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1
Bencherki, Youssef, Oussama El Idrissi Alami, Amine Moataz, Mohammed Dakir, Adil Debbagh, and Rachid Aboutaieb. "A Case of Primary Burkitt Lymphoma of the Bladder." European Journal of Medical and Health Sciences 3, no. 2 (April 26, 2021): 46–48. http://dx.doi.org/10.24018/ejmed.2021.3.2.798.
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The most frequent primary lymphomas of the bladder are the low-grade B-cell- derived non-Hodgkin’s lymphomas of the MALT type, including Burkitt’s lymphoma. Primary genitourinary localization of lymphomas is uncommon and, in particular supra vesical development of Burkitt lymphoma. The continuous progress of treatment by chemotherapy has changed the pejorative prognosis of this disease into a good one.
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Mugabe Byiringiro, Fiacre, Felix Manirakiza, Déogratias Ruhangaza, Thierry Zawadi Muvunyi, and Belson Rugwizangoga. "Pathology Characteristics of Lymphomas in Rwanda: A Retrospective Study." East African Health Research Journal 5, no. 2 (November 15, 2021): 170–73. http://dx.doi.org/10.24248/eahrj.v5i2.669.
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Background: Lymphomas have been a global challenge for many decades and despite measures for prevention and management, the incidence continues to increase. There are two main categories, which are Non-Hodgkin’s Lymphomas and Hodgkin’s Lymphomas and most common etiologies are environmental, genetic alteration, radiation and some viruses. Objective: To describe pathology characteristics of lymphomas in Rwanda based on Hematoxylin and Eosin stained glass slides and immuno histo chemistry, and classify them according to clinical aggressiveness. Patients and Methods: We conducted a retrospective observational and descriptive study from January 2013 to December 2019. Lymphoma cases were retrieved together with relevant clinical and pathological information, and reviewed by independent pathologists. Histological diagnosis was classified according to the 2008 World Health Organization system in order to assign clinical aggressiveness of the lymphoma. Results: Three hundred and six lymphoma cases were enrolled. Males contributed to 57% of all reviewed case, and slightly over 50% were young aged ≤35 years. Approximately 191 (62%) of cases were nodal lymphomas. Approximately one fifth (18%) of lymphoma cases were HIV positive. Most 213(70%) cases were Non-Hodgkin’s Lymphomas of aggressive forms 164(77%). Among 164 cases of aggressive Non-Hodgkin’s Lymphomas, diffuse large B cell lymphoma was the leading subtype 91(55.5%), followed by solid lymphoblastic lymphoma 32(19.5%) and Burkitt lymphoma 17(10.4%). Among all Hodgkin lymphoma cases, 90(97%) were classical Hodgkin lymphomaof nodular sclerosis subtype. Hodgkin lymphoma patients were younger compared to Non-Hodgkin’s Lymphomas patients (mean age of 24.78±16.3 years versus 38.6±22. 5years, p=.000). Conclusion: Substantial proportion of Lymphomapatients in Rwanda were also HIV positive. Interestingly, Non-Hodgkin’s Lymphomas in Rwanda are predominated by the most aggressive forms, and these mostly affect a younger population. Optimal characterisation of such cases, using advanced methods, is recommended.
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Strauchen, James A., and David Burstein. "Expression of X-Linked Inhibitor of Apoptosis Protein in Reactive Lymphoid Tissues, Non-Hodgkin’s Lymphomas, and Hodgkin’s Disease." Blood 106, no. 11 (November 16, 2005): 4655. http://dx.doi.org/10.1182/blood.v106.11.4655.4655.
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Abstract X-linked inhibitor of apoptosis protein (XIAP) is an important regulator of apoptosis which binds to and inhibits caspases-3, -7 and -9, blocking the caspase 9-mediated apoptosis pathway. This pathway is activated by p53 and DNA damage and may be an important determinant of responsiveness to chemotherapy. Apoptosis also plays a major role in the regulation of follicle center B-cell proliferation and BCL2-mediated inhibition of apoptosis is a key factor in B-cell lymphomagenesis. In this study we examined the expression of XIAP in 65 reactive and neoplastic lymphoid proliferations utilizing a monoclonal antibody to XIAP (#610763 BD Biosciences, San Jose, CA) and immunohistochemistry with avidin-biotin-complex immunoperoxidase technique on formalin-fixed, paraffin-embedded sections. In reactive lymph nodes and tonsils, expression of XIAP was limited to large noncleaved cells in follicle centers (5 of 6 cases). XIAP was absent in plasmacytoma (3 cases) and small lymphocytic lymphoma/chronic lymphocytic leukemia (1 case). XIAP was expressed in follicular lymphoma, predominantly in large noncleaved cells (6 of 9 cases) and in diffuse large B cell lymphoma (11 of 16 cases), including cases of T-cell/histiocyte-rich diffuse large B cell lymphoma (2 cases), primary mediastinal large B cell lymphoma (1 case), and posttransplantation diffuse large B cell lymphoma (1 case). XIAP was consistently expressed in Burkitt and Burkitt-like lymphoma (3 of 3 cases) and anaplastic large cell lymphoma (3 of 3 cases) and in one case of adult T cell leukemia/lymphoma. XIAP was variably expressed in marginal-zone B cell lymphoma, predominantly in large blasts (2 of 4 cases) and in mantle cell lymphoma (2 of 3 cases). XIAP was not detected in peripheral T cell lymphoma, unspecified (1 case), extranodal NK/T cell lymphoma, nasal type (1 case), precursor B cell lymphoblastic leukemia (1 case), or granulocytic sarcoma (1 case). XIAP was consistently expressed in the Reed-Sternberg and mononuclear Reed-Sternberg-variant cells of classical Hodgkin disease (9 of 9 cases) and the L+H Reed-Sternberg-variant cells of nodular lymphocyte predominance Hodgkin disease (3 of 3 cases). XIAP is expressed across a broad range of lymphoproliferative disorders, including classical and nodular lymphocyte predominance Hodgkin disease, diffuse large B cell lymphoma, follicular lymphoma, Burkitt lymphoma, marginal-zone and mantle cell lymphoma, and anaplastic large cell lymphoma. XIAP appears to be selectively expressed in the proliferating elements of these lymphomas. The possible prognostic and therapeutic significance of XIAP expression needs to be determined.
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Mussolin, Lara, Christine Damm-Welk, Marta Pillon, and Wilhelm Woessmann. "Minimal Disease Monitoring in Pediatric Non-Hodgkin’s Lymphoma: Current Clinical Application and Future Challenges." Cancers 13, no. 8 (April 15, 2021): 1907. http://dx.doi.org/10.3390/cancers13081907.
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Minimal residual disease (MRD) detection is established routine practice for treatment stratification in leukemia and used for treatment optimization in adult lymphomas. Minimal disease studies in childhood non-Hodgkin lymphomas are challenged by stratified treatment in different subtypes, high cure rates, low patient numbers, limited initial tumor material, and early progression. Current clinical applications differ between the subtypes. A prognostic value of minimal disseminated disease (MDD) could not yet be clearly established for lymphoblastic lymphoma using flow cytometry and PCR-based methods for T-cell receptor (TCR) or immunoglobulin (IG) rearrangements. MYC–IGH fusion sequences or IG rearrangements enable minimal disease detection in Burkitt lymphoma and -leukemia. An additional prognostic value of MDD in Burkitt lymphoma and early MRD in Burkitt leukemia is implicated by single studies with risk-adapted therapy. MDD and MRD determined by PCR for ALK-fusion transcripts are independent prognostic parameters for patients with ALK-positive anaplastic large cell lymphoma (ALCL). They are introduced in routine clinical practice and used for patient stratification in clinical studies. Early MRD might serve as an endpoint for clinical trials and for guiding individual therapy. Validation of MDD and MRD as prognostic parameters is required for all subtypes but ALCL. Next-generation sequencing-based methods may provide new options and applications for minimal disease evaluation in childhood lymphomas.
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Rathee, Neeraj Kumar, Nidhi Gupta, Sawant Sharma, and Hari Krishan Rathee. "Non-Hodgkin’s Lymphoma Breast in a lactating mother : Case Report." Nepal Journal of Epidemiology 12, no. 1 (March 31, 2022): 1163–70. http://dx.doi.org/10.3126/nje.v12i1.42975.
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Non-Hodgkin’s lymphoma of breast is a rare condition. NHL breast constitute about 0.5% of all malignancies of breast. NHL breast constitute nearly 1% of all cases of NHL. Among all subtypes of NHL, DLBCL (Diffuse large B-cell Lymphoma) is the most common type to be known. Marginal zone lymphoma (10-30%), follicular lymphoma (10-20%) and Burkit Lymphoma (5%) are other common histologic variants. Burkitt lymphoma is mainly seen in pregnant females or lactating females. Breast implant associated anapaestic large cell lymphoma (BIA-ALCL) constitutes remaining case. Thus, primary NHL of Breast is rare condition. DLBCL is most common histologic variant. We report here a rare case of primary NHL Breast. A 30 years old lactating mother came with history of swelling and nipple discharge from bilateral breast. -Treatment approach for low grade NHL breast is Radiotherapy only and for high grade NHL breast there is a role for combined modality approach that is chemotherapy followed by Radiotherapy with or without surgical intervention.
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Munira, Shirajam, Salama Afroze, Akhil Ranjon Biswas, and MA Khan. "Pattern of Immunophenotype Among the Cases of Lymphoma Attending in A Tertiary Level Hospital." Chattagram Maa-O-Shishu Hospital Medical College Journal 17, no. 2 (January 14, 2019): 21–25. http://dx.doi.org/10.3329/cmoshmcj.v17i2.39771.
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Background : To explore the relative frequency and different forms of lymphoma in tertiary level hospital.
Methods: This descriptive observational study was carried out in the Department of Hematology at Dhaka Medical College Hospital, Dhaka. Patients attended with solid tissue lymphoma in Outpatient, Inpatient and Lymphoma Clinic services of Department of Hematology and Bone Marrow Transplant, Dhaka Medical College Hospital, Dhaka were taken as study population as per inclusion criteria. A total of 63 patients with lymphoma diagnosed by histopathologically were selected initially, among them 53 were confirmed by immunohistochemistry taken as study population finally.
Results: Mean age was 39.2 ± 15.5 years, median age was 36 years within the range of 14 – 75 years. Males were predominant. Male female ratio was 4.3:1. Most of the samples were collected from cervical lymph node (84.1%). Most of the patients came with fatigue and significant weight loss. Maximum 42 (79.24%) cases were Non-Hodgkin’s lymphoma and 11 (20.75%) cases were Hodgkin’s lymphoma. Out of 42 non-Hodgkin’s lymphoma, 27 (64.3%) were B-cell lymphoma and 15 (35.7%) were T-cell lymphoma. Among B-cell lymphoma, 19 (45.2%) were diffuse large B cell lymphoma, three (7.1%) were follicular lymphoma, three (7.1%) were mantle cell lymphoma, one (2.4%) was spleenic marginal zone lymphoma and one (2.4%) was Burkitt lymphoma. Among T-cell lymphoma, nine (21.4%) were peripheral T-cell lymphoma and six (14.3%) were adult T lymphoblastic lymphoma. Out of 11 Hodgkin’s lymphoma, 10 (90.9%) were classical Hodgkin’s lymphoma and one (9.1%) nodular lymphocyte predominant. Among classical Hodgkin’s lymphoma, five (45.5%) were mixed cellularity, three (27.3%) were lymphocyte predominant and two (18.2%) were Nodular sclerosis. Out of 42 non-Hodgkin’s lymphoma, 13 (30.95%) were indolent, 21 (50.00%) were aggressive and eight (19.05%) were very aggressive.
Conclusion: In our study, it was found that 79.3% were non-Hodgkin lymphoma of which 64.3% were B-cell lymphoma & 35.7% were T-cell lymphoma and 20.7% cases were Hodgkin lymphoma of which 90.9% were classical Hodgkin’s lymphoma, 9.1% nodular lymphocyte predominant Hodgkin’s lymphoma.
