Non-endemic Burkitt's Lymphoma Research Articles

S3705 A Case of Multifocal Burkitt Lymphoma in an Immunocompromised Patient

Introduction: Primary non-Hodgkin’s lymphoma (NHL) of the GI tract accounts for less than 0.9% of all gastrointestinal tumors. 30-40% of all extranodal manifestations occur in the stomach during secondary involvement, however this is less common in non-endemic Burkitt lymphoma (BL). Primary BL of the GI tract is very rare, including involvement of the stomach, duodenum and pancreas, accounting for less than 1% of all NHL tumor growth, even in secondary disease. BL is associated with HIV and EBV, however in those with HIV/AIDS, the CD4 count is typically greater than 200 without presence of concomitant opportunistic infections. Case Description/Methods: A 52 YO M PMH HIV, AIDS, HCV, IV drug abuse presented with acute L sided back and abdominal pain. On arrival he was hypotensive, cachectic with temporal wasting and severe, diffuse abdominal tenderness and tenderness of his L paraspinal muscles and lumbar spine. Labs were significant for leukocytosis, normocytic anemia, AKI, elevated ALP, LDH and ESR, and UDS positive for cocaine and opiates. CT A/P showed a fracture of the L 9th rib and asymmetry of the gastric wall. MRI revealed multifocal osteomyelitis with an epidural abscess spanning T7-T9. He underwent I & D and pathology of the epidural abscess and ribs revealed Burkitt Lymphoma. ERCP/EUS findings included esophageal candidiasis, multiple masses and nodules within the stomach, duodenum, and pancreas with strictures throughout the CBD and lower third of the main bile duct. A biliary sphincterotomy was performed and biopsies of all specimens were positive for Burkitt Lymphoma. His hospitalization was complicated by a subdural hemorrhage, initially thought to be CNS involvement however MRI brain and CSF flow cytometry did not reveal brain metastasis. A bone scan showed increased uptake in the distal shaft of the L humerus and femur, and a CT chest revealed a 4 mm nodule, all concerning for metastasis. He also developed SBO for which he was treated with R-CODOX/R-IVAC chemotherapy to reduce tumor burden. G-CSF and intrathecal methotrexate were administered. His SBO resolved and he was discharged home to follow up with Oncology for further management. Discussion: We present an HIV patient with low CD4 counts who was diagnosed with BL of the bone, lymph nodes, duodenum, stomach, pancreas and small intestine. The primary site of BL is ultimately unknown due to his complex presentation, however primary and/or secondary involvement of the duodenum, pancreas, stomach and intestine is very rare in non-endemic BL.

Minimal relapse risk and early normalization of survival for patients with Burkitt lymphoma treated with intensive immunochemotherapy: an international study of 264 real-world patients.

Non-endemic Burkitt lymphoma (BL) is a rare germinal centre B-cell-derived malignancy with the genetic hallmark of MYC gene translocation and with rapid tumour growth as a distinct clinical feature. To investigate treatment outcomes, loss of lifetime and relapse risk in adult BL patients treated with intensive immunochemotherapy, retrospective clinic-based and population-based lymphoma registries from six countries were used to identify 264 real-world patients. The median age was 47years and the majority had advanced-stage disease and elevated LDH. Treatment protocols were R-CODOX-M/IVAC (47%), R-hyper-CVAD (16%), DA-EPOCH-R (11%), R-BFM/GMALL (25%) and other (2%) leading to an overall response rate of 89%. The two-year overall survival and event-free survival were 84% and 80% respectively. For patients in complete remission/unconfirmed, the two-year relapse risk was 6% but diminished to 0·6% for patients reaching 12months of post-remission event-free survival (pEFS12). The loss of lifetime for pEFS12 patients was 0·4 (95% CI: -0·7 to 2) months. In conclusion, real-world outcomes of adult BL are excellent following intensive immunochemotherapy. For pEFS12 patients, the relapse risk was low and life expectancy similar to that of a general population, which is important information for developing meaningful follow-up strategies with increased focus on survivorship and less focus on routine disease surveillance.

