# Leptomeningeal Carcinomatosis Secondary to  Gastroesophageal Adenocarcinoma:

Authors: Gunita Mitera; Daryl Roitman; Gina Pohani; Michael Brennan; Allen Fox; Cyril Danjoux; Emily Sinclair; Edward Chow
Journal: Scholarly Research Exchange
 (2009)

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## Abstract

We present a 68-year-old male with leptomeningeal carcinomatosis (LC) from gastroesophageal junction carcinoma. Three months following epirubicin, cisplatin, 5-flurouracil (ECF) chemotherapy, the patient suffered from gait imbalance, headache, and dysarthria. CT and MRI imaging revealed LC throughout the brain and spine. The patient was prescribed dexamethasone and treated with a course of palliative radiation to the whole brain, 2000cGy/5. Additionally, the regions of symptomatic disease in the spine included the top of L4 vertebrae to the bottom of the S2 vertebrae which was treated with 2000cGy/5, and the top of the C5 vertebrae to the bottom of the T4 vetebrae received 800cGy/1. The radiation treatment did provide short-term symptom control; however, the patient eventually passed away from his illness.  While LC remains a devastating complication of malignant disease, it has been rarely discussed in GI tumors, specifically GE junction adenocarcinomas. Therefore treatment options must be considered using first principles based on management of LC in more common disease sites. With early detection, and for patients with good performance status, palliative radiation utilizing hypofractionated regimens to sites of symptomatic involvement may improve quality of life for this group of unfortunate people.


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## Body

## 1. Introduction

Leptomeningeal
carcinomatosis (LC) results from “diffuse infiltration of the leptomeninges by
malignant cells originating from an extrameningeal primary tumor site” [1]. LC caused by metastatic gastroesophageal
adenocarcinoma has been rarely reported in the English literature. To date,
only two cases have been described, the first was in 2001 and the other in 2003
[2, 3]. LC has mostly been reported with breast cancer, prostate cancer, and
melanoma [2–5]. We describe
the third reported case of LC with brain involvement secondary to
adenocarcinoma of the gastroesophageal (GE) junction (Figure 1). In particular,
unlike the first two reported cases where supportive measures were used to
palliate symptoms; this is the first reported case where radiotherapy was used
to control local symptoms.Microscopic pathology slides from the GE junction biopsy
showing poorly differentiated adenocarcinoma.
(a)(b)


