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The golden hamster (Mesocricetus auratus) is commonly used as a promising model for Leishmania braziliensis infection developing skin-ulcerated lesions. However, different protocols using high concentration of parasites inoculated in the footpad result in severe clinical disease. Here, we further investigate the outcome of the site of infection and concentration of L. braziliensis parasites inoculated on the immunopathogenesis and clinical evolution. Initially, hamsters were infected in the ear dermis or hind footpad with a concentration of 1 × 105 parasites. Animals infected in the ear dermis developed a disease, with an increased parasite load that more closely resembled human cutaneous leishmaniasis lesions comparing to the group infected in the footpad. Next, we evaluated if different parasite concentrations (104 , 105 and 106 ) inoculated in the ear dermis would impact the course and clinical aspects of infection. Hamsters infected with 104 and 105 parasites developed mild lesions compared to the group infected with 106 that presented severe and persistent lesions. The parasite load varied between the different parasite concentrations. The inflammatory response was more intense when infection was initiated with 106 parasites accompanied by an increased initial expression of IL-4, IL-10 and arginase in the lymph node followed by expression of both pro-and anti-inflammatory cytokines comparing to groups infected with 104 and 105 parasites. In conclusion, the number of parasites inoculated, and the initial site of infection could influence the inflammatory response, and clinical presentation. Our results suggest that the ear dermis infection model induces a chronic disease that relates to immunopathological aspects of CL natural infection.

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AIMS: This study tested the protective effect of purified paraprobiotic Enterococcus faecalis (EC-12) and an E. faecalis-based formulation (Med LanS) on irinotecan-induced intestinal mucositis murine model. MAIN METHODS: C57BL/6 male mice received saline, irinotecan (75 mg/Kg, i.p.), EC-12 (0.3, 1, or 3 × 107 CFU/Kg, p.o.) + irinotecan or Med Lan-S (3 × 107 CFU/Kg, p.o.) + irinotecan. Body mass variation was assessed daily, and blood samples were collected for evaluating bacteremia and leukocyte count. The ileum was harvested for myeloperoxidase assay, histopathology, quantitative PCR, and immunofluorescence for macrophages (F4/80), TLR4, and IL-18 binding protein (IL-18BP). KEY FINDINGS: The best therapeutic strategy was EC-12 administration at 3 × 107 CFU/Kg, starting 1 week before irinotecan. EC-12 and Med Lan-S did not prevent the irinotecan-induced body mass loss or leukopenia but attenuated the neutrophil infiltration in the intestine and increased the villus/crypt ratio (P < 0.05). Additionally, EC-12 and Med Lan-S reduced the mRNA expression of Cldn-2, Ocln, and Tlr4 versus the irinotecan group (P < 0.05). Irinotecan also augmented the expression of Il-18, IL-18BP, the immunofluorescence of F4/80, and TLR4, while only EC-12 prevented the expression of all these markers. Remarkably, EC-12 and Med Lan inhibited the irinotecan-induced bacterial translocation to the blood. SIGNIFICANCE: Paraprobiotic E. faecalis EC-12 prevents the development of intestinal mucositis by downregulating the inflammatory response. Med Lan-S also protects from mucositis. Possibly, the complexity of the formulation accounts for an innate immune-driven protective mechanism.

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O tumor de Buschke-Löwenstein é uma doença rara, de transmissão sexual, associada ao papilomavírus humano, principalmente dos subtipos 6 e 11. Caracteriza-se como uma lesão exofítica, em forma de couve-flor, de progressão lenta, com alto poder de infiltração local. O seu principal fator de risco é a imunossupressão e o tratamento geralmente é cirúrgico, com ou sem terapias adjuvantes. O impacto na vida da paciente é grande, com altas taxas de recorrência após excisão cirúrgica. Relatamos 3 casos de condiloma gigante com achados histopatológicos diversos, com graus de infiltração e papilomatose variados.

