used to describes any distant metastasis identified at the time of diagnosis.  The following codes are used for cerebral meninges (C70.0) and brain (C71.0-C71.9)  
Code 00 indicates no metastasis. 
Code 10 is used for distant metastasis.  
Code 85 indicates drop metastases, which are circulating cells in the cerebrospinal fluid that have circulated to the spinal column and have begun to grow.
Code 99 is used when it is unknown if distant metastasis exist.  

## CS Metastasis at DiagnosisOther CNS and Other Endocrine  C70.1-9, C72.0—9, C75.1, C75,2, C75.3

- 00	No; None
- 10	Distant lymph node(s)
- 40	Distant metastasis except lymph nodes (code 10)
- 	Distant metastasis, NOS
- 	Carcinomatosis
- 50	(40) + (10)
- 99	Unknown; distant metastasis cannot be assessed; not documented in patient record

**Notes:**
	The following codes are used for Other parts of the CNS, which include spinal meninges (C70.1), meninges NOS (C70.9) and spinal cord, cranial nerves, and other parts of theCNS (C72.0-C72.9).   These codes are also used for the Other Endocrine glands schema that includes the pituitary gland (C75.1), craniopharyngeal duct (C75.2), and pineal gland (C75.3).
Code 00 indicates no metastasis.  
Code 10 is used for distant lymph node metastasis.  
Code 40 is used for distant metastasis other than distant lymph nodes.
Code 50 is used for a combination of distant lymph nodes and other distant metastasis.  
Code 99 is used when it is unknown if distant metastasis exists.  

## CS Site-specific Factor 1 (1) C70.0-C70.9, C71.0-C71.9, C72.0-C72.9

- 010	WHO Grade I
- 020	WHO Grade II
- 030	WHO Grade III
- 040	WHO Grade IV
- 999	Clinically diagnosed; grade unknown;
- 		Not documented in the medical record;
- 		Grade unknown, NOS

**Notes:**
The collaborative stage data fields include fields for site-specific factors which assist in validating the extent of disease at diagnosis and recording other prognostic information.  The WHO grade describes tumor aggressiveness for CNS tumors and is used by clinicians to estimate prognosis.  

WHO grade is coded in the data field “CS Site-Specific Factor 1” for meninges, brain, and spinal cord, cranial nerves, and other parts of the CNS. 

The codes in the data field are:
Code 010 	Grade 1
Code 020 	Grade II
Code 030 	Grade III 
Code 040	Grade IV 
Code 999	 WHO grade unknown or not documented. 

The WHO grade may be found on the pathology report.  If it is not recorded, code 999 should be used. 

## CS Site-specific Factor 1 (2)C70.0-C70.9, C71.0-C71.9, C72.0-C72.9C75.1- C75.3

- Code the WHO grade for CNS tumors in CS Site-specific factor 1.
- _Do not_ code WHO grade in the sixth digit histology data field.

**Notes:**
WHO grade should be coded in CS Site-Specific Factor 1.  WHO grade should not be coded in the sixth digit histology data field.  

## Possible Risk Factors

- Genetic predispositions for the development of brain tumors have been identified.
- Population-based studies suggest that no more than 4% are attributed to heredity.
- Several environmental factors that may be associated with CNS tumors.

**Notes:**
Although malignant and non-malignant CNS tumors have been the subject of  considerable study, why they occur is still unclear. 

Genetic predispositions to the development of brain tumors have been identified; however, population-based studies suggest that no more than 4% of these tumors can be attributed to heredity.  

Several environmental factors may be associated with CNS tumors, including ionizing radiation, electromagnetic fields, pesticides, sustained exposure to vinyl chlorides, and polycyclic hydrocarbons. 

## Possible Risk Factors

- Epstein-Barr virus in the DNA of primary lymphoma suggests a viral etiology for CNS tumors.
- Reference: “Surveillance of Primary Intracranial and Central Nervous System Tumors: Recommendations from the Brain Tumor Working Group.”

**Notes:**
The presence of the Epstein-Barr virus in the DNA of primary lymphoma suggests that a viral etiology for CNS tumors cannot be entirely ruled out.  Accurate and complete data are necessary to develop hypotheses for identifying the causes of CNS tumors. The heterogeneity of CNS tumors may mask their causes when histology-specific studies are limited by the number of available cases. This information can be found in “Surveillance of Primary Intracranial and Central Nervous System Tumors: Recommendations from the Brain Tumor Working Group, Appendix E.”

## Genetic Syndromes

- Genetic syndromes associated with multiple CNS tumors are:
- Neurofibromatosis I (von Recklinghausen’s disease)
- Neurofibromatosis II (bilateral acoustic neurofibromatosis)
- Von Hippel-Lindau disease
- Tuberous sclerosis (Bourneville-Pringle syndrome)
- Gorlin syndrome (Nevoid Basal Cell Carcinoma syndrome
- Hermans-Grosfeld-Spaas-Valk disease
- Li-Fraumeni syndrome
- Familial retinoblastoma
- Turcot syndrome (Adenomatous Polyposis syndrome)
- Cowden disease

**Notes:**
	Several genetic syndromes are associated with the occurrence of multiple CNS tumors.  Information on the incidence of these syndromes is incomplete because is no population-based data are available.  Genetic syndromes are not currently collected in any NAACCR data field.  

