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Abstract Background Primary testicular lymphoma (PTL) is relatively rare. The contralateral testis is a common site of PTL relapse; therefore, once complete remission is achieved, radiation therapy (RT) is administered to the contralateral testis to prevent relapse. Case presentation A 76-year-old man was diagnosed with PTL and received RT as described above. However, despite achieving and maintaining complete remission, a mass diagnosed as diffuse large B-cell lymphoma by tissue biopsy developed in the glans penis 6.5 years after prophylactic RT. We investigated whether the glans penile lymphoma was PTL relapse or a new malignancy by genomic analysis using next-generation sequencing of DNA extracted from two histopathological specimens. Conclusions We found the same variant allele fraction in four somatic genes (MYD88, IL7R, BLNK, and FLT3) at similar frequencies, indicating that the glans penile lymphoma had the same origin as the PTL. To the best of our knowledge, this is the first case report of PTL relapse in the glans penis.

Abstract Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.

Background: Primary testicular lymphoma (PTL) is relatively rare. The contralateral testis is a common site of PTL relapse; therefore, once complete remission is achieved, radiation therapy (RT) is administered to the contralateral testis to prevent relapse. Case presentation: A 76-year-old man was diagnosed with PTL and received RT as described above. However, despite achieving and maintaining complete remission, a mass diagnosed as diffuse large B-cell lymphoma by tissue biopsy developed in the glans penis 6.5 years after prophylactic RT. We investigated whether the glans penile lymphoma was PTL relapse or a new malignancy by genomic analysis using next-generation sequencing of DNA extracted from two histopathological specimens. Conclusions: We found the same variant allele fraction in four somatic genes (MYD88, IL7R, BLNK, and FLT3) at similar frequencies, indicating that the glans penile lymphoma had the same origin as the PTL. To the best of our knowledge, this is the first case report of PTL relapse in the glans penis. [ABSTRACT FROM AUTHOR]

Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients. [ABSTRACT FROM AUTHOR]

Lymphoma is a heterogeneous group of lymphocyte malignancies that may involve lymphatic tissue, bone marrow, or extranodal sites. The lecture provides a brief overview of the current state of the problem of diagnosis and treatment of primary testicular lymphoma. Primary testicular lymphoma (PTL) is a rare lymphoid malignancy. Though it is rare, PTL is the most common type of testicular tumor in men over 60 years of age. The most common histological type is diffuse large B-cell lymphoma. To date, there are no well-documented etiological or risk factors for PTL. In contrast to other common testicular neoplasms, there was no statistically significant association of PTL with cryptorchidism, trauma, chronic orchitis, or infertility. Ultrasound is generally the first-line imaging method used to characterize testicular lesions. PTL manifests itself in the form of a hypoechoic formation, which can take the form of either a single large formation or multiple small formations that occupy most of the testicular parenchyma or completely replace it. Systemic treatment, including orchiectomy, chemotherapy, radiation therapy, and intrathecal prophylaxis, is necessary for all patients with PTL. In addition to achieving complete remission, the goal of PTL treatment is to prevent recurrences in the contralateral testis and central nervous system. The presented information is supplemented by our own observation and images. Personal medical data is published with the written consent of the patient. In our case, the patient’s age was 38 years, which does not fall into the specified age group for primary testicular lymphoma. In our opinion, the publication of this clinical case and analysis of scientific literature on this topic are relevant.

Diffuse large B‐cell lymphoma (DLBCL) shows a high degree of clinical and biological heterogeneity. Primary testicular lymphoma (PTL) is an extranodal variant of DLBCL associated with a higher risk of recurrence, including contralateral testicles and central nervous system sanctuary sites. Several molecular aberrations, including somatic mutation of MYD88, CD79B, and upregulation of NF‐kB, PDL‐1, and PDL‐2, are thought to contribute to the pathogenesis and poor prognosis of PTL. However, additional biomarkers are needed that may improve the prognosis and help understand the PTL biology and lead to new therapeutic targets. RNA from diagnostic tissue biopsies of the PTL‐ABC subtype and matched nodal DLBCL‐ABC subtype patients was evaluated by mRNA and miRNA expression. Screening of 730 essential oncogenic genes was performed, and their epigenetic connections were examined using the nCounter PAN‐cancer pathway, and Human miRNA assays with the nCounter System (NanoString Technologies). PTL and nodal DLBCL patients were comparable in age, gender, and putative cell of origin (p > 0.05). Wilms tumor 1 (WT1) expression in PTL exceeded that in nodal DLBCL (>6‐fold; p = 0.01, FDR <0.01) and WT1 associated pathway genes THBS4, PTPN5, PLA2G2A, and IFNA17 were upregulated in PTL (>2.0‐fold, p < 0.01, FDR <0.01). Additionally, miRNAs targeting WT1 (hsa15a‐5p, hsa‐miR‐16‐5p, has‐miR‐361‐5p, has‐miR‐27b‐3p, has‐miR‐199a‐5p, has‐miR‐199b‐5p, has‐miR‐132‐3p, and hsa‐miR‐128‐3p) showed higher expression in PTL compared to nodal DLBCL (≥2.0‐fold; FDR 0.01). Lower expression of BMP7, LAMB3, GAS1, MMP7, and LAMC2 (>2.0‐fold, p < 0.01) was observed in PTL compared to nodal DLBCL. This research revealed higher WT1 expression in PTL relative to nodal DLBCL, suggesting that a specific miRNA subset may target WT1 expression and impact the PI3k/Akt pathway in PTL. Further investigation is needed to explore WT1's biological role in PTL and its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives To retrospectively investigate the clinical characteristics, prognosis, treatment, and therapy outcome of Chinese patients with primary testicular lymphoma (PTL).Methods we collected data of 49 PTL patients from four hospitals over 13 years. The median age was 63 years old. We described the clinical characteristics of the patients including the laterality, serum lactate dehydrogenase (LDH), pathology classification, stage, International prognostic index (IPI) scores and more.Results Complete remission (CR) was achieved in 34 patients and partial remission (PR) in 3 patients; Progressive disease (PD) was detected in 11 patients, and 10 patients died. The average progression-free survival (PFS) of all patients was 43.92 months, and the average overall survival (OS) was 47.55 months. The Ann Arbor stage, IPI score, and LDH were associated with OS, while Ann Arbor stage, IPI score, LDH, and histotype were significantly associated with PFS. Chemotherapy and radiotherapy following orchiectomy was associated with a significantly longer PFS.Conclusion Most patients can achieve CR after induced therapy or orchiectomy. However, there are many associated prognostic factors.

