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Absence of BRAF, NRAS, KRAS, HRAS mutations, and RET/PTC gene rearrangements distinguishes dominant nodules in Hashimoto thyroiditis from papillary thyroid carcinomas.
Endocr Pathol 2010; 21(2):73-9EP

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 paraffin-embedded 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.

Authors+Show Affiliations

Pathology Service, WRN219, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. psadow@partners.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

20012784

Citation

Sadow, Peter M., et al. "Absence of BRAF, NRAS, KRAS, HRAS Mutations, and RET/PTC Gene Rearrangements Distinguishes Dominant Nodules in Hashimoto Thyroiditis From Papillary Thyroid Carcinomas." Endocrine Pathology, vol. 21, no. 2, 2010, pp. 73-9.
Sadow PM, Heinrich MC, Corless CL, et al. Absence of BRAF, NRAS, KRAS, HRAS mutations, and RET/PTC gene rearrangements distinguishes dominant nodules in Hashimoto thyroiditis from papillary thyroid carcinomas. Endocr Pathol. 2010;21(2):73-9.
Sadow, P. M., Heinrich, M. C., Corless, C. L., Fletcher, J. A., & Nosé, V. (2010). Absence of BRAF, NRAS, KRAS, HRAS mutations, and RET/PTC gene rearrangements distinguishes dominant nodules in Hashimoto thyroiditis from papillary thyroid carcinomas. Endocrine Pathology, 21(2), pp. 73-9. doi:10.1007/s12022-009-9101-3.
Sadow PM, et al. Absence of BRAF, NRAS, KRAS, HRAS Mutations, and RET/PTC Gene Rearrangements Distinguishes Dominant Nodules in Hashimoto Thyroiditis From Papillary Thyroid Carcinomas. Endocr Pathol. 2010;21(2):73-9. PubMed PMID: 20012784.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR 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 C, AU - Corless,Christopher L, AU - Fletcher,Jonathan A, AU - Nosé,Vânia, PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/8/21/medline SP - 73 EP - 9 JF - Endocrine pathology JO - Endocr. Pathol. VL - 21 IS - 2 N2 - 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 paraffin-embedded 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. SN - 1559-0097 UR - https://www.unboundmedicine.com/medline/citation/20012784/Absence_of_BRAF_NRAS_KRAS_HRAS_mutations_and_RET/PTC_gene_rearrangements_distinguishes_dominant_nodules_in_Hashimoto_thyroiditis_from_papillary_thyroid_carcinomas_ L2 - https://dx.doi.org/10.1007/s12022-009-9101-3 DB - PRIME DP - Unbound Medicine ER -