Clinical, Pathological and Immunohistochemical Characteristics of Patients with Primary Testicular Lymphoma Undergoing Orchiectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Primary testicular lymphoma (PTL) is a rare and aggressive malignant tumour with no specific clinical symptoms. Large-scale evidence-based medical evidence to guide preoperative diagnosis is lacking at present. This study aimed to analyse the clinical, pathological and immunohistochemical characteristics of patients with PTL undergoing testicular resection surgery. METHODS: Literature on the clinical characteristics of patients with PTL undergoing orchiectomy was retrieved from databases, including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang Data. The search covered all available records from the inception of these databases until December 31, 2023. Data extraction was followed by a meta-analysis using Stata 15.0 software. RESULTS: A total of 22 articles and 475 cases of PTL were included. The meta-analysis revealed that 58.1% of patients with PTL undergoing orchiectomy were under 60 years old, and 41.9% were 60 years or older. The lesion is mostly located on the right side (55.1%). Common symptoms included testicular swelling and falling swelling (91.3%), hydrocele testis (31.0%) and testicular pain (23.0%). Ann Arbor stages I-IV accounted for 53.3%, 16.7%, 14.8% and 15.7%, respectively. Diffuse large B-cell lymphoma (DLBCL) cases were higher at 95.5% than NK/T-cell lymphoma cases at 8.2%. Amongst DLBCL cases, 69.3% were non-germinal centre B-cell (GCB) subtype, and 27.6% were GCB subtype. Immunohistochemistry markers showed 95.9% CD3 negative, 94.9% CD10 negative, 94.4% CD20 positive, 88.4% multiple myeloma oncogene-1 (MUM-1) negative, 73.6% B-cell lymphoma-6 (BCL-6) negative and 66.5% BCL-2 positive. Laboratory findings indicated that 70.4% of patients had a tumour proliferating cell nuclear antigen (Ki67) index of ≥80%, 36.0% had increased serum lactate dehydrogenase level and 22.9% had increased serum ß2-microglobulin level. CONCLUSIONS: PTL is rare, and it often occurs in elderly male patients. Common symptoms include testicular swelling and falling swelling, and the common histological type is DLBCL. Diagnosis should be based on histopathological characteristics and immunohistochemical examination.

Follow-Up of Patients Diagnosed With Germinal Testicular Tumors (Seminomas and Non-seminomatous) Treated With a Bone Marrow Transplant and a High Dose of Chemotherapy.

INTRODUCTION: Germinal testicular tumors are the most common malignant neoplasm in men around 20 to 34 years. Even though they are unusual, they have increased incidence in the last decade; they have an excellent prognosis and overall survival at five years, approximately 95%. Divergent data exists regarding treatment options in patients with first, second, and third relapses with conventional therapy. Some studies describe the possible benefit of using high-dose chemotherapy associated with a bone marrow transplant with variable results. METHODS:  The present study describes clinical outcomes, clinical response, mortality, overall survival, and progression-free survival to two years in a group of patients with germinal malignant tumors, seminoma versus non-seminomatous with evidence of progression of the disease at first, second, or third conventional chemotherapy regimens, and who received high dose chemotherapy and bone marrow transplantation at the National Cancer Institute between 2010 and 2021. RESULTS: A retrospective observational study of case series showed that 57% of patients in third-line therapy received high-dose chemotherapy and bone marrow transplantation, with progression disease median time from diagnosis more than two years. Patients in the post-graft period presented infectious complications (71%). The most common were febrile neutropenia (29%) with a mortality rate of 71% (n=5), progression-free survival of 2.3 months, and overall survival of 7.4 months. CONCLUSIONS:  These results show that in this group of patients, regimens with high-dose chemotherapy associated with bone marrow transplants, have a worse prognosis compared to other cohorts of patients, and may not be the best candidates for this rescue therapy.

Primary Retroperitoneal Lymph Node Dissection for Clinical Stage II A/B Seminomas: A Systematic Review and Meta-Analysis.