	Genetic syndromes associated with CNS tumors are: 
Neurofibromatosis I (von Recklinghausen’s Disease)
Neurofibromatosis II (bilateral acoustic neurofibromatosis)
Von Hippel-Lindau disease
tuberous sclerosis (Bourneville-Pringle Syndrome)
Gorlin syndrome (Nevoid Basal Cell Carcinoma Syndrome
Hermans-Grosfeld_Spaas-Valk disease)
 Li-Fraumeni syndrome
familial retinoblastoma
Turcot syndrome (adenomatous polyposis syndrome)
Cowden disease.

	If a syndrome is documented in the patient’s health record,  the data should be included in the narrative and the presence of these syndromes should be documented in text fields.

## Diagnostic Tools – Physical Exam

- Neurological examination
- Eye movements
- Vision
- Hearing
- Reflexes
- Balance and coordination
- Sense of smell and touch
- Abstract thinking
- Memory

**Notes:**
The first step in diagnosing a tumor in the brain or CNS is a neurological examination in which the physician evaluates eye movements, vision, hearing, reflexes, balance and coordination, the senses of smell and touch, abstract thinking, and memory.  The results help to determine if a tumor is present and what clinical work-up is needed.  Specific symptoms may also help identify the tumor location.  One-sided hearing loss, for example, is a symptom associated with acoustic neuroma, a tumor of the acoustic nerve.  Headache, muscle weakness, and seizures are symptoms of meningioma, a tumor of the cerebral or spinal meninges.  

## Diagnostic Tools: Radiology

- Computerized tomography (CT) scan
- Magnetic resonance imaging (MRI)
- Positron emission tomography (PET)
- Single photon emission computed tomography (SPECT)
- Magnetoencephalography (MEG)
- Angiography

**Notes:**
The first confirmation of CNS tumors is often diagnosis by computerized tomography (CT) or magnetic resonance imaging (MRI) scan.  CT scans use x-ray technology and a computer to view the intracranial and intervertebral structures and identify tumors.  CT may be used to identify the tumor location and type, as well as intracranial swelling or bleeding.  MRI is used to identify CNS tumors utilizing magnetic fields and a computer.  MRI provides a better picture of tumors that lie near bone. 

Positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetoencephalography (MEG) scans are not usually used as diagnostic tools.  PET is used to establish tumor grade, SPECT to determine if a tumor is low or high grade, and MEG to determine the function of the area of the brain that contains tumor.  All of these scans are used to help determine the best treatment course.  

Angiography may not be used in diagnosis, but it can help identify certain types of CNS tumors and make decisions before surgery. Dye is injected into blood vessels and then x-rays identify the dye.  Visualized blood vessels may help identify the tumor type or show if the tumor is near blood vessels that need to be avoided during surgery.  

## Diagnostic Tools: Laboratory tests

- Audiometry
- Electroencephalogram (EEG)
- Endocrine evaluation
- Evoked potentials
- Lumbar puncture
- Myelogram
- Perimetry

**Notes:**
Several laboratory tests are used to diagnose CNS tumors. 
Audiometry is a hearing test that aids in the diagnosis of acoustic neuroma. 
In patients having seizures, an electroencephalogram (EEG) is performed to evaluate the electrical currents inside the brain.  Abnormal currents may identify a brain tumor as the cause of the seizures.  
When an endocrine evaluation shows increased hormonal levels in blood and urine, a diagnosis of a tumor in the pituitary gland or hypothalamus is possible.
The electrical activity of a nerve is evaluated through evoked potentials testing which helps in the diagnosis of acoustic neuroma.  Evoked potentials testing may also be used during surgery to determine the role of specific nerves and avoid damaging them during surgery. 
Lumbar puncture is used to withdraw cerebrospinal fluid, which is examined for tumor cells and infection.  Menigioma, lymphoma, and pineal gland tumors can be identified through the evaluation of cerebrospinal fluid.  
A myelogram is the radiographic study of the spinal cord where a dye is injected into the spinal fluid.
Perimetry is the determination of the extent of the visual field for various types and intensities of stimuli. Perimetry is the quantification of the extent of the visual fields with a perimeter apparatus. Manual and computerized machines are used, but both are based on the same principles

## Diagnostic Tools

- Needle biopsy
- Needle inserted through a burr hole and tissue extracted for tissue diagnosis.
- Stereotactic biopsy
- Computer used to guided needle biopsy to   extract tissue.

**Notes:**
A biopsy is not usually the first method used to diagnose tumors.  However, biopsy is used to identify the cell type and aid in determining of the best course of treatment.  When a needle biopsy is performed, a small burr hole, is drilled into the skull.  The biopsy needle is inserted into the brain through the burr hole and tissue is removed by the needle.  A stereotactic biopsy uses a computer to guide the needle to the tumor to extract tissue. 

## College of American Pathologist   (CAP) Protocols

- Site-specific checklists
- Required to be completed in the health record in hospitals with COC-approved cancer programs for cases diagnosed January 1, 2004 and later.

- www.cap.org/cancerprotocols/protocols_index.html.

**Notes:**
The College of American Pathologists (CAP) has created site-specific protocols for pathologists to use when documenting pathologic information in patient health records.  The protocols are site specific and include a checklist, as well as background documentation information for the cytology or pathology report. A site specific checklist for each pathology specimen will be required in patient health records by the COC for approved hospital cancer programs for cases diagnosed on or after January 1, 2004.   

