Ronald Feitosa Pinheiro

Primary Breast Lymphoma: An Uncommon but Curable Disease

Primary malignant breast lymphoma (PBL) is a rare disease with an incidence of 0.04-0.5% of all malignant breast neoplasms. The majority of cases are B-cell lymphomas and the most common histologic type is diffuse large B-cell lymphoma (DLCL). In this study, we report our experience with three cases of PBL. The treatment was the same currently indicated for early stage aggressive NHL, i.e. anthracycline based chemotherapy followed by the involved field radiation therapy. Unfortunately, two patients underwent mastectomy to carry out correct diagnosis. The three patients are alive without any evidence of relapse after 24, 67 and 135 months of follow-up. Considering that aggressive NHL is very sensitive to chemotherapy, mastectomy should be avoided to preserve the quality of life of these patients, once surgery does not change the good prognosis of PBL.

FLT3 internal tandem duplication during myelodysplastic syndrome follow-up : a marker of transformation to acute myeloid leukemia

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by ineffective hematopoiesis and risk for evolving to acute leukemia. Some molecular abnormalities related to acute myeloid leukemia (AML) transformation have been reported, such as FLT3 (FMS-like tyrosine kinase 3) mutations. FLT3, a member of the class 3 receptor tyrosine kinase family, mediates stem cell proliferation and differentiation, and its mutations, internal tandem duplication (ITD) and Asp835, have been reported in rare MDS patients. We studied FLT3 ITD, prospectively, in 50 MDS patients at diagnosis, at 6 and 12 months follow-up, and at any other time-point if AML transformation was detected. FLT3 ITD was not observed at diagnosis, but during follow-up the mutation was present in 2 of 50 patients (4%). Of these, one case exhibited FLT3 ITD at the end of the 6 months of follow-up in approximately 8% of bone marrow cells; this case evolved into AML at 8 months, at which time FLT3 ITD was present in approximately 85% of bone marrow cells. The other case exhibited FLT3 ITD in 68% of bone marrow cells at 7 months, precisely at the time of AML transformation. Although rare in MDS, FLT3 ITD is associated with a high probability of evolution to AML.

Septic arthritis as the first sign of Candida tropicalis fungaemia in an acute lymphoid leukemia patient

Fungal infections caused by Candida species have increased in incidence during the past two decades in England, North America and Europe. Candidal arthritis is rare in patients who are not intravenous drug users or are who not using a prostheses. We report the case of a 24-year-old man with acute lymphoid leukemia, who developed Candida tropicalis arthritis during an aplastic period after chemotherapy. This is the eighth case described in the literature of C. tropicalis causing arthritis without intra-articular inoculation. We call attention to an unusual first sign of fungal infection: septic arthritis without intra-articular inoculation. However, this case differs from the other seven, since despite therapy a fast and lethal evolution was observed. We reviewed reported cases, incidence, risk factors, mortality and treatment of neutropenic patients with fungal infections.

Pioderma gangrenoso bolhoso e síndrome mielodisplásica

Pyoderma gangrenosum can present as a cutaneous manifestation of paraneoplastic syndromes. A case of bullous pyoderma gangrenosum associated with bicytopenia is described. During the complementary investigation, myelogram, bone marrow biopsy and karyotype were performed, and showed a pattern consistent with myelodysplastic syndrome. The patient was treated with dapsone with improvement. Pyoderma gangrenosum can be a manifestation of systemic diseases. The possibility of myelodysplastic syndrome should always be considered in patients with pyoderma gangrenosum associated with cytopenia. Pyoderma gangrenosum could indicate poorer prognosis in patients with systemic diseases.

Trisomy 22: a subclone marker?

Universidade Federal de Sao Paulo, Disciplina Hematol & Hemoterapia, Escola Paulista Med, EPM, BR-04023900 Sao Paulo, Brazil

Prognostic importance of Aurora Kinases and mitotic spindle genes transcript levels in Myelodysplastic syndrome

Myelodysplastic syndrome (MDS) are a heterogeneous group of clonal disease characterized by insufficiency of bone marrow, increase of apoptosis and increased risk of acute leukemia progression. Proteins related to the mitotic spindle (AURKA, AURKB, TPX2), to the mitotic checkpoint (MAD2, CDC20) and the regulation of the cell cycle (p21) are directly related to chromosomal stability and tumor development. This study aimed to evaluate the mRNA expression levels of these genes in 101 MDS patients using a real-time PCR methodology. We identified that CDC20 expression are increased in patients with dysmegakaryopoiesis (p=0.024), thrombocytopenia (p=0.000) and high-risk patients (p=0.014, 0.018) MAD2 expression are decreased in patients with 2 or 3 cytopenias (p=0.000) and neutrophil below 800/mm3. TPX2 is also overexpressed in patients presenting dysmegakaryopoiesis (p=0.009). A decrease in AURKA and AURKB expression were observed in patients with altered karyotype (p=0.000), who presented dysplasia in 3 lineages (p=0.000; 0.017) and hemoglobin inferior to 8g/dL (p=0.024). The expression of AURKA, AURKB and MAD2 (p=0.000; 0.001; 0.025) were decreased in patients with hypoplastic MDS, associated with high frequency of chromosomal alterations and high mortality rate. This study reaffirms the importance of aurora kinases and mitotic spindle genes to the pathogenesis and clinical evolution of MDS.

