Immunohistochemical profile of high-grade ductal carcinoma in situ of the breast

OBJECTIVE: To determine the frequency of the immunohistochemical profiles of a series of high-grade ductal carcinoma in situ of the breast. METHODS: One hundred and twenty-one cases of high-grade ductal carcinoma in situ, pure or associated with invasive mammary carcinoma, were identified from 2003 to 2008 and examined with immunohistochemistry for estrogen receptor, human epidermal growth factor receptor 2, cytokeratin 5, and epidermal growth factor receptor. The tumors were placed into five subgroups: luminal A, luminal B, HER2, basal-like, and “not classified”. RESULTS: The frequencies of the immunophenotypes of pure ductal carcinoma in situ were the following: luminal A (24/42 cases; 57.1%), luminal B (05/42 cases; 11.9%), HER2 (07/42 cases; 16.7%), basal-like phenotype (00/42 cases; 0%), and “not classified” (06/42 cases; 14.3%). The immunophenotypes of ductal carcinoma in situ associated with invasive carcinoma were the following: luminal A (46/79 cases; 58.2%), luminal B (10/79 cases; 12.7%), HER2 (06/79 cases; 7.6%), basal-like (06/79 cases; 7.6%), and “not classified” (11/79 cases; 13.9%). There was no significant difference in the immunophenotype frequencies between pure ductal carcinoma in situ and ductal carcinoma in situ associated with invasive carcinoma (p>0.05). High agreement was observed in immunophenotypes between both components (kappa=0.867). CONCLUSION: The most common immunophenotype of pure ductal carcinoma in situ was luminal A, followed by HER2. The basal-like phenotype was observed only in ductal carcinoma in situ associated with invasive carcinoma, which had a similar phenotype. .

Consultoria em patologia cirúrgica mamária: variabilidade interobservador no diagnóstico de lesões proliferativas intraductais atípicas / Consultation in breast surgical pathology: interobserver diagnostic variability of atypical intraductal proliferative lesions

OBJETIVO: Avaliar a concordância nos diagnósticos histopatológicos de lesões mamárias proliferativas intraductais entre patologistas gerais e especialistas em patologia mamária. MÉTODOS: Trata-se de estudo observacional e transversal, com análise de 209 lesões encaminhadas ao Laboratório de Patologia Mamária da Faculdade de Medicina da Universidade Federal de Minas Gerais para consultoria, no período de 2007 a 2011, comparando os diagnósticos originais com os após a revisão. Foram incluídos apenas os casos com solicitação formal de revisão e que apresentavam diagnóstico histopatológico no laudo original ou de revisão de lesões proliferativas, carcinoma ductal in situ puro, carcinoma ductal in situ com microinvasão ou associado a carcinoma invasor. A concordância percentual e o índice kappa foram utilizados para a análise estatística. RESULTADOS: Observamos moderada concordância nos diagnósticos originais de benignidade ou malignidade versus os diagnósticos de revisão (kappa=0,5; concordância percentual=83%). Após a revisão, o diagnóstico de malignidade foi confirmado em 140/163 casos (86%) e o diagnóstico de benignidade foi confirmado em 34/46 casos (74%). Quanto aos diagnósticos específicos, observamos concordância moderada entre o laudo original e de revisão (136/209 casos; kappa=0,5; concordância percentual=65%). A maior discordância foi observada nos casos de carcinoma ductal in situ com microinvasão (6/6 casos; 100%). Grande discordância foi observada nos casos de hiperplasia ductal atípica (16/30 casos; 53%) e carcinoma ductal in situ (25/75 casos; 33%). Em relação ao grau histológico do carcinoma ductal in situ, observou-se boa concordância entre os laudos originais e de revisão (29/39 casos; kappa=0,6; concordância percentual=74%). CONCLUSÃO: Nossos dados confirmam que as lesões mamárias proliferativas intraductais, em especial as hiperplasias ductais atípicas, o carcinoma ductal in situ e o carcinoma ductal in situ com microinvasão apresentam relevantes discordâncias nos diagnósticos histopatológicos, que podem induzir o clínico a erros nas decisões terapêuticas.

