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Follicular-derived neoplasms: Morphometric and genetic differences

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Abstract

Background: The distinction between follicular adenomas (FAs) and well differentiated follicular and papillary carcinomas is often a demanding task and sometimes only intuitive. Aim: We report an histomorphological evaluation of follicular neoplasms [FAs, follicular carcinomas (FCs), and follicular variant of papillary carcinomas (FVPTCs)], supported by a qualitative and quantitative image analysis and by a molecular characterization. Material and methods: Tumor fibrosis and haemorrhage, neoplastic capsule thickness, follicle diameter, number of neoplastic cells, nuclear diameter of neoplastic cells, vessels density, vessels area and intratumoral distribution were evaluated. Ras and BRAF mutations, RET/PTC1, RET/PTC3, and PAX8/PPARγ rearrangements were analyzed. Correlations with clinico-pathological features have been studied. Results: We found that FAs had a more extensive intratumoral haemorrhage, while malignant neoplasms were characterized by an evident fibrosis, higher cellularity and larger size. FVPTCs had higher nuclear diameter; cells count was higher in the minimally invasive follicular thyroid carcinomas, as well as a thickener neoplastic capsule. The CD34 stain showed a higher microvessel density in the FVPTCs group. A higher peripheral vessels distribution was observed only in malignant neoplasms. We observed overall Ras mutations in 2.4% of adenomas, in 41.5% of FVPTCs, and in 44.8% of FCs. It is outstanding that there is a marked difference in the Ras mutation distribution between the benign and malignant tumors in our series. Conclusions: We found that genotyping of Ras gene family together with an accurate analysis of selected morphological features could help in the differential diagnosis of follicular-derived thyroid neoplasms.

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References

  1. Castro MR, Gharib H. Continuing controversies in the management of thyroid nodules. Ann Intern Med 2005, 142: 926–31.

    Article  PubMed  Google Scholar 

  2. Delbridge L. Solitary thyroid nodule: current management. ANZ J Surg 2006, 76: 381–6.

    Article  PubMed  Google Scholar 

  3. Brooks AD, Shaha AR, DuMornay W, et al. Role of fine-needle aspiration biopsy and frozen section analysis in the surgical management of thyroid tumors. Ann Surg Oncol 2001, 8: 92–100.

    Article  PubMed  Google Scholar 

  4. Lowhagen T, Sprenger E. Cytologic presentation of thyroid tumors in aspiration biopsy smear. A review of 60 cases. Acta Cytol 1974, 18: 192–7.

    PubMed  Google Scholar 

  5. Lang W, Atay Z, Georgii A. [The cytological classification of follicular tumors in the thyroid gland (author’s transl)]. Virchows Arch A Pathol Anat Histol 1978, 378: 199–211.

    Article  PubMed  Google Scholar 

  6. Mulcahy MM, Cohen JI, Anderson PE, Ditamasso J, Schmidt W. Relative accuracy of fine-needle aspiration and frozen section in the diagnosis of well-differentiated thyroid cancer. Laryngoscope 1998, 108: 494–6.

    Article  PubMed  Google Scholar 

  7. Lloyd RV, Erickson LA, Casey MB, et al. Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am J Surg Pathol 2004, 28: 1336–40.

    Article  PubMed  Google Scholar 

  8. Giorgadze TA, Baloch ZW, Pasha T, Zhang PJ, Livolsi VA. Lymphatic and blood vessel density in the follicular patterned lesions of thyroid. Modern Pathol 2005, 18: 1424–31.

    Article  Google Scholar 

  9. DeLellis RA, Lloyd RV, Heitz PU, Eng C. World Health Organization Classification of Tumors. Pathology and genetics of tumors of endocrine organs. Lyon: IARC Press, 2004.

    Google Scholar 

  10. Salvatore G, Giannini R, Faviana P, et al. Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle aspiration diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab 2004, 89: 5175–80.

    Article  PubMed  Google Scholar 

  11. Nikiforov YE, Steward DL, Robinson-Smith TM, et al. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab 2009, 94: 2092–8.

    Article  PubMed  Google Scholar 

  12. Rajesh L, Dey P, Joshi K. Automated image morphometry of lobular breast carcinoma. AQCH 2002, 24: 81–4.

    Google Scholar 

  13. Ikeguchi M, Sakatani T, Endo K, Makino M, Kaibara N. Computerized nuclear morphometry is a useful technique for evaluating the high metastatic potential of colorectal adenocarcinoma. Cancer 1999, 86: 1944–51.

    Article  PubMed  Google Scholar 

  14. Reifen E, Noyek AM, Mullen JB. Nuclear morphometry and stereology in nasopharyngeal carcinoma. Laryngoscope 1992, 102: 53–5.

    Article  PubMed  Google Scholar 

  15. Duskova J. [Nuclear size and character of the nucleolar organizer in benign and malignant follicular tumors of the thyroid gland]. Cesk Patol 1992, 28: 201–6.

