Carcinoma ductal in situ: seguimiento de una población / Ductal carcinoma in situ: monitoring a population

Con la introducción de la mamografía, la incidencia del carcinoma ductal in situ (CDIS) se ha incrementado en los últimos 30 años. Estudios randomizados han demostrado la eficacia de la radioterapia y el tamoxifeno en reducir los segundos eventos luego de la cirugía conservadora de CDIS. Los objetivos de este trabajo fueron analizar las características de las pacientes con CDIS, los tratamientos realizados, la ocurrencia de segundos eventos y los factores de riesgo asociados a estos. Material y método: Se analizaron 50 pacientes con carcinoma ductal in situ tratadas en el Hospital Provincial Neuquén desde 1999 a 2012. Se recolectaron datos clínicos y anatomopatológicos. Se evaluó la ocurrencia de segundos eventos en relación con el cáncer de mama y factores de riesgo asociados. Se estimó la supervivencia libre de enfermedad y la supervivencia global. Resultados: Con un seguimiento medio de 86,5 meses, ocurrieron 5 segundos eventos en tres pacientes (6%): dos (el 4%) tuvieron recaída ipsilateral, una de ellas en forma de carcinoma ductal in situ y otra como carcinoma invasor; el tercer evento (2%) se presentó como carcinoma invasor contralateral. Todos ocurrieron en pacientes con tratamiento conservador (cirugía conservadora más radioterapia). Fueron factores de riesgo asociados: el alto grado nuclear, el subtipo comedo, la presencia de márgenes comprometidos y el no uso de tamoxifeno. Ocurrió una muerte en relación con la enfermedad (2%). La supervivencia libre de enfermedad fue del 94% y la global del 98%. Conclusiones: En nuestra población el carcinoma ductal in situ representa el 8% de los carcinomas mamarios. Se presentaron recaídas ipsilaterales en el 4% de la población y carcinoma invasor contralateral en el 2%. Las muertes correspondieron al 2% de la población...

Breast Microcalcifications: Diagnostic Outcomes According to Image-Guided Biopsy Method

OBJECTIVE: To evaluate the diagnostic outcomes of ultrasonography-guided core needle biopsy (US-CNB), US-guided vacuum-assisted biopsy (US-VAB), and stereotactic-guided vacuum-assisted biopsy (S-VAB) for diagnosing suspicious breast microcalcification. MATERIALS AND METHODS: We retrospectively reviewed 336 cases of suspicious breast microcalcification in patients who subsequently underwent image-guided biopsy. US-CNB was performed for US-visible microcalcifications associated with a mass (n = 28), US-VAB for US-visible microcalcifications without an associated mass (n = 59), and S-VAB for mammogram-only visible lesions (n = 249). Mammographic findings, biopsy failure rate, false-negative rate, and underestimation rate were analyzed. Histological diagnoses and the Breast Imaging Reporting and Data System (BI-RADS) categories were reported. RESULTS: Biopsy failure rates for US-CNB, US-VAB, and S-VAB were 7.1% (2/28), 0% (0/59), and 2.8% (7/249), respectively. Three false-negative cases were detected for US-CNB and two for S-VAB. The rates of biopsy-diagnosed ductal carcinoma in situ that were upgraded to invasive cancer at surgery were 41.7% (5/12), 12.9% (4/31), and 8.6% (3/35) for US-CNB, US-VAB, and S-VAB, respectively. Sonographically visible lesions were more likely to be malignant (66.2% [51/77] vs. 23.2% [46/198]; p < 0.001) or of higher BI-RADS category (61.0% [47/77] vs. 22.2% [44/198]; p < 0.001) than sonographically invisible lesions. CONCLUSION: Ultrasonography-guided vacuum-assisted biopsy is more accurate than US-CNB when suspicious microcalcifications are detected on US. Calcifications with malignant pathology are significantly more visible on US than benign lesions.