Inferior Outcomes for Older Patients in the Adolescent and Young Adult (AYA) Population with Burkitt Lymphoma Treated with Intensive Immunochemotherapy: An International Study of 108 Patients

Introduction: Non-endemic Burkitt lymphoma (BL) is a rare and highly aggressive B-cell malignancy, of whom a substantial number are adolescents and young adults (AYAs). In this particular group of patients, the balance between efficacy and long-term toxicities is of major concern, due to the long expected remaining lifetime. In this study, we investigated the outcomes for AYA patients treated with intensive immunochemotherapy. Patients and methods: Patients were identified through queries to clinic based and population-based lymphoma registries from six countries (Australia, Canada, Denmark, Norway, Sweden, and USA). All diagnoses were confirmed by local investigators; patients with classical BL histology plus detectable MYC translocation, were included. Patients between 18 and 39 years of age at diagnosis treated with intensive immunochemotherapy (DA-EPOCH-R or more intensively) were evaluated in pre-specified age groups. All treatment protocols included rituximab. Overall survival (OS) was defined as the time from diagnosis until death from any cause or censoring, while event-free survival (EFS) was defined as the time from diagnosis until unplanned re-treatment, progression/relapse, death, or censoring, whichever came first. Response evaluation was assessed using established response criteria based on CT and/or PET/CT imaging. Survival curves were computed using the Kaplan-Meier estimator. The cumulative incidence of relapse in patients reaching complete remission (CR) or CR unconfirmed (CRu) was computed by Aalen-Johansen estimator. The 5-year restricted loss of lifetime (RLOL) was defined as the area between the patient and general population survival curves until 5-years. The general population survival was retrieved from publicly available lifetables stratified on age, sex, calendar year, and country. Results: In total, 108 AYA BL patients were included. The median age was 30 years, ranging between 18 and 39 and 82% were male. The majority had advanced stage disease (Ann Arbor stage III-IV, 76%), extranodal involvement (87%), and elevated LDH (67%). Seven patients (6%) had CNS involvement at the time of diagnosis. The chemotherapy regimens used were CODOX-M/IVAC (51%), BFM/GMALL (34%), hyper-CVAD (7%), DA-EPOCH (5%), and others (3%). Among 74 patients for whom data on tumor lysis were available, 10 (14%) developed clinical tumor lysis upon start of chemotherapy, all presenting with advanced stage and extranodal disease. The response rate was 91% (89 in CR/CRu and 2% in partial remission). At a median follow-up of 53 months, 15 had an event and 10 died. The 2-year OS and EFS for the total population was 92% (87-97%, Figure 1) and 88% (82-94%), respectively. For 13 patients aged 18-21 2-year OS and EFS were both 100%, while 2-year OS and EFS for 43 patients aged 22-30 were 98% (93-100%) and 93% (85-100%), respectively. The 2-year OS and EFS for patients aged 31-39 were 86% (76-96%) and 80% (69-91%), respectively. For patients in CR/CRu and available date of response evaluation, the 2-year post-remission OS was 99% (97-100%) and the 2-year relapse risk was 2% (0-5%), with no relapses after 6 months. Compared to the general population, the RLOL was 0.8 months (-0.5-2.2 months). Nine patients did not respond to primary treatment (SD or PD), all which belonged to the age group 31-40 years (P<0.001 versus age group 18-30 years). The oldest age group had an inferior OS compared to younger patients (P=0.008), largely due to non-responders having poor subsequent survival with a 1-year OS of 33%. Conclusion: The outcomes of AYA BL patients following intensive immunochemotherapy are excellent with high remission rates and low risk of relapse in general. However, even among young patients age remained prognostic, with patients 31 years or older having inferior OS and lower response rate to first-line treatment. In patients achieving CR, survival was similar to that of the general population over the median follow-up of 4.5 years, illustrating the need to focus on survivorship issues in these individuals. Figure 1: Overall survival for BL patients following intensive immunochemotherapy for all patients and for age groups (18-21, 22-30, and 31-39 years). Figure 1 Disclosures Jørgensen: Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Holte:Novartis: Honoraria, Other: Advisory board. Molin:Roche Holding AG: Honoraria; Merck & Co., Inc.: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceuticals: Honoraria. Ekstroem Smedby:Takeda: Honoraria, Other: Grant funding, Research Funding; Celgene: Honoraria, Other: Grant funding, Research Funding; Janssen Cilag: Honoraria, Other: Grant funding, Research Funding. Song:Takeda: Honoraria; Celgene: Honoraria, Research Funding; Janssen: Honoraria; Amgen: Honoraria. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria. Cheah:Roche, Janssen, MSD, Gilead, Loxo Oncology, Acerta, BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel expenses; Celgene, Roche, Abbvie: Research Funding. El-Galaly:Roche: Employment, Other: Travel support; Takeda: Other: Travel support.