Chatt Maa Shi Hosp Med Coll J; Vol.17 (2); Jul 2018; Page 21-25
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Beltran, Brady, Domingo Morales, Pilar Quiñones, R. Salas, and Antonio A. Carrasco-Yalan. "Distribution and Pathology Characteristics of Non Hodgkin Lymphoma in Peru: A Study of 1014 Cases Using WHO Classification of Lymphoid Neoplasm." Blood 110, no. 11 (November 16, 2007): 4419. http://dx.doi.org/10.1182/blood.v110.11.4419.4419.
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Abstract BACKGROUND: The frequency of various subtypes of non-Hodgkin’s lymphoma (NHL) differs in various regions worldwide. OBJECTIVE: To investigate the clinical and pathological features of non-Hodgkin’s lymphoma (NHL) and to evaluate the applicability of the new WHO classification of lymphoid neoplasms. METHODS: According to the new WHO classification, a total of 1014 cases of non-Hodgkin’s lymphoma diagnosed during the period 2002–2006 were reviewed and reappraised with their morphological, immunological and clinical characteristics in one general hospital from Lima, Peru. All cases corresponded >18 years old. RESULTS: There were 535 males and 479 females, mean age was 62.1 years (range 18 – 97 years) and the median was 64 years. B-cell neoplasms accounted for 763 cases (75.2%) and T/NK-cell neoplasms for 189 (18.6%). Sixty two cases (6.1%) were not classified. It was seen compared to that in the other Asian countries. Indolent lymphomas accounted for 17%, and aggressive ones for 83%. Among indolent lymphomas follicular grade I and II were the most common subset while MALT was second with low frequency. Among the aggressive lymphomas diffuse large cell lymphoma (DLCL) was the most common subtype, and accounted for 58.8% of all B cell lymphomas. Mantle and Burkitt lymphoma were very low incidence. Among the T cell lymphomas, peripheral T cell lymphomas, mycosis fungoides, Adult T Lymphoma/Leukemia (ATLL), T/NK nasal type Lymphoma were the most common subtypes. Nodal NHL occurred in 52% and extranodal in 48% of the cases. The more common extranodal presentation was stomach (14.1%), skin (8.1%), small intestine (2.9%) and nose (2.3%) CONCLUSIONS: The high incidence of T cell lymphomas, extranodal presentation and reduced frequency of indolent lymphoma in the current study is comparable to that reported from Asian countries.
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Iványi, János László, Éva Marton, Márk Plander, Zoltán Vendel Engert, and Csaba Tóth. "Treatment outcome of primary testicular non-Hodgkin’s lymphoma." Orvosi Hetilap 154, no. 42 (October 2013): 1666–73. http://dx.doi.org/10.1556/oh.2013.29726.
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Introduction: Primary testicular lymphoma constitutes a rare subgroup among extranodal non-Hodgkin’s lymphomas. Because of its aggressive clinical behaviour due to high grade histological features developing mainly in older population, patients with this disease usually have a poor prognosis. Orchidectomy followed by combination immunochemotherapy is a traditional treatment method with a rather inferior outcome. Aim: In this retrospective survey the authors analysed the clinical presentation, pathological features and treatment results of patients with primary testicular lymphoma diagnosed and treated in their haematology centre between 2000–2012 Method: During this period 334 patients with aggressive non-Hodgkin’s lymphomas were treated, of whom 8 patients (2.39%; age between 23 and 86 years; median, 60 years) underwent semicastration for primary testicular lymphoma (7 patients had diffuse, large B-cell lymphoma and one patient had Burkitt-like lymphoma). According to the Ann Arbor staging system a limited stage I-IIE was diagnosed in 7 patients and advanced stage was found in one patient. All but one patients were treated with rituximab added to CHOP regimen (6 or 8 cycles in every 21 or 28 days), whereas one patient received radiotherapy only. Central nervous system intrathecal prophylaxis was used in one case and no preventive irradiation of the contralateral testis was used. Results: With a median follow-up of 50 months complete remission was observed in 7 patients. However, two patients died (one due to progression and one in remission from pulmonary solid tumour). Complete remission rate proved to be 87.5%, disease-free survival was between 13 and 152 months (median 38 months) and overall survival rates were between 17 and 156 months (median 43 months). The 5-year disease-free and overall survival rates were 37.5 %. Conclusions: The relatively favourable treatment outcome could be mainly explained by the high number of patients with early-stage of the disease, early surgical removal of testicular lymphomas and the use if immunochemotherapy. This therapeutic regimen was effective to prevent localized and distant relapses. Despite omission of regular prophylaxis of the central nervous system, no relapse was detected. Orv. Hetil., 154 (42), 1666–1673.
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Cooper, K., A. Gangadharan, R. S. Arora, R. Shukla, and B. Pizer. "Burkitt Lymphoma of Thyroid Gland in an Adolescent." Case Reports in Pediatrics 2014 (2014): 1–3. http://dx.doi.org/10.1155/2014/187467.
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Burkitt Lymphoma is a highly aggressive form of non-Hodgkin’s lymphoma that in nonendemic areas has abdominal primary sites. We report a very rare case of Burkitt lymphoma of the thyroid gland presenting as a rapidly growing thyroid swelling in a 14-year-old white Caucasian British male with no preexisting thyroid or medical problems. The diagnosis was confirmed by an open wedge biopsy following a fine needle aspiration. The patient was treated according to the Children’s Cancer and Leukaemia Group guidelines for BL—Group B protocol and currently is in remission.
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Thandra, Krishna C., Adam Barsouk, Kalyan Saginala, Sandeep Anand Padala, Alexander Barsouk, and Prashanth Rawla. "Epidemiology of Non-Hodgkin’s Lymphoma." Medical Sciences 9, no. 1 (January 30, 2021): 5. http://dx.doi.org/10.3390/medsci9010005.
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Non-Hodgins’s lymphoma (NHL) is the most common hematological malignancy worldwide, accounting for nearly 3% of cancer diagnoses and deaths. NHL is the seventh most prevalent cancer and has the sixth highest mortality among cancers in the US. NHL accounts for 4% of US cancer diagnoses, and incidence has increased 168% since 1975 (while survival has improved 158%). NHL is more common among men, those >65 years old, and those with autoimmune disease or a family history of hematological malignancies. NHL is a heterogenous disease, with each subtype associated with different risk factors. Marginal zone lymphoma (MZL) is strongly associated with Sjogren’s syndrome (SS) and Hashimoto’s thyroiditis, while peripheral T-cell lymphoma (PTCL) is most associated with celiac disease. Occupational exposures among farm workers or painters increases the risk of most of the common subtypes. Prior radiation treatment, obesity, and smoking are most highly associated with diffuse large B-cell lymphoma (DLBCL), while breast implants have been rarely associated with anaplastic large cell lymphoma (ALCL). Infection with Epstein–Barr Virus (EBV) is strongly associated with endemic Burkitts lymphoma. HIV and human herpes virus 8 (HHV-8), is predisposed to several subtypes of DLBCL, and human T-cell lymphoma virus (HTLV-1) is a causative agent of T-cell lymphomas. Obesity and vitamin D deficiency worsen NHL survival. Atopic diseases and alcohol consumption seem to be protective against NHL.
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Konjeti, Venkata Rajesh, Gerald M. Hefferman, Sravanthi Paluri, and Prerna Ganjoo. "Primary Pancreatic Burkitt’s Lymphoma: A Case Report and Review of the Literature." Case Reports in Gastrointestinal Medicine 2018 (2018): 1–4. http://dx.doi.org/10.1155/2018/5952315.
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Primary pancreatic lymphoma (PPL) is of very rare occurrence as an extra nodal site of Non-Hodgkin’s lymphoma (NHL). It represents less than 1% of NHL. Out of which Burkitt lymphoma of pancreas is of a rare presentation. It usually occurs in children and presenting in adults is uncommon. The prevalence of pancreatic Burkitt lymphoma is not known as the incidence is significantly low. Clinical features of PPL are predominantly nonspecific and can become difficult with associated inflammation of pancreas. Differentiation of lymphoma to adenocarcinoma is important as chemotherapy is the main stay of treatment in lymphoma. We report a case of 68-year-old female who presented with nonspecific symptoms and was found to have obstructive jaundice secondary to pancreatic head neoplasm which was proved to be pancreatic Burkitt lymphoma which is a rare presentation.
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Mossafa, Hossein, Diane Damotte, Anne Vincenneau, Isabelle Amouroux, Nareth Athken, Arache Djnabian, Roland Jeandel, et al. "c-Myc Amplification in Non Hodgkin’s-Lymphomas with Burkitt-Like Features Is Associated with a Poor Prognosis." Blood 104, no. 11 (November 16, 2004): 3266. http://dx.doi.org/10.1182/blood.v104.11.3266.3266.
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Abstract We retrospectively studied 15 newly diagnosed patients presenting with NHL and Burkitt-like cells (BLCs) after morphological examination and histology review (lymph-nodes: 7 cases, peripheral blood: 5 cases, bone marrow: 3 cases and spleen: 1 patient). Conventional cytogenetic analyses were performed at diagnosis on lymph nodes biopsies (n=6), peripheral blood lymphocytes (n=4), bone marrow (n=4) or spleen (n=1). FISH studies used commercially available probes: IGH/c-MYC fusion signals probes, IGH/Bcl-1 fusion signals probes, IGH/Bcl-2 fusion signals probes and c-Myc 8q24 probe to detect t(8;14)(q24;q32), t(11;14)(q13;q32), t(14;18)((q32;q21) and c-Myc amplification, respectively. Morphological examination and/or histology showed BLCs in all patients. Burkitt-like lymphoma (BLL) is a highly proliferative lymphoma that morphologically resembles Burkitt’s lymphoma (BL) but has more polymorph and pleiomorph cells or large lymphoid cells than BL. The mean percentage of Ki-67 positive cells was 80% (range, 70–100%). A normal karyotype was present in 3 cases and a complex karyotype was observed in 12 cases (80%). When combining conventional cytogenetic studies and FISH studies, t(8;14) or the variants t(2;8) or t(8;22) were never detected. In contrast t(11;14)(q13;q32) was found in 4 cases and t(14;18) in 6 cases. Interestingly, c-Myc amplification was observed in all cases with 3 to more than 9 copies in 10–77% metaphase or interphase cells. The diagnosis of follicular lymphoma (FL) was confirmed by a CD5− and CD10− immunologic profile, typical t(14;18) in 4/6 cases and IgH/Bcl-2 fusion gene in all cases. Four cases were classified as mantle cell lymphoma (MCL) with a blastoid variant: MCL diagnosis was established by lymph-node biopsy in 1 case, CD5+ and CD23+ expression in 3/4 cases and 2/4 cases respectively, typical t(11;14)(q13;q32) in 3 cases, complex caryotype including 11 and 14 chromosomal abnormalities in 1 case and IgH/Bcl-1 fusion gene in all cases. Two patients had marginal MZL with a CD5− and CD10− profile and a complex caryotype including +3 and +18. Two patients presented a DLBCL (CD19+, CD20+) with BLCs and one case was classified as T-NHL (CD2+, CD4+, T-cell receptor gene rearrangements) in leukemic phase with BLCs. All these 15 patients have a poor prognosis with a death occurring in 6 patients during the first month after diagnosis. The presence of BLCs was observed independently of the type of lymphomas, FL, MCL or MZL. c-MYC amplification was associated with BLCs and progressive disease. In conclusion, we identified a new subgroup of patients with NHL (14 B-NHL, 1 T-NHL) and a profile including a poor prognosis, Burkitt-like features at presentation without t(8;14)(q24;q32) or its variants and Myc amplification in all cases.
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Mazur, Grzegorz, Ilona Kryczek, Tomasz Wrobel, Dorota Dlubek, Aleksandra Klimczak, Emilia Jaskula, Michal Jelen, Andrzej Lange, and Kazimierz Kuliczkowski. "CCR5 Chemokine Receptor Expression Can Promote Disease Progression in Non-Hodgkin’s Lymphoma." Blood 108, no. 11 (November 16, 2006): 4645. http://dx.doi.org/10.1182/blood.v108.11.4645.4645.