Introduction: Primary testicular lymphoma (PTL) is a rare disease, accounting for <5% of all testicular malignancies and 1–2% of non-Hodgkin lymphoma cases. Diffuse large B-cell lymphoma (DLBCL) is the most common histological diagnosis. The literature data concerning PTL is scarce and based mainly on small series or retrospective studies. Methods and results: In this paper, we present six patients with DLBCL-PTL who were treated in the Department of Hematology and Bone Marrow Transplantation at Poznan University of Medical Science, Poland between 2006 and 2022. All the patients obtained complete remission (CR) after six cycles of R-CHOP-21 (cyclophosphamide, doxorubicin, vincristine and rituximab on day 1, and prednisolone on days 1–5, administered every 21 days for a total of eight cycles) as immunochemotherapy. Five of them additionally received prophylaxis of central nervous system involvement with intrathecal methotrexate/arabinoside cytosine. One patient received scrotal radiotherapy, and in another one radio- therapy is planned. Relapse was confirmed in one patient after 72 months in the contralateral testis, and the patient was successfully retreated. After a median follow-up of 146 (range 5–196) months, all patients remain alive and in CR. Conclusion: Despite all interpretative limitations, the current standard DLBCL-PTL therapy seems to be six courses of CHOP-R-21 combined with intrathecal metothrexate and scrotal irradiation. [ABSTRACT FROM AUTHOR]

Background/Aim: Primary testicular lymphoma (PTL) is an exceedingly rare and aggressive form of nonHodgkin’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 progressionfree 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 PTLDLBCL. 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 (ITMTX) (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. [ABSTRACT FROM AUTHOR]

Primary testicular lymphoma (PTL) is a rare variant of non-Hodgkin's lymphoma that is predominant in old age group. Painless testicular swelling is the most common presentation. The standard of care is surgery in the form of radical orchiectomy followed by adjuvant chemotherapy and central nervous system prophylaxis. Because of blood-testis barrier, contralateral testis acts as a sanctuary site for chemotherapy to act and hence scrototesticular radiation is advocated in order to reduce the chance of testicular relapse. Due to lack of any consensus simulation procedure, we propose here a step-by-step procedure for simulation of a case of PTL using a case scenario. [ABSTRACT FROM AUTHOR]

To retrospectively investigate the clinical characteristics, prognosis, treatment, and therapy outcome of Chinese patients with primary testicular lymphoma (PTL). we collected data of 49 PTL patients from four hospitals over 13 years. The median age was 63 years old. We described the clinical characteristics of the patients including the laterality, serum lactate dehydrogenase (LDH), pathology classification, stage, International prognostic index (IPI) scores and more. Complete remission (CR) was achieved in 34 patients and partial remission (PR) in 3 patients; Progressive disease (PD) was detected in 11 patients, and 10 patients died. The average progression-free survival (PFS) of all patients was 43.92 months, and the average overall survival (OS) was 47.55 months. The Ann Arbor stage, IPI score, and LDH were associated with OS, while Ann Arbor stage, IPI score, LDH, and histotype were significantly associated with PFS. Chemotherapy and radiotherapy following orchiectomy was associated with a significantly longer PFS. Most patients can achieve CR after induced therapy or orchiectomy. However, there are many associated prognostic factors. [ABSTRACT FROM AUTHOR]

Background: Primary testicular lymphoma (PTL) is a rare malignancy whose epidemiology and prognosis have not been studied., Materials and Methods: PTL patient data were collected from the SEER online database, and the data were divided into a training cohort and a validation cohort according to random assignment. The training cohort was subjected to a one-way COX regression analysis, and statistically significant differences were included in the multi-factor COX regression analysis and constructed nomograms. Forest plots were constructed based on risk factors. The validity of the nomograms was verified by observing the C-index size of the nomograms, the percentage of area under the ROC curve, and the degree of fit of the prediction curve in the calibration plot. The validation cohort verified the accuracy and applicability of the nomograms., Result: The patient's age, tumor histologic type, Ann Arbor stage, grade of differentiation, and whether or not they received radiation and chemotherapy were significantly associated with poor prognosis in PTL., Conclusion: The nomogram constructed based on multivariate COX regression analysis can predict the prognosis of PTL patients. The online visualization nomogram can help clinicians calculate the survival rate of PTL tumor patients and conduct personalized prognostic assessments for PTL tumor patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Zheng Yan,1 Shuna Yao,1 Yuanyuan Wang,2 Yanyan Liu,1 Zhihua Yao1 1Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Zhihua Yao; Yanyan LiuDepartment of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, No. 127 Dongming Road, Zhengzhou, Henan, 450008, People’s Republic of ChinaTel/Fax +86 371-65587791Email zlyyyaozhihua1260@zzu.edu.cn; yyliu@zzu.edu.cnAbstract: Primary testicular lymphoma (PTL) is a rare malignancy of testis. Although the multimodality treatment (including orchiectomy, systemic chemotherapy, scrotal radiotherapy, and preventive central nervous system (CNS)-targeted treatment) is widely used to treat PTL, recurrence, especially CNS recurrence, occurred frequently. Patients with relapsed PTL have a dismal prognosis and limited treatment options. In this report, we described the case of a 63-year-old man with early-stage PTL. The patient received the multimodality treatment, but CNS relapse occurred 3 months following the front-line therapy. We gave him a combined chemo-free regimen treatment, including rituximab, ibrutinib, and lenalidomide (RIL), based on the tumor’s gene mutation profile and the patient’s preference. A complete response was achieved after the first cycle of treatment. Whole-brain radiotherapy was delivered as consolidative treatment following three more cycles of RIL. Thereafter, ibrutinib and lenalidomide continued as maintenance treatment. As of the submission of this manuscript, the response has lasted for more than 16 months. Based on the case, we believe chemo-free regimen RIL might be a favorable approach for PTL patients with CNS relapse, especially those frail elderly patients, when alternative treatments are not available.Keywords: primary testicular lymphoma, chemo-free regimen, central nervous system relapse, case report

