Incidental Diagnosis of Leptomeningeal Disease in Breast Cancer with Brain Metastases- a Case Report with Review of Literature

Abstract

Background: Breast cancer is the most common malignancy in women worldwide, with 2.3 million new cases and 6,70,000 deaths reported in 2022 (Globocan). Metastatic breast cancer affects up to 30% of patients, with brain metastases occurring in approximately 25%, especially among Human epidermal growth factor receptor 2 (HER2) positive subtypes. Leptomeningeal disease (LMD), the dissemination of tumor cells to the leptomeninges and cerebrospinal fluid (CSF), is an uncommon but devastating complication. Diagnosing LMD is often challenging due to nonspecific symptoms and overlapping imaging features with infectious or inflammatory conditions. CSF cytology remains the gold standard, though newer diagnostic techniques such as CSF-based circulating tumor DNA (ctDNA) are emerging.

Case Presentation: We report a previously treated case of a 42-year-old premenopausal woman with HER2-positive, estrogen and progesterone receptor-negative, metastatic breast cancer, who presented with acute onset of altered sensorium, fever, and irritability. Magnetic Resonance Imaging (MRI) brain showed multiple enhancing lesions in the cerebral hemispheres, cerebellum, midbrain, and thalami, with surrounding edema. MR spectroscopy demonstrated reduced choline and elevated lipid-lactate peaks, initially suggesting an infective etiology, however, CSF cytology revealed malignant cells, with immunohistochemistry positive for GATA3 and PanCK, confirming leptomeningeal metastases of breast origin. She was planned for whole brain radiotherapy (WBRT) and intrathecal methotrexate.

Conclusion: This case highlights the diagnostic challenges of LMD in HER2-positive breast cancer. Radiological and spectroscopy findings may mimic infectious processes, especially in tuberculosis-endemic regions. In ambiguous cases, reliance on CSF cytology is crucial, and adjunctive molecular diagnostics like ctDNA may further enhance diagnostic yield. Leptomeningeal metastasis, though underdiagnosed, has significant therapeutic implications. Newer HER2-directed intrathecal therapies, advanced radiotherapy techniques such as craniospinal irradiation with helical tomotherapy or proton therapy, and evolving strategies for CSF drug delivery offer promising avenues for treatment. A high index of suspicion and early CSF evaluation can lead to timely diagnosis and potentially improved survival outcomes in this difficult to treat subset.