## Brain and Spinal CordCAP Protocols (1)

- Macroscopic
- Specimen type
- Specimen size
- Tumor site
- Tumor size

**Notes:**
	The checklist for the brain/spinal cord includes macroscopic and microscopic categories.  

The macroscopic categories are:
Specimen type: whether the specimen is from a biopsy or partial or total resection.  The registrar uses the information when coding surgical procedure of the primary site.  
Specimen size: greatest dimension of the specimen.  
Tumor site: different sites in the brain and CNS. The pathologist checks off  appropriate site. The registrar uses this information when determining the primary site.  
Tumor size: the tumor’s largest dimension.  The registrar uses this information when determining tumor size in the collaborative stage.

## Brain and Spinal CordCAP Protocols

- Microscopic
- Histologic type
- Histologic grade
- Margins
- Additional studies*
- Additional pathologic findings*
- Comments*
- *Not required for COC approval.

**Notes:**
Data elements with asterisks are not required by the COC to be completed for accreditation purposes.  

The microscopic categories are: 
Histologic type: indicates tumor morphologies commonly found in the brain and spinal cord, including non-malignant and malignant morphologies. The appropriate morphology is checked. The registrar uses the information when assigning morphology codes.
Histologic grade: On this form the histologic grade is used to indicate the WHO grade of the tumor.  If another grading system is used, it may be recorded in narrative form by the pathologist.  The registrar uses these data when recording WHO grade in a site-specific factor collaborative stage data field. This information is NOT used to assign the ICD-O-3 sixth digit.
Margins: indicate the post-surgical resection margins.  The registrar records the information in the Surgical margins of primary site data field. 
Additional studies: indicates additional pathologic findings
Comments: are not required by the COC for accreditation.   

## Treatment (1)

- Watchful waiting
- Surgery
- Radiation
- Chemotherapy
- Hormonal therapy
- Immunotherapy
- Hematologic Transplant
- 		and Endocrine procedures

**Notes:**
Treatment options for brain tumors are driven by cell type, size and location of tumor, comorbid conditions and overall health of the patient.  The first course of treatment for some patients with non-malignant CNS tumors is watchful waiting.  Over time the patient may receive surgery, radiation therapy, or some type of systemic therapy.  These treatments are considered subsequent treatment and are not coded in the abstract as first course treatment.  Some hospital cancer registries record subsequent treatment on their abstracts, but most central registries do not collect these data.  Health records should be reviewed carefully to delineate between first course and subsequent treatment.  When the original treatment plan documents that treatment will be delayed for a specific period of time, once the treatment is given, it may be recorded as the first course treatment.

## Treatment (2)

- Inoperable or inaccessible tumors may be treated with primary radiation and other systemic therapy:
- Chemotherapy, immunotherapy, and hormone therapy.
- Shunt insertion to reduce intracranial swelling is _not_ coded as surgical treatment.

**Notes:**
Patients with inoperable CNS tumors may be treated primarily with radiation  or systemic therapies, such as chemotherapy, immunotherapy, or hormone therapy.  

Surgery performed to treat symptoms, such as the insertion of a shunt to reduce swelling, is not coded as surgical treatment.  However, it may be coded as a palliative procedure by COC-approved cancer programs.

## Surgical Procedure of Primary Site

- Brain: Site-specific surgery codes
- Meninges
- Brain
- Spinal cord, cranial nerves, other CNS.

-  All Other Sites: Site-specific surgery codes
-  Pituitary gland
-  Craniopharyngeal duct
-  Pineal gland.

**Notes:**
CNS sites included in brain-related sites fall under two separate surgery schemes.
The brain codes include the brain and spinal cord as well as the meninges.
The Other sites include the pituitary and pineal glands,  and the craniopharyngeal duct.

## Surgical Procedure of Primary SiteC70-0-C70.9, C71.0-C71.9, C72.0-C72.9 (1)

- Code 10: Tumor destruction, NOS
- Laser surgery
- Laser surgery with photodynamic therapy
- Ultrasonic aspirator.
- No specimen sent to pathology from surgical procedure.

**Notes:**
The following Surgical procedure of primary site codes are used when the primary site is meninges, brain, spinal cord, cranial nerves, or other parts of the CNS.

Code 10 is assigned when a patient receives one of the listed treatments as the primary means of tumor destruction and no specimen is sent to pathology from a surgical procedure. 

This code includes laser surgery  which is when a tumor is destroyed by light energy from a laser.  This procedure may be assisted by stereotactic surgery which uses a computer image to guide the surgeon to the tumor to be destroyed.  

Laser surgery may also be combined with photodynamic therapy.  Photodynamic therapy involves the ingestion of a photosensitive drug. Treated cancer cells are exposed to a laser light when most of the photosensitizing agent has left healthy cells but is still present in the cancer cells. The photosensitizing agent absorbs the light and produces an active form of oxygen that destroys the treated cancer cells.

Ultrasonic aspiration uses ultrasonic waves to cause vibration. The vibration breaks the tumor into small pieces. The pieces are then aspirated.

## Surgical Procedure of Primary SiteC70-0-C70.9, C71.0-C71.9, C72.0-C72.9 (2)

- 20:Local Excision (biopsy) of tumor, 	lesion, or mass
- 	Specimen sent to pathology from surgical event.
- 40: Partial resection
- 55: Gross total resection
- 90: Surgery, NOS

**Notes:**
Code 20 is assigned when the most extensive surgery is a local excision or biopsy of the primary CNS tumor.  A specimen is obtained and pathologically examined.  Unlike for other sites, for meninges, brain, and other CNS, an incisional biopsy may be coded as the Surgical procedure of primary site. (See COC website for FORDS changes/corrections/clarifications for a change in the wording for code 20)

Code 40 is assigned for a partial resection  when part of the tumor is removed and there is visible residual tumor remaining after resection or debulking

Code 55 is assigned for a gross total resection  when all of the tumor is removed with no macroscopic tumor remaining. Microscopic tumor may be present.