## 2. Case History

A 68-year-old male presented with a history of progressive
dysphagia and weight loss, and was subsequently referred to a
gastroenterologist. Outpatient endoscopy revealed, in the lower esophagus, an
area of narrowing with significant ulceration, nodularity, and friability
consistent with neoplasm. The gastroesophageal junction was at 38 cm from the
incisors and the upper limit of the abnormality was at 34 cm from the incisors.
The stomach revealed mild diffuse antral erythema, and the duodenum appeared
normal. Biopsy of the gastroesophageal
junction lesion revealed poorly differentiated adenocarcinoma (Figure1). As
the patient also had a history of prostate cancer in 1997 that was treated with
surgical resection and radiation therapy, immunohistochemistry was
performed on the GE biopsy, revealing that the tumor cells were positive for CK7
and CDX2, and negative for CK20 and PSA, consistent with a primary
gastrointestinal adenocarcinoma. In addition, serum PSA levels had
remained stable with no evidence of recurrent prostate cancer. He also had a
history of hypertension and peptic ulcer disease, a remote history of smoking,
and reported drinking three to four alcoholic drinks per week.On examination,
his weight was 66.9 kg and his
height was 163.5 cm. His general physical examination including his abdominal
examination was normal. There was no evidence of clubbing, scleral icterus, or
peripheral lymphadenopathy.Computed
tomography (CT) revealed circumferential thickening involving eight centimeters
of the esophagus/stomach averaging 1.5 centimeters in thickness with associated
enlarged gastrohepatic and retroperitoneal lymph nodes as well as a 2.3
centimeter liver mass. There were two soft tissue nodules noted within the left
lung, each measuring 6 millimeters, and a less-defined density noted within the
right middle lobe. The impression was that of a gastroesophageal junction
carcinoma with lymph node metastatic disease. Endoscopic ultrasound revealed a
carcinoma, extending between 34 and 43 centimeters from the incisors to the
Z-line with a fundus perfectly normal, as well as the rest of the stomach. The
tumor penetrated through the muscularis propria at approximately 35
centimeters, invading the surrounding structures.He was treated
with standard epirubicin, cisplatin, 5-fluorouracil (ECF) chemotherapy from
September 2007 through March 2008 for a total of six cycles. Following 3 cycles
of chemotherapy, CT scans demonstrated an excellent response with decreased
esophageal/stomach thickening and decreased lymphadenopathy. The liver lesions
and lung nodules had also improved. After completion of six cycles of ECF
chemotherapy, further regression of the esophageal/stomach thickening was seen
and no liver metastases were identified. After completing his sixth cycle of
chemotherapy, the patient developed progressive fatigue and mucositis. Given
the excellent response to treatment and the significant toxicities experienced,
the patient elected to take a break from chemotherapy following the completion
of the sixth cycle of ECF.Three months
after discontinuing chemotherapy, the patient presented to the emergency
department with a two-day history of gait imbalance, headache, and dysarthria.
He had no other neurological symptoms. Contrast-enhanced head CT revealed
several enhancing lesions at the gray white junction throughout the cerebrum
and cerebellum consistent with CNS metastases. There was edema evident around
the lesions; the largest lesion measured 11 millimeters in the right frontal
lobe (Figure2). CT scan from the base of the skull to T6 revealed no definite
evidence of skeletal metastases. There were equivocal foci of enhancement
posteriorly within the upper thoracic spinal canal and/or cord. Concern about
meningeal and spinal cord metastases prompted further imaging. Subsequent MRI revealed diffuse drop
metastasis around the cervical and thoracic cords, associated with a large area of abnormal
signal in the cord, consistent with nodular leptomeningeal disease (Figure 3).Contrast-enhanced CT scan of the brain.
(a)(b)Figure 3
MRI of spinal cord.The patient was
started on dexamethasone and referred to the Rapid Response Radiotherapy Clinic
in Toronto, Canada. This clinic accepts
patients on an urgent basis for consideration of palliative radiation therapy.
The patient was treated with a course of palliative whole brain radiation
treatment, 2000cGy in 5 fractions using 6MV photons. Management of the
leptomeningeal carcinomatosis with radiation therapy was deferred because of
concerns of toxicity and would be reserved for any area of focal neurological
involvement.After the first
treatment of whole brain radiation therapy, the patient developed bowel and
bladder dysfunctions
and left-sided weakness, requiring admission to hospital. An urgent MRI of the
brain and spine revealed the same findings as previously mentioned. As a result
of the new neurological deficits, the patient was prescribed radiation to the
lumbar-sacral spine, specifically from the top of the L4 vertebrae to the
bottom of the S2 vertebrae. A prescription of 2000cGy in 5 fractions was given using
6MV photons, using a parallel opposing technique. Additionally, one fraction of
radiotherapy from the top of the C5 vertebrae to the bottom of the T4 vertebrae
was also prescribed to treat the localized pain described by the patient. This
was treated with a single 800cGy dose using 6MV photons with a direct posterior
beam. All three sites were delivered concurrently.The patient was
unable to return home due to persistent symptoms and was transferred to the
hospital of his treating oncologist. Given the patient poor performance status
and prognosis, there was no further chemotherapy recommended. The patient
symptoms which included urinary retention, bowel incontinence, neck pain, and
headaches resolved postradiation treatment. He regained control of his bowel
function and was able to ambulate with the assistance of a walker. The patient
was subsequently transferred to a palliative care facility. Following transfer,
the urinary retention returned about 1 week afterwards, requiring permanent
catheterization. However, the pain was under fairly good control, and there were no more complaints
of headache. However, about 3 weeks after transfer, the patient slowly
succumbed to his illness and passed away.


