Comparative histological analysis of spleens in pediatric patients with hemolytic anemias: Insights into the pathophysiological mechanisms of spleen destruction in sickle cell anemia.

While sickle cell anemia (SCA) and hereditary spherocytosis (HS) share common features of increased spleen erythrophagocytosis due to increased red blood cell (RBC) turnover, SCA is specifically characterized by susceptibility to infections. In this study, histological lesions in the spleens of pediatric patients with SCA were analyzed, in close correlation with past clinical history and comparatively to HS, healthy and transfused ß-thalassemia patients (TDT). An evaluation of red pulp elementary lesions (red pulp fibrosis, iron deposition, number of Gandy-Gamna, and RBC trapping) combined into a severity score was established, as well as B-cell follicles analysis. Quantification on digitalized slides of iron deposition, RBC trapping, and red pulp fibrosis was additionally performed. Spleens from 22 children with SCA, eight with HS, eight with TDT, and three healthy controls (HC) were analyzed. Median age at splenectomy was not different between SCA and HS patients, 6.05 years (range: 4.5-16.0) versus 4.75 (range: 2.2-9.5). Marked heterogeneity was found in SCA spleens in contrast to other conditions. Contrary to previous reports, B-cell follicles were generally preserved in SCA. While RBC trapping was significantly increased in both SCA and HS (compared to TDT and HC), quantitative fibrosis and overall red pulp severity score were significantly increased in SCA spleens compared to other conditions. Moreover, there was an inverse correlation between quantitative fibrosis and number of B-cell follicles, linking these two compartments as well as spleen fibrosis to infectious susceptibility in SCA, potentially through impaired red pulp macrophage scavenging and B-cell subpopulations defects.

Non-Hodgkin lymphoma in Romania: a single-centre experience.

Epidemiologic studies of non-Hodgkin lymphoma (NHL) in Eastern Europe are scarce in the literature. We report the experience of the "Ion Chiricuta" Institute of Oncology in Cluj-Napoca (IOCN), Romania, in the diagnosis and outcome of patients with NHL. We studied 184 consecutive NHL patients diagnosed in the Pathology Department of IOCN during the years 2004-2006. We also obtained epidemiological data from the Northwestern (NW) Cancer Registry. In the IOCN series, the most common lymphoma subtype was diffuse large B-cell lymphoma (43.5%), followed by the chronic lymphocytic leukaemia/small lymphocytic lymphoma (21.2%). T-cell lymphomas represented a small proportion (8.2%). The median age of the patients was 57 years, with a male-to-female ratio of 0.94. Patients with indolent B-cell lymphomas had the best overall survival, whereas those with mantle cell lymphoma had the worst survival. The NW Cancer Registry data showed that the occurrence of NHL in the NW region of Romania was higher in men [world age-standardized incidence rate/100 000 (ASR)-5.9; 95% CI 5.1-6.6] than in women (ASR-4.1; 95% CI 3.5-4.7) with age-standardized male-to-female ratio of 1.44 (p = 0.038). Chronic lymphocytic leukaemia/small lymphocytic lymphoma was the most common NHL in the NW region of Romania, accounting for 43% of all cases, followed by diffuse large B-cell lymphoma (36%). The 5-year, age-standardized cumulative relative survival for NHL in the County of Cluj in NW Romania, for the period of 2006-2010, was 51.4%, with 58.4% survival for men and 43.2% for women. Additional studies of NHL in Eastern Europe are needed. Copyright © 2015 John Wiley & Sons, Ltd.

Non-Hodgkin lymphoma in the developing world: review of 4539 cases from the International Non-Hodgkin Lymphoma Classification Project.

The distribution of non-Hodgkin lymphoma subtypes varies around the world, but a large systematic comparative study has never been done. In this study, we evaluated the clinical features and relative frequencies of non-Hodgkin lymphoma subtypes in five developing regions of the world and compared the findings to the developed world. Five expert hematopathologists classified 4848 consecutive cases of lymphoma from 26 centers in 24 countries using the World Health Organization classification, and 4539 (93.6%) were confirmed to be non-Hodgkin lymphoma, with a significantly greater number of males than females in the developing regions compared to the developed world (P<0.05). The median age at diagnosis was significantly lower for both low- and high-grade B-cell lymphoma in the developing regions. The developing regions had a significantly lower frequency of B-cell lymphoma (86.6%) and a higher frequency of T- and natural killer-cell lymphoma (13.4%) compared to the developed world (90.7% and 9.3%, respectively). Also, the developing regions had significantly more cases of high-grade B-cell lymphoma (59.6%) and fewer cases of low-grade B-cell lymphoma (22.7%) compared to the developed world (39.2% and 32.7%, respectively). Among the B-cell lymphomas, diffuse large B-cell lymphoma was the most common subtype (42.5%) in the developing regions. Burkitt lymphoma (2.2%), precursor B- and T-lymphoblastic leukemia/lymphoma (1.1% and 2.9%, respectively) and extranodal natural killer/T-cell lymphoma (2.2%) were also significantly increased in the developing regions. These findings suggest that differences in etiologic and host risk factors are likely responsible, and more detailed epidemiological studies are needed to better understand these differences.