Normalization of Survival and No Relapses after One Year in Adult Burkitt Lymphoma Patients Treated with Intensive Immunochemotherapy: An International Study of 159 Real-World Patients

Background: Non-endemic Burkitt lymphoma (BL) is a rare B-cell malignancy characterized by extreme tumor proliferation, frequent extranodal involvement, and the genetic hallmark of a MYC gene rearrangement. Despite an often dramatic initial presentation featuring tumor compression of vital organs and/or spontaneous tumor lysis syndrome, most patients who survive intensive immunochemotherapy induction are cured. Despite limited evidence of benefit, the current NCCN guidelines recommend that BL patients in CR are reviewed every 3 months for 2 years and every 6 months thereafter.Aims: To investigate outcomes, including relative survival and relapse risks conditional on event-free survival (EFS) milestones, in an international study of real-world BL patients treated with intensive immunochemotherapy.Patients and methods: This is a retrospective study of newly diagnosed BL patients identified from relevant population or hospital-based registers in Australia (Perth), Denmark (the Danish Lymphoma Registry), Sweden (the Swedish Lymphoma Registry) and Norway (Health Region South East). Patients who met the following criteria were included irrespective of HIV status: 1) age ≥18 years at diagnosis, 2) diagnosed during the period 2005-2017, 3) histology and immunohistochemistry consistent with BL, 4) MYC translocation detected by fluorescence in situ hybridization (FISH), and 5) intensive first line immunochemotherapy including rituximab (R-CHOEP or more intensive). Patient data were collected from registers and chart reviews. Overall survival (OS) was defined as time until death and EFS was defined as time to death, relapse/progression, or unplanned treatment, whichever came first. Prognostic features at baseline were evaluated using univariate Cox models with EFS as outcome. Standardized mortality ratios (SMRs), conditional relative survival estimates, and relapse risks were computed for the subset of patients achieving complete remission (CR or CRu), with follow-up measured from response evaluation and from different EFS milestones.Results: In total, 159 patients fulfilled the inclusion criteria of the study. The median age was 48 years (range 18-81) and the male:female ratio was 2.9. The baseline characteristics included stage III-IV (75%), elevated serum LDH (75%), extranodal involvement (83% - bone or bone marrow in 42% and CNS in 8%), B symptoms (60%), and ECOG performance score >1 (30%).The chemotherapy protocols used were CHOEP (2%), DA-EPOCH (13%), HYPER-CVAD (26%), CODOX-M/IVAC (28%), BFM or GMALL (31%), and others (1%). Clinical tumor lysis syndrome defined by severe electrolyte derangement, renal impairment, and/or cardiac arrhythmia, was noted in 16% of the patients, but no fatal episodes occurred. The overall response rate to first-line treatment was 88% (87% in CR/CRu) with 67% assessed by PET technology. The five-year EFS and OS estimates for the total population were 75% (95% CI 68-82%) and 82% (95% CI 76-88%), respectively, and the EFS and OS of patients <50 years of age were 81% (95% CI 71-90%) and 89% (95% CI 82-96%), respectively. In univariate analyses, age, advanced stage, and elevated LDH were associated with worse EFS. Among patients in CR/CRu (n=137), the 5-year EFS and OS from the time of response evaluation were 86% (95% CI 79-93%) and 91% (95% CI 86-96%), respectively. The 5-year cumulative incidence of relapse from the time of response assessment was 5% (95% CI 1-9%) in CR/CRu patients. The corresponding estimate was 3% (95% CI 0-6%) for patients alive after 6 months without events (EFS6), whereas no patients relapsed after 12 (EFS12, Figure 1). For CR/CRu patients, the 5-year relative survival after EFS6 and EFS12 was 97% (95% CI 93-102%) and 100% (95% CI 97-103%), respectively. In most subgroups, the SMRs gradually decreased with increased remission duration (Table 1).Conclusions: Outcomes of adult BL patients treated with intensive immunochemotherapy are excellent with no relapses occurring for patients reaching EFS12 and with a normalized relative survival after EFS6. For patients reaching EFS12, follow-up in late effects clinics, or discharging to primary care providers with a focus on survivorship issues rather than detection of recurrent lymphoma, should be considered. Updated analyses including patients from British Columbia (Canada) and the University of Iowa/Mayo Clinic SPORE MER register (USA) will be presented at the meeting. [Display omitted] DisclosuresMolin:Takeda Pharmaceuticals: Research Funding; Bristol-Myers Squibb: Honoraria; Roche Holding AG: Honoraria; Merck & Co., Inc: Honoraria. Ekstroem Smedby:Janssen Pharmaceuticals: Other: The Department have recieved partial funding from Janssen Pharmaceuticals.

