Definition: Medullary thyroid carcinoma (MTC) is an unusual neoplasm, accounting for 3-10% of all thyroid cancer cases. It occurs in a sporadic and hereditary form.
Clinical synopsis
May have other MEN 2 features
Painless thyroid mass
50% with node metastases at presentation
15% with distant metastases at presentation
Raised serum calcitonin levels
May present with other unusual endocrine paraneoplastic features.
Morphological synopsis
Irregular unencapsulated firm mass centrally in thyroid lobe
Usually unicentric
- except syndromic cases
Solid sheets, nests or trabeculae of tumor cells composed of varying proportions of:
- polygonal, round or spindle cells
- round / oval bland nuclei
- occasionally pleomorphic
rare mitoses
locally infiltrative
fibrovascular intervening stroma
- variable appearance
- may be hyalinized
- majority have amyloid areas (Congo red positive)
Immunohistochemistry
CEA+
- strong expression associated with worse prognosis
Calcitonin+
Chromogranin+
Synaptophysin+
TTF-1+
±S100 + : sustentacular cells peripherally
MEN associated cases
younger age
multicentric
bilateral
Epidemiology
Mainly adults when sporadic
Children affected when associated with MEN 2A, 2B and familial medullary thyroid carcinoma syndromes. It may even present in infancy in these syndromes
Medullary thyroid carcinoma (MTC) accounts for approximately 3% to 10% of all thyroid carcinomas.
The female to male ratio generally reported ratio is of 1.3/1.
Hereditary MTC often presents with bilateral tumors and is frequently associated with C-cell hyperplasia (CCH).
By means of calcitonin screening programs, MTCs could be detected at an early stage in families with MTC.
Germ-line mutations of the RET protooncogene, considered to be responsible for the hyperproliferative activity of C cells, are identified in family members at risk.
In contrast, sporadic forms of MTC rarely were detected at an early stage, because routine screening was not performed. Therefore, only scant data are available at pathogenesis and possible precursor lesions such as CCH.
Although in case reports, CCH has been reported to occur in apparently sporadic MTCs, it is generally assumed that sporadic MTC is not associated with CCH.
The occurrence of CCH in the absence of hereditary risk factors is considered to represent a reactive proliferation of C cells associated with a variety of thyroid and parathyroid disorders.
Serum calcitonin screening in patients without previously known familial risk factors for MTC has proved to be effective in early detection of sporadic forms of MTC.
Hence, more thyroidectomies, based on increase serum calcitonin levels alone, can be expected, and surgical pathologists will be faced with an increasing number of total thyroidectomies.
Specimens from these patients make it possible to study early forms of sporadic C-cell carcinoma and probable precursor lesions.
Staging
Tumors can be staged according to the International Union Against Cancer (UICC).
Classsification
With regard to predominant growth pattern and tumor cell morphology, tumors were classified as prototypic, follicular, spindle cell, or clear cell variants.
The presence of amyloid deposits can be recorded.
The percentage of calcitonin and CEA-positive cells can be estimated.
Allelotype
NF2 (75%) (14707871)
l-myc (44%) (14707871)
p53 (44%) (14707871)
Predisposition
multiple endocrine neoplasia (MEN)
Cowden disease (17603316)
See also
References
Albores-Saavedra J, LiVolsi VA, Williams ED. Medullary carcinoma. Semin Diagn Pathol. 1985 May;2(2):137-46. PMID: 3843691
McDermott MB, Swanson PE, Wick MR. Immunostains for collagen type IV discriminate between C-cell hyperplasia and microscopic medullary carcinoma in multiple endocrine neoplasia, type 2a. Hum Pathol 1995;26:1308-312. PMID: 8522302
