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Journal articles on the topic 'Microenviroment Lymphoma Primary Testicular Diffuse Large B-cell Lymphoma'

Author: Grafiati

Published: 14 March 2023

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1

Wang, Qi, Dafang Zheng, Damin Chai, Shiwu Wu, Xiaolin Wang, Shaonan Chen, Linhui Wu, Ruoxue Cao, and Yisheng Tao. "Primary testicular diffuse large B-cell lymphoma." Medicine 99, no. 12 (March 2020): e19463. http://dx.doi.org/10.1097/md.0000000000019463.

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2

Trama, Francesco, Ester Illiano, Achille Aveta, Savio Domenico Pandolfo, Giancarlo Bertuzzi, and Elisabetta Costantini. "Bilateral Primary testicular diffuse large B-CELL lymphoma." Urology Case Reports 38 (September 2021): 101733. http://dx.doi.org/10.1016/j.eucr.2021.101733.

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3

Drideb, Alami, and Bouchnafat Saddi. "Primary testicular diffuse large B-cell lymphoma in young patient: an uncommon presentation." Hematology & Transfusion International Journal 10, no. 4 (December 13, 2022): 104–5. http://dx.doi.org/10.15406/htij.2022.10.00290.

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Primary testicular lymphoma (PTL) is a rare form of extranodal lymphoma, this neoplasm is the most common malignant tumor of the testis in the elderly age, and the majority of cases are histologically diffuse large B-cell lymphoma (DLBCL), accounting for 80% to 98% of non-hodgkin lymphoma. Patients with primary testicular DLBCL show a continuously high risk of recurrence with no plateau in the survival curves and a tendency to involve other extranodal sites, especially the central nervous system and the contralateral testis. We report a rare and uncommon presentation of a primary testicular diffuse B cell lymphoma in young patient.

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4

Knežević, Snežana, Bojana Trikoš, and Ivan Gajović. "Primary testicular diffuse large B-cell lymphoma, presented as phlebothrombosis." Timocki medicinski glasnik 43, no. 2 (2018): 72–76. http://dx.doi.org/10.5937/tmg1802072k.

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5

Sadiq, Muhammad, Iftikhar Ahmad, Jamila Shuja, Zia Ullah Khan, and Khushnaseeb Ahmad. "Primary testicular diffuse large B-cell lymphoma: A case report." Egyptian Journal of Basic and Applied Sciences 4, no. 4 (December 2017): 358–60. http://dx.doi.org/10.1016/j.ejbas.2017.10.007.

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6

Horne, Matthew J., and Adebowale J. Adeniran. "Primary Diffuse Large B-Cell Lymphoma of the Testis." Archives of Pathology & Laboratory Medicine 135, no. 10 (October 1, 2011): 1363–67. http://dx.doi.org/10.5858/arpa.2010-0158-rs.

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In this short review, we discuss primary diffuse large B-cell lymphoma of the testis, an entity that is most commonly seen in older patients. The most common clinical presentation is a unilateral testicular mass. Microscopically, the tumor shows diffuse infiltration of lymphocytes between intact seminiferous tubules. Spermatogenic arrest, interstitial fibrosis, and tubular hyalinization are commonly seen. The tumor is positive for B-cell markers by immunohistochemistry. Treatment has traditionally been with orchiectomy and combination chemotherapy; however, only a minority of patients enjoy a prolonged disease-free survival. Differential diagnosis includes seminoma and viral and granulomatous orchitis.

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7

Cheah, Chan Y., Andrew Wirth, and John F. Seymour. "Primary testicular lymphoma." Blood 123, no. 4 (January 23, 2014): 486–93. http://dx.doi.org/10.1182/blood-2013-10-530659.

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Abstract Primary testicular lymphoma (PTL) is a rare, clinically aggressive form of extranodal lymphoma. The vast majority of cases are histologically diffuse large B-cell lymphoma, but rarer subtypes are clinically important and must be recognized. In this review, we discuss the incidence, clinical presentation, and prognostic factors of PTL and present a summary of the recent advances in our understanding of its pathophysiology, which may account for the characteristic clinical features. Although outcomes for patients with PTL have historically been poor, significant gains have been made with the successive addition of radiotherapy (RT), full-course anthracycline-based chemotherapy, rituximab and central nervous system–directed prophylaxis. We describe the larger retrospective series and prospective clinical trials and critically examine the role of RT. Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 21 days with intrathecal methotrexate and locoregional RT is the current international standard of care, a substantial minority of patients progress, representing an unmet medical need. Finally, we discuss new treatment approaches and recent discoveries that may translate into improved outcomes for patients with PTL.

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8

Hussein, Abdallah, Hachem Farouk, Bellouki Omar, Ibrahimi Ahmed, Al Sayegh Hachem, and Nouini Yassine. "Primary Testicular Diffuse Large B-cell Lymphoma Presenting in a Young Adult." Saudi Journal of Medicine 7, no. 6 (June 15, 2022): 342–45. http://dx.doi.org/10.36348/sjm.2022.v07i06.002.

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Primary testicular lymphoma is a rare type of extranodal non-Hodgkin lymphoma (NHL), its positive diagnosis is based on histopathological findings. Treatment modalities consist of surgical excision, chemotherapy, and radiation therapy but the accurate procedures are not standardized. The authors report a new case of primary testicular lymphoma, and we discuss its diagnostic and therapeutic aspects. Sperm cryopreservation was carried out. The patient was started on chemotherapy with cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (CHOP) regime.

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9

Horsanalı, Mustafa Ozan, Gürol Akan, and Saniye Sevim Tuncer. "Primary Testicular Diffuse Large B-cell Lymphoma: A Rare Case Report." Journal of Urological Surgery 8, no. 3 (September 1, 2021): 220–22. http://dx.doi.org/10.4274/jus.galenos.2021.2021.0009.

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10

Tsili, A. C., M. I. Argyropoulou, D. Giannakis, N. Sofikitis, and K. Tsampoulas. "Primary diffuse large B-cell testicular lymphoma: magnetic resonance imaging findings." Andrologia 44 (October 11, 2011): 845–47. http://dx.doi.org/10.1111/j.1439-0272.2011.01236.x.

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11

Guler, Yavuz, Burak Ucpinar, and Akif Erbin. "Diffuse Large B-cell Lymphoma of Testis: a Case Report and Current Literature Review." Folia Medica 62, no. 1 (March 31, 2020): 200–203. http://dx.doi.org/10.3897/folmed.62.e47874.

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Introduction: Testicular cancers detected in older males are mostly testicular lymphomas. Primary testicular lymphoma (PTL) is a rare, clinically aggressive form of extranodal lymphoma. In population-based studies, the  incidence of PTL is 0.09-0.26/100.000. The vast majority of PTL are diffuse large B-cell lymphoma (DLBCL).   Case presentation: We present a case of PTL diagnosed in a 68-year-old male patient and also, we discuss the incidence, clinical presentation, prognostic factors and management of this rare pathology in the light of current literature. Histopathological and immunohistochemical exams of the patient confirmed the diagnosis of DLBCL after radical orchiectomy. According to the internal prognostic index (IPI), patients’ IPI score was evaluated as 5 and according to Ann Arbor staging, patients’ stage was interpreted as grade 3E. Cyclophosphamide, vincristine, etoposide, and prednisolone chemotherapy was planned for the patient and until now, the patient received his first chemotherapy regimen.   Discussion: Primary testicular lymphoma should be kept in mind for every patient who admits with a testicular mass, especially in advanced age.  Misinterpreatation of the clinical findings can delay the definitive diagnosis. Primary testicular lymphoma should be managed with a multi-disciplinary team including urologists, medical and radiation oncologists. 

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12

Batlevi, Connie, Franck Rapaport, Lu Wang, Andrew M. Intlekofer, Amanda R. Copeland, Achim A. Jungbluth, Anne Reiner, et al. "Distinctive Genomic Alterations in Testicular Diffuse Large B Cell Lymphoma." Blood 126, no. 23 (December 3, 2015): 3655. http://dx.doi.org/10.1182/blood.v126.23.3655.3655.