    PubMed  Google Scholar 

  16. Nagashima T, Suzuki M, Nakajima N. Cytologic morphometric approach for the prediction of lymph node involvement in papillary thyroid cancer. AQCH 1997, 19: 49–54.

    Google Scholar 

  17. Nagashima T, Suzuki M, Oshida M, et al. Morphometry in the cytologic evaluation of thyroid follicular lesions. Cancer 1998, 84: 115–8.

    Article  PubMed  Google Scholar 

  18. Kaur A, Jayaram G. Thyroid tumors: cytomorphology of follicular neoplasms. Diagn Cytopathol 1991, 7: 469–72.

    Article  PubMed  Google Scholar 

  19. Priya SS, Sundaram S. Morphology to morphometry in cytological evaluation of thyroid lesions. J Cytol 2011, 28: 98–102.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Deshpande V, Kapila K, Sai KS, Verma K. Follicular neoplasms of the thyroid. Decision tree approach using morphologic and morphometric parameters. Acta Cytol 1997, 41: 369–76.

    Article  PubMed  Google Scholar 

  21. Lubitz CC, Faquin WC, Yang J, et al. Clinical and cytological features predictive of malignancy in thyroid follicular neoplasms. Thyroid 2010, 20: 25–31.

    Article  PubMed  Google Scholar 

  22. Adeniran AJ, Zhu Z, Gandhi M, et al. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol 2006, 30: 216–22.

    Article  PubMed  Google Scholar 

  23. van Slooten H, Schaberg A, Smeenk D, Moolenaar AJ. Morphologic characteristics of benign and malignant adrenocortical tumors. Cancer 1985, 55: 766–73.

    Article  PubMed  Google Scholar 

  24. Tse LL, Chan I, Chan JK. Capsular intravascular endothelial hyperplasia: a peculiar form of vasoproliferative lesion associated with thyroid carcinoma. Histopathology 2001, 39: 463–8.

    Article  PubMed  Google Scholar 

  25. Niimi K, Yoshizawa M, Nakajima T, Saku T. Vascular invasion in squamous cell carcinomas of human oral mucosa. Oral Oncol 2001, 37: 357–64.

    Article  PubMed  Google Scholar 

  26. Salizzoni M, Romagnoli R, Lupo F, et al. Microscopic vascular invasion detected by anti-CD34 immunohistochemistry as a predictor of recurrence of hepatocellular carcinoma after liver transplantation. Transplantation 2003, 76: 844–8.

    Article  PubMed  Google Scholar 

  27. Fogt F, Zimmerman RL, Ross HM, Daly T, Gausas RE. Identification of lymphatic vessels in malignant, adenomatous and normal colonic mucosa using the novel immunostain D2-40. Oncol Rep 2004, 11: 47–50.

    PubMed  Google Scholar 

  28. Kahn HJ, Marks A. A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors. Lab Invest 2002, 82: 1255–7.

    Article  PubMed  Google Scholar 

  29. Ramsden JD. Angiogenesis in the thyroid gland. J Endocrinol 2000, 166: 475–80.

    Article  PubMed  Google Scholar 

  30. Turner HE, Harris AL, Melmed S, Wass JA. Angiogenesis in endocrine tumors. Endocr Rev 2003, 24: 600–32.

    Article  PubMed  Google Scholar 

  31. Fellmer PT, Sato K, Tanaka R, et al. Vascular endothelial growth factor-C gene expression in papillary and follicular thyroid carcinomas. Surgery 1999, 126: 1056–61 (discussion 1061–2).

    Article  PubMed  Google Scholar 

  32. Hung CJ, Ginzinger DG, Zarnegar R, et al. Expression of vascular endothelial growth factor-C in benign and malignant thyroid tumors. J Clin Endocrinol Metab 2003, 88: 3694–9.

    Article  PubMed  Google Scholar 

  33. Vasko V, Ferrand M, Di Cristofaro J, Carayon P, Henry JF, de Micco C. Specific pattern of RAS oncogene mutations in follicular thyroid tumors. J Clin Endocrinol Metab 2003, 88: 2745–52.

    Article  PubMed  Google Scholar 

  34. Fukushima T, Takenoshita S. Roles of RAS and BRAF mutations in thyroid carcinogenesis. Fukushima J Med Sci 2005, 51: 67–75.

    Article  PubMed  Google Scholar 

  35. Frasca F, Nucera C, Pellegriti G, et al. BRAF(V600E) mutation and the biology of papillary thyroid cancer. Endocr Relat Cancer 2008, 15: 191–205.

    Article  PubMed  Google Scholar 

  36. Gupta N, Dasyam AK, Carty SE, et al. RAS mutations in thyroid FNA specimens are highly predictive of predominantly low-risk follicular-pattern cancers. J Clin Endocrinol Metab 2013, 98: E914–22.

    Article  PubMed  Google Scholar 

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Correspondence to F. Basolo MD, PhD.

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Proietti, A., Sartori, C., Borrelli, N. et al. Follicular-derived neoplasms: Morphometric and genetic differences. J Endocrinol Invest 36, 1055–1061 (2013). https://doi.org/10.3275/9063

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