Paraneoplastic Hyperthyroidism in Advanced Testicular Non-Seminomatous Germ Cell Tumors: Prevalence and Clinical Management.

INTRODUCTION: Paraneoplastic hyperthyroidism (PH) has been reported in patients with testicular germ cell tumors (GCTs), sporadically. This disorder is caused by extremely elevated serum levels of beta-human chorionic gonadotropin (bHCG). To date, little is known about the prevalence of PH, and its clinical features are poorly understood. The aim of the present study was to analyze the relative frequency and clinical features of PH in GCTs and evaluate their effects on therapeutic outcomes. METHODS: A cohort of 438 patients treated for testicular GCT from 2017 to 2023 was retrospectively analyzed for histology, age, clinical stage, and presence of PH. The clinical features of the patients with PH were evaluated descriptively. The relative frequency of PH was compared among the subgroups using descriptive statistical methods. RESULTS: Three patients with PH were identified; all had clinical symptoms of hyperthyroidism, suppressed serum levels of thyroid-stimulating hormone (TSH), and increased levels of tri-iodothyronin (fT3). All the patients had advanced, metastasized, and non-seminomatous GCTs. Serum bHCG levels ranged from 225,00 U/L to 1,520,000 U/L. The prevalence of PH was 0.7% in the entire GCT population and 60% in those with very high bHCG serum levels. All the patients received standard cisplatin-based chemotherapy along with thyrostatic treatment. The clinical symptoms of the hyperthyroidism rapidly disappeared. TSH levels normalized with decreasing bHCG levels. The PH treatment did not affect the therapeutic outcomes of the patients. CONCLUSION: PH may occur in 0.7% of all patients with GCT but may be present in up to 60% of patients with very high levels of bHCG. Measuring serum levels of TSH and fT3 should be performed in addition to routine diagnostic measures in all patients with poor prognosis GCTs. Thyrostatic medication is recommended for patients with the clinical symptoms of hyperthyroidism. Early recognition of hyperthyroidism and prompt intervention will reduce comorbidity and help optimize therapeutic outcomes.

Serum Levels of MicroRNA-371a-3p for Predicting the Histology of Postchemotherapy Residual Masses of Germ Cell Tumours.

BACKGROUND AND OBJECTIVE: Serum levels of microRNA-371a-3p (M371) represent a novel and sensitive biomarker of germ cell tumours (GCTs). This study analysed the utility of M371 to identify viable cancer (VC) in postchemotherapy (pc) residual masses with the underlying goal of avoiding overtreatment. METHODS: A multicentric, prospective diagnostic study was conducted in 180 GCT patients undergoing pc resection of residual masses. A correlation of M371 measurement results with the histological presence of VC in masses was found. A receiver operating characteristic analysis was performed for exploring the performance characteristics of the test. KEY FINDINGS AND LIMITATIONS: The sensitivity was found to be 68.9%, specificity 99.3%, area under the curve 0.813, positive predictive value 0.969, and negative predictive value 0.905; sensitivity is significantly associated with the percentage of VC in the mass. In specimens with ≤10% VC, there were 33.3% elevated M371 levels as opposed to 85.7% in specimens with >50% VC. Teratoma and somatic-type malignancy do not express M371. A lack of a central pathological review is a limitation. CONCLUSIONS AND CLINICAL IMPLICATIONS: The M371 test can identify 68.9% of patients with VC in pc masses. However, cases with <10% VC in the mass may escape detection. Teratoma does not express M371. The test alone cannot correctly identify patients requiring pc surgery, but it may be a tool for scheduling the extent of surgery. PATIENT SUMMARY: The microRNA-371a-3p (M371) test can identify about two-thirds of patients with viable cancer in residual metastatic masses following chemotherapy for germ cell tumours. Only masses with high percentages of viable cancer cells can be identified, and the histological subtype teratoma remains undetected with the test.

Myoid gonadal stromal tumor of the testis-the novel subtype of testicular gonadal stromal tumors: a case report and review of the literature.