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Abstract Background: Primary testicular diffuse large B cell lymphoma (DLBCL) is an uncommon malignancy portending a poor prognosis with increased risk of central nervous system disease. Phenotypically, most primary testicular lymphomas have a non-germinal center B-cell like (non-GCB) origin. To identify the genetic characteristics of testicular DLBCL, we evaluated DNA copy number and mutational profiling using SNP array and a next generation targeted sequencing platform. Methods: Twelve cases of testicular DLBCL with patient consent for tissue specimens and sufficient tumor tissue were retrospectively identified. Cell of origin was determined by Hans immunohistochemistry (IHC) model. We performed a custom, targeted deep-sequencing assay of 585 cancer genes (HemePACT) on matched tumor and normal pairs. Barcoded pools were sequenced on Illumina HiSeq 2500 to 500-1000x coverage per sample Sequencing was compared to a matched normal tissue control (N=10) if available or alternatively a pooled normal tissue control. We excluded all mutations either present at a high variant allele frequency in the matching germline samples, present in two databases of inherited variants (DBSNP and 1000 genomes) or present in one databases of inherited variants and absent from COSMIC. We evaluated copy number and allelic imbalance with an Affymetrix OncoScan SNP-array. IHC was performed for select genes. Results were compared to a panel of non-testicular DLBCL previously described (N=78). Results: The median age of the patients was 55.1 years (range 21.9-77.9). Patients had clinical stage IE (50%) and IV (50%) disease. All samples were sequenced from pre-treatment biopsies. Eleven of 12 patients were initially treated with R-CHOP chemotherapy, intrathecal methotrexate and radiation. Treatment history for one patient was unknown. We identified 124 mutations in 12 cases of testicular DLBCL. The most common mutation was MYD88 occurring in 10/12 patients (83%) with 6 mutations in non-GCB and 2 mutations in GCB (Fig 1A). The MYD88 L265P allele was most frequent and occurred in 9/12 patients (75%). The median MYD88 L265P variant allele frequency was 0.36 (range 0.07-0.51) with normal copy number status at that loci. In contrast, MYD88 mutations were less frequent in DLBCL without testicular involvement, 12/37 (32%) non-GCB and 3/41 (7%) GCB DLBCL, p<0.05 by Fisher's t-test (Fig 1B). Furthermore, mutations in CD79B were significantly more common in testicular DLBCL (5/12, 42%) versus non-testicular DLBCL (7/78, 9%). Concurrent mutations affecting the BCR receptor pathway was noted in 10/12 patients (83%): CD79B (5/12, 42%), TNFAIP3 (1/12, 8%), CARD11 (1/12, 8%) (Fig 1A). Frequency of TNFAIP3, CARD11 was not statistically significant between testicular versus non-testicular DLBCL. Other commonly mutated pathways include epigenetics (10/12, 83%) and immune recognition (6/12, 50%). Deregulation of immune recognition was noted by HLA-A (3/12, 25%) and beta-2-microglobulin (2/12, 17%) mutations as well as loss of HLA locus in 8/10 samples (80%) (Fig 1C). IHC revealed 6/10 (60%) cases with no MHC Class I expression of the tumor cells. MHC Class I negative cases also lacked B2M expression (3/6) or displayed mislocalization of B2M to the cytosol (3/6). PD-L1 was expressed by lymphoma cells as assayed by IHC in 1/10 (10%) cases but no amplification or mutation was identified. No copy gains of the 9p24.1, PD-1, PD-L1, PD-L2 locus were identified via HemePACT or SNP array. Although mutations in CDKN2A/B were not identified in HemePACT, SNP array confirmed loss of CDKN2A/B at the 9p21 loci in 3/10 cases (30%). Conclusion: Targeted genomic sequencing and SNP array analysis have identified a distinctive genetic pattern with alterations of MYD88, BCR pathway mutations, and immune recognition deficiency in testicular DLBCL compared to non-testicular DLBCL. These findings may have implications in guiding the design of future treatment strategies for testicular DLBCL. Disclosures Younes: Novartis: Research Funding; Janssen: Honoraria; Johnson and Johnson: Research Funding; Takeda Millenium: Honoraria; Seattle Genetics: Honoraria, Research Funding; Sanofi-Aventis: Honoraria; Bayer: Honoraria; Bristol Meyer Squibb: Honoraria; Curis: Research Funding; Celgene: Honoraria; Incyte: Honoraria.

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13

Robertus, JanLukas, Geert Harms, Tjasso Blokzijl, Daphne de Jong, Marije Booman, Stefano Rosati, Ed Schuuring, Philip M. Kluin, and Anke van den Berg. "MicroRNAs Specific for Immune-Privileged Diffuse Large B-Cell Lymphoma." Blood 110, no. 11 (November 16, 2007): 1566. http://dx.doi.org/10.1182/blood.v110.11.1566.1566.

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Abstract Introduction Primary diffuse large B-cell lymphomas (DLBCL) constitute a heterogeneous group of tumors with a great diversity in both clinical presentation and outcome. Besides nodal DLBCL, about 40% of these tumors present in different extranodal sites, both immune privileged sites such as the testis and the central nervous system (PCNSL) but also non immune privileged sites such as bone, stomach, skin and mediastinum. Remarkably each of these sites show a marked divergence in biological behavior. Recent studies have shown that certain non-coding short RNAs (22nt) called miRNAs may play a role in the pathogenesis of DLBCL. These miRNAs posttrancriptionally down regulate expression of genes. Aim of study To examine the expression levels of selected miRNAs in different DLBCL sites. Methods and Materials 51 cases of Ann Abour stage I and II primary DLBCL were divided into 4 groups; 19 nodal cases, 11 non-immune privileged site-associated (non-IP) extranodal cases, 9 PCNSL, and 12 testicular DLBCL. Each case was classified GCB or non-GCB using the algorithm as described by Hans et al. 13 miRNAs were selected from current literature on the basis of their involvement in B-cell lymphoma (miR-15, -16, -21, -221, -155, - 181a, -18a, -19, -20a, 17-3p, -17-5p and -92). The expression levels of the mature microRNAs were determined by qRT-PCR using Taqman miRNA assays. Results were compared by using 2−ΔCt and 2−ΔΔCt. Differences in expression levels between the four groups was tested using ANOVA. Results Of the selected microRNAs, miR-127, miR-17-5p and miR-221 show a significant difference in expression level between the immune privileged site-associated DLBCL (IP-DLBCL) and nodal DLBCL. Both miR-17-5p (p=0.0003) and miR-221 (p=0.0032) show an increased expression level in PCNSL compared to nodal DLBCL and miR-127 shows a significant increased level in testicular DLBCL compared to nodal (p=0.0011) and non-IP (p=0.0393) DLBCL. Also of interest is the fact that miR-17-5p and miR-127 show a significant difference in the level of expression between both PCNSL and testicular DLBCL. MiR-155 shows no significant difference in expression levels between nodal and extranodal DLBCL. Analysis on the basis of GCB and non-GCB classification is currently being undertaken. Conclusion In PCNSL miR-17-5p and miR-221 are specifically increased whereas miR-127 shows a specifically higher expression in testicular DLBCL when compared to non-IP and nodal DLBCL. Also PCNSL and testicular DLBCL differ in expression of miR-17-5p and miR-127. In contrast to previous reports miR-155 does not show any significant difference between nodal and extranodal groups. This may be caused by the selection of stage I or II primary DLBCL in contrast to previous publications which used a more heterogeneous group of DLBCL.

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14

Li, Dan, Peng Xie, and Can Mi. "Primary testicular diffuse large B-cell lymphoma shows an activated B-cell-like phenotype." Pathology - Research and Practice 206, no. 9 (September 2010): 611–15. http://dx.doi.org/10.1016/j.prp.2010.04.005.

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15

Pollari, Marjukka, Suvi-Katri Leivonen, and Sirpa Leppä. "Testicular Diffuse Large B-Cell Lymphoma—Clinical, Molecular, and Immunological Features." Cancers 13, no. 16 (August 11, 2021): 4049. http://dx.doi.org/10.3390/cancers13164049.