PURPOSE: To evaluate the agreement about the histopathological diagnosis of intraductal proliferative breast lesions between general pathologists and a specialist in breast pathology. METHODS: This was an observational, cross-sectional study of 209 lesions received in consultation at the Breast Pathology Laboratory of the School of Medicine, Federal University of Minas Gerais, from 2007 to 2011, comparing the original diagnosis and the review. We included only cases with a formal request for review and cases in which the original diagnosis or reviewer's diagnosis showed proliferative lesions, pure ductal carcinoma in situ, ductal carcinoma in situ associated with microinvasion or associated with invasive carcinoma. The kappa index and percent concordance were used in the statistical analyses. RESULTS: A moderate agreement was observed between the original histopathological diagnosis and the second opinion (kappa=0.5; percentual concordance=83%). After the review, the diagnosis of malignancy was confirmed in 140/163 cases (86%) and the diagnosis of benign lesions was confirmed in 34/46 cases (74%). Regarding specific diagnosis, we observed moderate agreement between the original diagnosis and the reviewer's diagnosis (136/209 cases; kappa=0.5; percent concordance=65%). The highest disagreement was observed in cases of ductal carcinoma in situ with microinvasion (6/6 cases; 100%). Important discordance was observed in cases of atypical ductal hyperplasia (16/30 cases; 53%) and ductal carcinoma in situ (25/75 cases; 33%). Regarding the histological grade of ductal carcinoma in situ, we observed good agreement between the original diagnosis and the review (29/39 cases; kappa=0.6, percent agreement=74%). CONCLUSION: Our data confirm that intraductal proliferative breast lesions, especially atypical ductal hyperplasia, ductal carcinoma in situ and ductal carcinoma in situ with microinvasion show relevant discrepancies in the histopathological diagnoses, which may induce errors in therapeutic decisions.

Contribuição da imuno-histoquímica na avaliação de fatores prognósticos e preditivos do câncer de mama e no diagnóstico de lesões mamárias / Contribution of immunohistochemistry to the assessment of prognostic and predictive factors of breast cancer and to the diagnosis of mammary lesions

OBJETIVO: Fazer análise crítica da contribuição da imuno-histoquímica na avaliação de fatores preditivos/prognósticos do câncer de mama, na pesquisa de micrometástases em linfonodos sentinela e no diagnóstico diferencial de lesões mamárias. MÉTODOS: Foi realizado estudo observacional retrospectivo de todos os casos de lesões mamárias e linfonodos sentinelas submetidas a estudo imuno-histoquímico no Laboratório de Patologia Mamária da Faculdade de Medicina da Universidade Federal de Minas Gerais (UFMG) entre 2001 e 2007. Os casos foram classificados de acordo com a indicação do estudo imuno-histoquímico em três categorias: avaliação de fatores preditivos/prognósticos, pesquisa de células epiteliais metastáticas em linfonodos sentinela e definição diagnóstica. RESULTADOS: Foram realizados exames imuno-histoquímicos de 1.294 casos, totalizando 4.101 reações com 21 anticorpos diferentes. Na maioria dos casos, a imuno-histoquímica foi realizada para avaliação de fatores preditivos/prognósticos (1.106 casos, 85,5 por cento), seguido de pesquisa de células epiteliais metastáticas em linfonodos sentinelas (134 casos, 10,6 por cento) e diagnóstico diferencial de lesões mamárias (51 casos, 3,9 por cento). Obtiveram-se reações de boa qualidade com importante contribuição do estudo imuno-histoquímico em 1.247 casos (96,4 por cento). Em 47 casos (3,6 por cento), o resultado foi inconclusivo devido a problemas de fixação (autólise) da fase pré-analítica. CONCLUSÃO: Nossos dados confirmam ser o estudo imuno-histoquímico importante ferramenta para avaliação de fatores preditivos e prognósticos do câncer de mama, pesquisa de micrometástases em linfonodos sentinelas e diagnóstico diferencial de lesões mamárias. A maior utilização da imuno-histoquímica foi para avaliação de fatores preditivos e prognósticos do câncer de mama.

OBJECTIVE: To critically analyze the contribution of immunohistochemistry to the assessment of prognostic and predictive factors of breast cancer, to the search for micrometastases in sentinel lymph nodes, and to the differential diagnosis of mammary lesions. METHODS: An observational retrospective study was carried out reviewing all cases of mammary lesions submitted to immunohistochemistry at the Breast Pathology Laboratory of Federal University of Minas Gerais between 2001 and 2007. According to immunohistochemistry indication, the cases were classified into three categories: assessment of prognostic and predictive factors, search for epithelial metastatic cells in sentinel lymph nodes and differential diagnosis. RESULTS: Immunohistochemistry was performed in 1,294 cases, with 4,101 reactions using 21 different antibodies. In most cases, immunohistochemistry was conducted to assess predictive/prognostic factors (1,106 cases, 85.5 percent), followed by search for epithelial metastatic cells in sentinel lymph nodes (134 cases, 10.6 percent) and differential diagnosis of breast lesions (51 cases, 3.9 percent). Good quality reactions, with significant contribution to the immunohistochemistry study, were obtained in 1,247 cases (96.4 percent). In 47 cases (3.6 percent) the results were inconclusive due to fixation problems (autolysis) in the pre-analytical phase. CONCLUSION: Our data confirm that the immunohistochemical study is an important tool to the assessment of predictive and prognostic factors, search for micrometastases in sentinel lymph nodes, and differential diagnosis of mammary lesions. The widest use of immunohistochemistry was in the assessment of predictive and prognostic factors of breast cancer.

Importância da segunda opinião em patologia cirúrgica mamária e suas implicações terapêuticas / Importance of a second opinion in breast surgical pathology and therapeutic implications

OBJETIVO: avaliar a concordância dos diagnósticos histopatológicos de lesões mamárias entre patologistas da comunidade e especialista em patologia mamária. MÉTODOS: foi realizado um estudo observacional, tipo coorte retrospectivo de 329 casos de lesões mamárias recebidas em consultoria para segunda opinião. Foram recebidas lâminas originais (152 casos), blocos de parafina (59 casos) ou lâminas e blocos (118 casos). Os casos foram revistos e os diagnósticos originais e os de revisão comparados, se avaliando a concordância no diagnóstico principal e na graduação nuclear dos casos de carcinoma ductal in situ e graduação histológica dos casos de carcinoma invasivo. Foram incluídos apenas casos com requisição de exame contendo dados clínicos e laudo anatomopatológico original final ou provisório. Para análise estatística foram usados o índice de kappa e a concordância percentual. RESULTADOS: a comparação geral entre os diagnósticos histopatológicos originais e pós-revisão evidenciou moderada concordância (índice de kappa=0,48) e concordância percentual de 59,9 por cento. Os diagnósticos de malignidade foram confirmados em 185/225 casos (82,2 por cento) e de lesões benignas em 89/104 casos (85,6 por cento). A maior concordância diagnóstica foi observada nos casos de carcinoma invasor (81 por cento) e as maiores discordâncias nos casos de carcinoma ductal in situ com microinvasão (74 por cento), carcinoma/neoplasia lobular in situ (70 por cento) e hiperplasias epiteliais atípicas (61 por cento). A análise do grau nuclear de 61 casos de carcinoma ductal in situ evidenciou moderada concordância (índice de kappa=0,52, concordância percentual=68,8 por cento). Foi observada boa concordância em relação ao grau histológico no carcinoma invasivo (índice de kappa=0,61, concordância percentual=74,3 por cento). CONCLUSÕES: os resultados mostram maior concordância no diagnóstico do carcinoma invasivo e menor concordância no diagnóstico de carcinoma ductal ...

PURPOSE: to evaluate the agreement between histopathologic diagnoses of breast lesions made by general pathologists and by a specialist in breast pathology. METHODS: a cohort retrospective study comparing histopathologic diagnoses of 329 cases of breast lesions received in consultation for a second opinion was carried out. The material received for consultation included slides (152 cases), paraffin blocks (59 cases) or slides and blocks (118 cases). Cases were reviewed and the original diagnoses and diagnoses from a specialist in breast pathology were compared. The main diagnoses, nuclear grade of ductal carcinoma in situ, and the histopathologic grade of invasive mammary carcinomas were evaluated. The kappa index and percentual concordance were used in the statistical analyses. RESULTS: a moderate agreement was observed between the original histopathologic diagnoses and the second opinion (kappa index=0.48; percentual concordance=59.9 percent). The diagnosis of malignancy was confirmed in 185/225 cases (82.2 percent) and diagnosis of benign lesions was confirmed in 89/104 cases (85.6 percent). The highest agreement was observed in the diagnosis of invasive mammary carcinomas (81 percent) and the highest disagreement was observed among diagnoses of ductal carcinoma in situ with microinvasion (74 percent), lobular carcinoma in situ (70 percent), and atypical epithelial hyperplasias (61 percent). There was a moderate agreement in the nuclear grade of ductal carcinoma in situ (kappa index=0.52; percentual concordance=68.8 percent), and good concordance in the histologic grade of invasive carcinomas (kappa index=0.61; percentual concordance=74.3). CONCLUSIONS: the results show higher concordance rate in the diagnosis of invasive carcinomas and lower concordance in the diagnosis of ductal carcinoma in situ with microinvasion and premalignant breast lesions, especially lobular neoplasia in situ, and atypical epithelial hyperplasias.

