Hypercalcaemia in Relapsed Medulloblastoma 8 Years Post-Diagnosis; Evidence to Support PTHrP Production by Medulloblastoma Cells

Abstract

Background: A 19-year-old male presented with symptomatic hypercalcaemia as the first manifestation of relapsed metastatic medulloblastoma. Management at the time of the initial presentation 8 years earlier was with surgical excision and craniospinal radiotherapy. His biochemistry at the time of relapse and studies of medulloblastoma cell lines provide an insight into the pathogenesis of his hypercalcaemia. Methods: Parathyroid hormone-related protein (PTHrP) was measured by immunoradiometric assay in blood, and in conditioned and control media from three medulloblastoma cell lines following 72 h growth. Results: The histology at initial presentation (11 years of age) and at the time of relapse (with bone marrow infiltration and widespread bony metastases) demonstrated medulloblastoma. Ionised calcium concentrations at relapse were 2.89 mmol/l and serum PTHrP levels were increased at the same time (2.7 pmol/l; normal range: 0.7–1.8 pmol/l). There was evidence of PTHrP production by one cell line (MHH-MED-8A) while results for both other lines tested were below the limit of detection. Conclusions: Relapse 8 years after diagnosis is unusual in medulloblastoma and for this relapse to manifest as hypercalcaemia is also very uncommon. Our investigations suggest that the clinical picture was a reflection of PTHrP production by medulloblastoma cells.

Approach to the Child with Hypercalcaemia

“…The condition known as humoral hypercalcaemia of malignancy is caused by systemic secretion of PTHrP by malignant tumours and has been reported in childhood acute lymphoblastic leukaemia [41] and other childhood malignancies, including medulloblastoma and hepatoblastoma [42,43] . PTHrP has similar actions to PTH and results in increased bone resorption and enhances renal retention of calcium.…”

“…Tumours that secrete 1,25(OH) 2 D, such as ovarian dysgerminoma, cause hypercalcaemia due to a combination of enhanced osteoclastic bone resorption and enhanced intestinal absorption of calcium [42] . Ectopic secretion of PTH is a very rare cause of hypercalcaemia in adults but has not been observed in children ( table 6 ).…”

A Practical Approach to Problems of Hypercalcaemia

“…The condition known as humoral hypercalcaemia of malignancy is caused by systemic secretion of PTHrP by malignant tumours and has been reported in childhood acute lymphoblastic leukaemia [27] and other childhood malignancies including medulloblastoma and hepatic sarcoma [28,29]. PTHrP has similar actions to PTH and results in increased bone resorption and enhances renal retention of calcium.…”