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Abstract Background: Non-Hodgkin’s lymphomas (nHL) represent heterogenous group of lymphoid malignancies derived from B and T lymphocytes, NK cells or histiocytes. Most of lymphomas are B-cell origin. Lymphoma cells can migrate to other organs and their migration could be linked to chemokines and their receptors. Chemokine receptors are expressed by many cell populations, including lymphoid cells, and their function is mediation of trafficking and localization particularly lymphocytes. CCR5 is predominantly expressed on Th1 cells, but also on dendritic cells, fibroblasts, endothelial and epithelial cells. Up-regulation of CCR5 expression is typical for nonneoplastic leukocytic infiltrates of nodal Hodgkin lymphoma. Its expression has been shown in hairy cell leukemia (HCL) and mantle cell lymphoma (MCL). Aim: The purpose of this study was to determine CCR5 expression in lymph nodes derived from patients with nHL comparing to control reactive lymph nodes and if there was any correlation between CCR5 expression and proliferation marker Ki-67 and international prognostic index (IPI). Material and methods: CCR5 gene expression was determined in 37 lymph nodes of lymphoma patients (26 B-cell lymphoma: 12 females and 14 males aged 26–73 years; 4 T-cell lymphoma: males aged 41–81 years; 7 Hodgkin’s lymphoma: 4 females and 3 males aged 21–58 years) and 25 reactive lymph nodes (15 females, 10 males, aged 18–59 years, median age 32 years). Gene expression was determined by the reverse transcription (RT)-polymerase chain reaction method. Scale of expression was 0–3 AU. Statistical analysis was performed using Kruskall-Wallis and Mann-Witney tests (p<0,05). Results: Most of lymphoma lymph nodes (25/37) showed low CCR5 expression (0–1 AU). In reactive lymph nodes 18/25 had also low CCR5 expression. In B-cell lymphomas high CCR5 expression characterized HCL, Burkitt’s lymphoma and diffuse large B-cell lymphoma nodes. In pts with higher CCR5 expression there was positive correlation with Ki-67 proliferation marker (p=0,016; coefficient = 0,34) and IPI (p=0,047; coefficient = 0,298). Conclusions: As there is a positive correlation between CCR5 expression and Ki-67 proliferation marker and IPI in non-Hodgkin’s lymphoma lymph nodes CCR5 may be associated with lymphoma progression.
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Colovic, Natasa, Nebojsa Radovanovic, Ana Vidovic, and Milica Colovic. "Primary Burkitt’s lymphoma of the stomach." Srpski arhiv za celokupno lekarstvo 139, no. 7-8 (2011): 523–26. http://dx.doi.org/10.2298/sarh1108523c.
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Introduction. Burkitt?s lymphoma belongs to the group of non-Hodgkin?s lymphomas with B immunophenotypic features of lymphoma cells. It has tendency for extranodal localization primarily in the gastrointestinal tract and retroperitoneum. Primary Burkitt?s lymphoma of the stomach is very rare. Stomach is most frequently involved secondarily, growing from intrabdominal tumorous mass into the stomach. Case Outline. The authors present a 30-year-old male in whom after 6 months duration of temporarily melaenas the diagnosis of Burkitt?s lymphoma was established by endoscopic examination and biopsy of ulceroinfiltrative lesion on the antral part of the stomach. The patient was in clinical stage IIE. After one cycle of chemotherapy according to protocol R-HyperCVAD, a subtotal distal gastrectomy and additional three cycles of the same chemotherapeutic protocol a complete remission was achieved. Conclusion. Burkitt?s lymphoma is a highly aggressive non-Hodgkin?s lymphoma often present in extranodal sites. It should be treated with systemic intensive chemotherapy and surgical removal of tumorous mass when possible. Long-term survival using the combination therapy is possible to achieve in 40-80% of patients.
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Barreto, José Henrique. "Burkitt Non-Hodgkin Lymphoma in childhood." Brazilian Journal of Infectious Diseases 9, no. 5 (October 2005): 445–46. http://dx.doi.org/10.1590/s1413-86702005000500029.
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Abdelmaksoud, Mostafa Mosbeh, Maram Kheder Alshareef, Alaa Osama Jamjoom, and Mohamed Tarek Hafez. "Ileocecal Burkitt’s Lymphoma Presenting as Acute Abdominal Pain." Case Reports in Oncology 13, no. 2 (August 14, 2020): 968–72. http://dx.doi.org/10.1159/000508998.
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Primary gastrointestinal non-Hodgkin’s lymphomas are rare tumors which account for about 0.9% of all gastrointestinal tract tumors. They are usually associated with inflammatory bowel disease, previous radiotherapy, and renal transplantation. We report a case of non-Hodgkin’s lymphoma involving the ileocecal region in a 46-year-old gentleman who presented with acute abdominal pain that mandated emergency laparotomy.
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Klumb, Claudete Esteves, Lídia Maria Magalhães de Resende, Claudio Gustavo Stefanoff, Carlos Humberto Vicuña, Ilana Zalcberg Renault, and Raquel Ciuvalschi Maia. "Burkitt-like lymphoma in an infant: a case report." Revista do Hospital das Clínicas 58, no. 1 (2003): 33–36. http://dx.doi.org/10.1590/s0041-87812003000100007.
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Childhood non-Hodgkin's lymphomas, including Burkitt and Burkitt-like, are rarely diagnosed in infants. A case of B-cell lymphoma in a 13-month-old girl with extensive abdominal disease, ascites, pleural effusion, and tumor lysis syndrome is reported. Phenotypic analysis showed a germinal center B-cell phenotype, and a B-cell clonality was confirmed by polymerase chain reaction. There was no evidence of Epstein-Barr and HIV infection. The case herein reported emphasizes the need for considering the diagnosis of lymphoma even in very young children.
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Höhn, Britta, Harris S. Soifer, Stephen J. Forman, and John J. Rossi. "Bifunctional siRNA Design Targeting Non-Hodgkin’s Lymphoma." Blood 110, no. 11 (November 16, 2007): 2357. http://dx.doi.org/10.1182/blood.v110.11.2357.2357.
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Abstract Non-Hodgkin’s lymphomas comprise a group of heterogeneous lymphoid malignancies that represent the fifth most common form of cancer in the United States. A hallmark of many types of B-cell lymphomas is the constitutive expression of oncogenes such as the transcription factors Bcl-6, STAT3 and c-Myc and the anti-apoptotic protein Bcl-2. Over expression of these genes causes uncontrolled proliferation and survival of malignant cells, making knockdown of these genes by RNA interference (RNAi) a rational strategy for therapeutic intervention. RNAi is a conserved endogenous mechanism in which small interfering RNAs (siRNAs) suppress target-specific gene expression by promoting mRNA degradation. We have designed potent Dicer-substrate siRNAs using different computer algorithms to predict accessible target sites in the mRNAs of B-cell lymphoma oncogene targets. The Dicer-substrate 27mers are designed asymmetrically, so that Dicer processing yields a predicted 21mer siRNA duplex for entry into RNA induced silencing complex (RISC). Dicer-substrate siRNAs show improved efficacy at lower concentrations compared with conventional 21mer siRNAs, suggesting the reduction of potential off-target effects. In addition, we have designed bifunctional siRNA duplexes that contain two fully target-complimentary antisense strands against two different target mRNAs, but that are only partially complementary to each other. In vitro cleavage assays indicate that our bifunctional siRNAs have sufficient complementarity to form stable duplexes and can be processed into smaller molecules by recombinant Dicer. When delivered to the Burkitt’s lymphoma cell line Raji by electroporation, the most effective siRNAs reduced target mRNA levels by ∼80% as determined by quantitative RT-PCR and immunoblot analysis. Silencing of transcription factors affected the expression of downstream target genes, indicating a relevant effect on growth on survival of lymphoma cells through oncogene down regulation by RNAi. One concern with RNAi-mediated therapy is the possible recognition of siRNA duplex by cell’s own response to double-stranded RNA (dsRNA) that could trigger an unwanted interferon response. To determine whether our Dicer-substrate siRNAs cause an interferon response, we monitored induction of the cellular dsRNA pathway by measuring gene expression of p56, OAS1 and interferon by quantitative RT-PCR after transfection of siRNAs in different cell lines. None of the analyzed siRNAs show a significant increase in the expression of interferon pathway related genes indicating that our selected siRNAs are powerful silencers of gene expression without inducing an interferon response. In future studies, these new identified siRNAs will be incorporated in nanoparticles or attached to antibodies / aptamers for cell-specific delivery to lymphoma cell lines to evaluate their potential alone or in combination with chemotherapeutic drugs in therapy for lymphoma.
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Guan, Hanfeng, Linka Xie, Frank Leithäuser, Lucia Flossbach, Peter Möller, Thomas Wirth, and Alexey Ushmorov. "KLF4 is a tumor suppressor in B-cell non-Hodgkin lymphoma and in classic Hodgkin lymphoma." Blood 116, no. 9 (September 2, 2010): 1469–78. http://dx.doi.org/10.1182/blood-2009-12-256446.
Full textAbstract:
The transcription factor KLF4 may act both as an oncogene and a tumor suppressor in a tissue-depending manner. In T- and pre-B-cell lymphoma, KLF4 was found to act as tumor suppressor. We found the KLF4 promoter methylated in B-cell lymphoma cell lines and in primary cases of B-cell lymphomas, namely, follicular lymphoma, diffuse large B-cell lymphoma, Burkitt lymphoma, and in classic Hodgkin lymphoma (cHL) cases. Promoter hypermethylation was associated with silencing of KLF4 expression. Conditional overexpression of KLF4 in Burkitt lymphoma cell lines moderately retarded proliferation, via cell-cycle arrest in G0/G1. In the cHL cell lines, KLF4 induced massive cell death that could partially be inhibited with Z-VAD.fmk. A quantitative reverse-transcribed polymerase chain reaction array revealed KLF4 target genes, including the proapoptotic gene BAK1. Using an shRNA-mediated knock-down approach, we found that BAK1 is largely responsible for KLF4-induced apoptosis. In addition, we found that KLF4 negatively regulates CXCL10, CD86, and MSC/ABF-1 genes. These genes are specifically up-regulated in HRS cells of cHL and known to be involved in establishing the cHL phenotype. We conclude that epigenetic silencing of KLF4 in B-cell lymphomas and particularly in cHL may favor lymphoma survival by loosening cell-cycle control and protecting from apoptosis.
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Sharma, Purva, Sakshi Singal, Patrick Costello, and Koyamangalath Krishnan. "Burkitt lymphoma: interpreting FISH testing for MYC gene rearrangements." BMJ Case Reports 15, no. 2 (February 2022): e246687. http://dx.doi.org/10.1136/bcr-2021-246687.
Full textAbstract:
Burkitt lymphoma is a highly aggressive B cell non-Hodgkin’s lymphoma characterised by translocation of MYC gene on chromosome 8. This translocation is usually detected by fluorescent in-situ hybridisation (FISH) studies as part of routine diagnostic work-up and prognostication. FISH testing is commonly done with the break-apart probe (BAP). This case illustrates how this testing can be falsely negative. This patient is a young male diagnosed with Stage I low-risk Burkitt with FISH negative for MYC translocation initially on BAP testing. Additional testing with dual FISH probe detected MYC/IGH translocation. FISH testing using BAPs alone may be falsely negative for MYC translocations creating a diagnostic challenge and compromising the treatment approach and assessment of prognosis.
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Moffitt, Andrea B., and Sandeep S. Dave. "Clinical Applications of the Genomic Landscape of Aggressive Non-Hodgkin Lymphoma." Journal of Clinical Oncology 35, no. 9 (March 20, 2017): 955–62. http://dx.doi.org/10.1200/jco.2016.71.7603.
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In this review, we examine the genomic landscapes of lymphomas that arise from B, T, and natural killer cells. Lymphomas represent a striking spectrum of clinical behaviors. Although some lymphomas are curable with standard therapy, the majority of the affected patients succumb to their disease. Here, the genetic underpinnings of these heterogeneous entities are reviewed. We consider B-cell lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, and primary mediastinal B-cell lymphoma. We also examine T-cell lymphomas, including anaplastic large-cell lymphoma, angioimmunoblastic T-cell lymphoma, cutaneous T-cell lymphoma, adult T-cell leukemia/lymphoma, and other peripheral T-cell lymphomas. Together, these malignancies make up most lymphomas diagnosed around the world. Genomic technologies, including microarrays and next-generation sequencing, have enabled a better understanding of the molecular underpinnings of these cancers. We describe the broad genomics findings that characterize these lymphoma types and discuss new therapeutic opportunities that arise from these findings.