The Buschke-Löwenstein Tumor is a rare, sexually transmitted disease, triggered by human papillomavirus, specially the subtypes 6 and 11. It is characterized as a cauliflower-shape exophytic mass, slowly progressive, with high local recurrence rates and high infiltration. The main risk factor is immunosuppression. Surgical treatment is usually preferred, with or without adjuvant therapy. It has a great impact on the patients' life, impairing their life quality. We report three cases of Giant Condyloma with diverse histopathological findings with varying degrees of infiltration and papillomatosis.

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Úlceras genitais são manifestações clínicas de etiologias diversas, o que pode dificultar o diagnóstico. Este relato de caso trata­se de mulher de 64 anos, com histórico de úlcera genital dolorosa há 4 meses, progressiva apesar do uso prévio de antiviral. Apresentava lesão ulcerada com comprometimento perianal. Histopatológico revelou neovascularização, edema e infiltrado inflamatório. Realizou tratamento com aciclovir endovenoso por 14 dias, com melhora parcial. O herpes simples crônico manifesta­se como verruga ou úlcera de pelo menos um mês, geralmente em imunossuprimidas. A resistência a agentes antivirais é uma complicação encontrada, mas a resposta ao tratamento costuma ser mais lenta do que nas infecções comuns.

Genital ulcers are clinical manifestations of diverse etiologies, which can make diagnosis difficult. This case report is about a 64­year­old woman with a history of progressive genital ulcer pain for 4 months, despite prior antiviral use. The ulcerated lesion showed perianal involvement. Histopathology revealed neovascularization, edema and inflammatory infiltrate. Despite the use of intravenous acyclovir for 14 days, the improvement was partial. Chronic herpes simplex reveals wart or ulcer of at least one month, usually in immunosuppressed patients. A resistance to antiviral agents is a complication factor, but the treatment response to common infections is usually slower.

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Objective: to analyze the relation of anatomopathological features and axillary involvement in cases of invasive ductal carcinoma. Methods: this is a cross-sectional study of 220 breast cancer patients submitted to radical mastectomy or quadrantectomy with axilar emptying, from the Mastology Service of the Assis Chateaubriand Maternity School, Ceará, Brazil. We submitted the tumors to histological processing and determined the histological (HG), tubular (TG) and nuclear (NG) grades, and the mitotic index (MI) by the classification of Scarff-Bloom-Richadson, verified the presence of angiolymphatic invasion (AI) and measured the largest tumor diameter (TD). We then correlated these variables with the presence of axillary metastases. Results: the mean patients'age was 56.81 years ± 13.28. Tumor size ranged from 0.13 to 22 cm, with an average of 2.23cm ± 2.79. HG3, TG3 and NG3 prevailed, respectively 107 (48.6%), 160 (72.7%) and 107 (48.6%). Mitotic indexes 1, 2 and 3 presented a homogeneous distribution, respectively 82 (37.2%), 68 (31%) and 70 (31.8%). We observed no relation between the HG, TG and NG with the occurrence of axillary metastases (p=0.07, p=0.22 and p=0.21, respectively). Mitotic indices 2 and 3 were related with the occurrence of axillary metastases (p=0.03). Tumors larger than 2cm and cases that presented angiolymphatic invasion had a higher index of axillary metastases (p=0.0003 and p<0.0001). Conclusion: elevated mitotic indexes, tumors with a diameter greater than 2cm and the presence of angiolymphatic invasion were individuallyassociatedwith the occurrence of axillary metastases.