INTRODUCTION: Chemotherapy and radiation therapy are considered standard treatments for stage II seminoma patients; however, these therapies are associated with long-term toxicities. Recently, retroperitoneal lymph node dissection has emerged as an alternative strategy, and the first three phase II trials were published in 2023 with promising results. The present study conducted a systematic review and meta-analysis to evaluate this surgery as an alternative treatment for stage IIA/B seminoma patients. PURPOSE: Seminomas are the most common testicular tumors, often affecting young adult males. Standard treatments for stage II seminomas include chemotherapy and radiation therapy, but these therapies are associated with long-term toxicities. Thus, identifying alternative strategies is paramount. Herein, we conducted a systematic review and meta-analysis to appraise the efficacy and safety of retroperitoneal lymph node dissection (RPLND) for treating this condition. METHODS: We systematically searched the PubMed, Embase, and Cochrane databases for studies evaluating RPLND as a primary treatment for stage II A/B seminomas. Using a random-effects model, single proportion and means and pooled 2-year recurrence-free survival rates with hazard rates and 95% CI were calculated. RESULTS: Seven studies were included, comprising 331 males with stage II seminomas. In the pooled analysis, the recurrence rate was 17.69% (95% CI 12.31-24.75), and the 2-year RFS rate was 81% (95% CI 0.77-0.86). The complication rate was 9.16% (95% CI 6.16-13.42), the Clavien-Dindo > 2 complication rate was 8.83% (95% CI 5.76-13.31), and the retrograde ejaculation rate was 7.01% (95% CI 3.54-13.40). The median operative time was 174.68 min (95% CI 122.17-249.76 min), median blood loss was 105.91 mL (95% CI 46.89-239.22 mL), and patients with no evidence of lymph node involvement ranged from 0-16%. CONCLUSIONS: Primary RPLNDs for treating stage IIA/B seminomas have favorable RFS rates, with low complication and recurrence rates. These findings provide evidence that this surgery is a viable alternative therapy for these patients.

Epidermoid cyst of the testis: A report of three cases.

Testicular epidermoid cysts have characteristic findings. Testicular tumor markers are negative in patients with epidermoid cysts. Clear margins and sole and small testicular tumors (20 mm or less) suggest the possibility of epidermoid cyst. Testicular-sparing surgery with intraoperative frozen section examination should be performed when suspecting epidermoid cysts. Testicular epidermoid cysts are rare tumors that account for 1% of all testicular tumors and are often clinically misdiagnosed as malignant lesions. We report three cases of epidermoid cysts. The chief manifestations were scrotal induration in two patients and pruritus scrotum in one. The median age of the patients was 23 years (18-30). All tumors were determined to be sole lesions (<20 mm in diameter). Testing for tumor markers in all patients revealed negative results. We could not rule out malignancy; hence, we performed high inguinal orchiectomy in all cases. Histologically, the inner walls of the cysts were lined with stratified squamous epithelium; their contents were keratinized. All patients were diagnosed with epidermoid cysts.

Rare Metastatic Embryonal Carcinoma Resembling Lymphoma: A Case Report

BACKGROUND: Embryonal carcinoma is a rare tissue type in germ cell tumors. According to our literature review, metastatic embryonal carcinoma misdiagnosed as lymphoma because of its high similarity to lymphoma is extremely rare and has not been reported yet. CASE PRESENTATION: A 46-year-old middle adulthood male presented with unexplained fever, night sweats, abdominal distension for 3 months, and weight loss of around 7kg during almost 6 months, which is extremely similar to lymphoma from the clinical features and imaging examinations. After a clear diagnosis, the case not only obtained the opportunity of surgery but was also exempted from radiotherapy. The treatment effect was good. We report a case of rare metastatic embryonal carcinoma, which can provide insight into the diagnosis and treatment of embryonal carcinoma. CONCLUSION: Metastatic embryonal carcinoma of abdominal lymph nodes can be highly similar to lymphoma; the diagnosis can only be based on clinical manifestations and imaging examination but also combined with patient history, tumor markers and biochemical examination. However, the final diagnosis depends on pathological biopsy.

Large Malignant Testicular/Paratesticular Tumors in Adolescence: Assessment of Gross Tumor Size in a Vulnerable Age Group.

