Case Of High-grade B-cell Lymphoma Research Articles

Clinical features and outcomes of digestive tract perforation in pediatric mature B-cell non-Hodgkin lymphoma

To summarize the clinical features and prognosis of pediatric mature B-cell non-Hodgkin lymphoma (mB-NHL) with digestive tract perforation. The clinical manifestations, laboratory and imaging examinations, treatment and outcomes of mB-NHL children complicated with digestive tract perforation admitted to Beijing Children's Hospital of Capital Medical University from January 2016 to June 2023 were retrospectively analyzed. A total of 12 patients were included, with 11 males and 1 female, aged 0.8-16.0 (7.5±5.4) years. Among them, there were 10 cases of Burkitt lymphoma, 1 case of high-grade B-cell lymphoma (HGBL) and 1 case of diffuse large B-cell lymphoma (DLBCL), respectively. Intestinal involvement was involved in all cases, with St.Jude staging ranging from stage Ⅲ to Ⅳ. Eleven cases had large abdominal mass. In 7 cases, abdominal X-ray examination showed free gas under the diaphragm. Eleven cases experienced digestive tract perforation after chemotherapy, and the time of perforation after initiation of chemotherapy was 2.0-111.0 (41.2±33.6) days. The most common site of perforation was ileum (6 cases), followed by gastric wall (2 cases), jejunum (1 case), colon (1 case) and appendix (1 case). Eight patients underwent surgery, and the time between surgery and re-chemotherapy was 7.0-45.0 (17.6±12.0) days. One case with perforation before chemotherapy died after giving up treatment. The remaining 11 cases received conservative treatment or surgical intervention, followed by regular chemotherapy after symptom and infection control. The follow-up time was 6.0-82.0 (45.0±26.1) months, and all survived.

Molecular characterization of a rare case of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 rearrangements.

Quadruple-hit lymphomas are extremely rare non-Hodgkin lymphomas with a reported dismal prognosis in the few reported cases. A "quadruple hit" has been defined by the presence of concurrent MYC, BCL2, BCL6, and CCND1 chromosomal rearrangements. We report a new case of a quadruple hit lymphoma in a 73-year-old Hispanic man who presented with an enlarging left-sided neck mass. Computed tomography showed a 1.9-cm mass in left the tonsil with bulky cervical lymphadenopathy. The presence of all four chromosomal rearrangements can reportedly occur with disease progression in both diffuse large B-cell lymphomas and mantle cell lymphomas. Further characterization of the tumor by next-generation sequencing may be of benefit to delineate between these two possibilities. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing were used to confirm and classify the diagnosis. Histologic sections of the cervical lymph node demonstrated an atypical lymphoid infiltrate with large and pleomorphic cells, which were positive for CD20, CD10, BCL1 (Cyclin D1), BCL2, BCL6, and cMYC and negative for CD5 and SOX11 on immunohistochemistry with a Ki-67 proliferative index of 70%. FISH demonstrated MYC, BCL2, BCL6, and CCND1 rearrangements and the diagnosis of high-grade B-cell lymphoma with MYC, BCL2, BCL6, and CCND1 was rendered. Our patient was treated with dose adjusted etoposide, doxorubicin, cyclophosphamide, prednisone, and rituximab chemotherapy and has been in remission for 20months.

High-grade B-cell lymphoma with concurrent MYC rearrangement and 11q aberrations: clinicopathologic, cytogenetic, and molecular characterization of 4 cases

High-grade B-cell lymphoma with 11q aberrations (LBL-11q) resembles Burkitt lymphoma (BL), is negative for MYC rearrangement, and harbors chromosome 11q aberrations. Rare cases of high-grade B-cell lymphoma with concurrent MYC rearrangement and 11q aberrations (HGBCL-MYC-11q) have been described. In this study we report the clinicopathologic, cytogenetic, and molecular findings in 4 such cases. Diagnoses were made on tissue or bone marrow biopsies. Karyotype, fluorescence in situ hybridization, genomic microarray analyses, and next-generation sequencing were performed. All patients were male (median age 39 years). Three cases were diagnosed as BL, while one was diagnosed as diffuse large B-cell lymphoma. Karyotypes (available in 2 patients) were complex. In one patient, copy number analysis showed gains at 1q21.1-q44 and 13q31.3, and loss of 13q34, abnormalities typically seen in BL. All of our cases showed two or more mutations that are recurrent in BL, including ID3, TP53, DDX3X, CCND3, FBXO1, and MYC. Two cases showed a GNA13 mutation, commonly seen in LBL-11q. Cases of HGBCL-MYC-11q display overlapping morphologic and immunophenotypic, as well as cytogenetic and molecular features between BL and LBL-11q, with a mutational landscape enriched for mutations recurrent in BL. Concurrent MYC rearrangement with 11q abnormalities is important to recognize especially since it has implications for their classification.