Objetivo: analisar a relação das características anatomopatológicas com o comprometimento axilar em casos de carcinoma ductal invasor. Métodos: estudo transversal de 220 pacientes com câncer de mama, submetidas à mastectomia radical ou quadrantectomia com esvaziamento axilar, oriundos do Serviço de Mastologia da Maternidade Escola Assis Chateaubriand, Ceará, Brasil. Os tumores foram submetidos a processamento histológico e, em seguida, foram determinados os graus histológico (GH), tubular (GT), nuclear (GN), índice mitótico (IM) pela classificação de Scarff-Bloom-Richadson, verificada a presença de invasão angiolinfática (IA) e mensurado o maior diâmetro do tumor (DT). Tais variáveis foram correlacionadas com a presença de metástases axilares. Resultados: a média de idade das pacientes foi 56,81 anos ± 13,28. O tamanho do tumor variou de 0,13 a 22 cm, com média de 2,23cm ± 2,79. Os GH3, GT3 e GN3 prevaleceram: n=107 (48,6%), n=160 (72,7%) e n=107 (48,6%), respectivamente. Os índices mitóticos 1, 2 e 3 apresentaram distribuição homogênea: n=82 (37,2%), n=68 (31%) e n=70 (31,8%), respectivamente. Não foi evidenciada relação do GH, GT e GN com a ocorrência de metástases axilares (p=0,07; p=0,22 e p=0,21). Índices mitóticos 2 e 3 apresentaram relação com a o ocorrência de metástases axilares (p=0,03). Tumores maiores do que 2cm e casos com invasão angiolinfática apresentaram maior índice de metástases axilares (p=0,0003 e p<0,0001). Conclusão: índices mitóticos elevados, tumores com diâmetro maior do que 2cm e presença de invasão angiolinfática apresentaram isoladamente relação com a ocorrência de metástases axilares.

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ABSTRACT Objective: to analyze the relation of anatomopathological features and axillary involvement in cases of invasive ductal carcinoma. Methods: this is a cross-sectional study of 220 breast cancer patients submitted to radical mastectomy or quadrantectomy with axilar emptying, from the Mastology Service of the Assis Chateaubriand Maternity School, Ceará, Brazil. We submitted the tumors to histological processing and determined the histological (HG), tubular (TG) and nuclear (NG) grades, and the mitotic index (MI) by the classification of Scarff-Bloom-Richadson, verified the presence of angiolymphatic invasion (AI) and measured the largest tumor diameter (TD). We then correlated these variables with the presence of axillary metastases. Results: the mean patients'age was 56.81 years ± 13.28. Tumor size ranged from 0.13 to 22 cm, with an average of 2.23cm ± 2.79. HG3, TG3 and NG3 prevailed, respectively 107 (48.6%), 160 (72.7%) and 107 (48.6%). Mitotic indexes 1, 2 and 3 presented a homogeneous distribution, respectively 82 (37.2%), 68 (31%) and 70 (31.8%). We observed no relation between the HG, TG and NG with the occurrence of axillary metastases (p=0.07, p=0.22 and p=0.21, respectively). Mitotic indices 2 and 3 were related with the occurrence of axillary metastases (p=0.03). Tumors larger than 2cm and cases that presented angiolymphatic invasion had a higher index of axillary metastases (p=0.0003 and p<0.0001). Conclusion: elevated mitotic indexes, tumors with a diameter greater than 2cm and the presence of angiolymphatic invasion were individuallyassociatedwith the occurrence of axillary metastases.