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Primary testicular lymphoma is a rare lymphoma entity, yet it is the most common testicular malignancy among elderly men. The majority of the cases represent non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) with aggressive clinical behavior and a relatively high relapse rate. Due to the rareness of the disease, no randomized clinical trials have been conducted and the currently recognized standard of care is based on retrospective analyses and few phase II trials. During recent years, the tumor microenvironment (TME) and tumor-related immunity have been the focus of many tumor biology studies, and the emergence of targeted therapies and checkpoint inhibitors has significantly modulated the field of cancer therapies. Testicular DLBCL (T-DLBCL) is presented in an immune-privileged site of the testis, and the roles of NF-κB pathway signaling, 9p24.1 aberrations, and tumor-infiltrating immune cells, especially immune checkpoint expressing lymphocytes and macrophages, seem to be unique compared to other lymphoma entities. Preliminary data on the use of immune checkpoint inhibitors in the treatment of T-DLBCL are promising and more studies are ongoing.

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16

Weissinger, Stephanie Ellen, Peter Moeller, Ralf Marienfeld, Johannes Bloehdorn, and Andreas Viardot. "Primary Extranodal Diffuse Large B-Cell Lymphomas Are Enriched for Mutations in MYD88 and CD79B." Blood 132, Supplement 1 (November 29, 2018): 1701. http://dx.doi.org/10.1182/blood-2018-99-114551.

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Abstract Introduction: Diffuse large B-cell lymphomas (DLBCLs) with mutations in MYD88 and CD79B are a distinct molecular subentity according to recent analysis ("MCD-type" according to R. Schmitz et al., N Engl J Med 2018; and partially "cluster 5" according to B. Chapuy et al., Nature Medicine 2018). Both mutations were found particularly in specific anatomical localizations. Methods: To evaluate the incidence of MYD88 and CD79B mutations in primary extranodal DLBCL, we analyzed 111 tumor specimens of 99 patients. We performed targeted resequencing analysis to detect MYD88, CD79B, CARD11 and BTK mutations. Results: MYD88 mutations were frequently found in primary CNS lymphoma (67%), lymphoma of Waldeyer´s ring and paranasal sinuses (ENT) (44%), breast (75%), testicular (60%) and cutaneous (50%); the majority of mutations (89%) were located on L265P. CD79B mutations were frequent in CNS lymphoma (57%), lymphoma of ENT (52%) and breast lymphoma (50%). Both mutations occur simultaneously in CNS lymphoma (48%) and ENT lymphoma (33%). CARD11 mutations were frequently found in CNS lymphoma (33%) and in ENT lymphoma (26%). BTK mutations were found rarely, with the highest frequency (11%) in ENT lymphoma. Conclusion: Both, mutations in CD79B and MYD88 are frequent in primary extranodal lymphoma particularly in CNS lymphoma, lymphoma of Waldeyer's ring and paranasal sinuses, testicular, cutaneous and breast lymphoma. These findings may contribute to establish targeted therapeutic intervention of B-cell signaling in this subentity. Disclosures Weissinger: Bristol-Myers Squibb: Research Funding. Viardot:BMS: Consultancy, Honoraria; Gilead Kite: Consultancy, Honoraria; Amgen: Consultancy; Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

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17

Mazloom, Ali, Nathan Fowler, Puneeth Iyengar, and Bouthaina S. Dabaja. "Primary Testicular Diffuse Large B-Cell Lymphoma, M.D. Anderson Cancer Center Experience." Blood 114, no. 22 (November 20, 2009): 2697. http://dx.doi.org/10.1182/blood.v114.22.2697.2697.

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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.

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18

Vega, Francisco, L. Jeffrey Medeiros, and Lynne V. Abruzzo. "Primary Paratesticular Lymphoma." Archives of Pathology & Laboratory Medicine 125, no. 3 (March 1, 2001): 428–32. http://dx.doi.org/10.5858/2001-125-0428-ppl.

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Abstract Non-Hodgkin lymphoma arising in the paratesticular organs without testicular involvement is rare. In most previously reported cases, the classification systems that were used are now outdated and/or immunologic studies were not done. We report the clinical and pathologic features of 2 cases of non-Hodgkin lymphoma arising in the epididymis and the spermatic cord. Patient 1 was a 35-year-old man who presented with a painless scrotal mass. Patient 2 was a 61-year-old man who presented with a right inguinal mass. Orchiectomy performed in both patients revealed a mass confined to the epididymis in patient 1 and to the spermatic cord in patient 2. Histologic examination in both cases revealed diffuse large cell lymphoma, and immunohistochemical studies supported B-cell lineage. Subsequent staging studies showed no other site of disease in patient 1 and an isolated mass anterior to the right psoas muscle in patient 2. Malignant lymphoma involving testicular adnexal structures without involvement of the testis is extremely uncommon. To our knowledge, only 6 cases confined to the epididymis and 12 cases confined to the spermatic cord have been reported previously.

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Al-Abbadi, Mousa A., Eyas M. Hattab, Musleh Tarawneh, Attilio Orazi, and Thomas M. Ulbright. "Primary Testicular and Paratesticular Lymphoma: A Retrospective Clinicopathologic Study of 34 Cases With Emphasis on Differential Diagnosis." Archives of Pathology & Laboratory Medicine 131, no. 7 (July 1, 2007): 1040–46. http://dx.doi.org/10.5858/2007-131-1040-ptapla.

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Abstract Context.—Recent reports indicate the rate of primary testicular lymphomas is on the rise and misdiagnosis can still occur. Objective.—To review and investigate the clinicopathologic features of primary testicular lymphoma with emphasis on the differential diagnosis. Discussion about the issue of misdiagnosis is also presented. Design.—Retrospective review of pathology archives in 3 medical centers for cases fulfilling criteria of primary testicular lymphoma or paratesticular lymphoma was carried out. Clinicopathologic and immunohistochemical features were studied and analyzed. Results.—The search identified 34 cases. Patients ranged from 4 to 87 years of age (mean, 55 years). All presented with a testicular/paratesticular mass and were stage I. The masses ranged from 2.5 to 13 cm (mean, 5.6 cm). Microscopically, the tumors often had an intertubular growth pattern or diffuse arrangement of predominantly large cells with pleomorphic, twisted nuclei and small nucleoli. Mitotic activity was brisk and apoptotic bodies were abundant. Thirty-two tumors were classified as diffuse large cell lymphomas; immunophenotype was determined in 21 of these and all were of B-cell type. The median survival was 96 months. The rate of initial misdiagnosis was unexpectedly high (5 cases, 15%). Conclusions.—Most cases of primary testicular lymphoma fall into the broad category of diffuse large cell lymphoma and the majority are B-cell type with particularly high proliferative activity when characterized by appropriate immunophenotyping. Misdiagnosis can occur, especially in those cases in which presentation occurs at an age similar to that for germ cell tumors, showing the need for caution and appropriate immunostaining when a testicular neoplasm has an atypical appearance for a germ cell tumor.

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Cao, Bing, Dong-Mei Ji, Xiao-Yan Zhou, Ti-Ping Zhao, Ye Guo, Zhong-Hua Wang, Jun-Ning Cao, Xi-Chun Hu, and Xiao-Nan Hong. "A clinical analysis of primary testicular diffuse large B-cell lymphoma in China." Hematology 16, no. 5 (September 2011): 291–97. http://dx.doi.org/10.1179/102453311x13085644680221.

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21

Miao, Yi, Lei Fan, Wei Xu, and Jianyong Li. "Laterality and Survival Outcomes in Patients with Primary Testicular Diffuse Large B Cell Lymphoma." Blood 134, Supplement_1 (November 13, 2019): 2903. http://dx.doi.org/10.1182/blood-2019-129952.

