# Presentation: 463850

## Non-Hodgkin’s Lymphoma

- Luis Fayad, MD
- Assistant Professor
- Clinical Medical Director Lymphoma/Myeloma Department

## Non-Hodgkin’s Lymphoma

- Non-Hodgkin’s lymphomas (NHL) are a heterogeneous group of malignant lymphomas.  There are many different subtypes, every few years the classification is updated.  Today, morphology, immunophenotype, molecular, cytogenetics, and other techniques are used for diagnosis.
- Treatment generally depends on the aggressiveness of the disease (indolent, aggressive, or very aggressive)
- Current ICD-9-CM diagnosis code range 200.0_ – 200.8_ and 202.0_ – 202.9_

## Behavior

- Indolent – these lymphomas grow slowly.  The majority of NHLs are considered indolent.  Indolent lymphomas are generally considered incurable with chemotherapy and/or radiation therapy.
- Aggressive – these lymphomas have a rapid growth pattern.  This is the second most common form of NHL and are curable with chemotherapy.
- Very Aggressive – these lymphomas grow very rapidly.  They account for a small proportion of NHLs and can be treated with chemotherapy.  Unless treated rapidly, these lymphomas can be life threatening.

## WHO/REAL Classification of Lymphoid Neoplasms

**B-Cell Neoplasms****	****	**
**	****Precursor B-cell neoplasm**
**	****	****Precursor B-lymphoblastic leukemia/lymphoma **
**	****	****	****(precursor B-acute lymphoblastic leukemia)**
**	****Mature (peripheral) B-neoplasms**
**	****B-cell chronic lymphocytic leukemia / small lymphocytic****	**** ****	****	****	****lymphoma****	****	**
**	****B-cell prolymphocytic leukemia**
**	****Lymphoplasmacytic lymphoma****‡**
**	****Splenic marginal zone B-cell lymphoma **
**	****	****	****(**_**+**_** villous lymphocytes)***
**	****Hairy cell leukemia****	****	****	**
**	****Plasma cell myeloma/plasmacytoma**
**	****Extranodal marginal zone B-cell lymphoma of MALT type**
**	****Nodal marginal zone B-cell lymphoma **
**	****	****	****(**_**+**_** monocytoid B cells)***
**	****Follicular lymphoma**
**	****Mantle cell lymphoma**
**	****Diffuse large B-cell lymphoma**
**	****	****Mediastinal large B-cell lymphoma**
**	****	****Primary effusion lymphoma****†**
**	****Burkitt’s lymphoma/Burkitt cell leukemia****§**
**T and NK-Cell Neoplasms**
**	****Precursor T-cell neoplasm**
**	****	****Precursor T-lymphoblastic leukemia/lymphoma**
**	****	****	****(precursor T-acute lymphoblastic leukemia **
** ****‡  ****Formerly known as lymphoplasmacytoid lymphoma or immunocytoma**
** ****II  ****Entities formally grouped under the heading large granular lymphocyte **
**    ****leukemia of T- and NK-cell types**
***  Provisional entities in the REAL classification**
**	**

