Australian and New Zealand Journal of Obstetrics and Gynaecology 2004; 44: 268– 269
Case Report
Blackwell Publishing, Ltd.
Carcinoma of uterine cervix
Carcinoma of uterine cervix primarily presenting as carcinomatous meningitis: A case report Rekha WUNTKAL,1 Amita MAHESHWARI,1 Rajendra A. KERKAR,1 Shubhada V. KANE2 and Hemant B. TONGAONKAR1 Departments of 1Genitourinary and Gynecology Oncology and 2Pathology, Tata Memorial Hospital, Mumbai, India
Introduction Cervical cancer is the most common cancer among women in India.1 The frequency of distant metastasis varies from 38 to 60% in various clinical and autopsy studies, with the liver, lung and bones being the most common sites in order of decreasing frequency. 2 Patients with cancer of the cervix presenting with carcinomatous meningitis is rare; only three cases have been reported so far in the English language of published medical reports (Medline search). Carcinomatous meningitis is an uncommon but devastating complication of malignancy. Most patients with meningeal carcinomatosis fare poorly; there is a rapid decline and death occurs within weeks after symptoms develop. The aim of treatment of carcinomatous meningitis is to palliate the patient’s symptoms and to improve the quality of life.3 We report a case of a woman with carcinoma cervix, whose initial presentation was carcinomatous meningitis.
Case report A 44-year-old woman presented with a recent onset (10 days) of severe headache, vomiting, seizures, and loss of vision. On examination, she was ill, irritable and restless. She was conscious and orientated; her cranial nerves were normal except for loss of vision and she had bilateral plantar extensor responses. Fundal examination showed bilateral papilloedema. Abdominal examination was normal. On pelvic examination, she had a large endocervical growth measuring >4 cm without involvement of the paracervical tissues or fornices (International Federation of Gynaecology and Obstetrics (FIGO), clinical stage IB2). The uterus was mildly enlarged, retroverted and mobile with both adnexae free. Biopsy of the endocervical growth was reported as poorly differentiated adenosquamous carcinoma of the cervix (Fig. 1). Cerebrospinal fluid (CSF) cytology showed poorly differentiated carcinoma cells compatible with the primary cancer (Fig. 2). Biochemical analysis of CSF showed sugar 12 mg /dL, protein 172 mg /dL, chloride 113 meq /L, white blood cell count 154 cells /mm3. Computed tomography (CT) scan of the brain, abdomen and pelvis was normal except for the large endocervical growth. Her haematological and biochemical parameters were normal. Her other metastatic work-up was normal. 268
A search for a second primary cancer more commonly metastatic to the central nervous system such as the lung, breast, malignant melanoma, kidney or gastrointestinal tract was undertaken, but did not reveal any evidence of primary growth. A final diagnosis of stage IV cancer of the uterine cervix was made and we treated her with intrathecal methotrexate, external beam cranial radiation therapy, parenteral dexamethasone and five cycles of systemic carboplatin chemotherapy. The CSF cytology for malignant cells was negative after this therapy. The patient was symptomatically improved by her treatment and died 5 months after diagnosis.
Discussion Carcinomatous meningitis is an uncommon but devastating complication of malignancy. Current estimates suggest that 5 –8% of patients with malignancy suffer from this complication. The most common primary cancers associated with this condition include breast, lung, melanoma, lymphoma and leukaemias.3 Meningeal carcinomatosis complicating gynaecological malignancy, when found, can usually be attributed to ovarian cancer.4 Central nervous system metastasis in cervical cancer is generally a late event occurring as part of disseminated disease, although exceptions have been noted.5 Cancer cells reach the meninges by haematogenous or lymphatic spread by growing around and along the nerves and blood vessels, or by spreading from adjacent bone or brain parenchymal tumour deposits. The CSF flow does not seem to play a major part in the spread of meningeal cancer cells.3 In all the reported cases to date, carcinomatous meningitis carried a dismal prognosis. All three patients presented primarily as carcinoma of the cervix, two as stage IB (FIGO) and one as stage IV (FIGO). After primary treatment for carcinoma of the cervix, the time to detection of meningeal metastases varied from 42 days to 40 months.4,6,7 Histologically,
Correspondence: Dr Rekha Wunktal, Clinical Fellow, Department of Genitourinary and Gynecology Oncology, Tata Memorial Hospital, Mumbai 400 012, India. Email:
[email protected] Received 23 October 2003; accepted 9 December 2003.
