Mantle Cell Lymphoma Under the Scope of Personalized Medicine: Perspective and Directions.

Mantle cell lymphoma (MCL) is a rare, incurable non-Hodgkin's lymphoma characterized by naive B cells infiltrating the lymphoid follicle's mantle zone. A key feature of MCL is the cytogenetic abnormality t(11;14) (q13:q14), found in 95% of cases, leading to Cyclin D1 overexpression resulting in uncontrolled cell cycle progression and genetic instability. Occasionally, Cyclin D2 or D3 overexpression can substitute for Cyclin D1, causing similar effects. The transcription factor SOX11 is a hallmark of classical Cyclin D1-positive MCL and also in cases without the typical t(11;14) abnormality, making it an important diagnostic marker. MCL's development necessitates secondary genetic changes, including mutations in the ATM, TP53, and NOTCH1 genes, with the TP53 mutation being the only genetic biomarker with established clinical prognostic value. The Mantle Cell Lymphoma International Prognostic Index (MIPI) score, which considers age, performance status, serum LDH levels, and leukocyte count, stratifies patients into risk groups. Histologic variants of MCL, such as classic, blastoid, and pleomorphic, offer additional prognostic information. Recent research highlights new mutations potentially tied to specific populations among MCL patients, suggesting the benefit of personalized management for better predicting outcomes like progression-free survival. This approach could lead to more effective, risk-adapted treatment strategies. However, challenges remain in patient stratification and in developing new therapeutic targets for MCL. This review synthesizes current knowledge on genetic mutations in MCL and their impact on prognosis. It aims to explore the prognostic value of genetic markers related to population traits, emphasizing the importance of tailored molecular medicine in MCL.

Prognostic Factors in Children and Adolescents with Lymphomas and Vertical Transmission of HIV in Rio de Janeiro, Brazil: A Multicentric Hospital-Based Survival Analysis Study.

Lymphomas related to HIV are generally aggressive and have a poor prognosis, despite the use of combined antiretroviral therapy (cART) and effective chemotherapy treatment. To determine survival and prognostic factors in children and adolescents living with HIV (CLWH) in Rio de Janeiro (RJ), Brazil, who developed lymphomas, we performed a retrospective and observational study of vertically infected CLWH aged from 0 to 20 incomplete years during1995 to 2018 at five reference centers for cancer and HIV/AIDS treatment. Of the 25 lymphomas, 19 were AIDS-defining malignancies (ADM) and 6 were non-AIDS-defining malignancies (NADM). The 5-year overall survival (OS) and 5-year event-free survival (EFS) probabilities were both 32.00% (95% CI = 13.72-50.23%), and the 5-year disease-free survival (DFS) probability was 53.30% (95% CI = 28.02-78.58%). In the multivariate Cox regression analysis, performance status 4 (PS 4) was considered a poor prognostic factor for OS (HR 4.85, 95% CI = 1.81-12.97, p = 0.002) and EFS (HR 4.95, 95% CI = 1.84-13.34, p = 0.002). For the DFS, higher CD4+ T-cell counts were considered a better prognostic factor (HR 0.86, 95% CI = 0.76-0.97, p = 0.017) in the multivariate Cox regression analysis. This study demonstrates, for the first time, survival and prognostic factors for CLWH who developed lymphomas in RJ, Brazil.

A Novel Constitutional t(3;8)(p26;q21) and ANKRD26 and SRP72 Variants in a Child with Myelodysplastic Neoplasm: Clinical Implications.

BACKGROUND: Childhood myelodysplastic neoplasm (cMDS) often raises concerns about an underlying germline predisposition, and its verification is necessary to guide therapeutic choice and allow family counseling. Here, we report a novel constitutional t(3;8)(p26;q21) in a child with MDS, inherited from the father, the ANKRD26 and SRP72 variants from the maternal origin, and the acquisition of molecular alterations during MDS evolution. CASE PRESENTATION: A 4-year-old girl showed repeated infections and severe neutropenia. Bone marrow presented hypocellularity with dysplastic features. The patient had a t(3;8)(p26;q21)c identified by G-banding and FISH analysis. The family nucleus investigation identified the paternal origin of the chromosomal translocation. The NGS study identified ANKRD26 and SRP72 variants of maternal origin. CGH-array analysis detected alterations in PRSS3P2 and KANSL genes. Immunohistochemistry showed abnormal p53 expression during the MDS evolution. CONCLUSION: This study shows for the first time, cytogenetic and genomic abnormalities inherited from the father and mother, respectively, and their clinical implications. It also shows the importance of investigating patients with constitutional cytogenetic alterations and/or germline variants to provide information to their family nucleus for genetic counseling and understanding of the pathogenesis of childhood MDS.