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Introduction: Patients with diffuse large B cell lymphoma (DLBCL) arising from the testis have a relatively poor outcome. Age, stage and use of radiation and surgery are important prognostic factors in patients with primary testicular DLBCL. Additionally, the study by Gundrum et al suggested that laterality was also an important predictor of outcomes in patients with primary testicular DLBCL, with left side involvement being associated poorer prognosis. However, most patients included in the study by Gundrum et al were diagnosed in the pre-rituximab era, therefore, the role of laterality in the prognostification of patients with primary testicular DLBCL remains to be explored. In this study, the Surveillance, Epidemiology, and End Results (SEER) database was used to evaluate the prognostic roles of laterality in patients with primary testicular DLBCL. Methods: Data from the SEER 18 Registries were used to conduct this study. Cases with newly-diagnosed testicular (International Classification of Diseases for Oncology, 3rd Edition [ICDO-3] codes 9823, sites: C62.0-C63.2) in the time period between 1973 and 2015 were included. Exclusion criteria included history of cancer, unknown laterality, unknown survival data and unknown cause of death. For each case we included age at the time of diagnosis, laterality (left, right, bilateral), SEER cause-specific death classification, survival months and vital status. Overall survival (OS) was defined as time from diagnosis to death or last follow-up and cancer-specific survival (CSS) was calculated as time from diagnosis to death from DLBCL or last follow-up. Survival curves were plotted by the Kaplan-Meier method and the log-rank test was used for comparison. P value was 2-sided and P<0.05 was considered to be statistically significant. All analyses were conducted using Graphpad Prism 6. Results: A total of 1213 patients were included in this analysis. The median follow-up was 43 months (interquartile range[IQR]: 13-90 months). Of these patients, 372 patients were diagnosed from 1973-2000 (pre-rituximab era) and 841 patients were diagnosed from 2001-2015 (rituximab era). We found that patients with bilateral testis involvement had a significantly decreased CSS (median CSS: 53 vs. 142 months, P=0.0035) and OS (median OS: 32 vs. 77 months, P=0.0008) compared with those with unilateral involvement. Patients with left-side involvement had a similar CSS (median CSS: 136 vs. 153 months, P=0.2997) and OS (median OS: 76 vs. 80 months, P=0.7360) compared to those with right-side involvement. For patients with left-side involvement, patients diagnosed in the rituximab era had a significantly longer CSS(hazards ratio[HR]: 0.4140, 95% confidence interval[CI]: 0.3065 to 0.5593, P<0.0001) (Figure 1A)and OS (HR: 0.5522, 95% CI: 0.3926 to 0.6340, P<0.0001 ) (Figure 1B) than those diagnosed in the pre-rituximab era. For patients with right-side involvement, patients diagnosed in the rituximab era had a significantly longer CSS (HR: 0.7146, 95% CI: 0.5218 to 0.9029, P=0.0057) (Figure 1A)and OS (HR: 0.7116, 95% CI: 0.5407 to 0.8311, P=0.0011) (Figure 1B)than those diagnosed in the pre-rituximab era. The different HRs suggested patients with left-side primary testicular DLBCL benefited more from the introduction of rituximab. Additionally, the improvement in median OS from the pre-rituximab era to the rituximab era was 68 months for patients with left-side involvement but only 35 months for patients with right-side involvement. Conclusion: our study demonstrated that laterality was not a prognostic factor for patients with primary testicular DLBCL. And the improvement in the prognosis from pre-rituximab era to rituximab era was more remarkable in primary testicular DLBCL patients with left-side involvement than those with right-side involvement. These data suggest primary testicular DLBCL from different sides had different responses to therapy and may have different biological characteristics. Figure 1 Disclosures No relevant conflicts of interest to declare.

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Olivares, Eduardo Poblano, and Jorge L. Olmos Gonzalez. "Testicular lymphoma in inguinal hernia." International Journal of Research in Medical Sciences 9, no. 9 (August 25, 2021): 2824. http://dx.doi.org/10.18203/2320-6012.ijrms20213206.

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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.

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Chatterjee, Debarghya, Rakesh Vakil, and Richa Jindal. "Testicular non-Hodgkin’s lymphoma – a rare tumor." International Surgery Journal 8, no. 8 (July 28, 2021): 2509. http://dx.doi.org/10.18203/2349-2902.isj20213159.

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Primary lymphoma of the testis is an exceedingly rare disease. We present a case of a 65 years old gentleman who presented with a brief history of testicular pain. Imaging studies and serum tumour markers indicated a testicular lesion of suspicious aetiology. High inguinal orchidectomy was performed. Histopathology and immunohistochemistry revealed diffuse large B-cell lymphoma. Positron emission tomography (PET) scan revealed a metabolically active retroperitoneal lymph node in aortocaval location. Subsequently he underwent chemotherapy with Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen plus intravenous Methotrexate, following which PET scan showed disappearance of the previously detected metabolically active lesion.

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Ho, J. C., J. Reddy, A. Mazloom, P. K. Allen, S. A. Milgrom, G. L. Smith, L. J. Medeiros, et al. "Radiation Therapy Improves Outcomes in Patients With Primary Testicular Diffuse Large B-cell Lymphoma." International Journal of Radiation Oncology*Biology*Physics 96, no. 2 (October 2016): S20. http://dx.doi.org/10.1016/j.ijrobp.2016.06.062.

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Twa, David D. W., Anja Mottok, Kerry J. Savage, and Christian Steidl. "The pathobiology of primary testicular diffuse large B-cell lymphoma: Implications for novel therapies." Blood Reviews 32, no. 3 (May 2018): 249–55. http://dx.doi.org/10.1016/j.blre.2017.12.001.

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SHAH, SHIVANI, SUSHANTH SREENIVASAN, PRAGNAN KANCHARLA, CYRUS KHAN, and YAZAN SAMHOURI. "Primary Testicular Lymphoma: Single Center Experience." Cancer Diagnosis & Prognosis 3, no. 2 (March 3, 2023): 139–44. http://dx.doi.org/10.21873/cdp.10192.

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Background/Aim: Primary testicular lymphoma (PTL) is an exceedingly rare and aggressive form of non-Hodgkin’s lymphoma; the most common subtype is diffuse large B-cell (DLBCL). Standard treatment includes orchiectomy, chemotherapy, central nervous system (CNS) prophylaxis, and prophylactic radiation to the contralateral testis. PTL can reoccur years after complete remission. Treatment to immune sanctuary sites, CNS and contralateral testis, is crucial in preventing relapse. There are limited data characterizing this entity and this study aimed to add to existing literature. Patients and Methods: This descriptive retrospective study characterized twelve patients with PTL from years 2010-2021 at Allegheny Health Network. Their demographic data, prognostic factors, treatment regimens, and relapse sites (if any) were tabulated. The mean progression-free survival (PFS) was calculated to describe our experience in treating PTL. Results: Twelve patients were diagnosed with PTL; 10/12 (83.33%) patients were diagnosed with ABC PTL-DLBCL. Median age of diagnosis was 67 years. Eight of the 12 (66.66%) were African American, 4/12 (33.33%) were Caucasian. At the time of diagnosis, 8/12 (66.66%) patients presented with an elevated lactate dehydrogenase (LDH) and 8/12 (66.66%) presented with a left testicular mass. Most were treated with R-CHOP (9/12), intrathecal methotrexate (IT-MTX) (10/12), and radiation to the contralateral testis (9/12). Three of the twelve (25%) patients relapsed. Median time to relapse was 8 months. Mean PFS was 50.417 months. Conclusion: We discuss our experience in treating PTL with RCHOP, IT-MTX, and irradiation to the contralateral testis and add to the limited pre-existing data that exist.

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Habermann, Thomas M. "Updates in the Management of Early-Stage Diffuse Large B-Cell Lymphoma." Journal of the National Comprehensive Cancer Network 19, no. 11.5 (November 2021): 1324–26. http://dx.doi.org/10.6004/jnccn.2021.5108.

