Primary Testicular Diffuse Large B-cell Research Articles

IELSG30 phase 2 trial: intravenous and intrathecal CNS prophylaxis in primary testicular diffuse large B-cell lymphoma

AbstractPrimary testicular diffuse large B-cell lymphoma (PTL) is characterized by high risk of contralateral testis and central nervous system (CNS) relapse. Chemoimmunotherapy with intrathecal (IT) CNS prophylaxis and contralateral testis irradiation eliminates contralateral recurrences and reduces CNS relapses. The IELSG30 phase 2 study investigated feasibility and activity of an intensified IT and IV CNS prophylaxis. Patients with stage I/II PTL who had not received treatment received 2 cycles of IV high-dose methotrexate (MTX) (1.5 g/m2) after 6 cycles of the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, every 21 days). IT liposomal cytarabine was administered on day 0 of cycles 2 to 5 of 21-day R-CHOP regimen. Contralateral testis radiotherapy (25-30 Gy) was recommended. Fifty-four patients (median age: 66 years) with stage I (n = 32) or II (n = 22) disease were treated with R-CHOP, 53 received at least 3 doses of IT cytarabine, 48 received at least 1 dose of IV MTX, and 50 received prophylactic radiotherapy. No unexpected toxicity occurred. At a median follow-up of 6 years, there was no CNS relapse; 7 patients progressed, and 8 died, with 5-year progression-free and overall survival rates of 91% (95% confidence interval [CI], 79-96) and 92% (95% CI, 81-97), respectively. Extranodal recurrence was documented in 6 patients (in 2 without nodal involvement). In 4 cases, the relapse occurred >6 years after treatment. Causes of death were lymphoma (n = 4), second primary malignancy (n = 1), cerebral vasculopathy (n = 1), unknown (n = 2). Intensive prophylaxis was feasible and effective in preventing CNS relapses. Late relapses, mainly at extranodal sites, represented the most relevant pattern of failure. This trial was registered at www.clinicaltrials.gov as #NCT00945724.

Improved Survival with Rituximab-Based Chemoimmunotherapy in Patients with Primary Testicular Diffuse Large B-Cell Lymphoma

Background: Primary testicular lymphoma (PTL) accounts for 1% to 2% of non-Hodgkin's lymphomas. Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of PTL, accounting for 80% to 98% of cases. The introduction of rituximab was a breakthrough in DLBCL treatment. However, the impact of rituximab on primary testicular DLBCL (PT-DLCBL) is controversial. A study by Gundrum et al (Gundrum JD, et al. J Clin Oncol 2009) found that PT-DLBCL survival did not improve in the rituximab era (i.e., after 2000). However, that study was based on a Surveillance, Epidemiology, and End Results (SEER) database cut-off of 2005. The follow-up period of PT-DLBCL patients in the rituximab era was relatively short, at only 4 years (from 2001 to 2005). Considering the wide use of rituximab in all kinds of DLCBL, we conducted a study based on the SEER database to evaluate the potential impact of the introduction of rituximab on PT-DLBCL. Methods: Data from the SEER 13 registries were analyzed in this study. Cases with PT-DLBCL diagnosed from 1992 to 2018 were included. Baseline characteristics, including age at diagnosis, laterality (left, right, bilateral), age, race, Ann Arbor stage, SEER cause-specific death classification, survival months, and vital status, were collected. Cancer-specific survival (CSS) was used as the study endpoint and defined as the time from diagnosis to death from DLBCL or last follow-up. The Kaplan-Meier method was used to build survival curves and the log-rank test used to compare groups. All p values were two-sided, and p-values < .05 considered statistically significant. All analyses were conducted using GraphPad PRISM 6. Results: A total of 961 patients were included in this analysis. Among them, 271 were diagnosed from 1992 through 2000 (pre-rituximab era) and 690 from 2001 through 2018 (rituximab era). In all, 435 patients showed unilateral left-side testicular involvement, 455 right-side, 63 bilateral, and 8 unknown. At last follow-up, 489 patients had died of PT-DLBCL. Patients diagnosed in the pre-rituximab era had more stage I disease than their counterparts in the rituximab era. No difference was found in age, race, or laterality across the two eras. For the entire cohort, there was a significant improvement in CSS in the rituximab era compared with the pre-rituximab era. The median CSS in the pre-rituximab era was 98 months compared to not reached in the rituximab era ( p = .001) (Figure 1A). We also compared the CSS of patients in different stages: early stage (I/II) or advanced stage (III/IV) in the pre-rituximab and rituximab eras. We found that CSS improved significantly in either early or advanced stage (early stage, p < .0017; advanced stage, p = .026; Figure 1B and 1C). We also explored the role of laterality in survival of PT-DLBCL. Compared with the pre-rituximab era, CSS of either left-side (Figure 1D) or right-side (Figure 1E) PT-DLBCL improved significantly (left-side, p < .001; right-side, p = .04) in the rituximab era. The introduction of rituximab decreased CSS by about 50% in patients with left-side PT-DLBCL but only about 30% in those with right-side disease, which indicated that patients with left-side (vs right-side) PT-DLBCL derived greater survival benefit from the introduction of rituximab. Conclusions: Survival of PT-DLBCL patients improved significantly in the rituximab era, with the survival curve reaching a plateau from the tenth year after treatment. Patients with left-side (vs right-side) PT-DLBCL derived greater survival benefit from the introduction of rituximab.

