Carcinoma bronquíolo-alveolar em leão-africano (Panthera leo)

Um caso de carcinoma bronquíolo-alveolar difuso do tipo misto foi diagnosticado em um leão-africano (Panthera leo), hospitalizado com sinais de dispnéia e emagrecimento progressivo. Em todos os lobos pulmonares havia múltiplos nódulos esbranquiçados, macios e homogêneos, de 0,2-0,5cm em diâmetro. Histologicamente, os nódulos eram constituídos por células neoplásicas arranjadas em alvéolos e papilas sustentados por moderado estroma fibrovascular, um padrão que lembrava a estrutura pulmonar pré-existente. Na reação pelo ácido periódico de Schiff (PAS) foi observada marcação positiva no citoplasma de numerosas células neoplásicas. Todas as células neoplásicas demonstraram forte e uniforme imunorreatividade citoplasmática para pancitoceratina. A marcação para o fator 1 de transcrição da tireóide (TTF-1) foi observada em focos nos núcleos das células neoplásicas das margens dos nódulos. Nas secções avaliadas para surfactante A, a marcação foi observada em múltiplas áreas focais, tanto no citoplasma como na membrana citoplasmática das células neoplásicas. O diagnóstico de carcinoma bronquíolo-alveolar difuso do tipo misto foi feito com base nos achados histológicos, histoquímicos e imuno-histoquímicos. Essa parece ser a primeira descrição de um neoplasma pulmonar primário maligno em leão-africano.

Carcinoma de células renais em bovinos

Foram encontrados nove casos de carcinoma de células renais em uma pesquisa de 586 tumores em bovinos provenientes de 6.706 necropsias realizadas nessa espécie num período de 45 anos (1964-2008). Seis bovinos morreram por complicações do tumor e três foram achados incidentais. Os bovinos acometidos por carcinoma de células renais demonstraram os seguintes sinais clínicos: perda de peso (5 casos), massas abdominais palpáveis (4 casos), dificuldade respiratória (4 casos), tosse (4 casos), hiporexia (3 casos), anorexia (2 casos), dor abdominal (2 casos) e febre (1 caso). Os sinais clínicos observados estavam relacionados ao comprometimento induzido pelas metástases, que foram observadas nos nove casos. As metástases foram observadas nos linfonodos abdominais, superfícies serosas, fígado e pulmão. Dois bovinos tinham tumor renal bilateral. Microscopicamente, foi observado o padrão tubular, sólido e um misto de sólido e tubular e tubulopapilífero. O tipo celular eosinofílico foi predominante, apenas um tumor sólido era constituído basicamente por células claras. Reação cirrosa variou de discreta à acentuada. Corpora amylaceae foi um achado comum. Todos os tumores marcaram positivamente para citoceratina AE1/AE3 com diferentes graus de intensidade. A imunomarcação para CD10 foi observada em todos os casos testados. CD10 marcou intensamente no CCR de células claras, nos demais a marcação foi observada de forma isolada e menos intensa. Três tumores marcaram de forma isolada e discreta para o anticorpo anti-PAX-2. A avaliação foi negativa para citoceratina 34β12, c-KIT (CD117), S-100, cromogranina A e apoproteína A surfactante. Os resultados obtidos indicam que CCR são incomuns em bovinos no Sul do Brasil com uma média de 1.3 casos para cada mil necropsias realizadas e que o anticorpo anti-CD10 é útil no diagnóstico de CCR em bovinos.

Fatores de risco associados à ocorrência de carcinoma de células escamosas em ruminantes e equinos no semiárido da Paraíba