Primary testicular lymphoma (PTL) is a rare Testicular neoplasm found in elderly patients. Imaging features in PTL presenting with contiguous involvement of spermatic cord and extension along gonadal vein have been rarely detailed before. We describe a case of a 50-year-old male who presented with complaints of scrotal swelling and abdominal discomfort. Imaging, which included Ultrasonography and contrast-enhanced computed tomography of chest-abdomen, showed features of aggressive-looking bilateral testicular mass lesions with the distinctive feature of contiguous spread along the spermatic cord and gonadal vein till retroperitoneum and disseminated chest and abdominal metastases. The distinctive feature of contiguous extension along the spermatic cord and gonadal vein can help suggest a diagnosis of PTL on imaging.

Abstract Primary testicular lymphoma (PTL), often appearing as focal masses in the scrotum and epididymides, is the most frequent testicular tumor in aged men. Although MYD88 and CD79B mutations were the most common genetic alterations observed, the gene mutation landscape of PTL remains poorly defined. In this study, we identified 1326 mutations involving 311 genes or regions in 90 PTL patients through next-generation sequencing (NGS). PTL patients with the TBL1XR1 mutation, irrespective of treatment therapy, had an inferior overall survival (OS) than TBL1XR1 WT (wild type) patients (p = 0.045). Moreover, patients with this mutation, treated with a CHOP regimen (CTX 750 mg/m2 iv, d1,8 ADM 50 mg/m2 iv, d1 VCR 1.4 mg/m2 iv, d1 PDN 100 mg/m2 po d1–5), had a poorer OS (p = 0.019). In addition, such patients were prone to have a more intensive infiltration of tumors (p = 0.025, x2 = 4.890). Thus, we speculated that patients with a TBL1XR1 mutation have poorer prognosis, partly due to greater invasion and infiltration of tumors. Our results suggest that the TBL1XR1 mutation can be used as an indicator to predict the prognosis of PTL and can be employed as a promising new target for treatment of PTL in the future.

Abstract Background To retrospectively investigate the clinical characteristics, initial treatment, relapse, therapy outcome, and prognosis of Chinese patients with primary testicular lymphoma (PTL) through analysis of the cases of our institute. Methods From December 2008 to July 2018, all patients with PTL were included in this study. Kaplan-Meier method was used to estimate PFS and OS. The Cox proportional hazards model was used to compare the survival times for groups of patients differing in terms of clinical and laboratory parameters. Results All 28 PTL patients (24 DLBCL, three NK/T lymphomas, and one Burkkit’s lymphoma) with a median age of 65.5 years were included in this study. Six patients were observed recurrence among all the 22 individuals evaluated. Following orchiectomy and systemic chemotherapy, with or without intrathecal prophylaxis, complete response was achieved in 15 (68%) patients. For DLBCL patients, the median progression-free survival (PFS) was 44.63 months (95% CI 17.71–71.56 months), and the median overall survival (OS) was 77.02 months (95% CI, 57.35–96.69 months). For all the DLBCL patients, the 5-year PFS and 5-year OS were 35.4% (95%CI, 14.8–56.0%) and 53.4% (95%CI, 30.1–76.7%). Without further chemotherapy following orchiectomy (HR = 3.4, P = 0.03) were associated with inferior PFS of DLBCL patients. Advanced Ann Arbor stage (HR =5.9, P = 0.009) and high (international prognostic index, IPI) score: 3–5 (HR =3.9, P = 0.04) were correlated with shorter OS of DLBCL patients. Conclusion This study confirms that PTL is an aggressive malignant with a poor prognosis. Limited Ann Arbor stage, further chemotherapy following orchiectomy, and low IPI score (less than 2) are correlated with superior survival for DLBCL patients.

Bilateral Primary testicular lymphoma (PTL) is a rare and aggressive non-Hodgkin extranodal lymphoma. Despite this low overall incidence, it is the most common testicular cancer in the elderly. PTL is characterized by spreading to non-contiguous extranodal sites (especially in SNC), high recurrence rate and poor prognosis. We report a case of a 55-year old man with advanced bilateral PTL without specific symptoms who underwent a combined multimodal approach.

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.

Aggressive large B-cell lymphomas (LBCLs) represent a frequent but clinically and molecularly heterogeneous group of tumors. Technological advances over the last decades prompted the development of different classification schemas to either sharpen diagnoses, dissect molecular heterogeneity, predict outcome, or identify rational treatment targets. Despite increased diagnostic precision and a noticeably improved molecular understanding of these lymphomas, clinical perspectives of patients largely remain unchanged. Recently, finished comprehensive genomic studies discovered genetically defined LBCL subtypes that predict outcome, provide insight into lymphomagenesis, and suggest rational therapies with the hope of generating patient-tailored treatments with increased perspective for patients in greatest need. Current and future efforts integrate multiomics studies and/or leverage single-cell technologies and will provide us with an even more fine-grained picture of LBCL biology. Here, we highlight examples of how high-throughput technologies aided in a better molecular understanding of LBCLs and provide examples of how to select rationally designed targeted treatment approaches that might personalize LBCL treatment and eventually improve patients' perspective in the near future. [ABSTRACT FROM AUTHOR]

Copyright of Practical Oncology Journal is the property of Journal of Practical Oncology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Large B-cell lymphomas (LBCLs) represent a frequent but clinically and morphologically heterogeneous group of tumors. Technological advances over the last 2 decades prompted the development of new classification schemas to sharpen diagnoses, dissect molecular heterogeneity, and identify rational treatment targets. Despite increased molecular understanding of these lymphomas, the clinical perspectives of patients largely remain unchanged. Recently finished comprehensive genomic studies discovered genetically defined LBCL subtypes that predict outcome, provide insight into lymphomagenesis, and suggest rational therapies with the hope of generating patient-tailored treatments with increased perspective for patients in greatest need. Here, we summarize notable examples of how high-throughput technologies aided in better molecular understanding of LBCLs and provided examples of rationally designed targeted treatments. [ABSTRACT FROM AUTHOR]