RESUMO Objetivo: analisar a relação das características anatomopatológicas com o comprometimento axilar em casos de carcinoma ductal invasor. Métodos: estudo transversal de 220 pacientes com câncer de mama, submetidas à mastectomia radical ou quadrantectomia com esvaziamento axilar, oriundos do Serviço de Mastologia da Maternidade Escola Assis Chateaubriand, Ceará, Brasil. Os tumores foram submetidos a processamento histológico e, em seguida, foram determinados os graus histológico (GH), tubular (GT), nuclear (GN), índice mitótico (IM) pela classificação de Scarff-Bloom-Richadson, verificada a presença de invasão angiolinfática (IA) e mensurado o maior diâmetro do tumor (DT). Tais variáveis foram correlacionadas com a presença de metástases axilares. Resultados: a média de idade das pacientes foi 56,81 anos ± 13,28. O tamanho do tumor variou de 0,13 a 22 cm, com média de 2,23cm ± 2,79. Os GH3, GT3 e GN3 prevaleceram: n=107 (48,6%), n=160 (72,7%) e n=107 (48,6%), respectivamente. Os índices mitóticos 1, 2 e 3 apresentaram distribuição homogênea: n=82 (37,2%), n=68 (31%) e n=70 (31,8%), respectivamente. Não foi evidenciada relação do GH, GT e GN com a ocorrência de metástases axilares (p=0,07; p=0,22 e p=0,21). Índices mitóticos 2 e 3 apresentaram relação com a o ocorrência de metástases axilares (p=0,03). Tumores maiores do que 2cm e casos com invasão angiolinfática apresentaram maior índice de metástases axilares (p=0,0003 e p<0,0001). Conclusão: índices mitóticos elevados, tumores com diâmetro maior do que 2cm e presença de invasão angiolinfática apresentaram isoladamente relação com a ocorrência de metástases axilares.

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Objective To evaluate the diagnostic utility of the p16ink4a protein expression as a marker for adenocarcinoma of the cervix. Methods In a cross-sectional study, p16ink4a expression was evaluated in 30 cervical biopsies from patients diagnosed with invasive adenocarcinoma from 2 reference clinics in Brazil, and compared with 18 biopsies of endocervical polyps (control cases). The performance of the tests for p16ink4a was evaluated using a conventional contingency table, and the Kappa (κ) index was used to evaluate the agreement of the marker with the tissue diagnosis. Results In total, 66% of the invasive adenocarcinoma cases were positive for p16ink4a. All of the adenomatous polyps cases used as negative controls were shown to be negative for p16ink4a. The marker showed a high sensitivity and a high negative predictive value. The Kappa index was good for p16ink4a (κ = 0.6). Conclusion Considering the strong association between the p16ink4a marker and the cervical adenocarcinoma, its use represents an important tool for reducing incorrect diagnoses of adenocarcinoma and thereby avoiding overtreatment.

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ABSTRACT Objective: To evaluate the diagnostic utility of the p16ink4a protein expression as a marker for adenocarcinoma of the cervix. Methods: In a cross-sectional study, p16ink4a expression was evaluated in 30 cervical biopsies from patients diagnosed with invasive adenocarcinoma from 2 reference clinics in Brazil, and compared with 18 biopsies of endocervical polyps (control cases). The performance of the tests for p16ink4a was evaluated using a conventional contingency table, and the Kappa (k) index was used to evaluate the agreement of the marker with the tissue diagnosis. Results: In total, 66% of the invasive adenocarcinoma cases were positive for p16ink4a. All of the adenomatous polyps cases used as negative controls were shown to be negative for p16ink4a. The marker showed a high sensitivity and a high negative predictive value. The Kappa index was good for p16ink4a (k 1/4 0.6). Conclusion: Considering the strong association between the p16ink4a marker and the cervical adenocarcinoma, its use represents an important tool for reducing incorrect diagnoses of adenocarcinoma and thereby avoiding overtreatment.

RESUMO Objetivo: Avaliar a utilidade diagnóstica da expressão da proteína p16ink4a como marcador de adenocarcinoma do colo. Métodos: Em estudo transversal, a expressão de p16ink4a foi avaliada em 30 biópsias cervicais de pacientes diagnosticadas com adenocarcinoma invasivo de colo uterino provenientes de dois serviços de referência no Brasil, comparando com achados em 18 biópsias de pólipos endocervicais (grupo de controle). Para avaliar a performance do teste, foi utilizada tabela de contingência convencional, e para avaliar a concordância com o diagnóstico, foi aplicado o índice de Kappa (k). Resultados: No total, 66% dos casos de adenocarcinoma invasivo foram positivos para p16ink4a. Todos os pólipos adenomatosos foram negativos para p16ink4a. O marcador mostrou uma alta sensibilidade e alto valor preditivo negativo. O índice de Kappa foi bom para p16ink4a (k 1/4 0.6). Conclusion: Considerando a forte associação entre o marcador p16ink4a e o adenocarcinoma cervical, seu uso representa uma ferramenta importante para reduzir o risco de diagnóstico incorreto de adenocarcinoma e, por conseguinte, evitar o excesso de tratamentos.