Neste trabalho descreve-se a frequência de carcinomas de células escamosas diagnosticados pelo Laboratório de Patologia Animal (LPA) do Hospital Veterinário da Universidade Federal de Campina Grande (UFCG) em bovinos, ovinos, caprinos e equinos no semiárido da Paraíba, durante o período de 1983 a 2010, analisando dados epidemiológicos e fatores de risco. Foi realizada a análise dos fatores de risco, mediante o teste de qui-quadrado de aderência, considerando como variáveis espécie, raça, sexo, idade e localização da massa tumoral. Durante o período foram registrados 3.153 diagnósticos provenientes de biópsias e necropsias. Destes, 81 casos (2,7%) foram de carcinomas de células escamosas. A frequência por espécie foi de 4% (42/1052) em bovinos, 2,5% (15/603) em equinos, 1,7% (12/709) em ovinos e 1,5% (12/789) em caprinos, sendo significativamente maior em bovinos (p<0,001). Todos os casos apresentavam características histológicas de CCE, variando apenas o grau de diferenciação celular. Em bovinos e caprinos, a frequência do tumor foi significativamente maior em animais adultos (p<0,001 e p<0,005, respectivamente). Nos bovinos a localização preferencial foi em olhos e região periocular (p<0,001) e nos ovinos na pele (p=0,018), principalmente na cabeça, enquanto que nas outras espécies não foram encontradas diferenças significantes na localização do tumor. Sugere-se que a maior frequência de CCE em bovinos deve-se à constituição do rebanho, formado predominantemente por fêmeas da raça Holandesa.

Carcinoma mamário pouco diferenciado em macaco-prego, Cebus sp. (Cebidae)

As neoplasias mamárias são raras em primatas não humanos, enquanto que nas mulheres apresentam alta incidência. O objetivo deste trabalho foi relatar a ocorrência e os resultados do tratamento de um Cebus sp. (fam. Cebidae) fêmea, com carcinoma mamário pouco diferenciado encaminhado ao Serviço de Atendimento de Animais Selvagens da Universidade Estadual do Centro-Oeste. À inspeção o animal apresentava aumento de volume em região mamária direita e ao exame radiográfico foram observados três pontos de radiopacidade, característicos de projétil balístico de arma de pressão, com um deles alojado ao centro da massa de tecido mamário Após estabilização, a paciente foi submetida à exérese cirúrgica de aumento de volume e o material foi encaminhado para análise histopatológica. O diagnóstico obtido foi de carcinoma de alto grau, compatível com carcinoma adenoescamoso. Após a retirada dos pontos a paciente foi encaminhada ao convívio de outros animais. Mais de 20 meses após a terapia cirúrgica não há sinais de recidiva. A paciente alimenta-se bem, convive normalmente com o grupo, sugerindo que a terapia adotada foi eficiente até o momento em alcançar qualidade de vida e aumento de sobrevida do animal.

Transitional cell carcinoma of urinary bladder with metastasis in lumbar vertebrae and spinal cord compression in an ocelot(Leopardus pardalis)

This paper reports a case of nonpapillary and infiltrative transitional cell carcinoma (TCC) of the urinary bladder with metastasis of lumbar vertebrae and spinal cord compression in an adult female ocelot (Leopardus pardalis), from the Mato Grosso state, Brazil. The ocelot had pelvic limb paralysis and skin ulcers in the posterior region of the body and was submitted to euthanasia procedure. At necropsy was observed a multilobulated and irregular shaped, yellowish to white nodule in the urinary bladder. The nodule had a soft consistency and arised from the mucosa of the urinary bladder extending throughout the muscular layers and the serosa. Nodules of similar appearance infiltrating the vertebral column the at L6 and L7 vertebrae with corresponding spinal canal invasion were also observed. The histological evaluation showed epithelial neoplastic proliferation in the urinary bladder with characteristics of nonpapillary and infiltrative TCC, with positive immunohistochemical staining for pancytokeratin, and strong immunostaining for cytokeratin of low molecular weight, and weak or absent labeling for high molecular weight cytokeratin. This is the first report of TCC of urinary bladder in ocelot in Brazil.

