Comparação das características nucleares da neoplasia tireoidiana folicular não invasiva com características nucleares do tipo carcinoma papilífero, do carcinoma papilífero de tireoide subtipo folicular e do carcinoma folicular através da análise digital de imagens em amostra citológica.
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2023-04-12
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Universidade Estadual Paulista (Unesp)
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INTRODUÇÃO: Neoplasia tireoidiana folicular não invasiva com características nucleares do tipo carcinoma papilífero (NIFTP) é um diagnóstico histológico. Além disso, existe grande sobreposição dos resultados na citologia de NIFTP, carcinoma papilífero de tireoide subtipo folicular (CPTSF) e carcinoma folicular (CF). Nos dias de hoje, não há substratos morfológicos para diferenciar essas entidades no exame citológico e assim, levantamos a hipótese, se a análise computadorizada das imagens nucleares, através da patologia digital, poderia auxiliar nessa diferenciação. OBJETIVO: Comparar material citológico de NIFTP e seus principais diagnósticos diferenciais, CPTSF e CF quanto aos parâmetros morfométricos e morfológicos nucleares através de técnica de análise digital de imagens, a fim de fortalecer a identificação de NIFTP ainda no pré-operatório. MÉTODOS: Estudo observacional analítico e retrospectivo que avaliou variáveis morfométricas nucleares do material citológico de nódulos tireoidianos, do período de 2017 a 2021, classificados histologicamente como CPTSF, NIFTP e CF no Instituto de Patologia de Araçatuba (IPAT), São Paulo, Brasil. Analisou-se cinco casos de cada entidade e dois citopatologistas revisaram todos os casos de acordo com o Sistema Bethesda. Informações clínicas como sexo, idade, tamanho do tumor e localização (lobo esquerdo, lobo direito, istmo) foram coletadas do relatório da punção aspirativa por agulha fina (PAAF). Imagens citológicas foram fotografadas e 1170 células de cada entidade foram analisadas digitalmente usando o software ImageJ, por análise cega. Um traçado manual e cuidadoso dos limites de cada núcleo na imagem fotografada foi realizado usando uma ferramenta de desenho para extração de dados. A avaliação morfométrica incluía área, perímetro, largura, altura e circularidade. Variáveis numéricas foram descritas pela média, mediana e seu mínimo e máximo (mín.; máx.). Kruskal-Wallis e teste de Dunn foram utilizados e as diferenças foram consideradas estatisticamente significativas se p < 0.05. RESULTADOS: Em todas as categorias, estavam distribuídos 4 mulheres e 1 homem. Entre os casos de CPTSF, a idade mediana foi de 48 anos. Quatro casos foram classificados como suspeitos para malignidade e um como maligno de acordo com o Sistema Bethesda. Todos os casos foram estadiados como pT1b pN0, com mediana do tamanho do nódulo de 1.3cm. Entre os casos de NIFTP, a mediana da idade foi de 40 anos. Todos os casos foram classificados como suspeitos para malignidade e a mediana do tamanho do nódulo foi de 1.5cm. Entre o CF, a mediana da idade foi de 45 anos, três casos foram classificados como suspeitos para neoplasia folicular/suspeito para neoplasia folicular, um caso suspeito para malignidade e um caso como atipia de significado indeterminado/neoplasia folicular de significado indeterminado. Nas três categorias analisadas, o tamanho do tumor foi diferente entre os grupos, sendo maior no grupo do CF (CPTSF: média: 1.4 cm vs. NIFTP: 1.54 cm vs. CF: 5.66 cm; p = 0.009). Em relação a análise nuclear, todas as variáveis tiveram diferença entre os grupos (p < 0.001), inferindo dessa forma, pelas variáveis serem interdependentes que o tamanho nuclear foi maior no grupo da NIFTP, que por sua vez foi maior que no grupo do CF. (NIFTP > CF > CPTSF). Quando avaliou-se dois grupos entre si, apenas a circularidade nuclear não foi diferente entre NIFTP e CF (p = 0.152). DISCUSSÃO/CONCLUSÃO: Comparativamente, a análise das imagens digitais com ênfase nos parâmetros nucleares foi diferente quanto ao tamanho entre NIFTP, CPTSF e CF em amostra citológica. Dessa forma, este instrumento tem potencial em acrescentar informações que possam auxiliar no diagnóstico dessas entidades ainda no pré-operatório. Sendo assim, mais estudos são necessários para criação de protocolos para estimular a aplicabilidade dos parâmetros morfológicos e morfométricos nucleares com enfoque na patologia digital para utilização de algoritmos e ferramentas que auxiliem na rotina diagnóstica do citopatologista.