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Several important updates have emerged in the management of early-stage diffuse large B-cell lymphoma. Three trials resulted in the approval of rituximab + cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) for use in these patients internationally. Furthermore, studies have been initiated to determine whether 4 or 6 cycles of this regimen should be administered without radiation therapy (RT). Six cycles of R-CHOP plus central nervous system (CNS) prophylaxis and prophylactic testicular RT are recommended for patients with extranodal disease occupying the testicles. Although controversial, there is a reasonable consensus in the literature to consider 6 cycles of R-CHOP plus involved-site RT and CNS prophylaxis for patients with extranodal disease of the breast. Patients with primary bone and gastric extranodal disease do not seem to derive a significant survival benefit from RT. Molecular subtype evaluations may change treatment approaches.

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Conrad, Amber L., and Ronald S. Go. "Contralateral testicular relapse after prophylactic radiation in a patient with primary testicular diffuse large B-cell lymphoma." European Journal of Haematology 83, no. 6 (December 2009): 603–5. http://dx.doi.org/10.1111/j.1600-0609.2009.01327.x.

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Mousa, M., and A. Meshref. "354P Survival trends of primary testicular diffuse large B-cell lymphoma: A population-based study." Annals of Oncology 27 (December 2016): ix110. http://dx.doi.org/10.1016/s0923-7534(21)00512-3.

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Kumar, YSunil, BanavasiS Girisha, KJayaprakash Shetty, HL Kishan Prasad, BD Impana, and Anuja Dasgupta. "Rare case of primary cutaneous diffuse large B-cell lymphoma-leg type with testicular infiltration." Journal of Cancer Research and Therapeutics 11, no. 4 (2015): 1046. http://dx.doi.org/10.4103/0973-1482.140786.

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Nakayama, Shoko, Taiji Yokote, Kazuki Iwaki, Yuji Hirata, Uta Nishiwaki, Toshikazu Akioka, Takuji Miyoshi, Yuki Masuda, Motomu Tsuji, and Toshiaki Hanafusa. "Multiple cytokine- and chemokine-producing primary testicular diffuse large B-cell lymphoma, not otherwise specified." Leukemia Research 36, no. 8 (August 2012): e171-e174. http://dx.doi.org/10.1016/j.leukres.2012.04.032.

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Totonchi, Kameel F., George Engel, Elliot Weisenberg, Douglas P. Rhone, and William R. Macon. "Testicular Natural Killer/T-Cell Lymphoma, Nasal Type, of True Natural Killer–Cell Origin." Archives of Pathology & Laboratory Medicine 126, no. 12 (December 1, 2002): 1527–29. http://dx.doi.org/10.5858/2002-126-1527-tnktcl.

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Abstract The majority of primary testicular lymphomas are of B-cell type. Other primary lymphomas are rarely encountered in the testes. Natural killer (NK)/T-cell lymphomas of nasal type are aggressive extranodal lymphomas associated with Epstein-Barr virus infection that are usually encountered in the upper aerodigestive tract. They also occur in the skin, soft tissue, and colon. Primary testicular NK/T-cell lymphomas are rarely reported. We describe the case of a 66-year-old Korean man who presented with right-sided painless testicular enlargement and underwent radical orchiectomy. Histologic examination revealed an angiocentric and angioinvasive infiltrate of medium to large tumor cells with moderately abundant pale pink cytoplasm and folded and indented pleomorphic nuclei. Paraffin immunohistochemical studies showed positivity of the tumor cells for CD45, TIA-1, granzyme B, CD56, and CD3ɛ. In situ hybridization showed diffuse positivity for Epstein-Barr virus–encoding RNA. The results of gene rearrangement studies for the γ chain of the T-cell receptor were negative. The results of paraffin immunohistochemical studies for CD20, CD8, CD45RO, beta f1, and ALK-1 were negative. An extensive workup showed no evidence of lymphoma outside the testes. We report a rare case of primary testicular NK/T-cell lymphoma of the nasal type of true NK-cell origin.

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Haslett, Nicholas, Adam Ulano, and John C. DeWitt. "Testicular Lymphoma manifesting as neurological symptoms due to secondary neurolymphomatosis: A case report." Case Reports in Clinical Pathology 8, no. 1 (January 27, 2021): 1. http://dx.doi.org/10.5430/crcp.v8n1p1.

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Neurolymphomatosis is a rare manifestation of lymphoma presenting as diffuse invasion and involvement of peripheral and spinal nerves. Due to the common presenting symptomatology of neurologic complaints localizing to the affected peripheral nerve, lymphoma as the underlying etiology can be diffificult to diagnose. Here we present the case of a gentleman presenting with right extremity neuropathic symptoms, subsequently discovered to have diffuse large B-cell lymphoma of testiticular orgin after nerve biopsy revealed neurolymphomatous involvement of a spinal nerve. This case highlights the importance of the consideration of neurolymphomatosis in the work up of neuropathic symptoms, as well as the full assessment for the site of primary involvement.

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Yang, Jing, Sha Zhu, Fuwen Pang, Miao Xu, Yiting Dong, Jianqi Hao, and Xuelei Ma. "Functional Parameters of 18F-FDG PET/CT in Patients with Primary Testicular Diffuse Large B-Cell Lymphoma." Contrast Media & Molecular Imaging 2018 (September 27, 2018): 1–7. http://dx.doi.org/10.1155/2018/8659826.

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Fluorine-18 fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT), a hybrid imaging technique that simultaneously provides functional and anatomical information, has been reported to be useful in lymphoma. The present study was to evaluate the functional parameters of 18F-FDG PET/CT in patients with testicular diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed medical records of 5095 patients with lymphoma who treated at West China Hospital between March 2003 and January 2017, and selected patients with 18F-FDG PET/CT findings and subsequently biopsy confirmed the invasion of testis with DLBCL. Maximum standardized uptake values (SUVmax), peak standardized uptake values (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the patients were measured. We evaluated the characteristics of 18F-FDG PET/CT in this population. Six patients ranged in age from 37 to 73 years (median age, 58 years) were included in the analysis. The mean SUVmax was 11.09 and varied between 7.20 and 19.75; mean SUVpeak was 9.56 and ranged between 6.79 and 14.39. In addition, mean MTV 42% was 18.4 and varied between 1.3 and 61.6; mean MTV 2.5 was 34.7 and varied significantly between 1.6 and 141.9. With regard to TLG, mean TLG 42% was 168.906 and ranged from 7.514 to 687.004, while mean TLG 2.5 was 253.972 and ranged from 8.400 to 1127.802. In conclusion, 18F-FDG PET/CT scan is a useful tool in patients with testicular DLBCL. SUV, MTV, and TLG may vary a lot in different patients. SUVmax of testicular DLBCL lesion is relatively higher than that of normal testis. Also, we provided a set of MTV and TLG data and firstly showed their significant correlation with overall survival, which indicated a potential prognostic value of MTV and TLG. However, studies with larger population are needed to confirm these findings.

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Muniesa, Cristina, Ramon M. Pujol, M. Teresa Estrach, Fernando Gallardo, M. Pilar García-Muret, Josefina Climent, Antonio Salar, and Octavio Servitje. "Primary cutaneous diffuse large B-cell lymphoma, leg type and secondary cutaneous involvement by testicular B-cell lymphoma share identical clinicopathological and immunophenotypical features." Journal of the American Academy of Dermatology 66, no. 4 (April 2012): 650–54. http://dx.doi.org/10.1016/j.jaad.2011.03.031.

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Kraan, W., M. van Keimpema, H. M. Horlings, E. J. M. Schilder-Tol, M. E. C. M. Oud, L. A. Noorduyn, P. M. Kluin, M. J. Kersten, M. Spaargaren, and S. T. Pals. "High prevalence of oncogenic MYD88 and CD79B mutations in primary testicular diffuse large B-cell lymphoma." Leukemia 28, no. 3 (November 20, 2013): 719–20. http://dx.doi.org/10.1038/leu.2013.348.

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Park, Byeong-Bae, Jong Gwang Kim, HyeonSeok Eom, Hyo Jin Kim, Hyuck Chan Kwon, Sung Yong Oh, Jung Hun Kang, et al. "Clinical Features and Treatment Outcomes of Primary Testicular Lymphoma." Blood 108, no. 11 (November 16, 2006): 4670. http://dx.doi.org/10.1182/blood.v108.11.4670.4670.

