OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2.

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.

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.

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.

OBJECTIVE: Epidermal growth factor receptor is involved in the pathogenesis of non-small cell lung cancer and has recently emerged as an important target for molecular therapeutics. The KRAS oncogene also plays an important role in the development of lung cancer. The aim of this study was to evaluate the frequency of epidermal growth factor receptor and KRAS mutations in a population of Brazilian patients with non-small cell lung cancer. METHODS: A total of 207 specimens from Brazilian patients with non-small cell lung cancer were analyzed for activating epidermal growth factor receptor and KRAS somatic mutations, and their associations with clinicopathological characteristics (including age, gender, ethnicity, smoking habits, and histological subtype) were examined. RESULTS: We identified 63 cases (30.4%) with epidermal growth factor receptor mutations and 30 cases (14.6%) with KRAS mutations. The most frequent epidermal growth factor receptor mutation we detected was a deletion in exon 19 (60.3%, 38 patients), followed by an L858R amino acid substitution in exon 21 (27%, 17 patients). The most common types of KRAS mutations were found in codon 12. There were no significant differences in epidermal growth factor receptor or KRAS mutations by gender or primary versus metastatic lung cancer. There was a higher prevalence of KRAS mutations in the non-Asian patients. Epidermal growth factor receptor mutations were more prevalent in adenocarcinomas than in non-adenocarcinoma histological types. Being a non-smoker was significantly associated with the prevalence of epidermal growth factor receptor mutations, but the prevalence of KRAS mutations was significantly associated with smoking. CONCLUSIONS: This study is the first to examine the prevalence of epidermal growth factor receptor and KRAS mutations in a Brazilian population sample with non-small cell lung cancer.

OBJECTIVE: Description of some of the clinical pathological characteristics of neuroendocrine tumors of the gastroenteropancreatic tract in Brazilian patients. INTRODUCTION: Neuroendocrine tumors arise in many organs and share common pathological features. In 2010, the World Health Organization published a new classification for neuroendocrine tumors using a three-tiered system that applies the terms neuroendocrine tumor Grade 1, neuroendocrine tumor Grade 2, and neuroendocrine carcinoma. The tumor grades are based on their mitotic rate and the Ki-67 index. In Brazil, information on neuroendocrine tumors of gastroenteropancreatic tract is scarce. METHODS: This study investigated clinicopathological features of 773 Brazilian gastroenteropancreatic neuroendocrine tumor cases from all the geographic regions of Brazil. All of the cases emerged from the files of a single institution (a large pathology reference laboratory) between 1997 and 2009. In addition, the gastroenteropancreatic neuroendocrine tumors were graded according to the new 2010 World Health Organization classification. RESULTS: Overall there were a higher number of neuroendocrine tumors in female over male. The lower ages were seen in patients with appendiceal tumors. The most common anatomic location involved was stomach followed by small and large intestines. All cases involving the appendix were of grade 1 and 92.1% of the neuroendocrine tumors of the esophagus were neuroendocrine carcinomas (grade 3). CONCLUSIONS: In this series, the proportion of NET cases in the total number of surgical pathology cases at our institution over the past 12 years is increasing.

OBJECTIVE: This study provides the clinical pathological characteristics of 1301 cases of pediatric/adolescent lymphomas in patients from different geographic regions of Brazil. METHODS: A retrospective analyses of diagnosed pediatric lymphoma cases in a 10-year period was performed. We believe that it represents the largest series of pediatric lymphomas presented from Brazil. RESULTS: Non-Hodgkin lymphomas represented 68% of the cases, including those of precursor (36%) and mature (64%) cell origin. Mature cell lymphomas comprised 81% of the B-cell phenotype and 19% of the T-cell phenotype. Hodgkin lymphomas represented 32% of all cases, including 87% of the classical type and 13% of nodular lymphocyte predominant type. The geographic distribution showed 38.4% of the cases in the Southeast region, 28.7% in the Northeast, 16.1% in the South, 8.8% in the North, and 8% in the Central-west region. The distribution by age groups was 15-18 years old, 33%; 11-14 years old, 26%; 6-10 years old, 24%; and 6 years old or younger, 17%. Among mature B-cell lymphomas, most of the cases were Burkitt lymphomas (65%), followed by diffuse large B-cell lymphomas (24%). In the mature T-cell group, anaplastic large cell lymphoma, ALK-positive was the most prevalent (57%), followed by peripheral T-cell lymphoma, then not otherwise specified (25%). In the group of classic Hodgkin lymphomas, the main histological subtype was nodular sclerosis (76%). Nodular lymphocyte predominance occurred more frequently than in other series. CONCLUSION: Some of the results found in this study may reflect the heterogeneous socioeconomical status and environmental factors of the Brazilian population in different regions.

