Cytological evaluation of thyroid tumors

The introduction of aspiration cytology into the preoperative diagnosis of thyroid disease in the 1970s has reduced the rate of thyroid surgery by 50% while increasing the rate of patients with neoplastic nodules undergoing surgery by 10-15% (according to some authors even up to 20-50%). Ultrasonography enables the detection of nonpalpable nodules, identification of suspicious nodules for performing fine-needle aspiration (FNA) biopsy and targeted cytological biopsy in order to obtain adequate material. Reduction of the number of unnecessary surgical procedures with an increase in the required surgery rate essentially depends on the specificity and sensitivity of the cytological diagnosis of benign and malignant thyroid tumors. Cytologic features of papillary carcinoma (~80% of malignancies) are clearly defined and include nuclear inclusions, irregular and overlapping nuclei, psammoma bodies and papillary formations with fibrovascular stroma. This form of thyroid neoplasm is rarely primarily diagnosed as a metastatic process in the cervical lymph nodes and even more rarely as metastasis to distant organs (lungs, etc.) when the size of the primary tumor in the thyroid is <1 cm. Follicular and Hurthle cell neoplasms (~ 20% of malignancies) display cytologic characteristics which may be compatible with a malignancy but are nondiagnostic. There are currently no genetic, morphologic or biochemical tests that are routinely used for differentiating between benign and malignant neoplasms in this category, apart from histopathology which implies capsular or vascular invasion. Many studies have demonstrated that TPO expression (MoAb 47) improves the specificity of the accurate diagnosis compared with cytology alone (83 vs. 55%). Galectin-3 shows strong and diffuse expression in all thyroid malignomas of the follicular origin (including papillary, follicular, Hurthle cell and anaplastic carcinoma), but also minimal expression in benign lesions. In the opinion of most surgeons, intraoperative biopsy and frozen sections have minimal value in the diagnosis of malignant and benign lesions in case of follicular or Hurthle cell tumors. Cytologic features of a follicular or Hurthle cell carcinoma include: minimal amounts of free colloid, high density cell population, predominance of isolated cells, syncytial clusters, multiple nucleoli and nuclear cytoplasmic inclusions (for Hurthle cell carcinoma). Medullary carcinoma (~ 1-5% of thyroid malignomas) is suspected when patients have a family history of medullary cancer or multiple endocrine neoplasia (MEN) Type 2. Mixed follicular-medullary carcinoma is even more uncommon type of thyroid malignancy. Cytologic characteristics suggesting this type of malignancy include: parafollicular differentiation, red granules in the cytoplasm, spindle-like cells with eccentric nuclei, and immunocytochemical positivity for calcitonin, chromogranin and NSE. Anaplastic carcinoma (<1% of thyroid malignancies) usually only occurs in elderly patients as a rapidly growing thyroid mass exhibiting extreme cellular pleomorphism, multinucleated and/or giant cells, and necrotic and blood-stained contents. Malignant lymphomas are often associated with Hashimoto's thyroiditis. These most frequently include non-Hodgkin's lymphomas (large B-cell, follicular or MALT lymphomas), clonal B-neoplasms of characteristic immunophenotypic features. Hodkin's lymphoma is extremely rare as primary thyroid lymphoma, also with characteristic morphology and immunophenotype. Other primary thyroid tumors of mesenchymal origins are particularly rare, benign and malignant variants alike: derived from the fatty tissue (lipomas or liposarcomas), stromal cells (fibromas or fibrosarcomas) or vascular cells (angiomas or angiosarcomas). Metastatic tumors are of lesser clinical significance than primary thyroid tumors. Hematogenic spread to the thyroid occurs mainly in advanced stages of pulmonary, large intestinal and renal carcinoma, melanoma, leukemia and lymphoma. The cytomorphologic picture accompanied by immunocytochemistry with tissue- or tumor- specific antigenes may aid in determining cellular origin of the tumor, differentiating primary from secondary tumors, as well as in recognizing the primary site of the tumor.