Skip to main content

Advertisement

SpringerLink
Log in

Follicular variant of papillary thyroid carcinoma (FVPTC): histological features, BRAF V600E mutation, and lymph node status

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Follicular variant of papillary thyroid carcinoma (FVPTC) is currently treated like conventional papillary thyroid carcinoma (cPTC). Recent reports indicate that encapsulated FVPTC behaves like follicular adenomas, while infiltrative FVPTC behaves like cPTC. This raises the possibility that histology and/or mutation status might help personalize management of FVPTC regarding extent of surgery, intensity of follow-up, and targeted therapy. This study correlates histological features, immunoreactivity for CK19, HBME, and Gal, and BRAF V600E mutation with lymph node (LN) metastasis and follow-up in FVPTC.

Methods

Forty-eight FVPTC (21 with regional lymph node metastasis [LN+] and 27 with negative lymph nodes [LN−]) were reviewed. Demographics, tumor focality, size, circumscription, follicular architecture, lymphovascular invasion, extrathyroidal extension (ETE), and margin status were charted. Macrodissected formalin-fixed paraffin-embedded sections from 47 (21 LN+ and 26 LN−) cases were analyzed for BRAF V600E (1799T>A) mutation using real-time PCR. Correlations between the variables and LN status were calculated.

Results

Sixty-two percent of cases with ETE demonstrated LN metastasis, while 59 % of cases with circumscribed tumors were LN−. In multivariable analysis, ETE and tumor size ≥1 cm were the best predictors of LN+ status, whereas in cases without ETE, the infiltrative pattern and tumor size provided the “best fit.” Immunostains and BRAF mutation status were not helpful. All four tumors that recurred were LN+, with infiltrative borders, and lacked the BRAF mutation.

Conclusions

Tumor circumscription, extrathyroidal extension, and tumor size ≥ 1.0 cm are predictors of lymph node status in FVPTC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Barroeta JE, Baloch ZW, Lal P, Pasha TL, Zhang PJ, LiVolsi VA (2006) Diagnostic value of differential expression of CK19, galectin-3, HBME-1, ERK, RET, and p16 in benign and malignant follicular-derived lesions of the thyroid: an immunohistochemical tissue microarray analysis. Endocr Pathol 17:225–234

    Article  CAS  PubMed  Google Scholar 

  • Chai YJ, Kim SJ, Kim SC et al (2014) BRAF mutation in follicular variant of papillary thyroid carcinoma is associated with unfavorable clinicopathological characteristics and malignant features on ultrasonography. Clin Endocrinol 81:432–439

    Article  CAS  Google Scholar 

  • Chem KT, Rosai J (1977) Follicular variant of thyroid papillary carcinoma: a clinicopathologic study of six cases. Am J Surg Pathol 1:123–130

    Article  CAS  PubMed  Google Scholar 

  • Daniels GH (2011) What if many follicular variant papillary thyroid carcinomas are not malignant? A review of follicular variant papillary thyroid carcinoma and a proposal for a new classification. Endocr Pract 17:768–787

    Article  PubMed  Google Scholar 

  • DeLellis RA, Williams ED (2004) Tumours of the thyroid and parathyroid. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C (eds) Pathology and genetics of tumours of endocrine organs. World Health Organization classification of tumors. IARC Press, Lyon

  • Eloy C, Santos J, Soares P, Sobrinho-Simoes M (2011a) The preeminence of growth pattern and invasiveness and the limited influence of BRAF and RAS mutations in the occurrence of papillary thyroid carcinoma lymph node metastases. Virchows Arch 459:265–276

    Article  CAS  PubMed  Google Scholar 

  • Eloy C, Santos J, Soares P, Sobrinho-Simoes M (2011b) Intratumoral lymph vessel density is related to presence of lymph node metastases and separates encapsulated from infiltrative papillary thyroid carcinoma. Virchows Arch 459:595–605

    Article  CAS  PubMed  Google Scholar 

  • Gupta S, Ajise O, Dultz L et al (2012) Follicular variant of papillary thyroid cancer: encapsulated, nonencapsulated, and diffuse—distinct biologic and clinical entities. Arch Otolaryngol Head Neck Surg 138:227–233

    Article  PubMed  Google Scholar 

  • Hazard JB, Crile CJ, Dinemore RS, Hawk WA, Kenyon R (1955) Neoplasms of the thyroid. Classification, morphology, and treatment. Arch Pathol Lab Med 59:502–513

