Title:Multiple Endocrine Neoplasia Type 2B Associated Mixed Medullary and Follicular Thyroid Carcinoma in A Chinese Patient with RET M918T Germline Mutation
Volume: 21
Issue: 3
Author(s): Xiao-Ping Qi, Guo-Bing Lin, Bo Chen, Feng Li, Zhi-Lie Cao, Wei-Hui Zheng and Jian-Qiang Zhao*
Affiliation:
- Department of Head and Neck Surgery, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, No.1 East Banshan Road, Hangzhou 310022, Zhejiang Province,China
Keywords:
Thyroid neoplasm, medullary thyroid carcinoma, mixed medullary-follicular carcinoma, multiple endocrine neoplasia
type 2B, RET proto-oncogene, M918T mutation.
Abstract:
Background: Mixed medullary and follicular thyroid carcinoma (MMFC) displays heterogeneous
morphological components and immunophenotypical features intermingled within the same
lesion, which is rare and most described in the sporadic form. We report herein a Chinese patient with
multiple endocrine neoplasia type 2B (MEN2B) harboring germline RET M918T and associated
MMFC.
Methods: A case of a 39-year-old male patient with MEN2B presented palpable neck masses in both
thyroid lobes (maximum sizes: left, 3.9 cm; right, 5.4 cm) and a definitive phenotype. Serum levels of
calcitonin (Ctn; >2000pg/mL), carcinoembryonic antigen (CEA; 719.27ng/mL), and thyroglobulin
(Tg; 98.54ng/mL) were high. Fine-needle aspiration cytology showed features positive for malignancy,
suggesting the possibility of medullary thyroid carcinoma (MTC). Total thyroidectomy, along with
extending bilateral neck lymph nodes dissection, and subsequently, genetics family screening were
performed.
Results: The histopathological examination yielded a diagnosis of MMFC that showed immunohistochemical
characteristic patterns of the component of MTC positive for Ctn and CEA, chromogranin A,
and the follicular carcinoma components were positive for Tg. Lymph node metastasis was observed
showing medullary tumoral cells positive for Ctn and follicular-like structures lacking tumor cells positive
for Tg staining (T4bN1bM0). Genetics screening confirmed RET M918T (c.2753T>C) mutation
manifested in the patient but was not detected in other family members. Follow up showed that the
serum Ctn, CEA and Tg levels respectively dropped to 54.38pg/ml, 4.16ng/mL and 0.04ng/mL 16
months after the surgery.
Conclusion: Particular and diverse patterns of MMFC should be recognized with immunostaining
features. MMFC occurring in a patient with MEN2B harboring RET M918T may be unique biological
behavior and the treatment is mostly radical surgery.