OBJECTIVE: We hypothesized that reticence to address a groin mass may result in late presentation of testicular/paratesticular malignancy in early puberty through adolescence. METHODS: Malignant testicular and paratesticular tumors (malignant germ cell tumors and rhabdomyosarcomas) diagnosed at our institution from 1994-2023 for patients aged 11-20 were included. Clinicopathologic features were recorded, and statistically analyzed. RESULTS: Eighty-five cases were identified. Patient ages ranged from 11 to 20 years (mean 17 years, median 16 years). The greatest tumor dimension ranged from 0.8 to 18.0 cm (mean 4.4 cm, median 3.5 cm). Ten tumors (11.8% of cases) were ≥10.0 cm. In the 11-13-year-old age group, 100% of tumors (3/3) were ≥10 cm. The proportion of tumors ≥10 cm was significantly higher in the 11-13-year-old age group than in either the 14-16-year-old (P<0.001) or 17-20-year-old (P<0.001) age groups. CONCLUSION: This adolescent cohort with malignant testicular and paratesticular tumors showed a high proportion (11.8%) of very large (≥10 cm) tumors. Although the reasons are unknown and likely multifactorial, this study suggests that adolescents, particularly the 11-13 year age group, are a vulnerable population.

Patients with testicular cancer receiving adjuvant chemotherapy: Compliance with follow-up in the first three years.

PURPOSE: The aim of this study was to investigate the compliance with follow-up in patients receiving adjuvant chemotherapy (ACT) for testicular cancer at two academic hospitals. MATERIALS AND METHODS: The study analyzed 104 patients with testicular tumors who had undergone surgery at least a year before and received ACT between March 2017 to March 2022. The mean follow-up was 29.2±16.2 (12-73) months. Patients were classified as fully compliant (100% compliance), moderately compliant (50-99%), poorly compliant (1-49%), and non-compliant (no attendance) according to their compliance with the follow-up schedule. RESULTS: At the end of the first year, 76% of patients were fully compliant. By the end of the second year, this number dropped to 50%. Furthermore, 25% of patients were identified as non-compliant in the second year and only 4.3% in the third year. When comparing patients who were compliant and non-compliant at first- and second-year follow-up, no statistically significant difference was found according to age, tumor size, disease stage, or ACT regimen (P=0.938, P=0.784, P=0.867, and P=0.282, respectively). CONCLUSION: This study showed that full compliance with follow-up gradually decreased over the years and that the factors examined were not able to predict this decrease. Prospective studies can help design individualized education and follow-up programs, considering each patient's tumor stage.

Risk for testicular germ cell tumors and spermatogenesis failure in post-pubertal undescended testes.

PURPOSE: Cryptorchidism is a well-defined risk factor for testicular germ cell tumors, whereas the underlying mechanisms have not been fully elucidated. Surgical procedures to reposition undescended testicles into the scrotum (orchidopexy) in early childhood are recommended both to increase fertility potential and to reduce the risk of developing testicular tumors. However, treatment in the post-pubertal period is controversial. The aim of this study is to review the histopathology of orchiectomy specimens and determination of spermatogenesis in post-pubertal patients with non-treated cryptorchidism. METHODS: Retrospective chart review was performed to assess the occurrence of TGCTs and determine spermatogenesis in post-pubertal individuals who underwent inguinal orchiectomy for undescended testis between January 2010 and December 2019. Age at the time of surgery, laterality, location of the undescended testis and pathology results were evaluated. All pathology specimens were reviewed by a blinded pathologist. RESULTS: There were 23 patients in the cohort with a mean age of 21 years (range 13-46 years). All testes were in the inguinal canal. Our results indicated that 1 patient had seminoma. In the histological evaluation of the remaining 22 patients in whom no tumor was detected, normal spermatogenesis was not observed in any patient. Further, seminiferous tubules were not found in 19 patients. Maturation arrest was detected in the remaining 3 patients. CONCLUSION: Testicular germ cell carcinoma was found in 4% of the patients who underwent post-pubertal orchiectomy. In addition, none of the undescended testes had normal spermatogenetic activity. Thus, orchiectomy should be considered in post-pubertal males with unilateral undescended testis that do not need the endocrinological activity of the testis.

Relapsed IgA Multiple Myeloma as Testicular Plasmacytoma after Quadrable Novel Therapy and Autologous Stem Cell Transplant: A Rare Case Report and Literature Review.

Introduction: Multiple myeloma (MM) is a clonal neoplasm of plasma cells that may manifest as an extramedullary disease in rare cases. Case Report: In this case report, we present the rare occurrence of testicular relapse in a 39-year-old patient with IgA MM after 3 years of remission. We discuss the clinical course and management of this unusual presentation and provide a comprehensive literature review of testicular involvement by MM. Conclusion: Despite advances in MM treatment, relapse remains common, highlighting the importance of careful follow-up and timely detection of disease recurrence at atypical sites. This case highlights the need for further research to standardize the diagnosis and treatment of testicular MM.

