scholarly journals Primary Testicular Lymphoma a Rare Extra Nodal Involvement of NHL

Author(s):  
R. Anantharamakrishnan ◽  
Senthil Kumar ◽  
K. Pranay ◽  
Rekadi Srinivasa Rao

Primary testicular lymphoma is a collection of neoplasms that constitutes only 1–9% of testicular tumors. Although uncommon in the general population, it is the most common type of malignant testicular tumor in men ≥50 years of age. There are various subtypes, including diffuse large B-cell lymphoma (DLBCL), Burkitt’s lymphoma and follicular lymphoma. In the adult testis, primary DLBCL represents the most frequent subtype of lymphoma (80–90%), whereas the majority of testicular lymphomas in children consist of secondary involvement by Burkitt’s lymphoma, DLBCL or lymphoblastic lymphoma. The typical clinical sign is a painless testicular mass of variable size that is usually unilateral. Primary testicular lymphoma may be identified during the initial presentation of primary or systemic malignant lymphomas, or during a clinical follow-up of patients with lymphoma. Historically, primary testicular lymphoma has been reported to exhibit a poor prognosis with an overall 5-year survival rate of 17–48%, particularly primary testicular DLBCL, whose clinical behavior has been reported to be aggressive and to demonstrate a high propensity to disseminate to the central nervous system (CNS) and skin at presentation and relapse. The underlying mechanisms responsible for this aggressive behaviour have yet to be elucidated. In the present study, a patient with primary testicular DLBCL was examined from histological examination and immunohistochemical staining in the diagnosis of testicular DLBCL.

Author(s):  
Eduardo Poblano Olivares ◽  
Jorge L. Olmos Gonzalez

Primary testicular lymphoma is a rare disease that has a higher incidence in patients over 60 years of age, presenting as an increase in volume in the inguinal region, which is usually painless and slow-growing. In the case that we present, it is a patient who was initially diagnosed with an indirect inguinal hernia due to the findings on examination and ultrasound, without presenting relevant findings in the laboratory studies, during the trans-operative we found testicular tumor compatible with diffuse large B-cell lymphoma, this being the most common variant of testicular lymphoma. This case emphasizes on importance of pre-operative suspicion in older age patients with increased volume in the groin region and without a clear diagnosis.


2017 ◽  
Vol 3 (3) ◽  
pp. 218-226 ◽  
Author(s):  
Gerhard Sissolak ◽  
Matthew Seftel ◽  
Thomas S. Uldrick ◽  
Tonya M. Esterhuizen ◽  
Nooroudien Mohamed ◽  
...  

Purpose Burkitt’s lymphoma (BL) is a common HIV-associated lymphoma in South Africa. B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt’s lymphoma (BL/DLBCL) also occurs in HIV infection. Outcomes of HIV-infected patients with BL or BL/DLBCL in a resource-constrained setting are not defined. Methods We performed a retrospective study of HIV-positive patients with BL or BL/DLBCL treated from 2004 to 2012 with curative intent at a publically funded academic medical center in South Africa. Differences between BL and BL/DLBCL, survival outcomes, and factors associated with survival were analyzed. Results There were 35 patients with either HIV-associated BL (24) or BL/DLBCL (11) who met study criteria. Median CD4+ T-lymphocyte count at lymphoma diagnosis was 188 cells/μL (range, 10 to 535 cells/μL). Patients with BL/DLBCL were significantly older and had less bone marrow involvement and lower baseline serum lactase dehydrogenase than patients with BL. Eighty-nine percent of patients presented with advanced disease, and 25% had baseline CNS involvement. Chemotherapy regimens consisted of cytoreduction with low-dose cyclophosphamide, vincristine, and prednisone followed by induction with vincristine, methotrexate, cyclophosphamide, doxorubicin and prednisone (LMB 86; 57%); hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine (hyper-CVAD; 20%); cyclophosphamide, doxorubicin, vincristine, and prednisone and high-dose methotrexate with leucovorin rescue on day 10 with accompanying prophylactic IT chemotherapy (Stanford regimen; 14%); and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP-like; 9%) regimens. Twenty-three patients received CNS treatment or prophylaxis, and 31 received concurrent combination antiretroviral therapy. Two-year overall survival was 38% (95% CI, 22% to 54%) and 2-year event-free survival was 23% (95% CI, 11% to 38%), with no difference between histologic subtypes. Common causes of death were infection (41%) and CNS disease progression or systemic relapse (41%). Conclusion Cure of HIV-associated BL and BL/DLBCL with intensive regimens is possible in resource-limited settings, but lower toxicity regimens, improved CNS prophylaxis, and increased resources for supportive care are required.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2421-2421 ◽  
Author(s):  
Ravi K. Amaravadi ◽  
Duonan Yu ◽  
Andrei Thomas-Tikhonenko ◽  
Craig B. Thompson