**Mature (peripheral) T neoplasms**
**	****	****T-cell chronic lymphocytic leukemia / small **
**	****	****	****lymphocytic lymphoma**
**	****	****T-cell prolymphocytic leukemia**
**	****	****T-cell granular lymphocytic leukemia****II**** **
**	****	****Aggressive NK leukemia**
**	****	****Adult T-cell lymphoma/leukemia (HTLV-1+)**
**	****	****Extranodal NK/T-cell lymphoma, nasal type****#**
**	****	****Enteropathy-like T-cell lymphoma****
**	****	****Hepatosplenic ****γδ**** T-cell lymphoma***
**	****	****Subcutaneous panniculitis-like T-cell lymphoma***
**	****	****Mycosis fungoides/S****ézary syndrome**
**	****	****Anaplastic large cell lymphoma, T/null cell, **
**	****	****	****primary  cutaneous type**
**	****	****Peripheral T-cell lymphoma, not otherwise **** ****characterized **
**	****	****Angioimmunoblastic T-cell lymphoma**
**	****	****Anaplastic large cell lymphoma, T/null cell, **
**	****	****	****primary systemic type**
**Hodgkin’s Lymphoma (Hodgkin’s Disease)**
**	****Nodular lymphocyte predominance Hodgkin’s lymphoma**
**	****Classic Hodgkin’s lymphoma**
**	****	****Nodular sclerosis Hodgkin’s lymphoma (grades 1 and 2)**
**	****	****Lymphocyte-rich classic Hodgkin’s lymphoma**
**	****	****Mixed cellularity Hodgkin’s lymphoma**
**	****	****Lymphocyte depletion Hodgkin’s lymphoma**
**	****	****†  ****Not described in REAL classification**
**	****	**** ****§   ****Includes the so-called Burkitt-like lymphomas****	**
**	****	****** Formerly known as intestinal T-cell lymphoma**
**	****	**** ****#  ****Formerly know as angiocentric lymphoma**

## Frequency of NHL Subtypes in Adults

**Indolent (35%)**

**Diffuse large****B-cell (31%)**

**Armitage et al. J Clin Oncol. 1998;16:2780****–****2795.**

**Mantle cell (6%)**

**Peripheral T-cell (6%)**

**Other subtypes with a ****frequency ********2% (9%)**

**Composite ****lymphomas (13%)**

**Notes:**
Key Point: The REAL/WHO classification system makes it possible to define clinically distinct types of NHL.1,2

This is a clinical evaluation of the REAL classifications in 1403 cases of NHL at 9 study sites worldwide.2
For most subtypes, diagnostic accuracy and reproducibility were ≥85%.2 
The most common NHL subtypes2
Indolent lymphomas	35%
Follicular lymphoma 	22%
Small lymphocytic lymphoma 	6%
Marginal zone B-cell MALT 	5%
Marginal zone B-cell nodal	1%
Lymphoplasmacytic	1%

Mantle cell lymphoma 	6%
Peripheral T-cell lymphoma 	6%
Diffuse large B-cell lymphoma 	31%
Composite lymphomas	13%

The Non-Hodgkin’s Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. Blood. 1997;89:3909–3918.
Armitage JO, Weisenburger DD, for the Non-Hodgkin’s Lymphoma Classification Project. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. J Clin Oncol. 1998;16:2780–2795. 

## Marginal Zone Lymphoma

- Indolent
- Currently codes to 202.8_
- Accounts for ~10% of all lymphomas
- Subcategories
- MALT (XRT?)
- Nodal
- Extra Nodal
- Splenic

## Mantle Cell Lymphoma

- Aggressive
- Currently codes to 202.8_
- Accounts for ~ 6% of all lymphomas
- Considered “incurable” with traditional RX
- Stem cell transplant is offered often as front-line consolidation treatment in “younger” patients

## Primary CNS Lymphoma

- Aggressive
- Currently codes to 202.8_
- Accounts for ~ 1-2% of all lymphomas
- Different chemotherapy treatments
- Often requires radiation to the brain:
- Brain dysfunction in younger patients
- Dementia in older patients

## Anaplastic Large Cell Lymphoma (ALCL)

- Aggressive
- Currently codes to 202.8_
- Accounts for ~ 2% of all lymphomas
- Two groups:
- ALCL ALK-1+ better prognosis, more common in younger patients and children
- ALCL ALK-1-negative : as bad as any other T-cell lymphoma

## Peripheral T-cell Lymphoma

- Aggressive
- Currently codes to 202.8_
- Accounts for ~ 7% of all lymphomas
- Worse prognosis, often associated with extranodal presentation
- Often requiring salvage treatment and transplant

## Large Cell Lymphoma

- Very Aggressive
- Currently codes to 200.0_
- Accounts for ~ 31% of all lymphomas

## Other Recommendations

- Changes to terminology
- Changes in disease process

## Questions?