Burkitt′s lymphoma masquerading as intestinal obstruction: An uncommon entity with variable clinical presentation

Small bowel lymphoma is a comparatively rare disease. Usually neither typical nor explicit symptoms are determined during its course and the first manifestation can be noticed when a complication occurs. Burkitt's lymphoma is a high-grade, aggressive and rapidly growing B-cell neoplasm, which has low long-term survival rates. Sporadic Burkitt's lymphoma accounts for 1-2% of lymphomas in adults and for 40% of lymphomas in children in the worldwide population. The abdomen is the most frequent site of onset in nonendemic (sporadic) Burkitt's lymphoma. Symptoms are often misleading and make diagnosis difficult. We present a case of a 5-year-old male child who presented with symptoms of acute intestinal obstruction. Emergency therapeutic and diagnostic laparotomy was performed and biopsy from thickened ileal wall was taken. Histopathologically, it was diagnosed as non-Hodgkin's lymphoma possibly Burkitt's lymphoma and confirmed on immunohistochemistry.

Extraocular Muscle Enlargement Leading to the Diagnoses of Burkitt Lymphoma and Acquired Immune Deficiency Syndrome

Orbital involvement in nonendemic Burkitt lymphoma is rare. The authors report a unique case of a patient who sought treatment for extraocular muscle enlargement without a concurrent orbital mass, which subsequently led to the diagnoses of Burkitt lymphoma and acquired immune deficiency syndrome in an adult patient. The case report adhered to the principles of the Declaration of Helsinki and Health Insurance Portability and Accountability Act compliance. This single case report was institutional review board exempt, given that it does not meet the definition of human subjects' research.

