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Thyroid Cytology locked

Adjunctive Diagnostic Value of Ancillary Techniques

Ultrafast Papanicolaou stain selectively swells the nuclei of papillary thyroid carcinoma, making their nuclear grooves disappear and making the swollen nuclei look like "watery grapes", while this staining method has no effect on nuclei of a follicular adenoma. This artifactual change is due to the disorganization of nuclear lamins and permits a confident distinction between a follicular adenoma and a follicular variant papillary carcinoma. Immunostaining with thyroid peroxidase antibody has been reported to be of value in distinguishing these two lesions, as malignant and benign follicular cells commonly stain negatively and positively with this antibody, respectively.

Ploidy determination has no value in distinguishing a follicular adenoma from a follicular carcinoma and immunostaining for p53, Ki-67 and Bcl-2 has no value in separating benign from malignant Hurthle cell tumors.

Genetics-molecular studies have been extensively carried out on tissue samples of different types of thyroid neoplasm since the past decade. However, only a few genetics-molecular studies on thyroid cells obtained by FNA have been recently published. Human telomerase reverse transcriptase (hTERT) gene expression, using reverse transcriptase-polymerase chain reaction, has been identified as a promising diagnostic marker in distinguishing benign from malignant tumors in materials obtained by FNA. It was found that 90 and 92.8% of thyroid carcinomas were positive for hTERT while 35 and 61.5% of benign thyroid nodules were positive for hTERT, respectively. Among the thyroid tumors with positive hTERT, there were eight of eight papillary, two of two Hurthle cell and three of four follicular carcinomas. BRAF point mutation and RET/thyroid PC rearrangements were found in 38% of thyroid PCs and refined the diagnosis of thyroid PC in five of fifteen cell samples that were considered either indeterminate or insufficient by cytology. No mutation was found in FNAs of follicular adenomas and non-toxic nodular goiters. These molecular markers were of adjunctive diagnostic value when the FNA diagnosis of TN was equivocal.

Powerful molecular techniques including microarray analysis and molecular profiling may have a significant role in the future evaluation of TNs, while providing impetus for further insight into the molecular pathogenesis of both benign and malignant TNs. Moreover, such techniques may allow deeper insight into both loss and gain of function of unidentified genes by examining panels of genes rather than one or a limited number of potential gene candidates. By analysis of cancer gene profiles for a cohort of 62 thyroid samples, Finley et al were able to distinguish between benign and malignant thyroid tumors. They reported a sensitivity of 91.7% and specificity of 96.2% for the detection of thyroid carcinomas of various types, including thyroid PC and its follicular variant and follicular carcinoma. Distinction of benign and malignant thyroid tumors and molecular classification of follicular thyroid tumors by gene profiling suggests that these powerful techniques may have significant diagnostic potential when used with FNA cytology. Molecular profiling may also permit the distinction between primary and metastatic malignancies when dealing with multiple suspicious nodules at various sites. Using material retrieved by FNA, Schoedel et al, compared loss of heterozygosity (LOH) patterns and demonstrated genetic kinship of multifocal carcinomas in the thyroid and a separate nodule in the lung, supporting a diagnosis of metastatic thyroid carcinoma to the lung rather than an independent lung neoplasm.

At present, techniques such as microarray analysis are limited by the amount of RNA that can be retrieved from a sample, thereby often limiting analysis to surgically resected samples. However, refinement of these techniques may make them applicable to FNA, with extraction of RNA from a cell block from which molecular analysis of FNA material may have significant diagnostic benefit.

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