Testicular biopsies in men with testicular microlithiasis and additional risk factors for cancer: A case series.

BACKGROUND: Testicular microlithiasis is the presence of small calcifications in the testicular parenchyma. The association between testicular microlithiasis and germ cell neoplasia in situ, a precursor to testicular cancer, is still unclear. OBJECTIVES: To determine the incidence of germ cell neoplasia in situ in men with testicular microlithiasis and evaluate the indication for testicular biopsy according to risk factors in the form of male infertility/reduced semen quality, testicular atrophy, and history of cryptorchidism. MATERIALS AND METHODS: This retrospective case series included all patients diagnosed with testicular microlithiasis who underwent testicular biopsies at three hospitals in Denmark between 2007 and 2021. The medical records of 167 patients were reviewed, and data on patient demographics, testicular microlithiasis characteristics, risk factors, histological findings, and treatments were collected. The main outcome measure was the incidence of germ cell neoplasia in situ in relation to each risk factor. The data were analyzed using descriptive statistics. Logistic regression was used to examine the odds ratio of germ cell neoplasia in situ in patients with testicular microlithiasis and testicular atrophy. RESULTS: Germ cell neoplasia in situ was found in 13 out of 167 patients (7.8% [95% confidence interval: 4.3, 13.2]). Eleven of these had testicular atrophy resulting in a significantly higher incidence in this group than other risk factors (odds ratio 9.36 [95% confidence interval: 2.41, 61.88]; p = 0.004). DISCUSSION: The study comprises the largest cohort to date of men who have undergone testicular biopsies because of testicular microlithiasis and additional risk factors. Limitations include its retrospective design, and relatively low absolute numbers of patients with germ cell neoplasia in situ on biopsies. CONCLUSION: This study found that men with testicular microlithiasis and testicular atrophy are at an increased risk of germ cell neoplasia in situ. Additionally, our results indicate that biopsies should be considered in men with a combination of subfertility and bilateral testicular microlithiasis. Our findings do not support testicular biopsies for men with testicular microlithiasis and other risk factors.

Giant bilateral prepubertal-type teratomas in a postpubertal patient: An illustrative case and review of the literature.

Prepubertal-type teratomas are uncommon, especially in postpubertal male patients. We document a case of a 28-year-old man with a lifelong history of bilateral testicular masses who presented with scrotal fistulas and no clinical evidence of extratesticular disease. Bilateral radical orchiectomies demonstrated large bilateral solid and cystic masses that contained grossly visible hairs. Microscopically, both tumors consisted of pure teratomas comprising a mixture of mature tissues derived from the three embryonic layers. Germ cell neoplasia in situ was not identified, and fluorescence in situ hybridization studies demonstrated the absence of i(12p), supporting a diagnosis of prepubertal-type teratoma. The absence of metastases in this patient with longstanding tumors highlights the benign nature of prepubertal-type teratomas affecting postpubertal patients. Furthermore, this case illustrates that at least a subset of prepubertal-type teratomas seen in adult men represent a late diagnosis of a largely pediatric entity. Additionally, we performed a comprehensive review of the literature on this topic.

Patients and general practitioner knowledge and perception of testicular self-examination for cancer.