Incidence and Clinical Description of Lymphomas in Children and Adolescents with Vertical Transmission of HIV in Rio de Janeiro, Brazil, in Pre- and Post-Combined Antiretroviral Therapy Eras: A Multicentric Hospital-Based Survival Analysis Study.

The incidence of cancer in children living with HIV (CLWH) is high and lymphomas are the most common type of cancer in this population. The combined antiretroviral therapy (cART) changed the natural history of HIV infection. To determine the incidence and profile of these CLWH malignancies in Rio de Janeiro (RJ), Brazil, we conducted a retrospective and observational study of vertically infected CLWH, ranging from 0−20 incomplete years, from 1995 to 2018, at five reference centers. The study period was divided into three eras in accordance with the widespread use of cART in Brazil. 1306 patients were included. Of the 25 lymphomas found, 19 were AIDS-defining malignancies (ADM); 6 were non-AIDS-defining malignancies (NADM). The incidence rate (IR) of lymphoma developing was 1.70 per 1000 children-year (95% CI 1.09−2.50). ADM development IR decreased from 2.09−1.75−0.19 per 1000 children-year (p < 0.001) through cART eras. Cumulative Nelson−Aalen hazards of developing ADM over a 20-year period were 3.73% in the Early-cART era, 3.07% in the Mid-cART era, and 0.32% in the Late-cART era (p = 0.013). This study demonstrates the IR of lymphoma in CLWH in RJ, Brazil, as well as the benefit of cART in reducing ADM and death occurrence in the Post-cART era.

Immunophenotypic shifts during minimal residual evaluation in a case of leukemic form of anaplastic large cell lymphoma ALK.

BACKGROUND: This study aims to describe immunophenotypic explorations at diagnosis and follow up of a pediatric patient with leukemic phase of ALK+ anaplastic large cell lymphoma (ALCL) by multiparametric flow cytometry (MFC). CASE: An 8-color MFC combination of antibodies allowed to identify neoplastic cells in concentrations until 0.02% during minimal residual disease (MRD) monitoring. Immunophenotypic shifts occurred in key markers as CD30, CD7, CD2, and CD5, however neoplastic cells were clearly discriminated from normal populations. CONCLUSION: MFC can be a useful tool for ALCL diagnosis and MRD monitoring and may support therapeutic decisions.

Flow Cytometry Immunophenotyping for Diagnostic Orientation and Classification of Pediatric Cancer Based on the EuroFlow Solid Tumor Orientation Tube (STOT).

Early diagnosis of pediatric cancer is key for adequate patient management and improved outcome. Although multiparameter flow cytometry (MFC) has proven of great utility in the diagnosis and classification of hematologic malignancies, its application to non-hematopoietic pediatric tumors remains limited. Here we designed and prospectively validated a new single eight-color antibody combination-solid tumor orientation tube, STOT-for diagnostic screening of pediatric cancer by MFC. A total of 476 samples (139 tumor mass, 138 bone marrow, 86 lymph node, 58 peripheral blood, and 55 other body fluid samples) from 296 patients with diagnostic suspicion of pediatric cancer were analyzed by MFC vs. conventional diagnostic procedures. STOT was designed after several design-test-evaluate-redesign cycles based on a large panel of monoclonal antibody combinations tested on 301 samples. In its final version, STOT consists of a single 8-color/12-marker antibody combination (CD99-CD8/numyogenin/CD4-EpCAM/CD56/GD2/smCD3-CD19/cyCD3-CD271/CD45). Prospective validation of STOT in 149 samples showed concordant results with the patient WHO/ICCC-3 diagnosis in 138/149 cases (92.6%). These included: 63/63 (100%) reactive/disease-free samples, 43/44 (98%) malignant and 4/4 (100%) benign non-hematopoietic tumors together with 28/38 (74%) leukemia/lymphoma cases; the only exception was Hodgkin lymphoma that required additional markers to be stained. In addition, STOT allowed accurate discrimination among the four most common subtypes of malignant CD45- CD56++ non-hematopoietic solid tumors: 13/13 (GD2++ numyogenin- CD271-/+ nuMyoD1- CD99- EpCAM-) neuroblastoma samples, 5/5 (GD2- numyogenin++ CD271++ nuMyoD1++ CD99-/+ EpCAM-) rhabdomyosarcomas, 2/2 (GD2-/+ numyogenin- CD271+ nuMyoD1- CD99+ EpCAM-) Ewing sarcoma family of tumors, and 7/7 (GD2- numyogenin- CD271+ nuMyoD1- CD99- EpCAM+) Wilms tumors. In summary, here we designed and validated a new standardized antibody combination and MFC assay for diagnostic screening of pediatric solid tumors that might contribute to fast and accurate diagnostic orientation and classification of pediatric cancer in routine clinical practice.