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Shibata, D., LM Weiss, AM Hernandez, BN Nathwani, L. Bernstein, and AM Levine. "Epstein-Barr virus-associated non-Hodgkin's lymphoma in patients infected with the human immunodeficiency virus [see comments]." Blood 81, no. 8 (April 15, 1993): 2102–9. http://dx.doi.org/10.1182/blood.v81.8.2102.2102.
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Abstract Lymphoproliferations associated with Epstein-Barr virus (EBV) commonly arise in settings of immune dysfunction, including human immunodeficiency virus (HIV) infection. In this study, EBV was associated with 39 of 59 (66%) HIV-related systemic lymphomas. Unlike the lymphoproliferations that arise in the setting of transplantation, the HIV-related lymphomas were monoclonal, as evaluated by Ig heavy chain rearrangements and EBV termini analysis, and associated (40%) with c-MYC rearrangements. Furthermore, analysis of multiple lymphoma tissues from one autopsy showed evidence that a single lymphoma clone was responsible for dissemination. The latent EBV nuclear antigen (EBNA- 1) transcripts detected in the HIV-related lymphomas were characteristic of the pattern found in Burkitt lymphoma (g1 EBNA1) and not in transplant-related lymphoproliferations. However, unlike Burkitt lymphoma, EBV latent membrane-associated protein (LMP) transcripts were also detected, thereby constituting an EBV expression pattern (g1 EBNA1+, LMP+) not previously observed in B-cell lymphomas. These findings demonstrate a high frequency of EBV-associated lymphomas in the setting of HIV infection that are distinct from the lymphoproliferations that arise during iatrogenic transplant-associated immuno-suppression or in the general population. However, it is also apparent that HIV-related lymphomas are biologically heterogeneous, which may reflect the multiple mechanisms or steps necessary for eventual malignant transformation.
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Shibata, D., LM Weiss, AM Hernandez, BN Nathwani, L. Bernstein, and AM Levine. "Epstein-Barr virus-associated non-Hodgkin's lymphoma in patients infected with the human immunodeficiency virus [see comments]." Blood 81, no. 8 (April 15, 1993): 2102–9. http://dx.doi.org/10.1182/blood.v81.8.2102.bloodjournal8182102.
Full textAbstract:
Lymphoproliferations associated with Epstein-Barr virus (EBV) commonly arise in settings of immune dysfunction, including human immunodeficiency virus (HIV) infection. In this study, EBV was associated with 39 of 59 (66%) HIV-related systemic lymphomas. Unlike the lymphoproliferations that arise in the setting of transplantation, the HIV-related lymphomas were monoclonal, as evaluated by Ig heavy chain rearrangements and EBV termini analysis, and associated (40%) with c-MYC rearrangements. Furthermore, analysis of multiple lymphoma tissues from one autopsy showed evidence that a single lymphoma clone was responsible for dissemination. The latent EBV nuclear antigen (EBNA- 1) transcripts detected in the HIV-related lymphomas were characteristic of the pattern found in Burkitt lymphoma (g1 EBNA1) and not in transplant-related lymphoproliferations. However, unlike Burkitt lymphoma, EBV latent membrane-associated protein (LMP) transcripts were also detected, thereby constituting an EBV expression pattern (g1 EBNA1+, LMP+) not previously observed in B-cell lymphomas. These findings demonstrate a high frequency of EBV-associated lymphomas in the setting of HIV infection that are distinct from the lymphoproliferations that arise during iatrogenic transplant-associated immuno-suppression or in the general population. However, it is also apparent that HIV-related lymphomas are biologically heterogeneous, which may reflect the multiple mechanisms or steps necessary for eventual malignant transformation.
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Leventhal, Brigid G., and Gregory J. Kato. "Childhood Hodgkin and Non-Hodgkin Lymphomas." Pediatrics In Review 12, no. 6 (December 1, 1990): 171–79. http://dx.doi.org/10.1542/pir.12.6.171.
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Lymphomas were recognized originally by Virchow as swellings of lymph nodes that were unrelated to tuberculosis or to other recognized pathology in the drainage area of the lymph node group. Lymphomas were not recognized initially as malignancies; proof of this came only in this century. Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), which together account for approximately 12% of childhood cancer, have become among the most curable of pediatric malignancies. Today, the projected cure rates for children in certain categories are as high as 90%. Recent advances in molecular biology have permitted immense strides in understanding the pathogenesis and biology of these two diseases. FACTORS PREDISPOSING TO LYMPHOMAS Of individuals with immune deficiency or defects of DNA repair function, 1% to 35% develop lymphomas. NHLs are highly associated with Wiskott-Aldrich syndrome, common variable immunodeficiency, severe combined immune deficiency syndrome, X-linked lymphoproliferative syndrome, and Bloom syndrome, and they are found in patients receiving immunosuppressive therapy following organ or bone marrow transplant. Both HLs and NHLs are seen with increased incidence in patients with ataxia-telangiectasia and acquired immunodeficiency syndrome. Epstein-Barr virus, first strongly implicated epidemiologically in African Burkitt lymphoma, appears to have a role in the pathogenesis of at least 20% of B-cell lymphomas.
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Mazur, Grzegorz, Ilona Kryczek, Tomasz Wrobel, Dorota Dlubek, Aleksandra Klimczak, Emilia Jaskula, Michal Jelen, Andrzej Lange, and Kazimierz Kuliczkowski. "CCL2 Chemokine Gene Expression in Lymph Nodes May Have Prognostic Value in Non-Hodgkin’s Lymphoma." Blood 108, no. 11 (November 16, 2006): 4644. http://dx.doi.org/10.1182/blood.v108.11.4644.4644.
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Abstract Background: Non-Hodgkin’s lymphomas (nHL) constitute complex group of lymphoproliferative disorders in which clinical outcome is difficult to predict at the moment of diagnosis. Formation of International Prognostic Index has provided criteria dividing patients into groups of risk, but still new prognostic factors are being searched. There are several reports that some chemokines including CCL2 play a role in progression of solid tumours (bladder, ovarian, non-small cell lung cancer) and increased level of CCL2 has been found in myeloma multiple. CCL2 is the chemokine produced by tumour cells and some stromal cells, such as: fibroblasts, endothelial cells and monocytes. CCL2 is chemoattractant for monocytes, T, NK and dendritic cells and basophlis. CCL2 has also angiogenic activity and is necessary for tumour growth and metastatic process. Aim: The purpose of this study was to evaluate gene expression of CCL2 chemokine in lymphoma and reactive lymph nodes. Material and methods: CCL2 gene expression was determined in 37 lymph nodes of lymphoma patients (26 B-cell lymphoma: 12 females and 14 males aged 26–73 years; 4 T-cell lymphoma: males aged 41–81 years; 7 Hodgkin’s lymphoma: 4 females and 3 males aged 21–58 years) and 25 reactive lymph nodes (15 females, 10 males, aged 18–59 years, median age 32 years). Gene expression was determined by the reverse transcription (RT)-polymerase chain reaction method. Scale of expression was 0–3 AU. Statistical analysis was performed using Kruskall-Wallis and Mann-Witney tests (p<0,05). Results: In lymphoma lymph nodes CCL2 expression was significantly higher (2–3 AU) than in reactive lymph nodes (p=0,0008). Increased CCL2 expression was detected in 19/26 (73%) B-cell lymphoma lymph nodes and all (4/4, 100%) T-cell lymphomas. In reactive lymph nodes 2 AU expression was observed in 7/25 cases (28%). Particularly high expression characterized diffuse large B-cell lymphomas and Burkitt lymphomas. Patients with high CCL2 expression had significantly shorter survival than those with low expression (p=0,004). There was positive correlation between CCL2 expression and Ki-67 proliferation marker (p<0,05; coefficient 0,39). Conclusions: CCL2 expression is higher in B-cell lymphoma lymph nodes than in reactive lymph nodes. Multivariate analysis has proved CCL2 as independent prognostic factor in nHL.
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Mukhopadhyay, Ashis, Melissa Adde, Ian Magrath, and Soma Mukhopadhyay. "Result of Paediatric Non Hodgkin’s Lymphoma with Intensified Short Duration Chemotherapy : A Result from Eastern India." Blood 112, no. 11 (November 16, 2008): 4952. http://dx.doi.org/10.1182/blood.v112.11.4952.4952.
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Abstract Background: The Non-Hodgkin’s Lymphomas (NHL) in childhood are usually high grade and diffuse histology. They require intensified short duration chemotherapy in contrast to adult NHL. The aim of our study was to observe the result of aggressive short duration chemotherapy in paediatric NHL. Materials & Methods: We included consecutive 160 paediatric NHL patients in paediatric haemato-oncology department of Netaji Subhash Chandra Bose Cancer Research Institute during period from June 1996 to December 2007. The inclusion criteria were patients less than 25 yrs of age with a diagnosis of NHL and Patients are clinically staged according to the St. Jude’s (Murphy’s) classification. Patients with > 25% blasts in the bone marrow were treated as leukemia and excluded from the study. Each patient received 3 cycles A and 3 cycles B of MCP842 protocol of INCTR. Response was assessed at the completion of 2cycles of chemotherapy (1 each of A and B). Result: A total of 160 previously untreated patients were entered in this study. The age range was 1 to 25 yrs (median 13.5). Fourty Eight (48) patients had Lymphoblastic Lymphoma (LL), 64 patients (40%) had Burkitt Lymphoma, 40 (25%) diffuse Large B Cell Lymphoma (DLCL) and 8 (5%) had Anaplastic Large Cell. The abdomen was the most common site (56%) of involvement followed by the mediastinum (15.62%). One hundred and Thirty four (134)(83.75%) patients achieved complete response after 2 cycles of therapy, 14 patients (8.75%) achieved partial response and 6 (3.75%) had no response, 6 (3.75%) were not evaluable. With median follow up of 4 & 1/2 yaers (range 7 months – 10 years) a total of 38 (23.75%)patients (19 LL, 13 Burkitt Lymphoma, 5 DLCL and 1 ALCL) have died. The causes of death were progressive disease in 26 (16.25%), infection in 6 (3.75%), tumour lysis in 4 (2.5%), hepatitis in 1 (0.63%), and unknown 1 (0.63%). One hundred and twenty two (122) patients (76.25%) are alive and in complete remission. The patients tolerated chemotherapy well. Grade IV febrile Neutropenia was seen in 34 patients (21.25%). Conclusion: Result of MCP 842 was promising and we will continue the protocol in future.
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Malik, Fahad, Manuel Gonzalez, and Wahib Zafar. "Burkitt Lymphoma of the Duodenum: An Uncommon Phenomenon." Case Reports in Gastrointestinal Medicine 2019 (March 7, 2019): 1–4. http://dx.doi.org/10.1155/2019/7313706.
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Burkitt lymphoma is an aggressively growing tumor commonly found in African children, involving the jaw and facial bones. Most non-Hodgkin lymphoma tumors involve extra nodal sites like the nervous system and gastrointestinal tract. A rare variant of this type of lymphoma is found in immunocompromised patients specifically in the gastrointestinal tract with accompanying gastrointestinal symptoms. Burkitt lymphoma is a malignancy that has commonly presented in GI tract but rarely in the duodenum. This clinical variant can commonly involve stomach, ileum, and cecum. However, there is very limited data available regarding the duodenal growth of this tumor. Duodenal involvement of Burkitt lymphoma is extremely rare and accounts for < 1% of all lymphomas. We present a case report of an older patient with a duodenal Burkitt lymphoma diagnosed by biopsy. A high suspicion should be present while treating immunocompromised patients with chronic abdominal symptoms especially with complications such as bleeding or occult positive testing. Early endoscopy intervention with biopsy can help identity and treat these conditions with improved outcomes for the patients.
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Blumenthal, R., R. Stein, R. Michell, and D. M. Goldenberg. "Anti-CD74-doxorubicin immunoconjugate (IMMU-110) is cytotoxic in non-Hodgkin’s lymphoma (NHL) models and overcomes MDR." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 7598. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.7598.