PURPOSE: Testicular cancer (TC) predominantly affects young men and early detection enhances survival. However, uncertainty surrounds the impact of population-wide screening. Testicular self-examination (TSE) is a simple detection method but there is a gap in current practices that needs to be assessed. Our goal was to assess the perceptions and knowledge of male subjects in the general population (MP) and general practitioners (GPs) regarding TSE for TC. METHODS: Two distinct surveys evaluating knowledge and perceptions of TSE for TC were administered to GPs and MP, aged 15‒45-years. Factors that could favour the realisation of TSE or improve the knowledge of TC were evaluated by multivariable logistic regression. RESULTS: Overall, 1048 GPs (mean (SD) age: 35.1 ± 10.3 years) and 1032 MP (mean (SD) age: 27 ± 8.2 years) answered the survey. Among the GPs, only 93 (8.9%) performed scrotal examination for TC screening. Although the majority (n = 993, 94.8%) were aware of the age of onset of TC, most (n = 768, 73.3%) did not know the overall survival rate from TC. GPs familiar with the guidelines were more likely to explain TSE to their patients (OR = 2.5 [95% CI 1.5‒4.1]; p < 0.01). Among the MP, 800 (77.5%) admitted that they did not know how to perform TSE and 486 (47.1%) did not know the main symptoms associated with TC. MP who had already undergone TC screening were more likely to be familiar with the main symptoms (OR = 2.1 [95% CI 1.6‒2.7]; p < 0.001) and MP who knew someone with TC or who had already undergone TC screening were more likely to be aware of the correct prevalence of TC (OR = 1.9 [95% CI 1.3‒2.7], p < 0.01; and OR = 1.6 [95% CI 1.2‒2.1], p < 0.01; respectively). CONCLUSION: The knowledge of both GPs and MP regarding TC could be improved. TSE screening and knowing someone close with TC improved the awareness of our subjects.

Change in telomere length and cardiovascular risk factors in testicular cancer survivors.

BACKGROUND: Testicular cancer (TC) survivors cured with chemotherapy (CT) are prone to develop cardiovascular diseases, as part of an accelerated aging phenotype. A mechanism contributing to these events can be telomere shortening. PATIENTS AND METHODS: In a prospective cohort of patients with disseminated TC who received cisplatin-based CT, mean absolute leukocyte telomere length (TL) was measured before and 1 year after start of treatment. Cardiovascular risk factors, including development of the metabolic syndrome and hypogonadism, were assessed before and up to 5 years after CT. RESULTS: For the whole group (n = 55), TL did not change 1 year after CT (5.7 (2.2-13.4) vs. 5.8 kb (1.6-19.2), P = 0.335). At baseline, patients with a BMI >30 kg/m2 (n = 12) had shorter TL (4.9 (2.2-13.4) vs. 6.3 kb (3.1-12.9), P = 0.045), while no age-dependent differences were measured. Patients with TL shortening after 1 year (n = 7) showed a significant increase in diastolic blood pressure (P = 0.007) and triglycerides (P = 0.003), compared to those with unchanged TL. There was no association between telomere shortening after 1 year or short TL at baseline (n = 7+11) and development of metabolic syndrome (25% vs. 21%; P = 0.777), or hypogonadism (38% vs. 17%; P = 0.120) after 5 years. CONCLUSIONS: A small subset of TC patients treated with cisplatin-based CT showed telomere shortening 1 year after treatment. This shortening was associated to a rise in diastolic blood pressure and triglycerides, but not to newly developed metabolic syndrome and hypogonadism after 5 years.

Primary Retroperitoneal Lymph Node Dissection for Seminoma Metastatic to the Retroperitoneum.

PURPOSE: Primary surgical treatment with retroperitoneal lymph node dissection aims to accurately stage and treat patients with node-positive pure seminoma while avoiding long-term risks of chemotherapy or radiation, traditional standard-of-care treatments. MATERIALS AND METHODS: We reported the pathologic and oncologic outcomes of patients with pure seminoma treated with primary retroperitoneal lymph node dissection in a retrospective, single-institution case series over 10 years. The primary outcome was 2-year recurrence-free survival stratified by adjuvant management strategy (surveillance vs adjuvant chemotherapy). RESULTS: Forty-five patients treated with primary retroperitoneal lymph node dissection for pure testicular seminoma metastatic to the retroperitoneum were identified. Median size of largest lymph node before surgery was 1.8 cm. Viable germ cell tumor, all of which was pure seminoma, was found in 96% (n=43) of patients. The median number of positive nodes and nodes removed was 2 and 54, respectively. Median positive pathologic node size was 2 cm (IQR 1.4-2.5 cm, range 0.1-5 cm). Four of 29 patients managed with postoperative surveillance experienced relapse; 2-year recurrence-free survival was 81%. Median follow-up for those managed with surveillance who did not relapse was 18.5 months. There were no relapses in the retroperitoneum, visceral recurrences, or deaths. Among the 16 patients who received adjuvant treatment, 1 patient experienced relapse in the pelvis at 19 months. CONCLUSIONS: Primary retroperitoneal lymph node dissection for pure seminoma with low-volume metastases to the retroperitoneum is safe and effective, allowing most patients to avoid long-term toxicities from chemotherapy or radiation.