title: Coexistence of paraganglioma/pheochromocytoma and papillary thyroid carcinoma: a four-case series analysis.
abstract: The paraganglioma (PGL)/pheochromocytoma (PHEO)-papillary thyroid carcinoma (PTC) dyad has been reported rarely. Whether the association is coincidental or results from an underlying genetic predisposition is difficult to ascertain. We analyzed clinical and molecular data on four unrelated patients identified and treated by one of us (MJB) at a tertiary center. Patients were screened for germline variants in a panel of candidate genes: RET, VHL, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX, PTEN, CDKN1B. All patients were female; median age at diagnosis of PGL/PHEO was 45 years and at diagnosis of PTC was 49.5 years. Only one patient had family history of thyroid cancer. PTC was multifocal in 2 cases, of the classical type in 2 cases and of the follicular type in 2 cases. Two patients harbored heterozygous germline variants of uncertain significance in the SDHB gene: Ser163Pro and Ala3Gly. The -79T>C polymorphism in the CDKN1B gene was present in all patients (3 in homozygous and 1 in heterozygous state). Results deriving from a comprehensive analysis of a panel of genes suggest that there is no single explanation for the association PGL/PHEO-PTC. It may occur through different mechanisms such as the combinatorial effect of different genetic variants, be a coincidental association or, alternatively, result from genetic variants in genes still awaiting identification.
authors.affiliation: Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Rua Professor Lima Basto, 1099-023, Lisbon, Portugal. mjbugalho@ipolisboa.min-saude.pt.|Unidade de Investigação de Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Rua Professor Lima Basto, 1099-023, Lisbon, Portugal. mjbugalho@ipolisboa.min-saude.pt.|NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056, Lisbon, Portugal. mjbugalho@ipolisboa.min-saude.pt.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Bugalho
authors.affiliation: Unidade de Investigação de Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Rua Professor Lima Basto, 1099-023, Lisbon, Portugal.
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Silva
authors.affiliation: Unidade de Investigação de Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E., Rua Professor Lima Basto, 1099-023, Lisbon, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Domingues
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000150:complications* / Q000235:genetics / Q000473:pathology; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000150:complications* / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000150:complications* / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D010673:Pheochromocytoma / Q000150:complications* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000150:complications* / Q000235:genetics / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: Inherited syndromes; Papillary thyroid carcinoma; Paraganglioma/pheochromocytoma