F. Duarte

Cutaneous manifestations associated with antiphospholipid antibodies

Background  Primary Antiphospholipid Antibody Syndrome (PAAS) is characterized by detection of antiphospholipid antibodies associated with venous or arterial thrombosis and/or miscarriages by patients with no other associated disease such as systemic lupus erythematosus (SLE). Primary Antiphospholipid Antibody Syndrome has many clinical manifestations of which dermatological ones are probably the most common. The purpose of this study was to determine the frequency of each cutaneous lesion, describing clinical features essential for diagnosis, in patients with Antiphospholipid Antibody Syndrome (AAS) attending Walter Cantídio University Hospital.

Multiple lymphoid nodules in bone marrow biopsy in immunocompetent patient with cytomegalovirus infection: an immunohistochemical analysis

In Brazil, a high prevalence of cytomegalovirus (CMV) infection has been documented. In immunocompetent adults CMV infection is usually asymptomatic and therefore morphologic and immunophenotypic bone marrow changes have rarely been described. The authors report the case of a previously healthy patient who developed fever of undetermined origin. The diagnosis of acute CMV infection was based on serological testing. A computed tomographic scan showed mediastinal lymphadenopathy. A bone marrow biopsy revealed a hypercellular haematopoiesis with eosinophilia and large mixed T- and B-cell lymphoid aggregates. In spite of bcl-2 positivity, their reactive nature was demonstrated. Polymerase chain reaction (PCR) and immunohistochemistry were unable to detect CMV-DNA in paraffin-embedded bone marrow sections. Much like in other systemic disorders, the lymphoid nodules in this case seemed to be caused by immunological mechanisms, possibly due to cytokines released in response to the systemic infectious process.

Avaliação do perfil hematológico de pacientes com leucemia linfocítica crônica (LLC-B) em um hemocentro estadual

Tem sido dada grande importância aos avancos na biologia molecular e genetica no estabelecimento de novos protocolos, bem como a descoberta de novos marcadores tumorais, uteis ao diagnostico e tratamento precoces de varias doencas neoplasicas, inclusive a leucemia linfocitica cronica de celulas B (LLC-B). Para avaliacao da atual significância do sistema de estadiamento clinico de Rai no prognostico de 50 pacientes com LLC-B em um hemocentro estadual, bem como para comparacao entre os resultados do estadiamento com valores sericos de LDH e CD38 ao diagnostico, foram coletados dos prontuarios dos pacientes dados referentes a contagem total de linfocitos e plaquetas, concentracao de hemoglobina, e tambem informacoes quanto a presenca ou ausencia de linfadenopatia e/ou organomegalia no periodo de admissao. Quando comparados os resultados do estadiamento com aqueles de outros estudos, observou-se uma situacao preocupante quanto ao percentual superior de pacientes ja classificados como de alto risco ao diagnostico. Este quadro de aparente atraso na deteccao da LLC-B foi em parte atribuido a dificuldade de acesso a centros especializados e/ou atraso na avaliacao hematologica. Alem disso, observaram-se incoerencias entre os valores de LDH e CD38, e entre estes e o sistema de classificacao clinica de Rai. Os resultados sugerem que este sistema de classificacao pode ainda ser util como panorama geral comparativo da LLC-B entre diferentes populacoes, mas tambem enfatizam a necessidade de modelos prognosticos especificos que considerem, alem dos dados clinicos e marcadores CD38 e LDH, outros indicadores mais precisos do status mutacional IgVH para prognosticos e terapias mais exatos.

