BACKGROUND
Thyroid nodules are very common, but only a small percentage of them ever turn out to be cancers of significance. Thyroid biopsies are performed to identify those nodules that require surgery. Biopsy results are ranked according to the risk of cancer in a system known as the Bethesda System. This system is: category I: nondiagnostic; category II: benign; category III: atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS); category IV: follicular neoplasm or Hürthle-cell neoplasm; category V: suspicious for cancer; and cagtegory VI: cancer. The higher the category, the higher the cancer risk. If this risk is low (category II), patients are usually followed with physical exam and periodic thyroid ultrasounds. If the risk is higher, surgery is usually recommended.

However, most studies that evaluated the accuracy the Bethesda System in determining thyroid cancer risk used a comparison to patients who underwent surgery. This may have led to some inaccurate results. This study was done to evaluate the risk of cancer in each Bethesda category by examining both surgical and long-term clinical outcomes in patients who did not undergo surgery.

THE FULL ARTICLE TITLE
Ng DL et al 2021 A large thyroid fine needle aspiration biopsy cohort with long-term population-based follow-up. Thyroid. Epub 2021 Jan 29. PMID: 33371796.

SUMMARY OF THE STUDY
The study involved all thyroid biopsies from a single pathology database at the University of California, San Francisco for 8 years from January 1997 to December 2004. All biopsies were recoded according to the most recent Bethesda grading system. Patients were then matched through July 2015 (average follow up 13.9 yrs) to the UCSF cancer registry and the California Cancer Registry and considered to be without cancer if they were not in either registry.

A total of 2233 patients with 2758 biopsy reports were available; 26 were excluded, for a final count of 2207. The average age was 48 years (range, 7–92) and 1880 patients (85.2%) were female. Of the 2207 test results, 236 (10.7%) were determined to be nondiagnostic, 1575 (71.4%) benign, 57 (2.58%) atypia of undetermined significance (AUS), 78 (3.53%) follicular lesion of undetermined significance (FLUS), 107 (4.85%) follicular neoplasm or Hürthle-cell neoplasm, 20 (0.9%) suspicious for malignancy, and 134 (6.07%) malignant. Average follow-up after the initial biopsy was 13.9 years (range, 10.5–18.4), and 279 (12.6%) patients were diagnosed with thyroid cancer during that period.

Thyroid cancer was ultimately identified in only a few patients with initially benign biopsies (cancer rate of 2.42 per 1000 person-years). Cancer was diagnosed only twice as often if the biopsy was non-diagnostic, 9 times as often for AUS/FLUS, 11 times as often for follicular neoplasm, and 49 times as often for suspicious for malignancy. Only 52 of the nodules with an initial benign biopsy (1575) ultimately were diagnosed with thyroid cancers and 29 of those were papillary thyroid microcarcinomas, which rarely spread beyond the thyroid. Only 15 patients died from their thyroid cancer and none of these patients had a benign biopsy initially.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study showed that thyroid biopsy and the Bethesda grading system are accurate in detecting thyroid cancer. Long-term follow up showed low rates of cancer in nondiagnostic biopsies. There was an extremely low rate of death when biopsy was benign or non-diagnostic. This information supports our current recommendations regarding handling of thyroid nodules. Patients with benign biopsies are unlikely to eventually need surgery for thyroid cancer. Even patients with non-diagnostic biopsies have a relatively low risk for cancer. The up to date Bethesda system of categorizing thyroid biopsy rarely misses a cancer of significance and patients should be reassured.

— Marjorie Safran

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