MTC is uncommon thyroid and neuendocrine tumor, deriving from C cells, which originate from the neural crest, which manufacture and secret calcitonin used as an effective MTC tumor marker [3]. Though its incidence remains unknown but it is estimated up to 3–5% of all thyroid malignancies and present in approximatively 0.4–1.4% of thyroid nodules [1]. MTC is known for its wide age range of occurrence with a peak in the 4th and 5th decades for sporadic forms but earlier age in hereditary ones and no predilection of sex or ethnicity [1.4.5].
The activation of the RET proto-oncogene is incriminated in the pathogenesis of MTC, its mutation may be inherited as germline mutations or sporadically in somatic mutations detected in 50% (20–80%) of patients [5.6].
Clinical presentation of MTC differs sporadic to familial forms; in the first, the lesions are usually unilateral, unicentric; whilst in the later are bilateral and multicentric [5]. In sporadic forms the common presentation includes thyroid nodules [1] and the presence of cervical lymph node metastasis with normal size thyroid is very rare, first described by Das et al[3] presenting a 48 years male, with a huge swelling of the left side of neck from the parotid region to supraclavicular one with normal-sized thyroid gland.
Family history or the presence of other disorders; endocrine or non-endocrine ones; such as pheochromocytoma, cutaneous neuromas and megacolon and so on; may lead to suspicion of the hereditary variety of MTC [1.5]. To note that up to 35% of the cases presenting palpable nodules have already cervical metastases and during follow-up up to 20–40% of patients will present distant metastases [5].
Biologically speaking, MTC‘s behavior is unpredictable and varies from indolent to rapidly progressive. Clinical symptoms such as flushing or diarrhea is usually found in advanced MTC, whereas the secretion of multiple peptides (histaminase, vasoactive intestinal peptide serotonin…) [5].
In view of the morphological diverseness and the resemblances of other primary tumors of thyroid, calcitonin manifestation is requisite for the pathohistological diagnosis of MTC. Typically, MTC tumor cells are polygonal to round with amphophilic cytoplasm and medium sized nucleus and those cells are spread in solid sheets separated by highly vascular stroma, hyalinised collagen and amyloid [3.7]. Fine needle aspiration smears shows classically isolated, oval to round, large polygonal or spindled cells, but fail to make a proper diagnosis [1.8].
Calcitonin is valuable specific and sensitive tumor marker used for diagnostic, extension, treatment, prediction of reoccurrence and prognostic; as its serum level is directly correlated with the tumor mass [3.5].
MTC curative, standard treatment consist of total thyroidectomy associated with central lymph node neck dissection that may be extended to unilateral or bilateral cervical lymph node dissection depending on imaging, calcitonin serum level and peroperative findings [5].
External beam radiotherapy has its place facing residual tumor or relapse, local/ locoregional and/or extranodal extension, but no benefit with adjuvant radiotherapy in completely resected disease has been proven and palliative radiotherapy is mainly used in painful bone metastases with or without pathologic fractures [5.9.10].
Unfortunately, there is no effective therapy for advanced inoperable and/or distant metastases disease [11], there is narrow response rates, and the data with chemotherapy [5]. However, there is a promising future due to the development of molecular targeted therapies, especially vandetanib or cabozantinibas they are approved, but nevertheless needing more clinical trials [1.5.12].