Chronic Granulomatous Disease and Myelodysplastic Syndrome in a Patient with a Novel Mutation in CYBB.

Chronic Granulomatous Disease (CGD) is an inborn error of immunity characterized by impaired phagocyte function, recurrent fungal and bacterial infections and granuloma formation in multiple organs. Pediatric myelodysplastic Syndrome (MDS) is a rare hematological stem cell disease that leads to an ineffective hematopoiesis with variable risk of evolution to acute leukemias. Both disorders are rare and have distinct pathophysiologic mechanisms, with no known association. A 7-month-old boy presenting with recurrent infections and anemia at age 2 months underwent immunological, hematological and genetic investigation that culminated in the diagnosis of both CGD and MDS. Next generation sequencing was performed and identified a silent variant predicted as of Uncertain Significance, located in the splicing site at the end of exon 5 in CYBB. CYBB variants account for at least two thirds of CGD cases, but no previous descriptions of this variant were found in ClinVar or The Human Gene Mutation Database (HGMD) databases. We were able to demonstrate an exon 5 skipping on the proband's cDNA, which strongly suggests the disruption of the NADPH oxidase complex, abrogating the formation of reactive oxygen species from neutrophils. Moreover, erythroid cell lineage could be also affected by NADPH oxidase complex damages. Further investigation is needed to evaluate the potential effect of CYBB gene alterations in hematopoiesis, as well as in MDS and CGD association.

Mature T/NK-Cell lymphomas of the oral and maxillofacial region: A multi-institutional collaborative study.

BACKGROUND: The diagnosis of oral and maxillofacial mature T/NK-cell neoplasms is challenging because of their rarity, morphological heterogeneity and complex immunophenotype with scarce available data describing their clinical and microscopic aspects. Therefore, in this study, we investigated a series of mature T/NK-cell neoplasms affecting this anatomical region and provided an updated literature review. METHODS: Cases diagnosed as mature T/NK-cell lymphomas affecting the oral and maxillofacial region were retrospectively retrieved from six pathology files and their diagnoses were confirmed using haematoxylin and eosin-stained slides, immunohistochemical reactions and in situ hybridization for Epstein-Barr virus (EBV) detection. Patients' clinical data were collected from their pathology forms. RESULTS: A total of 22 cases were included in this study. Eleven (50%) consisted of extranodal NK/T-cell lymphomas, nasal type; eight (36.4%) were peripheral T-cell lymphomas, NOS; two (9.1%) were adult T-cell leukaemia/lymphomas, and one (4.5%) was an ALK-positive anaplastic large cell lymphoma. Overall, males predominated, with a mean age of 55.7 years. The palate was the most affected site (50%), and tumours usually presented as destructive and painful ulcers. EBV was present in all cases of extranodal NK/T-cell lymphoma nasal type but was absent in the other subtypes. CONCLUSION: Among mature T/NK-cell lymphomas of the oral and maxillofacial region, extranodal NK/T-cell lymphoma, nasal type and peripheral T-cell lymphoma, NOS predominated. Older men were the most affected patients, and this heterogeneous group of neoplasms has a very aggressive clinical behaviour.

NADPH Oxidase 5 upregulation is associated with lymphoma aggressiveness.