Abstract Burkitt’s lymphoma is an example of an aggressive B cell neoplasm characterized by overexpression of the c-myc oncogene and frequent inactivation of the tumor suppressor gene p53. A non-transgenic mouse model of Burkitt’s lymphoma was generated by retroviral transduction of the human c-myc gene into bone marrow cells derived from the p53-estrogen receptor (p53ER) knock-in mouse. The resulting myc/p53ER cells produce an aggressive B cell lymphoma when injected subcutaneously into the flanks of syngeneic mice. When tumor-bearing mice are treated with tamoxifen intraperitoneally, the p53ER fusion protein is targeted to the nucleus where p53-dependent apoptosis can take place. On successive in vivo passages, cells develop the ability to survive p53 activation and escape p53ER-dependent apoptosis despite tamoxifen treatment and nuclear localization of the p53ER fusion protein. We hypothesized that cells resistant to p53-dependent apoptosis utilize autophagy as an essential survival mechanism. Thus, these tumors could be sensitive to chloroquine, a lysosomotropic inhibitor of autophagy that has been used extensively in humans as an antimalarial and for the treatment of rheumatoid arthritis. Daily intraperitoneal chloroquine or hydroxychloroquine treatment of mice bearing myc/p53ER tumors in the absence of tamoxifen resulted in a delay in tumor growth. When tamoxifen was added to induce nuclear localization of p53ER, mice that received tamoxifen plus chloroquine had a complete tumor response while mice that received tamoxifen plus saline had transient tumor shrinkage followed quickly by regrowth. Tamoxifen plus chloroquine treatment enhanced the expression of p53-dependent target genes and increased caspase activation compared to tamoxifen plus saline treatment. A higher percentage of cells in tumors treated with tamoxifen plus chloroquine underwent apoptosis compared to tumors treated with tamoxifen plus saline. Moreover, tumors that recurred in the mice treated with daily tamoxifen plus chloroquine did so after a significantly longer latency period then mice treated with tamoxifen plus saline. Recurrent tumors showed loss of expression of p53 target genes. Electron microscopy of recurrent tumors confirmed the accumulation of vacuoles in chloroquine treated tumors compared to controls, suggesting inhibition of lysosome function leads to the accumulation of ineffective autophagic vacuoles. These results indicate that inhibiting autophagy with lysosomotropic chloroquine derivatives could be a useful therapeutic addition to treatment regimens for aggressive B cell lymphomas.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 518-518 ◽  
Author(s):  
Dieter Hoelzer ◽  
Wolfgang Hiddemann ◽  
Anita Baumann ◽  
Hartmut Döhner ◽  
Ulrich Dührsen ◽  
...  