Code 90 is used for Surgery, NOS.

## Surgical Procedure of Primary SiteC75.1, C75.2, C75.3 (1)

- Code 10: Local tumor destruction, NOS
- Code 11: Photodynamic therapy
- Code 12: Electrocautery; fulguration
- Code 13: Cryosurgery
- Code 14: Laser
- No specimen is sent to pathology from surgical events 10-14.

**Notes:**
	The following Surgical procedure of primary site codes are used when the site is pituitary gland (C75.1), craniopharyngeal duct (C75.2), or pineal gland (C75.3).  These surgery codes are the ones used for “All other sites”.  

	Codes 10-14 are used when tumor destruction is performed, but no specimen sent to pathology.   

Code 10: is for local tumor destruction, NOS.  
Code 11: is for photodynamic therapy. 
Code 12: is for electrocautery. 
Code 13: is for cryosurgery. 
Code 14: is for laser surgery.

## Surgical Procedure of Primary SiteC75.1, C75.2, C75.3 (2)

- Code 20: Local tumor excision, NOS
- Code 26: Polypectomy
- Code 27: Excisional biopsy
- 	Any combination of 20 or 26-27 WITH
- 21:	Photodynamic therapy (PDT)
- 22:	Electrocautery
- 23:	Cyrosurgery
- 24:	Laser ablation

**Notes:**
	Codes 20-27 are used to code local tumor excision with a histologic specimen sent to pathology.  Polypectomy is not performed for these sites. 

Code 20 is used when the surgery is local tumor excision, NOS, with a pathologic specimen.  
Code 26, polypectomy, is not a procedure used for the intracranial glands.  
Code 27 is used for excisional biopsy which indicates that all visible tumor was removed; however, microscopic tumor may remain. This code is used when any of the codes 21 through 24 are used with local tumor excision, NOS, or Excisional biopsy.
Codes 21 through 24 are used for photodynamic therapy (PDT), electrocautery, cyrosurgery, or laser ablation when they are used alone (without an excisional biopsy). This includes cases in which the tissue removed is less than an excisional biopsy (code 27), which is defined as removing all visible tumor. (See COC website for FORDS changes, corrections, and clarifications)

## Surgical Procedure of Primary SiteC75.1, C75.2, C75.3 (3)

- Code 25: Laser excision
- 	Specimen sent to pathology from surgical event 20-27.
- Code 30: Simple or partial surgical removal of primary site.

**Notes:**
Code 25 is used for laser excision.

Codes 25-27 are also local tumor excision codes and are only used when a pathologic specimen is collected.  

Code 30, simple or partial surgical removal of the primary site, indicates that part of the gland was removed.  

## Surgical Procedure of Primary SiteC75.1, C75.2, C75.3 (4)

- Code 40: Total surgical removal of primary site; 	enucleation
- Code 50: Surgery stated to be “debulking”
- Code 60: Radical surgery
- Partial or total removal of the primary site WITH resection in continuity (partial or total removal) with other organs
- Code 90: Surgery, NOS

**Notes:**
Code 40, total surgical removal of the primary site, is used if the complete gland is resected.

Code 50 should be used when the surgery is described as debulking; however, debulking is not commonly used with intracranial glands.  

Code 60 is for radical surgery, in which all or part of the primary site was removed with a resection of other organs.  This also is unusual surgery for intracranial glands.

Code 90, surgery NOS, is used when the surgery was conducted at another facility and no additional information is available.

## Surgical Margins of the Primary Site

- Code final status of surgical margins
- COC-required data item.
- Serves as quality control measure for pathology reports.
- May be prognostic factor in recurrence.

**Notes:**
Other surgical data fields are completed for CNS tumors just as they are for other malignant primaries. Directions for coding the data field, Surgical Margins of the Primary Site, are found in FORDS, Section 2: Coding Instructions, page 137.  The final status of the margins should be coded after tumor removal. 

## Scope of Regional Lymph Node Surgery

- Identifies removal, biopsy, or aspiration of regional lymph node(s):
- NPCR-, COC-,  and SEER-required data item.
- Code 9: Meninges, brain, and spinal cord; cranial nerves; and other parts of the CNS.
- Code as appropriate: Pituitary gland, craniopharyngeal duct, and pineal gland.** **

**Notes:**
For the data field scope of regional lymph node surgery, the directions for coding are found in FORDS, Section 2: Coding Instructions, page 138.  For tumors of the meninges (C70.0-C70.9); brain (C71.0-C71.9); and spinal cord, cranial nerves, and other parts of the CNS (C72.0-C72.9), code 9 (unknown or not applicable) should be used. CNS sites have no regional lymph nodes for CNS sites.  

## Radiation Therapy (1) 

- Radiation codes indicate type of radiation therapy performed as part of the first course of treatment.
- Records modality of radiation therapy used to deliver significant regional dose to the primary volume of interest.
- COC-required data item.
- SEER collects these data from COC-approved facilities
- NPCR: Supplementary or recommended**.**

**Notes:**
Radiation treatment is used to treat non-malignant and malignant  CNS tumors.  Some central cancer registries collect data on  radiation therapy which is a required field for SEER but only recommended for NPCR.

