It is neuroendocrine neoplasm with C cell differentiation
Accounts for 5% to 10% of thyroid neoplasms
Tumor cells secrete calcitonin and increased levels of serum calcitonin is helpful for diagnosis and post operative follow up of patients
Other polypeptide hormones secreted by tumor cells are
Serotonin
ACTH
Vasoactive intestinal polypeptide
These tumros occur sporadically (in 70% cases) and in familial forms (30% of cases) with autosomal dominant inheritance. They occur in association with MEN syndrome (MEN 2A or 2B) or as familila tumors unassociated with MEN syndromes
Cytogenetics
Medullary carcinoma in MEN type 2 are associated with germline RET mutations that lead to constitutive activation of receptor
RET mutations are also present in one half of non-familial cases
Age –
Sporadic and familial – occur in adulthood with peak incidence in 4th and 5th decade
Those associated with MEN type – occur in younger patients in the first decade of life
Sex – Slight female predominance with female to male ratio of 1.3:1
Morphology
presents as unilateral solitary nodule in sporadic cases
Bilaterality and multicentricity is seen in familial cases
Gross –
Tumor is circumscribed, pale gray to tan with soft to firm in consistency
Areas of hemorrhage and necrosis are seen
Microscopy
Tumor is composed of round, polygonal to spindle shaped cells, arranged in nests, lobular, trabecular and follicular pattern
Some tumors show anaplastic cells which are small and may predominate
Stroma shows acellular amyloid deposits derived from calcitonin polypeptides
Familial medullary carcinomas show multicentric C – cell hyperplasia in the adjacent thyroid parenchyma which is absent in sporadic cases. It is considered to be precursor lesion in familial cases
Electron microscopy
reveals variable number of membranebound electron dense granules with in the cytoplasm of tumor cells
Clinical course
presents as a mass in the neck.
sometimes associated with dysphagia and hoarsness
some of the cases may present with paraneoplastic syndrome due to secretion of hormones like VIP and ACTH
Calcitonin and Carcinoembryogenic antigen produced by tumor cells act as biomarkers
Medullary carcinomas arising in context of MEN 2B are more aggressive and metastasize more frequently than sporadic form
Medullary carcinoma metastasizes to cervical lymph nodes and distant metastasis occurs to lungs, liver and bone
Treatment and prognosis
Treatment is total thyroidectomy
Prognosis for the younger patients (less than 40 Years ) is better than the elder patients