    CAS  Google Scholar 

  • Howitt BE, Jia Y, Sholl LM, Barletta JA (2013) Molecular alterations in partially-encapsulated or well-circumscribed follicular variant of papillary thyroid carcinoma. Thyroid 23:1256–1262

    Article  CAS  PubMed  Google Scholar 

  • Kim MI, Alexander EK (2012) Diagnostic use of molecular markers in the evaluation of thyroid nodules. Endocr Pract 18:796–802

    Article  PubMed  Google Scholar 

  • Lang BH, Lo CY, Chan WF, Lam AK, Wan KY (2006) Classical and follicular variant of papillary thyroid carcinoma: a comparative study on clinicopathologic features and long-term outcome. World J Surg 30:752–758

    Article  PubMed  Google Scholar 

  • Lee SR, Jung CK, Kim TE, Bae JS, Jung SL, Choi YJ, Kang CS (2013) Molecular genotyping of follicular variant papillary thyroid carcinoma correlates with diagnostic category of fine-needle aspiration cytology: values of RAS mutation testing. Thyroid 23:1416–1422

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lindsay S (1964) Pathology of the thyroid gland. In: Pitt-Rivers R, Trotter WR (eds) The thyroid gland, vol 2, 1st edn. Butterworths, Washington, DC, pp 223–270

    Google Scholar 

  • Lindsay S (1960) Carcinoma of the thyroid gland. A clinical and pathologic study of 293 patients at the University of California Hospital. Charles C. Thomas, Springfield

    Google Scholar 

  • Livolsi V (2003) Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival. Cancer 98:1997

    Article  PubMed  Google Scholar 

  • Lloyd RV, Erickson LA, Casey MB et al (2004) Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol 28:1336–1340

    Article  PubMed  Google Scholar 

  • Min HS, Lee C, Jung KC (2013) Correlation of immunohistochemical markers and BRAF mutation status with histological variants of papillary thyroid carcinoma in the Korean population. J Korean Med Sci 28:534–541

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rhee SJ, Hahn SY, Ko ES, Ryu JW, Ko EY, Shin JH (2014) Follicular variant of papillary thyroid carcinoma: distinct biologic behavior based on ultrasonographic features. Thyroid 24:683–688

    Article  PubMed  Google Scholar 

  • Rivera M, Ricarte-Filho J, Knauf J, Shaha A, Tuttle M, Fagin JA, Ghossein RA (2010) Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns. Mod Pathol 23:1191–1200

    Article  CAS  PubMed  Google Scholar 

  • Salajegheh A, Petcu EB, Smith RA, Lam AK (2008) Follicular variant of papillary thyroid carcinoma: a diagnostic challenge for clinicians and pathologists. Postgrad Med J 84:78–82

    Article  CAS  PubMed  Google Scholar 

  • Scognamiglio T, Hyjek E, Kao J, Chen YT (2006) Diagnostic usefulness of HBME1, galectin-3, CK19, and CITED1 and evaluation of their expression in encapsulated lesions with questionable features of papillary thyroid carcinoma. Am J Clin Pathol 126:700–708

    Article  CAS  PubMed  Google Scholar 

  • Virk RK, Van Dyke AL, Finkelstein A et al (2013) BRAF V600E mutation in papillary thyroid microcarcinoma: a genotype-phenotype correlation. Mod Pathol 26:62–70

    Article  CAS  PubMed  Google Scholar 

  • Vivero M, Kraft S, Barletta JA (2013) Risk stratification of follicular variant of papillary thyroid carcinoma. Thyroid 23:273–279

    Article  CAS  PubMed  Google Scholar 

  • Wallander M, Layfield LJ, Jarboe E et al (2010) Follicular variant of papillary carcinoma: reproducibility of histologic diagnosis and utility of HBME-1 immunohistochemistry and BRAF mutational analysis as diagnostic adjuncts. Appl Immunohistochem Mol Morphol 18:231–235

    Article  CAS  PubMed  Google Scholar 

  • Xing M (2005) BRAF mutation in thyroid cancer. Endocr Relat Cancer 12:245–262

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors have no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA

    Ann E. Walts & Shikha Bose

  2. Biostatistics Core, Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

    James M. Mirocha

Authors
  1. Ann E. Walts
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James M. Mirocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shikha Bose
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ann E. Walts.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Walts, A.E., Mirocha, J.M. & Bose, S. Follicular variant of papillary thyroid carcinoma (FVPTC): histological features, BRAF V600E mutation, and lymph node status. J Cancer Res Clin Oncol 141, 1749–1756 (2015). https://doi.org/10.1007/s00432-015-1939-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-015-1939-9

Keywords

Search

Navigation