Development and validation of a survival nomogram in patients with primary testicular diffuse large B-cell lymphoma.

We developed and validated a nomogram for overall survival (OS) and cancer-specific survival (CSS) prediction in patients with primary testicular diffuse large B-cell lymphoma (PT-DLBCL). Patients diagnosed with PT-DLBCL were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Independent prognostic factors were analyzed to establish a nomogram of OS and CSS. Patients were reclassified into high- and low-risk groups; survival was compared using Kaplan-Meier curves and log-rank tests. We collected 1099 PT-DLBCL cases (2000-2019) from SEER and randomized into training (n = 771) and validation (n = 328) cohorts. In univariate and multivariate Cox regression analyses, five prognostic indicators (age, treatment modality, diagnosis year, Ann Arbor stage, laterality) were used to establish a nomogram of OS and CSS. The nomogram demonstrated excellent discrimination and calibration, with concordance indices in the training and validation cohorts of 0.702 (95% confidence interval [CI], 0.677-0.727) and 0.705 (95% CI 0.67-0.74) for OS and 0.694 (95% CI 0.663-0.725) and 0.680 (95% CI 0.63-0.72) for CSS. The calibration curve and ROC analysis indicated good predictive capability of the nomogram. The constructed prognostic model showed good predictive value for PT-DLBCL to assist clinicians in developing individualized treatment strategies.

Unusually aggressive primary testicular diffuse large B-cell lymphoma initially presenting as systemic disseminating metastases in older adult men: a case report.

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. 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. 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.

What factors are associated with the prognosis of primary testicular diffuse large B-cell lymphoma? A study based on the SEER database.

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a relatively rare urological tumor with a high degree of malignancy and a poor prognosis. This study aimed to investigate the prognostic risk factors for survival of patients with PT-DLBCL, and then to construct a predictive model and verify its reliability. First, we selected subjects from the SEER database (2000-2018) and analyzed the survival of PT-DLBCL patients by Kaplan-Meier test. Then, we analyzed prognostic factors by Cox regression. Finally, the data from the training cohort were used to construct a prediction model and represented with a nomogram. We evaluated the nomogram using the consistency index (C-index), decision curve analysis (DCA), and the area under the subject operating characteristic curve (ROC). In addition, calibration curves were plotted to assess the agreement between the column plot model and the actual model. We identified five independent risk factors for patient prognosis affecting OS and CSS in patients with PT-DLBCL by univariate and multivariate analysis, including age, transversality, Ann Arbor staging, chemotherapy, and radiotherapy. According to the above factors, we constructed prognostic nomograms, and found that age contributed the most to the survival of patients with PT-DLBCL. The C-indexes for the nomogram of OS and CSS in the training cohort were 0.758 (0.716-0.799) and 0.763 (0.714-0.812), and in the validation cohort were OS and CSS 0.756 (0.697-0.815) and 0.748 (0.679-0.817). We produced the first nomogram of PT-DLBCL, and it can be used to evaluate the CSS and OS of patients to determine the prognosis of patients.

