Calcitonin-Negative Neuroendocrine Carcinoma of the Thyroid Gland: Case Report and Literature Review

Abstract

Calcitonin-negative neuroendocrine tumor (CNNET) of the thyroid is an extremely rare entity. In some of the previously reported cases within the literature, the terms “atypical medullary thyroid carcinoma,” “calcitonin-free oat cell carcinoma,” and “a distinct clinical entity” were applied to NETs without definitive evidence of calcitonin production. In the English-language literature, not only are there only few reported cases of CNNET, but the criteria for diagnosis in these cases are also controversial. Most of the current published cases were also treated surgically for local disease. We describe a case of NET of the thyroid with calcitonin, chromogranin A and thyroglobulin negativity, synaptophysin and TTF-1 positivity, and a high Ki-67 proliferation index with metastases in the cervical region as well as mediastinal adenopathies. This case was considered an unresectable thyroid carcinoma, and chemotherapy including cisplatin and etoposide was started as neoadjuvant treatment at the department of medical oncology. Total thyroidectomy plus bilateral and central cervical dissection was performed, and the patient underwent 2 cycles of adjuvant radiotherapy. Currently, the patient’s 18F-FDG-PET/CT findings show a complete response 17 months after diagnosis. In conclusion, CNNET of the thyroid is very rare and there is limited evidence regarding treatment in patients with metastases. Chemotherapy including cisplatin and etoposide as well as early aggressive surgical resection appears to positively impact patients’ survival.

Fine‐needle aspiration diagnosis of secondary malignant tumors of the thyroid gland: A single‐institution experience of 17 cases

“…Metastatic small‐cell neuroendocrine carcinomas were positive for Syn, CgA, and CD56, but also positive in small cell variant of medullary thyroid carcinomas, making calcitonin, the most critical in the diagnosis of medullary carcinomas, crucial 36 . Diagnosis of primary calcitonin‐negative neuroendocrine carcinoma of the thyroid gland requires caution, as this type of disease is very rare, with only a few cases reported, and metastasis elsewhere has to be completely ruled out 37–39 . Immunostaining for thyroid markers in combination with GATA‐3, mammaglobulin, and estrogen/progesterone receptors to aid in the differential diagnosis of metastatic breast carcinoma 18,40,41 .…”

“…36 Diagnosis of primary calcitonin-negative neuroendocrine carcinoma of the thyroid gland requires caution, as this type of disease is very rare, with only a few cases reported, and metastasis elsewhere has to be completely ruled out. [37][38][39] Immunostaining for thyroid markers in combination with GATA-3, mammaglobulin, and estrogen/ progesterone receptors to aid in the differential diagnosis of metastatic breast carcinoma. 18,40,41 GATA-3 can also be commonly expressed in intrathyroidal parathyroid hyperplasia and cervical paraganglioma.…”

Non-hyalinizing trabecular thyroid adenoma: A novel thyroid tumor with diagnostic pitfalls of hyalinizing trabecular adenoma and medullary thyroid carcinoma

“…However, calcitonin production was not detected in biochemical or immunohistochemical studies. On such occasions, calcitonin-negative neuroendocrine tumors, which are extremely rare, should be considered [7], but this possibility was denied due to the negativity of chromogranin A and synaptophysin. Furthermore, positivity for both TTF-1 and PAX8 in the present case con rmed that it was not a C-cell-derived tumor but a follicular cell origin [8,9].…”

Neuroendocrine Carcinoma of the Uterine Cervix With Metastases to the Thyroid Gland: A Case Report and Clinical Pathological Review

“…Less common sites of origin are the thyroid, skin, pituitary, adrenal, and genitourinary tract, whereas, in females, the most frequent site is the cervix. The majority of NETs are sporadic and are associated with multiple endocrine neoplasia type 1 (MEN-1), MEN-2, von Hippel-Lindau syndrome, neurofibromatosis, and tuberous sclerosis [1][2][3][4].…”

“…Interestingly, metastatic NETs to the thyroid can also mimic a primary NET of the thyroid, especially MTC. The incidence of metastases to the thyroid is low, occurring in malignant lymphoma, carcinomas of the breast, lung and kidney, head and neck tumors, and gastrointestinal tract malignancies; however, the most common origins of metastatic NET to the thyroid are lung, larynx, and gastrointestinal tract [1,4,5,[9][10][11][12][13]. The differentiation of metastatic disease from MTC can be usually seen with an immunohistochemical examination; secondary NETs of the thyroid usually are negative for calcitonin and carcinoembryonic antigen (CEA).…”