Abstract With short intensive chemotherapy mainly based on HDMTX, fractionated alkylators and HDAC outcome of Burkitt’s NHL and mature B-ALL (B-ALL) in adults could be improved substantially to CR rates of 80% and overall survival (OS) of 50–70% (Hoelzer et al, Blood, 1996). Further intensification - namely increase of MTX dose - failed to improve these results. Therefore the German Multicenter Study Group for Adult ALL (GMALL) invented in 2002 a new protocol for mature B-ALL/Burkitt and other high-grade NHL, namely primary mediastinal (med) DLBCL, including 6x Rituximab® 375 mg/m2 before each chemo cycle and two R maintenance cycles. In addition 2 cycles based on HDAC 2 g /m2 were included. HDMTX was 1,5 g/m2 in the protocol for younger pts (<55 yrs). Older pts (>55 yrs) received a dose reduced regimen without HDAC and with MTX at 500 mg/m2. 227 pts with Burkitt (27=Burkitt-like), B-ALL or med DLBCL aged between 16 and 78 enrolled between 09/02 and 12/06 were evaluable for response after the first two cycles. The median age was 36 yrs for Burkitt, 46 for B-ALL and 35 for med DLBCL; 18%, 41% and 12% were older than 55 yrs respectively. The subgroups were characterised as follows: 115 Burkitt (stage III–IV 52%, extranodal inv. 78%, aaIPI >1 47%), 70 B-ALL, 42 med DLBCL (stage III–IV 55%, extranodal inv. 71%, aaIPI >1 61%). The CR rate was 90% in Burkitt, 83% in B-ALL and 69% in med DLBCL; death under therapy occurred in 3%, 11% and 0% respectively. The overall survival at 3 yrs was 91% for Burkitt, 79% for B-ALL and 90% for med DLBCL in pts at the age of 15–55 yrs and 84%, 39% and 67% (N=5) respectively in pts >55 yrs. CNS relapses were observed in 3 out of 22 older CR patients with B-ALL whereas in younger pts the CNS relapse rate was 0. CNS relapses are among the reasons for inferior outcome in elderly B-ALL in contrast to elderly pts with Burkitt or med DLBCL. CNS relapse rate may hopefully be reduced by inclusion of an intermediate dose ARAC cycle in the elderly B-ALL. There was no difference in OS between pts with Burkitt (92%) vs Burkitt-like NHL (86%). Since no prognostic factors could be identified in younger pts, there was no need for SCT in CR1. Major grade III/IV toxicity was hematological (28–37%) and mucositis (36%, 37%, 28% in cycles A1, B1, C1 respectively). Compared to the previous GMLL trial B-NHL90 (without Rituximab) with 270 pts the OS of 272 patients (including LBL, LCAL, DLBCL) at 3 yrs improved significantly from 54% to 80% (p<.0001) overall, 56% to 85% (p<.0001) in younger and 39% to 65% (p=.01) in older pts. In this largest prospective study of adult Burkitt’s lymphoma/leukemia and med DLBCL the combination of Rituximab and 6 short intensive chemo cycles was feasible and lead to an OS of 90% in NHL and 79% in mature B-ALL in the younger patient cohort. Even in older pts with Burkitt’s NHL survival was 84%. The further aim is now to reduce toxicity, namely mucositis.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5268-5268
Author(s):  
Majdi SM Hamarshi ◽  
Maha abu Kishk ◽  
Mahmoud Mahafzah ◽  
Jami Walloch