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Abstract We investigated clinical features and clinical outcomes of patients with primary testicular non-Hodgkin lymphoma (NHL) between 1996 and 2006. Thirty-eight cases were identified from clinical records. The median age was 59 years (range 41–81). Disease was classified as stages I in 13 cases, stages II in 15 and stages III-IV in 10. Diffuse large B-cell lymphoma was diagnosed in 92% of cases. All patients received orchiectomy. Twenty-three (61%) had orchiectomy and chemotherapy, 13 (34%) had orchiectomy, chemotherapy and involved field radiotherapy. All chemotherapy regimens which were used to patients in this study contained an anthracycline. Central nervous system (CNS) prophylaxis was performed in 6 (16%) patients and 10 (26%) patients were received prophylactic irradiation or surgery on the contralateral testis. In 33 evaluable patients, 4 (12%) had immediate disease progression following orchiectomy or on systemic treatment. A complete response was seen in the remaining 25 (76%) patients, irrespective of treatment modality. The median duration of follow-up was 25 months (range 2.5–122). Recurrence occurred in 18 patients and the most frequent site (45%) was the CNS: 4 in brain parenchyma, 3 in meninges, and 1 in both. Nine (36%) patients relapsed following a complete response and median time to relapse was 10 months. Overall median progression free survival (PFS) was 21 months. Twelve (32%) patients were died during follow-up: 10 died of causes related to their lymphoma and 2 were treatment-related mortality. Estimated median overall survival (OS) was 45 months for the entire patients. Significant survival differences between low/low intermediate and high intermediate/high risk of IPI were observed in OS (p=0.001). Primary testicular NHL was frequent in older patients, and has a poor prognosis although large proportion of this disease was loco-regional stage. Most of patients have died of disease related causes and their frequent relapse site was brain or meninges. Therefore, additional CNS prophylaxis including cranial irradiation and intrathecal chemotherapy to chemotherapy and involved field irradiation after orchiectomy should be considered as an effective treatment modality for improving survival.

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Sutrisno, Sony. "Imaging Diagnosis of Testicular Lymphoma in Young Male Patient: Incidental Finding in Ultrasonography." Open Access Macedonian Journal of Medical Sciences 11, no. C (January 18, 2023): 30–32. http://dx.doi.org/10.3889/oamjms.2023.11335.

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BACKGROUND: Ultrasonography is a common diagnostic procedure in patients with testicular abnormalities. Primary testicular lymphoma (PTL) is rarely discovered and is more common among elderly populations. CASE PRESENTATION: This case describes a young male patient with a history of painless testicular enlargement. Ultrasonography reveals an incidental finding of hypoechoic echo structural mass and increased vascularity using color Doppler ultrasonography. The further pathological examination discovered the findings indicative of a non-Hodgkin, diffuse, and large B-cell lymphoma. These distinctive features should be helpful in suggesting a diagnosis of PTL on imaging. CONCLUSION: PTL is a rare and aggressive extranodal NHL. Despite its low incidence, it is an extremely rare testicular cancer at a young age. Careful ultrasound imaging examination should be applied in patients with testicular enlargement. The presence of hypoechoic echostructural and an increase in vascularity should be considered for the possibility of a diagnosis of primary testicular tumor.

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Zucca, E., A. Conconi, T. I. Mughal, A. H. Sarris, J. F. Seymour, U. Vitolo, R. Klasa, et al. "Patterns of Outcome and Prognostic Factors in Primary Large-Cell Lymphoma of the Testis in a Survey by the International Extranodal Lymphoma Study Group." Journal of Clinical Oncology 21, no. 1 (January 1, 2003): 20–27. http://dx.doi.org/10.1200/jco.2003.11.141.

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Purpose: To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell lymphomas (DLCL). Patients and Methods: A retrospective international survey of 373 patients with primary testicular DLCL. Results: Most patients presented with localized disease (stage I to II), and the median age at diagnosis was 66 years (range, 19 to 91 years). Anthracycline-based chemotherapy was administered to 255 patients (68%), and prophylactic intrathecal chemotherapy was given to 68 patients (18%); 133 patients (36%) received prophylactic scrotal radiotherapy. Median overall survival was 4.8 years, and median progression-free survival was 4 years. The survival curves showed no clear evidence of a substantial proportion of cured patients. A favorable international prognostic index score (IPI), no B-symptoms, the use of anthracyclines, and prophylactic scrotal radiotherapy were significantly associated with longer survival at multivariate analysis. However, even for patients with stage I disease and good-risk IPI, the outcome seems worse than what was reported for DLCL at other sites. At a median follow-up of 7.6 years, 195 patients (52%) had relapsed. Extranodal recurrence was reported in 140 cases. Relapses in CNS were detected in 56 patients (15%) up to 10 years after presentation. A continuous risk of recurrence in the contralateral testis was seen in patients not receiving scrotal radiotherapy. Conclusion: Testicular DLCL is characterized by a particularly high risk of extranodal relapse even in cases with localized disease at diagnosis. Anthracycline-based chemotherapy, CNS prophylaxis, and contralateral testicular irradiation seem to improve the outcome. Their efficacy is under evaluation in a prospective clinical trial.

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Kim, Jeongseok, Dok Hyun Yoon, Inkeun Park, Shin Kim, Jung Sun Park, Sang-Wook Lee, Jooryung Huh, Chan-Sik Park, and Cheolwon Suh. "Treatment of primary testicular diffuse large B cell lymphoma without prophylactic intrathecal chemotherapy: a single center experience." Blood Research 49, no. 3 (2014): 170. http://dx.doi.org/10.5045/br.2014.49.3.170.

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Shen, Ye, Lihong Wang, Jinping Ou, Bingjie Wang, and Xinan Cen. "Loss of 5-hydroxymethylcytosine as a Poor Prognostic Factor for Primary Testicular Diffuse Large B-cell Lymphoma." International Journal of Medical Sciences 19, no. 2 (2022): 225–32. http://dx.doi.org/10.7150/ijms.65517.

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Guo, Dan, Lemin Hong, Hao Ji, Yuwen Jiang, Ling Lu, Xinfeng Wang, and Hongming Huang. "The Mutation of BTG2 Gene Predicts a Poor Outcome in Primary Testicular Diffuse Large B-Cell Lymphoma." Journal of Inflammation Research Volume 15 (March 2022): 1757–69. http://dx.doi.org/10.2147/jir.s341355.

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43

Takeuchi, Toshifumi, Motoko Yamaguchi, Kyoko Kobayashi, Kana Miyazaki, Hiroshi Imai, Ryoichi Ono, Isao Tawara, Tetsuya Nosaka, Kyosuke Tanaka, and Naoyuki Katayama. "MYD88, CD79B, and CD79A Gene Mutations in CD5-Positive Diffuse Large B-Cell Lymphoma." Blood 128, no. 22 (December 2, 2016): 1861. http://dx.doi.org/10.1182/blood.v128.22.1861.1861.

