Resumo Um dos maiores dilemas diante de uma lâmina de citopatologia é o diagnóstico diferencial de lesões foliculares da tiroide agrupadas como lesões de padrão folicular e que incluem; bócio, adenoma (AF) e carcinoma foliculares (CF), carcinoma papilífero variante folicular (CPVF) e a neoplasia folicular não invasiva com características nucleares papilares (NIFTP) (Uno de los mayores dilemas que presenta una muestra de citopatología es el diagnóstico diferencial de las lesiones foliculares tiroideas reunidas como lesiones de patrón folicular, que incluyen: bocio, adenoma folicular [AF], carcinoma folicular (CF), variante folicular del carcinoma papilar [VFCP] y la neoplasia folicular no invasiva con características nucleares de tipo papilar [NIFTP, por su sigla en inglés]. Tais lesões compartilham muitas características, o que faz com que a identificação adequada de lesões foliculares malignas represente um desafio. A citologia obtida através de punção aspirativa por agulha fina (PAAF) é o método padrão mais efetivo para diagnóstico em nódulos de tiroide, mas sua eficácia diagnóstica diminui nitidamente em lesões de padrão folicular da tiroide (La citología por punción y aspiración con aguja fina [PAAF]) es el método estándar más eficaz para el diagnóstico de los nódulos tiroideos, pero su eficacia diagnóstica se ve notablemente reducida en las lesiones de patrón folicular de la tiroides). Assim, uma série de ferramentas auxiliares ao diagnóstico, como a morfometria e a análise de textura nuclear, têm sido utilizadas cada vez mais na prática do patologista, como ferramenta objetiva e reproduzível. São técnicas que dependem da incorporação de softwares para análise digital de imagens e podem agregar acurácia à análise morfológica clássica e à imunohistoquímica na avaliação de lesões de padrão folicular (para el análisis de imágenes digitales y puede agregar precisión al análisis morfológico clásico y la inmunohistoquímica en la evaluación de lesiones de patrón folicular). Somando-se à imunocitoquímica e às técnicas moleculares, a morfometria permite a estimativa de parâmetros identificados em células individuais e representam uma ferramenta que, a partir de parâmetros quantitativos, traduz parâmetros confiáveis para classificação objetiva de malignidade. O objetivo deste estudo é rever as características nucleares e seu papel no diagnóstico de lesões foliculares da tiroide (es revisar las características nucleares y su papel en el diagnóstico de las lesiones foliculares tiroideas).

Abstract One of the biggest dilemmas facing a cytopathology slide is the differential diagnosis of follicular thyroid lesions, grouped as follicular pattern lesions, which include goiter, follicular adenoma (FA) and follicular carcinoma (FC), follicular variant of papillary thyroid carcinoma (FVPTC) and non-invasive follicular thyroid neoplasm with papillary like nuclear features (NIFTP). Such lesions share many characteristics, which makes the proper identification of malignant follicular lesions a challenge. The cytology obtained through fine needle aspiration puncture (FNAB) is the most effective standard method for diagnosis in thyroid nodules, but its diagnostic efficacy clearly decreases in lesions of thyroid follicular pattern. Thus, a series of auxiliary tools for diagnosis, such as morphometry and nuclear texture analysis, have been increasingly used in the pathologist's practice, as an objective and reproducible tool. These are techniques, which depend on the incorporation of software to digital image analysis and can add accuracy to classical morphological analysis and immunohistochemistry in the evaluation of follicular pattern lesions. In addition to immunocytochemistry and molecular techniques, morphometry allows the estimation of parameters identified in individual cells and represents a tool that, based on quantitative parameters, translates reliable parameters for objective classification of malignancy. The aim of this study is to review the nuclear characteristics and their role in the diagnosis of follicular thyroid lesions.

OBJECTIVES: Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3+ lymphocyte infiltration in differentiated thyroid carcinoma cells. METHODS: We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues. RESULTS: We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3+ lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion, and in patients with concurrent chronic lymphocytic thyroiditis. CONCLUSIONS: We demonstrated FoxP3 expression in differentiated thyroid carcinoma cells and found evidence that this expression may exert an important influence on several features of tumor aggressiveness.

O uso cada vez mais freqüente de métodos diagnósticos simples e efetivos tem contribuído significativamente para um aumento no diagnóstico de câncer da tiróide nos últimos anos. Entretanto, existem importantes evidências de que muitos dos microcarcinomas papilíferos têm um comportamento indolente e podem nunca evoluir para cânceres clínicos. Existe, portanto, uma necessidade urgente de desenvolver novas ferramentas capazes de predizer quais os tumores tiroidianos que permanecerão silenciosos e quais desenvolverão comportamento agressivo. Há uma série de marcadores clínicos de evolução bem estabelecidos e alguns estudos recentes sugerem que dados laboratoriais e métodos de imagem podem ser úteis. Marcadores moleculares também vêm sendo ativamente investigados e alguns, como BRAF, os genes GST e polimorfismos de p53, parecem promissores. Além disso, marcadores imunocitoquímicos e a medida da natureza fractal da cromatina podem aumentar a especificidade do diagnóstico anatomopatológico e ajudar a predizer o prognóstico. Existe uma necessidade imperiosa de elaborarmos diretrizes destinadas a selecionar os nódulos que merecem prosseguimento em sua avaliação, assim como novos métodos capazes de identificar lesões mais agressivas entre os geralmente indolentes tumores tiroidianos.

The large use of simple and effective diagnostic tools has significantly contributed to the increase in diagnosis of thyroid cancer over the past years. However, there is compelling evidence that most micropapillary carcinomas have an indolent behavior and may never evolve into clinical cancers. Therefore, there is an urgent need for new tools able to predict which thyroid cancers will remain silent, and which thyroid cancers will present an aggressive behavior. There are a number of well-established clinical predictors of malignancy and recent studies have suggested that some of the patient’s laboratory data and image methods may be useful. Molecular markers have also been increasingly tested and some of them appear to be very promising, such as BRAF, a few GST genes and p53 polymorphisms. In addition, modern tools, such as immunocytochemical markers, and the measure of the fractal nature of chromatin organization may increase the specificity of the pathological diagnosis of malignancy and help ascertain the prognosis. Guidelines designed to select nodules for further evaluation, as well as new methods aimed at distinguishing carcinomas of higher aggressiveness among the usually indolent thyroid tumors are an utmost necessity.