## 3. Discussion

Leptomeningeal
carcinomatosis is a serious metastatic complication of solid tumors. Its
related morbidity can be devastating to patients. The median survival despite
treatment is between 3–6 months. The
occurrence of LC remains to be relatively uncommon; however, there is no
precise published estimate of its incidence. It has, generally, been quoted as
occurring in approximately 5% of cancer patients [2, 3, 5].
For patients with solid tumors, the incidence of LC can range from 4–15%. Postmortem
results of 2375 patients published in 2005 by Memorial Sloan-Kettering Cancer
Centre found an incidence of 8%. LC may occur at any stage of a neoplastic
disease as either a presenting sign or late complication. LC mainly manifests
in primary breast (12–14%), lung (10–26%), and
melanoma (17–25%) [1].While the
incidence of LC from a GI primary cancer has been reported to be between 4–14%, it is worth
examining this statistic further [1]. A literature review published by Lisenko
et al. of the incidence of LC from solid tumors from 1975–2001 found only 7
out of 210 patients to have a stomach cancer primary (3.33%) and 1 out of 210
patients to have LC from a GE junction tumor (0.48%) [4]. Ku at el. have documented an
incidence of LC from a colorectal cancer primary to be approximately 1–3% [5], and according to Okumura et
al. there have only been 3 reported cases in the literature of LC from
esophageal cancer [3, 6]. Since gastroesophageal tumors may be classified as
either gastric or esophageal, or else placed in their own separate category, it
is useful to review its treatment as a separate category within GI cancers. To
our knowledge, there have only been two case reports of the management of LC
from a gastroesophageal junction primary cancer [4, 7] (Table 1). All three
cases presented with histology of adenocarcinoma, and this was consistent with
the most commonly reported histology in the literature [2, 4, 7]. Table 2
compares our case with the most common cerebral, cranial nerve, and spinal
signs and symptoms of LC.Table 1
Two reported cases (cases 1 and 2) of leptomeningeal carcinomatosis secondary to
gastroesophageal adenocarcinoma compared with the current case report (case 3).
Patient demographicsCase 1 (2001)Case 2 (2003)Case 3 (2008)Age at primary diagnosis (years)475067SexMaleMaleMalePresenting symptoms related to LCNoneConfusion, fluctuating levels of consciousnessLeft-sided weakness; urinary incontinence; constipation for 5 daysOther sites of metastasesMediastinal, supraclavicular lymph nodes, lungs, skin, adrenal glandNoneBrain; liver; lung; spinal vertebraePathologyPoorly to moderately differentiated adenocarcinomaAdenocarcinomaPoorly differentiated adenocarcinomaHeadacheNoneNoneYesMental statusConfusionConfusionNormalNeurological signs and symptomsNoneNoneLeft-sided weakness; urinary incontinence; constipation for 5 daysCT (head) findingsNormalProminent nodular enhancement involving meningesHead: demonstrate diffuse brain metastasesSpine: sclerosis of vertebrae;
disc degeneration; and hyperdensity; no comment on LCMRI findingsNot orderedNot orderedNodular LC throughout the spinal cordCSF cytologyPositivePositiveNot orderedTreatment for LCPalliative care measuresPalliative care measuresRadiation to symptomatic areas; referral for intrathecal chemotherapy after
radiotherapyOutcomeNo mention of final outcomePatient level of consciousness continued to deteriorate and passed away 5 months
after the initial onset of symptomsGood symptom control, recurrent urine retention following radiation, passed away 3-4 weeks posttreatmentTable 2
The most common cerebral, cranial nerve, and spinal signs and symptoms.
SymptomInitially (%)At any time (%)SignInitially (%)At any time (%)Cerebral*Headache3840Papilledema1212Mental change2530Abnormal mental status5050Nausea/vomiting1220Seizures1415Gait difficulty4668Extensor plantar(s)5066Cranial nerveVisual loss812Ocular muscle paresis3038Diplopia820Trigeminal neuropathy1214Hearing loss69Facial weakness2526*Dysphagia24Hearing loss2020Spinal*Pain2540*Nuchal rigidity1617*Back1850Reflex absence/decrease6076Radicular1225Dermatomal sensory loss5050Paresthesias1042*Lower motor neuron weakness7878*Weakness2250———*Indicates signs or symptoms which this case presented with [1].**Total may be more than 100% as patients may have more than one sign or symptom.Our patient
presented to our clinic with neurological spinal symptoms and headaches,
however, experienced no change in mental status. Since LC from the GE junction
is not well documented in the literature, this case was managed with the same
rationale as LC from other primary adenocarcinomas. Lumbar puncture, CT, and
MRI are used to diagnose leptomeningeal carcinomatosis. CT and MRI of the brain
and spine can be used to diagnose leptomeningeal carcinomatosis; however, MRI
with T1-weighted gadolinium-enhanced sequencing is the gold standard for
delineating changes in the spinal cord. In particular, it can detect abnormal
meningeal enhancement that is characteristic of LC. MRI is also 1.5–2 times more
specific and sensitive for LC [4]. Particularly, detecting LC from solid tumors
on MRI as compared to hematological cancers is easier [1]. Interestingly, in our
reported case the CT scan of the spinal cord was reported as normal. However,