Bilateral Oral Non-Endemic Burkitt Lymphoma

Bilateral Oral Non-Endemic Burkitt Lymphoma

AIDS-related lymphomas in Nigeria

Aggressive non-Hodgkin's lymphoma (NHL), including primary central nervous system (CNS) lymphoma, lymphoblastic lymphoma and non-endemic Burkitt's lymphoma have been recognized as AIDS-defining cancers in most developed countries. However, HIV/AIDS epidemics appear not to have been associated with higher incidence of lymphomas in Africa. We therefore carried out this study to highlight the significance or otherwise of HIV/AIDS epidemics in the pathogenesis of lymphomas in a population of Nigerians with the disease. Since January 1993 to the present, all patients with haematologic cancers are routinely screened (following appropriate counseling) for HIV infection. Patients with a histological diagnosis of malignant chronic lymphoproliferative diseases {non-Hodgkin lymphoma (NHL), chronic lymphocytic leukaemia (CLL), Burkitt's lymphoma (BL) and Hodgkin lymphoma (HL)} at the Obafemi Awolowo University Teaching Hospitals' Complex, Ile-Ife from January 1993 to August 2008 were noted. Those patients confirmed to be HIV/AIDS positive among the cohort with lymphomas were retrospectively studied using their clinical case notes. Data obtained were analyzed using appropriate descriptive and inferential statistics. A total of 391 patients were histologically confirmed to have lymphoma {NHL-109, (27.9%); CLL-76, (19.4%); BL-178, (45.5%) and HL-28, (7.2%)} during the study period. Nine patients (2.3%) were confirmed to be HIV- positive, all within the age bracket 24-60 (median = 50) years. Six of these, five males and one female, ages 24-60 (median = 37.5) years, had NHL while another three, all females (age 50 - 68 years; median = 56 years) had CLL. None of the patients with HL and BL were HIV positive. Patients with NHL presented at advanced stage of the disease (at least clinical stage IIIb), and all those with CLL presented at stage C of the International Working Party Classification. All the HIV-positive patients with NHL succumbed to the disease within one to three weeks of admission into the hospital. The prevalence of AIDS-related lymphomas is 2.3% compared to 4.4% found in the general population. However, it is interesting that no single case of AIDS-associated BL was seen, despite the fact that Burkitt's lymphoma is endemic in this part of the world. All the patients presented at a very advanced stage of the disease with significantly shortened survival.

Chemotherapie des nicht-endemischen Burkitt-Lymphoms

14 patients (12 men, 2 women, mean age 26.3 [15-47] years) with histologically confirmed Burkitt's lymphoma were subjected between 1984 and 1989 to chemotherapy originally developed for treating lymphomas in children. Treatment consisted of medium doses of methotrexate, cyclophosphamide, teniposide, cytarabine, adriamycin and prednisone, intrathecal administration of methotrexate and if necessary prophylactic or therapeutic irradiation of the cranium. Most of the patients (64%) were in advanced stages of the disease. The rate of complete remissions was 100%. Four patients (29%) had a recurrence. Side effects were leukopenia (WHO grade III and IV) in 71%, grade III anaemia in 43% and grade III-IV thrombopenia in 29% of the patients. Considerable mucositides in 5 of the 14 patients (36%), and in one case a tumour lysis syndrome with transient renal insufficiency were other therapy-induced side effects. These results suggest that this treatment course can be successful also in non-endemic Burkitt's lymphoma in adolescents and adults.

Nonendemic Burkitt Lymphoma Presenting With an Atypical Clinical Picture

Primary appendiceal Burkitt lymphomas are rare occurring in 0.015% of all gastrointestinal lymphomas. Presentation of such lymphomas with peritonitis and obstructive jaundice owing to its subhepatic location is even more unusual. Burkitt lymphoma is very rare in children below 5 years old. We will present a 3-year-old boy with primary appendiceal lymphoma whose first symptom was obstructive jaundice caused by a ruptured retrocecal subhepatic appendix which in essence is a combination of all 3 mentioned occurrences complicated with acute abdomen.

Burkitt's Lymphoma: An Unusual Cause of Obstructive Jaundice

Biliary obstruction secondary to malignancy is a common clinical problem. Rarely, biliary obstruction is due to non-Hodgkin's lymphoma. Obstructive jaundice in these patients usually presents late in the course of the disease. Burkitt's lymphoma is a subtype of non-Hodgkin's lymphoma. Unlike other forms of non-Hodgkin's lymphoma, Burkitt's lymphoma presents as an extranodal disease. We present the case of a patient suffering from non-endemic Burkitt's lymphoma whose initial presenting symptom was obstructive jaundice.

Sporadic Burkitt's lymphoma of the head and neck in the pediatric population

Burkitt's lymphoma (BL) is one of the fastest growing malignancies in the pediatric population in the United States. BL is a high-grade B-cell Non-Hodgkin's lymphoma (NHL) which exists in endemic, sporadic, and human immunodeficiency-associated subtypes. The African, or endemic, variant usually involves the maxilla and other facial bones while head and neck manifestations in non-endemic BL are rare. We present three unusual present ations of sporadic BL stemming from Waldeyer's ring and the orbit. The clinical and pathologic features of BL are reviewed.