Background: To retrospectively investigate the clinical characteristics, initial treatment, relapse, therapy outcome, and prognosis of Chinese patients with primary testicular lymphoma (PTL) through analysis of the cases of our institute.Methods: From December 2008 to July 2018, all patients with PTL were included in this study. Kaplan-Meier method was used to estimate PFS and OS. The Cox proportional hazards model was used to compare the survival times for groups of patients differing in terms of clinical and laboratory parameters.Results: All 28 PTL patients (24 DLBCL, three NK/T lymphomas, and one Burkkit's lymphoma) with a median age of 65.5 years were included in this study. Six patients were observed recurrence among all the 22 individuals evaluated. Following orchiectomy and systemic chemotherapy, with or without intrathecal prophylaxis, complete response was achieved in 15 (68%) patients. For DLBCL patients, the median progression-free survival (PFS) was 44.63 months (95% CI 17.71-71.56 months), and the median overall survival (OS) was 77.02 months (95% CI, 57.35-96.69 months). For all the DLBCL patients, the 5-year PFS and 5-year OS were 35.4% (95%CI, 14.8-56.0%) and 53.4% (95%CI, 30.1-76.7%). Without further chemotherapy following orchiectomy (HR = 3.4, P = 0.03) were associated with inferior PFS of DLBCL patients. Advanced Ann Arbor stage (HR =5.9, P = 0.009) and high (international prognostic index, IPI) score: 3-5 (HR =3.9, P = 0.04) were correlated with shorter OS of DLBCL patients.Conclusion: This study confirms that PTL is an aggressive malignant with a poor prognosis. Limited Ann Arbor stage, further chemotherapy following orchiectomy, and low IPI score (less than 2) are correlated with superior survival for DLBCL patients. [ABSTRACT FROM AUTHOR]

Primary testicular lymphoma (PTL) frequently relapses in the central nervous system (CNS) despite prophylactic intrathecal chemotherapy, and the outcome for CNS recurrence of PTL is very poor. We report a case of isolated CNS recurrence of bilateral PTL. Our patient achieved complete response (CR) after rituximab-combination chemotherapy for PTL. Approximately five years later, isolated CNS recurrence of PTL occurred. Our patient achieved CR again after high-dose methotrexate therapy and autologous stem cell transplantation (ASCT) with a conditioning regimen of thiotepa and busulfan as a consolidation therapy. The secondary failure of platelet recovery, probably caused by busulfan, occurred after the platelet engraftment. Our patient has remained in CR for over three years. The treatment strategy for CNS recurrence of PTL is mainly whole-brain radiotherapy or high-dose methotrexate-based chemotherapy; however, CNS recurrence of PTL may occur again even after achieving CR. ASCT with a conditioning regimen of thiotepa and busulfan is the optimal consolidation therapy for secondary CNS lymphoma. To the best of our knowledge, this is the second reported case of a patient with isolated CNS recurrence of PTL successfully treated by ASCT with a conditioning regimen of thiotepa and busulfan as a consolidation therapy.

Purpose: In this study, we investigated the prevalence of CD79B and MYD88 mutations and their relation to clinical characteristics in a cohort of Chinese patients with primary testicular diffuse large B cell lymphoma (PT-DLBCL). Patients and methods: We examined the mutational status of CD79B and MYD88 by Sanger sequencing, and the gene amplification and protein expression of MYD88 in tissue samples from 30 cases of PT-DLBCL by quantitative polymerase chain reaction and immunohistochemistry, respectively. Western blotting was used to analyze phosphorylated STAT3 (p-STAT3) and phosphorylated p65 (p-p65) protein expression in cell lines harboring retroviral constructs for WT MYD88 or MYD88 mutant. Results: Immunophenotypically, MYD88 protein staining was positive in 26/30 (86.67%) cases, and 23/30 (76.7%) cases tested positive for p65 in the nucleus. Genetically, CD79B mutation was found in 13/30 (43.3%) cases, whereas the MYD88L265P mutation was found in 18/30 (60.0%) cases. Interestingly, CD79B and MYD88 mutations were more prevalent in the non-germinal center B cell (GCB) subtype (83.3% and 76.9%, respectively) and were relatively rare in the GCB subtype (16.7% and 23.1%, respectively). Furthermore, although MYD88 was significantly amplified in PT-DLBCL, the amplification status showed no correlation with its mutational status and protein expression. Clinicopathological comparison between the mutant and wild-type group showed that both CD79B mutation and MYD88L265P were not significantly correlated with age, anatomical site, Ann Arbor stage, non-GCB/GCB subtype, p65 protein expression, BCL-2 protein expression, or BCL-2/c-MYC double expression (P>0.05). Survival analyses showed that high IPI and advanced stage (stage III–IV) associated with worse outcome (P<0.05). The expression of p-STAT3 and p-p65 protein was upregulated in the mutant group, indicating that MYD88 mutant activated NF-κB and JAK–STAT3 signaling. Conclusion: Our results suggest that MYD88 and CD79B mutations are important drivers of immune-privileged site-associated DLBCL and highlight potential therapeutic targets for personalized treatment. [ABSTRACT FROM AUTHOR]