Relapse of Ocular Lymphoma following Primary Testicular Diffuse Large B-cell Lymphoma

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The single-cell landscape reveals unique tumor subsets and microenvironments associated with poor clinical outcomes in primary testicular diffuse large B-cell lymphoma

The single-cell landscape reveals unique tumor subsets and microenvironments associated with poor clinical outcomes in primary testicular diffuse large B-cell lymphoma

Clinical Characteristics and Prognosis of Patients with Primary Testicular Diffuse Large B-Cell Lymphoma

To analyze the clinical manifestations, therapeutic response and prognosis of patients with primary testicular diffuse large B-cell lymphoma (PT-DLBCL). Thirty-eight patients with PT-DLBCL were enrolled, who hospitalized from January 2010 to April 2021, and their clinical characteristics, treatment regimen and efficacy were collected and analyzed retrospectively. The median age of the patients was 56 years old (ranged from 38 to 79 years). There were 4 cases (10.5%) with bilateral lesions, 13 cases (34.2%) with left lesions, and 21 cases (55.3%) right lesions. There were 2 cases(5.3%) with B symptoms, 6 cases (15.8%) of germinal center B-cell-like(GCB) subtype and 32 cases(84.2%) of non-GCB subtype. Efficacy was evaluated in 36 cases, including 10 cases with CHOP regimen, 21 cases with R-CHOP regimen (7 cases were treated with rituximab combined with high-dose methotrexate injection chemotherapy at intervals of R-CHOP regimen), and 5 cases with other regimens. In 36 patients, the efficacy evaluation of initial chemotherapy showed that the overall response rate (ORR) was 86.1%, 29 cases (80.6%) reached complete response (CR), and 2 cases (5.5%) reached partial response (PR). The R-CHOP group was superior to CHOP group in ORR (95.2% vs 60.0%, P=0.027) and CR (90.4% vs 50.0%, P=0.022). Of the 36 patients, 7 cases had central nervous system(CNS) recurrence and 4 cases had contralateral testicular recurrence. Compared with the CHOP group, the CNS recurrence rate in the R-CHOP group was significantly lower (4.8% vs 50.0%, P=0.007), and the testicular recurrence rate in the R-CHOP group was also lower than the CHOP group, but the difference was not statistically significant (4.8% vs 30.0%, P=0.087). The median follow-up time was 27(3-135) months, and the 5-year PFS and OS were 71% and 74%, respectively. Kaplan-Meier univariate analysis showed that the R-CHOP regimen significantly improved the patients' PFS (P=0.024) and OS (P=0.025) compared with the CHOP regimen. PT-DLBCL is mainly treated with comprehensive treatment. Compared with CHOP regimen, R-CHOP regimen can improve the CR rate and ORR, reduce CNS recurrence and contralateral testicular recurrence, and improve the patients' survival. Patients may benefit from high-dose methotrexate combined with rituximab interlaced with R-CHOP regimen.

Primary testicular diffuse large B-cell lymphoma in young patient: an uncommon presentation

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.

Untargeted Metabolomics of Cerebrospinal Fluid in Patients with Primary Central Nervous System Lymphoma

Primary central nervous system lymphoma (PCNSL) is characterized by a high degree of malignancy and poor prognosis. The current diagnostic techniques include cerebrospinal fluid (CSF) metabolomics examination, imaging examination, needle biopsy, etc., but each examination has certain limitations, and it is difficult for the early identification and diagnosis of the disease. In terms of treatment, relapse and refractory, neurotoxicity and drug resistance are still the main problems currently faced. Metabolomics can measure the composition of metabolites and the dynamic changes of metabolites in cell models, tissues, organs or the whole organism, and has been widely used in disease diagnosis, efficacy evaluation, nutrition and other fields. Ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS/ technology) has been be used to observe the metabolites changes in CSF. Here, we aimed to explore the application value of metabolomics in the diagnosis and prognosis evaluation of PCNSL. From January 2021 to December 2021, CSF samples from 37 DLBCL patients were collected in Shengli Oilfield Central Hospital and Shandong Cancer Hospital, including 20 male patients and 17 female patients. These patients fall into 4 groups based on clinical presentations: 12 patients in PCNSL group (CNS group), 5 patients in primary testicular diffuse large B-cell lymphoma (DLBCL) group (TE group), 10 patients in Germinal center B (GCB) cell-like DLBCL without central nervous system infiltration (GCB group), and 10 patients in non-GCB DLBCL group without central nervous system infiltration (non-GCB group). The CSF samples were collected before clinical treatment, and the samples were analyzed with UPLC-HRMS/technology. For data analysis, principal component analysis (PCA) was carried out on the obtained components, and the partial least squares discriminant analysis model (PLS-DA) was used for diversification analysis. Analytes with P<0.05 and VIP>1 were considered differential metabolites. The Venn diagram was used to narrow the range of metabolites. By using MetaboAnalyst 5.0 software, pathway enrichment analysis was performed on the identified differential metabolites in CSF, and the corresponding P value was obtained. The metabolic pathways that have a significant effect in CNS group vs TE group, CNS group vs GCB group and GCB group vs non-GCB group were glycerophospholipid metabolism and sphingolipid metabolism. The metabolic pathway that has a significant effect in CNS group vs non-GCB group and TE group vs non-GCB group was glycerophospholipid metabolism. Fatty acid degradation and fatty acid elongation were the significant effects metabolic pathway in TE group vs non-GCB group. We applied Venn diagrams to narrow the range of differential metabolites. There were 47 differential metabolites in the CSF of patients in the PCNSL group vs the non-PCNSL group (Figure 1). Compared with the non-PCNSL group, 33 metabolites such as 3-Hydroxyisovalerylcarnitine, Hesperetin 3'-O-sulfate, and Arteether were up-regulated and 14 metabolites such as Pentaglutamyl folate, Calcipotriol and N-Hexadecanoylpyrrolidine were down-regulated in the CSF of patients in the PCNSL group. In the CNS infiltration high-risk group and the CNS infiltration low-risk group, there were 16 differential metabolites (Figure 2). Compared with the patients in the CNS infiltration low-risk group, 8 metabolites such as 3-Allylphenol sulfate, p-Aminobenzoic acid and 2,3,4-Trichlorophenol were up-regulated and 8 metabolites such as Palmitaldehyde, Carboxamide and Rioprostil were down-regulated in the CNS infiltration high-risk group. In conclusion, glycerophospholipid, sphingolipid, and fatty acid metabolites were the three most important abnormal lipid metabolites existed in PCNSL. This finding may have some value in the development of diagnosis and prognostic tools for evaluating CSF in patients with PCNSL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Primary Testicular Diffuse Large B-cell Lymphoma Presenting in a Young Adult

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.

The Mutation of BTG2 Gene Predicts a Poor Outcome in Primary Testicular Diffuse Large B-Cell Lymphoma.

IntroductionPrimary testicular diffuse large B-cell lymphoma (PT-DLBCL) is a rare and aggressive form of mature B-cell lymphoma commonly found in elder males, but its genetic features are poorly understood. In this study, we had performed target-sequencing of 360 lymphoma-related genes on 76 PT-DLBCL patients with a median age of 65 (33–89). Our data provide a comprehensive understanding of the landscape of mutations in a small subset of PT-DLBCL.MethodsA total of 76 PT-DLBCL patients were sequenced, and their clinical data and follow-up data were collected. The relationship between mutated genes, clinical data and prognosis and survival of PT-DLBCL patients was retrospectively analyzed by statistical software.ResultsWe observed a median of 15 protein-altering variants per patient in our data and was identified recurrent oncogenic mutations of 360 lymphoma-related genes involved in PT-DLBCL, including PIM1 (74%), MYD88 (50%), KMT2D (38%), KMT2C (34%), BTG2 (34%), TBL1XR1 (34%) and ETV6 (24%). Compared with classic DLBCL, PT-DLBCL showed an increased mutation frequency of PIM1, MYD88, BTG2, while NOTCH1 appeared exclusive mutated with PIM1, MSH3 and ETV6. Cox risk model regression analysis showed that age ≥60 years, IPI 3–5 points, BTG2 gene mutation and extranodal organ invasion suggested poor prognosis. Finally, we constructed an OS predict model of PT-DLBCL patients using above factors with a high accuracy.ConclusionIn conclusion, our results revealed genomic characterization of PT-DLBCL, and the mutation of BTG2 was an independent factor predicting a poor prognosis.

Loss of 5-hydroxymethylcytosine as a Poor Prognostic Factor for Primary Testicular Diffuse Large B-cell Lymphoma.

Background: 5-Hydroxymethylcytosine (5-hmC), a stable epigenetic marker, is closely related to tumor staging, recurrence and survival, but the prognostic value of 5-hmC in primary testicular diffuse large B-cell lymphoma (PT-DLBCL) remains unclear. This study aimed to investigate the 5-hmC expression in PT-DLBCL and evaluate its prognostic value.Methods: A total of 34 patients with PT-DLBCL treated in the Department of Hematology from August 2000 to August 2020 were included in this study. The expression of 5-hmC in PT-DLBCL tissues and normal testicular tissues were assessed by immunohistochemistry. 5-hmC staining is estimated as a percentage under every nuclear staining intensity score (0-3), 0 or 1 of which were regarded as 5-hmC reduction. The quantification of 5-hmC reduction is defined as the percentage of cells with 5-hmC staining scores of 0 and 1. According 5-hmC reduction of 80%, a 5-hmC reduction of <80% is regarded as "5-hmC high-level group", and a 5-hmC reduction of ≥80% is regarded as "5-hmC low-level group". Furthermore, Cox regression model was used to evaluate the prognostic value of all covariates.Results: The median percentage of 5-hmC reduction in the PT-DLBCL group was 77.50% (60%-90%), the median 5-hmC reduction in the normal testicular tissues was 30% (20%-50%). Compared with normal testicular tissue, 5-hmC levels in PT-DLBCL tissue were significantly decreased (p<0.05). Of the 34 PT-DLBCL patients, 17 had tumors with relatively low 5-hmC expression (5-hmC reduction of ≥80%) and 17 had tumors with relatively high 5-hmC expression (5-hmC reduction of < 80%). 5-hmC expression was negatively correlated with international prognostic index (p = 0.037), while there was no significant difference in 5-hmC decrease among different groups of age at diagnosis, lactate dehydrogenase, testicular lymphoma involvement (unilateral or bilateral), Ki-67 and tumor diameter. Relatively low 5-hmC expression indicated shorter overall survival (OS) (5-year OS 50.2% vs 81.3%, p=0.022) and progression-free survival (PFS) (5-year PFS 38.5% vs 70.7%, p=0.001). Cox multivariate analysis of IPI (2-3 vs. 0-1), intrathecal prophylaxis (No vs. Yes), and 5-hmC reduction (≥80% vs. <80%) showed that 5-hmC reduction ≥80% (hazard ratio: 7.252, p = 0.005) and not receiving intrathecal prophylaxis (hazard ratio: 7.207, p =0.001) are independent risk factors for poor prognosis of PT-DLBCL.Conclusion: Our results suggested that 5-hmC decline can be identified as a poor prognostic predictor for PT-DLBCL. It is necessary to further explore the underlying mechanism of this epigenetic marker to identify methods to re-establish 5-hmC levels and provide new targets for cancer therapy.

The importance of genomic predictors for clinical outcome of hematological malignancies

The importance of genomic predictors for clinical outcome of hematological malignancies

Clinical analysis of primary testicular diffuse large B-cell lymphoma

Objective To investigate the clinical features, diagnosis, treatment and prognosis of primary testicular diffuse large B-cell lymphoma (PT-DLBCL). Methods The clinical data of 2 patients with PT-DLBCL in the Second People's Hospital of Lianyungang treated in May 2013 and April 2018 was retrospectively analyzed. The clinical features, diagnosis, treatment and prognosis of PT-DLBCL were summarized with review of these 2 cases combining with other 42 cases reported in domestic literature. Results Case 1, a 71 years old man, complained of bilateral scrotal enlargement with pain and discomfort for 2 months. Case 2, an 85 years old man, presented with left scrotal mass for 3 months. All 2 patients underwent orchiectomy. Both of the 2 patients were diagnosed as PT-DLBCL and non-germinal center B-cell (non-GCB) subtype and had Ann Arbor stage ⅠE after operation. Case 1 received only 2 cycles of CHOP (cyclophosphamide, epirubicin, vincristine, prednisone) due to lack of financial support. Case 2 refused chemotherapy and right testis irradiation because of advanced age. They were followed up for 71 months and 12 months, respectively. They were both alive without recurrence at last time of the follow-up. The median age of 44 patients (2 cases in this study and 42 cases reported in the domestic literature) was 64 years old (range 45-87 years old). The most common symptom was unilateral painless testicular swelling (left testis 17 cases and right testis 24 cases). Twenty-one patients were Ann Arbor stage Ⅰ, 6 patients were stage Ⅱ, 6 patients were stage Ⅲ, and 11 patients were stage Ⅳ. Thirty-one patients were non-GCB subtype. Twelve patients were international prognostic index (IPI) score ≥3. Serum lactate dehydrogenase (LDH) level was elevated in 13 patients. All patients underwent orchiectomy. CHOP/R-CHOP chemotherapy was given to 40 patients and prophylactic radiation to contralateral testis was given to 12 patients. Twenty-two patients received prophylactic intrathecal chemotherapy. After a median follow-up of 17 months (range 3-135 months), 14 patients died and the median overall survival time was 13 months (range 3-96 months). Conclusions PT-DLBCL is rare. Its diagnosis mainly depends on pathology, with the majority of patients diagnosed in early Ann Arbor clinical stage and non-GCB subtype. The radical orchiectomy and R-CHOP chemotherapy is recommended due to local relapse and systemic dissemination. It is curable in the early stage while patients with advanced stage have a very poor prognosis. Prophylactic radiation to contralateral testis and intrathecal chemotherapy can decrease the risk of recurrence. Key words: Testicular neoplasms; Lymphoma, large B-cell, diffuse; Diagnosis; Treatment; Prognosis

Prognostic Significance of LDH Ratio in Serum/Cerebral Spinal Fluid of Patients with Primary Testicular Diffuse Large B-Cell Lymphoma.

ObjectivePrimary testicular diffuse large B-cell lymphoma (PT-DLBCL) is relatively rare, and risk factors of this disease are still not well understood. This study aims to identify clinical features and prognostic factors of PT-DLBCL patients.MethodsThirty-two patients were included in this retrospective study who were diagnosed as PT-DLBCL and treated in Fudan University Shanghai Cancer Center between November 2010 and May 2018. The demographic details, clinico-pathological characteristics of the patients were summarized, and the impact on progression-free survival (PFS) and overall survival (OS) was analyzed.ResultsThe median age of the patients was 57 (range 36–76) years old. All patients received rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 4–6 cycles and central nervous system (CNS) prophylaxis, with a CR rate 87.5% and an ORR 96.9%. Nineteen patients continued prophylactic contralateral testis radiation therapy (PCTRT) in our hospital. The 3-year PFS and OS rates were 79% and 92%, respectively. None of the 19 patients who received PCTRT experienced local recurrence. All three patients who suffered from CNS relapse were germinal center B-cell subtype. Kaplan–Meier analyses showed that PT-DLBCL patients with late-stage (Stage IV) (P =0.022), higher IPI score (IPI≥ 2) (P =0.017), B symptoms (P =0.004), and elevated LDH level (P =0.03) had a shorter PFS. More importantly, we found that patients with the ratio of the LDH level in serum to that in CSF ≥ 6.5 suffered from a worse PFS (P =0.028).ConclusionOur work revealed that staging IV, IPI score ≥2, having B symptoms and elevated LDH level were risk factors for PT-DLBCL patients. Significantly, the PT-DLBCL patients with a high ratio of LDH level in serum to that in CSF were indicated to have a worse PFS.

First Case Report of Primary Testicular Diffuse Large B-Cell Lymphoma from the Western Region of Saudi Arabia

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.

First Case Report of Primary Testicular Diffuse Large B-Cell Lymphoma from the Western Region of Saudi Arabia

First Case Report of Primary Testicular Diffuse Large B-Cell Lymphoma from the Western Region of Saudi Arabia

Primary testicular diffuse large B-cell lymphoma: a single center experience

Objective To review the experience of the clinical diagnosis and treatment of primary testicular diffuse large B-cell lymphoma. Methods A review was made who were treated in the Tumor Hospital of Zhengzhou University from January 2011 to November 2018. The average age of the patients was 58 years old, with 4 cases in left side and 8 cases in right side. All patients were admitted to hospital with painless testicle mass. Solid mass of testis were detected by ultrasound with no abnormality in tumor markers. All patients underwent orchiectomy and followed by chemotherapy. Results Twelve primary testicular lymphoma (PTL) were identified by pathology, with 8 cases in phase I, 2 cases in phase II, 1 case in phase III , and 1 case in phase IV. The mean follow-up was 31 months. Inguinal orchiectomy was recommended as a diagnositc and initial therapy. All patients underwent R-CHOP/CHOP chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine and prednisone with or without rituximab, including 6 cases with R-CHOP and 6 cases with CHOP. Nine of 12 patients underwent intrathecal prophylatic chemotherapy and 6 of 12 patients underwent contralateral testicle radiotherapy. Relapse occured in 2 patient with CHOP in central nervous system and died of the disease. One case with CHOP relapsed in abdominal cavity. No contralateral testicle relapse was observed. Conclusions PTL is a rare extranodal lymphoma. Painless testicle tumor in men over 50 years old should suspect of this disease. Inguinal orchiectomy is an important part of the treatment, which combines systemic chemotherapy and prophylactic modalities such as radiotherapy of contralateral testis and/or central nervous system (CNS) prophylaxis. Key words: Lymphoma, B cell; Testis; Treatment; Prognosis

Clinicopathological and fluorescence in situ hibridisation analysis ofprimary testicular diffuse large B-cell lymphoma: asingle-centre case series.

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) represents arare and aggressive extranodal non-Hodgkin's lymphoma (NHL) with some specific features that differ from other NHLs. Formalin fixed, paraffin wax embedded (FFPE) samples of21 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 ofthecontralateral 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%). Themajority ofPT-DLBCL (80.9%) had anon-germinal centre B-cell-like immunophenotype. Immunohistochemical staining showed increased c-Myc protein expression in thePT-DLBCL group compared to thecontrol group (p=0.016). MYC rearrangement was detected in 1 of14 (7.0%), and MYC amplification in 3 of14 (21.0%) patients. One ofthe14 cases (7.0%) in thePT DLBCL group showed BCL2 rearrangement, and four of14 (28.05%) cases showed BCL2 amplification. Complete remission (CR) was achieved in 75.0% ofPT-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 theneed for amore personalised treatment approach.