Role of cerebrospinal fluid cytology in 'carcinomatous meningitis' masquerading as 'tuberculoma'.

Sir,

Cerebrospinal fluid (CSF) examination for malignant cells is a time-honored procedure, used in the diagnosis of primary and metastatic central nervous system (CNS) tumors including hematolymphoid neoplasms. Its utility in assessing the results of therapy has also been stressed.[1] An early diagnosis of neoplastic meningitis may assist in palliation and stabilization of the patient, preventing further deterioration.[2] Major studies have shown 20-40% of patients harboring malignant CNS tumors to manifest with a positive CSF cytology.[1] Neoplastic meningitis is seen in 5-10% of patients with solid tumors such as carcinoma of the breast/lung, malignant melanoma and rarely gastric carcinoma.[2] Clinically[2] and even by radiological means such as computed tomography or magnetic resonance imaging (MRI), tuberculoma/tuberculous meningitis may mimic a brain tumor/neoplastic meningitis.[345] Prognosis of patients with CNS metastasis is poor[2] while, the patients with tuberculoma respond well to antituberculous therapy (ATT).[34] Hence, a distinction between the two conditions is critical. Although, a brain biopsy is useful, it is not always a feasible option.[4] In a situation like this, a simple CSF cytology proves more useful.[234] We report a case to exemplify this fact.

Our patient, a 36-year-old female was being investigated for giddiness, vomiting and headache of 7 days duration. She had bilateral lateral rectus palsy, but no neck rigidity. A prior CSF examination from the side-laboratory had shown 100% lymphocytes. Magnetic resonance imaging (MRI)-brain was suggestive of tuberculosis with leptomeningeal enhancing lesions; based on which an ATT with steroids had also been started. At this stage, a contrast enhanced computed tomography (CECT) of the brain suggested a possibility of metastasis and a repeat CSF examination was carried out. May-Grünwald-Giemsa and Papanicolaou stained smears of the centrifuged CSF sample showed discrete as well as, a few tiny clusters of pleomorphic malignant cells exhibiting a glandular pattern, vesicular nuclei with prominent nucleoli and a few cells displaying cytoplasmic vacuolations [Figure 1a]. Features were consistent with an adenocarcinoma-deposit. Subsequently, the patient had a downhill course, developed left-sided hemiplegia and died within a week of admission. The post-mortem brain biopsy confirmed the metastatic adenocarcinoma [Figure 1b] with immunohistochemical markers favoring an ovarian origin, with a positive expression of cytokeratin 7 (CK 7), carcinoembryonic antigen (CEA) and cancer antigen (CA)-125 [Figure 1b inset]; and negativity for CK 20 and estrogen receptor.

Figure 1

(a) A cerebrospinal fluid smear showing clusters of malignant cells in an inflammatory cellular background (MGG, ×200); inset shows atypical cells with mucin vacuoles indicative of adenocarcinoma (MGG, ×400), (b) the post-mortem biopsy of brain showing adenocarcinoma cells exhibiting pleomorphic, vesicular nuclei and prominent nucleoli (H and E, ×400); inset shows positive expression of cancer antigen-125 suggestive of an ovarian primary (IHC, ×400)

However, no details are available regarding the ovaries as the patient was admitted with clinical history suggestive of tuberculous meningitis. Significance of this case is that even a detailed clinical examination had failed to identify the malignant lesion. An MRI and initial CSF examination from the side-laboratory were indicative of tuberculosis, due to which ATT was also started. Only a CECT performed at later stage suggested the possibility of metastasis. The second CSF sample examined by the cytopathologists confirmed the CECT diagnosis. We assume that the malignant cells in the initial sample, perhaps, were overlooked in the side laboratory due to inexperience of the technician, who reported it. This emphasizes the need for CSF samples to be examined by an experienced cytopathologist in order, not to miss out a crucial finding in a critical situation.