COC-approved cancer programs collect more specific radiation therapy data.  Data collected in the field, Radiation treatment volume, describes the anatomical structures targeted by regional radiation therapy. The coding directions for the field are found in FORDS, Section 2: Coding Instructions, pages 151 through 154. 

## Radiation Therapy (2)

- Beam radiation
- Codes 20 – 29:
- Conventional radiation therapy: from an external beam directed at the tumor.
- Energy is orthovoltage, cobalt, photon, and/or electron.
- Code 30: Boron neutron capture therapy 	(BNCT)
- Code 31: Intensity-modulated radiation 	therapy (IMRT)

**Notes:**
The general category of beam radiation includes several types of radiation therapy.  Beam radiation is most often fractionated, meaning that doses of radiation are delivered over a specified time period. 

Codes 20 through 29 are assigned when conventional radiation therapy is delivered by external beam to the tumor.  The radiation is delivered by orthovoltage (code 21), cobalt (code 22), or linear accelerator.  Orthovoltage and cobalt are old technologies that are rarely used to administer conventional radiation therapy to CNS sites.  

Linear accelerators deliver radiation using photon or electron energy.  The amount of photon energy delivered determines the code.  Photon energy is assigned codes 23 through 27.  Electron energy is assigned code 28, and mixed photon and electron energy is assigned code 29.  

A patient receiving boron neutron capture therapy (BNCT), code 30, ingests a boron compound that concentrates in the tumor cells.  External beam radiation is delivered using neutron energy.  The boron concentrated in the tumor cells captures the neutron energy and destroys the tumor cells without damaging normal tissues. BNCT is not yet widely available. 

Intensity-modulated radiation therapy, code 31, is a type of conformal radiation.  A linear accelerator delivers energy in three dimensional beams that conform to the shape of the tumor.  The intensity of the beams change as radiation is delivered allowing for short bursts of high intensity energy without damaging normal tissues.  

## Radiation Therapy (3)

- Beam radiation
- Code 32: Conformal radiation
- Code 40: Particle or proton beam
- Code 41: Stereotactic radiosurgery, NOS
- Code 42: Linac radiosurgery
- Code 43: Gamma knife

**Notes:**
Code 32, conformal radiation, also uses three dimensional beams of energy from a linear accelerator that conform to the shape of the tumor, but the intensity of the radiation delivered does not change.  Conformal radiation allows for the delivery of more intense radiation without damaging normal tissues.  The codes for IMRT and conformal radiation should only be assigned when the specific therapy is documented in the health record.
Code 40 is used for particle or proton beam radiosurgery  A cyclotron, an adapted nuclear reactor, produces proton particle beams that conform to the shape of the tumor.  Particle beam radiosurgery is used for deep seated tumors such as tumors in the pituitary gland.  The treatment is usually fractionated.  The use of this technology is growing but not yet widespread. 
Code 41 is assigned when the health record documents that the patient received stereotactic radiosurgery, but the specific type of radiosurgery is not documented.  Stereotactic radiosurgery is used for patients with localized intracranial tumors that are difficult to access through conventional surgery. Several types of stereotactic radiosurgery exist. Stereotactic radiosurgery is radiation therapy, not surgery, that is given focally in high doses with the use of a computer.  Blocks are used to ensure that the radiation is delivered only to the tumor and not to surrounding normal tissues.  It may be delivered in a single session or fractionated.  
Code 42, linac radiosurgery, uses an adapted linear accelerator to deliver fractionated doses of radiation to the tumor.  The beams are adjusted to the shape of the tumor.
Code 43, gamma knife radiosurgery, delivers focal radiation adjusted to the tumor shape using cobalt in a single dose.  Because the beams are adjusted to deliver radiation only to the tumor, little or no damage is done to normal tissues surrounding the tumor.  

## Radiation Therapy (3)

- Tumors typically treated with stereotactic radiosurgery include:

- Acoustic neuroma
- Chordoma
- Pineal tumor
- Astrocytoma

- Craniopharyngioma
- Hemangioblastoma
- Pituitary adenomal tumor

**Notes:**
Tumor types treated with stereotactic radiosurgery include:
acoustic neuroma
craniopharyngioma
chordoma
hemangioblastoma
pineal tumor
pituitary adenoma
glial tumor
astrocytoma. 

	It is important to remember that this discussion is in regards to first course of treatment.  Sometimes radiosurgery is given as subsequent treatment and should not be coded as part of first course therapy.

## Radiation Therapy (4)

- Radioactive implants
- Code 50: Brachytherapy, radiation 			implants, radiation seeding, 		radioactive implants, interstitial 		implants, intracavitary radiation 	NOS
- Code 51: Intracavitary radiation with low 		dose rate applicators (Cesium-		137, Fletcher applicator)

**Notes:**
	Radioactive implants are radiation sources placed directly into the tumor.  They are used to treat small tumors and are considered local therapy.  For some patients, more surgery follows the use of radioactive implants to remove the dead tumor cells.  Radioactive implants are often a boost modality after regional radiation with external beam. For CNS tumors, radioactive implants are often adjuvant therapy. The radioactive implants are placed in the tumor bed after partial or complete tumor resection. 

 Code 50 is used if therapy is described as brachytherapy, radiation implants, radiation seeding, radioactive implants, interstitial implants, or intracavitary radiation and NOS. 