Retrieval Rate and Accuracy of Ultrasound-Guided 14-G Semi-Automated Core Needle Biopsy of Breast Microcalcifications

OBJECTIVE: To evaluate the retrieval rate and accuracy of ultrasound (US)-guided 14-G semi-automated core needle biopsy (CNB) for microcalcifications in the breast. MATERIALS AND METHODS: US-guided 14-G semi-automated CNB procedures and specimen radiography were performed for 33 cases of suspicious microcalcifications apparent on sonography. The accuracy of 14-G semi-automated CNB and radiology-pathology concordance were analyzed and the microcalcification characteristics between groups with successful and failed retrieval were compared. RESULTS: Thirty lesions were successfully retrieved and the microcalcification retrieval rate was 90.9% (30/33). Thirty lesions were successfully retrieved. Twenty five were finally diagnosed as malignant (10 invasive ductal carcinoma, 15 ductal carcinoma in situ [DCIS]) and five as benign. After surgery and mammographic follow-up, the 25 malignant lesions comprised 12 invasive ductal carcinoma and 13 DCIS. Three lesions in the failed retrieval group (one DCIS and two benign) were finally diagnosed as two DCIS and one benign after surgery. The accuracy of 14-G semi-automated CNB was 90.9% (30/33) because of two DCIS underestimates and one false-negative diagnosis. The discordance rate was significantly higher in the failed retrieval group than in the successful retrieval group (66.7% vs. 6.7%; p < 0.05). Punctate calcifications were significantly more common in the failed retrieval group than in the successful retrieval group (66.7% vs. 3.7%; p < 0.05). CONCLUSION: US-guided 14-G semi-automated CNB could be a useful procedure for suspicious microcalcifications in the breast those are apparent on sonography.

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. .

Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ

OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may provide clinically useful information regarding the risk of progression to invasive disease. .

Comparison of nuclear grade and immunohistochemical features in situ and invasive components of ductal carcinoma of breast / Comparação do grau nuclear e perfil imunoistoquímico nos componentes in situ e invasivo de carcinoma mamário

PURPOSE:To compare the prognostic and predictive features between in situ and invasive components of ductal breast carcinomas. METHODS:We selected 146 consecutive breast samples with ductal carcinoma in situ (DCIS) associated with adjacent invasive breast carcinoma (IBC). We evaluated nuclear grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR) in both components, in situ and invasive, and the Ki-67 percentage of cells in the invasive part. The DCIS and IBC were classified in molecular surrogate types determined by the immunohistochemical profile as luminal (RE/PR-positive/ HER2-negative), triple-positive (RE/RP/HER2-positive), HER2-enriched (ER/PR-negative/HER2-positive), and triple-negative (RE/RP/HER2-negative). Discrimination between luminal A and luminal B was not performed due to statistical purposes. Correlations between the categories in the two groups were made using the Spearman correlation method. RESULTS:There was a significant correlation between nuclear grade (p<0.0001), expression of RE/RP (p<0.0001), overexpression of HER2 (p<0.0001), expression of EGFR (p<0.0001), and molecular profile (p<0.0001) between components in situ and IBC. CK 5/6 showed different distribution in DCIS and IBC, presenting a significant association with the triple-negative phenotype in IBC, but a negative association among DCIS. CONCLUSIONS: Our results suggest that classical prognostic and predictive features of IBC are already determined in the preinvasive stage of the disease. However the role of CK5/6 in invasive carcinoma may be different from the precursor lesions.

OBJETIVO: Comparar características prognósticas e preditivas entre os componentes in situ e invasivo de carcinomas ductais da mama. MÉTODOS: Selecionamos 146 amostras mamárias consecutivas com carcinoma ductal in situ (CDIS) associado com carcinoma invasivo (CI) adjacente. Avaliamos grau nuclear e a expressão imunoistoquímica de receptor de estrogênio (RE), receptor de progesterona (RP), receptor do fator de crescimento epidérmico humano 2 (HER2), citoqueratina 5/6 (CK5/6) e o receptor do fator de crescimento epidérmico (EGFR) em ambos componentes, in situ e invasor, e a porcentagem de células marcadas pelo Ki-67 no componente invasivo. CDIS e CI foram classificados nos tipos moleculares, determinados pelo perfil imunoistoquímico, como luminal (RE/RP-positivo/HER2-negativo), triplo-positivo (RE/RP/HER2-positivo), HER2-puro (RE/RP-negativo/HER2-positivo) e triplo-negativo (RE/RP/HER2-negativo). A discriminação entre luminal A e Luminal B não foi feita por motivos estatísticos. Correlações entre as categorias dos dois grupos foram feitas pelo método de correlação de Spearman. RESULTADOS: Houve significante associação entre grau nuclear (p<0,0001), expressão de RE/RP) (p<0,0001), superexpressão de HER2 (p<0,0001), expressão de EGFR (p<0,0001) e perfil molecular (p<0,0001) entre os componentes in situ e invasivo. CK5/6 mostrou distribuição distinta em CDIS e CI, apresentando significante associação com o fenótipo triplo-negativo em CI, mas uma associação negativa ente os CDIS. CONCLUSÕES:Nossos resultados sugerem que as características prognósticas e preditivas clássicas dos CI estão já determinadas no estágio pré-invasivo da doença. Entretanto, o papel da CK5/6 no carcinoma invasivo pode ser diferente daquele das lesões precursoras.

