P53 loss and BRAF V600E mutation suggest potentially divergent pathways to aggressiveness in high grade...

High-grade differentiated thyroid carcinoma (HGDTC) is a newly defined tumor entity in the 2022 WHO classification of thyroid tumors. Its diagnostic criteria, molecular characteristics, and clinical management system are still not fully developed, posing significant challenges for clinical diagnosis and treatment.

Case 1 was a 75-year-old female who complained of intermittent cough for over a month. Color Doppler ultrasound of the neck indicated diffuse changes in the thyroid tissue, with nodules in the right lobe of the thyroid accompanied by coarse calcification. The mass was completely resected, and the postoperative pathology confirmed high-grade differentiated thyroid carcinoma. The microscopic manifestation was follicular carcinoma (30% in the solid area and 70% in the non-solid area). Immunohistochemical detection of P53 showed abnormal complete absence of expression in the solid area and non-solid area of the tumor cells. The patient was followed up for 5 months after surgery, and no tumor recurrence was observed. Case 2 was an 88-year-old female who complained of a mass in the anterior neck region for over 10 months, with intermittent rupture and bleeding for half a day. The mass was partially resected, and the postoperative pathology confirmed high-grade differentiated thyroid carcinoma. The microscopic manifestation was a mixture of the shoe-peg subtype (50%) and the classic subtype (50%). Immunohistochemical detection showed that the proliferation index in the hotspot area of Ki-67 was 20% in the shoe-peg subtype area and 10% in the classic subtype area. Molecular detection showed: BRAF V600E mutation. Follow-up for 3 months showed no disease progression.

The P53 mutant immunophenotype may be an important immunological marker for the transformation of follicular thyroid carcinoma to high grade. The appearance of the shoe-peg morphology and increased Ki-67 proliferation index in the background of BRAF V600E mutation may be an important factor for the high-grade transformation of papillary carcinoma; The diagnosis of HGDTC should strictly follow the 2022 WHO standards, and an integrated diagnostic approach using histological morphology + immunohistochemistry + molecular detection can provide a basis for the diagnosis, prognosis assessment, and individualized treatment of HGDTC.