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Abstract INTRODUCTION Diffuse large B-cell lymphoma (DLBCL) is regarded as a clinicopathologically heterogeneous group of lymphomas and is classified as activated B-cell-like (ABC) DLBCL or germinal center B-cell-like (GCB) DLBCL based on the cell-of-origin (COO). Nuclear factor-kappa B (NF-kB) activation is indispensable for ABC DLBCL cell survival. Genes in the NF-kB signaling pathway, such as myeloid differentiation factor 88 (MYD88) and CD79B, are mutated in 20-40% of ABC DLBCLs. CD5 is expressed in approximately 10% of DLBCLs. CD5-positive (CD5+) diffuse large B-cell lymphoma (DLBCL) is characterized by frequent central nervous system (CNS) relapse and a predominant activated B-cell-like nature. Primary DLBCL in sanctuary sites (DLBCL-SS) also shows these features, and more than 70% of the patients exhibit MYD88 (L265P) and CD79B mutations. This study aimed to ascertain the frequencies of MYD88 (L265P), CD79B, and CD79A mutations in CD5+ DLBCL and to determine whether CD5+DLBCL shows the same features as DLBCL-SS in terms of gene mutations. PATIENTS AND METHODS This study included 40 patients with CD5+DLBCL. All the patients were diagnosed with DLBCL, not otherwise specified, according to the 2008 WHO classification between 1993 and 2014 at Mie University Hospital. CD5 expression in tumor cells was analyzed by immunohistochemistry using frozen sections or by flow cytometry. Mutation analysis was performed by direct sequencing. RESULTS Direct sequencing was successful with samples from all 40 patients with CD5+ DLBCL. The median age was 64 years (range: 15 to 91 years). The COO classification was determined by gene expression profiling (GEP) in 29 patients. In the other 11 patients, the COO was identified by immunohistochemistry according to Hans' criteria. Thirty-six (90%) cases were confirmed as ABC/non-germinal center DLBCL. Two patients fulfilled the criteria for primary testicular DLBCL. One patient had systemic CD5+ DLBCL with bone and brain involvement. None of the other patients had CNS involvement at diagnosis. The MYD88 L265P mutation was identified in 13 (33%) of the cases, and no other MYD88 mutations were found. CD79B mutations were detected in 15 (38%) cases, and 10 of these cases overlapped with the MYD88-mutated group. One of the two patients with testicular involvement had double mutations. The other had MYD88 mutation alone. One patient with brain involvement had double mutations. Only one case (3%) had a CD79A mutation as well as CD79B and MYD88 mutations. The incidence of MYD88 L265P, CD79B, and CD79A mutations in ABC/non-GCB DLBCLs was 13/36 (36%), 14/36 (39%), and 1/36 (3%), respectively. Of the 15 cases with a CD79B mutation, 14 had missense mutations in an immunoreceptor tyrosine-based activation motif (ITAM) domain; all of these mutations occurred in the first tyrosine of the ITAM (Y196H [7/14], Y196S [4/14], Y196N [2/14], and Y196C [1/14]), and two cases showed double mutations (Y196H/H225Y and Y196S/K219R). One case had a 13-base deletion in exon 5 before the first tyrosine of the ITAM. MYD88 and CD79B mutations were associated with localized disease (P = 0.038 and P = 0.003, respectively). Clinical information on first-line treatment was available for 38 patients. Before 2002, anthracycline-containing chemotherapies without rituximab were selected as first-line treatment. Since 2002, CHOP chemotherapy with rituximab (R-CHOP) has predominated. For this reason, 18 patients who were treated with R-CHOP were included in the survival analysis in this study. The COO of these 18 patients was confirmed as ABC/non-GCB DLBCL. Two patients with primary testicular lymphoma and one with CD5+ DLBCL with brain involvement were not included in this cohort of 18 patients. With a median follow-up of 7.1 years, there was no significant difference in overall survival based on MYD88 mutation status (P = 0.98) or CD79B mutation status (P= 0.69). CONCLUSIONS To the best of our knowledge, this is the first study toreport the frequency of MYD88, CD79B, and CD79A mutations in the largest cohort of CD5+ DLBCLpatients. The incidence of MYD88 and CD79B mutations in CD5+ DLBCL is lower than that in DLBCL-SS, suggesting that CD5+DLBCL is not the same disease as DLBCL-SS. Disclosures Takeuchi: Chugai: Honoraria. Yamaguchi:Chugai: Honoraria; Eisai: Honoraria; Takeda: Honoraria; Kyowa-Hakko Kirin: Honoraria; Zenyaku: Honoraria. Miyazaki:Eisai: Honoraria; Kyowa Kirin: Honoraria; Chugai: Honoraria. Tawara:Astellas: Honoraria. Katayama:Bristol-Myers Squibb Japan: Honoraria; Alexion Pharmaceuticals: Honoraria; Eisai: Honoraria; Taisho Toyama Pharma: Honoraria; Nippon Shinyaku: Honoraria; Kyowa Hakko Kirin: Honoraria, Research Funding; Astellas: Honoraria, Research Funding; Dainippon Sumitomo Pharma: Honoraria; Chugai: Honoraria, Research Funding; Takeda: Honoraria; Shire: Honoraria; Daiichi Sankyo: Honoraria; Shionogi: Honoraria; Celgene: Honoraria; Pfizer: Honoraria.

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Gavrilenko, Andrey N., Nikita P. Volkov, Daniil I. Shmidt, Alexey Y. Polushin, Elena Kondakova, Kirill V. Lepik, Yuri R. Zalaylov, et al. "Nivolumab in Primary CNS Lymphoma and Primary Testicular Lymphoma with CNS Involvement: Single Center Experience." Blood 136, Supplement 1 (November 5, 2020): 4. http://dx.doi.org/10.1182/blood-2020-138924.

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Background.Most patients with primary CNS lymphoma (PCNSL), an aggressive extranodal lymphoma confined to the CNS, have a poor prognosis in spite of development of chemotherapy regimens. First-line treatment consists of high-dose methotrexate-based (HD-MTX) regimen followed by consolidation with autologous stem cell transplantation or whole brain radiotherapy. Given that this tumor manifests predominantly in older patients with median age of 65 years, many patients are unable to tolerate intensive chemotherapy. Moreover, most patients eventually present with relapsed or refractory (r/r) disease. Relapse or refractory (r/r) PCNSL has a poor prognosis with median overall survival not exceeding 3.5 months (Langner-Lemercier et al, 2016) and these patients should be offered a clinical trial whenever possible. These groups are in need of safe, tolerable and effective therapeutic approaches. Primary testicular lymphoma (PTL) shares biological and clinical similarities with PCNSL and often present with CNS involvement. Such patients are also in need of new approaches, especially if they are refractory or not suitable to HD-MTX. Given high PD-1/PD-L1 expression in tumor microenvironment (Berghoff, 2014), immune checkpoint inhibitors were successfully tested in r/r PCNSL and PTL setting. However, data are still scarce and limited to case series (Nayak et al., 2017; Graber et al. 2020). Here we present Pavlov University experience of the treatment of PCNSL and PTL with CNS involvement with PD-1 inhibitor nivolumab. Methods.Eight patients, 2 men and 6 women, with PCNSL and one patient with PTL with CNS involvement treated at the Pavlov University between 2017 and 2020 were included into analysis. Median age at a diagnosis was 62 (28-66) years. Two patients (22%) had ECOG score 3-4 and therefore could not be considered for intensive MTX containing frontline treatment. In all of the cases the tumor histological type was diffuse large B-cell lymphoma. All patients had parenchymal involvement: 7 patients had multifocal disease; deep structures were involved in 2 patients. One patient had leptomeningeal involvement. Nivolumab was used in a first-line setting in 2 patients (22%). In 7 (78%) patients with relapsed/refractory disease, the median number of treatment lines prior to nivolumab was 1 (1-7). Nivolumab was given every 2 weeks in the 100 mg dose. Adverse events were defined according to NCI CTC-AE 5.0. Results.At the time of analysis, the median follow-up was 18 (3-44) months. Median number of nivolumab cycles was 10 (2-23). Seven (78%) patients had an objective response: complete response in 3 patients (33.3%) and partial response in 4 patients (44.4%). Two patients (22.2%) were refractory to treatment. Two-year overall survival (OS) was 44% with median OS of 12 months. Two-year progression-free survival (PFS) was 26% with median of PFS 12 months. Оne responder had a moderate increase of tumor volume on MRI after two months of therapy followed by complete disappearance of brain lesions on sequential imaging at 4 months after treatment initiation. Nivolumab therapy appeared safe with only one patient (11%) having severe adverse event, namely grade 3 alanine aminotransferase and aspartate aminotransferase increase. Conclusion.Nivolumab appears to be safe and effective therapy in PCNSL and PTL with CNS involvement both in first-line and r/r setting. However, in our cohort majority of patients relapsed that suggest that consolidation therapy after remission induction with nivolumab may be crucial for long-term remissions. We also demonstrate that pseudoprogression might be also observed in PCNSL during immunotherapy. Large-scale trials are needed to generate strong evidence for the use of PD-1 inhibitors in PCNSL. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Nivolumab is an anti-PD-1 inhibitor approved for classical Hodgkin lymphoma. There is early clinical data suggesting the efficiency of nivolumab in PCNS lymphoma (Nayak, 2017)

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Albasri, Abdulkader, Mohammed A. Elkablawy, Ahmed Abdelbadie, Akbar S. Hussainy, and Abdelaziz R. Aljohani. "First Case Report of Primary Testicular Diffuse Large B-Cell Lymphoma from the Western Region of Saudi Arabia." Yemeni Journal for Medical Sciences 13, no. 1 (October 3, 2019): 35–38. http://dx.doi.org/10.20428/yjms.13.1.5.

