Follicular variant of papillary carcinoma. Cytologic and histologic correlation.

The cytologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPTC) can be difficult owing to the paucity of nuclear changes of papillary carcinoma and overlapping features with other follicular-derived lesions. We report our fine-needle aspiration (FNA) experience with 17 histologically proved cases of FVPTC with a preceding FNA. All cases showed increased cellularity and a background of moderate to abundant thin watery colloid with variable amounts of thick eosinophilic colloid. The cells were arranged mainly in monolayer sheets and syncytial fragments; occasional microfollicle formation with abundant fine eosinophilic cytoplasm was seen. Nuclear enlargement was a consistent finding in all cases. Only 5 cases showed prominent nuclear features of papillary carcinoma. Histologic examination showed encapsulated follicular-patterned nodules with multifocal random distribution of nuclear features of papillary carcinoma that were more pronounced in the subcapsular locations of the lesions. This morphologic heterogeneity explains the variability seen in FNA specimens of FVPTC and may result in false-negative diagnoses. We believe that these findings should be considered when interpreting follicular lesions; suspicion of an FVPTC should be conveyed in the cytopathology report, which may prompt intraoperative assessment to avoid a second surgical intervention for completion thyroidectomy.

Nuclear envelope organization in papillary thyroid carcinoma.

Papillary thyroid carcinomas (PTCs) have characteristic nuclear shape changes compared to follicular-type thyroid epithelium. We tested the hypothesis that the altered nuclear shape results from altered distribution or expression of the major structural proteins of the nuclear envelope. Lamin A, lamin B1, lamin C, lamin B receptor (LBR), lamina-associated polypeptide 2 (LAP2), emerin, and nuclear pores were examined. PTC's with typical nuclear features by H&E were compared to non-neoplastic thyroid and follicular neoplasms using confocal microscopy, and semi-quantitative immunoblotting. Lamin A/C, lamin B1, LAP2, emerin, and nuclear pores all extend throughout the grooves and intranuclear inclusions of PTC. Their distribution and fluorescent intensity is not predictably altered relative to nuclear envelope irregularities. By immunoblotting, the abundance (per cell) and electrophoretic mobilities of lamin A, lamin B1, lamin C, emerin, and LAP2 proteins do not distinguish PTC, normal thyroid, or follicular neoplasms. These results do not support previously published predictions that lamin A/C expression is related to a loss of proliferative activity. At least three LAP2 isoforms are identified in normal and neoplastic thyroid. LBR is sparse or undetectable in all the thyroid samples. The results suggest that the irregular nuclear shape of PTC is not determined by these nuclear envelope structural proteins per se. We review the structure of the nuclear envelope, the major factors that determine nuclear shape, and the possible functional consequences of its alteration in PTC.

Multinucleated giant cells in fine needle aspirates. Can they help differentiate papillary thyroid cancer from benign nodular goiter?

OBJECTIVE: To determine whether multinucleated giant cells (MGCs) in fine needle aspirates can help differentiate papillary thyroid carcinoma (PTC) from benign nodular goiter (BNG). STUDY DESIGN: Specimens from 100 cases of PTC and 100 cases of BNG with surgical and pathologic proof were randomly retrieved. The morphologic characteristics and frequency distribution of the maximal size and number of MGC nuclei were analyzed. A retrospective review of medical records was also undertaken. RESULTS: MGCs were twice as frequent (40%) in PTC than in BNG (26%) (odds ratio = 1.90). Most MGCs in BNG tended to be smaller and ovoid, with foamy cytoplasm, and had fewer nuclei. No MGC in BNG was > 116 microns in diameter or had > 27 nuclei. In contrast, MGCs in PTC were more diverse in size, shape, cytoplasm and number of nuclei. No significant association was found between the presence or nature of MGCs and disease extent in PTC. CONCLUSION: The presence of large MGCs with dense cytoplasm in a thyroid nodule without clinical evidence of thyroiditis should prompt careful exclusion of associated PTC.

The encapsulated follicular variant of papillary thyroid carcinoma: back to the drawing board.

The encapsulated follicular variant of papillary carcinoma has become one of the most common diagnoses in thyroid tumor pathology. However, serious issues remain regarding the reproducibility of the diagnosis, its position in the scheme of thyroid neoplasms, and the clinical implications of the diagnosis. Strict morphologic criteria should be applied to its microscopic recognition, especially in regard to the nuclear features. The generally indolent behavior of this tumor should be recognized in order to avoid overtreatment.

[Contribution of nuclear texture analysis for the differential diagnosis of follicular lesions of the thyroid: comparison to immunohistochemical markers]. / Contribuição da análise de textura do núcleo celular para o diagnóstico diferencial de lesões foliculares da tireoide: comparação com marcadores imunoistoquímicos.

OBJECTIVE AND METHODS: To investigate the utility of nuclear chromatin texture assessment in the differential diagnosis of follicular patterned lesions, by means of examining 76 samples previously submitted to the immunohistochemical protein analysis of HBME-1, CK-19 and galectina-3. RESULTS: HBME-1 confirmed to be the most sensitive marker of malignancy. A series of morphometric, densitometric and texture variables were useful in the discrimination of the different types of follicular lesions. Among these variables, r(2), a parameter related to the granularity of the nucleus presented the best accuracy, sensitivity, specificity and positive and negative predictive values, distinguishing benign from malignant lesions. CONCLUSION: The morphometric analysis of nuclear chromatin images may add accuracy to the differential diagnosis of follicular patterned lesions.

Loss of polarity and de novo expression of the beta 1 family of integrins in thyroid tumors.

The expression and cell-membrane distribution of the beta 1 family of integrins (very-late-activation antigens, VLA) were investigated in benign and malignant human thyroid tumors. We compared tissue samples of normal glands, nodular goiters, adenomas and carcinomas. We also examined 3 thyroid-carcinoma cell lines cultured in vitro. The expression of subunits of the beta 1 family of integrins was assessed by flow cytometry and specific antibodies in dispersed single-cell suspensions and by immunofluorescence on frozen tissue sections. In contrast to the heterogeneity of the expression of beta 1 integrins observed in other tumors, thyroid neoplastic lesions showed a remarkably constant VLA profile. In all tumors, benign as well as malignant, and in carcinoma cell lines, all sub-units of beta 1 integrins were expressed at high levels. While sub-units alpha 1, alpha 3, alpha 5, alpha 6 and occasionally alpha 2 were also present in a cell sub-set of normal glands and nodular goiters, expression of alpha 4 was restricted to neoplastic lesions; this integrin can be therefore considered an antigen associated with thyroid tumors. It has been reported that in normal glands and in nodular goiters, the expression of beta 1 integrins is restricted to the basal-cell membrane. Immunofluorescence on tissue sections showed instead that, in adenomas and carcinomas, the polarized distribution of these integrins on the cell membrane is lost.

Contribuição da análise de textura do núcleo celular para o diagnóstico diferencial de lesões foliculares da tireoide: comparação com marcadores imunoistoquímicos / Contribution of nuclear texture analysis for the differential diagnosis of follicular lesions of the thyroid: comparison to immunohistochemical markers

OBJETIVO E MÉTODOS: Com o propósito de investigar a contribuição do exame da cromatina nuclear no diagnóstico diferencial das lesões foliculares da glândula tireoide, foram estudadas 76 amostras previamente submetidas à análise de expressão proteica de HBME-1, CK-19 e galectina-3. RESULTADOS: HBME-1 confirmou-se como o mais sensível marcador imunoistoquímico de malignidade. Uma série de variáveis morfométricas, densitométricas e de textura foram úteis na distinção entre os diferentes tipos de lesão folicular. Entre essas variáveis, o r², parâmetro relacionado à granularidade do núcleo, apresentou a melhor acurácia, sensibilidade, especificidade, valor preditivo positivo e negativo, diferenciando lesões benignas de malignas. CONCLUSÃO: A morfometria analítica de imagem da cromatina nuclear pode acrescentar acurácia ao diagnóstico diferencial das lesões de padrão folicular.

OBJECTIVE AND METHODS: To investigate the utility of nuclear chromatin texture assessment in the differential diagnosis of follicular patterned lesions, by means of examining 76 samples previously submitted to the immunohistochemical protein analysis of HBME-1, CK-19 and galectina-3. RESULTS: HBME-1 confirmed to be the most sensitive marker of malignancy. A series of morphometric, densitometric and texture variables were useful in the discrimination of the different types of follicular lesions. Among these variables, r², a parameter related to the granularity of the nucleus presented the best accuracy, sensitivity, specificity and positive and negative predictive values, distinguishing benign from malignant lesions. CONCLUSION: The morphometric analysis of nuclear chromatin images may add accuracy to the differential diagnosis of follicular patterned lesions.