Paracoccidioidomycosis in patients with lymphoma and review of published literature.

This paper describes four new cases of lymphomas, two Hodgkin lymphomas and two non-Hodgkin lymphomas in patients with paracoccidioidomycosis. All had mycosis diagnosed before lymphomas with Paracoccidioides brasiliensis demonstrated in several lymph nodes, as seen in the disseminated form of the disease. When lymphoma was diagnosed, one patient was under regular paracoccidioidomycosis treatment and in clinic-serological remission for this disease, another was under regular treatment but with clinic-serological mycosis activity, one had abandoned paracoccidioidomycosis treatment 6 years earlier, and the other had not yet received any kind of antifungal drugs. Three patients received treatment for lymphomas with one remaining in remission until now, one achieving tumor remission which relapsed years later, and one having only residual lymphoma in bone marrow for a decade but clinically well. All three experienced paracoccidioidomycosis clinical remission, however, serology became negative just in one. Similar previously described cases were reviewed: five Hodgkin lymphomas, three non-Hodgkin lymphomas, and one described only as "lymphoma" without specifying type; a summary of their findings is presented. Finally, there is also a brief discussion on the possible pathophysiological mechanisms involved in the concomitance of these two disorders.

Diffuse large B-cell lymphoma: morphologic and immunohistochemical analysis of bone marrow for staging, with emphasis on lymphoid aggregates.

Diffuse large B-Cell lymphoma (DLBCL) may infiltrate bone marrow (BM) and evaluation of BM plays an important role in DLBCL staging. This study used BM samples from DLBCL patients for staging and analyzed the use of immunohistochemistry in the diagnostic management of these cases by the pathologist. Patients with DLBCL submitted to BM biopsy/aspiration for staging were studied according to clinical aspects, morphologic aspects, and expression of CD20 and CD3. The characteristics of lymphoid aggregates in the bone marrow and the power of histopathological diagnosis were studied, with immunohistochemistry as the gold standard for the decision of a neoplastic infiltration definition. An isolated morphological analysis showed low sensitivity (42.9%) for lymphoma detection in BM, which is disadvantageous. The median of three lymphoid aggregates in the BM (p-value = 0.02) and the presence of increased reticulin fibers (grade 2) in the lymphoid aggregate (p-value = 0.01) had significant associations with neoplastic infiltration. A morphological analysis must be accompanied by an immunohistochemical analysis in all cases, or when this is not possible, in cases with two or more lymphoid aggregates or an increase of reticulin within them.

Uncommon trans-iliac bone faecal fistula in a leukaemic patient.

This is a rare case of an elderly woman diagnosed with acute myeloid leukaemia secondary to myelodysplastic syndrome who presented a spontaneous trans-iliac bone faecal fistula probably related to an incarcerated inguinal hernia and neutropaenia. As far as we know, this is the first described case of a trans-iliac bone faecal fistula.

p53 and p21 expression in bone marrow clots of megaloblastic anemia patients.

The pathogenesis of megaloblastic hemopathies (MH) is centered on the deficiency of vitamin B12 and folic acid with interruption of erythrocyte maturation. This study researched the participation of p53 and p21 in the pathophysiology of the disease. A retrospective study enrolled 95 patients with histopathologic diagnosis by biopsy or bone marrow clot (BMB/BMC), with clinical review and immunohistochemical study in tissue microarray (TMA) for p53 and p21, detailing their marking location. All patients had BMC and only 11 had BMB. The CMO was a differential of this study and it allowed an expanded sample. In the TMA, 63.7% (58/91) of the samples were immunopositive for p53; and 35.2% (31/88) were immunopositive for p21. Nuclear staining, divergent from the literature, was observed in 17.3% (10/58) among those p53+ and in 38.7% (12/31) among those p21+. The pattern of immunostaining showed non-significant differences (P=0.474) regarding morphologic and clinical aspects. The positivity for both may indicate an effective balance between apoptosis and anti-apoptotic action. Excessive inhibition of apoptosis would contribute to high global cellularity, but without functional maturation effectiveness. In conclusion, there is p21 and/or p53 immunoexpression in most cases of this study and there is no clear association between immunoexpression pattern and patient outcome. Unlike the literature, we also found a percentage of nuclear immunostaining, but the finding was not statistically significant. Combination of p21 and p53 results created different possibilities of pathologic interpretation for MH, reinforcing the importance of studies similar to this one.

