RESUMO Racional: Mutações KRAS são eventos importantes na carcinogênese colorretal como preditores negativos de resposta ao tratamento. Objetivo: Investigar a associação de características clinicopatológicas com mutações no KRAS em pacientes com câncer colorretal tratados. Métodos: Sessenta e nove pacientes com câncer colorretal metastáticos ao diagnóstico ou posteriormente foram analisados. As técnicas de sequenciamento direto e pirosequenciamento foram relacionadas ao éxon 2 do KRAS e o diagnóstico da mutação e seu tipo foram determinados. Resultados: A mutação KRAS foi identificada em 43,4% dos pacientes, c.35G>T (p.G12V), c.35G>A (p.G12D) e c.38G>A (p.G13D). Não foi encontrada correlação entre a mutação KRAS e a idade (p=0,646) ou o gênero (p=0,815). No entanto, o grupo mutado apresentou níveis mais altos de CEA na admissão (p=0,048). A mutação do códon 13 foi associada ao envolvimento de mais de um local metastático na progressão da doença (p=0,029); não houve associação entre o local primário do tumor e o diagnóstico de mutação (p=0,568); a doença primária do cólon foi associada com pior sobrevida global (p=0,009). Conclusão: A mutação KRAS foi identificada em quase metade dos pacientes. O grupo KRAS mutado apresentou níveis mais altos de CEA na admissão e a mutação no códon 13 foi associada ao envolvimento de mais de um local metastático no curso da doença. A doença do cólon foi associada com pior sobrevida global.

ABSTRACT Background: KRAS mutations are important events in colorectal carcinogenesis, as well as negative predictors of response to EGFR inhibitors treatment. Aim: To investigate the association of clinical-pathological features with KRAS mutations in colorectal cancer patients treated. Methods: Data from 69 patients with colorectal cancer either metastatic at diagnosis or later, were retrospectively analyzed. The direct sequencing and pyrosequencing techniques were related to KRAS exon 2. The mutation diagnosis and its type were determined. Results: KRAS mutation was identified in 43.4% of patients. The most common was c.35G>T (p.G12V), c.35G>A (p.G12D) and c.38G>A (p.G13D). No correlation was found between KRAS mutation and age (p=0.646) or gender (p=0.815). However, mutated group had higher CEA levels at admission (p=0.048) and codon 13 mutation was associated with involvement of more than one metastatic site in disease progression (p=0.029). Although there was no association between primary tumor site and mutation diagnosis (p=0.568), primary colon was associated with worse overall survival (p=0.009). Conclusion: The KRAS mutation was identified in almost half of patients. Mutated KRAS group had higher levels of CEA at admission and the mutation at codon 13 was associated with involvement of more than one metastatic site in the course of the disease. Colon disease was associated with the worst overall survival.

Abstract: Pigmented purpuric dermatoses (PPD) include a spectrum of diseases with different clinical aspects, but with similar histopathological features. Specific clinical findings allow the division of PPD in variants. Schamberg's disease is the most common. Treatment is sometimes ineffective and recurrences are common. There are reports of patients who responded well to the use of colchicine. We report the case of a 32-year-old woman, previously healthy, with a history of onset of asymptomatic lesions in legs. She presented purpuric skin eruptions and brownish stains diffusely distributed in the lower limbs. Biopsy was compatible with PPD. We decided for the introduction of colchicine, with good clinical response. The patient has been followed on outpatient basis for ten months without recurrence.

Abstract: A 54 year-old woman with a 3-year history of rheumatoid arthritis (RA) consulted us because of weight loss, fever and skin eruption. On physical examination, erythematous plaques with a pseudo-vesicular appearance were seen on the back of both shoulders. Histological examination was consistent with rheumatoid neutrophilic dermatosis (RND). After three days of prednisone treatment, the skin eruption resolved. RND is a rare cutaneous manifestation of seropositive RA, characterized by asymptomatic, symmetrical erythematous plaques with a pseudo-vesicular appearance. Histology characteristically reveals a dense, neutrophilic infiltrate with leucocitoclasis but without other signs of vasculitis. Lesions may resolve spontaneously or with RA treatment. This case illustrates an uncommon skin manifestation of active rheumatoid arthritis.

RESUMO O objetivo do estudo foi avaliar os efeitos da desnutrição protéico-calórica em camundongos isogênicos da linhagem BALB/c inoculados com Lacazia loboi, empregando parâmetros nutricionais e histopatológicos. Foram constituídos quatro grupos: G1- inoculados com restrição dietética; G2- não inoculados com restrição dietética; G3- inoculados sem restrição dietética; G4- não inoculados sem restrição dietética. Após instalada a desnutrição, os animais foram inoculados via intradérmica no coxim plantar e após quatro meses foram sacrificados para remoção do coxim plantar, fígado e baço. A infecção não exerceu grande influência no peso corporal dos camundongos. O peso do fígado e baço apresentou redução nos grupos desnutridos em comparação aos grupos nutridos. A lesão macroscópica, a viabilidade e o número total de fungos dos coxins plantares dos camundongos inoculados revelaram aumento no G3 quando comparado com o G1. Em relação à análise histopatológica dos coxins plantares observou-se aumento da celularidade global na composição do granuloma no G3 em relação ao G1, com grande número de macrófagos e células gigantes multinucleadas, discretos números de linfócitos estavam presentes em G3 e aumentados no G1. Os resultados sugerem que existe grande interação entre nutrição e doença de Jorge Lobo.

SUMMARY The aim of this study was to evaluate the effects of the protein-calorie malnutrition in BALB/c isogenic mice infected with Lacazia loboi, employing nutritional and histopathological parameters. Four groups were composed: G1: inoculated with restricted diet, G2: not inoculated with restricted diet, G3: inoculated with regular diet, G4: not inoculated with regular diet. Once malnutrition had been imposed, the animals were inoculated intradermally in the footpad and after four months, were sacrificed for the excision of the footpad, liver and spleen. The infection did not exert great influence on the body weight of the mice. The weight of the liver and spleen showed reduction in the undernourished groups when compared to the nourished groups. The macroscopic lesions, viability index and total number of fungi found in the footpads of the infected mice were increased in G3 when compared to G1. Regarding the histopathological analysis of the footpad, a global cellularity increase in the composition of the granuloma was observed in G3 when compared to G1, with large numbers of macrophages and multinucleated giant cells, discrete numbers of lymphocytes were present in G3 and an increase was observed in G1. The results suggest that there is considerable interaction between Jorge Lobo's disease and nutrition.

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease.