Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412.

Mastocytosis are myeloproliferative neoplasms commonly related to gain-of-function mutations involving the tyrosine kinase domain of KIT. We herein report a case of familial systemic mastocytosis with the rare KIT K509I germ line mutation affecting two family members: mother and daughter. In vitro treatment with imatinib, dasatinib and PKC412 reduced cell viability of primary mast cells harboring KIT K509I mutation. However, imatinib was more effective in inducing apoptosis of neoplastic mast cells. Both patients with familial systemic mastocytosis had remarkable hematological and skin improvement after three months of imatinib treatment, suggesting that it may be an effective front line therapy for patients harboring KIT K509I mutation.

Differences in estrogen and progesterone receptor expression in endometrial polyps and atrophic endometrium of postmenopausal women with and without exposure to tamoxifen.

Postmenopausal women who use tamoxifen present with an increased incidence of endometrial alterations, such as polyps and hyperplasia, in addition to a higher risk of malignant endometrial neoplasms. Among these endometrial changes, polyps are the most common, with a pathogenesis associated with hormonal influence. The objective of this study was to compare the expression of estrogen receptors (ERs) and progesterone receptors (PRs) in endometrial polyps from tamoxifen users with that in endometrial polyps and the atrophic endometrium of postmenopausal tamoxifen non-users. Among women undergoing surgical hysteroscopy, 84 tamoxifen users with benign endometrial polyps were selected. This group was compared to 84 samples of atrophic endometrium and to 252 benign polyps from postmenopausal women who were not treated with tamoxifen. The expression of ER/PR was assessed by immunohistochemical analysis, according to the percentage of stained cells, intensity of nuclear staining and final score. The polyps from tamoxifen users exhibited a higher expression of ER and PR in the glandular epithelium and stroma compared to the atrophic endometrium (P<0.0001). Compared to the polyps from women not treated with tamoxifen, tamoxifen users exhibited a higher PR expression in the epithelium (P=0.0014) and stroma (P=0.0056), with no difference in the expression of ER. In conclusion, endometrial polyps frequently exhibit an increase in ER expression, regardless of tamoxifen use. High levels of PR expression appear to be consistent with the estrogen agonist effects of tamoxifen.

A pituitary adenoma secreting follicle-stimulating hormone with ovarian hyperstimulation: treatment using a gonadotropin-releasing hormone antagonist.

OBJECTIVE: To describe the management of a patient with a pituitary adenoma secreting follicle-stimulating hormone (FSH) associated with ovarian hyperstimulation who was treated with a gonadotropin-releasing hormone (GnRH) antagonist. DESIGN: Case report. SETTING: University teaching hospital. PATIENT(S): A woman of reproductive age with secondary amenorrhea and ovarian hyperstimulation due to a pituitary adenoma secreting FSH, which persisted after transsphenoidal surgery. INTERVENTION(S): Clinical treatment with a GnRH antagonist. MAIN OUTCOME MEASURE(S): A decrease in serum estradiol levels. RESULT(S): During the treatment period, ovarian hyperstimulation decreased as shown by a reduction in estradiol levels and an improvement in the patient's clinical condition and in the ultrasonography parameters. CONCLUSION(S): The GnRH antagonist was found to be effective for the short-term treatment of ovarian hyperstimulation secondary to a pituitary adenoma secreting FSH, thus representing a therapeutic option that should be taken into consideration in such cases.

A utilidade da citologia por punção com agulha fina aliada a imunofenotipagem no diagnóstico dos linfomas não-Hodgkin / Diagnosis of non-Hodgkin's lymphoma combining immunophenotyping and fine needle aspiration

A classificação para linfomas não-Hodgkin (LNH) proposta pela Organização Mundial da Saúde (OMS) enfatiza a importância do imunofenótipo para o diagnóstico. O objetivo deste estudo foi avaliar a utilidade da citologia combinada a citometria de fluxo para o diagnóstico de LNH, utilizando um painel de anticorpos monoclonais e estudo do ciclo celular. O material foi obtido através de aspiração de linfonodos por agulha fina de 78 pacientes. O painel de anticorpos monoclonais para análise em citometria de fluxo foi o seguinte: CD19/CD10, CD20/CD5, CD23, CD38/CD7, CD3/CD4, CD3/CD8, kappa/lambda. O diagnóstico final foi confirmado pela histologia convencional, considerada gold standard. Em 85 por cento dos casos a citologia associada a imunofenotipagem e porcentagem de células em fase S permitiram um diagnóstico correto. Nos demais casos foi possível diferenciar linfomas B ou T e estimar grau de agressividade. O painel, embora pequeno, foi suficiente exceto para os anaplásicos e subclassificação dos linfomas T. Nestes casos, a morfologia foi mais importante que imunofenótipo, sendo este seguro apenas para linfomas linfoblásticos. A fração de fase S mostrou-se importante para diferenciar linfomas indolentes e de alto grau. Concluímos que esta técnica é uma boa alternativa para o diagnóstico de linfomas não-Hodgkin. Permite um diagnóstico rápido, menos invasivo, podendo ser repetida quando necessário, agilizando o tratamento.