Bone marrow necrosis related to paracoccidioidomycosis: the first eight cases identified at autopsy.

AIMS: To report the first eight bone marrow necrosis (BMN) cases related to paracoccidioidomycosis (PCM) from patient autopsies with well-documented bone marrow (BM) histology and cytology. METHODS AND RESULTS: A retrospective evaluation was performed on BM specimens from eight autopsied patients from Botucatu University Hospital with PCM-related BMN. Relevant BMN literature was searched and analysed. CONCLUSIONS: All eight patients had acute PCM. Six had histological only (biopsies) and two cytological only (smears) specimens. Five biopsy specimens revealed severe and one mild coagulation patterned necrotic areas. Five had osteonecrosis. The cytological specimens also showed typical BMN patterns. Paracoccidioides brasiliensis yeast forms were visible within necrotic areas in all cases.

Bone Marrow Aspirate Clot: A Useful Technique in Diagnosis and Follow-Up of Hematological Disorders.

Bone marrow biopsy is a diagnostic tool largely used in the evaluation of a broad number of disorders that could affect the hematopoietic system. Differently, bone marrow aspirate clot technique is rarely performed even though it has been described in literature. Here, we highlight the utility of the bone marrow aspirate clot, exemplifying through the discussion of three clinical cases in which this technique was used for diagnosis and follow-up purposes: megaloblastic hemopathy, multiple myeloma, and chronic lymphocytic leukemia. Bone marrow clot analysis increases sensitivity to diagnose hemopathies and offers the possibility of morphological evaluation and anatomopathological study, with the advantage of not needing decalcification processes, hence improving antigenic expression in immunohistochemical and FISH techniques. It is an easy-to-perform technique, offering a quick, reliable, and more comfortable procedure for patients.

Double-hit lymphomas: clinical, morphological, immunohistochemical and cytogenetic study in a series of Brazilian patients with high-grade non-Hodgkin lymphoma.

BACKGROUND: Double-hit lymphomas (DHL) are rare high-grade neoplasms characterized by two translocations: one involving the gene MYC and another involving genes BCL2 or BCL6, whose diagnosis depends on cytogenetic examination. This research studied DHL and morphological and/or immunophenotypic factors associated with the detection of these translocations in a group of high-grade non-Hodgkin lymphoma cases. METHOD: Clinical and morphological reviews of 120 cases diagnosed with diffuse large B-cell lymphoma and Burkitt lymphoma were conducted. Immunohistochemistry (CD20, CD79a, PAX5, CD10, Bcl6, Bcl2, MUM1, TDT and Myc) and fluorescence in situ hybridization for detection of MYC, BCL2 and BCL6 gene translocations were performed in a tissue microarray platform. RESULTS: Three cases of DHL were detected: two with translocations of MYC and BCL2 and one with translocations of MYC and BCL6, all leading to death in less than six months. Among 90 cytogenetically evaluable biopsies, associations were determined between immunohistochemistry and fluorescence in situ hybridization for MYC (p = 0.036) and BCL2 (p = 0.001). However, these showed only regular agreement, indicated by Kappa values of 0.23 [0.0;0.49] and 0.35 [0.13;0.56], respectively. "Starry sky" morphology was strongly associated with MYC positivity (p = 0.01). The detection of three cases of DHL, all resulting in death, confirms the rarity and aggressiveness of this neoplasm. CONCLUSIONS: The "starry sky" morphological pattern and immunohistochemical expression of Myc and Bcl2 represent possible selection factors for additional cytogenetic diagnostic testing.

Bullous leukemia cutis mimicking facial cellulitis.

Bullous leukemia cutis is an uncommon clinical manifestation of cutaneous infiltration by leukemic cells, from B-cell chronic lymphocytic leukemia. We present the case of a 67-year-old, female, chronic lymphocytic leukemia patient. She was taking chlorambucil and developed facial edema with erythema and warmth, misjudged as facial cellulitis. Two days later, she developed bullous lesions in the arms, legs, neck and face. The histopathology of facial and bullous lesions confirmed leukemia cutis. All lesions disappeared following the administration of rituximab combined with cycles of fludarabine and cyclophosphamide. Although soft tissue infections are common complications in patients undergoing chemotherapy, leukemia cutis can also resemble cellulitis.

[Isolated Richter's syndrome in central nervous system: case report].