Non-Hodgkin lymphoma in Southern Africa: review of 487 cases from The International Non-Hodgkin Lymphoma Classification Project.

Comparative data on the distribution of non-Hodgkin lymphoma (NHL) subtypes in Southern Africa (SAF) is scarce. In this study, five expert haematopathologists classified 487 consecutive cases of NHL from SAF using the World Health Organization classification, and compared the results to North America (NA) and Western Europe (WEU). Southern Africa had a significantly lower proportion of low-grade (LG) B-NHL (34·3%) and a higher proportion of high-grade (HG) B-NHL (51·5%) compared to WEU (54·5% and 36·4%) and NA (56·1% and 34·3%). High-grade Burkitt-like lymphoma was significantly more common in SAF (8·2%) than in WEU (2·4%) and NA (2·5%), most likely due to human immunodeficiency virus infection. When SAF patients were divided by race, whites had a significantly higher frequency of LG B-NHL (60·4%) and a lower frequency of HG B-NHL (32·7%) compared to blacks (22·5% and 62·6%), whereas the other races were intermediate. Whites and other races had a significantly higher frequency of follicular lymphoma and a lower frequency of Burkitt-like lymphoma compared to blacks. The median ages of whites with LG B-NHL, HG B-NHL and T-NHL (64, 56 and 67 years) were significantly higher than those of blacks (55, 41 and 34 years). Epidemiological studies are needed to better understand these differences.

Non-Hodgkin lymphoma in the Far East: review of 730 cases from the international non-Hodgkin lymphoma classification project.

Large and systematic studies of non-Hodgkin lymphoma (NHL) in the Far East (FE) with good comparative data are scarce in the literature. In this study, five expert hematopathologists classified 730 consecutive cases of newly-diagnosed NHL from four sites in the FE (excluding Japan) using the World Health Organization classification. The results were compared to 399 cases from North America (NA). We found a significantly higher male to female ratio in the FE compared to NA (1.7 versus 1.1; p < 0.05). The median ages of patients with low-grade (LG) and high-grade (HG) B-NHL in the FE (58 and 51 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). The FE had a significantly lower relative frequency of B-NHL and a higher frequency of T-NHL (82 vs. 18 %) compared to NA (90.5 vs. 9.5 %). Among mature B cell lymphomas, the FE had a significantly higher relative frequency of HG B-NHL (54.8 %) and a lower frequency of LG B-NHL (27.2 %) than NA (34.3 and 56.1 %, respectively). Diffuse large B cell lymphoma was more common in the FE (49.4 %) compared to NA (29.3 %), whereas the relative frequency of follicular lymphoma was lower in the FE (9.4 %) compared to NA (33.6 %). Among T-NHL, nasal NK/T cell NHL was more frequent in the FE (5.2 %) compared to NA (0 %). Peripheral T cell lymphoma was also more common in the FE (9.1 %) than in NA (5.3 %). Further epidemiologic studies are needed to better understand the pathobiology of these differences.

Relative frequency of non-Hodgkin lymphoma subtypes in selected centres in North Africa, the middle east and India: a review of 971 cases.

Comparative data regarding the distribution of non-Hodgkin lymphoma (NHL) subtypes in North Africa, the Middle East and India (NAF/ME/IN) is scarce in the literature. In this study, we evaluated the relative frequencies of NHL subtypes in this region. Five expert haematopathologists classified 971 consecutive cases of newly-diagnosed NHL from five countries in NAF/ME/IN. After review, 890 cases (91·7%) were confirmed to be NHL and compared to 399 cases from North America (NA). The male-to-female ratio was significantly higher in NAF/ME/IN (1·8) compared to NA (1·1; P< 0·05). The median ages of patients with low-grade (LG) and high-grade (HG) B-NHL in NAF/ME/IN (56 and 52 years, respectively) were significantly lower than in NA (64 and 68 years, respectively). In NAF/ME/IN, a significantly lower proportion of LG B-NHL (28·4%) and a higher proportion of HG B-NHL (58·4%) were found compared to NA (56·1% and 34·3%, respectively). Diffuse large B-cell lymphoma was more common in NAF/ME/IN (49·4%) compared to NA (29·3%), whereas follicular lymphoma was less common in NAF/ME/IN (12·4%) than in NA (33·6%). In conclusion, we found significant differences in NHL subtypes and clinical features between NAF/ME/IN and NA. Epidemiological studies are needed to better understand the pathobiology of these differences.