Analysis of SH2D1A mutations in patients with severe Epstein-Barr virus infections, Burkitt's lymphoma, and Hodgkin's lymphoma.

Mutations or deletions in the SH2D1A (src homology 2 domain protein 1A) gene result in a severe immunodeficiency called X-linked lymphoproliferative (XLP) disease. XLP is primarily characterized by a defective immune response against the Epstein-Barr virus (EBV), resulting in an unusually severe and often fatal clinical course following EBV infection. The second major cause of death is the development of B cell lymphomas, both in EBV-infected and EBV-negative patients. To study whether the clinical manifestation of XLP gene defects and/or polymorphisms extends beyond the classically recognized phenotype, we analyzed patients for the presence of SH2D1A gene alterations who presented with fatal or nonfatal, yet unusually severe or chronic EBV infections, and other possibly EBV-associated diseases, such as Hodgkin's lymphomas or nonendemic Burkitt's lymphomas and Burkitt-type leukemias. We identified mutations of the SH2D1A gene only in the majority of patients presenting with fatal mononucleosis or an XLP family history, but not in any of the other patients studied. The only alteration determined was a polymorphism in the 5' region of the SH2D1A gene both in patient groups as well as in controls.

Tissue Inhibitor of Metalloproteinase (TIMP)-1 Induces Differentiation and an Antiapoptotic Phenotype in Germinal Center B Cells

AbstractTissue inhibitors of metalloproteinases (TIMPs) have been shown to be multifunctional factors. Contrasting with their enzyme-inhibitory activity, TIMPs also promote cell growth. Previously, we have reported an enhanced expression of TIMP-1 by normal reactive B cells and high-grade lymphomas. In the present study, a series of Burkitt's lymphoma (BL) cell lines were analyzed for their expression of TIMP-1. TIMP-1 expression correlates with upregulation of activation and survival markers. TIMP-1–negative cells express the phenotype associated with group I BL lines and Epstein-Barr virus (EBV)-negative, nonendemic BLs (CD10+, CD38+, sIg+, and CD77+). However, TIMP-1+ BL lines showed group II/III BL phenotype, downregulation of the above markers, and upregulation and secretion of the activation marker CD23. Also, TIMP-1+ cells have high levels of CD40 expression. To determine whether TIMP-1 is directly involved in the BL phenotype, an EBV-negative BL line JD38 was infected with timp-1–expressing retrovirus and analyzed. In the absence of EBV, upregulation of TIMP-1 is sufficient to induce the same phenotype seen in TIMP-1+, EBV+ BL lines (CD10−, CD38−, sIg−, CD77−, CD23+, CD40 bright). This study not only suggests a role for TIMP-1 in BLs, but also supports its value as a prognostic factor.This is a US government work. There are no restrictions on its use.

Terminal deoxynucleotidyl transferase staining of malignant lymphomas in paraffin sections: a useful method for the diagnosis of lymphoblastic lymphoma.

Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase located in the cell nucleus which catalyses the polymerization of deoxynucleotides at the 3'hydroxyl ends of oligo- or polydeoxynucleotide initiators without a template. TdT is known as a useful marker for the diagnosis of acute lymphoblastic leukaemia/lymphoma, but its detection usually requires fresh tissue specimens or cell suspensions, using either an enzyme analysis or immuno-fluorescence or -peroxidase staining. Until the recent development of the use of microwave-treated paraffin sections for immunoperoxidase staining, detection of TdT in paraffin sections required rather complicated processes. This new simple technique was applied to paraffin sections from the tumour tissue specimens of 16 patients with lymphoblastic lymphoma and of seven patients with non-endemic Burkitt's lymphoma, which is sometimes difficult to differentiate from lymphoblastic lymphoma because of their similar clinicopathological characteristics. In addition, as a control, ten cases each were examined of adult T-cell leukaemia/lymphoma (ATLL) and angioimmunoblastic lymphoma (AILD), which are both peripheral T-cell lymphomas. The tumour cells from 15 of the 16 (94 per cent) patients with lymphoblastic lymphoma were found to be TdT-positive. The specificity of the anti-TdT antibody used was confirmed by immunoblot and the specific 60 kD band was detected only in a specimen of lymphoblastic lymphoma. These results show that the immunostaining of TdT on paraffin-embedded sections is a useful method for differentiating lymphoblastic lymphoma from other lymphomas. This method is applicable to a routine diagnostic service.