Diffuse large cell non Hodgkin's lymphoma associated with chronic lymphoid leukemia (CLL), or Richter's syndrome, is a rare and serious complication. Isolated Richter's syndrome in the central nervous system is very rare; only 12 cases have been reported. We describe a 74-year-old patient with diffuse large cell non Hodgkin's lymphoma in the right frontal region with the appearance of multiform glioblastoma.

The Brazilian Pediatric Myelodysplastic Cooperative Group strategies: are they relevant to improve educational approach and correct diagnosis?

Brazil is a wide country with huge contrasts. Its peculiarities can highlight environmental factors that could influence the frequencies of different cancers. The standard treatment and results achieved from several different areas of the country may not be found in others. The establishment of a national cooperative group has the potential to improve outcomes. The The Brazilian Cooperative Group on Pediatric Patients with Myelodysplastic Syndrome (BCG-MDS-PED) was first organized in January 1997 as a working group of hematologists, pediatric oncologists, pediatric-hematologists, molecular biologists and other professionals in order to study pediatric (age <18 years) MDS. Six distinct subcommittees constituted with members from several universities: cytology, histopathology, clinical, cytogenetics, molecular biology and epidemiology. The goals of the BCG-MDS-PED were: (i) to offer support for diagnosis and orientation for treatment; (ii) educational support for the colleagues all over the country and (iii) research on pathogenesis and new approaches for pediatric MDS patients. There are socio-economical differences among the five regions of the country. The BCG-MDS-PED believes that it is absolutely necessary to study the clinical, cellular, molecular and epidemiological aspects of MDS, taking in account these peculiar differences among populations and regions. Since 1997, 114 pediatric cases were referred to the BCG-MDS-PED from 21 centres. Seven Brazilian states have sent cases to the group, 31 patients were referred from universities, 73 patients from pediatric oncology units (foundations ) and 10 patients came from private clinics. Some of these patients have been followed up and/or treated by the physician who referred them to the BCG-MDS-PED for confirmation of the initial diagnosis. The majority of these physicians have required orientation on diagnostic and treatment issues, as well as to complete cytogenetic and molecular studies. From these 114 patients, 64 patients were confirmed as MDS. We believe that, the more numerous the MDS-studied cases, the more experienced will be the referee group on clinical and laboratory features on childhood MDS in Brazil.

Treatment of pediatric myelodysplastic syndromes and juvenile myelomonocytic leukemia: the Brazilian experience in the past decade.

BACKGROUND: Therapy strategies for myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) vary considerably. OBJECTIVE: To review the treatment of Brazilian children who were diagnosed with MDS or JMML in the past decade and reported to the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). RESULTS: Of 173 children reported to the BCG-MDS-PED from January 1997 to January 2003 with a suspected diagnosis of MDS or JMML, 91 had the diagnosis confirmed after central review of the bone marrow aspirate and biopsy. Information on previous treatments was available for 78 MDS/JMML patients. Treatment varied from different schedules of low-dose (14%) and standard-dose chemotherapy (50%), granulocyte-colony-stimulating factor (G-CSF 7%), interferon (5%), steroids (2%) and erythropoietin (2%) to allogeneic stem-cell transplantation (SCT) (14%). No survival advantage could be demonstrated based on Hasle's classification or based on treatment. CONCLUSION: This report reflects the current practice in treating Brazilian children with MDS/JMML without specific Cooperative Group guidelines. Treatment modalities were very heterogeneous. The strategies for implementing a national protocol should consider international guidelines and focus on local experience and available resources.

Hodgkin disease in adult and juvenile groups from two different geographic regions in Brazil: characterization of clinicopathologic aspects and relationship with Epstein-Barr virus infection.

We analyzed clinicopathologic data, immunophenotype, and Epstein-Barr virus (EBV) status in 96 cases of Hodgkin disease (HD) in juveniles (younger than 20 years) and adults (20 years or older) from 2 distinctive states in Brazil. We studied 34 juvenile (group 1) and 16 adult (group 2) cases from Ceara and 31 juvenile (group 3) and 15 adult (group 4) cases from São Paulo. Ceara has a socioeconomic profile similar to a developing country; São Paulo is in better economic condition. Mixed cellularity (MC) was the major histologic subtype among groups 1 (22 [65%]), 3 (21 [68%]), and 4 (7 [47%]); nodular sclerosis (NS) was more frequent in group 2 (8 [50%]). EBV infection was observed in 61 cases (64%), including the following (among others): group 1, MC, 22 (65%) and NS, 4 (12%); group 2, NS, 3 (19%) and MC, 2 (12%); group 3, MC, 16 (52%) and NS, 1 (3%); and group 4, MC, 7 (47%). There was predominance of EBV+ HD cases in group 1 compared with group 3. HD in Brazilian patients is highly associated with EBV infection, but geographic differences reflect histologic subtypes and age distribution.