BACKGROUND: Sex cord gonadal stromal tumors compose less than 10% of all testicular neoplasms and consist of a variety of histological subtypes. In 2016, the World Health Organization introduced a novel subtype, the myoid gonadal stromal tumor, that consists of spindle-shaped cells with immunohistologic features of muscle cells. Only few cases have been reported to date. Due to its rarity and owing to its only recent introduction, the current knowledge about myoid gonadal stromal tumor is limited, and particularly, appropriate clinical management is still ill-defined. CASE PRESENTATION: A 47-year-old man of Caucasian descent presented with nonspecific scrotal discomfort. A roundish and well demarcated hypoechoic mass of 8.5 mm in diameter was detected in the cranial region of the left testis. Serum tumor marker levels were within normal ranges. Testis-sparing surgery revealed a 9-mm whitish, hard mass with sharp surgical margin. Histologically, the neoplasm consisted of microfibrillar tissue with spindle-shaped cells harboring elongated nuclei. Immunohistochemical work-up disclosed expression of desmin, small muscle actin, and S100 protein giving evidence for the myogenic nature of the neoplastic cells. There was no indication of malignancy, neither histologically nor clinically. Follow-up of 1 year was uneventful. CONCLUSION: A literature survey revealed 22 previous cases of myoid gonadal stromal tumor. The median age was 37 years, the median size of the neoplasm was 20 mm, and there was no side-preponderance. Myoid gonadal stromal tumor is not much different from other subtypes of gonadal stromal tumors nor from testicular gem cell tumors regarding age and laterality; however, tumor size is smaller in myoid gonadal stromal tumors than in germ cell tumors. Although rarely performed so far, testis-sparing surgery probably constitutes an appropriate treatment of this neoplasm. Myoid gonadal stromal tumor represents an emerging novel entity of benign testicular new growths that caregivers of patients with testicular tumors should be aware of.

Subsets of preoperative sex hormones in testicular germ cell cancer: a retrospective multicenter study.

Preoperative homeostasis of sex hormones in testicular germ cell tumor (TGCT) patients is scarcely characterized. We aimed to explore regulation of sex hormones and their implications for histopathological parameters and prognosis in TGCT using a data-driven explorative approach. Pre-surgery serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) and prolactin were measured in a retrospective multicenter TGCT cohort (n = 518). Clusters of patients were defined by latent class analysis. Clinical, pathologic and survival parameters were compared between the clusters by statistical hypothesis testing, Random Forest modeling and Peto-Peto test. Cancer tissue expression of sex hormone-related genes was explored in the publicly available TCGA cohort (n = 149). We included 354 patients with pure seminoma and 164 patients with non-seminomatous germ cell tumors (NSGCT), with a median age of 36 years. Three hormonal clusters were defined: 'neutral' (n = 228) with normal sex hormone homeostasis, 'testicle' (n = 91) with elevated T and E2, low pituitary hormones, and finally 'pituitary' subset (n = 103) with increased FSH and LH paralleled by low-to-normal levels of the gonadal hormones. Relapse-free survival in the hormonal subsets was comparable (p = 0.64). Cancer tissue expression of luteinizing hormone- and follicle-stimulating hormone-coding genes was significantly higher in seminomas, while genes of T and E2 biosynthesis enzymes were strongly upregulated in NSGCT. Substantial percentages of TGCT patients are at increased risk of sex hormone dysfunction at primary diagnosis before orchiectomy. TGCT may directly influence systemic hormonal homeostasis by in-situ synthesis of sex hormones.

Unilateral, Small, Benign, Late-Onset, Large-Cell Calcifying Sertoli Cell Tumor: A Case Report.

Large-cell calcifying Sertoli cell tumor (LCCST) is a rare, testicular sex cord, gonadal stromal tumor that belongs to the histological subgroup of Sertoli cell tumors. LCCSTs may involve malignant potential. However, metastasis is a rare phenomenon. We describe a case of benign late-onset LCCST with testis-sparing surgery. Modern imaging techniques were useful for considering organ-sparing surgery. The ultrasound of a 37-year-old man disclosed a sharp demarcated and strong hyper-echoic lesion sized 1.5 cm, with broad dorsal acoustic shadowing. Testicular tumor markers, including lactate dehydrogenase (LDH), alpha-fetoprotein (AFP), and Beta-human chorionic gonadotropin (ß-HCG) did not reveal any pathological finding. Contrast-enhanced MRI of the pelvis showed a ring-shaped tumor with a strong contrast medium enhancement. Sections of the tumor showed a hard mass with a white calcified ring. A frozen section examination of the testicular tumor did not indicate malignancy. Histologic examination revealed a prominent and noticeable calcification of approximately 3 mm thickness. Tumor cells presented in the form of solid nests, tubules, and cords. Our present case differs from previously reported LCCST cases because the tumor was unilateral, smaller in size, and presented in an older patient.

