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The capacity of multiple myeloma cells to generate parathyroid hormone-related protein (PTHrP) has been examined by in situ assessment of PTHrP mRNA and PTHrP protein in myeloma cells of patients in whom the disease was associated with the development of hypercalcaemia. The presence of PTHrP mRNA was evaluated by in situ hybridization using an antisense riboprobe, and PTHrP by immunohistochemistry using a monoclonal antibody, in archival bone marrow trephine specimens from 17 patients. PTHrP mRNA was detected in myeloma cells in 16 of the 17 patients, indicating a high frequency of PTHrP gene expression in myeloma cells in these subjects. PTHrP protein was, on the other hand, detected in the myeloma cells of only five of these patients. The impact of the mercury-based fixation and decalcification procedure used for processing the bone marrow trephine specimens was assessed to determine the influence of this process on the outcome of the immunohistochemical assay for PTHrP. It was shown that this preparative procedure resulted in a marked reduction of immunohistochemically detectable PTHrP, which provides a possible explanation for the lower frequency of positivity for PTHrP in myeloma cells in the bone marrow specimens. The present findings are consistent with the view that PTHrP can be generated in myeloma cells in vivo, and could contribute to osteolysis and hypercalcaemia, as in patients with cancer.

Nesidioblastosis is a well-recognized cause of persistent hypoglycaemia in neonates. We describe the case of a 24-year-old woman who presented with hyperinsulinaemic hypoglycaemia in whom an insulinoma could not be identified at operation which resulted in her undergoing a subtotal distal pancreatectomy. Histological examination revealed the presence of nesidioblastosis. The finding of nesidioblastosis in adults has been reported previously, albeit rarely. We report the use of in situ hybridization to characterize the patterns of insulin and proglucagon gene expression in the resected pancreas. Insulin expression was observed in both the islets and also the isolated nesidioblasts. The alpha-cells of the islets had lost their usual peripheral distribution suggesting that not only is insulin gene expression dysregulated but that the islets are structurally abnormal.