Genomics and Epigenomics in Parathyroid Neoplasia: from Bench to Surgical Pathology Practice

Abstract

The majority of parathyroid disease encountered in routine practice is due to single parathyroid adenoma, of which the majority arise as sporadic tumors. This is usually a straightforward diagnosis in endocrine pathology when in the appropriate clinical setting, although subsets of cases will exhibit atypical histological features that may warrant additional immunohistochemical and genetic analyses to estimate the malignant potential. Parathyroid carcinomas on the other hand, are bona fide malignant tumors characterized by their unequivocal invasion demonstrated through routine histology or metastasis. The ultimate endpoint for any molecular marker discovered through laboratory investigations is to be introduced in clinical routine practice and guide the surgical pathologist in terms of diagnostics and prognostication. For parathyroid tumors, the two main diagnostic challenges include the distinction between parathyroid adenoma and parathyroid carcinoma, as well as the pinpointing of hereditable disease for familial screening purposes. While numerous markers on genetic, epigenetic, and protein levels have been proposed as discriminative in these aspects, this review aims to condense the scientific coverage of these enigmatic topics and to propose a focused surgical pathology approach to the subject.

Cyto‐morphological features of parathyroid lesions: Fine‐needle aspiration cytology series from an endocrine tumor referral center

“…The resting phase correspond to the inactive chief cell and is characterized by the accumulation of glycogen and lipid droplets and thus have a bright appearance by light microscopy (clear chief cells). Similarly, intracellular fat tissue content has been proven to inversely correlate with the endocrine activity in normal and neoplastic parathyroid glands 16 . As most pathological parathyroid glands contain various amount of conventional chief cells and clear chief cells, this correlation between metabolic activity and cellular phenotypes opens a window for the cell proportions and characteristics to differ from the time of the FNAC performed and the subsequent surgical removal.…”

Parafibromin Abnormalities in Ossifying Fibroma

“…While loss of parafibromin immunoreactivity was not uniformly seen in the ossifying fibromas examined in this study, parafibromin staining is routinely positive in histologically similar benign fibro-osseous jaw lesions of other etiologies, both in the present study and another study [ 7 ]. Parafibromin staining therefore could be useful as a diagnostic tool in equivocal cases, in a similar manner to its use in parathyroid tumors with atypical features suggestive of, but not unequivocal for, carcinoma [ 32 , 33 , 41 ].…”

CaSR expression in normal parathyroid and PHPT: new insights into pathogenesis from an autopsy-based study

“…Parathyroid adenoma was defined as a single enlarged gland with a well-circumscribed or encapsulated diffusely hypercellular lesion. Parathyroid hyperplasia was defined as cases with multi-glandular disease showing diffuse or nodular hypercellularity of more than one gland [3]. The largest of these glands was used for performing immunohistochemistry (IHC).…”

“…Increased serum calcium level activates CaSR, which inhibits PTH secretion and parathyroid cell proliferation [2]. CaSR is mutated at germline level in familial hypocalciuric hypercalcemia type 1 and subsets of cases with familial isolated hyperparathyroidism [3].…”