Classification of non-Hodgkin lymphoma in South-eastern Europe: review of 632 cases from the international non-Hodgkin lymphoma classification project.

The distribution of non-Hodgkin lymphoma (NHL) subtypes varies around the world, but a systematic study of South-eastern Europe (SEEU) has never been done. Therefore, we evaluated the relative frequencies of NHL subtypes in three SEEU countries--Croatia, Romania and Macedonia. Five expert haematopathologists reviewed 632 consecutive cases of newly diagnosed NHL from the three SEEU countries using the World Health Organization classification. The results were compared to 399 cases from North America (NA) and 580 cases from Western Europe (WEU). The proportions of B- and T-cell NHL and the sex distribution in SEEU were similar to WEU and NA. However, the median ages of patients with low- and high-grade B-NHL in SEEU (60 and 59 years, respectively) were significantly lower than in NA (64 and 68 years, respectively; P < 0·05). SEEU had a significantly lower proportion of low-grade B-NHL (46·6%) and higher proportion of high-grade B-NHL (44·5%) compared to both WEU (54·5% and 36·4%, respectively) and NA (56·1% and 34·3%, respectively). There were no significant differences in the relative frequencies of T-NHL subtypes. This study provides new insights into differences in the relative frequencies of NHL subtypes in different geographic regions. Epidemiological studies are needed to better characterize and explain these differences.

Classification of non-Hodgkin lymphoma in Algeria according to the World Health Organization classification.

The relative distribution of non-Hodgkin lymphoma (NHL) subtypes differs markedly around the world. The aim of this study was to report this distribution in Algeria. A panel of four hematopathologists classified 197 consecutive cases according to the World Health Organization classification, including 87.3% B-cell and 12.7% T- or natural killer (NK)-cell NHLs. This series was compared with similar cohorts from Western Europe (WEU) and North America (NA). Algeria had a significantly higher frequency of diffuse large B-cell lymphoma (DLBCL: 52.8%) and a lower frequency of follicular lymphoma (FL: 13.2%) compared with WEU (DLBCL: 32.2%; FL: 20.0%) and NA (DLBCL: 29.3%; FL: 33.6%). The frequency of mantle cell lymphoma was lower in Algeria (2.5%) compared with WEU (8.3%). Smaller differences were also found among the NK/T-cell lymphomas. In conclusion, we found important differences between Algeria and Western countries, and further epidemiologic studies are needed to explain these differences.

Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases.

The distribution of non-Hodgkin lymphoma (NHL) subtypes differs around the world but a systematic study of Latin America has not been done. Therefore, we evaluated the relative frequencies of NHL subtypes in Central and South America (CSA). Five expert hematopathologists classified consecutive cases of NHL from 5 CSA countries using the WHO classification and compared them to 400 cases from North America (NA). Among the 1028 CSA cases, the proportions of B- and T-cell NHL and the sex distribution were similar to NA. However, the median age of B-cell NHL in CSA (59 years) was significantly lower than in NA (66 years; P < .0001). The distribution of high-grade (52.9%) and low-grade (47.1%) mature B-cell NHL in CSA was also significantly different from NA (37.5% and 62.5%; P < .0001). Diffuse large B-cell lymphoma was more common in CSA (40%) than in NA (29.2%; P < .0001), whereas the frequency of follicular lymphoma was similar in Argentina (34.1%) and NA (33.8%), and higher than the rest of CSA (17%; P < .001). Extranodal NK/T-cell NHL was also more common in CSA (P < .0001). Our study provides new objective evidence that the distribution of NHL subtypes varies significantly by geographic region and should prompt epidemiologic studies to explain these differences.

Non-Hodgkin lymphoma in Chile: a review of 207 consecutive adult cases by a panel of five expert hematopathologists.