Carcinoma hepatocelular metastático em Jaguatirica (Leopardus pardalis )

RESUMO: O carcinoma hepatocelular (CHC) é uma neoplasia rara nos animais domésticos e em espécies selvagens foi relatado somente em antílopes, veado, cães da pradaria e furões, mas não existem relatos em Leopardus pardalis (jaguatirica). Este trabalho descreve um caso de carcinoma hepatocelular metastático em uma fêmea felina de aproximadamente 18 anos de idade, da espécie Leopardus pardalis, proveniente do Parque Zoobotânico de Teresina-PI, com histórico de anorexia, apatia e evolução ao óbito que foi encaminhada ao Setor de Patologia Animal da Universidade Federal do Piauí para exame anatomopatológico. À necropsia foram observadas duas nodulações de aproximadamente 8,0cm de diâmetro no fígado, de coloração variando da brancacenta ao vermelhado claro, amarelada a vermelho escuro, subdivididas em lóbulos por tecido conjuntivo. No pâncreas foram observadas múltiplas nodulações de aproximadamente 1,0 cm de diâmetro, com superfície lisa, consistência firme, coloração vermelho-amarelada. A superfície de corte dos rins também apresentava várias nodulações milimétricas de distribuição multifocal, na região córtico-medular, consistência firme, coloração branco-acinzentada ou amarelada, sugerindo metástase. Os fragmentos das lesões de fígado foram coletados e no exame microscópico observaram-se proliferação de hepatócitos em cordões bem diferenciados, formando trabéculas com espessura de três ou mais células. Os hepatócitos apresentavam-se volumosos, pleomórficos, com citoplasma eosinofílico. Na coloração com PAS constataram-se, regularmente, acúmulo de glicogênio nos hepatócitos neoplásicos. A confirmação foi feita pela técnica de imunoistoquímica, utilizando-se anticorpo monoclonal (Hepatocyte Specific Antigen). Os achados anatomohistopatológicos, e o auxilio da imunoistoquímica permitiram concluir pelo diagnóstico de hepatocarcinoma trabecular metastático em Leopardus pardalis criado em cativeiro.

Complications of surgical treatment of cervical carcinoma

A total of 302 patients with stage Ib and IIa cervical carcinoma were submitted to radical hysterectomy and lymphadenectomy during the period from 1980 to 1994. The morbidity rate was 37.5% and the mortality rate 0.6%. The most common intraoperative complications were injuries to the great pelvic vessels and the most frequent postoperative complications involved the urinary tract. The leading causes of morbidity were urinary infection (20.8%), bladder dysfunction (9.2%) and ureteral fistulas (2.9%). Although the rate of complications was high, morbidity has been decreasing over the last five years. Thus, radical hysterectomy continues to be one of the methods for the treatment of early cervical carcinoma that presents an acceptable 5-year survival rate.

Analysis of p53 expression and proliferative assessment using PCNA in localized prostate carcinoma

The surgical specimens from 51 men submitted to radical prostatectomy for localized prostate cancer were examined by immunohistochemistry using proliferation cell nuclear antigen (PCNA) monoclonal antibody to evaluate the proliferative index (PI). The relationship between PI, biological variables and p53 protein expression was evaluated by immunohistochemistry. PI was low in invasive localized prostate carcinoma (mean, 12.4%) and the incidence of PCNA-positive cells was significantly higher in tumors with p53 expression (P = 0.0226). There was no statistical difference in PCNA values when biological parameters such as Gleason score, tumor volume, extraprostatic involvement, seminal vesicle infiltration or lymph node metastasis were considered. We conclude that proliferative activity is usually low in prostate carcinoma but is correlated with p53 immune staining, indicating that p53 is important in cell cycle control in this neoplasm.

Clinical results of the use of mitotane for adrenocortical carcinoma

Mitotane (o,p'-DDD) acts mainly as an inhibitor of intramitochondrial pregnenolone and cortisol synthesis. Its adrenolytic effect depends on metabolic activation due to conversion to o,p'-DDA and o,p'-DDE. The drug has been used for 40 years in the treatment of adrenocortical carcinoma, mainly its regional and metastatic stage, as an adjuvant to surgical resection of the tumor. In the medical literature there are controversial opinions about its efficacy for the treatment of adrenocortical carcinoma. In our experience, mitotane administered immediately after surgery appeared to be much more efficient than when administered later. We have administered this drug in all cases of microscopically confirmed adrenocortical carcinoma, irrespectively of stage at the time of surgery, for fear of a false too optimistic classification. In our series of 82 patients with adrenocortical carcinoma, 59 patients have been treated with mitotane, 32 of them immediately after surgery, and 27 with a delay of 2 to 24 months. Today there are 18 survivors in the group of patients treated with mitotane soon after the operation and only 6 survivors in the group receiving mitotane with a delay. All patients were simultaneously given replacement therapy. Undesired effects of mitotane administration included increased aminotransferase and alkaline phosphatase activity, decreased white cell, platelet or red cell number, and myasthenia. Furthermore, we used mitotane with good results in Cushing's syndrome of non-malignant origin as pre-treatment before surgery or in long-term treatment for patients with poor tolerance of other adrenal inhibitors.