Clinical analysis of 11 cases of high-grade B-cell lymphoma in children

Clinical analysis of 11 cases of high-grade B-cell lymphoma in children

Clinicopathological features and prognosis of high-grade B-cell lymphoma with MYC and bcl-2 and/or bcl-6 rearrangements

Objective: To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma (HGBL) involving combined rearrangements of MYC, bcl-2 and bcl-6. Methods: A total of 1 138 cases of large B cell lymphoma (LBL) that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization (FISH) with probes against MYC, bcl-2 and bcl-6. The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed. Results: Among the 1 138 LBL, 45 (4.0%) cases had combined rearrangements of MYC, bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, 14 HGBL cases with MYC and bcl-2 rearrangements, and 25 HGBL cases with MYC and bcl-6 rearrangements. Of these 45 patients, 29 patients were male, and 16 patients were female, aged 29 to 83 years. HGBL with MYC, bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell (GCB) subtype using the Hans algorithm. HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype (68.0%) and the non-GCB subtype (32.0%). The vast majority of HGBL cases had a high Ki-67 proliferation index. Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level. Also, some patients had clinical features including elevated plasma β2-microglobulin levels, B symptoms, and bone marrow involvement. The IPI scores and LDH levels were significantly different between the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements (P<0.05). Compared with the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement (P<0.05). There were no significant differences in the prognosis among HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the cases with MYC and bcl-2 rearrangements, and the cases with MYC and bcl-6 rearrangements (P>0.05). Conclusions: HGBL with MYC, bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival. To reduce misdiagnosis and improve diagnostic accuracy, it is necessary to assess the patients' clinical features and conduct histopathological, immunohistochemical and FISH analyses.

High-Grade B-Cell Lymphoma Not Otherwise Specified (HGBL, NOS) in the Maxillary Sinus Mimicking Periapical Inflammation: Case Report and Review of the Literature

High-grade B-cell lymphoma not otherwise specified is listed as a new group in the WHO 2017 statement as a subtype of aggressive, mature B-cell lymphomas with a poor prognosis. To our knowledge, no description of this genetic type of maxillary lymphoma has appeared in the literature until now; thus, our case provides valuable data on its symptoms, clinical behavior, response to treatment and survival rate. The present report describes the early diagnosis and treatment of an extremely rare histological subtype of B-cell lymphoma, a case of high-grade B-cell lymphoma not otherwise specified, localized in the maxillary sinus and mimicking signs and symptoms of periapical inflammation. After chemotherapy, the presented patient showed complete remission without relapse and systemic spread. As far as we know, this is the first reported case of this rare type of lymphoma associated with the maxillary sinus. Considering that high-grade B-cell lymphomas are aggressive tumors with rapid growth and poor prognosis, which are often misdiagnosed in the early stages as inflammatory disease, it is relevant to highlight the importance of a detailed evaluation of clinical signs and radiological findings during diagnosis, especially if they contradict each other.

High Grade B Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements Depict a High Complexity on the Cytogenetic, but Not on the Molecular Genetic Level and Show MYC Mutations As Prognostic Marker