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7598 Background: The internalizing LL1 anti-CD74 antibody is an optimal agent for delivering drugs, toxins, or radionuclides to CD74+ cancer cells. Here, we investigated the efficacy of IMMU-110 (Immunomedics, Inc.) in common follicular and aggressive types of NHL cells and in two disseminated non-Burkitt NHL models. Methods: CD74, MDR and MRP expression on NHL cell lines was determined by flow cytometry. In vitro cytotoxicity was assessed by cell cycle analysis of propidium iodide (PI)-stained cells and by measuring apoptotic cells using FITC-Annexin V and PI. In vivo therapy of a single 350-μg dose of IMMU-110 was evaluated in disseminated SUDHL4 and FSCCL. Results: Raji and Daudi Burkitt lines express similar amounts of CD74 (>93% positive cells and a MCF=35), yet a 3-day treatment with 0.8 μg/ml of IMMU-110 results is 18.4% of Raji and 67.9% of Daudi cells in Sub-Go. Aside from Daudi cells that respond with cells shifting into Sub-Go, most other NHL cell lines experience a G2/M block (44%-82% of cells) in response to a 3-day exposure to IMMU-110. Both MDR- and MDR+ NHL cells responded to IMMU-110. Kaplan Meier analysis showed a significant increase in survival of both SUDHL4 (MDR-/MRP-)- and FSCCL (MDR+/MRP+)-bearing SCID mice (P < 0.025) with 100% survival of treated mice vs. 38% survival of untreated mice at 70–77 days post cell implantation. Conclusions: IMMU-110 is cytotoxic in non-Burkitt and in Burkitt NHL cell lines. The magnitude of the cytotoxic response is not related to the amount of CD74 expressed on the cell surface. IMMU-110 is therapeutic in drug-sensitive (SUDHL4) and drug-resistant (FSCCL) NHL models, suggesting that antibody targeting can bypass the MDR drug efflux system that prevents free doxorubicin from being therapeutic. [Table: see text] [Table: see text]
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Al Sbihi, Ali, Nouraldeen Manasrah, Dahlia Sano, and Sarah Lonardo. "Early-stage Burkitt lymphoma remained in remission 7 years from diagnosis after only one cycle of chemoimmunotherapy." BMJ Case Reports 14, no. 4 (April 2021): e240925. http://dx.doi.org/10.1136/bcr-2020-240925.
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Burkitt lymphoma (BL) is a rare, mature, fast-growing and highly aggressive B-cell neoplasm. It has a high-proliferation rate with distinctive genetic changes in the C-MYC oncogene. Treatment usually requires intense and frequent chemotherapy regimens with central nervous system prophylaxis as the usual regimens used for other non-Hodgkin’s lymphoma yield poor survival in BL. This report discusses a patient who was diagnosed with a stage II, high-grade BL who received one cycle of intense chemotherapy and refused further treatment. That patient remained in complete remission in his last follow-up; 7 years from diagnosis without requiring other therapies for his lymphoma.
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Corti, Marcelo, Maria Florencia Villafane, Alicia Bistmans, Ana Campitelli, and Marina Narbaitz. "Soft-tissue masses as presentation of non-Hodgkin's lymphoma in AIDS patients." Anais Brasileiros de Dermatologia 88, no. 4 (August 2013): 631–34. http://dx.doi.org/10.1590/abd1806-4841.20132138.
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Primary soft tissue Non-Hodgkin lymphomas are very rare and account only for 0.1 % of the cases. Generally, Non-Hodgkin lymphomas of the soft tissue present as large subcutaneous masses without evidence of nodal or skin involvement. We describe four cases of primary Non-Hodgkin lymphomas of the soft tissue in patients infected with the human immunodeficiency virus. The most common site of involvement was the chest wall in all the patients; histopathological and immunophenotypic examination of the biopsy smears revealed two cases of plasmablastic lymphomas, one Burkitt and one diffuse large B-cell lymphoma. Non-Hodgkin lymphomas should be included in the differential diagnosis of soft tissue masses in human immunodeficiency virus - seropositive patients.
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Kostakoglu, Lale, Stanley J. Goldsmith, Anjaly Chandramouly, Erez Vidan, Sumeet Verma, and Morton Coleman. "FDG-PET Demonstrates Different Metabolic Activities among Lymphoma Subtypes." Blood 106, no. 11 (November 16, 2005): 4699. http://dx.doi.org/10.1182/blood.v106.11.4699.4699.
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Abstract Lymphomas may often present with more than one pathologic type in the same individual. This study assesses the variability of FDG uptake values as determined by SUV’s in various lymphoma subtypes to serve as a platform for differentiating and confirming the pathologic diagnosis in all disease sites. Methods: We retrospectively evaluated the PET-CT studies of 184 lymphoma patients at initial staging or at relapse prior to therapy. Lymphoma subtypes were classified according to the WHO classification. SUV’s were obtained in a total of 1120 nodal or extranodal disease sites in 11 lymphoma subtypes. Mean SUV’s were calculated for each lymphoma subtype by dividing the total maximum SUV’s by the number of disease sites in all patients. Consequently, mean SUV +/− SD and SUV range were determined and correlated with histologic diagnosis as shown in the Table. Results: Results are summarized in Table 1. The highest mean SUV’s were obtained in aggressive non-Hodgkin’s lymphomas (NHL) followed by Hodgkin’s disease (HD) and indolent NHL. Starting from the subtype with the highest mean SUV of the means and in a rank of decreasing order, the subtypes of lymphoma are as follows; Burkitts, DLCL, T cell rich B cell, natural killer T cell, HD, Anaplastic T-cell, mantle cell, marginal zone, follicular, T cell peripheral and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Conclusions: While SUV’s may be quite variable, a general pattern does exist for each lymphoma subtype. A major discrepancy between the SUV’s and histologic diagnosis should be assessed by repeat biopsy. SUV Distribution Among Subtypes of Lymphoma* Type of Lymphoma Patient Number Mean+/−SD Range *Table does not cover all lymphoma subtypes studied in this study due to limited space, HD: Hodgkins Disease NHL: Non Hodgkins lymphoma, DLCL: Diffuse large cell lymphoma, CLL/SLL: Chronic lymphocytic leukemia/small lymphocytic lymphoma HD 45 7.5+/−3.7 2–22 Mantle cell 8 6.8+/−4.9 2.1–21 DLCL 58 11.3+/−7.3 2.2–58 T cell Rich B cell 5 9.1+/−5.5 4–25 Burkitts 9 11.8+/−10.5 2–44 Follicular 30 5.1+/−2.7 1.6–11 CLL/SLL 11 3.0+/−1.5 1.1–8.8 Marginal Zone 10 5.5+/−3.8 2.1–21
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Moulana, Dr Amna, Dr Mohamed El Tahmoudy, Dr Riyazuddin Ansari, Dr Bushra Ahmed shaikh, and Dr Arjumand Moulana. "Primary Ovarian Lymphoma in Late Pregnancy: A Case Report." Saudi Journal of Pathology and Microbiology 7, no. 4 (April 29, 2022): 177–79. http://dx.doi.org/10.36348/sjpm.2022.v07i04.004.
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Involvement of the ovary with malignant lymphoma is a well-known late manifestation of disseminated nodal disease. Primary ovarian Burkitt lymphoma is very rare and mainly affects young children. We present a case of a 25-year old woman at 37 weeks pregnant with sporadic Burkitt lymphoma who presented as having ovarian cancer. The patient was managed via elective cesarean section and unilateral oophorectomy. Histopathological examination and immunohistochemical stains were carried out, revealing non-Hodgkin B-cell Burkitt lymphoma. After the diagnosis, the patient was referred to the oncology center for chemotherapy.
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Ikezoe, Takayuki, Tamotsu Takeuchi, Chie Nishioka, Yoshihiro Adachi, Mutsuo Furihata, H. Phillip Koeffler, and Akihito Yokoyama. "Analysis of Aurora B Kinase in Non-Hodgkin’s Lymphoma." Blood 112, no. 11 (November 16, 2008): 1610. http://dx.doi.org/10.1182/blood.v112.11.1610.1610.
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Abstract Aurora B kinase is one of the key regulators of mitosis and has been reported to be over-expressed in a various malignancies including acute myelogenous leukemia; however, expression of Aurora B in non-Hodgkin’s lymphoma (NHL) and its role in lymphoma genesis remain to be fully elucidated. This study explored the levels of Aurora B in seventy four lymph nodes and tumor specimens excised operatively from individuals with various types of NHLs including diffuse large B cell lymphoma (n=22, DLBCL), follicular lymphoma (n=12, FL), Burkitt’s lymphoma (n=10, BL), mantle cell lymphoma (n=4, MCL), mucosa associated lymphoid tissue (n=4, MALT), adult T-cell leukemia/lymphoma (n=11, ATL), peripheral T-cell lymphoma (n=8, PTCL), and Hodgkin’s lymphoma (n=3, HL). Immunohistochemical examination found that DLBCL (11/22, 50 %) and BL (8/10, 80 %) cells highly (percentage of positive cells, >20 %) expressed Aurora B in their nucleus. On the other hand, FL (11/12, 92 %), MCL (1/4, 25 %), and MALT (1/4, 25 %) cells slightly (percentage of positive cells, 5–20 %) expressed Aurora B and none of them, except for one case of FL, highly expressed this protein kinase, suggesting that expression of Aurora B correlated with histological grade in B cell NHLs (p=0.0004). We next examined whether Aurora B could be a molecular target for treatment of NHLs utilizing BALM-14, -18, and -27, Daudi, Ramos, and Raji Burkitt’s lymphoma/leukemia cells. Exposure of these cells to AZD1152, a selective inhibitor of Aurora B kinase, potently induced apoptosis in association with activation of caspase 3, as measured by annexin V staining and Western blot analysis, respectively. Moreover, we found that AZD1152 synergistically enhanced the effects of vincristine (VCR), a tubulin depolymerizing agent, to induce growth arrest and apoptosis of these cells. Further experiments found that VCR increased levels of the phosphorylated forms of Aurora B (p-Aurora B) via activation of c-Jun N-terminal kinase (JNK), which was blocked in the presence of AZD1152 in BALM-27 cells. Taken together, Aurora B kinase is a promising molecular target for treatment of individuals with aggressive types of NHLs. The combined administration of AZD1152 and the conventional chemotherapeutic agents to patients with NHL warrants further investigation.
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Davies, Kimberly, Matthew Barth, Saro Armenian, Anthony N. Audino, Phillip Barnette, Branko Cuglievan, Hilda Ding, et al. "Pediatric Aggressive Mature B-Cell Lymphomas, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology." Journal of the National Comprehensive Cancer Network 18, no. 8 (August 2020): 1105–23. http://dx.doi.org/10.6004/jnccn.2020.0036.
Full textAbstract:
Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.
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Monabati, Ahmad, S. Mohammad Rakei, Perikala V. Kumar, Moosa Taghipoor, and Abbas Rahimi. "Primary Burkitt lymphoma of the brain in an immunocompetent patient." Journal of Neurosurgery 96, no. 6 (June 2002): 1127–29. http://dx.doi.org/10.3171/jns.2002.96.6.1127.
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✓ Primary central nervous system (CNS) lymphoma is rare and is most often seen in immunodeficient patients. The majority of these tumors are the non-Hodgkin type and are high grade. Primary Burkitt lymphoma of the CNS in immunocompetent individuals has rarely been reported. The authors treated a 49-year-old woman who presented with left-sided weakness that had lasted 1.5 months. Magnetic resonance imaging revealed an oval mass in the left parietal region, with central necrosis and peripheral edema, and no attachment to the leptomeninges or ependyma. Pathological examination yielded a diagnosis of typical Burkitt lymphoma. Six months postoperatively, the patient is ambulatory and has improving neurological signs. This is a typical case of primary Burkitt lymphoma of the brain in an immunocompetent patient, which is a very rare event. The imaging pattern of the lesion is not typical of brain lymphomas and can result in an incorrect preoperative diagnosis of other brain tumors, such as glioblastoma multiforme. The patient's treatment and follow-up review are discussed.