OBJECTIVES: Lymphomas are a heterogeneous set of malignant neoplasias of lymphoid B and NK/T mature and immature cells at various stages of differentiation. Genetic and molecular biology tools are used to appropriately classify the type and prognosis of the lymphomas, which have implications in therapeutic effectiveness. Among them, the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase (NOX5) enzymes have been explored. This study analyzed the expression of NADPH oxidase 5 in lymphoma tissue according to the degree of tumor aggressiveness. METHODS: Slides from 64 patients with lymphoma who had paraffin-embedded tissue available were reviewed by two independent, experienced pathologists. They classified tumors according to the WHO classification (2017). NOX5 expression in tissues was assessed by immunohistochemical staining using a tissue microarray. The assay was interpreted using a scoring system of 0, 1, 2, and 3, for cytoplasmic staining of NOX5 corresponding to negative, weak, intermediate, and strong staining, respectively. We compared the expression of NOX5 in patients with aggressive versus non-aggressive lymphomas. RESULTS: NOX5 expression was positive in 100% (27/27) of aggressive lymphomas and in 19% (7/37) of non-aggressive ones. The seven patients with positive expression of NOX5 presented intermediate staining (2); strong staining (3) was observed only in tissues of aggressive lymphomas, and negative and weak staining (0 and 1) were observed only in non-aggressive lymphomas. CONCLUSIONS: Aggressive lymphomas overexpress NOX5 protein. The higher NOX5 expression in aggressive lymphomas can suggest an involvement of this enzyme on the acquisition of an aggressive phenotype in lymphoid neoplasia.

Anaplastic Large Cell Lymphoma with Oral Manifestation: A Series of Four Cases and Literature Review.

The aim of this study was to describe the clinicopathological and immunohistochemical features of four cases of anaplastic large cell lymphoma (ALCL) diagnosed through oral manifestations. Clinical data were collected from charts of a single oral pathology laboratory over a 5-year period (2014-2019) and all cases were evaluated by conventional hematoxylin and eosin staining and an extended immunohistochemical panel comprising CD45, CD20, CD3, CD4, CD7, CD30, CD99, CD138, cytokeratin AE1/AE3, EMA, ALK, MUM-1 and Ki-67. The study included 3 male (75%) and 1 female (25%) patients, with a median age of 44 years. The most common intraoral affected site was the alveolar ridge (50%). Clinically, all cases were characterized as an ulcerated bleeding mass. Microscopically, proliferation of anaplastic large lymphoid cells with medium to large-sized, abundant amphophilic to eosinophilic cytoplasm and eccentric nuclei were observed. All cases were positive for CD30, while two cases strongly express ALK. Two patients died of the disease. Careful correlation of clinical, morphological and immunohistochemical data are necessary to establish the diagnosis of oral manifestation of ALCL since its microscopical features may mimic other malignant tumors. Clinicians and pathologists should consider ALCL in the differential diagnosis when evaluating oral ulcerated swellings exhibiting large lymphoid cells in patients with lymphadenopathy.

NADPH Oxidase 5 upregulation is associated with lymphoma aggressiveness

SUMMARY OBJECTIVES Lymphomas are a heterogeneous set of malignant neoplasias of lymphoid B and NK/T mature and immature cells at various stages of differentiation. Genetic and molecular biology tools are used to appropriately classify the type and prognosis of the lymphomas, which have implications in therapeutic effectiveness. Among them, the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase (NOX5) enzymes have been explored. This study analyzed the expression of NADPH oxidase 5 in lymphoma tissue according to the degree of tumor aggressiveness. METHODS Slides from 64 patients with lymphoma who had paraffin-embedded tissue available were reviewed by two independent, experienced pathologists. They classified tumors according to the WHO classification (2017). NOX5 expression in tissues was assessed by immunohistochemical staining using a tissue microarray. The assay was interpreted using a scoring system of 0, 1, 2, and 3, for cytoplasmic staining of NOX5 corresponding to negative, weak, intermediate, and strong staining, respectively. We compared the expression of NOX5 in patients with aggressive versus non-aggressive lymphomas. RESULTS NOX5 expression was positive in 100% (27/27) of aggressive lymphomas and in 19% (7/37) of non-aggressive ones. The seven patients with positive expression of NOX5 presented intermediate staining (2); strong staining (3) was observed only in tissues of aggressive lymphomas, and negative and weak staining (0 and 1) were observed only in non-aggressive lymphomas. CONCLUSIONS Aggressive lymphomas overexpress NOX5 protein. The higher NOX5 expression in aggressive lymphomas can suggest an involvement of this enzyme on the acquisition of an aggressive phenotype in lymphoid neoplasia.

