Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations.

Departments of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, 231 Albert Sabin Way, PO Box 670529, Cincinnati, OH 45267-0529, USA.
American Journal of Clinical Pathology (Impact Factor: 3.01). 08/2003; 120(1):71-7. DOI: 10.1309/ND8D-9LAJ-TRCT-G6QD
Source: PubMed

ABSTRACT The follicular variant (FV) of papillary thyroid carcinoma is characterized by a follicular growth pattern and cytologic features of papillary carcinoma. ret/PTC rearrangements are common in classic papillary thyroid carcinoma (PTC) and PAX8-PPAR gamma and ras mutations in follicular thyroid carcinoma. Their prevalence in FV has not been established. We studied these genetic alterations and clinical-pathologic features in 30 FV cases and compared those with 46 non-FV papillary carcinomas. FV cases revealed 1 ret/PTC rearrangement (3%) and 13 ras mutations (43%). Non-FV cases harbored 13 ret/PTC (28%) (P = .006) and no ras mutations (P = .0002). No PAX8-PPAR gamma was found in either group. FV cases demonstrated a significantly higher prevalence of tumor encapsulation, angiovascular invasion, and poorly differentiated areas and a lower rate of lymph node metastases. These data indicate that the FV of papillary carcinoma has a distinct set of molecular alterations and is characterized by a high frequency of ras point mutations.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Follicular variant of papillary thyroid carcinoma (FVPTC), particularly the encapsulated subtype, often causes a diagnostic dilemma. We reconfirmed the molecular profiles in a large number of FVPTCs and investigated the efficacy of the preoperative mutational analysis in indeterminate thyroid nodules. BRAF V600E/K601E and RAS mutational analysis was performed on 187 FVPTCs. Of these, 132 (70.6%) had a point mutation in one of the BRAF V600E (n = 57), BRAF K601E (n = 11), or RAS (n = 64) genes. All mutations were mutually exclusive. The most common RAS mutations were at NRAS codon 61. FNA aspirates from 564 indeterminate nodules were prospectively tested for BRAF and RAS mutation and the surgical outcome was correlated with the mutational status. Fifty-seven and 47 cases were positive for BRAF and RAS mutation, respectively. Twenty-seven RAS-positive patients underwent surgery and all except one patient had FVPTC. The PPV and accuracy of RAS mutational analysis for predicting FVPTC were 96% and 84%, respectively. BRAF or RAS mutations were present in more than two-thirds of FVPTCs and these were mutually exclusive. BRAF mutational analysis followed by N, H, and KRAS codon 61 mutational analysis in indeterminate thyroid nodules would streamline the management of patients with malignancies, mostly FVPTC.
    01/2015; 2015:1-8. DOI:10.1155/2015/697068
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Thyroid nodules are less common in children than adults, but the risk of malignancy in thyroid nodules is much higher in children. The ability to characterize pediatric thyroid nodules has improved with the use of ultrasound guided fine needle aspiration, the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) classification system, and expanded molecular testing. Nevertheless, stratification criteria to predict thyroid malignancy in children are poorly defined. Our objective was to determine if clinical presentation and molecular genetics could predict malignancy in pediatric thyroid nodules. Methods: Retrospective chart review of patients < 18 years of age at Children's Hospital of Pittsburgh of UPMC with the diagnosis of a thyroid nodule from January 2007-January 2012 was conducted. Eighty-nine subjects fulfilled the inclusion criteria: 1) thyroid nodule > 0.8cm and biopsy (n=76) or 2) thyroid nodule > 0.8 cm, no biopsy, and ultrasound follow-up for at least 2 years (n=13). Results: Twenty four (27%) of 89 patients were diagnosed with thyroid cancer (50% papillary thyroid carcinoma (PTC), 50% follicular variant of papillary thyroid carcinoma (FVPTC)). Features associated with malignancy included larger nodule size, palpable nodule, or palpable lymphadenopathy. There were no differences in presenting features between those diagnosed with PTC compared with FVPTC. Thyroid malignancy was diagnosed in all nine patients with a molecular abnormality (BRAF, RAS, RET/PTC, PAX8/PPARĪ³). Conclusions: Clinical features, FNA cytology, and molecular genetics are valuable tools to discriminate benign from malignant nodules in pediatric patients. This information is important to direct subsequent clinical management.
    Thyroid: official journal of the American Thyroid Association 01/2015; 25(4). DOI:10.1089/thy.2014.0312 · 3.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid carcinomas of follicular epithelial derivation are common and generally well-behaved malignancies with excellent cure and survival rates. However, a subset of these carcinomas, whether well-differentiated, poorly differentiated, or anaplastic, is highly aggressive, manifesting with local invasion, recurrence, and distant metastasis. The recognition of dedifferentiation is of paramount importance. In addition, the challenge for Pathologists is to identify the rare aggressive differentiated carcinomas so that treatment may be tailored appropriately. Thus, histological subtyping and documentation of other aggressive features such as widespread invasion and angioinvasion are critical. Mutational analyses in the past decade have delineated the molecular alterations responsible for thyroid carcinogenesis and progression, allowing greater sub-classification and prognostication of thyroid carcinomas. This review article highlights important aggressive morphologic features and molecular mutations associated with thyroid carcinoma.
    Head and Neck Pathology 03/2015; 9(1). DOI:10.1007/s12105-015-0619-z