In multifocal thyroid cancer, the small BRAF-like focus often drives the nodal spread

Design

Single-institution retrospective clinicopathological study

Population

626 thyroidectomies with follicular-cell carcinoma; 63 with discordant drivers

Primary outcome

Prevalence and features of coexisting RAS-like and BRAF-like carcinomas

Effect

25.7% of multifocal cases discordant; 9 of 10 nodal metastases from the smaller focus

This single-institution review, published in July 2026, examined 626 thyroidectomies containing follicular-cell-derived carcinoma between 2019 and 2025. Multifocal disease was present in 245 (39%), and in 63 of those the gland held both a RAS-like and a BRAF V600E-like carcinoma, confirmed by BRAF V600E and NRAS Q61R immunohistochemistry.

RAS-like tumours were larger (median 2.3 cm) than BRAF-like tumours (median 0.6 cm). HBME-1, CK19 and galectin-3 were more often positive in BRAF-like tumours. Lymphatic invasion and nodal metastasis came mostly from the BRAF-like papillary carcinoma — in nine of ten nodal cases, from the smaller focus.

A report that stages and characterises only the dominant nodule may describe the wrong tumour. Each focus deserves its own histotype, and where the morphology suggests a BRAF-like papillary carcinoma, its features should be reported even if it measures a few millimetres.

• Report histotype, size and invasion for each carcinoma focus, not only the dominant nodule
• Look for a small BRAF-like papillary carcinoma in glands with a large RAS-like tumour
• Consider BRAF V600E immunohistochemistry where foci look morphologically discordant
• Correlate nodal metastases with the focus they resemble

Why it matters

Risk stratification built on the largest nodule can miss the tumour that determines nodal disease.

Don't overread it

A single-centre retrospective series with ten nodal events cannot establish how often this occurs elsewhere.

The statistics, in plain English

This is a descriptive series from one centre, with ten nodal metastases in total. The pattern is striking but rests on small numbers, so the proportion of metastases arising from the small focus is imprecise.

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