Utilizing Immunoglobulin G4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis.

BACKGRUOUND: Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished. METHODS: This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm2 were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery. RESULTS: Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm2 was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT. CONCLUSION: This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.

A Matched-Pair Analysis of Nuclear Morphologic Features Between Core Needle Biopsy and Surgical Specimen in Thyroid Tumors Using a Deep Learning Model.

Core needle biopsy (CNB) is a method that can be used as an alternative to fine-needle aspiration for the sampling of thyroid nodules to provide a preoperative diagnosis. Nuclear atypia is of paramount importance in diagnosing thyroid tumors. We aimed to identify the differences in nuclear morphologic features between CNB and surgical specimens. Quantitative image analysis was performed on whole slide images (WSI) of paired CNB and surgical specimens from 50 follicular cell-derived tumors including adenoma, non-invasive follicular thyroid neoplasm with papillary-like nuclear features, and carcinoma. The nuclear features of tumor cells were extracted from WSI using a pre-trained deep-learning model. In matched-pair analysis, the ratios (surgical specimens-to-CNB) of the mean nuclear diameters and the areas of the tumor cells were 1:0.75-0.85 and 1:0.54-0.73 according to the tumor types, respectively. The ratio of the nuclear optical density of tumor cells was 1.68-2.44 times higher in CNB specimens than it was in their corresponding surgical specimens. The significant nuclear size reduction and optical density increase in CNB were most prominent in papillary carcinoma cells. Normal follicular cells showed nuclear size reduction in CNB but no change in nuclear optical density between CNB and surgical specimens. Nuclear vacuolar artifacts mimicking nuclear pseudoinclusions were frequently seen in CNB regardless of the tumor types. In conclusion, tumor cells in CNB showed marked nuclear shrinkage, darker nuclear staining, and nuclear vacuolar changes. Awareness of the morphological differences according to the sampling types can facilitate correct diagnosis in thyroid histopathology.