Absence of BRAF, NRAS, KRAS, HRAS mutations, and RET/PTC gene rearrangements distinguishes dominant nodules in hashimoto thyroiditis from papillary thyroid carcinomas

Peter M. Sadow, Michael Heinrich, Christopher Corless, Jonathan A. Fletcher, Vânia Nosé

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Dominant nodules within Hashimoto thyroiditis (HT) may present with unique morphological features that overlap with but are not diagnostic of papillary thyroid carcinoma (PTC). Activating BRAF point mutations, RAS aberrations, and RET rearrangements are mutually exclusive events in the oncogenesis of papillary thyroid carcinoma, and RET rearrangements have been previously described in dominant nodules of HT. We identified 28 cases of Hashimoto thyroiditis with a dominant nodule, from 345 consecutive HT thyroidectomies. Screening for BRAF, RET, KRAS, NRAS, and HRAS mutations, as well as RET-PTC1 and RET-PTC3 rearrangements, was performed on paraffinembedded material from 17 of these dominant nodules. Patients ranged in age from 29 to 76 years and were predominantly female, and the nodules ranged from 1.5 to 6.2 cm. No BRAF or RAS mutations or RET-PTC rearrangements were identified in a dominant nodule, including those with atypical, worrisome histopathologic features. Of ten cases with diagnostic concomitant or incidental papillary carcinoma, three had a V600E point mutation in BRAF, and one case had a BRAF exon 15 deletion (600-604E), while the dominant nodules were negative for mutation, supporting the notion that dominant nodules are neither malignant nor precursor lesions, and strict histological, clinical, and molecular criteria must be met for the diagnosis of papillary thyroid carcinoma.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalEndocrine Pathology
Volume21
Issue number2
DOIs
StatePublished - Jun 2010

Fingerprint

Hashimoto Disease
Gene Rearrangement
Mutation
Point Mutation
Papillary Carcinoma
Thyroidectomy
Exons
Carcinogenesis
Papillary Thyroid cancer

Keywords

  • BRAF
  • Dominant nodule
  • Hashimoto thyroiditis
  • HRAS
  • KRAS
  • NRAS
  • Papillary thyroid carcinoma
  • RET-PTC

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Absence of BRAF, NRAS, KRAS, HRAS mutations, and RET/PTC gene rearrangements distinguishes dominant nodules in hashimoto thyroiditis from papillary thyroid carcinomas",
abstract = "Dominant nodules within Hashimoto thyroiditis (HT) may present with unique morphological features that overlap with but are not diagnostic of papillary thyroid carcinoma (PTC). Activating BRAF point mutations, RAS aberrations, and RET rearrangements are mutually exclusive events in the oncogenesis of papillary thyroid carcinoma, and RET rearrangements have been previously described in dominant nodules of HT. We identified 28 cases of Hashimoto thyroiditis with a dominant nodule, from 345 consecutive HT thyroidectomies. Screening for BRAF, RET, KRAS, NRAS, and HRAS mutations, as well as RET-PTC1 and RET-PTC3 rearrangements, was performed on paraffinembedded material from 17 of these dominant nodules. Patients ranged in age from 29 to 76 years and were predominantly female, and the nodules ranged from 1.5 to 6.2 cm. No BRAF or RAS mutations or RET-PTC rearrangements were identified in a dominant nodule, including those with atypical, worrisome histopathologic features. Of ten cases with diagnostic concomitant or incidental papillary carcinoma, three had a V600E point mutation in BRAF, and one case had a BRAF exon 15 deletion (600-604E), while the dominant nodules were negative for mutation, supporting the notion that dominant nodules are neither malignant nor precursor lesions, and strict histological, clinical, and molecular criteria must be met for the diagnosis of papillary thyroid carcinoma.",
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T1 - Absence of BRAF, NRAS, KRAS, HRAS mutations, and RET/PTC gene rearrangements distinguishes dominant nodules in hashimoto thyroiditis from papillary thyroid carcinomas

AU - Sadow, Peter M.

AU - Heinrich, Michael

AU - Corless, Christopher

AU - Fletcher, Jonathan A.

AU - Nosé, Vânia

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