Functional differences between two morphologically distinct cell subpopulations within a human colorectal carcinoma cell line

The LISP-I human colorectal adenocarcinoma cell line was isolated from a hepatic metastasis at the Ludwig Institute, São Paulo, SP, Brazil. The objective of the present study was to isolate morphologically different subpopulations within the LISP-I cell line, and characterize some of their behavioral aspects such as adhesion to and migration towards extracellular matrix components, expression of intercellular adhesion molecules and tumorigenicity in vitro. Once isolated, the subpopulations were submitted to adhesion and migration assays on laminin and fibronectin (crucial proteins to invasion and metastasis), as well as to anchorage-independent growth. Two morphologically different subpopulations were isolated: LISP-A10 and LISP-E11. LISP-A10 presents a differentiated epithelial pattern, and LISP-E11 is fibroblastoid, suggesting a poorly differentiated pattern. LISP-A10 expressed the two intercellular adhesion molecules tested, carcinoembryonic antigen (CEA) and desmoglein, while LISP-E11 expressed only low amounts of CEA. On the other hand, adhesion to laminin and fibronectin as well as migration towards these extracellular matrix proteins were higher in LISP-E11, as expected from its poorly differentiated phenotype. Both subpopulations showed anchorage-independent growth on a semi-solid substrate. These results raise the possibility that the heterogeneity found in the LISP-I cell line, which might have contributed to its ability to metastasize, was due to at least two different subpopulations herein identified.

P-selectin, carcinoma metastasis and heparin: novel mechanistic connections with therapeutic implications

Metastasis is a multistep cascade initiated when malignant cells penetrate the tissue surrounding the primary tumor and enter the bloodstream. Classic studies indicated that blood platelets form complexes around tumor cells in the circulation and facilitate metastases. In other work, the anticoagulant drug heparin diminished metastasis in murine models, as well is in preliminary human studies. However, attempts to follow up the latter observation using vitamin K antagonists failed, indicating that the primary mechanism of heparin action was unrelated to its anticoagulant properties. Other studies showed that the overexpression of sialylated fucosylated glycans in human carcinomas is associated with a poor prognosis. We have now brought all these observations together into one mechanistic explanation, which has therapeutic implications. Carcinoma cells expressing sialylated fucosylated mucins can interact with platelets, leukocytes and endothelium via the selectin family of cell adhesion molecules. The initial organ colonization of intravenously injected carcinoma cells is attenuated in P-selectin-deficient mice, in mice receiving tumor cells pretreated with O-sialoglycoprotease (to selectively remove mucins from cell surfaces), or in mice receiving a single dose of heparin prior to tumor cell injection. In each case, we found that formation of a platelet coating on cancer cells was impeded, allowing increased access of leukocytes to the tumor cells. Several weeks later, all animals showed a decrease in the extent of established metastasis, indicating a long-lasting effect of the short-term intervention. The absence of obvious synergism amongst the three treatments suggests that they all act via a common pathway. Thus, a major mechanism of heparin action in cancer may be inhibition of P-selectin-mediated platelet coating of tumor cells during the initial phase of the metastatic process. We therefore suggest that heparin use in cancer be re-explored, specifically during the time interval between initial visualization of a primary tumor until just after definitive surgical removal.