INTRODUCTION: Up to now non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a histological diagnosis. In the current post-NIFTP era, the challenge is to suspect the diagnosis, even in the preoperative period. We hypothesized that computerized analysis of nuclear images could differentiate NIFTP from papillary thyroid carcinoma follicular subtype (PTCFS) and follicular carcinoma (FC) influencing patient’s management (lobectomy vs. total thyroidectomy) in the context of high risk for NIFTP. METHODS: We performed a retrospective analytical observational study based on nuclear morphometric variables of the cytological material of thyroid nodules classified as PTCFS, NIFTP, and FC. Five cases of each entity were analyzed. Two cytopathologists reviewed all cases according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We recorded sex, age, tumor size, and location (left lobe, right lobe, isthmus) from fine-needle aspirate reports. Cytological slides were photographed, and 1170 cells for each entity were analyzed digitally. The captured images were evaluated using free software (ImageJ) blindly. The morphometric evaluation included area, perimeter, width, height, and circularity. Numerical variables were expressed as mean, medians, minimum, and maximum (min; max). Kruskal-Wallis and Dunn’s tests were used with a 5% significance level. RESULTS: In all categories, there were four women and one man. Among PTCSF cases, the median age was 48 years. Four cases were classified as suspicious for malignancy and one as malignant, according to TBSRTC. All cases were staged as pT1b pN0. Among NIFTP cases, the median age was 40 years. All cases were classified as suspicious of malignancy. Among FC cases, the median age was 45 years; three cases were classified as suspicious for follicular neoplasm, one case was suspicious for malignancy, and one case was a follicular lesion of undetermined significance. Tumor size was larger in the FC group (CPTSF: mean: 1.4 cm vs. NIFTP: 1.54 cm vs. FC: 5.66 cm; p = 0.009). Regarding nuclear analysis, all variables differed among the three groups (p < 0.001). Once the variables are interdependent, these data indicated that nuclear size was greater in the NIFTP group followed by CF and CPTSF. DISCUSSION/CONCLUSION: Comparatively, the analysis of digital images with emphasis on nuclear parameters was different regarding nuclear size among NIFTP, CPTSF and CF in cytological specimens. Thus, this instrument has the potential to add information that may help in the diagnosis for NIFTP, even during the preoperative period. Additional studies are needed to create protocols, evaluate the applicability of nuclear morphological and morphometric parameters focusing on digital pathology, and create algorithms and tools to assist the cytopathologist’s diagnostic routine.
INTRODUCTION: Up to now non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a histological diagnosis. In the current post-NIFTP era, the challenge is to suspect the diagnosis, even in the preoperative period. We hypothesized that computerized analysis of nuclear images could differentiate NIFTP from papillary thyroid carcinoma follicular subtype (PTCFS) and follicular carcinoma (FC) influencing patient’s management (lobectomy vs. total thyroidectomy) in the context of high risk for NIFTP. METHODS: We performed a retrospective analytical observational study based on nuclear morphometric variables of the cytological material of thyroid nodules classified as PTCFS, NIFTP, and FC. Five cases of each entity were analyzed. Two cytopathologists reviewed all cases according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We recorded sex, age, tumor size, and location (left lobe, right lobe, isthmus) from fine-needle aspirate reports. Cytological slides were photographed, and 1170 cells for each entity were analyzed digitally. The captured images were evaluated using free software (ImageJ) blindly. The morphometric evaluation included area, perimeter, width, height, and circularity. Numerical variables were expressed as mean, medians, minimum, and maximum (min; max). Kruskal-Wallis and Dunn’s tests were used with a 5% significance level. RESULTS: In all categories, there were four women and one man. Among PTCSF cases, the median age was 48 years. Four cases were classified as suspicious for malignancy and one as malignant, according to TBSRTC. All cases were staged as pT1b pN0. Among NIFTP cases, the median age was 40 years. All cases were classified as suspicious of malignancy. Among FC cases, the median age was 45 years; three cases were classified as suspicious for follicular neoplasm, one case was suspicious for malignancy, and one case was a follicular lesion of undetermined significance. Tumor size was larger in the FC group (CPTSF: mean: 1.4 cm vs. NIFTP: 1.54 cm vs. FC: 5.66 cm; p = 0.009). Regarding nuclear analysis, all variables differed among the three groups (p < 0.001). Once the variables are interdependent, these data indicated that nuclear size was greater in the NIFTP group followed by CF and CPTSF. DISCUSSION/CONCLUSION: Comparatively, the analysis of digital images with emphasis on nuclear parameters was different regarding nuclear size among NIFTP, CPTSF and CF in cytological specimens. Thus, this instrument has the potential to add information that may help in the diagnosis for NIFTP, even during the preoperative period. Additional studies are needed to create protocols, evaluate the applicability of nuclear morphological and morphometric parameters focusing on digital pathology, and create algorithms and tools to assist the cytopathologist’s diagnostic routine.
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Tireóide - Cãncer, Avaliação nuclear carcinoma folicular, Avaliação nuclear carcinoma papilífero tireoide subtipo folicular, Câncer papilífero da tireoide, Patologia digital de imagens, Citologia tireoidiana