Seminoma of testis with isolated bony metastasis at presentation.

Germ cell tumor (GCT) comprises more than 95% of cases of all testicular tumor. Seminomas are a type of GCT where majority of patient presents with favorable outcome. Metastasis to nonpulmonary are rare scenarios and are grouped as intermediate risk. Most of the patients relapse in pulmonary or nonpulmonary sites within 2 years of treatment completion. However, bony metastasis (BM) on presentation is a rare condition. Here, we report a case of 37-year-old man diagnosed with stage I seminoma and underwent orchidectomy. Positron-emission tomography computed tomography scan after surgery revealed isolated bony metastasis in the left sacrum. Based on this, confirmatory diagnosis of Stage IIIc seminoma was made for which he received four cycles of bleomycin, etoposide, and cisplatin followed by palliative Radiotherapy (RT) to the metastatic region. After 1 year of follow-up, the patient is well and alive with no symptoms.

Comparison between free ß subunit of human chorionic gonadotropin (hCG) and total hCG assays in adults with testicular cancer.

OBJECTIVES: We tested the hypothesis that the free-ß subunit (ßhCG) is diagnostically more sensitive with total hCG assays (hCGt) not detecting all tumours secreting ßhCG. The effects of sex, age, and renal failure were investigated as secondary objectives. METHODS: We compared ßhCG with hCGt in 204 testicular cancer patients (99 seminomas, 105 non-seminonatous germ cell tumours). The effects of sex and age were determined in 125 male and 138 female controls and that of renal failure was investigated in 119 haemodialysis patients. Biochemical assessment of gonadal status was performed with LH, FSH, oestradiol and testosterone. RESULTS: Discordant results were common with isolated increases of hCGt observed in 32 (15.7 %) and ßhCG in 14 (6.9 %) patients. Primary hypogonadism was the most common cause of isolated hCGt increases. After therapeutic interventions ßhCG decreased below its upper reference more rapidly than hCGt. We observed unequivocal false negative results in two patients with non-seminomatous germ cell tumours. Both occurred in patients with clinical tumour recurrences; in one instance we observed a false negative hCGt while in the second false negative ßhCG's were documented in serial samples. CONCLUSIONS: The similar false negative rates did not support the hypothesis that ßhCG will detect more patients with testicular cancer than hCGt. In contrast to hCGt, ßhCG was unaffected by primary hypogonadism which is a predictably frequent complication in testicular cancer patients. We therefore recommend ßhCG as the preferred biomarker in testicular cancer.

Evaluation of the M371-Test Under Real-life Conditions for Diagnosis and Follow Up of Testicular Germ Cell Tumors.

BACKGROUND/AIM: The aim of the study was to establish the performance of the M371-Test on the Thermocycler Rotor-GeneQ (Qiagen) platform for diagnosis and follow-up of testicular tumors and to evaluate the test under real-life conditions in comparison to the classical markers alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (ß-HCG) and lactate dehydrogenase (LDH). PATIENTS AND METHODS: Forty-four patients, of median age 29 years (range=24-84) were included in this prospective study at our institution between March 2021 and September 2022. Of the 44 patients, 23 had a suspicion of testicular cancer (TC) and 21 were under follow-up for TC. In total, 96 M371-Tests were performed and compared with AFP, ß-HCG, LDH using histological diagnosis and/or computer tomography (CT) scan as the gold standard. RESULTS: In the patients with suspicion of TC, the M371-Test showed a sensitivity of 73.7%, AFP of 21%, LDH of 31.6% and ß-HCG of 42.1%. In the patients under follow-up for TC, the M371-Test showed a sensitivity of 86.4%, AFP of 50%, LDH of 31.8% and ß-HCG of 63.6%. In germ cell tumours (GCT)/non-seminomas, M371-Test had a sensitivity of 83.3%, AFP of 77.8%, LDH of 38.9% and ß-HCG of 66.7%. In GCT/seminomas, M371-Test had a sensitivity of 85%, AFP of 5%, LDH of 30% and ß-HCG of 50%. CONCLUSION: Under real life conditions performed on the real-time Thermocycler Rotor-GeneQ (Qiagen) platform, the M371-Test shows an outstanding performance and is far beyond the sensitivity of the classical markers for detecting GCTs and in the follow-up of patients after GCT, especially in seminomas.