Expression of c-erbB-2, p53 and c-myc proteins in male breast carcinoma: Comparison with traditional prognostic factors and survival

There are few data evaluating biological markers for men with breast cancer. The purpose of the present study was to analyze the expression of the oncogenes c-erbB-2 and c-myc and of the suppressor gene p53 by immunohistochemical techniques in archival paraffin-embedded tissue blocks of 48 male breast cancer patients, treated at the A.C. Camargo Cancer Hospital, São Paulo, SP, Brazil. The results were compared with clinicopathological prognostic features. Immunopositivity of c-erbB-2, p53 and c-myc was detected in 62.5, 16.7 and 20.8% of the cases analyzed, respectively. Estrogen and progesterone receptors were positive in 75 and 69% of the cases, respectively. Increasing staging was statistically associated with c-erbB-2 (P = 0.04) and weakly related to p53 positivity (P = 0.06). No significant correlation between specific survival rate (determined by the log rank test) and the molecular markers analyzed was found, whereas the number of compromised lymph nodes and advanced TNM (tumor, node, metastasis) staging were associated with diminished survival.

Intercellular contact-dependent survival of human A549, NCI-H596 and NCI-H520 non-small cell lung carcinoma cell lines

In the present study, we examined the relationship between cell phenotype and cell survival of three human non-small cell lung carcinoma cell lines (A549, NCI-H596 and NCI-H520). Cells in exponential growth at various densities were incubated for 24 h at 37ºC in a 5% CO2 humidified atmosphere and then exposed to UV radiation for 1 min (256 nm, 40 W, source-to-target distance 100 cm). After two days the surviving cells were quantified by sulforhodamine ß staining and DNA fragmentation assay. The differences in UV sensitivity at 60 x 10³ cells/cm² among the cell lines were not related to the proliferative state of the cells but to the extent of intercellular contact. In contrast to A549 and NCI-H596, irradiated NCI-H520 cells presented lower DNA fragmentation and an aggregated cell culture phenotype even prior to confluence, suggesting that a contact-effect mechanism provides further protection against UV radiation.

c-Myc protein expression is not an independent prognostic predictor in cervical squamous cell carcinoma

The c-myc protein is known to regulate the cell cycle, and its down-regulation can lead to cell death by apoptosis. The role of c-myc protein as an independent prognostic determinant in cervical cancer is controversial. In the present study, a cohort of 220 Brazilian women (mean age 53.4 years) with FIGO stage I, II and III (21, 28 and 51%, respectively) cervical squamous cell carcinomas was analyzed for c-myc protein expression using immunohistochemistry. The disease-free survival and relapse-rate were analyzed using univariate (Kaplan-Meier) survival analysis for 116 women who completed the standard FIGO treatment and were followed up for 5 years. Positive c-myc staining was detected in 40% of carcinomas, 29% being grade 1, 9% grade 2, and 2% grade 3. The distribution of positive c-myc according to FIGO stage was 19% (17 women) in stage I, 33% (29) in stage II, and 48% (43) in stage III of disease. During the 60-month follow-up, disease-free survival in univariate (Kaplan-Meier) survival analysis (116 women) was lower for women with c-myc-positive tumors, i.e., 60.5, 47.5 and 36.6% at 12, 36, and 60 months, respectively (not significant). The present data suggest that immunohistochemical demonstration of c-myc does not possess any prognostic value independent of FIGO stage, and as such is unlikely to be a useful prognostic marker in cervical squamous cell carcinoma.

Presence of ductal carcinoma in situ confers an improved prognosis for patients with T1N0M0 invasive breast carcinoma

We have retrospectively analyzed a series of 155 sequential cases of T1N0M0 ductal carcinomas of which 51 tumors had a ductal carcinoma in situ (DCIS) component for correlation between the presence of DCIS and clinicopathological variables, recurrence and patient survival. No correlations between the presence of DCIS and age, menopausal status, size, estrogen or progesterone receptors were found. High-grade infiltrative tumors tended not to present a DCIS component (P = 0.08). Patients with tumors associated with DCIS form a subgroup with few recurrences (P = 0.003) and good survival (P = 0.008). When tumors were classified by size, an association between large tumors (>1.0 cm) and increased recurrence and shortened overall survival was found. The presence of DCIS in this subgroup significantly reduced the relative risk of death.