TERMINAL DEOXYNUCLEOTIDYL TRANSFERASE STAINING OF MALIGNANT LYMPHOMAS IN PARAFFIN SECTIONS: A USEFUL METHOD FOR THE DIAGNOSIS OF LYMPHOBLASTIC LYMPHOMA

Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase located in the cell nucleus which catalyses the polymerization of deoxynucleotides at the 3′ hydroxyl ends of oligo- or polydeoxynucleotide initiators without a template. TdT is known as a useful marker for the diagnosis of acute lymphoblastic leukaemia/lymphoma, but its detection usually requires fresh tissue specimens or cell suspensions, using either an enzyme analysis or immuno-fluorescence or -peroxidase staining. Until the recent development of the use of microwave-treated paraffin sections for immunoperoxidase staining, detection of TdT in paraffin sections required rather complicated processes. This new simple technique was applied to paraffin sections from the tumour tissue specimens of 16 patients with lymphoblastic lymphoma and of seven patients with non-endemic Burkitt's lymphoma, which is sometimes difficult to differentiate from lymphoblastic lymphoma because of their similar clinicopathological characteristics. In addition, as a control, ten cases each were examined of adult T-cell leukaemia/lymphoma (ATLL) and angioimmunoblastic lymphoma (AILD), which are both peripheral T-cell lymphomas. The tumour cells from 15 of the 16 (94 per cent) patients with lymphoblastic lymphoma were found to be TdT-positive. The specificity of the anti-TdT antibody used was confirmed by immunoblot and the specific 60 kD band was detected only in a specimen of lymphoblastic lymphoma. These results show that the immunostaining of TdT on paraffin-embedded sections is a useful method for differentiating lymphoblastic lymphoma from other lymphomas. This method is applicable to a routine diagnostic service. © 1997 John Wiley & Sons, Ltd.

Immunophenotypic analysis of childhood Burkitt's lymphoma in the West Midlands 1957-1986.

To analyse the immunophenotype of a large number of non-endemic Burkitt's lymphomas to determine whether a B cell phenotype is consistently recognisable using formalin fixed, paraffin wax embedded archival material and a standard panel of commercially available antibodies. Archival material was obtained from 30 cases of childhood Burkitt's lymphoma registered with the West Midlands Regional Children's Tumour Research Group. These were analysed by a standard avidin biotin complex immunoperoxidase method using antibodies to CD45, CD43, CD30, CD20, CD15, and immunoglobulin heavy and light chains. There was a high incidence of the CD45RB and CD20 immunophenotypes, with a clearly recognisable B cell lineage even in archival material. IgM was identifiable in 13 of the 23 (56.5%) cases tested. Only three of 17 (18%) cases expressed CD30. Positive membrane staining with CD45RO was observed in two (6.7%) cases. A B cell lineage can be identified in Burkitt's lymphoma in formalin fixed, paraffin wax embedded material, even in archival tissue. There was a low incidence of membrane staining with CD45RO which is a potential source of diagnostic confusion.

Burkitt's Lymphoma of the Parapharyngeal Space

Burkitt's lymphoma is quite rare outside of Africa. It is even more uncommon for this nonendemic form of the disease to present in the head and neck region. To our knowledge, nonendemic Burkitt's lymphoma has not been previously reported arising from the parapharyngeal space. We review the case of a 10-year-old boy who presented with an asymptomatic mass at the angle of the mandible several weeks after blunt trauma to that area. We discuss the evaluation of this mass, including the results of computed tomography and magnetic resonance imaging, along with the findings of histopathologic and cytogenetic studies. We also discuss the differential diagnosis of parapharyngeal lesions, paying particular attention to the workup and management of Burkitt's lymphoma. Since Burkitt's lymphoma has the highest growth rate of any tumor in man, rapid diagnosis and immediate treatment are important and likely to improve outcome.