The distribution of subtypes of non-Hodgkin lymphoma (NHL) in Latin America is not well known. This Chilean study included 207 consecutive cases of NHL diagnosed at five cancer centers in the capital, Santiago, and one center in Viña del Mar. All cases were reviewed and classified independently by five expert hematopathologists according to the 2001 World Health Organization classification of NHL. A consensus diagnosis of NHL was reached in 195 of the 207 cases (94%). B-cell lymphomas constituted 88% of NHL, and diffuse large B-cell lymphoma (DLBCL, 38.5%) and follicular lymphoma (25.1%) were the most common subtypes. There was a high frequency of marginal zone B-cell lymphoma (10.3%), as well as of extranodal natural killer (NK)/T-cell lymphoma, nasal type (2.6%) and adult T-cell leukemia/lymphoma (0.5%). Extranodal presentation was seen in 74 of the 195 cases (38%) and the most common extranodal presentation was in the stomach (37.6%). The most common gastric lymphoma was DLBCL (54.5%) followed by mucosa-associated lymphoid tissue (MALT) lymphoma (41%). Overall, the frequency of NHL subtypes in Chile is between that reported in Western and Eastern countries, which is probably a reflection of the admixture of ethnicities as well as the environment and socioeconomic status of its population.

Classification of non-Hodgkin lymphomas in Guatemala according to the World Health Organization system.

The aim of this study is to report the relative frequencies of non-Hodgkin lymphoma (NHL) subtypes in Guatemala. A panel of five hematopathologists reviewed 226 consecutive biopsies and classified them according to the 2001 World Health Organization (WHO) classification. The 83 cases of diffuse large B-cell lymphoma (DLBCL) were further subclassified into germinal center B-cell-like (GCB) and non-GCB subtypes. Of the 226 cases, 194 (86%) were confirmed as NHL, including 169 (87%) B-cell and 25 (13%) T- or natural killer (NK)-cell NHL. The most common subtype was DLBCL (44.3%), and the most frequent subtype among T- and NK-cell NHL was extranodal NK/T-cell lymphoma, nasal type (7.8% of all NHL). A comparison of the frequencies of NHL subtypes between Guatemala and other parts of the world showed that Guatemala is most similar to the Middle East and Asia. However, there is no significant difference in the frequency of the DLBCL subtypes compared to North America and Europe.

Epstein-Barr virus and Hodgkin's lymphoma in Cairo, Egypt.

Fifty-five consecutive cases of Hodgkin's lymphoma (HL), collected between 1996 and 1998 from Cairo, Egypt, were histologically subtyped, phenotyped, and then studied for the presence of Epstein-Barr virus (EBV). We used immunohistochemical stains for EBV latent membrane protein 1 (LMP-1) and in situ hybridization stains for EBV-encoded small RNA (EBER-1) transcripts. Forty-five cases (82%) had classic HL (cHL), and ten cases (18%) had nodular lymphocyte predominant HL (NLPHL), with each group expressing its typical phenotype. LMP-1 stains were positive in 63% and 0% of cHL and NLPHL cases, respectively. EBER-positive Reed-Sternberg cells and variants were also present in 62% and 0% of each group, respectively. The cHL cases showed variable EBER positivity: nodular sclerosis, 58%; mixed cellularity, 100%; lymphocyte depletion, 100%; and unclassifiable, 67%. Our findings are similar to those from other developing countries and point towards a pathogenic role of EBV in cHL.

Revisión histopatológica de 20 casos de linfoma de Hodgkin infantil (0-14 años) provenientes de áreas de deficiente situación socioeconómica / Histopathological revision of 20 cases of Hodgkin's lymphoma of infants (0-14 years) coming from areas of poor socioeconomical conditions

Los resultados obtenidos en la revisión histopatológica de 20 casos con confirmación de su baja situación socioeconómica han mostrado que la totalidad de los mismos correspondieron a una forma histológica de mejor pronóstico y, por ende, a una aplicación terapéutica de menor agresividad para el paciente, permitiendo a su vez actuar sobre la hipotética causa primaria de la enfermedad con medidas dedicadas a mejorar la respuesta inmune del niño.

The results obtained from histopathological revision of 20 cases with corroboration of their bad socioeconomical condition proof about the total of the casuistry to pertain into a good prognostic histological type, and for this reason submitted to a low aggresive chemotherapy treatment for the patient, and consecutively to put in action the therapeutic to restore the immunological response.

