| Abstract|| |
Neoplastic meningitis is seen in five to ten percent of patients with solid tumors and is characterized by multifocal neurological signs and symptoms. The diagnosis is established by imaging, cerebrospinal fluid (CSF) cytology, and radioisotope CSF flow studies. Gastric adenocarcinoma is a rare cause of neoplastic meningitis. We review here CSF cytology results from our Oncology center obtained over two years and report three cases of gastric adenocarcinoma with cytologically positive CSF.
Keywords: Cerebrospinal fluid; gastric adenocarcinoma; neoplastic meningitis.
|How to cite this article:|
Kotwal SA, Bisht S, Dawar R. Metastatic gastric adenocarcinoma to the cerebrospinal fluid: A report of three cases. J Cytol 2008;25:25-7
|How to cite this URL:|
Kotwal SA, Bisht S, Dawar R. Metastatic gastric adenocarcinoma to the cerebrospinal fluid: A report of three cases. J Cytol [serial online] 2008 [cited 2020 May 28];25:25-7. Available from: http://www.jcytol.org/text.asp?2008/25/1/25/40655
| Introduction|| |
Neoplastic meningitis (NM) develops in five to ten percent of patients with solid tumors and the incidence seems to be increasing.  The disease is more commonly seen in patients with disseminated progressive systemic disease. Common solid tumors causing NM are carcinoma of the breast, lung, and malignant melanoma. Gastric carcinomas rarely metastasize to the brain. The overall prognosis remains dismal in spite of chemotherapy (systemic and intrathecal) and radiotherapy directed at the intracranial metastatic site(s).  We report here three cases of metastatic gastric adenocarcinoma to the cerebrospinal fluid (CSF) and analyze pointers to the observed increase in incidence.
| Case Reports|| |
A 33 year-old woman presented with pain in her abdomen. On examination, she was found to have ascitis, which was then tapped and found to have malignant cells. Guided fine needle aspiration (FNA) of enlarged mesenteric lymph nodes showed metastatic adenocarcinoma. Upper gastrointestinal endoscopy revealed an irregular gastric growth (3 cm × 4 cm) with central necrosis, present in the cardia and the fundus. Biopsy was found to reveal mucin-secreting adenocarcinoma. Spiral computed tomography (CT) of the head showed foci of vasogenic edema in the parietal and frontal lobes. Magnetic resonance imaging (MRI) brought out leptomeningeal metastasis with white matter edema and enhancing nodules. CSF examined subsequently was positive for malignant cells. With a diagnosis of Stage IV carcinoma of the stomach, she was given two cycles of Pacletaxel and Carboplatin over three weeks along with palliative radiotherapy (36 gGy) to the skull.
A 38 year-old female, a known diabetic, presented with abdominal distension since one and half months. She also had headache and sporadic vomiting. Ultrasound of the abdomen showed multiple homogeneous, soft tissue mass lesions in the lower abdomen and pelvis with bilateral adnexal masses, moderate ascitis, omental thickening, bilateral adrenal masses, and peripancreatic lymph nodes. She had sclerotic lesions in the sternum, dorsolumbar vertebrae, sacrum, and both iliac bones. MRI of the brain did not show any definite intracranial lesion. Radioisotope bone scan revealed multiple skeletal metastases. Upper gastrointestinal endoscopy showed three antral ulcers, each 0.5 cm in diameter, around the pyloric ring. Biopsy was diagnostic of signet ring adenocarcinoma. MRI of the head done as a part of the metastatic work-up, showed metastatic infiltration of the marrow of the skull and petrous temporal bases with a lesion in the temporal fossa. Ascitic fluid and CSF were positive for malignant cells. Treatment with cranial radiotherapy, intrathecal chemotherapy followed by systemic chemotherapy was planned with palliative intent.
A 60 year-old male presented with complaints of pain in the abdomen and vomiting. Upper gastrointestinal endoscopy revealed a nodular ulcerated lesion in the fundus and body of the stomach. Ultrasound showed diffuse mural thickening of the stomach (linitis plastica) with perigastric streaking and omental and mesenteric edema. Endoscopic biopsy of the stomach lesion revealed a diagnosis of a moderately differentiated adenocarcinoma. The patient was planned for neoadjuvant chemotherapy followed by total gastrectomy and adjuvant chemotherapy. After six cycles, symptoms improved and a good radiological response was seen. Within six months however, he developed fever, weakness, and his consciousness worsened in three days. Contrast-enhanced computed tomography (CECT) of the head showed diffuse cerebral atrophy. Meningitis was suspected and the CSF examined was positive for metastatic adenocarcinoma. Intrathecal triple drug therapy was given but his condition worsened and the patient expired within one week.
The CSF samples were processed by the Cytospin method and the smears stained with May-Grünwald-Giemsa and Papinocolaou stains. Smears from the three cases showed similar findings. Tumor cells were large with ample cytoplasm, pleomorphic vesicular nuclei, and prominent nucleoli [Figure - 1]. Cytoplasmic mucin was seen in two of the cases on mucicarmine staining. In addition, follow-up CSF tappings done during intrathecal drug administration showed macrophages.
| Discussion|| |
Cancer cells seed the leptomeninges by hematogenous dissemination and infiltration through arachnoid vessels or the choroid plexus. Once inside the leptomeningeal compartment, the tumor cells spread by bulk CSF flow. Although a gold standard, cytological examination is extremely insensitive with 40-50% of NM showing negative cytology. 
We reviewed records of CSF-positive patients with solid tumors seen over the last two years (26 patients). CSF examination was done to look for NM in solid malignancies only in patients with clinicoradiological findings suggesting intracranial metastasis. Of these, gastrointestinal carcinoma showed highest positivity followed by carcinoma of the breast and lung.
The presenting clinical symptoms in our patients were headache, vomiting, and decreasing consciousness. Imaging studies like MRI and CECT are very useful in demonstrating leptomeningeal metastasis. The primary tumor was extensive and NM was present at the time of the initial diagnosis in two of our patients. Similar reports in literature suggest that NM can occur before it is possible to identify a clinically obvious primary. 
A retrospective study conducted at the MD Anderson Cancer Centre of CSF-positive cases between 1944 and 2002 reported the incidence of NM in gastric cancer as 3.52% and conclude that its incidence has increased in the past several years.  Increased detection with better imaging modalities may be the cause of this observation. Another factor may be the more effective therapy available for systemic cancer resulting in a subset of surviving patients now at a risk of late stage development of this complication.
In fact, older literature has reports on leptomeningeal involvement as a secondary event in already diagnosed gastric cancer. NM in asymptomatic cases of gastric adenocarcinoma, as in two of our cases, is even rarer. 
In spite of systemic and intrathecal chemotherapy, subsequent CSF taps remained positive in all our cases. NM in gastric carcinoma portends a significant worsening of prognosis with survival ranging from 2 to 38 weeks (median four to five) after its diagnosis.  Although earlier recognition of NM in gastrointestinal malignancies is supposed to have a significant impact on patient outcome from palliative and survival standpoints, even focused treatment by oncophysicians has not improved the outcome. However, it offers palliation and often affords stabilization and protection from further deterioration.
| Acknowledgment|| |
Dr. Meenu Walia and Dr. Praveen Bansal, Medical oncologists, Dharamshila Cancer Hospital and Research Centre, Delhi - 110096, India.
| References|| |
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Department of Pathology and Blood Transfusion, Dharamshila Cancer Hospital and Research Centre, Vasundhra Enclave, Delhi - 110 096
Source of Support: None, Conflict of Interest: None
[Figure - 1]