Background: In the revised WHO classification of 2016, cases of large B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements were categorized as “HGBL (high grade B cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements)”, except for cases that fulfill the criteria for a follicular or lymphoblastic lymphoma. A detailed molecular analysis of these cases and comparison of accompanying aberrations has not been available to date.Aims: Evaluation of associated genetic alterations and prognosis in HGBL cases with rearrangement of (i) MYC + BCL2 , (ii) MYC + BCL6 or (iii) MYC + BCL2+BCL6.Patient cohorts and methods: The total cohort comprised 70 cases with MYC and BCL2 and/or BCL6 rearrangements (39 male, 31 female). Cases were selected by detection of the rearrangements by FISH (fluorescence in situ hybridization), cases diagnosed as CLL, follicular or lymphoblastic lymphoma were excluded. Median age was 67 years (range: 44-87 years). All patients were investigated using chromosome banding analysis (CBA) and FISH using probes for MYC , IGH-BCL2 and BCL6 . Additionally, mutation analyses of ATM , BCL2, BIRC3, BRAF, BTK, CBL, CSF3R, CSNK1A1, CXCR4, EGR2, ETNK1, FBXW7, FLT3, ID3, IDH1, IDH2, KIT, KLF2, KRAS, MAP2K1, MYC, MYD88, NFKBIE, NOTCH2, PHF6, PLCG2, POT1, PTPN11, SAMHD1, SETBP1, SF3B1, SRSF2, STAT3, STAT5B, TET2, TP53, U2AF1, UBR5, WT1, XPO1 and ZRSR2 was performed. Variants of unknown significance were excluded from statistical analysis.Results: We identified 33/70 cases with rearrangement of MYC + BCL2 , 10/70 cases with MYC + BCL6 and 27/70 cases with MYC + BCL2 + BCL6 (47%, 14% and 39%, respectively). In the total cohort, CBA revealed a complex karyotype (>3 abnormalities) in 59/70 (84%) of patients, 10/70 (14%) harbored an aberrant but non-complex karyotype, whereas in 2/70 (3%) of cases, CBA analyses failed due to insufficient cell proliferation. Regarding the subgroups, a complex karyotype was observed in 82%, 80% and 89% of cases, respectively (for MYC + BCL2 , MYC + BCL6 and MYC + BCL2 + BCL6 rearrangement). If only aberrations additional to MYC / BCL2 / BCL6 rearrangements were calculated, >3 aberrations were detected in 64% of cases (67%, 70% and 60%, respectively). The most frequent additional aberrations included 13q deletions, +12, gain of 1q and 6q deletions. Median number of additional cytogenetic aberrations was n=8 (range: 0-36). Despite the high cytogenetic complexity, the frequency of TP53 deletions was relatively low (6% in the total cohort), three of them harboured a concomitant TP53 mutation in the other allele. Mutation analyses of 40 genes revealed a median number of n=1 mutations in the total cohort with no differences between the three subgroups. The range of the number of molecular mutations was 0-3 (0 mutations: 31%; 1 mutation: 44%; 2 mutations: 20%; 3 mutations: 5%). Interestingly, out of the 40 genes analysed, mutations were almost exclusively detected in BCL2 (40%), MYC (21%) and TP53 (21%) in the total cohort. Other recurrent mutations were observed for ID3 and PHF6 only (3%, respectively). Cases with MYC+BCL6 rearrangement showed a higher - although not statistically significant - frequency of MYC mutations compared to the other cases (40% vs. 18%), while BCL2 mutations were rarely detected in this subgroup (10% vs. 45%, p=0.033). Of note, mutations in TP53 were found to show a trend towards a lower frequency in cases with a “triple hit” (MYC+BCL2+BCL6 ) in comparison to the “double hit” cases (MYC+BCL2 and MYC+BCL6 ) (11% vs. 28%).Median overall survival (OS) in the total cohort was 61 months. Cases with MYC + BCL2 showed a shorter OS compared to cases with MYC+BCL2+BCL6 rearrangements, although this was not statistically significant (37 vs.61 months). Unfortunately, OS could not be determined for cases with MYC+BCL6 due to the low number of cases. Mutations in MYC, but not in BCL2 or TP53 , showed a negative impact on OS in the total cohort (16 vs. 61 months, p=0.046).Conclusion: 1) Cases with rearrangements in MYC , BCL2 and/or BCL6 depict a high complexity on the cytogenetic, but not on the molecular genetic level. 2) Molecular mutations are almost exclusively detected in BCL2 , MYC and TP53. 3) Cases with MYC+BCL6 rearrangements differ from the other subgroups by showing a higher frequency of MYC mutations and a lower frequency of mutations in BCL2 . 4) Mutations in MYC negatively impact on OS. 5) Thus, our data support the current WHO classification and complement it on a molecular level. DisclosuresStengel:MLL Munich Leukemia Laboratory: Employment. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Meggendorfer:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

