The Role of Parafibromin, Galectin-3, HBME-1, and Ki-67 in the Differential Diagnosis of Parathyroid Tumors

Abstract

The number of PCs in our series was small so our data mostly reflects the immunohistochemical characteristics of PAs. Parafibromin expression, galectin-3 negativity, and a Ki-67 proliferation index under 1% were estimated as beneficial in the differential diagnosis of difficult parathyroid tumors.

Atypical parathyroid adenomas: challenging lesions in the differential diagnosis of endocrine tumors

“…A significant heterogeneity of the loss of parafibromin staining ranging from 0 to 50% has been observed in atypical parathyroid adenomas across studies (Table 3). Of note, two studies reported a positive parafibromin expression either in atypical or benign adenomas, and loss of staining was observed in 100 and 31% of parathyroid carcinomas, respectively, suggesting that atypical adenomas might be considered as benign lesions (Fernandez-Ranvier et al 2009, Karaarslan et al 2015. In line with these results, Kruiff and coworkers found that atypical adenomas mostly had a positive staining of parafibromin (61%).…”

“…Other authors did not find any utility of Ki-67 staining to distinguish carcinoma from atypical adenoma (Quinn et al 2015, Hosny Mohammed et al 2017. In this regard, one study unexpectedly found low Ki-67 expression both in carcinomas and atypical adenomas (100 and 83%, respectively) (Karaarslan et al 2015) (Table 3). When Ki-67 overexpression was combined with galectin-3 overexpression and/or parafibromin loss (see below), the sensitivity and specificity in the differential diagnosis greatly increased (Hosny Mohammed et al 2017).…”

“…Different criteria have been used to evaluate parafibromin immunostaining among studies. Our group as well as others have defined as negative the complete or diffuse absence of nuclear parafibromin staining in all neoplastic cells in the presence of an internal positive control represented by the endothelial cells within the parathyroid tumors and/or rim of normal parathyroid tissue surrounding the tumor (Juhlin et al 2006, 2007, Cetani et al 2007, Fernandez-Ranvier et al 2009, Guarnieri et al 2012, Sulaiman et al 2012a, Kruijff et al 2014, Karaarslan et al 2015. At variance, other authors have regarded partial or focal loss as sufficient to indicate negative staining, providing a higher diagnostic sensitivity as demonstrated by Hu and coworkers in their meta-analysis (Hu et al 2016).…”

“…In contrast, galectin-3 overexpression is rarely found in benign parathyroid adenoma (Kumari et al 2016). Of note, Karaaslan and coworkers found a significant difference in the percentage of diffuse staining (>30% extent of staining) of galectin-3 between carcinomas, atypical adenomas and adenomas, but when considering the presence of focal positivity (≤30% extent of staining) alone, the distinction between the three groups was no more seen (Karaarslan et al 2015).…”

MECHANISMS IN ENDOCRINOLOGY: Neurodevelopmental disorders in children born to mothers with thyroid dysfunction: evidence of fetal programming?

“…Thyroid hormone abnormalities and thyroid autoimmunity have been considered both as the outcome and as the exposure in a fetal programing hypothesis. A number of studies, including studies in twins, have evaluated the association between birth weight and adult thyroid function as the outcome, and some studies have reported an association between fetal growth characteristics and the later presence of thyroid autoantibodies and adult thyroid function (25,26), whereas others found no association (27,28,29).…”