RESUMO OBJETIVOS Os linfomas são um grupo heterogêneo de neoplasias malignas de células linfoides B e NK/T maduras e imaturas em vários estágios de diferenciação. Ferramentas de biologia molecular e genética são usadas para classificar adequadamente o tipo e o prognóstico dos linfomas, os quais têm implicações na eficácia terapêutica. Entre eles, as enzimas nicotinamida adenina dinucleótido fosfato oxidase (NADPH) oxidase (NOX5) foram exploradas. Este estudo analisou a expressão da NADPH oxidase 5 em linfomas de acordo com o grau de agressividade tumoral. MÉTODOS As lâminas de 64 pacientes com linfoma, que tinham tecido embebido em parafina disponível, foram revisadas por dois patologistas experientes independentemente. Eles utilizaram a classificação da OMS (2017). A expressão de NOX5 nos tecidos foi avaliada por coloração imuno-histoquímica utilizando microarray de tecido. O ensaio foi interpretado com um sistema de pontuação de 0, 1, 2 e 3, para coloração citoplasmática de NOX5 correspondente à coloração negativa, fraca, intermediária e forte, respectivamente. Comparamos a expressão de NOX5 em pacientes com linfomas agressivos versus não agressivos. RESULTADOS A expressão de NOX5 foi positiva em 100% (27/27) dos linfomas agressivos e em 19% (7/37) dos linfomas não agressivos. Os sete pacientes com expressão positiva de NOX5 apresentaram coloração intermediária (2); coloração forte (3) foi observada apenas em tecidos de linfomas agressivos, e negativos e fracos (0 e 1) observados apenas em linfomas não agressivos. CONCLUSÕES Linfomas agressivos superexpressam a proteína NOX5. A expressão aumentada de NOX5 em linfomas agressivos pode sugerir um envolvimento dessa enzima na aquisição de um fenótipo agressivo na neoplasia linfoide.

DUOX1 Silencing in Mammary Cell Alters the Response to Genotoxic Stress.

DUOX1 is an H2O2-generating enzyme related to a wide range of biological features, such as hormone synthesis, host defense, cellular proliferation, and fertilization. DUOX1 is frequently downregulated in lung and liver cancers, suggesting a tumor suppressor role for this enzyme. Here, we show that DUOX1 expression is decreased in breast cancer cell lines and also in breast cancers when compared to the nontumor counterpart. In order to address the role of DUOX1 in breast cells, we stably knocked down the expression of DUOX1 in nontumor mammary cells (MCF12A) with shRNA. This led to higher cell proliferation rates and decreased migration and adhesion properties, which are typical features for transformed cells. After genotoxic stress induced by doxorubicin, DUOX1-silenced cells showed reduced IL-6 and IL-8 secretion and increased apoptosis levels. Furthermore, the cell proliferation rate was higher in DUOX1-silenced cells after doxorubicin medication in comparison to control cells. In conclusion, we demonstrate here that DUOX1 is silenced in breast cancer, which seems to be involved in breast carcinogenesis.

Treatment outcomes for Hodgkin lymphoma: First report from the Brazilian Prospective Registry.

Data about Hodgkin lymphoma (HL) in developing countries are scarce and suggest the existence of substantial disparities in healthcare and outcomes in large areas of the world. In 2009, a prospective registry of HL was implemented in Brazil. Web-based data were contributed by 20 institutions across the country participating in the Brazilian Prospective Hodgkin's Lymphoma Registry. The aim of this study was to present the clinical features and outcomes of newly diagnosed patients with HL aged 13 to 90 years. Multivariate Cox regression models were used to estimate progression-free (PFS) and overall survival (OS) by clinical factors. A total of 674 patients with classical HL were analysed, with a median follow-up of 37 months. Median age was 30 years (13-90). The median time from the onset of symptoms to diagnosis was 6 months (0-60). Only 6% of patients had early favourable disease, while 65% had advanced disease. Stage IVB was present in 26% and a high-risk International Prognostic Score in 38%. Doxorubicin, bleomycin, vinblastine, and dacarbazine was used in 93%. The median dose of radiotherapy was 36 Gy for localized disease and 32 Gy for advanced disease. The 3 year PFS in early favourable, early unfavourable, and advanced disease were 95%, 88%, and 66%, respectively. High-risk International Prognostic Score, advanced disease, and age greater than or equal to 60 were independently associated with poorer PFS and OS; performance status greater than or equal to 2 was also associated with a poorer OS. Poor-risk patients predominated. Radiation doses for localized disease appear higher than current recommendations. Outcomes appear inferior in developing countries than in developed countries. Delayed diagnosis is probably a major factor underlying these findings. Scattered reports from developing nations suggest that many aspects of standard care in developed countries remain unmet needs for populations living in developing countries. The present report contributes to this body of data, with a proper description of what is currently achieved in urban areas in Brazil.