The Value of Cellblock in Diagnosing Pancreatic Lymphomas

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the diagnostic tool of choice for pancreatic solid mass lesions. Pancreatic lymphomas represent an infrequent and challenging cytologic diagnosis. Our aim was to determine the diagnostic value of cellblock (CB) in the diagnosis of pancreatic lymphomas. Methods: We retrieved pancreatic EUS-FNAs performed over 10-years from our institution’s database. We correlated the cytologic and CB diagnosis with the histologic diagnosis as a gold standard. Results: We found 5 cases (2 women and 3 men; age range, 37–66 years [average age, 52 years]) of pancreatic lymphomas with histologic follow-up biopsies. They included 1 case of T-cell lymphoma (TCL), 1 case of plasma cell neoplasm (multiple myeloma [MM]), 1 case of diffuse large B-cell lymphoma (DLBCL), 1 case of classic Hodgkin lymphoma (HL), and 1 case of high-grade B-cell lymphoma (HGBCL). Cytologically, the cases of HL and DLBCL were suspected, the cases of TCL and MM were confused with undifferentiated carcinoma and neuroendocrine carcinoma, and the case of HGBCL was inconclusive. CB samples were of value in highlighting the morphologic details of lymphomas and allowed confirmation, proper classification, and grading of the lymphomas using immunohistochemistry that matched tissue biopsies. Conclusions: EUS-FNA smears with CBs are helpful diagnostic tools, differentiating lymphomas from other malignancies and from nonneoplastic lymphocyte-rich lesions. CBs allow proper classification and grading of cases of pancreatic lymphomas.

Distinct molecular profile of IRF4-rearranged large B-cell lymphoma

AbstractPediatric large B-cell lymphomas (LBCLs) share morphological and phenotypic features with adult types but have better prognosis. The higher frequency of some subtypes such as LBCL with IRF4 rearrangement (LBCL-IRF4) in children suggests that some age-related biological differences may exist. To characterize the genetic and molecular heterogeneity of these tumors, we studied 31 diffuse LBCLs (DLBCLs), not otherwise specified (NOS); 20 LBCL-IRF4 cases; and 12 cases of high-grade B-cell lymphoma (HGBCL), NOS in patients ≤25 years using an integrated approach, including targeted gene sequencing, copy-number arrays, and gene expression profiling. Each subgroup displayed different molecular profiles. LBCL-IRF4 had frequent mutations in IRF4 and NF-κB pathway genes (CARD11, CD79B, and MYD88), losses of 17p13 and gains of chromosome 7, 11q12.3-q25, whereas DLBCL, NOS was predominantly of germinal center B-cell (GCB) subtype and carried gene mutations similar to the adult counterpart (eg, SOCS1 and KMT2D), gains of 2p16/REL, and losses of 19p13/CD70. A subset of HGBCL, NOS displayed recurrent alterations of Burkitt lymphoma–related genes such as MYC, ID3, and DDX3X and homozygous deletions of 9p21/CDKN2A, whereas other cases were genetically closer to GCB DLBCL. Factors related to unfavorable outcome were age >18 years; activated B-cell (ABC) DLBCL profile, HGBCL, NOS, high genetic complexity, 1q21-q44 gains, 2p16/REL gains/amplifications, 19p13/CD70 homozygous deletions, and TP53 and MYC mutations. In conclusion, these findings further unravel the molecular heterogeneity of pediatric and young adult LBCL, improve the classification of this group of tumors, and provide new parameters for risk stratification.

Leukemic presentation of high-grade B cell lymphoma with MYC and BCL2 rearrangement—a series of two cases and review of literature

High-grade B cell lymphoma (HGBL) is a recently introduced category of aggressive mature B cell lymphoma which is clinically and biologically distinct from diffuse large B cell lymphoma (DLBCL), NOS, and Burkitt Lymphoma. HGBL consists of two categories; the first category includes HGBL with MYC and BCL2 and/or BCL6 rearrangement which is so-called double or triple hit lymphoma. The second category includes HGBL, NOS which lacks genetic double or triple hit; however, its morphology is intermediate between DLBCL and Burkitt lymphoma or appear blastoid. Clinically, patients present with advanced disease, bone marrow involvement, elevated lactate dehydrogenase (LDH), extranodal disease which includes CNS involvement and a high international prognostic index (IPI). Leukemic presentation has been described in various types of B and T cell non-Hodgkin lymphoma; however, peripheral blood involvement as an initial presentation is seldom described in the literature for HGBL with MYC and BCL2 rearrangement. Here, we report two cases of HGBL whose initial presentation was leukocytosis with peripheral blood involvement mimicking acute leukemia.

