Medullary thyroid carcinoma with double negative calcitonin and CEA: a case report and update of literature review

Abstract

Background Medullary thyroid carcinoma is a malignant uncommon and aggressive tumour of the parafollicular C cells. In about 75% of cases it is sporadic while, in case of RET mutation, it is associated to multiple endocrine neoplasia type 2 (25% of cases). The biochemical features of medullary thyroid carcinoma include the production of calcitonin and carcinoembryogenic antigen. The above-mentioned features are useful in the diagnostic process as well as in the follow up and in the prognostication of the disease. Even if calcitonin elevation is strongly associated to MTC, it can also be found increased in many pathological different conditions as pregnancy, lactation, C-cells hyperplasia, autoimmune thyroiditis, end stage renal disease, lung and prostate cancer and several neuroendocrine tumours. Major medullary thyroid tumours are usually connected to high doses of circulating calcitonin, in fact non-secretory variants have hardly been described. Case presentation We herein report the case of a 59 years old male, who had undergone total thyroidectomy for multinodular goiter with negative preoperative calcitonin, showing medullary thyroid carcinoma at definitive pathology. To the best of our knowledge, this is the first case documenting a non-secretory medullary thyroid carcinoma, with double negative markers at the time of diagnosis and at the relapse. Conclusion A Literature review underlining pathological hypothesis, differential diagnosis and alternative and innovative biomarkers to identify non-secretory medullary thyroid carcinoma was carried out.

Calcitonin negative medullary thyroid cancer in ectopic thyroid tissue: a rare diagnosis in an unusual location

“…This revealed on staining that almost half of the cases showed positivity for CT and CEA, and that 41 out of 43 tested cases showed positivity of CgA. 2 Our case specimen was negative for CT, but showed positivity for CEA, chromogranin and TTF-1.…”

“…The remaining 25% are hereditary secondary to RET proto-oncogene germline mutation which is associated with multiple endocrine neoplasia (MEN) type 2. 2 Calcitonin (CT) and carcinoembryonic antigen (CEA) levels are typically elevated in MTC and consequently may be used as diagnostic biochemical markers and as markers of disease recurrence or progression. In particular CT, a 32 amino acid linear polypeptide, is considered a highly sensitive and specific biochemical marker owing to its secretion by parafollicular C cells.…”

Do medullary thyroid carcinoma patients with high calcitonin require bilateral neck lymph node clearance? A case report

“…However, it should be noted that the possibility of MTC cannot be completely excluded when preoperative calcitonin and CEA are negative. Gambardell et al [ 23 ] have reported cases of calcitonin and CEA-negative MTC.…”

Calcitonin-secreting neuroendocrine neoplasms of the lung: a systematic review and narrative synthesis

“…A possible explanation for this is the method CTN was tested in the past. The initial approach was using radioimmunoassay, which lacked sensitivity and specificity, and so this led to a two-sided immunoradiometric assay developed in the late 1980s (8). In the early 2000s there was movement to fluorescent and chemiluminescent tests, which were more accurate.…”

“…Parafollicular cells are part of the neuroendocrine system and originate from primordial C cells (8,9). The gene Calc-1 creates procalcitonin, which is cleaved by a convertase enzyme to create CTN (5).…”