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Primary testicular lymphoma (PTL) represents 1-2% of all types of non-Hodgkin lymphomas (NHLs) and 1-10% of testicular neoplasms. Up to the best of my knowledge, this is the first case of PTL of the diffuse large B-cell lymphoma (DLBCL) in a 60-year-old man presented with a painless mass in the left testis as revealed by physical examination in a tertiary care hospital in Al-Madinah Al-Munwarah in the western region of the Kingdom of Saudi Arabia (KSA). Radiological examination revealed a large well-defined heterogeneous predominantly hypo-echoic mass with increased vascularity in the upper portion of the testis. On the other hand, histopathological examination revealed a tumor involving the whole left testis, which was large (measuring 6 3.5 3.3 cm), solid and dark red with focal areas of hemorrhage and epididymal infiltration. Immunohistochemistry showed positivity of leucocyte common antigen (LCA), pan B-cell marker (CD20) and negativity of pan T-cell marker (CD3). Other immunohistochemical markers such as CD10, placental alkaline phosphatase (PLAP), cytokeratin, vimentin, desmin and S100 protein were also negative. However, there was a marked expression of Ki67 and Bcl2 markers. Accordingly, the diagnosis of DLBCL was established. The tumor was classified as stage I according to the Ann Arbor system. The case was treated by orchiectomy followed by prophylactic anthracycline-based chemotherapy and irradiation of the contralateral testis and central nervous system.

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Al-Abbadi, Mousa A., Eyas M. Hattab, Musleh S. Tarawneh, Samir S. Amr, Attilio Orazi, and Thomas M. Ulbright. "Primary testicular diffuse large B-cell lymphoma belongs to the nongerminal center B-cell-like subgroup: a study of 18 cases." Modern Pathology 19, no. 12 (September 22, 2006): 1521–27. http://dx.doi.org/10.1038/modpathol.3800691.

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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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Zhou, De, Changqian Bao, Xiujin Ye, Lixia Zhu, Jingjing Zhu, Li Li, Mingyu Zhu, et al. "Clinical and histological features of primary testicular diffuse large B-cell lymphoma: a single center experience in China." Oncotarget 8, no. 68 (July 31, 2017): 112384–89. http://dx.doi.org/10.18632/oncotarget.19736.

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Albasri, Abdulkader, Mohammed Elkablawy, Ahmed Abdelbadie, Akbar Hussainy, and Abdelaziz Aljohani. "First Case Report of Primary Testicular Diffuse Large B-Cell Lymphoma from the Western Region of Saudi Arabia." Yemeni Journal of Medical Sciences 13, no. 1 (October 1, 2019): 35–38. http://dx.doi.org/10.20428/yjms.13.1.c1.

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Kim, Hidong, Laura Harper, Thomas M. Habermann, Grzegorz S. Nowakowski, Carrie A. Thompson, Patrick Johnston, Thomas E. Witzig, et al. "Clinical Significance of Testicular FDG-PET/CT Uptake in Aggressive Lymphomas." Blood 132, Supplement 1 (November 29, 2018): 5401. http://dx.doi.org/10.1182/blood-2018-99-117711.

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Abstract Introduction Primary testicular lymphoma (PTL) and testicular involvement of systemic lymphoma (secondary testicular lymphoma, STL) are uncommon. Most testicular lymphomas are aggressive B-cell lymphomas and portend a high risk of extranodal relapse, including CNS relapse. As such, when testicular lymphoma is identified, the management strategy is often changed to include CNS prophylaxis. It is, therefore, essential to evaluate testicular involvement in diagnosis and staging. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a standard imaging modality to stage aggressive lymphoma. Physiologic testicular FDG activity can be challenging to distinguish from involvement by lymphoma given a wide range of normal. An imaging threshold for testicular PET uptake would be clinically relevant and would help guide management. We compare testicular FDG avidity in testicular lymphoma with physiologic testicular FDG avidity. Methods Records of patients (pts) diagnosed with PTL or STL from 2002-2018 enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource were reviewed, yielding 36 pts with testicular lymphoma. Physiologic testicular avidity by FDG PET/CT was determined from analysis of 70 randomly selected patients who received FDG PET/CT from 2013-2018 prior to treatment for non-lymphoma indications including pulmonary nodule, lung carcinoma, head & neck squamous cell carcinoma, gastrointestinal carcinomas, and metastatic melanoma, without known hematologic malignancy, testicular pathology, or history of testicular infection/surgery by medical chart review. Imaging parameters compared in this analysis were SUVmax and SUVmean. All FDG PET/CT exams were reviewed centrally by a nuclear medicine radiologist and a radiology resident. Results Of the 36 pts with testicular lymphoma, 19 had an orchiectomy prior to FDG PET/CT and 7 pts did not have a staging FDG PET/CT scan. Of the 10 pts with intact testes at the time of staging FDG PET/CT, 1 pt with low-grade lymphoma was excluded. 9 pts with aggressive lymphomas were included in this analysis: 7 pts with diffuse large B cell lymphoma (DLBCL), and 1 pt each with Burkitt lymphoma and peripheral T-cell lymphoma, not otherwise specified. Testicular lymphoma was diagnosed by orchiectomy in 3 pts, and by percutaneous biopsy in 3 pts. 3 pts did not have tissue sampling of testes or scrotal contents, but had an overtly FDG-avid testicle highly suggestive of lymphomatous involvement. These 3 pts had biopsy-proven lymphoma in parotid, bone marrow, and stomach, respectively, with mean testicular SUVmax 6.8 among the 3 pts. The median age in this analysis cohort was 62 years (range 35-88). Of the 7 analyzed DLBCL pts, 6 were non-germinal center B-cell, and 1 was germinal center B-cell. The 70 control pts had a median age of 55 years (range 18-90). In known testicular lymphoma cases and control pts, SUVmax and SUVmean were assessed from the most FDG-avid testicle. Median SUVmax for the testicular lymphoma cases was 13.3 (range 5.5-29.9), compared to a median of 3.8 (range 2.1-5.5) for controls (Wilcoxon p <0.0001). Median SUVmean for testicular lymphoma was 9.2 (range 3.3-18.6), compared to a median of 3.1 (range 1.8-4.8) for controls (Wilcoxon p <0.0001) (Figure). Based on this dataset, an SUVmax cutoff of 5.0 has a sensitivity of 100% (95% CI 66.3-100) and a specificity of 98.6% (98% CI 92.3-99.9) for the detection of testicular involvement by an aggressive lymphoma. Conclusions FDG PET/CT shows significantly greater FDG avidity for testicular aggressive lymphomas as compared with physiologic testicular FDG uptake in this single institution study with centralized radiology review of cases and controls. Testicular FDG avidity greater than an SUVmax 5.0 in staging aggressive lymphoma is highly suggestive for testicular involvement, warranting follow-up clinical exam and ultrasound, at a minimum. In addition, testicles with SUVmax <5.0 in a patient with known lymphoma but no symptoms or signs of testicular involvement should be considered negative for the purposes of staging and treatment planning. A pragmatic limitation of this study is that most patients with testicular involvement of lymphoma underwent orchiectomy prior to FDG PET/CT scan, which decreased our sample size. Larger, pooled studies would be helpful to validate these clinically relevant findings. Figure. Figure. Disclosures Witzig: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

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