High-grade B-Cell lymphoma with MYC and BCL6 rearrangements associated with Richter transformation of chronic lymphocytic leukemia

Richter transformation (RT), or Richter syndrome, is defined as the transformation of chronic lymphocytic leukemia (CLL) to an aggressive B-cell lymphoma. The vast majority, up to 99%, transform into diffuse large B-cell lymphoma (DLBCL), with a small subset (<1%) becoming classical Hodgkin lymphoma. Approximately half of RT cases progress through a pathway involving dysregulation of C-MYC. High-grade B-cell lymphoma (HGBL) is a recent diagnostic category of aggressive B-cell lymphomas set forth in the updated 2017 WHO Classification of Hematopoietic and Lymphoid Tissues. HGBL with MYC and BCL2 and/or BCL6 rearrangements, formerly “double-hit” and “triple-hit” lymphomas, comprise the majority of HGBL cases. Patients with HGBL have a worse prognosis than those with diffuse large B-cell lymphoma. We present a case of RT with rearrangements of MYC and BCL6. To our knowledge, there are no reported cases of RT with a “double-hit” lymphoma genotype.

Distribution of lymphomas in Turkey: data of 4239 cases from a single institution using the WHO classification

Background/aim: Lymphoma cases diagnosed at one of the largest tertiary reference centers in Turkey were reviewed and findings were compared to those reported from other regions of the world. Materials and methods: Lymphomas diagnosed between 2000 and 2017 in the pathology laboratory of Hacettepe University were identified. A total of 4239 cases were analyzed. The WHO 2008 classification was used. Results: Hodgkin lymphomas accounted for almost 20% of cases. T-cell lymphomas were much more frequent (23% of our non- Hodgkin lymphoma (NHL) cases) in comparison to all other regions of the world. The reason for this difference was the high frequency of mycosis fungoides (MF) cases. We had significantly more cases of high-grade B-cell lymphoma (43.9% of NHLs) and fewer cases of low-grade B-cell lymphoma (33.5% of NHLs) in comparison to the rates of developed regions of the world and the reverse was true when compared to developing parts of the world. Burkitt lymphoma frequency (4% of NHLs) was also higher than in most parts of the world. Conclusion: Our data reveal that the frequency of MF, Burkitt lymphoma, and Hodgkin lymphoma are considerably higher, whereas follicular lymphoma rates are considerably lower than in most other parts of the world.

A Rare Case of High-Grade B-cell Lymphoma Involving the Colon and Small Bowel

A Rare Case of High-Grade B-cell Lymphoma Involving the Colon and Small Bowel

LMO2-negative Expression Predicts the Presence of MYC Translocations in Aggressive B-Cell Lymphomas

MYC translocation is a defining feature of Burkitt lymphoma (BL), and the new category of high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 translocations, and occurs in 6% to 15% of diffuse large B-cell lymphomas (DLBCLs). The low incidence of MYC translocations in DLBCL makes the genetic study of all these lymphomas cumbersome. Strategies based on an initial immunophenotypic screening to select cases with a high probability of carrying the translocation may be useful. LMO2 is a germinal center marker expressed in most lymphomas originated in these cells. Mining gene expression profiling studies, we observed LMO2 downregulation in BL and large B-cell lymphoma (LBCL) with MYC translocations, and postulated that LMO2 protein expression could assist to identify such cases. We analyzed LMO2 protein expression in 46 BLs and 284 LBCL. LMO2 was expressed in 1/46 (2%) BL cases, 146/268 (54.5%) DLBCL cases, and 2/16 (12.5%) high-grade B-cell lymphoma cases with MYC and BCL2 and/or BCL6 translocations. All BLs carried MYC translocation (P<0.001), whereas LMO2 was only positive in 6/42 (14%) LBCL with MYC translocation (P<0.001). The relationship between LMO2 negativity and MYC translocation was further analyzed in different subsets of tumors according to CD10 expression and cell of origin. Lack of LMO2 expression was associated with the detection of MYC translocations with high sensitivity (87%), specificity (87%), positive predictive value and negative predictive value (74% and 94%, respectively), and accuracy (87%) in CD10 LBCL. Comparing LMO2 and MYC protein expression, all statistic measures of performance of LMO2 surpassed MYC in CD10 LBCL. These findings suggest that LMO2 loss may be a good predictor for the presence of MYC translocation in CD10 LBCL.