Familial Testicular Germ Cell Tumor in Two Brothers With Emery Dreifuss Muscular Dystrophy Caused by an FHL-1 Mutation: A Case Report.

Testicular germ cell tumor (GCT) is a rare disease, accounting for no more than 1.5% of all neoplasms in males, but represents the most common tumors in adolescents and young men in Western countries. There is also consensus about the involvement of genetic factors in the etiology of testicular GCT. Familial occurrence of testicular GCT is observed in 1-2% of all cases with GCT. We report the unique case of two brothers, both afflicted with inherited Emery-Dreifuss muscular dystrophy (EDMD) and both developing testicular GCT in young adulthood. EDMD is a rare muscular dystrophy, characterized by the triad of joint contractures, slowly progressive muscle weakness, and cardiac involvement. EDMD is not a homogeneous clinical entity because it is associated with various gene mutations. One common mutation relates to the Four and a half Limb domain protein 1 (FHL-1) gene. To date, there have been no GCT cases linked with FHL-1 mutations and no malignant disease has been found associated with EDMD.

Tertiary Syphilitic Gumma Mimicking Testicular Neoplasms.

Palpable testicular masses in men aged 20 to 50 years usually represent testicular germ cell tumors. Diagnostic work-up involves ultrasound examination as well as serum tumor markers alpha fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase, and particularly the novel marker M371. Orchidectomy is mandatory for germ cell tumors. We report the rare case of testicular involvement by tertiary syphilis mimicking testicular neoplasms with testis-sparing management. A 46-year-old Caucasian male presented with a painless firm mass in the right testicle and multiple cutaneous plaques at the skin of the scrotum, penis and right forearm. Testicular serum tumor markers were negative. Syphilis Rapid Plasma Reagin test and Treponema pallidum immunoglobulin antibodies tests were positive. Radiological examination revealed bilateral testicular lesions as well as bipulmonal pleural-based opacities. Conservative management was attempted and treatment with ceftriaxone (2 g/day) intravenously for 14 days was administered. The testicular findings improved rapidly and significantly during antibiotic treatment. Radiological follow-up examinations after two weeks and two months showed further regression of the testicular and pulmonary lesions. This case represents an extremely rare testicular manifestation of tertiary syphilis. Due to rising syphilis incidence in Europe, tertiary syphilis with formation of gumma should be a differential diagnosis of testicular tumor. Thus, syphilis-specific treatment is safe and orchidectomy can be avoided.

Impact of Sarcopenia on Functional and Oncological Outcomes After Radical Prostatectomy.

Introduction and Objectives: Knowledge about the significance of sarcopenia (muscle loss) in prostate cancer (PCa) patients is limited. The aim of this study was to determine the influence of skeletal muscle index (SMI) on early functional and pathological outcome in patients undergoing radical prostatectomy (RP). Materials and Methods: One hundred randomly chosen patients who received RP between November 2016 and April 2017 at Martini-Klinik (Hamburg, Germany) were retrospectively assessed. SMI (skeletal muscle mass cross-sectional area at L3/m2) was measured by preoperative staging computed tomography scans at L3 level. Cox regression analysis was applied to determine the impact of SMI on post-operative outcome. Follow-up was 12 months. Continence was defined as no more than one safety pad per day. Results: Mean age of the cohort was 63.6 years. Mean SMI was 54.06 cm2/m2 (range, 40.65-74.58 cm2/m2). Of the patients, 41.4% had pT2, 28.7% had pT3a, and 29.9% had pT3b or pT4 PCa. SMI revealed to be without significant correlation on tumor stage. Follow-up data of 55 patients were available for early functional outcome analysis. SMI showed no significant influence on erectile function in multivariable Cox regression analysis. In multivariable Cox regression analysis, SMI turned out to have no influence on continence rates 6 weeks after surgery. Conclusion: The present study shows that patients undergoing RP have a wide range of SMI. Unlike in other urological malignancies, there was no significant impact of SMI on early functional outcome and pathological outcome. A larger cohort is needed to confirm these results.