Code 51 is used if the implants are intracavitary, or in a cavity, and the application is low dose rate with Cesium-138 or a Fletcher applicator.  

## Radiation Therapy (5)

- Radioactive implants (continued)
- Code 52: Intracavitary radiation with high 	dose rate applicator
- Code 53: Interstitial radiation with low 		dose rate sources
- Code 54: Interstitial radiation with high 		dose rate sources
- Code 55: Low dose rate interstitial or 		intracavitary radium

**Notes:**
Code 52 is also for intracavitary implants, but the application is high dose rate.  

Code 53 is assigned for low dose rate interstitial radiotherapy

Code 54 is assigned for high dose rate interstitial radiotherapy.  Interstitial indicates that the implant is placed in tissue.  

Code 55 is assigned when interstitial or intracavitary radium is implanted, however, this is used infrequently.

## Chemotherapy (1)

- Record type of chemotherapy administered as first course of treatment:
- Code 01: Chemotherapy, NOS
- Code 02: Single-agent chemotherapy
- Code 03: Multi-agent chemotherapy

**Notes:**
The chemotherapy codes are defined in FORDS, Section 2: Coding Instructions, pages 171 and 172.  

Chemotherapy may be administered as only one drug (a single agen)t, or a combination of drugs (multi-agent).  A change in the drugs administered may indicate a change in treatment course, and the new drugs may not be first course of treatment and are not coded in the data field.  Chemotherapy for malignant CNS tumors may be administered in combination with ancillary drugs. 

The ancillary drugs are not coded as part of the chemotherapy.  

## Chemotherapy (2)

- Blood-brain barrier
- Protects the brain from foreign substances, including chemotherapy.
- May be disrupted by receptor-mediated permeabilizers.
- Intrathecal chemotherapy
- Drugs directly injected into the cerebrospinal fluid by spinal injection or Ommaya reservoir.

**Notes:**
An obstacle in treating CNS tumors with chemotherapy is disruption of the blood-brain barrier.  The blood-brain barrier protects the brain from foreign substances that cause infection and functional problems.  Tumor cells in the brain are also protected when chemotherapy drugs cannot infiltrate the blood-brain barrier. Synthetic substances called receptor-mediated permeabilizers are administered to temporarily open the blood-brain barrier and allow chemotherapy drugs into the brain.  The receptor-mediated permeabilizers are not coded as chemotherapy.  

Intrathecal administration of chemotherapy avoids the blood-brain barrier because the drugs are injected directly into the cerebrospinal fluid.  The injection is given in the lower part of the spinal column.  Another method of intrathecal administration is through a catheter called an Ommaya reservoir.  The Ommaya reservoir is placed on the scalp and chemotherapy drugs are injected into the catheter and find their way to the cerebrospinal fluid.  The Ommaya reservoir is often used for administration of chemotherapy to children.  

## Chemotherapy (3)

- Interstitial chemotherapy
- Administered directly to involved tissues.
- Polymer wafers soaked in a chemotherapeutic agent are inserted in the tumor bed after tumor resection.

**Notes:**
Interstitial chemotherapy is administered directly to tissues involved with tumor.  Polymer wafers soaked in a chemotherapeutic agent are inserted in the tumor bed after tumor resection.  This method of administration avoids the blood-brain barrier and keeps the medication from affecting normal body tissues.  The method of administration of chemotherapy is not included in the code.

## Hormone Therapy

- Record systemic hormonal agents administered as first course of treatment.
- Tamoxifen and RU-486 (Mifepristone) may be used to treat meningioma.
- Steroids given to treat swelling caused by CNS tumors are not coded as hormone therapy.

**Notes:**
The codes for hormone therapy are in FORDS, Section 2: Coding instructions, pages 175 and 176. 

Hormone therapy is used to treat non-malignant CNS tumors, but in most cases the treatment is for tumor recurrence, rather than first course of  treatment.  Tamoxifen and RU-486 may be used to treat meningioma. When patients receive hormone therapy for CNS tumors, the record should be  carefully reviewed  to determine if the treatment was given as first-course therapy or to treat tumor recurrence.  For some primary sites, the administration of steroids is coded as hormone therapy.  

Steroids are often given to patients with non-malignant CNS tumors to treat intracranial swelling.  Steroids are not hormone therapy for CNS tumors and should not be coded in the data field.  Steroid administration for swelling may be coded by COC-approved cancer programs as palliative procedures.

## Immunotherapy (1)

- Record whether immunotherapeutic agents were administered as first course of treatment:
- _Angiogenesis inhibitors_ block the development of new blood vessels and starve the tumor.
- _Interleukins_ are growth factors that manipulate the tumor’s ability to grow.

**Notes:**
The codes for immunotherapy are in FORDS, Section 2:Coding instructions, pages 179 and 180.  The use of immunotherapy to treat non-malignant CNS tumors is increasing but it is not usually a  first course of treatment.  Immunotherapy, also known as biologic response modifier, uses the body’s immune system to fight cancer by changing the biologic response to the tumor. 

Angiogenesis inhibitors block the development of blood vessels.  Without new blood vessels, tumors lose their blood supply and starve.  The drug, thalidomide, and interferons that occur naturally in the body are angiogenesis inhibitors.  

Intereukins are growth factors.  When used for immunotherapy, they manipulate the tumor’s ability to grow.  

## Immunotherapy (2)

- _Gene therapy_ replaces or repairs the gene responsible for tumor growth.
- _Vaccine therapy_ allows the immune system to detect the tumor antigens and attack the tumor cells.