PELI1 expression is correlated with MYC and BCL6 expression and associated with poor prognosis in diffuse large B-cell lymphoma

AbstractPELI is a family of E3 ubiquitin ligases that regulate protein activity through a post-translational modification, ubiquitination. While PELI1 has been found to play a pivotal role in inflammatory processes through the activation of Toll-like receptor signaling and the NF-kB pathway, the role of PELI1 in oncogenesis has not been the subject of much investigation. We aimed to explore PELI1 expression in various malignant lymphomas and identify clinicopathologic significance. Immunohistochemistry for PELI1 was performed on a total of 502 cases, including 406 B-cell, 76 T or NK-cell, and 20 Hodgkin lymphomas. High expression of PELI1 was found in high-grade B-cell lymphoma cases such as diffuse large B-cell lymphoma, Burkitt lymphoma, and plasmablastic lymphoma, whereas low-grade B-cell lymphoma, T/NK-cell lymphoma, and Hodgkin lymphoma cases showed very low levels of expression. In vitro cell line studies, the results of western blot, and RT-PCR were concordant with those of the immunohistochemical results; RL7, Pfeiffer, SUDHL-2, DOHH2, and Ramos cell lines showed high levels of PELI1 protein and mRNA expression. In 182 diffuse large B-cell lymphoma, PELI1 expression was positively correlated with the expression of MYC, BCL6, BCL2, and MUM1 (Spearman's ρ=0.427, 0.507, 0.246, and 0.137, respectively; P<0.001, <0.001, 0.001, and 0.066, respectively). In diffuse large B-cell lymphoma, high expression of PELI1 was associated with frequent bone marrow involvement (P=0.013) and shorter relapse-free survival (P=0.002). Our results suggest that PELI1 might participate in B-cell maturation or oncogenic activation of aggressive B-cell lymphomas, both during and after germinal center stages.

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.

A Case Report of the Primary Lung Lymphoma

The primary lymphoma in the lung is very rare. Moot of the primary pulmonary lymphomas, which represent 3-4 % of extra-nodal lymphomas, are low-grade B-cell lymphoma. The low-grade B-cell lymphomas progress slowly and the prognosis of these are more favorable than that of the nodal lymphomas. However, high-grade forms progress rapidly with more severe course. The diagnosis of primary pulmonary lymphomas generally relies on the histopathologic findings of lung specimens obtained by surgical excision of the lesions or open-lung biopsy. Recently, less aggressive biopsies(transbronchial, transthoracic) and/or immunocyto-chemical, immunochemical and gene rearrangement studies on materials obtained by bronchoalveolar lavage have been used occasionally. The treatment of the primary pulmonary lymphomas has not been precisely codified. Several clinical data suggest that limited surgery or non-aggressive chemotherapy can provide long-term survival in patients with such slowly developing neoplasm, and demonstrated the need for the development of noninvasive diagnootic methods. In this study, we report a case of high-grade B-cell lymphoma of the lung which was treated with combination chemotherapy.

Frequent deletions of 6q23-24 in B-cell non-Hodgkin's lymphomas detected by fluorescence in situ hybridization.

Deletions of the long arm of chromosome 6 (6q) are among the most frequent chromosome aberrations in malignant lymphomas and often occur as secondary changes in addition to typical translocations, such as t(14;18). Using fluorescence in situ hybridization (FISH) with two YAC probes hybridizing to 6q23-24 and with the centromeric probe D6Z1 as internal control, we studied 31 cases of low-grade and eight cases of high-grade B-cell lymphoma. Deletions of 6q23-24 were detected in 21 patients (56.8%) by FISH, compared to 13 patients (33.3%) by chromosome analysis. Deletions of 6q23-24 were found by FISH in 5 of 13 cases of small lymphocytic lymphoma, in 2 of 3 cases of mantle cell lymphoma, in 10 of 14 cases of t(14;18) positive low-grade follicular lymphoma, and in 4 of 8 cases of high-grade follicular lymphoma. This study shows that deletions of 6q23-24 are more frequent in B-cell lymphomas than previously suggested and that they can be detected more sensitively by FISH than by chromosome analysis. Contrary to previous reports indicating that the region 6q23-24 is preferentially deleted in low-grade lymphomas without t(14;18), our results indicate that deletions of 6q23-24 appear to be common in other pathological subsets of B-cell lymphoma as well, especially in follicular lymphomas with t(14;18).