[Burned-out testicular germ cell tumors: a clinicopathological analysis of three cases].

Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 µg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.

A giant intra-abdominal right testicular seminoma in a bilateral undescended testicle: a case report.

Cryptorchidism is the most common congenital malformation of the male genitourinary tract. An undescended testicle has a 10% chance of developing cancer, with an intra-abdominal testicle having the highest risk. We present a 24-year-old man with a history of bilateral cryptorchidism, complaining of lower abdominal mass for two months. An abdominal computed tomography scan showed an intra-abdominal mass lesion measuring 13 x 9 cm and displacing the bladder caudally. Exploratory laparotomy revealed a right intra-abdominal testicular tumor. A right orchiectomy and left orchidopexy was performed. Histopathological examination revealed a testicular seminoma. The patient was discharged without complications and was referred to the oncology department for chemotherapy and further management. Our findings support the early treatment and close monitoring of cases of cryptorchidism due to the risk of malignancy as well as the necessity of routine scrotal examinations in all males presenting with an abdominal mass.

H&E and OCT4/CD34 for the assessment of lympho-vascular invasion in seminoma and embryonal carcinoma.

BACKGROUND: Lymphovascular invasion (LVI) is a relevant prognostic factor in germ cell tumors of the testis (GCTT), and it is included in the pT stage. However, its detection on hematoxylin and eosin (H&E) slides is very challenging, and previous studies reported fair to moderate inter-observer agreement among dedicated uropathologists. In the present study, we tested H&E and a recently developed in-house double staining for OCT4/CD34 to detect LVI in GCTT. METHODS: Nine authors [5 non-uropathologists and 4 uropathologists] independently evaluated 34 consecutive and retrospectively enrolled cases of GCTT. We assessed the inter-observer agreement (Fleiss's Kappa) with both H&E and OCT4/CD34. Besides, we compared the consensus diagnosis on both H&E and OCT4/CD34-stained sections with the original diagnosis to evaluate the pT re-staging (McNemar test) and identify the sources of disagreement. RESULTS: The inter-observer agreement among uropathologists plus non-uropathologists was fair with both H&E (KF=0.398; p < 0.001) and OCT4/CD34 (KF=0.312; p < 0.001). OCT4/CD34 (KF=0.290; p < 0.001) slightly reduces the inter-observer agreement compared to H&E (KF=0.321; p < 0.001) for non-uropathologists; in contrast, OCT4/CD34 (KF=0.293; p < 0.001) significantly reduces the inter-observer agreement compared to H&E (KF=0.529; p < 0.001) for uropathologists, changing it from moderate to fair. Consensus diagnosis with H&E modified the LVI status of the original diagnosis in 8/34 (23.5 %) cases (p: 0.070), with pT re-staging in 2/34 (5.9 %) cases (p: 0.500). Consensus diagnosis with OCT4/CD34 modified the LVI status of the original diagnosis in 8/34 (23.5 %) cases (p: 0.289), with pT re-staging in 3/34 (8.8 %) cases (p: 0.250). The consensus diagnosis with OCT4/CD34 modified the consensus diagnosis with H&E in 8/34 (23.5 %) cases (p: 0.727), and these findings resulted in pT-restaging in 3/34 (8.8 %) cases (p: 0.500). The sources of disagreement among uropathologists were: H&E [artefactual clefts misinterpreted as LVI in 4/6 (66.7 %) cases and true foci of LVI misinterpreted as clusters of histiocytes within the vessels in 2/6 (33.3 %) cases], OCT4/CD34 [artefactual clefts misinterpreted as LVI in 2/8 (25 %) cases, true LVI misinterpreted as artefactual clefts in 2/8 (25 %) cases or floaters in 4/8 (50 %) cases]. CONCLUSIONS: OCT4/CD34 does not improve the inter-observer agreement for the assessment of LVI in OCT4(+) GCTT. Consensus diagnosis with H&E modifies the LVI status in a significant number of cases, resulting in changes of the pT stage in a relatively small subgroup. Consensus diagnosis with OCT4/CD34 provides little additional benefit since it cannot exclude mimickers of LVI such as floaters and artefactual clefts. These results argue against the adoption of this diagnostic tool for the routine assessment of OCT4(+) GCTT.

