Hypercalcemia Unmasks Peripheral T-Cell Lymphoma, NOS: A Case Report

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is an uncommon and aggressive subtype of mature T-cell lymphomas, representing a heterogeneous group of malignancies without specific defining immunophenotypic or genetic features. It often presents with systemic “B” symptoms, generalized lymphadenopathy, and extranodal involvement. Diagnosis requires the exclusion of other well-defined T-cell lymphoma subtypes through detailed histopathological and immunohistochemical evaluation. Hypercalcemia is a recognized paraneoplastic manifestation in various cancers, particularly in solid tumors and some hematological malignancies; however, it is rarely the initial presentation of PTCL-NOS. We report the case of a 53-year-old female who presented with persistent fatigue, and vague abdominal discomfort. Laboratory investigations revealed severe hypercalcemia with normal renal function and intact parathyroid hormone levels. Imaging demonstrated diffuse bone marrow infiltration without radiological evidence of lytic bone lesions. Bone marrow biopsy showed diffuse infiltration by atypical lymphoid cells, and immunohistochemistry confirmed the diagnosis of PTCL-NOS. Hypercalcemia was attributed to a paraneoplastic mechanism mediated by parathyroid hormone related protein by the lymphoma cells. Following initiation of combination chemotherapy all systemic symptoms improved. This case highlights an unusual presentation of PTCL-NOS, where severe hypercalcemia preceded other overt clinical signs. The absence of lytic lesions and the rapid correction of calcium levels with lymphoma-directed therapy further support a humoral paraneoplastic process rather than direct bone destruction. It also underscores the need for a thorough and systematic diagnostic workup in patients presenting with unexplained hypercalcemia, particularly when conventional etiologies have been excluded. It also highlights the importance of considering PTCL-NOS as part of the differential diagnosis in such atypical clinical scenarios, enabling timely diagnosis and appropriate management.