关键词: 甲状腺髓样癌, 儿童青少年, 免疫组织化学, 降钙素, 预后

Abstract: Background and purpose: Medullary thyroid carcinoma (MTC) is a rare disease in children and adolescents, which is seldom reported in China. The purpose of this study was to explore its clinicopathological features, diagnosis and prognostic factors, and to improve the understanding of MTC. Methods: Data of 10 cases of MTC in children and adolescents were collected from Fujian Cancer Hospital from January 2007 to May 2021, and clinical features, morphology, immunophenotype, gene mutation, and outcome were analyzed. Results: There were 6 sporadic cases, and 4 cases with family history, aged 10-20 years with a mean of 17 years. All showed elevated serum calcitonin (CT) and carcinoembryonic antigen (CEA). Bilateral thyroid lesions were found in 9 patients. The tumor diameter was 0.2-3.5 cm, with a median diameter of 1.5 cm. Microscopically, the tumor presented a patchy, nest- shaped, or beamlike distribution, with invasive growth pattern and surrounding satellite nodules. Papillary and follicular structures were also observed in some cases. The cells were round and oval, mixed with some spindle cells and plasmacytoid cells. A few giant cells and intranuclear pseudo-inclusions were also found. Different degrees of fibrosis/amyloid deposition were observed in the tumor stroma, with occasional calcification and sand bodies. Synaptophysin (Syn), chromogranin A (CgA), cluster of differentiation (CD56), CT, CEA, thyroid transcription factor-1 (TTF-1) and Congo red staining were positive for tumor cells, while thyroglobulin (Tg) was negative. The M918T mutation in RET gene was the most common genetic change in MTC. Among all of the 10 cases, the serum CT and CEA of 8 cases were reduced to normal levels after operation, without recurrence/metastasis (biochemical cure) during the follow-up period (27-98 months, with an average of 62 months). One patient was non-biochemical cure, and cervical lymph node dissection was performed twice at 75 and 108 months postoperatively. Another patient died of tumor 6 months after surgery, which presented high-grade nuclei (polymorphic, prominent nucleoli, mitotic  ＞ 3/10HPF), high proliferation index (Ki- 67 was 20%), numerous intravascular tumor thrombi and focal coagulant necrosis. Conclusion: The majority of MTC in children and adolescents have bilateral thyroid involvement. Bilateral thyroidectomy is the best therapeutic theatment for removing potential hidden lesions and prevent recurrence. The elevation of serum CT and CEA is an important clinical feature. High nuclear grade, high Ki-67 proliferation index, intravascular tumor thrombus and necrosis are important prognostic indicators.

Key words: Medullary thyroid carcinoma, Children and adolescents, Immunohistochemistry, Calcitonin, Prognosis