Malignant humoral hypercalcemia associated with angiotropic large B cell lymphoma

Angiotropic large B cell lymphoma (angiotropic LCL) or intravascular large cell lymphoma (IVLCL) was diagnosed by liver and bone marrow biopsies and immunohistochemical studies in a 52 year old Caucasian male. IVLCL is a very rare disease characterized by widespread intravascular proliferation of lymphoma cells. Although it most commonly affects the central nervous system or skin and occasionally bone marrow, angiotropic LCL may be present without evidence of localized disease, as seen initially in our patient. To date, only a few cases of intravascular malignant lymphomatosis associated with parathyroid hormone related protein (PTH-rP) induced humoral hypercalcemia have been published. Our extraordinary case was diagnosed mainly by liver biopsy. The neoplastic lymphoid cells stained diffusely and strongly positive with CD-20 (Pan B) and were negative for CD-3 (Pan T) immunostain. The most significant, initial clinical finding was severe, unexplained hypercalcemia (until 18.6 mg/dl). Plasma PTH-rP showed a ten-fold increase at 8 pmol/L (normal value less than 0.8 pmol/L). Very unusual cytogenic abnormalities were found. The patient received the massive third generation combination chemotherapy comprising of Methotrexate, Doxorubicine, Cyclophosphamide, Vincristine, Prednisone and Bleomycin and developed, complete although temporary, clinical, humoral and cytogenetic remission.