A 45-year-old man from the Caribbean presents with generalized lymphadenopathy, skin nodules, lytic bone lesions, and a serum calcium of 13.5 mg/dL. Smear shows atypical lymphoid cells with deeply lobulated, cloverleaf-shaped nuclei. Hypercalcemia in this disorder is attributed to which mechanism?
- A Osteoclast activation mediated by tumor-derived cytokines such as RANKL and M-CSF ✓
- B Secretion of PTH-related protein by neoplastic cells
- C Increased 1-alpha-hydroxylase activity producing excess calcitriol
- D Direct destruction of bone by infiltrating lymphoma cells
Correct answer: A. Osteoclast activation mediated by tumor-derived cytokines such as RANKL and M-CSF
Explanation
This is adult T-cell leukemia/lymphoma caused by HTLV-1, characterized by cutaneous lesions, hypercalcemia, lytic lesions, and flower or cloverleaf cells. The hypercalcemia results from osteoclast activation driven by tumor cytokines including RANKL, M-CSF, and PTH-related peptide released by the neoplastic T cells. PTHrP alone as the principal driver is more typical of squamous cell cancers, and excess calcitriol occurs in lymphoma-associated hypercalcemia of other types.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.