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.

Thyroid paraganglioma accompanied by lymph node metastasis or trachea invasion: A case report

“…Catecholamine hypersecretion can be occasionally detected in malignant paraganglioma, defined by distant metastases or extensive local invasion into adjacent tissue ( 20 ). However, as reported in the present study and previous literature ( 4 – 6 ), the levels of catecholamine were not increased in TP, which can be differentiated from other paragangliomas. Similarly, a correct diagnosis could not be established preoperatively by FNAB, except for by immunohistochemistry, until the introduction of the novel method using cell block material ( 21 ).…”

“…The diagnosis of TP is challenging, not due to its low prevalence (only 60 cases have been reported), but the cytologic and histopathologic similarities with other thyroid tumors, such as medullary thyroid carcinoma (MTC) ( 4 , 5 ). The examination of immunohistochemical staining serves an important role in the definitive diagnosis; however, to the best of our knowledge, the malignant potential of TP remains unknown ( 3 , 6 , 7 ). Since it was described by Van Miert ( 8 ) in 1964, TP has been commonly considered to have low malignant potential ( 1 , 9 , 10 ).…”

Concomitant paraganglioma and thyroid carcinoma: A case report

“…MEN is characterized by thyroid, adrenal medulla, and parathyroid neuro-endocrine cell proliferation or tumor, and the clinical manifestations are MTC, PHEO, and primary parathyroid primary hyperparathyroidism[5,6]. A few cases were reported to exhibit combinations of PHEO, abdominal paraganglioma, and papillary thyroid carcinoma[7,8]. However, the coexistence of head and neck paraganglioma and papillary thyroid carcinoma was extremely rare and only reported in three cases (Table 1).…”

Simultaneous Pheochromocytoma, Paraganglioma, and Papillary Thyroid Carcinoma without Known Mutation

“…From our review of literature of the studies found with simultaneous pheochromocytoma/paraganglioma and papillary thyroid carcinoma, the most comprehensive one was a four-case series analysis. It consisted of four female patients, one of them with synchronous PTC and PGL; 2 had heterozygous germline variants in SDHB and the four of them had -79 T>C CDKN1B gene polymorphism (3 homozygous and 1 in heterozygous state) [ 6 ]. This gene is not routinely tested in the panel for pheochromocytoma [ 7 , 8 ].…”