Molecular phenotypes of ductal carcinoma-in-situ and invasive ductal carcinoma: A comparative study.

Aims and Objectives: This study was aimed at analyzing the prevalence of molecular phenotypes in invasive ductal carcinoma (IDC) and coexisting ductal carcinoma-in-situ (DCIS) and to correlate with clinicopathological features. Materials and Methods: In this study, 75 cases of IDC with coexisting DCIS were included. Molecular phenotype was determined using expression of estrogen receptor, progesterone receptor, HER2/neu, and cytokeratin 5/6. Statistical analysis was performed for correlation between molecular phenotypes and clinicopathologic parameters. Results: Of the 75 cases, the invasive component in all cases was IDC-not otherwise specified. About one-third of our patients were post-menopausal. The most common molecular phenotype was luminal A (45.3%) followed by HER2-expressing type (24%). In all cases, the molecular phenotype was identical in DCIS and the invasive component. HER2-expressing tumors were found to be larger in size with frequent nodal involvement. On statistical analysis, tumor size and grade were found to correlate with the molecular phenotype. Conclusion: In conclusion, the molecular phenotype in DCIS correlates well with that of coexisting IDC, suggesting that DCIS is a precursor lesion in these tumors. This correlation of molecular phenotype can be utilized in prediction of phenotype of the invasive component in a case with in-situ carcinoma.

Cyclooxygenase-2 and human epidermal growth factor receptor type 2 (HER-2) expression simultaneously in invasive and in situ breast ductal carcinoma / Expressão da ciclo-oxigenase-2 e receptor tipo 2 do fator de crescimento epidérmico humano (HER-2) simultaneamente em carcinoma ductal de mama in situ e invasivo

CONTEXT AND OBJECTIVE: Cyclooxygenase-2 (COX-2) and human epidermal growth factor receptor type 2 (HER-2) are associated with tumorigenesis. Studies have shown that HER-2 can regulate COX-2 expression. The aim of this study was to evaluate the correlation between COX-2 and HER-2 expression in normal breast epithelium and in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) present in the same breast. DESIGN AND SETTING: Cross-sectional study at the Mastology Unit of the Department of Gynecology and Obstetrics, Santa Casa de Misericórdia de São Paulo Hospital. METHODS: COX-2 and HER-2 were detected using immunohistochemistry on 100 tissue fragments. HER-2 > +2 was subjected to fluorescence in situ hybridization (FISH). RESULTS: COX-2 expression was detected in 87 percent, 85 percent and 75 percent of IDC, DCIS and normal epithelium, respectively. HER-2 expression was detected in 34 percent of IDC and 34 percent of DCIS. COX-2 in DCIS correlated with HER-2 in IDC (P = 0.049) and DCIS (P = 0.049). COX-2 in normal epithelium correlated with HER-2 in IDC (P = 0.046) and DCIS (P = 0.046). COX-2 in IDC was not associated with HER-2 (P = 0.235). Comparison between COX-2 and HER-2 in DCIS showed that there was a statistically significant difference with regard to nuclear grades II and III and presence of comedonecrosis (P < 0.001). In IDC, there was significant expression with nuclear grades II and III and histological grade II (P < 0.001). CONCLUSIONS: Our findings provide evidence that HER-2 and COX-2 regulate each other.

