Objective: To evaluate the relationship of the cytomorphology of medullary thyroid carcinomas (MTC) between family members with the same RET proto-oncogene mutation. Study Design: Review of the fine-needle aspiration slides of 13 cases with MTC proven by surgery and pathology from 5 unrelated families with either multiple endocrine neoplasia (MEN) type 2A or familial MTC (FMTC). Results: Small, round, and abundant large oval-to-polygonal cells were major cytomorphologic findings in 66.7% of family members with exon 11, codon 634 TGC → CGC germline mutation. Small, round cells and only a few or no polygonal cells were found in 66.7% of family members with exon 11, codon 634 TGC → TTC germline mutation and in 100% of family members with codon 634 TGC → TGG germline mutations, as well as in 100% of family members with exon 10, codon 620 TGC → GGC germline mutation. Conclusions: The high rate of similarity of cytomorphology (66.7–100%) in the family members with MEN type 2A or FMTC might be related to the same etiology in the production of MTC in the same family. The relationship of the respective cytomorphology with the long-term prognosis is worth elucidating further.

Elisei R, Romei C, Cosci B, Agate L, Bottici V, Molinaro E, Sculli M, Miccoli P, Basolo F, Grasso L, Pacini F, Pinchera A: RET genetic screening in patients with medullary thyroid cancer and their relatives: experience with 807 individuals at one center. J Clin Endocrinol Metab 2007;92:4725–4729.
Szinnai G, Meier C, Komminoth P, Zumsteg UW: Review of multiple endocrine neoplasia type 2A in children: therapeutic results of early thyroidectomy and prognostic value of codon analysis. Pediatrics 2003;111:E132–E139.
Schimke RN, Hartmann WH, Prout TE, Rimoin DL: Syndrome of bilateral pheochromocytoma, medullary thyroid carcinoma and multiple neuromas: a possible regulatory defect in the differentiation of chromaffin tissue. N Engl J Med 1968;279:1–7.
Mulligan LM, Ponder BA: Genetic basis of endocrine disease: multiple endocrine neoplasia type 2. J Clin Endocrinol Metab 1995;80:1989–1995.
Eng C, Smith DP, Mulligan LM, Healey CS, Zvelebil MJ, Stonehouse TJ, Ponder MA, Jackson CE, Waterfield MD, Ponder BA: A novel point mutation in the tyrosine kinase domain of the RET proto-oncogene in sporadic medullary thyroid carcinoma and in a family with FMTC. Oncogene 1995;10:509–513.
Lips CJ, Landsvater RM, Höppener JW, Geerdink RA, Blijham G, van Veen JM, van Gils AP, de Wit MJ, Zewald RA, Berends MJ, Beemer FA, Brouwers-Smalbraak J, Jansen R, van Amstel HKP, van Vroonhoven T, Vroom TM: Clinical screening as compared with DNA analysis in families with multiple endocrine neoplasia type 2A. N Engl J Med 1994;331:828–835.
Chang TC, Wu SL, Hsiao YL: Medullary thyroid carcinoma: pitfalls in diagnosis by fine needle aspiration cytology and relationship of cytomorphology to RET proto-oncogene mutations. Acta Cytol 2005;49:477–482.
Riu CH: A new rapid method of staining thin blood film: first report. J Formos Med Assoc 1953;52:348–352.
Hsieh MH, Hsiao YL, Chang TC: Fine needle aspiration cytology stained with Riu’s method in quicker diagnosis of medullary thyroid carcinoma. J Formos Med Assoc 2007;106:728–735.
Wu SL, Chang TC, Huang CN, Chuang LM, Chang TJ: Germline RET proto-oncogene mutations in two Taiwanese families with multiple endocrine neoplasia type 2A. J Formos Med Assoc 1998;97:614–618.
Mendonça ME, Ramos S, Soares J: Medullary carcinoma of thyroid: a re-evaluation of the cytological criteria of diagnosis. Cytopathology 1991;2:93–102.
Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJ, Lombardi G, Mannelli M, Pacini F, Ponder BA, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA Jr, Marx SJ: Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001;86:5658–5671.
Frank-Raue K, Döhring J, Scheumann G, Rondot S, Lorenz A, Schulze E, Dralle H, Raue F, Leidig-Bruckner G: New mutations in the RET protooncogene-L881V – associated with medullary thyroid carcinoma and -R770Q – in a patient with mixed medullar/follicular thyroid tumour. Exp Clin Endocrinol Diabetes 2010;118:550–553.
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