The present study evaluated programmed cell death-ligand 1 (PD-L1) expression in tumor cells and in the tumor microenvironment (TME) and its association with clinical data in primary testicular diffuse large B cell lymphoma (DLBCL). PD-L1 was determined by immunohistochemistry in 30 patients with primary testicular DLBCL and assessed for associations with clinical characteristics, progression-free survival (PFS) and overall survival (OS). The mean patient age was 62.2 years. Overall, 10 (33.3%) patients had advanced-stage (stage III/IV) disease and 14 (46.7%) patients had an International Prognostic Index (IPI) of ≥3. The median follow-up time following orchiectomy was 23.5 months. During this time, 10 (33.3%) patients experienced disease progression and 11 (36.7%) patients succumbed. PD-L1 expression in tumor cells and in the TME was detected in 20 (66.7%) and 13 (43.3%) patients, respectively. PD-L1 expression on tumor cells and in the TME was higher in those at an early stage compared with patients with an advanced stage of disease (P=0.045 and 0.017, respectively). In addition, PD-L1 expression in tumor cells was higher in patients with a low IPI compared with those with a high IPI (P=0.019). A Kaplan-Meier analysis identified no association of PD-L1 expression on tumor cells with PFS (P=0.763) or OS (P=0.531), or of PD-L1 expression in the TME with PFS (P=0.572) or OS (P=0.934). The present study demonstrated that PD-L1 expression in tumor cells and in the TME was higher in patients at an early stage of disease compared with those at an advanced stage, and that PD-L1 expression on tumor cells was higher in patients with a low IPI than in those with a high IPI. Furthermore, PD-L1 expression in tumor cells and in the TME was not associated with PFS or OS. [ABSTRACT FROM AUTHOR]

Testicular lymphoma is a rare malignancy affecting mainly elderly men, the majority representing diffuse large B-cell lymphoma (DLBCL). Its relapse rate is higher than that of nodal DLBCL, often affecting the central nervous system (CNS) with dismal prognosis. We searched for patients with testicular DLBCL (T-DLBCL) involvement from the pathology databases of Southern Finland University Hospitals and the Danish Lymphoma Registry. Clinical information was collected, and outcomes between treatment modalities were evaluated. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were assessed using Kaplan–Meier and Cox proportional hazards methods. We identified 235 patients; of whom, 192 were treated with curative anthracycline-based chemotherapy. Full survival data were available for 189 patients. In univariate analysis, intravenous CNS-directed chemotherapy, and irradiation or orchiectomy of the contralateral testis translated into favourable PFS, DSS and OS, particularly among the elderly patients (each p ≤ 0.023). Intrathecal chemotherapy had no impact outcome. In multivariate analyses, the advantage of intravenous CNS-directed chemotherapy (hazard ration [HR] for OS, 0.419; 95% confidence interval [CI], 0.256–0.686; p = 0.001) and prophylactic treatment of contralateral testis (HR for OS, 0.514; 95% CI, 0.338–0.782; p = 0.002) was maintained. Rituximab improved survival only among high-risk patients (International Prognostic Index≥3, p = 0.019). The cumulative risk of CNS progression was 8.4% and did not differ between treatment modalities. The results support the use of CNS-directed chemotherapy and prophylactic treatment of the contralateral testis in patients with T-DLBCL involvement. Survival benefit appears resulting from better control of systemic disease rather than prevention of CNS progression. • Intravenous central nervous system (CNS)–directed chemotherapy translates to superior survival in testicular lymphoma. • Phophylactic treatment of contralateral testis is associated with improved survival. • Intrathecal CNS-directed chemotherapy does not have impact on survival. • The benefit of rituximab is seen only among the patients with high International Prognostic Index. [ABSTRACT FROM AUTHOR]

Objective To improve the level of awareness,diagnosis and treatment of primary testicular lymphoma (PTL) by analysing the clinical features and evaluating the effects of different treatment modes on the prognosis. By applying the research results to the clinic and assessingthe prognosis, we can improve the quality of life of PTL patients and prolong their survival. Methods Clinical data of 52 patients with PTL in Tumor Hospital of Yunnan Province from May 1994 to March 2016 were retrospectively analyzed. Results (1) 52 cases of PTL patients' median age was 60.4 years. There were 41 cases in phase I and IV. The median OS was 25.47 months. The first symptom of the disease was manifested as testicular enlargement or palpable mass in 50 cases. Only a few patients who were in late stage of disease had B symptoms. 22 cases with other diseases associated with testis or adjacent tissues and organs. 17 cases of infiltration with contralateral testis or CNS were found during the diagnosis and treatment. The main pathological type was B cells, of which diffuse large B-cell lymphoma accounted for 42 cases. (2) For patients with the same stage and the common general conditions, single treatment and non- steroidal chemotherapy were prognostic factors of OS (P＜0.05). The total number of chemotherapy cycles < 6 was a factor of poor prognosis in patients with IE/IIE stage (P＜0.05). The use ofrituximab was not significantly related toOS (P＞0.05). Conclusions The invasive ability of this disease is extremely strong, and the overall prognosis is very poor. For patients with the same stage and the common general conditions, the use of comprehensive treatment methods, the anthracycline- containing chemotherapy regimens and chemotherapy cycles ≥ 6 can improve the prognosis to some extent. [ABSTRACT FROM AUTHOR]

Primary testicular lymphoma (PTL) is a rare lymphoid malignancy. The present retrospective study aimed to investigate the demographic characteristics and survival of patients with PTL, as well as the associated prognostic factors, using a population-based database. All adults diagnosed with PTL in the Surveillance, Epidemiology, and End Results database were identified between 1973 and 2013. The Kaplan-Meier method was used to estimate cause-specific survival (CSS). Log-rank test or multivariate Cox regression model was used to assess the influence of demographic and clinical parameters on CSS. A total of 1,169 patients with PTL were identified from the database, and the median age was 70 years. The predominant histological subtype was diffuse large B-cell lymphoma, which affected 82.9% (970/1,169) of patients, and 68.6% (802/1,169) of patients had early stage disease (stages I–II). Patients >70 years, those diagnosed at the earlier time period, or those who had advanced-stage symptoms had the worst 5-year CSS rates; however, treatment with rituximab significantly improved the 5-year CSS. In conclusion, this retrospective study presented data from the largest cohort of patients with PTL and described the effects of rituximab on the CSS of patients with PTL. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to evaluate the clinical characteristics, pathology, treatment outcomes, and survival of primary testicular lymphoma (PTL) patients treated at our hospital after 1990. Related literature was reviewed. Materials and methods: We retrospectively enrolled patients diagnosed with PTL between January 1990 and September 2013 in our institute. Clinical features, pathology, and overall survival were analyzed. Results: 24 patients were enrolled. They had a mean age at diagnosis of 65.0 years (range 10–84 y), mean follow-up duration 57.0 months (range 3–182 mo), and median overall survival of 38 months (range 4.0–184.7 mo). The most common pathology subtype was diffuse large B-cell lymphoma (n = 21, 87.5%). Fourteen patients (58.3%) achieved complete remission of disease and five patients (20.8%) achieved partial remission after treatment. Three patients had a relapse of disease after complete remission: one in the brain parenchyma, one in the pelvis soft tissue and omentum, and one in the left pyriform muscle. Three patients had metastasis after partial remission of disease: two in the brain parenchyma and one in the cauda equina. By univariate analysis, the factors significantly associated with superior overall survival were primary tumor diameter < 7.5 cm, serum lactate dehydrogenase ≤ 250 U/L, Ann-Arbor Stage IE/II, and International Prognostic Index (IPI) ≤ 1 (p

Primary testicular lymphoma (PTL) is an uncommon neoplasm (

Neurological symptoms induced by the infiltration of malignant lymphoma into the nervous systems are subsumed under the term neurolymphomatosis (NL). Here, we report the case of a 30-year-old Japanese man with primary testicular lymphoma complicated, as seen in various neurological findings, by secondary NL prior to testicular swelling. Painless right scrotal enlargement was noticed more than 1 month after the appearance of neurological complications such as right upper extremity numbness, dysarthria, facial palsy, and diplopia. Proactive investigation and biopsies of extranodal sites at high risk of central nervous system infiltration of malignant lymphoma, such as the testes, should be considered when secondary NL is suspected based on imaging findings.

There are 1% to 2% of lymphoma cases that include the testis as primary testicular non-Hodgkin lymphoma (NHL). In 35% of cases, it involves both testes and is usually seen as a painless testicular mass. Therefore, in most cases, the management option is radical orchiectomy. The overall prognosis in these cases is poor, as most cases are associated with systemic disease. We report a case of a 42-year-old male who presented with painless right scrotal swelling for three months. The only serologic marker of solid tumors that was elevated was βHCG; others were unremarkable. Ultrasonography was initially ordered as well and showed a heterogeneous intra-testicular lesion of relatively low echogenicity. According to the given age, epidemiology, and clinical presentation, the suspicion of a germ cell tumor was highly likely. Therefore, a right radical inguinal orchiectomy was done, and the specimen was sent for histopathology, which came back as B-cell non-Hodgkin lymphoma. The clinical presentation and the overall picture of the investigations made in this case mimicked a germ cell tumor presentation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alnemer et al.)

Background/aim: B-cell lymphomas are characterized by diverse genetic anomalies affecting B-cell differentiation. To expand targeted therapies, an in-depth grasp of the molecular dynamics in the germinal center (GC) is vital. Transducin β-like 1 X-linked receptor 1 (TBL1XR1) and nuclear receptor corepressor 1 (NCOR1) are instrumental within the GC, modulating myriad oncogenic pathways. Their prognostic roles in various cancers are established, yet their precise impact on B-cell lymphoma is elusive., Materials and Methods: Digital RNA quantification (Nanostring) of previously curated 188 B-cell lymphoma specimens across four subtypes, follicular lymphoma (FL), diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), primary testicular lymphoma (PTL), and plasmablastic lymphoma (PBL), was reanalyzed with focus on TBL1XR1 and NCOR1 expression, juxtaposing them with 730 ontogenically linked genes., Results: Notably, TBL1XR1 expression was significantly elevated in the PTL- ABC-subtype versus DLBCL-NOS- ABC-subtype (p<0.001), with no marked disparity in GCB-subtypes between them. The median TBL1XR1 expression was remarkably diminished in FL, yet, intriguingly, GCB-subtypes of DLBCL-NOS exhibited significantly enhanced expression compared to FL (p=0.001). In contrast, NCOR1's expression trajectory was consistent across DLBCL-NOS, PTL, and PBL. A strong inverse correlation between TBL1XR1 and NCOR1 was observed in PBL (p=0.001). Importantly, TBL1XR1's pronounced association with several DNA Damage repair (DDR) genes was noted suggesting influence on DNA repair. TBL1XR1-DDR gene signature was further validated employing a public data set of DLBCL-NOS., Conclusion: Our exploratory findings unravel the expression patterns of TBL1XR1/NCOR1 in B-cell lymphoma variants. The TBL1XR1-DDR genes connection offers insights into potential DNA repair roles, paving avenues for innovative therapies in B-cell lymphomas., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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-yearold man presented with a painless mass in the left testis as revealed by physical examination in a tertiary care hospital in Al- Madinah Al-Munawarah 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. [ABSTRACT FROM AUTHOR]

Objective: Primary testicular lymphoma (PTL) is a form of extra-nodal lymphoma originating from the testicles. Currently, positron emission tomography (PET) with glucose analogue 18F-fluorodeoxyglucose (18F-FDG) is the most popular and widely used modality for evaluating tumor metabolism, and PTL usually displays increased 18F-FDG uptake. Despite the rapid increase in clinical applications of FDG PET/ computed tomography (CT), its role in PTL has neither been clearly defined nor reviewed systematically. This study reviews the usefulness and limitation of FDG PET/CT in the diagnosis and treatment of PTL. Methods: This study included 12 patients with PTL between 2004 and 2015. We retrospectively examined PET/CT results along with patient outcome. The maximum standardized uptake value (SUVmax) was calculated. Results: The mean overall survival (OS) and disease-free survival (DFS) was 44.5 months and 35.5 months, respectively. The mean SUVmax was identified as 18.5 in recurrent/metastatic group. The 1-year and 3-year OS was 94% and 69%, while the 1-year and 2-year DFS was 93.5% and 56%, respectively. Conclusion: FDG PET/CT is very helpful in both staging and evaluating treatment response. Although it is not a perfect tool in the initial diagnosis, it might aid in the differential diagnosis of challenging testicular tumors. Pre-treatment and posttreatment FDG uptake values may also have a prognostic value in patients with PTL. [ABSTRACT FROM AUTHOR]

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) represents a rare and aggressive extranodal non-Hodgkin's lymphoma (NHL) with some specific features that differ from other NHLs. Formalin fixed, paraffin wax embedded (FFPE) samples of 21 PT-DLBCLs and 30 comparative patients with DLBCL were analysed. All PT-DLBCL patients were treated with rituximab-containing regimens, intrathecal prophylaxis (10 patients), and irradiation of the contralateral testis (9 patients). FFPE samples were additionally analysed by immunohistochemistry (Bcl-2, c-Myc protein expression) and fluorescence in situ hybridisation (FISH) (BCL2 and MYC). The patients with PT-DLBCL (median age 48.5 years), had low frequency of B symptoms (28.6%) and were often diagnosed in I and II Ann Arbor clinical stage (66.0%). The majority of PT-DLBCL (80.9%) had a non-germinal centre B-cell-like immunophenotype. Immunohistochemical staining showed increased c-Myc protein expression in the PT-DLBCL group compared to the control group (p = 0.016). MYC rearrangement was detected in 1 of 14 (7.0%), and MYC amplification in 3 of 14 (21.0%) patients. One of the 14 cases (7.0%) in the PT DLBCL group showed BCL2 rearrangement, and four of 14 (28.05%) cases showed BCL2 amplification. Complete remission (CR) was achieved in 75.0% of PT-DLBCL patients who had superior survival compared to those who did not achieve CR (median 48 vs. 21 months, p = 0.012). Patients with PT-DLBCL express some immunohistochemical, biological, and clinical features that might differentiate them from nodal and extranodal DLBCL patients, indicating the need for a more personalised treatment approach. [ABSTRACT FROM AUTHOR]

Here, we report a case of 71 years old male, presenting with a left sided testicular tumor without any reported inguinal, abdominal or peripheral lymphadenopathy, diagnosed as Non-Hodgkins lymphoma of testis on histo-pathological examination and confirmed by immunohistochemistry (IHC).

Primary testicular lymphoma, is a rare testis tumor that accounts for only less than 9% of all testis tumors. In the preoperative period, it is extremely difficult to distinguish this tumor from other testis tumors. Its diagnosis is done by histological analysis. Most commonly encountered histological type is diffuse large Bcell lymphoma. Adjuvant radiotheraphy and/or chemotheraphy is given after orchiectomy. Prognosis is worse than other testis tumors. Non-metastatic tumors indicates good prognosis within one year. Ongoing research in patients with primary testicular lymphoma, are on efficacy of adjuvant theraphies and preventive and cure effect on extranodal extension to central nervous system which is the most common site for recurrency. There are conflicting results because of the small number of patient size. Here we present two cases with primary testicular lymphoma at the ages 71 and 82.

• We have 2 cohorts: 1) PTL patients diagnosed between 2000 and 2017 and 2) PTL patients diagnosed between 1983 and 2017 (lower sample size as this is from a registry that includes lower number of US states). We hoped that cohort 1 would reflect a more contemporary cohort which would have received R-CHOP treatment for PTL. • We stratified patients by age ≤50 and >50. We hoped this would make this a stronger paper and different from previous similar study that used age 70 as cut-off to stratify patients. Primary testicular non-Hodgkin's lymphoma (PTL) is a very rare disease, comprising 1% of all non-Hodgkin's lymphoma and <5% of all cases of testicular tumors. With a median age at diagnosis of 67 years, PTL is the most common testicular malignancy in men aged >60 years. There is limited published data on PTL incidence and outcomes in younger patients. The aim of this study is to compare the clinical parameters and survival outcomes between the patients older and younger than 50. The SEER database was queried for all patients diagnosed with PTL between 1983 and 2017. Data collected consisted of demographic, and clinical parameters, including staging, pathological assessments, and survival data. Patients were stratified according to their age and compared. There was a total of 1,581 patients diagnosed with PTL between the year 2000 and 2017, of whom 215 (13.6%) were younger than 50 years old. The median age at diagnosis was 41 (interquartile range [IQR] 1–50), and 72 (IQR 51–95) years old for patients ≤50 and patients > 50 years of age, respectively. Comparison of younger and older patients detected similarities in disease laterality (92% vs. 94%, P = 0.38) and Ann Arbor stage I to II at diagnosis (76% vs. 75%, P = 0.59). The most common diffuse large B-cell lymphoma (DLBCL) subtype was more common in older patients (61% vs. 87%, P < 0.001). Radical orchiectomy (71% vs. 79%, P = 0.004) and radiation treatment (40% vs. 37%, P = 0.49) rates were comparable between both groups. However, a higher proportion of younger patients underwent chemotherapy (83% vs. 72%, P < 0.001). Patients ≤50 and >50 years old had a hazard ratio (HR) of 0.63 (95% CI: 0.57–0.71) and 0.34 (95% CI: 0.31–0.37), respectively, for 10-year OS with a median survival time for patients >50 of 5.75 years (95% CI: 5.25–6.33), P < 0.001. Patients ≤50 years old had a HR of 0.33 (95% CI: 0.26–0.40) compared to HR of 0.40 (95% CI: 0.37–0.43) in patients >50 years old for cumulative disease-specific mortality (DSM, P = 0.0204). Age >50 years was associated with worse DSM with a HR of 1.39 (95% CI: 1.05– 1.86, P = 0.024). Ann Arbor stage II and higher was also associated with worse DSM, while undergoing surgery, radiotherapy, and chemotherapy were associated with improved DSM. PTL is the most common testicular malignancy in men older than 60 years of age, but more than a quarter of the patients are younger than 60 and more than 13% are ≤50 years. Younger patients are more likely to receive chemotherapy and radiation, and overall do better in terms of DSM. Being younger, having a lower Ann Arbor stage and being treated with chemotherapy and radiotherapy increase the chances of survival. [ABSTRACT FROM AUTHOR]

