Reinterpretation of the clinical and biological behaviors of papillary thyroid carcinoma subtypes within the 2022 WHO classification: a cross-sectional study of 768 cases.

BACKGROUND

Limited comprehensive evaluations have been conducted to date regarding the clinical behavior of papillary thyroid carcinoma (PTC) subtypes based on the 2022 World Health Organization (WHO) classification of thyroid neoplasms.

METHODS

A total of 768 patients who underwent surgical treatment for PTC were retrospectively categorized into 12 subtypes according to the 2022 WHO classification system. Clinical and pathological variables including incidence rate, age at onset, sex, anatomical location of lesions, lesion size, presence of lymph node metastasis, capsular invasion, tumor microenvironmental features, familial predisposition, and gene mutations were comparatively analyzed across these subtypes.

RESULTS

Among the 12 identified subtypes, the diffuse sclerosing subtype (DSS) demonstrated the highest incidence, followed by the encapsulated subtype (ES) and the subtype with fibromatosis/fasciitis-like stroma (WF/FLS). The spindle cell subtype (SCS) exhibited the lowest incidence. An annual increase in the incidence of WF/FLS subtypes was observed. Multifocal lesion occurrence was significantly more frequent in individuals with the DSS subtype compared to the overall PTC cohort (p < 0.05). Lymph node metastasis rates were notably elevated in the hobnail subtype (HS), tall cell subtype (TCS), DSS, and Warthin-like subtype (WLS). The prevalence of Hashimoto's thyroiditis was significantly lower in the ES subtype (p < 0.05) and significantly higher in the WLS subtype (p < 0.001), relative to the broader PTC population. Subtypes including Solid subtype (SS), WF/FLS, HS, and WLS demonstrated higher frequencies of familial tumor history. Although gene mutation rates were elevated across all subtypes, no statistically significant differences were identified among them.

CONCLUSION

Papillary thyroid carcinoma subtypes defined by the 2022 WHO classification exhibit distinct demographic, pathological, and molecular profiles. Subtypes such as hobnail, tall cell, diffuse sclerosing, and Warthin-like show aggressive features, while encapsulated, infiltrative follicular, and oncocytic types follow indolent courses.The high familial rate and increasing trend of the WF/FLS subtype provide novel insight into its possible genetic and microenvironmental influences. Recognizing these subtype-based differences may refine surgical decision-making, risk stratification, and postoperative surveillance strategies.