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Objetivo: Estabelecer o grau histológico das metástases axilares em casos de câncer de mama do tipo ductal invasor e comparar com os achados do tumor primário. Métodos: Estudo transversal de envolvendo 69 casos de câncer de mama do tipo ductal invasivo, oriundos do serviço de Mastologia da Maternidade Escola Assis Chateaubriand, Ceará, Brasil, com suas respectivas metástases axilares. Os tumores primários da mama e os linfonodos metastáticos foram submetidos ao processamento histológico e, em seguida, foram determinados os graus histológico (GH), tubular (GT), nuclear (GN) e índice mitótico (IM) na mama e na axila pela classificação de Scarff-Bloom-Richadson. Resultados: Os GH mais elevados predominaram entre os tumores primários, sendo 52,2% classificados como GH 3. Quando comparadas ao tumor primário, as metástases axilares evidenciaram uma frequência maior de GH 3 (66,7%), GT 3 (85,5%), GN 3 (58%) e GM 2 (58%). A formação tubular foi menor nas metástases axilares (p=0,04). Conclusão: Os implantes axilares apresentaram morfologia tecidual mais desorganizada formando menos túbulos quando comparados aos tumores primários da mama. Entretanto, não houve diferença significativa do GH entre o tumor primário e a metástase axilar em nossa amostra.

Objective: To establish the histological grade of the axillary metastases in invasive ductal breast cancer cases and to compare it with the findings from the primary tumor. Methods: Cross-sectional study involving 69 cases of invasive ductal breast cancer from the mastology service of Assis Chateaubriand Maternity School, Ceará, Brazil, and their respective axillary metastases. The breast primary tumors and metastatic lymph nodes were subjected to histological processing and the histological grade (HG), tubular grade (TG), nuclear grade (NG) and mitotic index (MI) of the breast and axilla were subsequently determined by the Scarff-Bloom-Richardson grading system. Results: The highest HG prevailed among the primary tumors, with 52,2% classified as HG 3. When compared to the primary tumor, the axillary metastases showed a higher frequency of HG 3 (66,7%), TG 3 (85,5%), NG 3 (58%) and MI 2 (58%). Conclusion: The axillary implants revealed a more disorganized tissue morphology, which formed a lower number of tubules when compared to the breast primary tumors. However, there was no significant difference in the HG between the primary tumor and axillary metastasis in this sample.

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OBJECTIVE: We aimed to assess the cytological findings from fine-needle aspiration (FNA) of breast lesions with conventional smear (CS) and SurePath® (SP) cytology. STUDY DESIGN: This was a cross-sectional study of women who underwent FNA from January 2012 to June 2013 for breast lesions with benign ultrasonography impressions in Fortaleza, Brazil. Two groups were formed. The first was composed of 102 samples subjected to CS and the second of 65 samples subjected to SP. The number of smears, the cellularity and the diagnostic hypotheses were compared. Fisher's exact tests with 95% confidence intervals were applied. RESULTS: The women ranged in age from 22 to 75 years. SP cytology indicated greater cellularity than CS for the cystic lesions (p < 0.05). In the CS group, 72.5% of the samples required 3-4 slides, but in the SP group, only 9.2% required a second slide. The cellularity of the cystic samples was significantly greater with the SP method (p < 0.01). CONCLUSION: In FNA cytology of the breast, SP is a tool that is comparable to CS, but with the added benefits of better cellularity results for cystic lesions and requiring fewer slides for analysis.

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