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Klimova, N. V., A. O. Ramzina, A. A. Gaus, I. V. Bazhukhina, and Yu G. Karpenko. "HIV-associated non-Hodgkin’s Lymphomas (Literature Review with Own Clinical Cases)." Radiology - Practice, no. 5 (September 2, 2022): 57–68. http://dx.doi.org/10.52560/2713-0118-2022-5-57-68.
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This article provides a review of the literature on HIV-associated tumors (HATs) such as diffuse large B-cell lymphoma, Burkitt’s lymphoma, plasmablastic lymphoma, and anal canal lymphoma. The presented material is supplemented with own observations and illustrative material.
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Sandlund, John T., and Mike G. Martin. "Non-Hodgkin lymphoma across the pediatric and adolescent and young adult age spectrum." Hematology 2016, no. 1 (December 2, 2016): 589–97. http://dx.doi.org/10.1182/asheducation-2016.1.589.
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Abstract The non-Hodgkin lymphomas (NHLs) occurring in children and adolescents and young adults (AYA) are characterized by various age-related differences in tumor biology and survival. Children generally present with high-grade lymphomas, such as Burkitt lymphoma, diffuse large B-cell lymphoma, lymphoblastic lymphoma, and anaplastic large cell lymphoma, whereas low-grade histologic subtypes, such as follicular lymphoma, occur more frequently with increasing age. Treatment outcome for children with NHL is generally superior to that observed in adults. Factors contributing to this discrepancy include psychosocial factors, patient factors, and differences in tumor biology and therapy. These factors will be reviewed, with particular attention to the biological features of diffuse large B-cell lymphoma and anaplastic large cell lymphoma and corresponding therapeutic challenges. Novel targeting agents have been developed, which have been shown to be active in some patients. There is clearly a need for treatment protocols with eligibility criteria that cover the full span of the pediatric and AYA age range and that incorporate detailed molecular characterization of the tumors.
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Harker-Murray, Paul D., Lauren Pommert, and Matthew J. Barth. "Novel Therapies Potentially Available for Pediatric B-Cell Non-Hodgkin Lymphoma." Journal of the National Comprehensive Cancer Network 18, no. 8 (August 2020): 1125–34. http://dx.doi.org/10.6004/jnccn.2020.7608.
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Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary mediastinal B-cell lymphoma are the most common aggressive pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs). Despite excellent survival with current chemotherapy regimens, therapy for Burkitt lymphoma and DLBCL has a high incidence of short- and long-term toxicities. Patients who experience relapse generally have a very poor prognosis. Therefore, novel approaches using targeted therapies to reduce toxicities and improve outcomes in the relapse setting are needed. The addition of rituximab, a monoclonal antibody against CD20, to upfront therapy has improved survival outcomes for high-risk patients and may allow decreased total chemotherapy in those with low-risk disease. Antibody–drug conjugates have been combined with chemotherapy in relapsed/refractory (R/R) NHL, and multiple antibody–drug conjugates are in development. Additionally, bispecific T-cell–engaging antibody constructs and autologous CAR T-cells have been successful in the treatment of R/R acute leukemias and are now being applied to R/R B-NHL with some successes. PD-L1 and PD-L2 on tumor cells can be targeted with checkpoint inhibitors, which restore T-cell–mediated immunity and antitumor responses and can be added to conventional chemotherapy and immune-directed therapies to augment responses. Lastly, trials of small molecule inhibitors targeting cell signaling pathways in NHL subtypes are underway. This article reviews many of the targeted therapies under development that could be considered for future trials in R/R pediatric mature B-NHL.
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Luria-Pérez, Rosendo, Yolanda Rocio Peña-Alonso, Daniel Dimitri Hernández-Cueto, Altagracia Maldonado-Valenzuela, Guillermina Juliana Baay-Guzmán, Guadalupe Diaz-Elizondo, Luis Andrés Lara-Martínez, et al. "HIF-1a Expression and Implication in the Resistance Regulation and Malignancy in Pediatric Lymphomas Non-Hodgkin’s Tissue Arrays." Blood 112, no. 11 (November 16, 2008): 5308. http://dx.doi.org/10.1182/blood.v112.11.5308.5308.
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Abstract The Non-Hodgkin lymphomas are one of the most common of pediatric tumor, represent a group of curable tumors whose therapeutically success depends mainly in an early diagnosis, a combined therapy and a correct stratification according to prognosis factors. Several molecules have been reported as prognosis factors in cancer. However, some patients become refractory to such treatments. Alternative treatment modalities include immunotherapy, though, even in the presence of an effective anti-tumor response, the tumor develops mechanisms of resistance to apoptotic stimuli and cross-resistance to immune-mediated cytotoxicity. The transcription factor HIF-1 a (Hypoxia-inducible factor-1a) has been associated to the expression of different genes related to cancer (e.g SDF-1 and VEGF) and is considered as a prognostic factor in several types of cancers such as: leukemia, oropharyngeal cancer, neck cancer and ovarian carcinoma among others. However until now there is no clear evidence that the expression of HIF-1a is involve in the pathogenesis of pediatric Non-Hodgkin lymphomas. Hence, we hypothesized that one mechanism of pediatric Non-Hodgkin lymphomas immune escape may be due to overexpression of HIF-1a and VEGF. This hypothesis was tested using Tissue Microarrays (TMA) of formalin fixed, paraffin embedded sections of 70 untreated pediatric patients with different Non-Hodgkin lymphomas, obtained from the Children’s Mexican Hospital, Federico Gomez (Mexico, City). Cases included since 2000 to 2006, tumors were classified as: Burkitt lymphoma (BL, 19 cases), large B cell lymphoma (LBCL, 6 cases), lymphoblastic lymphoma (LL, 13 cases), anaplastic large cell lymphoma (ALCL, 12 cases), Hodgkin lymphoma (HL, 10 cases), and other type of lymphomas (10 cases). Staining by immunohistochemistry was performed to determine the expression levels of HIF-1a. The immunostaining was scored and both the percent of positive cells and the intensity were recorded and the data were analyzed statistically. Preliminary analyses show a very high cytoplasm and nuclear overexpression of HIF-1a in tumor tissue compared with the control (non tumor tissue or reactive hyperplasia). Quantitative analysis of HIF-1a expression among the different tumor tissue show a significant statistical difference (p=0.0124, ANOVA), results of Tukey analysis for reactive hyperplasia (RH) and tumor tissue were: RH vs LL p = 0.0001, RH vs LBCL p = 0.0148, RH vs ALCL p < 0.04, RH vs BL p = 0.001, RH vs others p= 0.001. These studies suggest that overexpression of HIF-1 a may be involved in the pathogenesis of some pediatric Non-Hodgkin lymphomas (LL, LCGB, LCGA and BL) and is potential biomarker. Furthermore, inhibitors of HIF-1 a expression/activity may be targets for therapeutic intervention when combined with immunotherapy.
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Grygalewicz, Beata. "Metody cytogenetyki molekularnej w różnicowaniu agresywnych B-NHL." Acta Haematologica Polonica 50, no. 3 (September 28, 2019): 109–15. http://dx.doi.org/10.2478/ahp-2019-0018.
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StreszczenieB-komórkowe agresywne chłoniaki nieziarnicze (B-cell non-Hodgkin lymphoma – B-NHL) to heterogenna grupa nowotworów układu chłonnego, wywodząca się z obwodowych limfocytów B. Aberracje cytogenetyczne towarzyszące B-NHL to najczęściej translokacje onkogenów takich jak MYC, BCL2, BCL6 w okolice genowych loci dla łańcuchów ciężkich lub lekkich immunoglobulin. W niektórych przypadkach dochodzi do wystąpienia kilku wymienionych aberracji jednocześnie, tak jak w przypadkach przebiegających z równoczesną translokacją genów MYC i BCL2 (double hit), niekiedy także z obecnością rearanżacji BCL6 (triple hit). Takie chłoniaki cechuje szczególnie agresywny przebieg kliniczny. Obecnie molekularna diagnostyka cytogenetyczna przy użyciu techniki fluorescencyjnej hybrydyzacji in situ (FISH) oraz, w niektórych przypadkach, aCGH jest niezbędnym narzędziem rozpoznawania, klasyfikowania i oceny stopnia zaawansowania agresywnych, nieziarniczych chłoniaków B-komórkowych. Technika mikromacierzy CGH (aCGH) była kluczowym elementem wyróżnienia prowizorycznej grupy chłoniaków Burkitt-like z aberracją chromosomu 11q (Burkitt-like lymphoma with 11q aberration – BLL, 11q) w najnowszej klasyfikacji nowotworów układu chłonnego Światowej Organizacji Zdrowia (World Health Organization – WHO) z 2016 r. Omówione zostaną sposoby różnicowania na poziomie cytogenetycznym takich chłoniaków jak: chłoniak Burkitta (Burkitt lymphoma – BL), chłoniak rozlany z dużych komórek B (diffuse large B-cell lymphoma – DLBCL) oraz 2 nowych jednostek klasyfikacji WHO 2016, czyli chłoniaka z komórek B wysokiego stopnia złośliwości z obecnością translokacji MYC i BCL2 i/lub BCL6 (high-grade B-cell lymphoma HGBL, with MYC and BCL2 and/or BCL6 translocations) oraz chłoniaka BLL, 11q.
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Lanfermann, H., W. Heindel, J. Schaper, R. Schröder, M. L. Hansmann, R. Lehrke, R. I. Ernestus, and K. Lackner. "CT and MR imaging in primary cerebral Non-Hodgkin's lymphoma." Acta Radiologica 38, no. 2 (March 1997): 259–67. http://dx.doi.org/10.1080/02841859709172060.
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Purpose: to determine the morphological appearance and topographical distribution of primary cerebral non-Hodgkin's lymphoma (NHL). Material and Methods: CT and MR examinations of 68 patients with primary cerebral NHL were analyzed. the NHLs were classified by the Kiel classification and im-munohistological data, as centroblastic (25), immunoblastic (24), lymphoblastic (5), Burkitt (1), non-subclassifiable type B (11), and T-cell lymphoma (2). Results: Centroblastic lymphomas tended to predominate in the parietal lobe (56.5%) and the corpus callosum (59.1%) while immunoblastic lymphomas were mainly distributed in the frontal lobe (52.8%). About 2/3 of all NHLs showed a multi-focal occurrence. Important for differential diagnosis, ventricular involvement was proved in 83.3% of these cases. in the remaining 26 patients with a solitary lymphoma, a periventricular location could be detected in only 8 cases. Central necroses were frequent in HIV-positive patients (7/11, 63.6%) but rare in the HIV-negative patients (9/57,15.8%). on T2-weighted SE MR images, 8/11 centroblastic lymphomas gave a signal that was isointense with, or lower than, that of the contralateral white matter, while 8/10 immunoblastic lymphomas gave a higher signal. Conclusion: the radiological finding of multifocal brain lesions with ventricular involvement is relatively specific for primary cerebral NHL. However, subclassification on the basis of the CT or MR imaging results is not yet possible.
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Mai, B., A. Berumen, A. Herrmann, and L. Chen. "Discordant Lymphoma: A Sequential Case of Burkitt Lymphoma and Classic Hodgkin Lymphoma." American Journal of Clinical Pathology 154, Supplement_1 (October 2020): S109—S110. http://dx.doi.org/10.1093/ajcp/aqaa161.239.