Abstract Introduction: Chromosomal translocations are common in non-Hodgkin’s lymphomas (NHL), most frequently involving the genes bcl-2 in the t(14;18) of follicular lymphoma (FL), c-myc in the t(8;14) of Burkitt’s lymphoma (BL) and bcl-6 in the t(3;14) of follicular or diffuse large B-cell (DLBC) lymphoma. We report the clinical features, pathology and genetic findings in an exceedingly rare case of Burkitt’s lymphoma that showed concurrent involvement of these three chromosomal loci. Case Report: This is a 65 year old Caucasian female who presented with a rapidly growing right supraclavicular lymph node over a few weeks. FNA biopsy showed typical morphology of Burkitt’s lymphoma. Similar morphologic features were found on the bone marrow biopsy. There was widespread disease with no CNS involvement. Flow cytometry from peripheral blood and immunohistochemistry on the cellblock showed B-cell phenotype positive for CD 10, CD19, CD20 (negative CD20 by immunohistochemistry), HLA-DR, cytoplasmic CD79a, and negative for CD34 and TdT. The interesting finding was the lack expression of surface or cytoplasmic immunoglobulin and expression of weak Bcl-6. Almost 90–95% expressed Ki67. The cytogenetic analysis reportedly demonstrated a complex karyotype t(3;8;14), and t(14;18) involving c-myc (8q24), bcl-2 (18q21), and bcl-6 (3q27). After 7 cycles of hyper CVAD-R she had bone marrow biopsy which showed residual disease. She also had a biopsy confirmed relapse as left arm nodule and left leg nodular infiltrate at 8 and 12 months form the diagnosis, respectively. Discussion: This is a complex case of high grade B-cell lymphoma with morphology suggestive of Burkitt’s lymphoma. However the classification was challenging by the lack of surface immunoglobulin expression that might be expected in mature B-cell neoplasm “DLBCL, FL”, and the lack of TdT and CD34 that might be expected in precursor B-cell neoplasm “BL”. The diagnosis was highly dependent on the cytogenetic findings, which was significant for the presence of t(8;14) albeit in a three way translocation t(3;8;14), and t(14;18) involving c-myc (8q24), bcl-2 (18q21), and bcl-6 (3q27). The lymphoma was therefore described as “Burkitt’s transformation”. This is a rare translocation pattern, but has been described in follicular lymphoma, grade 3; diffuse large cell lymphoma; and Burkitt’s lymphoma. Conclusion: BL might lack surface immunoglobulin expression making the diagnosis of high grade B-cell lymphoma challenging if based on the morphology and immunophenotyping alone. The cytogentetic findings better delineate sub-types of lymphoma. Molecular evidence of multiple oncogene deregulations, especially when involving the c-myc gene, appears to be associated with a dire clinical outcome.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2685-2685
Author(s):  
Yvette L. Kasamon ◽  
Robert A. Brodsky ◽  
Michael J. Borowitz ◽  
Pamela A. Crilley ◽  
Richard F. Ambinder ◽  
...  