Clinicopathological and Immunohistochemical Study of Head and Neck Langerhans Cell Histiocytosis from Latin America.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplastic proliferation with variable clinical behavior caused by the accumulation of CD1a+/CD207+ histiocytes, associated with a variable number of eosinophils, lymphocytes, plasma cells and multinucleated giant cells, most commonly observed in male children. LCH is uncommon in the head and neck region, occurring as ulcerated and reddened plaques or nodules that cause destruction of adjacent soft tissues and bone. The exact etiology of LCH is still unknown and controversial, with possible etiologic role of viruses, including Epstein-Barr virus (EBV). The aim of this study was to describe the clinicopathologic and immunohistochemical features of patients with LCH of the head and neck region. Clinical data from 19 patients with LCH were obtained from the archives of the Federal University of Rio de Janeiro and the Clinical Head and Neck Center of Guatemala. All cases were submitted to morphological, immunohistochemical analysis with CD1a, CD207, CD3, CD20, CD68, S-100 and Ki-67 and in situ hybridization for EBV. Ten cases were female and 9 male, with mean age of 11.5 years. Fourteen cases were located in the oral cavity, three cases in lymph nodes, and two cases in the scalp. In regard to the oral lesions, 13 cases were intra-osseous with six cases in anterior mandible, five cases in posterior mandible, and two cases in posterior maxilla while one case was located exclusively in the gingiva. The inflammatory pattern showed variation in the number of plasma cells, eosinophils and lymphocytes, while tumor cells were positive for CD1a, S-100 and CD68 in all cases, and positive for CD207 in 18 cases. In situ hybridization for EBV were negative in all cases.

Lower socioeconomic status is independently associated with shorter survival in Hodgkin Lymphoma patients-An analysis from the Brazilian Hodgkin Lymphoma Registry.

Socioeconomic status (SES) is a well-known determinant of outcomes in cancer. The purpose of this study was to analyze the impact of the SES on the outcomes of Hodgkin lymphoma (HL) patients from the Brazilian Prospective HL Registry. SES stratification was done using an individual asset/education-based household index. A total of 624 classical HL patients with diagnosis from January/2009 to December/2014, and treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine), were analyzed. The median follow-up was 35.6 months, and 33% were classified as lower SES. The 3-year progression- free survival (PFS) in higher and lower SES were 78 and 64% (p < 0.0001), respectively. The 3-year overall survival (OS) in higher and lower SES were 94 and 82% (p < 0.0001), respectively. Lower SES patients were more likely to be ≥ 60 years (16 vs. 8%, p = 0.003), and to present higher risk International Prognostic score (IPS) (44 vs. 31%, p = 0.004) and advanced disease (71 vs. 58%, p = 0.003). After adjustments for potential confounders, lower SES remained independently associated with poorer survival (HR = 3.12 [1.86-5.22] for OS and HR = 1.66 [1.19-2.32] for PFS). The fatality ratio during treatment was 7.5 and 1.3% for lower and higher SES (p = 0.0001). Infections and treatment toxicity accounted for 81% of these deaths. SES is an independent factor associated with shorter survival in HL in Brazil. Potential underlying mechanisms associated with the impact of SES are delayed diagnosis and poorer education. Educational and socio-economic support interventions must be tested in this vulnerable population.