Early histopathological changes in bone marrow of Paracoccidioides brasiliensis-infected mice

The involvement of bone marrow in the pathology of experimental P. brasiliensis infection in BALB/c mice was investigated. The histopathological features of bone marrow induced by the fungus were correlated with hematological changes in peripheral blood from 1 to 28 days post-infection. Intense lymphopenia and moderate neutrophilia were detected. The early changes in bone marrow included (i) maturation arrest characterized by an increase immature blood cell precursors, mainly of granulocytic origin, (ii) intense vascular congestion when compared with the vessels of normal marrow, and (iii) an increased number of megakaryocytes. The normal histological pattern of bone marrow was restored by 28 days post-infection. No histologically recognizable lesion, such as granuloma formation or an abnormal cellular infiltrate, which could indicate the presence of the P. brasiliensis in bone marrow, was observed. In addition, special stains were unable to detect the fungus. The mechanisms responsible for the alterations described here are still unclear but are probably related to more general phenomena affecting the host rather than the direct damage of the precursors cells by P. brasiliensis.

Diagnosis of hepatitis C virus in Brazilian blood donors using a reverse transcriptase nested polymerase chain reaction: comparison with enzyme immunoassay and recombinant protein immunoblot assay

Screening blood donations for anti-HCV antibodies and alanine aminotransferase (ALT) serum levels generally prevents the transmission of hepatitis C virus (HCV) by transfusion. The aim of the present study was to evaluate the efficiency of the enzyme immunoassay (EIA) screening policy in identifying potentially infectious blood donors capable to transmit hepatitis C through blood transfusion. We have used a reverse transcriptase (RT)-nested polymerase chain reaction (PCR) to investigate the presence of HCV-RNA in blood donors. The prevalence of HCV-RNA positive individuals was compared with the recombinant immunoblot assay (RIBA-2) results in order to assess the usefulness of both tests as confirmatory assays. Both tests results were also compared with the EIA-2 OD/C ratio (optical densities of the samples divided by the cut off value). ALT results were expressed as the ALT quotient (qALT), calculated dividing the ALT value of the samples by the maximum normal value (53UI/l) for the method. Donors (n=178) were divided into five groups according to their EIA anti-HCV status and qALT: group A (EIA > or = 3, ALT<1), group B (EIA > or = 3, ALT>1), group C (1<=EIA<3, ALT<1), group D (1<=EIA<3, ALT>1) and group E (EIA<=0.7). HCV sequences were detected by RT-nested PCR, using primers for the most conserved region of viral genome. RIBA-2 was applied to the same samples. In group A (n=6), all samples were positive by RT-nested PCR and RIBA-2. Among 124 samples in group B, 120 (96.8 percent) were RIBA-2 positive and 4 (3.2 percent) were RIBA-2 indeterminate but were seropositive for antigen c22.3. In group B, 109 (87.9 percent) of the RIBA-2 positive samples were also RT-nested PCR positive, as well as were all RIBA-2 indeterminate samples. In group C, all samples (n=9) were RT-nested PCR negative: 4 (44.4 percent) were also RIBA-2 negative, 4 (44.4 percent) were RIBA-2 positive and 1 (11.1 percent) was RIBA-2 indeterminate. HCV-RNA was detected by RT-nested PCR in 3 (37.5 percent) out of 8 samples in group D. Only one of them was also RIBA-2 positive, all the others were RIBA-2 indeterminate. All of the group E samples (controls) were RT- nested PCR and RIBA-2 negative. Our study suggests a strong relation between anti-HCV EIA-2 ratio > or = 3 and detectable HCV-RNA by RT-nested PCR. We have also noted that blood donors with RIBA-2 indeterminate presented a high degree of detectable HCV-RNA using RT-nested PCR...

Edema agudo pulmonar fatal pós transplante autólogo de medula óssea com célula progenitora periférica condicionado com o protocolo BEAM / Fatal acute lung edema after autologous bone marrow transplantation with peripherical steem cell conditioning BEAM protocol

Este relato apresenta um caso de paciente jovem com linfoma näo Hodgkin refratário que apresentou um edema pulmonar agudo fatal após transplante autólogo de células-tronco periféricas. Embora a causa exata do mecanismo do evento seja desconhecida, o texto discute todas as possibilidades, incluindo anafilaxia ao dimetilsulfoxido e disfunçäo cardíaca ventricular transitória secundária ao regime de condicionamento.

Amigdalite crônica / Chronic tonsillitis

O termo amigdalite crônica foi usado durante muito tempo para afecçöes repetitivas das amígdalas. Os patologistas têm empregado, de modo geral, este termo quando o exame das amígdalas encontram infiltrado linfoplasmocitário. Atualmente chamamos a este achado de reticulaçäo de cripta, sendo sinal de atividade amigdaliana. Os autores fazem estudo comparativo entre a história clínica do paciente e o laudo do exame histopatológico. Verificou-se que, mesmo em paciente sem queixas de amigdalites, o laudo do patologista era de amigdalite crônica. Os autores ainda sugerem uma nova classificaçäo das patologias amigdalianas baseadas nos graus de reticulaçäo, presença de plasmócitos, fases dos centros germinativos e suas quantidades