Carcinoma ductal in situ da mama: critérios para diagnóstico e abordagem em hospitais públicos de Belo Horizonte / Approach of ductal carcinoma in situ of the breast in three public hospitals in Belo Horizonte

OBJETIVOS: avaliar os aspectos clínicos, radiológicos, anátomo-patológicos e terapêuticos de uma série de casos de carcinoma ductal in situ (CDIS) da mama de pacientes atendidos em três hospitais públicos de Belo Horizonte (MG). MÉTODOS: foram selecionados dos arquivos médicos todos os casos de câncer de mama diagnosticados entre os anos de 1985 e 2000, encontrando-se 179 casos com diagnóstico de CDIS. Fez-se revisão anátomo-patológica das lâminas e obtiveram-se dados clínicos completos, mamografias e informações sobre tratamento em 85 casos. RESULTADOS: a maioria dos casos eram assintomáticos e os diagnósticos foram feitos pela mamografia (68,2 por cento), sendo as microcalcificações a alteração radiológica mais freqüente. Houve aumento progressivo no diagnóstico de CDIS ao longo dos anos simultâneo à introdução do exame periódico mamográfico. Houve concordância entre o diagnóstico inicial e após a revisão histopatológica em 72,9 por cento dos casos. Em três casos, o diagnóstico original de CDIS não foi confirmado pela revisão, tratando-se de hiperplasias com atipias. O achado de microcalcificações radiológicas foi confirmado no estudo histopatológico em 95,6 por cento. A metade dos pacientes foi submetida à mastectomia. Nos casos submetidos à linfadenectomia axilar, todos os linfonodos dissecados foram negativos para metástases. CONCLUSÕES: os dados encontrados estão de acordo com a literatura, que mostra um aumento do diagnóstico do CDIS a partir de 1990. Houve importante variação interobservador entre os diagnósticos anátomo-patológicos iniciais e os da revisão, sendo que os diagnósticos iniciais tendiam para malignidade. Houve grande número de tratamentos mais radicais como a mastectomia e esvaziamentos axilares, que provavelmente, com os conhecimentos atuais, seriam substituídos por tratamentos conservadores e biópsia do linfonodo sentinela.

PURPOSE: to evaluate the clinical, radiological therapeutic and anatomo-pathological aspects in a series of patients with breast ductal carcinoma in situ (DCIS), attended in three public hospitals in Belo Horizonte (MG). METHODS: 179 cases of DCIS, that were selected from all the patients who had been diagnosed with breast cancer between 1985 and 2000, were studied retrospectively. After reviewing all the tissue sections, it was possible to collect all the clinical data, mammogram and treatment information of 85 cases. RESULTS: most patients were not symptomatic and the diagnosis had been done by mammogram (68.2 percent), being the microcalcification the most common radiological alteration. There has been a progressive increase in the diagnosis of DCIS along the years, following the introduction of periodical mammographic screening. The initial histopathological diagnosis and the review agreed in 72.9 percent of cases. In three cases, the original diagnosis of DCIS was not confirmed, being classified as atypical hyperplasia. Mammogram microcalcifications were confirmed in the pathological analysis in 95.6 percent of cases. Half of the patients was treated with mastectomy. All lymph nodes from axillary dissection were negative for metastases. CONCLUSIONS: The present study is in agreement with the recent literature, which shows an increase in the diagnosis of DCIS since 1990. There has been a great interobserver variation since the initial pathological diagnosis, which tended to malignancy and the present review. There were a great number of radical treatments, such as mastectomy and axillary dissection, which would probably be replaced by conservative treatment and sentinel lymph node biopsy nowadays, according to recent knowledge.

Valor do estudo radiológico do tórax no diagnóstico de disfunçäo ventricular esquerda na doença de Chagas / Value of the radiological study of the thorax for diagnosing left ventricular dysfunction in Chagas' disease

OBJECTIVE: To determine the value of the radiological study of the thorax for diagnosing left ventricular dilation and left ventricular systolic dysfunction in patients with Chagas' disease. METHODS: A cross-sectional study of 166 consecutive patients with Chagas' disease and no other associated diseases. The patients underwent cardiac assessment with chest radiography and Doppler echocardiography. Sensitivity, specificity, and positive and negative predictive values of chest radiography were calculated to detect left ventricular dysfunction and the accuracy of the cardiothoracic ratio in the diagnosis of left ventricular dysfunction with the area below the ROC curve. The cardiothoracic ratio was correlated with the left ventricular ejection fraction and the left ventricular diastolic diameter. RESULTS: The abnormal chest radiogram had a sensitivity of 50 percent, specificity of 80.5 percent, and positive and negative predictive values of 51.2 percent and 79.8 percent, respectively, in the diagnosis of left ventricular dysfunction. The cardiothoracic ratio showed a weak correlation with left ventricular ejection fraction (r=-0.23) and left ventricular diastolic diameter (r=0.30). The area calculated under the ROC curve was 0.734. CONCLUSION: The radiological study of the thorax is not an accurate indicator of left ventricular dysfunction; its use as a screening method to initially approach the patient with Chagas' disease should be reevaluated