**Notes:**
Gene therapy is the treatment of disease by either replacing damaged or abnormal genes with normal ones, or by providing new genetic instructions to help fight disease. 

Specific immunotherapy or the use of tumor vaccines involves  immunization to boost the cancer patient’s immune response specifically against his or her own tumor. It relies on the presence of tumor-associated antigens on the surface of the malignant cells and the ability of those antigens to produce a host immune response.

## Hematologic Transplant and Endocrine Procedures

- Identify systemic therapeutic procedures administered as first course of treatment:
- Code 10: Bone marrow transplant, NOS
- Code 11: Autologous bone marrow transplant
- Code 12: Allogeneic bone marrow transplant
- Code 20: Stem cell harvest
- Code 30: Endocrine surgery and/or endocrine 		radiation therapy
- Code 40: Combination of endocrine surgery 		and/or radiation with transplant 	procedure

**Notes:**
	Hematologic transplant procedures are not used as treatment for non-malignant CNS tumors.  Children with malignant brain tumors, neuroblastoma, or lymphoma may be treated with bone marrow transplant or peripheral blood stem cell transplant.  The patients receive high-dose chemotherapy or radiation therapy to destroy the tumor cells, but the therapy also destroys the bone marrow and stem cells.  The marrow or stem cell transplant is given following the chemotherapy or radiation therapy to replace the destroyed bone marrow or stem cells.  

Code 10 is used for bone marrow transplant, NOS.  
Code 11 is used for documented autologous bone marrow transplant. Autologous means the donated marrow came from the patient. 
Code 12 is used for documented allogeneic bone marrow transplant.  Allogeneic means the marrow was donated by a person other than the patient.  
Code 20 is assigned when peripheral blood stem cell transplantation or stem cell harvest is performed.  
Code 30 is used when either surgery or radiation therapy are used as endocrine therapy. An example would be an orchiectomy for prostate cancer. 
Code 40 is used when endocrine surgery or radiation therapy are used in conjunction with a transplant procedure.

	Hematologic transplant procedures are not used to treat malignant CNS tumors in adults. The health record should be carefully reviewed to determine if the hematologic transplant procedure was given as part of first course of treatment.

## Technical IssuesEdit Checks

- NAACCR Edits Committee is developing and modifying data edits to accommodate data collection of non-malignant CNS tumors.

**Notes:**
Data edits must be changed to allow for the collection of non-malignant behavior codes. They must also allow the collection of non-malignant CNS tumor histologies by central and hospital cancer registries not already collecting the tumors prior to January 1, 2004. 

Appendix A, the ICD-O-3 Primary Brain and CNS Site and Histology Listing, lists acceptable site and morphology combinations.  Edits for these site and histology combinations will have to be added or changed.

The NAACCR Edits committee is currently making the needed changes in standard edits matafiles. 

Commercial and private cancer registry software vendors will need to incorporates these changes in their software.

## Technical IssuesData Analysis Recommendations

- Report and analyze data for non-malignant CNS tumors separately from malignant tumors.
- Footnote that pilocytic astrocytomas are included in the analysis for malignant brain tumors for continuity of trends.
- Review the standard site and histology groupings for tabulating estimates of these tumors to allow comparability of information across registries.

**Notes:**
Currently, no policy exists on how non-malignant and malignant CNS tumors should be reported and analyzed.  The NAACCR Registry Operations Subcommittee forwarded a recommendation to the NAACCR board in July 2003 suggesting that non-malignant CNS tumors be reported and analyzed separately from malignant tumors in general reports. 

For special data reports, registrars should determine if the data to be analyzed should include CNS tumors irrespective of behavior.   The clinician or epidemiologist may want to study CNS tumors of all behaviors
Historically, cancer registries have displayed lymphoma data separately regardless of the site of origin.  For some studies, the researcher may want CNS lymphoma data included with other CNS data. 

Olfactory tumors of the nasal cavity are not analyzed by registries with CNS tumors.  Some researchers want these data included with the CNS tumors.  Registrars should work closely with the researcher to ensure that the data needed for the study are included.  

Which sites and histologies are included in the analysis should be documented clearly.

## References

- Manuals, Articles, Reports
*A Primer of Brain Tumors*, 1998; American Brain Tumor Association, Des Plaines, IL; 800-886-2282 (can link to the manual through their website: _[www.abta.org](http://www.abta.org/)_)
- Gershman S, Surawicz T, McLaughlin V, Rousseau V. Completeness of Reporting of Brain and Other Central Nervous System Neoplasms. *Journal of Registry Management*, Winter 2001, Volume 28, Number 4.

**Notes:**
Here is a listing of  some manuals, articles, and reports that may be useful.

## References

- Manuals, Articles, Reports (continued)
- Fritz A, Percy C, Jack V, Shanmugaratnam K, Sobin V, Parkin D M , Whelan S. *International Classification of Diseases for Oncology*, 3rd ed. Geneva: World Health Organization, 2000
- Report:  *Surveillance of Primary Intracranial and Central Nervous System Tumors:  Recommendations from the Brain Tumor Working Group*, National Coordinating Council for Cancer Surveillance, September 1998

## References

- Websites
- American Brain Tumor Association _[www.abta.org](http://www.abta.org/)_
- American College of Surgeons, Commission on Cancer Information, Facility Oncology Data Standards (FORDS) _[www.facs.org/dept/cancer/index.html](http://www.facs.org/dept/cancer/index.html)_
- American Joint Committee on Cancer, Collaborative Stage Documentation _[www.edits.cx/cs](http://www.edits.cx/cs/)__[/](http://www.edits.cx/cs/)_

**Notes:**
Here are some websites that you may find useful. Some very long URLs (website addresses) have wrapped around into more that one line ,but the entire URL must be used, not just the 1st line.