Carcinoma of uterine cervix
Figure 1 Photomicrograph showing adenosquamous carcinoma of the cervix (haematoxylin and eosin stain, magnification ×20).
Figure 2 Photomicrograph showing carcinoma cells in cerebrospinal fluid.
two patients had squamous cell carcinomas6,7 and one patient had adenocarcinoma of the cervix.4 Our patient primarily presented with carcinomatous meningitis detected by the presence of malignant cells in CSF, but after the work-up she was found to have adenosquamous carcinoma of the uterine cervix. This is the first reported instance of an adenosquamous carcinoma of the cervix causing carcinomatous meningitis. The CT scan compatible with the diagnosis of leptomeningeal metastases include contrast enhancement of the basal cisterns and hydrocephalus without a mass obstructing CSF pathways.4 The CT scan of the brain showed no abnormality in our patient. Despite advances in neuroimaging techniques, the single most important diagnostic test for leptomeningeal metastasis remains CSF examination and demonstration of malignant cells in CSF.4 In the three cases reported earlier, one patient received whole brain and spine radiotherapy, intrathecal methotrexate
and methyl chloroethylnitrosourea;6 one patient received whole brain radiotherapy, intrathecal methotrexate, and decadron;4 and one patient was treated symptomatically.7 There was no improvement in symptoms and all the three patients deteriorated and died within weeks after diagnosis. The standard treatment for neoplastic meningitis includes single agent intrathecal chemotherapy and external beam radiation therapy. Radiation is generally administered to mass lesions evident on neuroimaging studies and symptomatic sites. Intrathecal chemotherapy is given to treat tumour cells in CSF and leptomeningeal surfaces, as systemic therapy is generally not effective because of the poor drug penetration through the blood–brain barrier. Patients receiving this combined treatment clear CSF of malignant cells approximately half the time, but less often have complete resolution of neurologic symptoms and signs.4 Our patient received intrathecal methotrexate, external beam cranial radiation therapy, parenteral dexamethasone and five cycles of systemic carboplatin chemotherapy. Cytologic examination of the CSF showed no malignant cells after completion of this treatment. The patient was symptomatically better and survived for 5 months after establishing the diagnosis. This is the longest reported survival in carcinomatous meningitis arising from carcinoma of the cervix. Our patient was extremely unusual in that she presented primarily with carcinomatous meningitis arising from an adenosquamous carcinoma of the cervix. In addition to intrathecal methotrexate, external beam cranial radiation therapy and parenteral dexamethasone, effective palliation with marginal prolongation of survival may be possible with the use of systemic chemotherapy in patients with meningeal carcinomatosis.
References 1 National Cancer Registry. Annual Report 1986. New Delhi: Indian Council of Medical Research, 1986; 20 –33. 2 Carlson V, Delclos L, Fletcher GH. Distant metastasis in squamous cell carcinoma of uterine cervix. Radiology. 1967; 88: 961– 966. 3 Jayson GC, Howell A. Carcinomatous meningitis in solid tumours. Ann Oncol. 1996; 7: 773 –786. 4 Aboulafia DM, Taylor LP, Crane RD, Yon JL, Rudolph RH. Carcinomatous meningitis complicating cervical cancer: a clinicopathologic study and literature review. Gynecol Oncol. 1996; 60: 313 –318. 5 Kumar L, Tanwar RK, T, Singh SP. Intracranial metastases from carcinoma cervix and review of literature. Gynecol Oncol. 1992; 46: 391–392. 6 Wead JC Jr, Creasman WT. Meningeal carcinomatosis secondary to advanced squamous cell carcinoma of cervix. Gynecol Oncol. 1975; 3: 201–204. 7 Welthman AM, Morrison G, Ingram E. A meningeal metastases of squamous cell carcinoma uterine cervix: Case report and review of literature. Diagn Cytopathol. 1987; 3: 170 –172.
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