Cytological and histopatological specimens of young woman, aged 22, with medullary carcinoma of thyroid gland associated with multiple endocrine neoplasia type 2A presented. She had elevated calcitonin levels, and RET
The slides represent fine-needle biopsy of right and left lobes of thyroid gland stained with HE, histopatological specimen of surgically excised tissue stained with HE (upper part is from the right lobe and lower one is from the left), and histopatological specimen of surgically excised lymph nodes (upper part contains nodes from the right side of neck and lower one - from the left) respectively.
See on virtual slides:
Fine-needle biopsy specimens of right and left lobes of thyroid gland contain spindly cells with nuclei of different forms and sizes, that are of "salt and pepper" pattern, and amyloid, that is charactericstic for medullary carcinoma of thyroid gland. Some of cells have epithelioid features with eosinophilic abundant cytoplasm and oval eccentrically located nucleus. Besides, few cells have plasmacytoid features.
Histopathological specimen of the right lobe of thyroid and right side lymph nodes: there is a tumor with maximum dimension of 7 mm, and there are seats of C cells hyperplasia and chronic inflammation in the tissue of the right lobe of thyroid; there are metastases (not wider than 3 mm) in two lymph nodes of three excised.
Histopathological specimen of the left lobe of thyroid and left side lymph nodes: there is a multifocal tumor immediate to surgical excision margin, and there are seats of C cells hyperplasia and chronic inflammation in the tissue of the left lobe of thyroid; there are metastases (not wider than 4 mm) in three lymph nodes of four excised.
Immunophenotype (not shown here): Calcitonin +, Chromogranin A +, Synaptophysin +. MIB-1 + in 1%.
What is medullary carcinoma of thyroid gland:
Medullary carcinoma of the thyroid gland (MTC) is a distinct thyroid carcinoma that originates in the parafollicular C cells of the thyroid gland. C cells are calcitonin-producing ones, but if transformed malignantly they can produce calcitonin, prostaglandins, serotonin, somatostatin, bombesin, VIP, etc.
MTC is the third most common of all thyroid cancers (5%-8%) after papillary and follicular thyroid cancers. In 75% of patients isolated, or sporadic, MTC occurs, though MTC may be a part of multiple endocrine neoplasia (MEN) type 2A (bilateral medullary carcinoma or C cell hyperplasia, and pheochromocytoma, and hyperparathyroidism) and 2B (medullary carcinoma, and pheochromocytoma, and mucosal ganglioneuromas - tumors in the mouth, and only rarely hyperparathyroidism) syndromes, and in some cases has an inheritable non-MEN mode of transmission. Isolated MTC typically demonstrates a relatively indolent biologic progression. While regional lymph node metastases are possible, the lesion may not spread outside of the cervical region until several months later. MTC associated with MEN syndromes may have a more aggressive course, which also depends on associated comorbidities.
Peak incidence of isolated MTC occurs in the fifth or sixth decade of life, and peak incidence of MTC associated with MEN 2A or 2B occurs during the second or third decade of life. The treatment is surgical, however targeted therapy clinical trials (early stages) have shown promising results and tolerable toxicity. For now, approximately 86% of treated patients with MTC live at least 5 years after diagnosis. Overall 10-year survival rate is 65% - it is 90% when all the disease is confined to the thyroid gland, 70% with spread to cervical lymph nodes, and 20% when spread to distant sites is present.
Diagnosis of MTC can be verified by fine-needle aspiration biopsy. Most often smear is composed of large epitelial cells with abundant cytoplasm of irregular shape and large, hyperchromatic, often excentric nuclei, provided with prominent nucleoli. But there are tumor variants, composed wholly, or in part, of spindly, elongated cells (as presented in the case) or of small cancer cells. Presence of amyloid is a characterisic component of MTC.
Histologically, the tumors are richly vascularised, and fibrovascular stroma is usually intercalated between cells. Sometimes, amyloid material, consisting of calcitonin prohormone, may occur in the MTC stroma. Perhaps most importantly, immunohistochemical diagnosis of MTC can be made by demonstrating calcitonin in MTC cells. Sporadic MTC usually is unilateral and C cells hyperplasia seats are usually absent, but in association with MEN syndromes, it always is bilateral and multicentric and C cells hyperplasia seats are present as a rule. RET protoonkogene presence is characteristic for MTC associated with MEN syndromes also.
Medullary carcinoma of thyroid gland in literature:
- A. Machens, K. Lorenz, and H. Dralle: Constitutive RET tyrosine kinase activation in hereditary medullary thyroid cancer: clinical opportunities. J Intern Med 266:114-125, 2009
- Carlo Capella et al: Multiple endocrine cell types in thyroid medullary carcinoma. Virch Arch 377(2):111-128, 1978
- C.E. Dent, J. Faccini, and A. Hodsman: Medullary carcinoma of thyroid gland in a girl aged 10 years. Arch Dis Child. 51(3): 223-226, 1976.
- Kamaljeet Singh, Mehar C Sharma, Deepali Jain, and Rajinder Kumar: Melanotic medullary carcinoma of thyroid - report of a rare case with brief review of literature. Diagnostic Pathology 3:2, 2008
- Michitoshi Osaka, Jun Soga, Youichi Tamiya, and Tsutomu Suzuki: Dedifferentiation of neoplastic cells in medullary thyroid carcinoma: Report of a case. Surg Today 29(11):1189-1194, 1999
- P.R. Gordon, A.G. Huvos, E.W. Strong: Medullary carcinoma of the thyroid gland.A clinicopathologic study of 40 cases. Cancer 31(4):915-924, 1973
- Soren Schroder et al: Prognostic factors in medullary thyroid carcinomas. Survival in relation to age, sex, stage, histology, immunocytochemistry, and DNA content. Cancer 61(4):806-816, 1988
- W. van Veelen et al: Medullary thyroid carcinoma and biomarkers: past, present and future. J Intern Med 266:126-140, 2009
- Anastasios K Konstantakos et al: Thyroid, Medullary Carcinoma. Medline.
- PathConsult: Medullary Carcinoma.
Case prepared by:
Jacek Sygut, Janusz Kopczynski, Piotr Faszczewski, Roman Bastow,
Zaklad Patologii Nowotworow, Swietokrzyskie Centrum Onkologii.