Post-Ganglionic Horner's Syndrome: An Unusual Presentation of Non-Hodgkin Lymphoma.

In this paper, we present the rare case of a patient with cervical lymphadenopathy diagnosed as a T-cell-rich B-cell non-Hodgkin lymphoma that manifested Horner's syndrome due to a post-ganglionic sympathetic neuron lesion caused by the tumor.

Acute lymphoblastic leukemia: primary bone manifestation with hypercalcemia in a child / Leucemia linfoblástica aguda: manifestação óssea primária com hipercalcemia em criança

ABSTRACT Primary bone manifestation associated with hypercalcemia is an infrequent presentation of acute lymphoblastic leukemia (ALL) in children. An 8-year-old girl was admitted with bone and abdomen pain, vomiting, fever, headache, anemia, elevated serum calcium and normal parathyroid hormone levels. Bone radiographs: osteolytic lesions. Bone marrow biopsy showed an infiltration by ALL with immunohistochemical positivity for CD45, CD20, CD79a, TdT and CD10, clinically characterized by hypercalcemia, multifocal osteolytic lesions and single cytopenia. Bone marrow biopsy was a relevant aid in establishing the diagnosis of multifocal osteolytic lesions, associated with hypercalcemia.

RESUMO Apresentação óssea primária associada à hipercalcemia é manifestação clinicolaboratorial infrequente de leucemia linfoblástica aguda (LLA) em crianças. Relatamos o caso de uma criança do sexo feminino, 8 anos, admitida com dores ósseas e no abdômen associadas a vômitos, febre, cefaleia, anemia, hipercalcemia e níveis de paratormônio normais. Radiografias ósseas apresentaram lesões osteolíticas. Biópsia de medula óssea demonstrou infiltração por LLA com positividade imuno-histoquímica para CD45, CD79a, TdT e CD10, clinicamente caracterizada por hipercalcemia, lesões osteolíticas multifocais e citopenia única. A biópsia de medula óssea é importante ferramenta no estabelecimento do diagnóstico de lesões osteolíticas multifocais associada à hipercalcemia.

Serum levels of interleukins 6, 10, and 13 before and after treatment of classic Hodgkin lymphoma.

CONTEXT: Interleukins (ILs) 6, 10, and 13 seem to be important in the pathogenesis of Hodgkin lymphoma (HL), but there is insufficient data on the serum levels of these cytokines in patients with HL. OBJECTIVES: To evaluate serum levels of IL-6, IL-10, and IL-13 before and after HL treatment and to determine their potential association with clinical and laboratory parameters. DESIGN: Serum IL-6, IL-10, and IL-13 levels were quantified in the serum of 27 patients with HL by enzyme-linked immunosorbent assay. Results were evaluated against clinical and laboratory parameters, response to treatment, and presence of infection by the Epstein-Barr virus. As a control group, serum samples from 26 healthy blood donors were evaluated the same way. RESULTS: Pretreatment serum levels of IL-6 and IL-10 were significantly higher in patients with HL (P < .001), and a significant decrease was observed after treatment (P < .001). Serum IL-13 was undetectable in both patient and control groups. Serum IL-6 was higher in patients with abdominal involvement (P  =  .02), hepatomegaly (P  =  .03), B symptoms (P  =  .02), and anemia (P  =  .02). Serum IL-10 levels were higher in patients with hypoalbuminemia (P  =  .04). No association with EBV status was observed. Lymphocytopenia and B symptoms were accurate predictors of IL-6 serum levels before treatment, and higher pretreatment levels of IL-6 were observed in patients with treatment failure (P  =  .03). CONCLUSIONS: Serum levels of IL-6 and IL-10 were frequently elevated in patients with HL and decreased substantially after conventional chemotherapy. The association of elevated IL-6 and IL-10 levels in serum with some clinical and laboratory features suggests those ILs may be useful biomarkers for monitoring the HL disease and its response to chemotherapy.