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Abstract Casestudy A discordant lymphoma is a rare condition in which two or more subtypes of lymphomas can occur in different anatomic sites; the distinct sub-classifications can present concurrently or sequentially. We present a rare case of a second primary Classic Hodgkin Lymphoma (CHL) several years after achieving remission from an unusual presentation of a non-Hodgkin lymphoma (NHL). Results A 40-year-old HIV-positive male presented to the emergency department for acute cholecystitis. Sections of his gallbladder revealed atypical monomorphic lymphocyte infiltrate that were diffusely positive for CD10, CD20, BCL6, and PAX5, and negative for BCL2, CD5, Cyclin D1, and MUM1. The proliferation index by Ki-67 was 100%. EBER ISH is positive. A FISH assay for the C-MYC break apart probe and dual fusion of IgH and BCL2 showed a rearrangement of 8q24, highly suspicions for a 8;14 translocation, classically seen in Burkitt Lymphoma (BL). Subsequently, he was placed on RA-DA-EPOCH and achieved remission. Seven years later, he presented with nausea, vomiting, headaches, and blurry vision. An excisional biopsy of his right cervical lymph node was performed. The histological sections showed effaced nodal architecture with sclerotic fibrosis and necrosis. There were scattered Hodgkin cells/Reed-Sternberg (HRS) cells in the background of lymphocytes, plasma cells, histiocytes, and eosinophils. The HRS cells were positive for CD15, CD20 (weak), CD30, BCL6, MUM1, and PAX5 (weak), and negative for ALK, CD10, and CD45. EBER ISH was positive and HHV8 was negative. These features were consistent with a CHL, nodular sclerosis subtype. Conclusion Malignancies in HIV patients pose a unique challenge as they often possess distinct characteristics distinct, including unique aspects of tumor localization, atypical pathological features, unusual growth behavior, and advanced stage at presentation. Epstein-Barr virus (EBV) is strongly linked with several HIV-associated lymphomas, as it encodes several proteins including LMP-1, LMP-2A, BHRF-1, EBNA-3A, and EBNA-3C that are implicated in the development of NHLs. The identification of discordant lymphomas may have variable prognoses and different treatment modalities. In addition, the study of such discordant lymphoma cases may provide more insight on the etiology and inter-relationship of clonal evolution in lymphoma.
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Momah, Uju, Jennifer Brewer, Anthony Tran, and David Shapiro. "NCMP-06. METASTATIC CENTRAL NERVOUS SYSTEM DISEASE SECONDARY TO BURKITT LYMPHOMA IN A PATIENT WITH PRIOR HISTORY OF MELANOMA." Neuro-Oncology 22, Supplement_2 (November 2020): ii124. http://dx.doi.org/10.1093/neuonc/noaa215.518.
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Abstract Sporadic Burkitt’s Lymphoma accounts for only 1–2% of Non Hodgkin’s Lymphoma, and metastasizes to the central nervous system (CNS) is uncommon, occurring in about 13–17% of adult patients. 1 Melanoma is far more likely to metastasize to the CNS, occurring in about 37% of adult patients.2 Here we present the case of a 69 year old Gambian female with a prior medical history of plantar melanoma. She initially presented to her primary care provider with back pain and adenopathy, and was referred to surgical consultation for diagnosis and concern for recurrent melanoma. Her workup revealed metastatic Burkitt’s Lymphoma with disease in the abdomen, lungs and likely CNS involvement. This report chronicles her disease course and approach to management.
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Krsmanovic, Pavle, Heidi Mocikova, Kamila Chramostova, Magdalena Klanova, Marie Trnkova, Michal Pesta, Peter Laslo, et al. "Circulating microRNAs in Cerebrospinal Fluid and Plasma: Sensitive Tool for Detection of Secondary CNS Involvement, Monitoring of Therapy and Prediction of CNS Relapse in Aggressive B-NHL Lymphomas." Cancers 14, no. 9 (May 6, 2022): 2305. http://dx.doi.org/10.3390/cancers14092305.
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Lymphoma with secondary central nervous system (CNS) involvement represents one of the most aggressive malignancies, with poor prognosis and high mortality. New diagnostic tools for its early detection, response evaluation, and CNS relapse prediction are needed. We analyzed circulating microRNAs in the cerebrospinal fluid (CSF) and plasma of 162 patients with aggressive B-cell non-Hodgkin’s lymphomas (B-NHL) and compared their levels in CNS-involving lymphomas versus in systemic lymphomas, at diagnosis and during treatment and CNS relapse. We identified a set of five oncogenic microRNAs (miR-19a, miR-20a, miR-21, miR-92a, and miR-155) in CSF that detect, with high sensitivity, secondary CNS lymphoma involvement in aggressive B-NHL, including DLBCL, MCL, and Burkitt lymphoma. Their combination into an oncomiR index enables the separation of CNS lymphomas from systemic lymphomas or nonmalignant controls with high sensitivity and specificity, and high Receiver Operating Characteristics (DLBCL AUC = 0.96, MCL = 0.93, BL = 1.0). Longitudinal analysis showed that oncomiR levels reflect treatment efficacy and clinical outcomes, allowing their monitoring and prediction. In contrast to conventional methods, CSF oncomiRs enable detection of early and residual CNS involvement, as well as parenchymal involvement. These circulating oncomiRs increase 1–4 months before CNS relapse, allowing its early detection and improving the prediction of CNS relapse risk in DLBCL. Similar effects were detectable, to a lesser extent, in plasma.
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Li, Pei-Chuan, Imran N. Siddiqi, Eric Y. Loo, Yinfei Kong, Wendy Cozen, Chieh-Hsi Wu, and Jean Chen Shih. "Monoamine Oxidase a (MAO A) Is Expressed Selectively in Reed-Sternberg Cells of Classical Hodgkin Lymphoma." Blood 126, no. 23 (December 3, 2015): 3864. http://dx.doi.org/10.1182/blood.v126.23.3864.3864.
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Abstract Monoamine oxidase A (MAO A) is a mitochondrial enzyme, which catalyzes oxidative deamination of neurotransmitters or dietary amines and produces H2O2. Recent work indicates that MAO A is overexpressed in prostate cancer. Inhibiting its activity suppresses tumorigenesis and metastasis. In this study, we showed that Hodgkin lymphoma (HL)-derived L1236 cells express high MAO A activity, while other human lymphoma cell lines examined, including both Hodgkin and non-Hodgkin lymphoma, do not express MAO A. We also analyzed MAO A expression by immunohistochemistry in formalin-fixed paraffin-embedded classical Hodgkin (n=88), nodular lymphocyte predominant Hodgkin (n=8) and non-Hodgkin lymphoma (diffuse large B-cell lymphoma, n=54; follicular, n=33; Burkitt lymphoma, n= 19; mantle cell lymphoma, n= 13). We found that 60% of the classical Hodgkin lymphoma (cHL) cases demonstrated at least some MAO A expression by the neoplastic Reed-Sternberg cells and 30% of the tumors show strong/uniform expression. In contrast, no MAO A activity was seen in normal lymphoid tissue, nodular lymphocyte predominant Hodgkin lymphoma or non-Hodgkin lymphomas. The MAO inhibitor clorgyline inhibited MAO A activity (IC50 of 8.3×10-9 M) and was cytotoxic (IC50 of 30 μM) to L1236 cells. In addition, clorgyline reduced the cell proliferation, colony formation, and invasion of L1236 cells in vitro. Taken together, we have shown for the first time that MAO A is expressed selectively in Reed-Sternberg cells of cHL. Our results suggest that MAO A may be a biomarker for classical Hodgkin lymphoma Reed-Sternberg cells and may provide biological insights as well as a potential therapeutic target. Disclosures No relevant conflicts of interest to declare.
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Gordon, Max J., and Alexey V. Danilov. "Prognostic Markers in Cardiac Non-Hodgkin Lymphoma: A Retrospective Review." Blood 126, no. 23 (December 3, 2015): 5007. http://dx.doi.org/10.1182/blood.v126.23.5007.5007.
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Abstract Introduction: Cardiac involvement by Non-Hodgkin lymphoma (NHL) occurs by several distinct mechanisms: primary extra-nodal disease, direct extension, hematogenous or lymphatic spread. While it is not an uncommon autopsy finding, it is rarely deemed to be clinically significant. By contrast, extranodal involvement by NHL is associted with inferior outcomes. Here we performed a retrospective review of 91 published cases of NHL with biopsy-proven cardiac disease to evaluate its clinical significance and impact on outcomes. Methods: A literature search using Pubmed was performed between 1990 and 2015. Inclusion criteria were biopsy proven lymphoma, age greater than or equal to 18, no history of bone marrow transplant and direct involvement of the pericardium and or myocardium. Survival data was only analyzed from patients without HIV/AIDS. Log-rank (Mantel-Cox) test was used to calculate survival. Age comparisons were calculated using an unpaired t-test with a two-tailed p-value and one-way ANOVA. Results: Ninety-one cases met inclusion criteria for the review. The mean age was 55 years (range 19-90 years). Patients with Burkitt lymphoma and HIV/AIDS were younger (p=0.016). Of patients with pathological evidence of cardiac involvement, diffuse large B-cell lymphoma (DLBCL) was the most common NHL subtype (52% of cases), followed by T-cell lymphoma (16%), Burkitt Lymphoma (8%) and small lymphocytic lymphoma (SLL, 6%). Chest pain was the most frequent presenting symptom (Table). Table. N=91 (%) Age: 18-60 >60 (60-90) 48 (53) 43 (47) Sex: Male Female 60 (66) 31 (34) Lymphoma type: Burkitt SLL DLBCL Follicular T-Cell Not specified 8 (9) 6 (7) 52 (57) 2 (2) 15 (16) 8 (9) Treatment: Chemotherapy Chemo and radiation Radiation Surgery None Unreported 25 (28) 6 (6) 1 (1) 4 (4) 11 (12) 44 (49) HIV/AIDS: Infected Non-infected 17 (19) 74 (81) Presenting clinical syndrome: Arrhythmia Chest pain CHF/Dyspnea Constitutional symptoms SVC syndrome Heart Block Stroke Sudden Death Other Unreported 2 (2) 10 (12) 31 (34) 6 (7) 4 (4) 4 (4) 3 (3) 3 (3) 8 (9) 20 (22) Forty-eight patients had primary cardiac lymphoma, which was defined as de novo lymphomatous involvement confined to the myocardium and/or pericardium, 41 patients had secondary disease and two were indeterminate. Patients with primary cardiac lymphoma were older (60 years, 95% CI, 55-59 years, versus 50 years, 95% CI, 47-53 years, p=0.006). Survival data were available for 54 patients. Of note, ~50% of patients did not receive therapy. Median survival was 3 months for all patients. The median survival of patients with T-cell lymphoma was 2 months, versus 4 months in the B-cell lymphoma subgroup (p=0.20). The median survival of patients with indolent B-cell lymphoma (SLL) was 37.5 months versus 4 months in patients with aggressive lymphoma (DLBCL and Burkitt, p=0.77). We found that female sex was associated with a trend towards improved outcome (median survival of 12 versus 3 months, p=0.63). Furthermore, patients diagnosed with primary (de novo) cardiac lymphomas also had better survival, 4 versus 2 months (p=0.23), possibly reflecting the more aggresive nature of relapsed disease. On further analysis, patients who were alive one month after diagnosis had a median survival of 18 months versus 3 months for all patients in this cohort (p=0.032). Furthermore, patients with primary B-cell lymphoma had superior survival to patients with T-cell lymphoma and/or secondary disease (median survival not reached vs 2.5 months, p=0.027). We also found that patients who received chemotherapy had a median survival of 18 months versus 1 month for those who did not (p=0.003). Discussion: Symptomatic cardiac involvement by NHL is rare. While it appears to be more common in DLBCL, it is seen across multiple indolent and aggressive NHL subtypes and is more common in men, typically presenting in the 6th decade of life. The outcomes of patients with NHL with cardiac involvement are poor, particularly among those with aggressive subtypes. However, patients who are candidates for chemotherapy and who survive beyond one month, particularly those with de novo (primary) cardiac B-cell lymphoma, are more likely to achieve long-term survival. Pathological lymphomatous involvement of cardiac tissue needs to be considered as part of differential diagnosis during work-up of patients with NHL. Disclosures No relevant conflicts of interest to declare.
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Zhang, Jenny, Dereje Jima, Qingquan Liu, Andrea Moffitt, Magdalena Czader, Eric D. Hsi, Yuri Fedirow, et al. "The Genetic Landscape Of Mantle Cell Lymphoma and The Epigenetic Origins Of Lineage Specific Mutations." Blood 122, no. 21 (November 15, 2013): 347. http://dx.doi.org/10.1182/blood.v122.21.347.347.