Abstract Abstract 2685 Poster Board II-661 Background: Although standard therapies cure most adolescents and young adults with Burkitt's lymphoma/leukemia (BL), older patients (pts) have an inferior prognosis with an estimated 1-year survival of 50%. The inferior outcome is attributable to both insufficient efficacy and excess toxicity. Cyclophosphamide (Cy) has long been recognized to be arguably the most active agent in BL. Prior work at our institution showed that high-dose Cy, equivalent to transplantation doses, could be given without stem cell rescue with minimal toxicity even in older pts. Patients and Methods: A phase II trial for pts age ≥ 30, based on intensive Cy and incorporating rituximab but no anthracycline, was developed with a primary endpoint of 1-year overall survival. Entry requirements included newly diagnosed BL or atypical BL; any performance status (PS); HIV negative; and no significant cardiac dysfunction. Renal failure, even if necessitating dialysis, was permitted if it was acute. Treatment consisted of 3 cycles, with successive cycles beginning on day 15 or when ANC was ≥ 500/μL. Cycles 1 and 2 consisted of Cy 1500 mg/m2 IV day 1; vincristine 1.4 mg/m2 (2 mg cap) day 1; prednisone 100 mg days 1-5; rituximab 375 mg/m2 IV days 1 and 8; methotrexate 3 g/m2 IV day 8 with leucovorin rescue; cytarabine 100 mg intrathecally days 1, 4, and 11; and filgrastim. Cycle 3 consisted of rituximab 375 mg/m2 IV day 1; high-dose Cy (50 mg/kg IV days 2, 3, 4, and 5) with uroprotection; filgrastim; and rituximab 375 mg/m2 IV weekly for 4 weeks once ANC was ≥ 1000/μL. Eligibility for cycle 3 included ECOG PS < 4; no disease progression or uncontrolled meningeal disease; not on dialysis; and transaminases ' 5X upper limit of normal. Results: A prespecified interim analysis of the first 12 of a planned 20 evaluable pts is presented. Diagnosis was BL in 8 and atypical BL/unclassifiable high-grade lymphoma with features intermediate between BL and diffuse large B-cell lymphoma in 4. Median age was 56 (range 34 – 75), 8/12 (67%) had Ann Arbor stage III/IV disease, and all were high-risk by Magrath's criteria. PS ranged from 0 to 4. Two pts received hemodialysis on presentation. For all pts, actuarial event-free survival and overall survival (Figure) are 66% and 75%, respectively, at both 1 year and 2 years after treatment initiation. Three pts died during cycle 1: tumor lysis syndrome on day 1, neutropenic sepsis on day 8, multiorgan failure on day 46 after respiratory arrest on day 20. All of the other 9 pts completed protocol therapy: 8 (89%) achieved anatomic CR/CRu as well as a complete metabolic response by PET, and are event-free at a median of 29 months (range < 1 – 44 months) after therapy completion. The remaining pt had residual marrow disease followed by progression and is in remission 1 year after myeloablative allogeneic BMT. Adverse events in these 9 pts included 7 neutropenic fevers; 1 non-neutropenic bacteremia; and 1 self-limited episode of pericarditis with rapid atrial fibrillation. Grade 3 peripheral neuropathy was limited to 2 pts. The planned dose intensity was achievable: median time to cycle 2 was 15 days (14 – 21), and median time from start of cycle 1 to start of cycle 3 was 31 days (28 – 35). Median time to neutrophil recovery after the last dose of Cy was 16 days (10 – 21); median time to platelets ≥ 20,000/μL, without transfusion in the preceding week, was 22 days (0 – 30). Early stopping criteria for response or all-cause mortality have not been met. Conclusion: A very short regimen based on intensive Cy without anthracycline produces a high rate of durable CR's in older, poorer-risk pts with BL or atypical BL. Disclosures: Kasamon: Genentech: Research Funding. Swinnen:Genentech: Consultancy, Research Funding; Enzon: Consultancy; Abbot: Consultancy, Research Funding.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2697-2697
Author(s):  
Ali Mazloom ◽  
Nathan Fowler ◽  
Puneeth Iyengar ◽  
Bouthaina S. Dabaja

Abstract Abstract 2697 Poster Board II-673 Background: Primary testicular lymphoma (PTL) is the most common testicular neoplasm in males over the age of 60, representing 1% to 7% of all testicular malignancies. Histologically, the most common subtype of PTL is diffuse large B-cell lymphoma (DLBCL) representing 80–90% of diagnosed tumors. Primary testicular lymphoma has a tendency to disseminate to the contralateral testis and the central nervous system. Treatment approaches can include loco-regional treatment regimens (orchiectomy, radiotherapy) and systemic chemotherapy with or without intra-thecal chemoprophylaxis. The purpose of this study is to determine the clinical characteristics, patterns of failure, and survival of patients with PTL at our institution and to determine any correlation between outcome and treatment strategies. Methods: We retrospectively reviewed the medical records of patients with diffuse large B cell lymphoma of the testis. All patients were diagnosed and managed at the University of Texas MD Anderson Cancer Center between 1964 and 2008. Pathological diagnosis of DLBCL of the testis was made from orchiectomy specimens or fine needle aspiration of the testis. Factors analyzed included: age, stage at diagnosis, presence of b-symptoms, serum lactate dehydrogenase (LDH), beta-2 microglobulin, and modality of treatment. Cox proportional hazards model was used to generate hazard ratios for prognostic factors that affect the overall survival (OS) and disease free survival (DFS). Estimates of survival were calculated using the Kaplan-Meier method and the log-rank test was used to compare OS and DFS by the type of treatment. Results: Seventy-five patients with DLBCL of the testis were identified. The median age at diagnosis was 64 years (range 22 – 82). Ann Arbor stage I was present in 34 (45%), stage II in 13 (17%), stage III in 4 (5%), stage IV in 23 (31%), and unknown in 1 (1%). On univariate analysis, patients with advanced stage disease (stage III and IV; p = 0.042), elevated serum LDH levels (p = 0.029), B-symptoms at presentation (p = 0.003), and high-intermediate and high IPI score (p = 0.013), had a significantly decreased OS and DFS. The 5-years OS and DFS for all patients was 53.3%, and 45.9%, respectively. Treatment details are described in Table 1. A greater proportion of patients who received trimodality regimen (doxorubicin based chemotherapy, scrotal RT, and intrathecal methotrexate) had limited stage disease compared to those receiving less than a trimodality approach, however this variation was not statistically significant (71% vs 60%; p = 0.374, chi-square test). The 5-year OS and DFS for those treated with trimodality regimen was 90.4% and 79.5%, respectively, while for those treated with doxorubicin-based chemotherapy and testicular irradiation but without intrathecal chemotherapy it was 63.5%, and 55.6%, respectively, and for those treated with doxorubicin-based chemotherapy alone it was 39.3%, and 28.6% (p = 0.009 for OS and p = 0.012 for DFS). Figures 1 & 2 Conclusion: Prognostic factors for DLBCL of the testis include stage, LDH, B-symptoms, and IPI score. Patients with DLBCL of the testis who received trimodality regimen (doxorubicin based chemotherapy combined with scrotal RT and intrathecal chemotherapy) had significantly improved OS and DFS, which support the use of this approach as standard of care. Disclosures: No relevant conflicts of interest to declare.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13554-e13554
Author(s):  
Sung Hsin Kuo ◽  
Li-Tzong Chen ◽  
Kun-Huei Yeh ◽  
Hui-Jen Tsai ◽  
Hsiao-Wei Lee ◽  
...  