CONTEXTO E OBJETIVO: Ciclo-oxigenase (COX-2) e receptor tipo 2 do fator de crescimento epidérmico humano (HER-2) estão associados com tumorigênese. Estudos mostraram que HER-2 pode regular a expressão de COX-2. O objetivo deste estudo foi avaliar a correlação entre expressão da COX-2 e HER-2 no epitélio normal de mama, no carcinoma ductal in situ (DCIS) e carcinoma ductal invasivo (IDC) presentes na mesma mama. TIPO DE ESTUDO E LOCAL: Estudo transversal na clínica de Mastologia do Departamento de Obstetrícia e Ginecologia do Hospital da Santa Casa de Misericórdia de São Paulo. MÉTODOS: A detecção da COX-2 e HER-2 foi realizada por imunoistoquímica em 100 fragmentos teciduais. HER-2 > +2 foi submetido a hibridização fluorescente in situ (FISH). RESULTADOS: Expressão de COX-2 foi detectada em 87 por cento, 85 por cento e 75 por cento dos IDC, DCIS e epitélio normal, respectivamente. Expressão de HER-2 foi detectada em 34 por cento dos IDC e 34 por cento de DCIS. COX-2 em DCIS correlacionou-se com HER-2 em IDC (P = 0,049) e DCIS (P = 0,049). COX-2 no epitélio normal correlacionou-se com HER-2 em IDC (P = 0,046) e DCIS (P = 0,046). COX-2 no IDC não foi associada com HER-2 (P = 0,235). Quando comparado COX-2 com HER-2 em DCIS houve diferença estatisticamente significante com relação ao grau nuclear II e III e presença de comedonecrose (P < 0,001) e no IDC, houve expressão significativa no grau nuclear II e III e histológico II (P < 0,001). CONCLUSÕES: Nossos achados mostram evidências que HER-2 e COX-2 se autorregulam.

Linfonodo sentinela em câncer de mama: situações especiais na prática clínica / Sentinel lymph node biopsy in breast cancer: special situations in clinical practice

A biópsia do linfonodo sentinela já é um procedimento consagrado tanto em nivel nacional quanto internacional para a avaliação da axila de pacientes com câncer de mama diagnosticado na sua fase inicial. Porém, ainda existem algumas situações que geram dúvidas tanto sobre a melhor abordagem, quanto o tratamento. Nos últimos anos, temos observado um crescente interesse em relação à biópsia do linfonodo sentinela (BLS) e na maneira como urilizá-la em algumas situações especiais como no carcinoma ductal in situ (CDIS), quando há drenagem para a mamária interna, câncer de mama na gravidez, mastectomia profilática e tratamento quimioterápico sistêmico pré-operatório (quimioterapia sistêmica neoadjuvante - QT neo). Existem diversos estudos prospectivos em andamento para se estabelecer a condura ideal. Porém, enquanto os resultados não são publicados, necessitamos nos atualizar com relação à melhor maneira de abordá-los. Este artigo tentou apresentar, de maneira clara e resumida, o que há de mais recente publicado em relação à essas situações.

The sentinel lymph node biopsy is an accepted procedure at a national and international level to study the axillary status of patients with early-stage breast cancer. However there are some special situations that create some doubts about the better way to diagnostic and to threat it. In the last years we have seen a greatest interest in sentinel lymph node biopsy (SINB) and in the manner how to use it in some special situations like ductal carcinoma in situ, when there is migration to internal mammary lymph nodes, breast cancer and pregnancy, during prophylactic mastectomy and systemic therapy before surgery (preoperative chemotherapy). There are several prospective studies going on, with the intent to determine the ideal treatment for these special situations. While these results are not published, we must be aware of the better way to treat them. This article tries to show, in an easy and clear way, what have been published recently about these situations.

Carcinoma de mama en el hombre: revisión de casos / Breast carcinoma in men: report of cases

El objetivo del presente trabajo es presentar el comportamiento clínico patológico de 8 pacientes del sexo masculino con carcinoma de la mama, atendidos en el Instituto Oncológico "Dr. Luis Razetti" durante los años 2004-2005. El cáncer de mama en hombres representó el 2,33 por ciento, 37,5 por ciento fueron adenocarcinoma ductal infiltrante, 37,5 por ciento estadio IIIA, 87,5 por ciento se trató con mastectomías radicales modificadas, 57,25 por ciento expresan receptores de estrógenos, 28,57 por ciento sobre expresan Her2neu, 37,5 por ciento recibió adyuvancia, 62,5 por ciento con tamoxifeno, el seguimiento promedio fue de 44 meses, 37,5 por ciento de recaídas local y 62,5 por ciento están libres de enfermedad a los 5 años. El cáncer de mama en hombres es muy poco frecuente. El tratamiento primario es la cirugía, siguiendo los mismos lineamientos para la adyuvancia que en las mujeres.

The objective of the present work is analyzing the clinic pathologic status of 8 patients of sex male, attending in the Oncological Institute "Dr. Luis Razetti" during the 2004-2005 years. The breast cancer in male represented the 2.33 percent, in 37.5 percent of them were ductal infiltrante adenocarcinoma, 37.5 percent were state IIIA,87.5 percent were treated with surgery: Modified radical mastectomy, 57.25 percent express estrogen receptors, 28,57 percent over express Her2neu. 37.5 percent received adjuvant, 62.5 percent with tamoxifen, the average of periodic control was 44 month, and 37.5 percent of local recurrence and 62.5 percent of the patients are free of disease to 5 years. The breast cancer in male is less frequent. The primary treatment is surgery, with the same form to the adjuvant as in women.

