Jiang, Liuyan

Abstract Background Central nervous system (CNS) involvement by mycosis fungoides (MF) is an uncommon but serious manifestation of advanced disease. Large-cell transformation (LCT) is associated with aggressive clinical behavior and increased risk of extracutaneous dissemination; however, CNS involvement remains rare and is infrequently confirmed by molecular studies. Case Presentation: We report a 77-year-old man with a 13-year history of MF who presented with progressive generalized weakness, gait instability, and weight loss. Brain magnetic resonance imaging demonstrated multiple bilateral enhancing intraparenchymal lesions concerning for primary CNS lymphoma. Cerebrospinal fluid cytology and flow cytometry were nondiagnostic. Stereotactic biopsy of a right frontal lesion revealed diffuse infiltration of brain parenchyma by large atypical lymphoid cells with a predominantly perivascular distribution. By immunohistochemistry, the lymphocytes express CD3, TCRβF1, CD30, and demonstrate diffuse p53 overexpression, complete loss of p16, and a high proliferative index (70–80%). Comparison with a prior skin biopsy which showed typical MF morphology with limited CD30 expression (< 10% of atypical lymphocytes). Polymerase chain reaction–based T-cell receptor gene rearrangement studies performed on both CNS and skin specimens demonstrated similar clonal rearrangements, confirming CNS dissemination of the original MF clone with large-cell transformation. Discussion CNS involvement in MF is rare and may occur years after the initial diagnosis, particularly in the setting of transformation. This case highlights several important features, including multifocal intraparenchymal CNS disease, nondiagnostic cerebrospinal fluid studies, and molecular confirmation of clonal relatedness between skin and CNS lesions. These findings underscore the limitations of cerebrospinal fluid-based diagnostic studies and emphasize the importance of tissue biopsy and molecular analysis in establishing the diagnosis. Conclusion We describe a rare case of MF with large-cell transformation presenting as multifocal intraparenchymal CNS disease. Molecular demonstration of identical T-cell receptor rearrangements in skin and brain lesions provided definitive evidence of metastatic dissemination. Recognition of this rare complication is essential, as new neurologic symptoms in patients with MF should prompt evaluation for CNS involvement regardless of the extent of active cutaneous disease.

Myeloid sarcoma (MS) is a tumor mass involving any extramedullary site composed of myeloid-lineage blasts with myeloid, myelomonocytic, or monocytic differentiation. Distinguishing MS from malignant histiocytic neoplasms (MHNs) is diagnostically challenging due to morphologic and immunophenotypic overlap, particularly for MS with monocytic differentiation, which can mimic MHNs, especially the subtypes of histiocytic sarcoma and interdigitating dendritic cell sarcoma, leading to potential misdiagnosis and inappropriate management. Cyclin D1 overexpression is implicated in MHNs, but its utility in differentiating these entities has not been systematically characterized. We evaluated cyclin D1 immunostaining in 43 MS cases and 30 MHNs. The median age at MS diagnosis was 59 years (range: 0.1 to 90), while the median age at MHN diagnosis was 62 years (range: 9 to 90), with heterogeneous sites of involvement. Cyclin D1 evaluation showed 100% MHNs with strong cyclin D1 positivity in ≥50% tumor cells, compared with 7% MS with weak-to-intermediate positivity in a minor subset of tumor cells. Additional immunohistochemical evaluation showed no difference in PU.1 expression in MHNs (93%) versus MS (84%) but demonstrated a higher proportion of OCT2-positivity in MHNs over MS (52% vs. 23%, P <0.05). Our study demonstrates a high sensitivity (100%) and specificity (93%) in utilizing cyclin D1 to distinguish MHNs (mature phenotype) from MS (immature phenotype) in diagnostic practice. It is particularly valuable in challenging scenarios of MS with the absence of immature/myeloid lineage-defining markers (MPO, CD34, or CD117) and provides a cost-effective tool to resolve this diagnostic pitfall, ensuring an accurate subclassification.