One case not meeting criteria for NIFTP maintained the diagnosis of encapsulated FVPTC without invasion but demonstrated significant mitotic activity (three mitoses/ten HPF) and lacked lymph node metastases and BRAFV600E mutation.
This study correlates histological features, immunoreactivity for CK19, HBME, and Gal, and BRAFV600E mutation with lymph node (LN) metastasis and follow-up in FVPTC.
Expression profiling in FVPTCs and FAs, all of which were negative for a BRAF mutation, revealed 55 transcripts that were significantly differentially expressed, 40 of which were upregulated and 15 downregulated in FVPTCs vs. FAs.
These data support the hypothesis that FVPTC is composed of distinct biological entities, with one class being identified by BRAF mutation and support the use of clinical genotyping assays that detect a diverse array of rearrangements involving ALK and PPARγ.
Encapsulated FVPTCs have been reported to have virtually no recurrence risk or metastatic potential and to harbor RAS mutations but not BRAF mutations.
To investigate the frequency of BRAF mutations and HBME-1 immunopositivity, in a series of FVPTCs in which the diagnosis was established by 100% consensus among a panel of 6 surgical pathologists.
BRAF mutations were only detected in FVPTC (10%); the BRAF mutations in these cases (K601E and G474R) are different from the typical BRAF(V600E) mutation of conventional PTCs.
In conclusion, EWD-PTC and FVPTC share similar histologic features, but they are different tumors with different molecular biologic and clinical manifestations.
FVPTC was significantly less likely to be classified sonographically as malignant (U5) (p = 0.006) or suspicious/malignant (U4/5) (p = 0.009) than conventional PTC.
The surgical resection specimen demonstrated FVPTC in 20 (74%) cases, classical type PTC in two (7%), solid variant of PTC in one (4%), and follicular thyroid carcinoma in four (15%).
FNAC diagnoses of FVPTC included benign (5%), atypia of undetermined significance (19%), follicular neoplasm/suspicious for follicular neoplasm (14%), suspicious for PTC (29%), and PTC (34%).
In the thyroid, the PAX8-PPARG fusion is present in the neoplastic lesions that have a follicular architecture-follicular thyroid carcinoma (FTC) and follicular variant of papillary thyroid carcinoma (FVPTC), and less frequently in follicular thyroid adenoma (FTA), while the presence of RET/PTC fusions are largely restricted to papillary thyroid carcinoma (PTC).
RET-PTC and PAX8-PPARgamma rearrangements and mutations of the neuroblastoma RAS viral oncogene homolog N-RAS at codon 61 were the most common genetic alterations in FVPTCs.
In sharp contrast to the findings in classical PTC (4% of cases), CGH analysis demonstrated that both FVPTC (59% of cases) and FTA/FTC (36% of cases) were commonly characterized by aneuploidy (P = 0.0002).
FVPTC was significantly less likely to be classified sonographically as malignant (U5) (p = 0.006) or suspicious/malignant (U4/5) (p = 0.009) than conventional PTC.