Malacoplaquia pulmonar associada à imunodeficiência por HTLV-1 e HIV / Pulmonary malakoplakia associated with immunodeficiency by HTLV-1 and HIV

Malakoplakia is a rare chronic inflammatory disease often confused with neoplasia. In this paper we report two cases of pulmonary Malakoplakia, both with typical clinical diagnosis of tuberculosis and lung cancer. A patient with human T-lymphotropic virus type I (HTLV-1) and diagnosis of adult T-cell leukemia/lymphoma, and another patient with human immunodeficiency virus (HIV), which was treated for tuberculosis, but, after pulmonary lobectomy, was evidenced Rodococosis equi, progressed to death...

Malacoplaquia é uma rara doença inflamatória crônica muitas vezes confundida com neoplasia. Neste artigo, relatam-se dois casos de malacoplaquia pulmonar, ambos com quadro clínico sugestivo de tuberculose e neoplasia pulmonar. Uma paciente com vírus T-linfotrópico humano tipo I (HTLV-1) e diagnóstico de leucemia/linfoma de células T do adulto, e um paciente com vírus da imunodeficiência humana (HIV), tratado para tuberculose, mas após lobectomia pulmonar foi evidenciado Rodococose equi, evoluindo para óbito...

Contribution of multiparameter flow cytometry immunophenotyping to the diagnostic screening and classification of pediatric cancer.

Pediatric cancer is a relatively rare and heterogeneous group of hematological and non-hematological malignancies which require multiple procedures for its diagnostic screening and classification. Until now, flow cytometry (FC) has not been systematically applied to the diagnostic work-up of such malignancies, particularly for solid tumors. Here we evaluated a FC panel of markers for the diagnostic screening of pediatric cancer and further classification of pediatric solid tumors. The proposed strategy aims at the differential diagnosis between tumoral vs. reactive samples, and hematological vs. non-hematological malignancies, and the subclassification of solid tumors. In total, 52 samples from 40 patients suspicious of containing tumor cells were analyzed by FC in parallel to conventional diagnostic procedures. The overall concordance rate between both approaches was of 96% (50/52 diagnostic samples), with 100% agreement for all reactive/inflammatory and non-infiltrated samples as well as for those corresponding to solid tumors (n = 35), with only two false negative cases diagnosed with Hodgkin lymphoma and anaplastic lymphoma, respectively. Moreover, clear discrimination between samples infiltrated by hematopoietic vs. non-hematopoietic tumor cells was systematically achieved. Distinct subtypes of solid tumors showed different protein expression profiles, allowing for the differential diagnosis of neuroblastoma (CD56(hi)/GD2(+)/CD81(hi)), primitive neuroectodermal tumors (CD271(hi)/CD99(+)), Wilms tumors (>1 cell population), rhabdomyosarcoma (nuMYOD1(+)/numyogenin(+)), carcinomas (CD45(-)/EpCAM(+)), germ cell tumors (CD56(+)/CD45(-)/NG2(+)/CD10(+)) and eventually also hemangiopericytomas (CD45(-)/CD34(+)). In summary, our results show that multiparameter FC provides fast and useful complementary data to routine histopathology for the diagnostic screening and classification of pediatric cancer.

Changing patterns of AIDS: impact on the indications and diagnostic yield of bone marrow biopsies.

After the advent of HAART, the clinical course of HIV infection has dramatically improved. Therefore, it seems appropriate to reevaluate the performance of bone marrow biopsy (BMB) as a diagnostic tool. The aim of the present study was to compare the reasons for performing a BMB and its diagnostic yield in HIV-patients before and after HAART. A total of 165 BMB specimens obtained from HIV-infected patients receiving care at the Hospital of Universidade Federal do Rio de Janeiro in two different periods (1986-1994 and 1999-2004) were analysed. The main reason for BMB examination in the first period was fever (88%), which decreased in the second period (57%, p < 0.0001), when cytopenia (51%) was the leading reason for BMB, whereas in the first period it accounted for only 30% (p = 0.008). A definitive diagnosis (infection, granulomas or lymphomas) was obtained in 28% of patients in the first period and in 19% during the second period (p = 0.20). The diagnosis turned out as infections decreased from 16% in period 1 to 2% in period 2 (p = 0.003). Despite the the limitations in the evaluation of fever, the use of BMB must be considered on an individual basis, whenever less invasive alternatives have been exhausted, and should be complemented by a bone marrow aspiration for microbiological studies.