Revisión histopatológica de 20 casos de linfoma de Hodgkin infantil (0-14 años) provenientes de áreas de deficiente situación socioeconómica / Histopathological revision of 20 cases of Hodgkins lymphoma of infants (0-14 years) coming from areas of poor socioeconomical conditions

Los resultados obtenidos en la revisión histopatológica de 20 casos con confirmación de su baja situación socioeconómica han mostrado que la totalidad de los mismos correspondieron a una forma histológica de mejor pronóstico y, por ende, a una aplicación terapéutica de menor agresividad para el paciente, permitiendo a su vez actuar sobre la hipotética causa primaria de la enfermedad con medidas dedicadas a mejorar la respuesta inmune del niño. (AU)

The results obtained from histopathological revision of 20 cases with corroboration of their bad socioeconomical condition proof about the total of the casuistry to pertain into a good prognostic histological type, and for this reason submitted to a low aggresive chemotherapy treatment for the patient, and consecutively to put in action the therapeutic to restore the immunological response. (AU)

The detection of CD14 and CD16 in paraffin-embedded bone marrow biopsies is useful for the diagnosis of chronic myelomonocytic leukemia.

Histopathological study of bone marrow biopsy (BMB) in chronic myelomonocytic leukemia (CMML) is often difficult and might benefit from an immunohistochemical approach. We immunostained 15 cases of CMML, focusing at two new antibodies staining for CD14 and CD16 on paraffin-embedded tissues. CD68 (KP1), CD68 (PG-M1), and CD163 were not differentially expressed between CMML and chronic myelogenous leukemia (CML). In CMML BMB, we found a significant increase in the number of CD14+ monocytes. This increase was made of dispersed cells in the interstitium, often exhibiting bilobated nuclei, and being difficult to differentiate from neutrophils. There was no expansion of CD16+ monocyte-like cells. However, we found a significant decrease in the number of granulocytes expressing CD16, MPO, and CD15 in CMML compared to CML and control BMB, probably related to dysgranulopoiesis. Indeed, BMB immunohistochemistry can be helpful in CMML by identifying both the monocyte expansion with CD14 and the dysgranulopoiesis with CD16.

Nodal follicular helper T-cell lymphoma may present with different patterns. A case report.

We report the case of a 62-year-old patient presenting with 3 different patterns of follicular helper T-cell lymphoma. The patient initially presented with angioimmunoblastic T-cell lymphoma. A nodal relapse in the form of follicular T-cell lymphoma with a progressively transformed germinal center pattern occurred 8 years later. Two years later, this was followed by another relapse presenting as a predominantly large-cell peripheral T-cell lymphoma, unspecified. All neoplastic cells expressed CD3, CD5, and CD2, with some neoplastic cells also expressing CD7. These cells also expressed CD4, with some expressing CD10, bcl-6, CXCL13, and programmed death-1, all of which are characteristic of the normal subset of follicular T-helper cells. The immunophenotype showed a progressive increase in the proportion of cells expressing CD10, bcl-6, CXCL13, and programmed death-1 from the first to the last lymphoma. In addition, neoplastic T cells from the last biopsy sample expressed CD20.

Composite mantle cell and follicular lymphoma. A case report.

We describe the association of 2 types of small B-cell lymphomas with different morphologic and immunophenotype patterns inside the same lymph node. Morphologically distinct zones were detected and studied with immunohistochemistry analyses. Most of the areas examined were characteristic of classic mantle cell lymphoma (CD20+, CD5+, cyclin D1+) with nodular and mantle zone areas. However, other areas had the morphologic and immunohistochemistry pattern of follicular lymphoma (CD20+, CD10+, Bcl2+). The diagnosis of both lymphomas was confirmed by polymerase chain reaction detection of both Bcl-1 MTC and Bcl-2 MBR rearrangements. DNA degradation in fixed tissue prevented a complete polymerase chain reaction analysis of immunoglobulin heavy chain rearrangements, but a single immunoglobulin H rearrangement was detected at the FR3 locus. These findings confirm the presence of a monoclonal cell population but do not demonstrate the same clonal origin for both lymphoma populations.

[Histopathologic pattern of hyperplasia of bone marrow hematogones (medullar b lymphoid cell precursors) occurring after treatment of idiopathic myelofibrosis]. / Aspect histopathologique d'une hyperplasie médullaire osseuse des hématogones (précurseurs lymphoïdes B médullaires) au cours d'une myélofibrose idiopathique traitée.

Hematogones are bone marrow precursors of B-lymphoid cells which are morphologically difficult to distinguish from blasts and/or from small lymphocytes. We report the case of a patient presenting idiopathic myelofibrosis with minimal myeloid blastic transformation causing severe pancytopenia, treated by allograft and showing in a bone marrow biopsy, a hyperplasia of B-lymphoid cells. Histopathology and immunohistochemistry identified these cells as hyperplasia of hematogones and not a transformation into lymphoblastic acute leukaemia. The cytology of a myelogram confirmed the diagnosis.