Low Back Pain During Streptokinase Infusion

We report the case of a 57-year-old male patient with severe low back pain during streptokinase infusion administered to treat typical chest pain and elevation of the ST segment in the inferior wall. We reviewed the literature, emphasizing the differential diagnosis, the pathophysiology, and management of the event.

Does soy increase blood counts in myelodysplastic syndromes

As sindromes mielodisplasicas (SMD) sao um grupo das doencas clonais de celulas-tronco caracterizado por hematopoese ineficaz, hiperproliferacao de medula ossea, citopenias no sangue periferico e risco de transformacao para leucemia aguda. Decidimos investigar os efeitos de um concentrado de soja em pacientes com SMD com base no fato de termos o seguimento de uma paciente japonesa, de 61 anos de idade, que foi diagnosticada em 2003 com SMD, citopenia refrataria com displasia subtipo multilinhagens (hemoglobina = 11 g/dL; contagem de globulos brancos = 2.500/uL e plaquetas = 25.000/uL; medula com displasia leve e cariotipo normal; hemoglobinuria paroxistica excluida), e que comecou a usar a soja como suplemento alimentar em maio de 2004, apresentando gradual aumento da contagem das celulas sanguineas, atingindo a normalizacao cerca de oito meses depois. Entre os componentes da soja, os principais compostos com propriedades anticarcinogenese sao as isoflavonas (Ge nisteina e daidzeina). Com base nessas linhas de evidencia, foi proposto oferecer diariamente um concentrado de soja padrao, por um periodo minimo de tres meses e maximo de doze meses, a 14 pacientes ambulatoriais, na tentativa de avaliar, prospectivamente, o possivel aumento de hemoglobina, neutrofilos e plaquetas. Um grupo controle historico foi utilizado para comparar os resultados. O uso de um concentrado de soja de forma padronizada foi associado ao aumento na contagem de neutrofilos e/ou de plaquetas em alguns casos, mas aumentos espontâneos tambem foram observados em controles historicos. Este estudo preliminar nao permite estabelecer relacao entre o uso de soja e o aumento na contagem sanguinea.

Linfoma não Hodgkin primário da coluna vertebral

O linfoma primario do osso (LPO) e uma condicao extremamente rara, habitualmente confundida com outras lesoes osseas primarias. E responsavel por cerca de 3%-5% de todos os tumores malignos no osso e 4%-7% de todos os linfomas naoHodgkin extranodais. Caracteriza-se pelo envolvimento de um ou varios locais osseos, com ou sem comprometimento de linfonodos regionais e visceras. Histopatologicamente, o linfoma non Hodgkin de grandes celulas B representa a maioria dos casos de LPO. Ossos longos sao mais frequentemente comprometidos, e o femur e o sitio mais acometido. Osso iliaco e da coluna vertebral tambem podem ser atingidos. Relatamos um caso raro de linfoma nao Hodgkin da vertebra em mulher de 41 anos. A imuno-histoquimica revelou CD20 e CD45 positivos. Ela foi diagnosticada com linfoma primario difuso de grandes celulas B da coluna vertebral. O estudo histopatologico da medula ossea nao detectou infiltracao por hemopatia linfoide. A paciente foi tratada com quimioterapia CHOP juntamente com etoposide, seguida de radioterapia (dose total = 3600cGy) na regiao toraco-lombar. Nao houve evidencia de recidiva em um periodo de vinte meses de acompanhamento.

Síndrome mielodisplásica secundária à quimio ou radioterapia: SMD relacionada a tratamento

The leukaemogenic effect of chemotherapeutic agents after treatment for other malignancies have been well described. Myelodysplastic syndrome secondary to chemo- and radiotherapy (MDS-t) usually develops four to seven years after the initial exposure to chemotherapy frequently involving young patients, shows a high incidence of transformation to AML, is associated with severe cytopenias, trilineage dysplasia, reduced marrow cellularity and fibrosis, and presents an incidence of chromosomal abnormalities of up to 80% of the cases. The most common abnormalities are related to chromosomes 5 and 7. Alkylating agents have been considered the most common drugs associated with MDS-t. High dose chemotherapy used as part of the conditioning regimen prior to bone marrow transplantation as well as traditional regimens such as COPP/ABV and BEACOPP have also been associated with MDS-t. Recently, drugs such as azathioprine, rituximab and cladribine have been reported as causes too. Due to the increasing survival of patients suffering from other malignancies, MDS-t results as a mutagenic effect of these therapies and is related to poor prognosis.