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Medullary carcinoma of thyroid:

It is a rare tumor of thyroid constituting of less than 10% of thyroid tumors. These are neuroendocrine tumors of thyroid derived from parafollicular cells of thyroid which are also called as C cells. Like the normal C cells the medullary carcinomas also secrete Calcitonin. Measurement of levels of calcitonin helps in diagnosis and post operative management and follow-up of the patients.

Association of Medullary carcinoma:

    • Multiple endocrine neoplasm syndrome type 2A (MEN2A) or sipple syndrome
    • MEN 2B or known as mucosal neuroma syndrome
    • Familial Non-MEN medullary thyroid carcinoma
    • It usually arises sporadically. 10-20% cases  are familial
    • Associated with mutations in RET oncogene

MEN2A or sipple syndrome:

It includes medullary thyroid cancer, c-cell hyperplasia, adrenal pheochromocytoma, adrenal medullary hyperplasia and parathyroid hyperplasia.

MEN2B or mucosal neuroma syndrome:

It consists of medullary thyroid carcinoma, c-cell hyperplasia, pheochromocytoma, adrenal medullary hyperplasia,mucosal neuromas, gastrointestinal ganglioneuromas and musculoskeletal abnormalities.

Clinical presentation:

Painless, firm thyroid nodule.                                              

    • Sporadic cases:
      • Adulthood 40-50years age
      • More common in women                                
    • Familial cases:
      • Young age
      • Equal sex ratio
      • Bilaterality and multicentricity is common 

Gross features:

    • Usually circumscribed lesion
    • Firm, pale gray to tan on cut-surface
    • Larger lesions may show necrosis and hemorrhage

Microscopic features:

    • Cells arranged in nests or trabeculae separated by varying amount of stoma
    • Cells are round, polygonal, oval or spindle shaped
    • Uniform nuclei with low nuclear to cytoplasmic ratio
    • Mtosis are seen
    • Stroma contains amyloid

Special stains and immunohistochemistry:

    • Amyloid is highlighted by Congo-red as Salmon-pink on light microscope and apple-green colour on birefringence
    • Calcitonin is positive within the cytoplasm as well as in stroma

These tumors are important to diagnose due to their aggressive  nature. First degree relatives of the affected family member should undergo genetic screening and a positive result should be followed by prophylactic total thyroidectomy.

Other thyroid tumors:

Sclerosing mucoepidermoid carcinoma with eosinophilia:

It arises in the background of lymphocytic thyroiditis. Cells are arranged in small sheets, trabeculae and strands with dense fibrosis in background. Numerous eosinophils are also present. These may metastasize to lymph nodes or show capsular and vascular invasion but overall survival rate is better. These are negative for  thyroglobulin and calcitonin and are positive for CK.

Malignant lymphoma:

It can arise as a primary tumor or may inolve thyroid secondarily as a part of systemic disease. Women are frequently involved and the patients are usually older. Arises in setting of Hashimoto thyroiditis usually.

Large, flesy masses, tan to gray in colour. These may shoe extrathyroidal extension also. Microscopy resembles the lymphoma of any other site. Usual subtype occurring in thyroid is Diffuse large B-Cell lymphoma. Lymphoepithelial lesion is a common finding that consists of thyroid follicles infiltrated with neoplastic lymphoid cells .

Treatment of lymphoma depends on staging of disease so it is important to see for the proper staging of tumor. If the tumor is widespread chemotherapy is done. If the tumor is localized then radiotherapy with or without adjuvant chemotherapy is done. The prognosis of localized lymphoma of thyroid is excellent.

Metastatic tumors:

Thyroid can be involved directly by carcinomas of larynx, pharynx, trachea and esophagus. It can be involved by hematogenous or lymphatic route in addition to direct extension.


Dr Saadia Hafeez



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