RESUMO
Pheochromocytomas (PCCs) and paragangliomas (PGLs) (known as PPGL in combination) are rare neuroendocrine tumors of the adrenal medulla and extra-adrenal ganglia. About 40% of the patients with PPGL have a hereditary predisposition. Here we present a case-series of 19 unrelated Colombian patients with a clinical diagnosis of PPGL tumors that underwent germline genetic testing as part of the Hereditary Cancer Program developed at the Instituto Nacional de Cancerología, Colombia (INC-C), the largest reference cancer center in the country. Ten of 19 patients (52.63%) were identified as carriers of a pathogenic/likely pathogenic (P/LP) germline variant in a known susceptibility gene. The majority of the P/LP variants were in the SDHB gene (9/10): one corresponded to a nonsense variant c.268C>T (p.Arg90*) and eight cases were found to be carriers of a recurrent CNV consisting of a large deletion of one copy of exon 1, explaining 42% (8/19) of all the affected cases. Only one additional case was found to be a carrier of a missense mutation in the VHL gene: c.355T>C (p.Phe119Leu). Our study highlights the major role of SDHB in Colombian patients with a clinical diagnosis of PGL/PCC tumors and supports the recommendation of including the analysis of large deletions/duplications of the SDHB gene as part of the genetic counselling to improve the detection rate of hereditary cases and their clinical care.
RESUMO
Resumen La hipercalcemia maligna mediada por péptido relacionado con hormona paratiroidea (PR-PTH) es una manifestación poco común en tumores neuroendocrinos. Presentamos dos pacientes con tumores neuroendocrinos de páncreas con metástasis a hígado pero sin compromiso óseo en quienes se evidenció hipercalcemia maligna asociada a elevación de PR-PTH, con PTH suprimida. En ambos casos se logró normalizar temporalmente la calcemia con el uso de análogos de somatostatina, pero durante la evolución se requirió adición de bisfosfonatos en uno de ellos. Con la discusión de estos casos, la revisión de la literatura y de los casos similares publicados esperamos contribuir al mejor conocimiento de esta enfermedad.
Abstract Parathyroid hormone-related peptide-mediated hypercalcaemia (PTH-rp) is rare in patients with neuroendocrine tumours. The clinical cases are thus presented on two patients with pancreatic neuroendocrine tumours with liver metastases, but without bone involvement and with hypercalcaemia associated with elevated PTH-rp and with PTH suppressed. In both cases, it was possible to temporarily bring the calcium levels back to normal with the use of somatostatin analogues, but during the course of the disease, the addition of bisphosphonates was required in one of them. With the discussion of these cases and the review of the literature and similar published cases, it is hoped to contribute to provide better knowledge of this disease.