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Follicular epithelial dysplasia (FED) is described as Hashimoto thyroiditis-related atypia and is thought to be a possible precancerous lesion. Dysplasia as an interface between normal state and carcinoma is described in a wide range of diseases and carcinogenesis chains. On the other hand, inflammation-related atypia and cancerogenesis is also widely studied. In this study, we retrospectively analyzed 91 specimens of thyroid gland surgical resections with FED during a 10-year-period at the university hospital pathology department. The study population consisted of 68 females and 15 males aged between 22 and 86 years. The preoperative cytology diagnoses had mainly been in the indeterminate categories with prevailing AUS/FLUS results in the FED-only group (p = 0.005) and suspicious for malignancy and malignant in the group with FED plus adjacent malignancy. The decision for surgery was malignancy related in 48.2% of the cases. The lesions were sized 0.1–3.5 mm and multifocal in 45.1% of the cases. Immunohistochemically, the atypical cells were cyclin D1-positive in 67.5%, galectin-3 in 72.7%, CK19 in 85.7%, and HBME-1 in 87.0% of cases. In conclusion, FED is suggested to be a pathogenetic link between inflammation-related atypia and papillary carcinoma and thus a premalignant precursor of papillary carcinoma in HT as 36.1% of the specimens contained also papillary carcinoma in the present study. Both histopathological nuclear features and the immunoprofile of FED are widely shared with that of papillary carcinoma. [ABSTRACT FROM AUTHOR]

There is evidence that programmed death-ligand 1 (PD-L1) is expressed by thyroid follicular epithelium in thyroiditis, but the role of PD-L1 in papillary thyroid carcinoma (PTC) is poorly understood. We aimed to determine whether (1) the presence of background chronic lymphocytic thyroiditis (CLT) or Hashimoto thyroiditis (HT) influenced the expression of PD-L1 in benign follicular epithelium or in PTC and (2) if PD-L1 expression in PTC persisted with lymph node metastasis. We performed immunohistochemistry (IHC) for PD-L1 on formalin-fixed paraffin-embedded tissues. We first studied five cases of unremarkable thyroid, five cases of CLT, and five cases of HT without carcinoma. We subsequently performed PD-L1 IHC on ten cases of PTC arising in normal thyroid, ten cases of PTC arising in CLT, and ten cases of PTC arising in HT. Whenever available, we evaluated corresponding synchronous lymph node metastases from all cases for PD-L1 expression. PD-L1 expression was increased (10-90%) in all five cases of HT, only minimal expressed (1-5%) in two of five cases of CLT, and not expressed in five cases of unremarkable thyroid. PTC arising in normal thyroid or CLT nearly uniformly lacked PD-L1 expression. In contrast, PTC arising in HT demonstrated significant PD-L1 expression, which persisted in corresponding lymph node metastases. Background non-neoplastic follicular epithelium in the HT cases also demonstrated PD-L1 expression. Thyroid follicular epithelium in HT demonstrates increased PD-L1 expression, and PTC arising in a background of HT shows increased PD-L1 expression, which is retained with metastasis. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathologic entity characterized by both IgG4+ plasma cell infiltration and fibrosis in one or more organs, prototypically pancreas or salivary/lacrimal glands. IgG4-RD in the thyroid (IgG4-RTD) is an area of active study, and the relationship between IgG4-RTD and Hashimoto thyroiditis is not fully delineated due to their overlapping histologic features. Retrospective review was performed of all thyroidectomy cases demonstrating lymphocytic inflammation at a single institution over a 4-year period. Approximately half (23/38) of patients had a clinical diagnosis of Hashimoto thyroiditis (HT). Nine of the 38 patients had increased absolute and relative numbers of IgG4+ plasma cells. Patients with a clinical diagnosis of HT had increased lymphoplasmacytic inflammation, but the relative proportion of IgG4+ plasma cells was not increased compared to patients without HT. There was no correlation between IgG4 levels and the amount of fibrosis in patients with or without HT. Patients identified as having the fibrosing variant of HT were not more likely to have increased levels of IgG4+ plasma cells than those without. There is significant morphologic and immunohistochemical overlap between HT and IgG4-RTD. Future studies to identify specific characteristics of IgG4-RTD involving the thyroid are necessary to accurately define this entity. [ABSTRACT FROM AUTHOR]

Dominant nodules within Hashimoto thyroiditis (HT) may present with unique morphological features that overlap with but are not diagnostic of papillary thyroid carcinoma (PTC). Activating BRAF point mutations, RAS aberrations, and RET rearrangements are mutually exclusive events in the oncogenesis of papillary thyroid carcinoma, and RET rearrangements have been previously described in dominant nodules of HT. We identified 28 cases of Hashimoto thyroiditis with a dominant nodule, from 345 consecutive HT thyroidectomies. Screening for BRAF, RET, KRAS, NRAS, and HRAS mutations, as well as RET- PTC1 and RET- PTC3 rearrangements, was performed on paraffin-embedded material from 17 of these dominant nodules. Patients ranged in age from 29 to 76 years and were predominantly female, and the nodules ranged from 1.5 to 6.2 cm. No BRAF or RAS mutations or RET-PTC rearrangements were identified in a dominant nodule, including those with atypical, worrisome histopathologic features. Of ten cases with diagnostic concomitant or incidental papillary carcinoma, three had a V600E point mutation in BRAF, and one case had a BRAF exon 15 deletion (600–604E), while the dominant nodules were negative for mutation, supporting the notion that dominant nodules are neither malignant nor precursor lesions, and strict histological, clinical, and molecular criteria must be met for the diagnosis of papillary thyroid carcinoma. [ABSTRACT FROM AUTHOR]

Chimerism in an individual refers to the coexistence of cells arising from two distinct organisms. It can arise iatrogenically via transplant or blood transfusion, and physiologically via twin to twin transfer, or from trafficking between mother and fetus during pregnancy. Many of the diseases associated with microchimerism affect the endocrine system (e.g., autoimmune thyroid disease and diabetes mellitus type 1). Microchimerism is relevant to endocrine pathology because (a) it is associated with pregnancy, a condition of complex endocrine physiology; (b) materno-fetal and feto-maternal cellular migration must involve the placenta, itself an endocrine organ; and (c) in some species, chimerism results in states of intersexuality, a condition intimately involved with endocrine physiology. Studies of feto-maternal microchimerism in the thyroid have documented the presence of fetal cells in association with Hashimoto thyroiditis, Graves’ disease, thyroid adenoma, and papillary thyroid carcinoma. Studies of materno-fetal microchimerism have documented the presence of maternal cells in juvenile diabetes and other pediatric conditions. Microchimerism plays a potential role in the repair of diseased thyroid and pancreatic tissues. [ABSTRACT FROM AUTHOR]