OBJECTIVE: To compare the frequency and immunohistochemical profiles of triple-negative breast carcinomas in younger and older women. METHODS AND RESULTS: We selected patients diagnosed with triple-negative breast carcinomas. The groups examined were women who were 35 years old or younger between 1997 and 2007 (n = 74) and, for comparison, women who were 60 years old or older (n = 19, consecutive cases). All formalin-fixed and paraffin-embedded tumor samples were reviewed and immunohistochemically stained for ER, PR, HER2, Ki-67 antigen, epidermal growth factor receptor, cytokeratin 5/6, p53, vimentin, CD117, and p63 using tissue microarrays blocks. Triple-negative breast carcinomas corresponded to 34.6% (74/213) of the carcinomas from the younger patients and 16.2% (19/117) of the carcinomas from the older patients (p = 0.002). No significant differences in the frequency of the basal phenotype were observed in the two patient groups based on CK5/6 and/or epidermal growth factor receptor expression (74.3% vs. 68.4%). However, triple-negative breast carcinomas in the older patients presented a higher frequency of CK5/6 expression compared to those of younger patients (42.1% vs. 9.6%; p = 0.005), whereas triplenegative breast carcinomas of younger patients had a higher expression level of epidermal growth factor receptor (71.6% vs. 47.3%). CONCLUSIONS: These results show that there were significant molecular differences between the triple-negative basal-like breast carcinomas that were diagnosed in younger women and those that were diagnosed in older women. These findings may provide a basis for describing the more aggressive phenotype of the triple-negative breast carcinomas observed in younger women.

INTRODUÇÃO: A hiperexpressão de human epidermal growth factor receptor (HER-2/neu) e a amplificação do seu gene são indicadores de formas mais agressivas do câncer de mama. A Food and Drug Administration (FDA) aprovou o teste denominado HercepTest® com a finalidade de selecionar pacientes com indicação para o uso de um anticorpo humanizado anti-HER-2/neu (trastuzumab), com efeito terapêutico comprovado. OBJETIVOS: O presente trabalho tem como objetivo comparar os resultados obtidos pelos métodos imuno-histoquímicos LSAB®+ com a utilização de anticorpo A0485 e HercepTest®. Material e métodos: Foram utilizados 50 casos de carcinoma de mama nos quais a pesquisa da hiperexpressão de HER-2 pelo método LSAB®+ já havia sido realizada. Foi repetida a pesquisa da hiperexpessão de HER-2/neu nos mesmos casos, utilizando-se o método do HercepTest®. RESULTADOS: 34 casos foram considerados negativos pelos dois métodos, com escore 0 pelo método HercepTest®. Destes, 12 obtiveram escore 1+ e 22 obtiveram escore 0 pelo método LSAB®+. Em oito casos, o escore foi 2+ pelos dois métodos. Escore 3+ foi encontrado também em oito casos pelos dois métodos. DISCUSSÃO: O método mais prático utilizado em laboratório de rotina diagnóstica para investigar a hiperexpressão de HER-2/neu é o estudo imuno-histoquímico. Em função de muitas variáveis, como tempo de fixação, tipo de fixador, duração da fixação, método de recuperação antigênica e tipo de anticorpo utilizado, pode haver divergência de resultados. CONCLUSÃO: O presente estudo concluiu que o método HercepTest®demonstrou resultados equivalentes aos resultados obtidos pelo método LSAB®+ em carcinoma de mama.

INTRODUCTION: The overexpression of human epidermal growth factor receptor (HER-2/neu) protein and the amplification of its gene are indicators of more aggressive behavior in breast cancer. The Food and Drug Administration (FDA) has approved HercepTest® with the goal of selecting patients to be elegible for treatment with the humanized murine monoclonal antibody anti-HER-2/neu (trastuzumab). AIMS: The aim of the present study was to compare the results of HER-2/neu expression using routine immunohistochemistry method LSAB®+ (Dakocytomation polyclonal antibody A0485) and HercepTest®. MATERIAL AND METHODS: 50 cases of breast carcinoma previously evaluated for HER-2/neu expression by routine immunohistochemistry using the LSAB+ method were included. These cases were also evaluated for HER-2/neu expression using HercepTest® for comparison. Results: 34 cases of breast carcinoma were negative for HER-2/neu expression by the two methods, with score 0 by HercepTest®. In 12 and 22 cases, respectively, score 1+ and 0 were observed by the LSAB®+ method. In eight cases, score 2+ was present by both methods. Score 3+ was found in eight cases also by both methods. DISCUSSION: The most common method used in routine clinical practice to determine HER-2/neu status is immunohistochemistry. Variability of HER-2/neu results can be caused by a number of variables including time of fixation, methods of epitope retrieval and type of primary antibodies used. CONCLUSION: The conclusion of the present study was that LSAB®+ and HercepTest® revealed equivalent results for HER-2/neu expression in breast carcinoma.

Condrossarcoma é o sarcoma mais freqüente da laringe. Sua incidência é maior na cartilagem cricóide do que nas outras cartilagens da laringe, sendo raro que ele se origine na epiglote. Relatamos no texto um caso de condrossarcoma originado na epiglote, no qual foi realizada laringectomia subtotal com crico-hioidopexia - e realizamos revisão da literatura.

Chondrosarcoma is the most frequent sarcoma of the larynx. It is more prevalent in the cricoid and less prevalent in the other laryngeal cartilages. Chondrosarcoma is rarely located in the epiglottis. We reported a case of epiglottis chondrosarcoma that was treated with a supracricoid laryngectomy with cricohyoidopexy.