Bone marrow fibrosis at diagnosis is associated with TP53 overexpression and adverse prognosis in low‐risk myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is a heterogeneous group of stem cell clonal alterations, culminating in a high risk of progression to acute myeloid leukaemia (AML) (Greenberg et al, 2012). The prognosis of these patients is commonly determined by the International Prognostic Score System (IPSS), which considers the number of cytopenias, cytogenetic alterations and number of blasts in the bone marrow at diagnosis. Patients with a lower risk of progression to AML are classified as low risk; however, a subgroup of these patients develops a disease with an aggressive course and a lower survival rate (Mittelman et al, 2010). This clinical heterogeneity reinforces the need to identify auxiliary markers for prognostic stratification systems. Bone marrow fibrosis is a histological finding in approximately 10–20% of patients with de novo MDS; however, MDS with fibrosis is not yet recognized as a distinct entity and its prognostic role is still under debate (Ramos et al, 2016). The immunohistochemical expression of TP53 has been used as a predictive marker for mutations in the TP53 gene in several haematological diseases due to the low-cost and easy to perform technique (Kulasekararaj et al, 2013). Moreover, studies have demonstrated that TP53 expression is an independent adverse prognostic factor in patients with highrisk MDS, being associated with complex karyotype and therapy-related MDS (Kulasekararaj et al, 2013). Therefore, the present study investigated the impact of bone marrow fibrosis and TP53 expression at diagnosis on the clinical characteristics and overall survival of patients with low-risk MDS. Seventy-three low-risk MDS patients treated at a reference University Hospital in the northeast of Brazil participated in the study. Patients were stratified according to the IPSS and revised IPSS (IPSS-R) criteria (Greenberg et al, 2012). Clinical data at diagnosis, such as karyotype, complete blood count, number of blasts, presence of fibrosis and evolution to death or AML, were collected from medical records. TP53 expression was determined by immunohistochemistry, according to Shah et al (2012). Briefly, 5-lm sections of bone marrow were incubated with the p53-DO7 monoclonal antibody (Dako, Santa Clara, CA, USA). TP53 protein was identified by the ABC – peroxidase technique, staining with 3,30-Diaminobenzidine (DAB; Dako), and counterstaining with haematoxylin. The percentage and intensity of TP53 staining was assessed based on a total manual count of 1000 granulocytic precursors. TP53 expression was defined as positive for a strong nuclear staining pattern, according to the Modified Quick Score (Kulasekararaj et al, 2013) in at least 1% of the cells analysed (Saft et al, 2014). Patients were stratified for the presence of bone marrow fibrosis at diagnosis according to the criteria used by the European Myelofibrosis Network (Thiele et al, 2005). The study was approved by the Research Ethics Committee of the Federal University of Cear a (protocol #129/12) and all patients agreed to participate. Statistical analysis was performed using the GraphPad Prism 5.0 software (GraphPad Software Inc., La Jolla, CA, USA), using chi-square and Student’s t or Mann–Whitney test, according data normality, verified by Kolmogorov–Smirnov test. The Kaplan–Meier curve was performed to verify differences in overall survival. Significance was set at P < 0 05. The median age of the study patients was 65 years, with a predominance of females (64 3% females and 35 7% males). Most of the patients (49 32%) were classified as single-lineage dysplasia, followed by multi-lineage dysplasia (41 09%), MDS with ringed sideroblasts (6 85%) and MDS with isolated del(5q) (2 74%). Patients with bone marrow fibrosis (MF-2 and MF-3) had significantly lower haemoglobin and haematocrit values at diagnosis when compared to patients without fibrosis (MF-0 and MF-1) (P = 0 001). High TP53 expression was associated with the presence of bone marrow fibrosis (P = 0 008). There was no difference between the other analysed parameters (Table I). Patients with bone marrow fibrosis [P = 0 0007, hazard ratio (HR) = 0 02, 95% confidence interval (CI) = 0 002– 0 20] and high TP53 expression (P = 0 0039, HR = 14 34, 95% CI = 2 0–102 8) had lower overall survival when compared to patients without these findings. Overall survival in patients with bone marrow fibrosis (MF-2 and MF-3) did not demonstrate a significant difference regarding TP53 expression (P = 0 3794, HR = 2 62, 95% CI = 0 34–17 40) (Fig 1). Some studies have reported on the importance of bone marrow fibrosis in prognostic characteristics and survival of patients with de novo MDS; however, the role of these Correspondence