e13554 Background: We recently reported that autocrine BAFF (B cell–activating factor belonging to the TNF family) signal transduction pathway contributes to H. pylori-independent growth of gastric diffuse large B-cell lymphoma (DLBCL) (Blood 2008;112:2927-34; Ann Hematol 2010;89:431-6). In this study, we sought to investigate whether activation of BAFF signaling pathway can promote the survival and proliferation of aggressive B-cell lymphoma. Methods: Seven aggressive NHL cell lines (EBV-negative Burkitt’s lymphoma (Ramos), EBV-positive Burkitt’s lymphoma (Raji), EBV-negative undifferentiated lymphoma (MC116), activated B cell (ABC)-like DLBCL (OCI-Ly3, OCI-Ly10), and germinal center B cell (GCB)-like DLBCL (OCI-Ly7, and Pfeiffer) were used in this study. Cell cycle was analyzed by flow cytometry. The DNA-binding activity of NF-kB was determined by the luciferase assay. Expression of non-canonical NF-κB signatures-related proteins (BAFF, BAFF-R, NIK, cIAP1, TRAF2, cIAP1/2, TRAF3, IKKa, p100, p52 and RelB, BCL10, BCL3, and STAT3) was assessed by immunoblotting. Results: Our results showed that in GCB-DLBCL cell lines, activation of BAFF induced recruitment and degradation of TRAF3, which resulted in NIK kinase accumulation, BCL10 Ser138 phosphorylation, IKKa phosphorylation, and NF-kB p100 processing, thereby resulting in continuous activation of non-canonical NF-kB pathway. This phenomenon also resulted in BCL3 nuclear translocation and STAT3 activation, and subsequently activated STAT3 downstream-regulated genes (BCL2, survivin, and cyclin D1). Furthermore, we found that inhibition of BAFF by short hairpin RNA (shRNA) suppressed the growth of ABC-DLBCL cells and Burkitt lymphoma cells through the down-regulation of BAFF/BAFF-R/TRAF3/NIK/BCL3/NF-kB signaling pathway. Conclusions: Our results indicate that constitutive BAFF signaling activates NIK-induced non-canonical NF-kB signaling pathway in aggressive B-cell lymphoma, and inhibition of BAFF is particularly effective in the treatment of this subgroup of tumors.


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