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Abstract Mantle cell lymphoma is an uncommon form of non Hodgkin lymphoma that is characterized by poor responsiveness to chemotherapy and a high rate of mortality. While translocation of CCND1 is a defining feature of the disease, the role of collaborating somatic mutations that contribute to mantle cell lymphoma remains to be better defined. In this study, we sought to better understand the patterns of mutations that occur in tumors derived from closely related stages of B cell differentiation. We began by performing exome sequencing in 55 cases of mantle cell lymphoma to broadly identify the mutational landscape of the disease. We then defined the chromatin structure of the normal counterpart B cells (naïve and germinal center B cells respectively) for mantle cell lymphoma and Burkitt lymphoma by profiling their epigenetic markers using chromatin immunoprecipitation followed by sequencing (ChIP-seq). We found that the somatic mutational profiles of mantle cell lymphoma and Burkitt lymphomas overlapped strongly with areas of open chromatin in their normal counterpart B cells, identifying B cell developmental lineage as a factor in the acquisition of somatic mutations. We identified somatic mutations affecting 311 genes in at least one tumor/germline pair among MCL cases. These variants were not present in publicly available data from normal controls including dbSNP135, the 1000 Genomes Project and available exome sequencing data from healthy individuals without lymphoma. We further required each of the identified genes to have a minimum of two rare and predicted functional variants for genes already in COSMIC, and three such variants in novel genes. The most frequently mutated genes in mantle cell lymphoma were ATM (41.9%), CCND1 (14%) and TP53 (18.6%). Other frequently mutated genes included known oncogenes and tumor suppressor genes such as RB1, SMARCA4, and APC. Our data also implicated a number of genes not previously associated with mantle cell lymphoma, including POT1, FAT4 and ROBO2. Silencing mutations (frameshift and nonsense mutations) comprised a sizeable fraction of the genetic events in ATM, MLL3, RB1 and ROBO2, suggesting that those alterations result in a loss of function in mantle cell lymphoma. To better understand the genetic differences between common non Hodgkin lymphomas, we examined exome sequencing data that we and others have generated from Burkitt lymphoma and diffuse large B cell lymphoma (DLBCL). We identified all genes that were mutated in roughly 10% of at least one lymphoma type and differentially mutated relative to at least one of the other lymphoma types (P<0.05, Fisher’s exact test). We found a number of genes that were predominantly mutated in each type. Mutations in ATM, CCND1, POT1 and RB1 occurred mostly in mantle cell lymphoma. Mutations in ID3 and MYC occurred predominantly in Burkitt lymphoma. Mutations in PIM1, FRMPD1 and CREBBP occurred mostly in DLBCLs. A number of genes had overlapping patterns of mutations between two or more of the diseases, including MLL3, TP53, ARID1A and SETD2. We sought to define the relationship between the epigenetically determined chromatin state of normal B cells and the lymphomas that are thought to arise from them. We began by FACS-sorting normal naïve B cells, germinal center B cells and memory B cells from otherwise normal individuals undergoing tonsillectomy. We profiled the chromatin structure and epigenetic state of the normal B cells through chIP-seq on 6 different markers: H3K4me1, H3K4me3, H3Ac, H3K27me3, H4K36me3, and CTCF. Using these epigenetic markers, differences in open chromatin between naïve B cells and germinal center B cells were computed for genes that were differentially mutated in mantle cell lymphoma and Burkitt lymphoma. We found that difference in gene mutation frequency between mantle cell lymphoma and Burkitt lymphoma is highly associated with differences in open chromatin in their corresponding cells of origin (P=0.02, Fisher's exact test). Our work demonstrates that the sequencing of relatively uncommon tumors such as mantle cell lymphoma and Burkitt lymphoma afford not only new insights into the genetics of these tumors, but also allow us to better examine the broader effects of lineage and epigenetic alterations in cancer. This work thus provides an important starting point for understanding the genetic diversity of mantle cell lymphomas and the interplay between genetic and epigenetic alterations in cancer. Disclosures: No relevant conflicts of interest to declare.
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Arami, Siamak, and Alexandr Svec. "Immunohistochemistry in Staging Bone Marrow Biopsy Specimens: a Useful Adjunct for Morphological Diagnosis in Non Hodgkin’s Lymphoma." Blood 124, no. 21 (December 6, 2014): 5393. http://dx.doi.org/10.1182/blood.v124.21.5393.5393.
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Abstract Background: Morphological examination of bone marrow trephine biopsy represents a standard method for non-Hodgkin’s lymphomas (NHL) staging. Immunohistochemistry staining of bone marrow trephine specimens has been widely used in haematological malignancies due to its high applicability and sensitivity at diagnosis. However, the routine use of immunohistochemistry in the clinical settings when there is no obvious morphological (light microscopic) evidence of lymphoma in the bone marrow trephine, is not yet well established universally. We assessed the value of immunohistochemistry (by using a standard basic panel of anti-CD20 and anti-CD3 staining) in detecting involvement by NHL in routinely processed bone marrow trephine specimens with no obvious morphological involvement with lymphoma. Methods: This study involved 56 randomly selected paraffin wax embedded, formalin fixed bone marrow trephine specimens between February 2011 and September 2013 from three teaching hospitals in Northeast, UK. 49 patients (87%) had B-cell NHL: diffuse large B cell lymphoma (DLBCL) 43% (n=24), follicular lymphoma (FL) 18% (n=10), marginal zone lymphoma (MZL) 9% (n=5), mantle cell lymphoma (MCL) 7% (n=4), lymphoplasmacytic lymphoma (LPL) 6% (n=3) and Burkitt’s lymphoma (BL) 6% (n=3). 7 cases (12%) had T/NK lymphomas. There was no obvious morphological evidence of bone marrow infiltration as all samples were reviewed by two examiners. All specimens were stained with the anti-CD20 and anti-CD3 antibodies. Results: Concordant results were found in 50 samples (89%), as both investigations were reported negative. 6 of the 56 cases (11%) with no morphological evidence of involvement by NHL on routine stains, were positive on immunohistochemistry. Considering histology, discrepant results were noted more frequently in T/NK lymphomas (42%; 3 of 7 cases) comparing to B-cell NHLs (6%; 2 cases of DLBCL and 1 case of FL). In all six cases the lymphoid infiltrates had diffuse pattern. Conclusions: Our results indicate that immunohistochemistry can detect a subgroup of NHL patients with bone marrow involvement beyond discriminatory level of conventional stains (Haematoxylin & Eosin and Giemsa), thereby contributing to accuracy of staging and treatment planning. Rational application of immunohistochemistry is a cost-effective & valuable method in routine investigation of staging bone marrow trephine biopsies. Disclosures No relevant conflicts of interest to declare.
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Rapier-Sharman, Naomi, and Brett E. Pickett. "Abstract 2709: Transcriptomic meta-analysis of non-Hodgkin’s B-cell lymphomas reveals reliance on pathways associated with extracellular matrix." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2709. http://dx.doi.org/10.1158/1538-7445.am2022-2709.
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Abstract We report here the results of a transcriptomic meta-analysis of public data for B-cell Non-Hodgkin’s Lymphomas (BCNHL). In 2016, there were 461,000 cases of Non-Hodgkin’s lymphoma worldwide, resulting in 240,000 deaths that year. BCNHLs pose a significant disease burden worldwide, making up 85-90% of BCNHL cases. BCNHL subtypes include Burkitt’s lymphoma, marginal-zone B-cell lymphomas, follicular lymphoma, diffuse large B-cell lymphoma, and mantle cell lymphoma. There is a growing need to understand the mechanisms of BCNHL pathology. The scientific community has spent a great deal of time and effort to identify the hallmarks of cancer. Since cancers of different subtypes can be considered parallel systems, we have performed a meta-analysis including as many BCNHL subtypes as possible to determine common underlying mechanisms. We performed a transcriptomic meta-analysis of publicly available RNA-sequencing data for BCNHL, consisting of 322 relevant samples across seven distinct studies in the NCBI Gene Expression Omnibus (GEO). To our knowledge, no BCNHL meta-analysis of this magnitude has previously been performed. We found ~10,400 significant differentially expressed genes (FDR p-value <= 0.05) and 33 significantly modulated pathways (FDR p-value <= 0.05). We observed potential common mechanisms for BCNHL’s differentially expressed genes and signaling pathways. Our findings include a significant class of proteoglycans not previously associated with lymphomas as well as significant upregulation of extracellular matrix-associated proteins. This meta-analysis offers fresh insights into the inner workings and mechanisms of B-cell lymphomas that could give rise to improved diagnostics and/or therapeutics. Citation Format: Naomi Rapier-Sharman, Brett E. Pickett. Transcriptomic meta-analysis of non-Hodgkin’s B-cell lymphomas reveals reliance on pathways associated with extracellular matrix [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2709.
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Ruan, Jia, Elizabeth Hyjek, Andrea T. Hooper, Loic Vincent, Pouneh Kermani, Paul J. Christos, Sherry Ikalowych, et al. "Stromal Incorporation of VEGFR-1+, CD68+ and α-SMA+ Hemangiogenic Cells Correlates with Histologic Subtype in Non-Hodgkin’s Lymphoma." Blood 106, no. 11 (November 16, 2005): 1930. http://dx.doi.org/10.1182/blood.v106.11.1930.1930.
Full textAbstract:
Abstract BACKGROUND: Tumor stromal environment has been increasingly recognized to contribute to tumorigenesis. Vascular endothelial growth factor receptor-1+ (VEGFR-1+) hematopoietic cells and alpha-smooth muscle actin+ (α-SMA+) stromal cells both contribute to tumor neo-angiogenesis. However, their roles in promoting neo-angiogenesis specifically in human lymphomas remain unknown. METHODS: We examined the spatial localization of vascular and stromal cells expressing CD34 (vasculature), α-SMA (stromal cells), VEGFR-1 (hematopoietic cells and neo-vessels) and CD68 (myelomonocytic hematopoietic cells) by immunohistochemistry in 42 cases of non-Hodgkin’s lymphoma (NHL) specimens, which include diffuse large B-cell lymphoma (DLBCL, n=28), Burkitt lymphoma (BL, n=2), follicular lymphoma (FL, n=7), and chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL, n=5). RESULTS: There was a significant increase in CD68+ hematopoietic cells and a profound increase in the tissue hemangiogenic index, as defined by the degree of infiltration of both VEGFR-1+ neo-vessels and CD68+ cells, in aggressive lymphomas including DLBCL as compared to the indolent subtypes. Specifically, CD68 cell counts (mean±S.E. in 200X high power field (HPF)) for aggressive vs. indolent vs. benign hyperplasia were: 235.48±16.91 (n=30) vs. 35.98±4.48 (n=12) vs. 79.06±12.41 (n=5), p<0.0001 by ANOVA test; hemangiogenic index for DLBCL vs. CLL vs. FL: 18.14±1.27% (n=5) vs. 3.39±0.97% (n=4) vs. 6.08±1.26% (n=5), p< 0.0001. Transformed DLBCL (from indolent subtypes) had a similar increase in CD68+ cells compared to de novo DLBCL (193.97±58.10 (n=5) vs. 241.77±18.15 (n=23), p=0.81). In DLBCL, CD68+ cells were localized to the peri-endothelial region of the VEGFR-1+ neo-vessels and stromal compartment. Remarkably, although the expression of alpha-smooth muscle actin (α-SMA) was barely detectable in the aggressive subtypes, there was a profound diffuse increase of α-SMA throughout the stromal compartment of CLL/SLL. Surprisingly, there was no correlation between the CD34+ microvessel density (MVD) and the lymphoma subtypes (aggressive vs. indolent vs. benign hyperplasia: 39.29±3.42 vs. 41.88±5.38 vs. 47.92±5.84, p=0.61). CONCLUSIONS: These data introduce the novel concept that the extent of vessel density has no correlation with the histologic grade of lymphomas. However, the stromal hemangiogenic index, as quantified by the incorporation of CD68+, VEGFR-1+, and α-SMA+ cells, correlates with NHL subtypes. Increased incorporation of pro-angiogenic CD68+ cells and diminished localization of α-SMA+ cells to the peri-vascular zone may contribute to enhanced neo-angiogenesis and tumor growth in DLBCL; while decrease in the CD68+ cells and increase in the α-SMA+ cells may promote neo-vessel stability in CLL/SLL. Thus stromal hemangiogenic components in lymphoma could potentially be targeted for therapeutic intervention.