TNM staging and classification (familial and nonfamilial) of breast cancer in Jordanian females.

Purpose : Staging of breast tumor has important implications for treatment and prognosis. This study aims at pinpointing the frequency of each stage among familial and nonfamilial breast cancers. Materials and Methods : Ninety-nine Jordanian females diagnosed with familial and nonfamilial breast cancer between 2000 and 2002 were enrolled in this study All breast cancer cases were staged according to the TNM classification into in situ, early invasive, advanced invasive and metastatic. Results : Forty-three cases were familial breast cancer and 56 were nonfamilial. One female breast cancer was diagnosed with ductal carcinoma in situ (DCIS) cancer. Fifty cases were diagnosed in early stages of invasive breast cancer, of which 31 cases were familial, 29 cases were classified as advanced invasive, where 21 cases were nonfamilial and 19 cases were metastatic stage of breast cancer, with 16 nonfamilial cases. Stage 2b was the most common stage of early invasive cases and represented 48% of the early stage of breast cancer. On the other hand, among cases diagnosed with advanced invasive breast cancer, stage 3a was the most common stage and represented 89.6% of the advanced stage. Interestingly, all cases of stage 3a belonged to TNM stages of T2N2M0 and T3N1M0. The tumor size in all cases of Jordanian females diagnosed with advanced invasive breast cancer exceeded 2 cm in size due to selection bias from symptomatic women in our study. Conclusion : The incidence of nonfamilial breast cancer was slightly higher than that of the familial type amongst studied the Jordanian females studied. The early invasive stage of breast cancer was more common in the familial while the advanced invasive and metastatic breast cancer cases were encountered more often in the nonfamilial type. Our study was based on a small sample and symptomatic women. Therefore, more research with larger population samples is needed to confirm this conclusion.

Expressão da proteína erbB-2 e dos receptores de hormônios na transição das regiões in situ para invasora de tumores da mama / ErbB-2 expression and hormone receptor status in areas of transition from in situ to invasive ductal breast carcinoma

OBJETIVOS: avaliar a expressão de erbB-2 e dos receptores hormonais para estrógeno e progesterona (RE/RP) nas regiões de transição entre as frações in situ e invasoras de neoplasias ductais da mama (CDIS e CDI, respectivamente). MÉTODOS: oitenta e cinco casos de neoplasias mamárias, contendo regiões contíguas de CDIS e CDI, foram selecionados. Espécimes histológicos das áreas de CDIS e de CDI foram obtidos através da técnica de tissue microarray (TMA). As expressões da erbB-2 e dos RE/RP foram avaliadas por meio de imunoistoquímica convencional. A comparação da expressão da erbB-2 e dos RE/RP nas frações in situ e invasoras da mama foi realizada com emprego do teste de McNemar. Os intervalos de confiança foram determinados em 5 por cento (p=0,05). Foram calculados coeficientes de correlação intraclasse (ICC) para avaliar a concordância na tabulação cruzada da expressão de erbB-2 e RE/RP nas frações de CDIS e CDI. RESULTADOS: a expressão da erbB-2 não diferiu entre as áreas de CDIS e CDI (p=0,38). Comparando caso a caso suas áreas de CDIS e CDI, houve boa concordância na expressão da erbB-2 (coeficiente de correlação intraclasse, ICC=0,64), dos RP (ICC = 0,71) e dos RE (ICC = 0,64). Considerando apenas tumores cujo componente in situ apresentasse áreas de necrose (comedo), o ICC para erbB-2 foi de 0,4, comparado a 0,6 no conjunto completo de casos. Os ICC não diferiram substancialmente daqueles obtidos com o conjunto completo de espécimes em relação aos RE/RP: para RE, ICC=0,7 (versus 0,7 no conjunto completo), e para RP, ICC=0,7 (versus 0,6 no conjunto completo). CONCLUSÕES: nossos achados sugerem que as expressões de erbB-2 e RE/RP não diferem nos componentes contíguos in situ e invasivo em tumores ductais da mama.

