Breast cancer relapsing as carcinomatous meningitis. (Letters to the Editor).

To the Editor: Carcinomatous meningitis is an underdiagnosed complication of solid tumors. Autopsy data suggest a prevalence of 20% in patients who die as a result of systemic cancer. (1) It is usually suspected in patients with widely disseminated disease who present with neurologic symptoms and in whom routine imaging studies fail to show central nervous system metastases. We recently treated a patient with a history of breast cancer whose sole manifestation of relapse was neurologic deficits secondary to carcinomatous meningitis.

The patient was a 63-year-old white woman who underwent biopsy of a suspicious right-sided breast lesion detected with routine mammography in June 2001. The mammogram showed a Grade II infiltrating lobular carcinoma, for which the patient underwent modified radical mastectomy. Fourteen sampled axillary lymph nodes were negative for tumor. The tumor cells expressed estrogen and progesterone receptors and were negative for HER-2/neu overexpression. Subsequently, she underwent four cycles of adjuvant chemotherapy with doxorubicin and cyclophosphamide and was placed on tamoxifen therapy afterward. She was followed closely with periodic mammography and remained disease-free until February 2003, when she developed weakness in her lower limbs. Her neurologic deficits worsened during the next few weeks, and she soon became nonambulatory. A physical examination revealed that she had right-sided ptosis and decreased muscle strength (3/5) in both lower limbs. Her deep tendon reflexes could not be elicited. The rest of t he physical examination, including the breast examination, was unremarkable. Nerve conduction studies were consistent with bilateral L5 and S1 radiculopathy. Gadolinium-enhanced MRI scans of her head and spine were unremarkable. Cerebrospinal fluid (CSF) analysis revealed elevated proteins (98 mg/dl) and no pleocytosis but low glucose (8 mg/dl). The cytologic examination initially did not show any malignant cells, but a second CSF sample was found to have mucin-containing malignant cells consistent with breast primary. A mammogram and a CT scan of chest, abdomen, and pelvis did not show any evidence of metastatic disease. Intrathecal chemotherapy was recommended, but the patient opted for comfort care only.

This case report highlights the need to maintain a high index of suspicion for carcinomatous meningitis in patients with a history of cancer who present with neurologic deficits. Low CSF glucose is a clue to the diagnosis, even in the absence of pleocytosis. Gadolinium-enhanced MRI can provide definitive evidence of leptomeningeal metastases, although its reported sensitivity is only 75%. (2) CSF cytology remains the "gold standard" for diagnosis, and its sensitivity approaches 98% for three or more CSF samples per patient. (3) Timely diagnosis with appropriate treatment has led to long-term disease-free survival in some patients with breast cancer. (4)

Sumit Gaur, MD

Department of Hematology-Oncology

St. Elizabeth's Medical Center

Boston, MA

References

(1.) Posner JB. Neurologic Complications of Cancer. Philadelphia, F.A. Davis Co., 1995, p 143.

(2.) Straathof CS, de Bruin HG, Dippel DW, Vecht CJ. The diagnostic accuracy of magnetic resonance imaging and cerebrospinal fluid cytology in leptomeningeal metastasis. J Neurol 1999;246:810-814.

(3.) Glantz MJ, Cole BF, Glantz LK, Cobb J, Mills P, Lekos A, et al. Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer 1998;82:733-739.

(4.) Moots PL, Harrison MB, Vandenberg SR. Prolonged survival in carcinomatous meningitis associated with breast cancer. South Med J 1995;88:357-362.