Aberrant CD4 Expression in Plasma Cell Myeloma With Unusual Morphology: A Rare Diagnostic Pitfall

Plasma cell myeloma (PCM) is a clonal plasma cell neoplasm diagnosed by its characteristic morphology and immunophenotype. Rarely, it shows significant morphological and immunophenotypic heterogeneity, mimicking other hematolymphoid malignancies. This case highlights PCM with deceptive morphology and aberrant T-cell marker expression, underscoring a key diagnostic pitfall. A 62-year-old female presented with an indurated lesion on the left lateral aspect of the tongue and left shoulder swelling for one month, with associated constitutional symptoms. Laboratory investigations showed anemia, raised lactate dehydrogenase, serum creatinine, and serum calcium levels. Biopsy from both sites revealed a neoplasm composed of small- to medium-sized cells in diffuse sheets with mild nuclear pleomorphism. Immunohistochemistry done on the tongue lesion revealed positivity for CD138, CD38, light chain kappa, and CD4, with a Ki-67 index of 90%. A similar immunohistochemical profile was identified in the shoulder lesion. Both lesions were diagnosed as plasmacytoma, prompting evaluation for PCM. Imaging demonstrated an enhancing soft tissue density on the anterior half of the tongue, multiple sclerotic and lytic lesions, multiple metastatic lymph nodes, and multiple nodular deposits in the cervical region. Subsequent bone marrow examination revealed 90% marrow plasmacytosis with kappa light chain restriction, confirmed by immunohistochemistry. This concluded in a final diagnosis of PCM with kappa light chain restriction and aberrant CD4 positivity. The diagnosis was corroborated with further myeloma workup, which revealed an M band in serum electrophoresis, markedly elevated serum kappa free light chain, kappa:lambda ratio, and serum IgG. Diagnosis of PCM becomes challenging in atypical presentations, lacking classical morphology and immunophenotype, necessitating a comprehensive immunohistochemical panel and close clinicopathological correlation while accounting for lineage infidelity in poorly differentiated hematologic neoplasms to avoid diagnostic pitfalls.