Primary testicular lymphoma (PTL) accounts for 1-2% of all nonHodgkin lymphomas (NHL), 4% of extranodal nonHodgkin lymphomas, and ~9% of testicular malignancies. A rare subtype of PTL is primary testicular diffuse large B-cell lymphoma (PT-DLBCL), which may initially present as disseminating metastasis in older adult males and has a poor prognosis., Case Presentation: Herein, the authors describe the case of a 64-year-old man with the chief complaint of a painless unilateral scrotal mass. Computed tomography scans of the abdomen and a pelvic examination demonstrated a left testicular tumor with multiple lymphadenopathies partially aggregated in the para-aortic area and disseminated to multiple soft tissues and organs. Subsequently, the patient underwent a left radical orchiectomy. Pathological and immunohistochemical examinations confirmed the diagnosis of left PT-DLBCL with systemic disseminating metastases., Clinical Discussion: PTL often aggressively spreads to other extranodal organs, such as the contralateral testis, central nervous system, lung, pleura, Waldeyer's ring, and soft tissues. In men over 60 years of age, PT-DLBCL is the most common testicular malignancy. However, extensive systemic metastasis as the initial presentation is extremely rare. PT-DLBCL has a dismal prognosis and requires radical orchiectomy followed by multimodal therapy and central nervous system prophylaxis or systemic intervention to improve survival., Conclusion: The diagnosis of PT-DLBCL through preoperative and imaging examinations is often challenging. Thus, histopathology and immunohistochemical markers play a crucial and valuable role in the definite diagnosis and differential diagnosis of PTLs., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Primary testicular lymphoma (PTL) is a rare testicular malignancy, despite being considered the most common testicular tumor in patients older than 60 years. Primary testicular lymphoma represents only 1%-9% of testicular neoplasms. Few studies have been published regarding its clinical features and management. This study aimed to analyze the clinical characteristics and outcomes of PTL., Materials and Methods: Orchiectomy specimens of 15 patients with PTL diagnosed during 2000-2020 at our institution were retrospectively studied. We collected information on demographic data, clinical features, management aspects, and outcomes of PTL treatment. Kaplan-Meier survival curves and Cox regression analyses were used to study survival., Results: The median patient age was 69 years (interquartile range, 61-72 years). The most prevalent clinical presentation was testicular swelling (80%), and only 13.33% of the patients presented with systemic symptoms. Central nervous system involvement was detected in 6 patients (40%). Of the 15 patients, 5 (33.33%) had stage IE and 10 (66.67%) had stage IVE lymphoma. Diffuse large B-cell lymphoma was the most common histological subtype. Twelve patients (80%) received chemotherapy. During follow-up, 4 patients (26.67%) relapsed. The recurrence rate in the contralateral testicle was 13.33%. The median cancer-specific survival was 21.58 months (95% confidence interval, 0-43.95 months). Univariate Cox regression analysis showed that central nervous system involvement and International Prognostic Index score were significantly associated with shorter cancer-specific survival., Conclusions: Primary testicular lymphoma has a high relapse rate and poor prognosis. Management strategies typically include radical orchiectomy and systemic chemotherapy. Central nervous system involvement and International Prognostic Index scores were associated with lymphoma-specific survival., Competing Interests: No conflict of interest has been declared by the authors., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is produced during the metabolism of sphingolipid by sphingosine kinase. S1P has been implicated in the migration and trafficking of lymphocytes and several lymphoid malignancies through S1P receptors. Moreover, the overexpression of sphingosine-1-phosphate receptor 1 (S1 PR1) has been correlated with the constitutive activation of signal transducer and activator of transcription ( STAT)3 and poor prognosis of diffuse large B-cell lymphoma ( DLBCL). Thus, in this study, we examined the expression of S1 PR1 in 198 DLBCL samples collected from nodal and various extranodal sites and sub-classified formalin-fixed paraffin-embedded tissue samples into germinal centre B-cell-like ( GCB) and non- GCB subgroups using immunohistochemistry. These analyses showed S1 PR1 overexpression in 15·7% of all cases with DLBCL and in 54·2% of 24 cases with primary testicular ( PT)- DLBCL; S1 PR1 expression correlated with S1 PR1 mRNA expression and STAT3 phosphorylation in fresh samples. Analyses of data from a single institution suggested that S1 PR1 overexpression was an independent negative prognostic marker in 68 patients with DLBCL of clinical stages I and II. The present high prevalence of S1 PR1 overexpression warrants the consideration of PT- DLBCL as a distinct disease subtype and suggests the potential of the S1P/S1 PR1 axis as a therapeutic target. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study is to evaluate the clinical characteristics, pathology, treatment outcomes, and survival of primary testicular lymphoma (PTL) patients treated at our hospital after 1990. Related literature was reviewed. Materials and methods We retrospectively enrolled patients diagnosed with PTL between January 1990 and September 2013 in our institute. Clinical features, pathology, and overall survival were analyzed. Results 24 patients were enrolled. They had a mean age at diagnosis of 65.0 years (range 10–84 y), mean follow-up duration 57.0 months (range 3–182 mo), and median overall survival of 38 months (range 4.0–184.7 mo). The most common pathology subtype was diffuse large B-cell lymphoma ( n = 21, 87.5%). Fourteen patients (58.3%) achieved complete remission of disease and five patients (20.8%) achieved partial remission after treatment. Three patients had a relapse of disease after complete remission: one in the brain parenchyma, one in the pelvis soft tissue and omentum, and one in the left pyriform muscle. Three patients had metastasis after partial remission of disease: two in the brain parenchyma and one in the cauda equina. By univariate analysis, the factors significantly associated with superior overall survival were primary tumor diameter < 7.5 cm, serum lactate dehydrogenase ≤ 250 U/L, Ann-Arbor Stage IE/II, and International Prognostic Index (IPI) ≤ 1 ( p < 0.05). Rituximab-containing treatment did not show overall survival benefits in our series. By multivariate analysis, IPI ≤ 1 showed statistical significance ( p = 0.019), suggesting a potential prognostic value of IPI in evaluating PTL patients. Conclusions The overall survival of PTL patients is poor, especially those with extensive disease (Stage III/IV). The IPI have a prognostic role in PTL. The use of rituximab in the treatment regimen of PTL does not seem to improve survival in our series. [ABSTRACT FROM AUTHOR]