PURPOSE: to evaluate the expression of erbB-2 and of the estrogen and progesterone (ER/P) hormonal receptors in the transition regions between the in situ and the invasive fractions of ductal breast neoplasia (ISDC and IDC, respectively). METHODS: Eighty-five cases of breast neoplasia, containing contiguous ISDC and IDC areas, were selected. Histological specimens from the ISDC and the IDC areas were obtained through the tissue microarray (TMA) technique. The erbB-2 and the ER/PR expressions were evaluated through conventional immunohistochemistry. The McNemar's test was used for the comparative analysis of the expressions of erbB-2 protein and the ER/PR in the in situ and invasive regions of the tumors. The confidence intervals were set to 5 percent (p=0.05). Intraclass correlation coefficients (ICC) were calculated to assess the cross-tabulation agreement of the erbB-2 and the ER/PR expression in the ISDC and the IDC areas. RESULTS: the erbB-2 expression has not differed between the ISDC and the IDC areas (p=0.38). Comparing the two areas in each case, there was agreement in the expression of erbB-2 (ICC=0.64), PR (ICC=0.71) and ER (ICC=0.64). Restricting the analysis to tumors with the in situ component harboring necrosis (comedo), the ICC for erbB-2 was 0.4, compared to 0.6 for the whole sample. In this select group, the ICC for PR/ER did not differ substantially from those obtained with the complete dataset: as for the ER, ICC=0.7 (versus 0.7 for the entire sample) and for PR, ICC=0.7 (versus 0.6 for the entire sample). CONCLUSIONS: our findings suggest that the erbB-2 and the ER/PR expressions do not differ in the contiguous in situ and invasive components of breast ductal tumors.

Expressão da aromatase em carcinomas de mama ductais invasivo e in situ presentes na mesma mama / Aromatase expression in invasive and in situ ductal carcinoma present in the same breast

OBJETIVO: Avaliar expressão da enzima aromatase nos carcinomas de mama ductais invasivos (CDI), in situ (CDIS), no epitélio e estromas adjacentes. MÉTODOS: Foram avaliados 45 espécimes cirúrgicos provenientes de mastectomias e quadrantectomias com CDI e CDIS concomitantes de pacientes com estadios clínicos I e II. A análise da expressão da enzima aromatase foi realizada por meio de anticorpos policlonais antiaromatase e categorização das amostras de acordo com intensidade e número de células coradas. RESULTADOS: Nos 45 casos de CDI a expressão da aromatase foi positiva em 32 espécimes (71 por cento) e negativa em 13 (29 por cento). Nos casos de CDIS, a positividade foi idêntica à observada no CDI, mostrando correlação positiva. No epitélio normal constatou-se expressão positiva em 19 casos (42,2 por cento) e negativa nos outros 26 (57,8 por cento), mostrando correlação positiva estatisticamente (p<0,01), quando comparada com CDI e CDIS. Na análise do estroma normal a expressão da aromatase foi observada em apenas sete (15,5 por cento) dos 45 casos avaliados, não apresentando correlação com nenhuma variável analisada para expressão da aromatase. A presença da aromatase no estroma tumoral foi positiva em 36 casos (80 por cento) e negativa em 9 (20 por cento), mostrando correlação estatisticamente com a expressão no CDI (p<0,01) e no CDIS (p<0,01). Ao se comparar a expressão da aromatase no CDI, CDIS, epitélio normal e estroma tumoral com os graus nuclear e histológico, tamanho tumoral e idade da paciente, não foram encontradas diferenças estatisticamente significantes. CONCLUSÃO: Os resultados revelaram alta correlação entre expressão da aromatase no CDI, CDIS, epitélio normal e estroma tumoral, sugerindo possível mecanismo de ação autócrina e parácrina desta enzima na gênese do câncer de mama.

OBJECTIVE: to evaluate the expression of aromatase in simultaneously invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). METHODS: forty-five surgical samples were obtained from mastectomy and quadrantectomy with simultaneous IDC and DCIS of stage I and II patients. Aromatase was evaluated using antibodies anti-aromatase and the samples classified in accordance with the number and intensity of stained cells. RESULTS: Aromatase was expressed positively in 32(71 percent) and negatively in 13(29 percent) of the cases in the IDC. The same results were obtained in the DCIS showing a perfect positive correlation. In the normal epithelium,aromatase was positive in 19(42.2 percent) and negative in 26 (57.8 percent) and a positive correlation, statistically significant was obtained when compared with IDC and DCIS(p<0.01). Concerning the normal stroma, positivity was only 7 (15.5 percent) showing no correlation with aromatase expression. Aromatase was positive in 36(80 percent) of the tumor stroma and this result was statistically significant as in the IDC and DCIS. Comparing results of aromatase expression with nuclear grade, histological grade, tumor size and age no difference was found. CONCLUSION: our results demonstrated high correlation between aromatase expression in IDC, DCIS, normal epithelium and tumor stroma showing a possible autocrine and paracrine mechanism of this enzyme in breast cancer.

