Riedel thyroiditis (RT) is a rare immune-mediated inflammatory disease that destroys the thyroid parenchyma, replacing it with storiform fibrosis extending to the extrathyroidal tissue. Secondary fibrotic lesions can be associated as parts of the systemic IgG4-related disease. We present the case of a 52-year-old female patient who presented initially with subacute thyroiditis when corticosteroid treatment was initiated. After a year, compressive respiratory symptoms and dysphagia appear, and fine-needle aspiration cytology is performed to rule out malignancy, but without results. Thyroidectomy is performed, and histopathology shows scleroatrophic thyroiditis, with chronic inflammatory infiltrate containing eosinophils extending in the neighboring tissue, rare atrophic follicles, and obliterative vasculitis. Immunohistochemistry proves abundant plasma cells with IgG4 secretion; the macrophage is mainly the M2 subtype. RT is diagnosed, and a CT (computed tomography) scan is performed to detect peritracheal fibrosis and subtle pulmonary modifications. A literature review was performed that situates our findings in the context of the current literature. The last part discusses the immuno-inflammatory mechanisms behind IgG4-related diseases.

Aggressive thyroid carcinomas—anaplastic (ATC) and poorly differentiated (PDTC)—are rare but highly lethal malignant entities. Their immunophenotypical characterization is still incomplete, and no standardized diagnostic algorithms have been used. Our study retrospectively analyzes 40 thyroidectomy cases as follows: 12 ATC and 28 PDTC from 2014 to 2024 by evaluating clinical data, histopathological aspects, molecular analysis for presence of BRAFV600E and TERTC228/250T mutations, as well as immunohistochemical expression of BRAF_V600E, total BRAF, K-RAS, TERT, PAX-8, TTF-1, P53, and Ki-67. BRAF_V600E was present in 70% of cases, with higher prevalence in ATC. Total BRAF correlated positively with K-RAS and TERT and negatively with BRAF_V600E. TERT abnormal expression was highly prevalent in over 90% of cases, while loss of TTF-1 and PAX-8 is associated with anaplastic transformation. Ki-67 proliferative index had significantly higher values in ATC, thus supporting its role as a marker for aggressiveness. On univariate analysis, higher Ki-67 indices and lymph node invasion are independent predictor factors for the presence of metastases. However, on multivariate analysis, they both lose significance. Upon multivariate analysis, loss of TTF-1 and tumor necrosis were significant predictors for anaplastic histotype. Specific BRAF_V600E immunohistochemistry may be a good screening tool for the BRAF_V600E mutation. Molecularly, there is a relatively frequent association of the BRAFV600E mutation and TERTC228, mainly in the PDTC subgroup. Patterns of marker expression suggest that BRAF or RAF activation with subsequent loss of TTF-1 or PAX-8, TERT upregulation, and TP53 alteration are frequent occurrences in aggressive thyroid carcinomas. The association between TTF-1 loss and anaplastic transformation, presence of necrosis alongside BRAF_V600E, underlines their diagnostic potential in subclassifying aggressive thyroid carcinomas.