it was the MRI that detected the nodular LC throughout the spine. The nodular
intradural enhancement is documented in the literature as a common finding for
LC [1].Further workup
for leptomeningeal carcinomatosis is obtained in cerebral spinal fluid (CSF)
from a lumbar puncture test. However, 40–50% of patients
will have a false negative result upon initial cytology [1]. The two cases documented in
the literature did obtain a positive cytology report, while in our case CSF was
not obtained. This is because a diagnosis through cerebrospinal fluid cytologic
examination or by gadolinium-enhanced MRI scans of the brain and spine is equally acceptable. As
a result, relying on imaging results to make the diagnosis of LC prevented any
delay in treatment for this patient.For LC that
arises from solid tumors, the intent of treatment is palliative. Surgery is
often reserved for relief of hydrocephalus. Radiotherapy to the whole spine is
usually deemed to be very toxic for this patient population. Thus, radiotherapy
is often reserved for focal palliative treatment to symptomatic sites or bulky
areas of disease as visualized on imaging [1, 8].
Additionally, intrathecal chemotherapy (commonly methotrexate) can also be
offered adjuvantly to patients who have low-tumor burden, good performance
status, and a relatively good prognosis. However, to date the optimal treatment
regime has not been defined and therapeutic outcomes remain poor [5, 9]. Given that the median
survival without treatment is 4–6 weeks, a
combination of radiation and chemotherapy for such patients has shown an improvement
in 50% of cases along with prolonging the median survival [4]. While the two
reported cases in the literature were not offered any active treatments, our
patient did receive focal radiotherapy due to his relatively good performance
status and his eagerness to receive active treatment. Particularly,
lumbar-sacral irradiation (top of L4 vertebrae to bottom of sacrum) was
prescribed to provide relief of pain and stabilize the cauda equine symptoms
the patient was experiencing (left-sided weakness, urinary incontinence, and
constipation). Additionally, since the patient was complaining of focal nuchal
rigidity and pain, a single 800cGy using 6MV was also prescribed to the neck to
help alleviate this particular symptom. This did prove to provide symptom
relief for a short duration of time, arguably providing him with an improved
quality of life for that time period.The treatment
care plan executed for this particularly rare case of leptomeningeal
carcinomatosis from a primary GE junction adenocarcinoma was in keeping with
documented standards of care for symptomatic LC from solid tumors. However, to
date the optimal treatment regime has not been defined and therapeutic outcomes
unfortunately remain poor. A review of LC in gastric carcinomas (which behave
similarly to GE junction tumors) suggests that good performance status and use
of intrathecal chemotherapy were independent prognostic factors for survival
[10]. In this case, the patient was treated with radiotherapy because of good
performance status at the time of treatment. However, he was unfit to undergo
further chemotherapy, particularly because of ongoing toxicity from previous
ECF treatment. When comparing this case to the others in the literature, the
ultimate outcomes were very short survivals, as predicted. It is unclear why
radiotherapy was not used in these other cases, and it can be postulated that
the benefit would have been minimal in the first case [4], given the
extensiveness of extraaxial disease. In the second case [7], it seems that the
patient poor performance status precluded any form of active treatment. It was
also mentioned in that paper that earlier identification of disease may
influence the overall poor outcome. It is, therefore, important to utilize the
literature on more common sites of LC involvement, including breast and
melanoma, in order to individualize patient treatment. If LC is identified
early and is localized to the CNS, with good performance status, this may
influence the use of radiotherapy and/or chemotherapy as a treatment modality. However,
one must determine if the treatment will do more harm than good, especially as
time intervals to death remain so short once LC is diagnosed. Therefore,
although the goal of treatment for such cases should always be to provide
symptom relief if possible, this should also always be balanced against the
quality of life that the patient and family wish to accept for the remainder of
their illness.


## 4. Conclusion

Leptomeningeal
carcinomatosis remains a devastating complication of malignant disease. It has been rarely discussed in GI tumors,
specifically GE junction adenocarcinomas.  Treatment is supportive in nature. Because of
the scarcity in the literature, one must utilize first principles based on
management of LC in more common disease sites. If identified early, and in
patients with good performance status, palliative radiation utilizing
hypofractionated regimens ranging from 800cGy/1 to 2000 cGy/5, to sites of
symptomatic involvement may play a role in improving quality of life for
patients, despite the poor life expectancy in this group of unfortunate people.



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