Cellular proliferation and genetic events involved in the genesis of Burkitt lymphoma (BL) in immune compromised patients

A mathematical model simulating lymphomagenesis based on the two-hit theory of carcinogenesis is presented by contrasting the biologic variables responsible for a high risk of developing Burkitt lymphoma (BL) in three immunosuppressed groups with that of nonendemic BL. In this model, the pro-B lymphocyte is considered to be the target for BL-specific translocations such as t(8;14). With repeated mitosis, the target cell pool expands in the high-risk individual, and, thereby, the opportunities for a spontaneous translocation to arise are increased. The chromosomal translocation endows the target cell with survival advantages, and, hence, lymphoma develops. Modeling results demonstrate that this increased cell proliferation is sufficient in accounting entirely for the increase in tumor prevalence. Preventing enhanced cellular proliferation by obviating immune deficiency and treating patients with agents that restore immunity or have antiviral and antiproliferative properties prior to conversion from polyclonal B-cell proliferation to monoclonal malignancy could obviate the development of BL.

The role of surgery in abdominal Burkitt's lymphoma

The abdomen is the most frequent site of involvement in nonendemic Burkitt's lymphoma (small noncleaved cell). Some authors have proposed a role for extensive surgical resection or “second look” laparotomy in these patients. We retrospectively reviewed our series of 53 patients with Burkitt's lymphoma (1977 to 1990) to assess the role of surgery in their treatment. Patients were 2.5 to 21 years of age (median, 9.5 years) and 44 were males. The primary site of disease was the abdomen (38), head and neck (12), axilla (1), and bone marrow (2). Twenty-four of the 38 patients with abdominal primaries underwent laparotomy. Twelve of these patients presented with acute abdominal symptoms (right lower quadrant pain or intestinal obstruction) and at exploration underwent resection of the primary tumor. Ten of these 12 patients achieved grossly complete excision of tumor (9 had disease limited to the ileocecal area and adjacent mesentery and one had exophytic tumor adherent to the liver, which was excised). Of note, only 1 of these 12 patients had metastatic disease outside of the abdomen. The remaining 12 patients who underwent laparotomy had an incisional biopsy performed. Of the 14 patients who did not have a laparotomy, the diagnosis was made by bone marrow biopsy (6), and/or cytology of pleural fluid or ascites (6), lymph node biopsy (1), testicular biopsy (1), tibial biopsy (1), and percutaneous biopsy (1). Murphy staging for these 38 patients was: stage II (10), stage III (19), stage IV (5), and B cell acute lymphoblastic leukemia (ALL) (4). All patients received cyclophosphamide-containing combination chemotherapy regimens and stage III/IV/B cell ALL patients received central nervous system (CNS) prophylaxis. Between 1977 and 1982, 5 patients with stage II received whole abdominal irradiation. Patient survival without recurrent disease corresponded with stage at presentation: 9 of 10 stage II, 8 of 19 stage III, 1 of 5 stage IV, and 2 of 4 B cell ALL patients (follow-up of survivors: median, 8.3 years; range, 9 months to 11 years). In only 3 patients was a second look procedure performed because of questionable residual local disease. One of those 3 patients had viable tumor and he suffered a CNS relapse shortly after surgery. Only 1 patient in the entire group had an isolated recurrence in the abdomen. All of the other 12 patients who relapsed had tumor involving either CNS (5), bone marrow (3), testes (4), liver (2), and/or thorax (3). Four of these 12 also had local abdominal recurrence. We conclude that exploratory surgery for the purpose of resection of the primary tumor is only justified for patients with limited ileocecal and mesenteric involvement who are likely to present with signs of intestinal obstruction or abdominal pain. These patients have a high likelihood of disease-free survival probably due to limited disease at presentation. Extensive surgical procedures in patients with more advanced abdominal involvement will often result in only partial resections as metastatic disease is frequently present. Persistent or recurrent local abdominal disease following chemotherapy are infrequent events limiting the role for delayed primary or “second look” procedures.