Carcinoma in situ dentro de un fibroadenoma de mama: tres casos clínicos / Carcinoma within a fibroadenoma of the breast: report of three cases

El fibroadenoma (FA) es un tumor frecuente de la mama que se presenta usualmente en la segunda y tercera década de la vida. Los carcinomas de la mama raramente se desarrollan dentro de un FA, existiendo alrededor de 200 casos descritos en la literatura. Nosotros reportamos la presencia de carcinoma ductal in s/fu(CDIS) al interior de un FA en tres pacientes mujeres de 31, 45 y 47 años. La presencia de microcalcificaciones en dos pacientes y la sospecha de un papiloma intraductal en la tercera, determinaron la necesidad de mastectomía parcial y el consiguiente hallazgo de CDIS al interior de un FA. En dos casos hubo presencia de CDIS extenso en el parénquima mamario adyacente y fueron sometidas finalmente a una mastectomía total. Recomendamos un seguimiento estricto en mujeres con FA a partir de la cuarta década de la vida. En pacientes con lesiones mamarias pro I iterativas o con CDIS que presentan además un FA, se recomienda vigilancia del FA o resección de éste al momento de extirpar el CDIS.

The fibroadenoma (FA) is a common tumor of the breast that usually occurs in the second or third decade of Ufe. The carcinomas of the breast rarely arising within a FA, with around 200 cases reported in the literature. We report the presence of DCIS within a FA on three female patients of 31, 45 and 47 years old. Due to the presence of microcalcifications in two patients and the suspicion of an intraductal papilloma in the third, they underwent a partial mastectomy with the consequent finding of DCIS inside a FA. In two cases there were extensive DCIS in the adjacent breast parenchyma and finally they underwent a total mastectomy. We recommend a strict follow up in women with FA from the fourth decade of life. In patients with proliferatives breast lesions or DCIS that simultaneously presenting a FA, we recommend surveillance of FA or remove it at the same time of the resection of DCIS.

Carcinoma mamário dentro de fibroadenoma: relato de dois casos / Breast carcinoma within fibroadenoma - two cases reports

O fibroadenoma é um tumor benigno mais comum da mama. Trata-se de neoplasia mista com componentes epiteliais e estromais. As taxas de frequencia de malignização do componente epitelial do fibroadenoma referidas na literatura são muito baixas (0,3%). Na maioria das vezes o carcinoma associado a fibroadenoma apresenta-se no estágio in situ e tem bom prognóstico. O objetivo deste trabalho é descrever dois casos clínicos de carcinoma dentro de fibroadenoma atendidos no Hospital do Câncer – Instituto do Câncer do Ceará (ICC). Primeiro caso: paciente, 51 anos, submetida à excisão local de nódulo à direita. O anatomopatológico evidenciou fibroadenoma associado a carcinoma lobular in situ. Segundo caso: paciente 42 anos mastectomizada à esquerda em 2005, apresentou nódulo em mama direita cuja punção guiada por ultra-sonografia foi compatível com carcinoma. Submeteu-se a quadrantectomia com pesquisa de linfonodo sentinela. O estudo histopatológico demonstrou carcinoma ductal in situ dentro de fibroadenoma e em tecido periférico.

Fibroadenoma is the most common benign tumor of the breast. It is a mixed neoplasm with epithelial and stromal components. Malignancy rates for the epithelial component reported in the literature are very low (0.3%). Usually carcinomas associated with fibroadenomas are in the in situ stage and have a favorable prognosis. The objective of the present paper was to report two clinical cases of carcinoma arising in fibroadenoma in patients attending the Ceará Cancer Institute (Fortaleza, Brazil). Case 1: 51-year old patient submitted to local excision of node in the right breast. The pathoanatomical examination revealed fibroadenoma associated with lobular carcinoma in situ. Case 2: 42-year old patient with left breast mastectomized in 2005 presenting with node in the right breast. Ultrasound-guided biopsy compatible with carcinoma. The patient was submitted to quadrantectomy and sentinel lymph node biopsy. The histopathological examination revealed ductal carcinoma in situ arising in fibroadenoma and peripheral tissues.

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.