## References

- Websites (continued)
- Brain and Neurosurgery Information Center _[www.brain-surgery.com/index.html](http://www.brain-surgery.com/index.html)_
- Brain and Spinal Cord Tumors: Hope through Research _[www.ninds.nih.gov/health_and_medical/pubs/brain_tumor_hope_through_research.htm](http://www.ninds.nih.gov/health_and_medical/pubs/brain_tumor_hope_through_research.htm)_
- Brain Tumor Guide _[http://virtualtrials.com/faq/toc.cfm](http://virtualtrials.com/faq/toc.cfm)_
- Central Brain Tumor Registry of the United States _[www.cbtrus.org/page2t.htm](http://www.cbtrus.org/page2t.htm)_

## References

- Websites (continued)
- College of American Pathologists (CAP), Protocol – Brain _[ftp://ftp.cap.org/cancerprotocols/Brain03_p.doc](ftp://ftp.cap.org/cancerprotocols/Brain03_p.doc)_
- Illustrated Glossary of Radiology: Anatomy, Examinations and Procedures; Department of Radiology and Radiological Services, The Uniformed Services University of the Health Sciences
- 	_[http://](http://rad.usuhs.mil/glossary.html)__[rad.usuhs.mil/glossary.html](http://rad.usuhs.mil/glossary.html)_

## References

- Websites (continued)
- International RadioSurgery Association _[www.isra.org/index.html](http://www.isra.org/index.html)_
- National Brain Tumor Radiosurgery Association _[www.braintumors.com/radiosurgery/radiosrugery.info#TWO](http://www.braintumors.com/radiosurgery/radiosrugery.info#TWO)_
- NCI Brain Tumor Home Page _[www.nci.nih.gov/cancer_information/cancer_type/brain_tumor](http://www.nci.nih.gov/cancer_information/cancer_type/brain_tumor/)__[/](http://www.nci.nih.gov/cancer_information/cancer_type/brain_tumor/)_

## References

- Websites (continued)
- PDQ Cancer Information Summaries: Adult Treatment _[www.cancer.gov/cancerinfo/pdq/adulttreatment](http://www.cancer.gov/cancerinfo/pdq/adulttreatment)_
- PDQ Cancer Information Summaries: Pediatric Treatment _[www.cancer.gov/cancerinfo/pdq/pediatrictreatment](http://www.cancer.gov/cancerinfo/pdq/pediatrictreatment)_
- The Brain Tumor Foundation _[www.braintumorfoundation.org/neurosurgery/ss3_3.htm](http://www.braintumorfoundation.org/neurosurgery/ss3_3.htm)_

## Acknowledgments (1)

- Prepared by
- Shannon Vann, CTR
- for the
- North American Association of Central Cancer Registries (NAACCR)
- This training presentation was supported by contract #200-2001-00044 from CDC.  The content of this training presentation does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

## Acknowledgments (2)

**Sponsors**
**Centers for Disease Control and Prevention**
**National Program for Cancer Registries**
**National Cancer Institute**
**Surveillance, Epidemiology and End Results Program**
**North American Association of Central Cancer Registries**
**American Joint Committee on Cancer**
**Collaborative Stage Task Force**

## Acknowledgments (3)

**CDC National Program of Cancer Registries Planning Committee**
- Kimberly Cantrell
- Gayle G. Clutter
- Faye Floyd
- Michael Lanzilotta
- Frances Michaud

## Acknowledgments (4)

**Materials Review Committee**
- Trista Aarnes-Leong	St. Vincent Medical Center, NAACCR** **Registry Operations Subcommittee,
- Susan Bolick-Aldrich	South Carolina Central Cancer Registry, NAACCR Registry Operations 	Subcommittee, Chair, Co-chair, Registry Operations Committee
- Gayle Clutter	CDC National Program of Cancer Registries, Registry Operations Subcommittee, 	National Coordination Council on Cancer Surveillance Brain Tumor Working 	Group, Chair
- Faye Floyd	CDC National Program of Cancer Registries
- April Fritz	NCI Surveillance, Epidemiology and End Results Program, Registry Operations 	Subcommittee
- Elaine Hamlyn	Canadian Cancer Registry, Registry Operations Subcommittee,
- Holly Howe	North American Association of Central Cancer Registries, Executive Director
- Betsy Kohler	New Jersey State Cancer Registry, NAACCR Education Committee
- Carol Kruchko	Central Brain Tumor Registry of the United States, Registry Operations 	Subcommittee, National Coordination Council on Cancer Surveillance Brain 	Tumor Working Group
- Donna Morrel	Cancer Surveillance Program of Los Angeles. Registry Operations Subcommittee
- Linda Mulvihill	North Carolina Central Cancer Registry, Registry Operations Subcommittee
- Wendy Scharber	Minnesota Cancer Surveillance Program
- James Smirniotopoulos	Professor of Radiology, Uniformed Services University, Registry 			Operations Subcommittee
- Katheryne Vance	California Cancer Registry, Registry Operations Subcommittee
- Valerie Vesich	American College of Surgeons, Commission on Cancer, Registry Operations 	Subcommittee