A case of acute lymphoblastic leukemia accompanied with the production of parathyroid hormone-related protein

Hypercalcemia accompanied with malignant tumors is generally classified into two categories, namely with or without bone metastasis. As for the latter, bone resorption-stimulating factors produced by tumor cells, such as parathyroid hormone-related protein (PTHrP), show hormone-like effects and promote a bone resorption. Many cases have been reported regarding the production of TPTHrP in adult T cell leukemia (ATL), but few have been reported with acute lymphoblastic leukemia (ALL). We report here a similar case with ALL. A 12-year-old male presented with fever, petechiae and thrombocytopenia, and was diagnosed as ALL. We started the induction therapy and confirmed complete remission. Later, he relapsed 3 times without symptoms apart from hypercalcemia at the beginning. Elevation of the serum calcium level followed by a rise of lymphoblastic cells was recognized. Bone metastasis was excluded since bone mineral density and serum mid region PTH were normal and no abnormal findings were noticed on X rays and 99mTc bone scintigraphy. However, his urinary PTHrP level was high, and his lymphoblastic cells staining immunocytochemically with the monoclonal antibodies against the C-terminal region of PTHrP showed a positively brownish color. Finally, he died of pulmonary aspergillosis. Hypercalcemia was not related to serum PTH or bone metastasis. ATL viral infection reported as a cause of PTHrP production was also excluded from several experimental data. Therefore, we concluded that lymphoblastic cells directly produced PTHrP, and that this PTHrP played an important role in the induction of hypercalcemia.