Tratamiento del carcicoma ductal in situ / Treatment of ductal carcinoma in situ

El Carcicoma Ductal In Situ (CDIS) se diagnostica preferentemente por el hallazgo de microcalcificaciones en la mamografía. El tratamiento consiste en cirugía conservadora asociada a radioterapia post operatoria en caso de que la relación del tamaño de la lesión y el tamaño de la mama lo permita, o mastectomía total seguida o no de reconstrucción inmediata, en caso de lesiones extensas o multicéntricas. Aún no se logra identificar con precisión un subgrupo de pacientes que tratadas con cirugía conservadora, no requiera radioterapia. La disección axilar no está indicada en casos de CDIS puros. La biopsia del ganglio centinela se recomienda en situaciones especiales, las cuales se enumeran. El tratamiento adyuvante con tamoxifeno está indicado en las pacientes con receptores de estrógenos positivos. En este subgrupo de pacientes, la indicación de tamoxifeno debe ser discutida con cada paciente, dados los efectos secundarios de este medicamento. La elección del mejor tratamiento para una paciente en particular, debe considerar la extensión de la enfermedad y tiene que compatibilizar la obtención de márgenes sanos con un buen resultado cosmético, además de tomar en cuenta la preferencia de la paciente.

Carcinoma ductal in situ: classificação e recomendações ao patologista cirúrugico / In situ ductal carcinoma: classification and guidelines for the surgical pathologist

Com o advento da mamografia preventiva de rotina, o diagnóstico de lesões precoces e de carcinoma ductal in situ da mama tem aumentado progressivamente nos últimos 10 anos. A classificação do carcinoma ductal in situ obedece basicamente parâmetros morfológicos como atipia e presença de necrose. No entanto, várias classificações diferentes foram propostas ao longo dos anos, com abordagens nem sempre equivalentes. Neste trabalho, abordamos criticamente as diferentes classificações disponíveis em ordem cronológica de aparecimento e sua aplicabilidade na rotina diagnóstica e terapêutica destas lesões.

In the past ten years, the introduction of screening mammography in breast cancer detection progressively increased the rate of diagnosis of premalignant lesions, such as in situ ductal carcinoma of the breast. Classification of in situ ductal carcinoma basically obeys morphological parameters, such as presence of atypia or necrosis. However, multiple different classifications have been proposed by distinct groups, with not always comparable approaches. In this review, we enlist the main working classifications available chronologically disposed along with diagnosis and therapeutic remarks, their applicability and reproducibility.

Histochemical study of N-acetygalactosamine containing glycoconjugate in intraductal carcinoma of the breast by HPA lectin

Glycoconjugates are a class of glycoproteins or glycolipids, their terminal sugars are responsible for cell-cell and/or cell-extracellular matrix interactions. Aberrant glycosylation of these compounds are one of the most important aspects of cellular transformation, metastasis and escape of tumoral cells from immune system and resistance to antineoplastic drugs. Recent studies showed that patients with HPA [helix pomatia agglutinin] positive intraductal carcinoma cells have worse prognosis compared to patients with HPA negative cells. The aim of the present study was to define the presence of GalNac terminal sugar in glycoconjugate of different grades of intraductal breast carcinoma and to compare the degree and the pattern of reactivity of tumoral cells to HPA lectin. Material and The paraffin blocks belonging to 20 patients of intraductal carcinoma was chosen from pathology archive of Khatam-Al-Anbia hospital in Zahedan and 5-7 micrometer sections were prepared. Two expert pathologists determined histopathological grading independently. The lectin histochemistry was performed using HPA. The same observers determined histochemical grading. Data were analyzed by NPAR [non-parametric] test of Mann Whitney. Results of this study revealed that the pattern and the degree of histochemical reactivity of neoplastic cells differ in all grades of intraductal carcinoma. Histochemical staining showed significant difference between grades of intraductal carcinoma of the breast [p<0.003]. The lowest reactivity was seen in grade I and the highest in grade III. Furthermore, the reaction of tumoral cells was primarily confined to apical surfaces of cells in grade I, to the Golgi zone in grade II, and to a diffuse cytoplasmic distribution in grade III Our data suggest that the HPA reactivity of tumoral cells were different in all grades of intraductal carcinoma. The tumor cells showed aberrant glycosylation, which occurred in the course of anaplastic changes. It seems that our data suggest a potential and clinically important role of HPA reactivity to predict the invasive nature of malignant tumoral cells of intraductal carcinoma of the breast