Leptomeningeal Carcinomatosis: A Diagnosis Challenge

Leptomeningeal carcinomatosis (LC) in patients with disseminated cancer has a grave prognosis and limited therapeutic options. Diagnosis is delayed due to low CSF volume and scant cellularity. This quality improvement project was undertaken to evaluate the diagnostic performance of CSF cytology in cases with radiologic evidence and the utility of immunohistochemical (IHC) testing in stratifying atypical cases.

A 5 years retrospective review of CSF cytology, oncology notes, and MRIs from patients with non-hematologic malignancy and clinical evidence of LC was performed. A total of 39 CSF samples from 28 patients with carcinomas were identified. Cytospins were prepared, and IHC was ordered at the discretion of the pathologist. Root cause analysis was applied to examine factors contributing to equivocal results.

Of the 39 CSF samples, 49% were classified as positive for malignancy on CSF cytology, 12 as atypical/suspicious, and 8 as negative. Sixteen samples underwent IHC analysis, 11 of which confirmed the positive cytology results. IHC stains were performed only in 2 of the 12 atypical cases. Root cause analysis identified several contributors to diagnostic limitations: (1) small CSF volumes divided across multiple tests; (2) hypocellularity; (3) absence of standardized protocols for IHC use; and (4) pathologist reluctance to order IHC on cytology smears. In all cases where performed, IHC findings correlated with clinical and radiologic impressions.

This project highlights limitations of CSF cytology alone in diagnosing LC and demonstrates that adjunctive IHC testing improves diagnostic accuracy. Incorporation of IHC into routine evaluation of equivocal cases should be considered.