Germ cell neoplasms of the testis: Update for 2022.

Germ cell neoplasia in situ (GCNIS) is the precursor of both seminomatous and non-seminomatous germ cell tumors. It consists of distended tubules that may have either intratubular seminoma or intratubular embryonal carcinoma cells. Many invasive non-seminomatous tumors contain a mixture of tumor types, which are reviewed here. Morphology, aided by a panel of immunostains, can determine the presence and percent of embryonal carcinoma, yolk sac tumor, choriocarcinoma, or teratoma in such tumors. Use of immunostains, required for diagnosis in perhaps 25% of testicular neoplasms, is reviewed. Changes of classification in the AJCC (8th edition) in 2016 are discussed, including the partitioning of two tumor types: the central role of chromosome 12p amplification allows both teratoma and yolk sac tumor to be divided into prepubertal types (lacking amplification) and post-pubertal types. Occasionally, sex cord-stromal tumors, hematolymphoid tumors, or epididymal adenomatoid tumors enter the differential diagnosis of germ cell neoplasms.

Sarcomatoid Spermatocytic Tumour: Report of a Rare Case and Literature Review.

Spermatocytic tumour (ST) accounts for 1% of testicular germ cell tumours. It is an indolent neoplasm with good prognosis. In approximately 6% of STs, sarcomatous dedifferentiation may occur, portending an aggressive behaviour and representing a significant diagnostic challenge that can lead to its misdiagnosis. Herein, we report the clinicopathological features of a patient with a sarcomatoid spermatocytic tumor, initially diagnosed as mixed germ cell tumour, who was referred to our institution with lung metastases mainly composed of rhabdomyosarcomatous elements. This case report illustrates the importance of recognizing this entity for adequate management of these patients.

A case of soft-tissue tumor over the sternum: A rare case report.

The objective is to report a rare case of extragonadal seminoma over the manubrium sterni on the chest wall. A 42-year-old male patient, a chronic alcoholic for 10 years presented with a firm mass of approximate size 10 cm × 12 cm overlying the manubrium part of the sternum. A clinical diagnosis of soft-tissue tumor was made. All relevant preoperative workup was done. Fine-needle aspiration cytology of the mass was suggestive of serous cystic lesion with chronic inflammation. Wide local excision of the mass and primary closure of the wound was done, followed by histopathological examination. Unanticipatedly, on histology, the mass turned out to be extragonadal seminoma. Postoperative wound healing was satisfactory. Subsequently, the patient underwent adjuvant chemotherapy. Primary extragonadal seminoma itself is a rare tumor that affects mainly young people with mediastinum as the most commonly involved site and has higher chances of metastasis. This case of extragonadal seminoma (extragonadal germ cell tumour) over manubrium sterni without any mediastinal involvement in a patient in early forties presenting as soft-tissue tumor, itself is a rarer entity and perhaps one of the kinds. Hence, the case needs to be reported and further progression and prevention have to be discussed.

Hypercalcaemia and acute kidney injury: A rare presentation of seminoma.

Hypercalcaemia is common in patients with malignancy, but is rare in seminoma with only eight cases reported in the literature. We present an unusual case of a 36-year-old man who presented with hypercalcaemia and stage 3 acute kidney injury. He presented initially with headache and malaise, and was found to have markedly deranged blood tests. He underwent a renal biopsy before imaging confirmed an unexpected large abdominal mass, which was confirmed histologically to be a seminoma. He was referred to a tertiary oncology centre, and underwent emergency chemotherapy and radical resection with no evidence of recurrence to this date and with return to normocalcaemia.

Role of Lactate Dehydrogenase in Identifying Relapse for Patients With Stage I Testicular Cancer on Surveillance.

PURPOSE: Tumor markers alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase assume a key role in the management of testicular germ cell tumors. While alpha-fetoprotein and human chorionic gonadotropin have modest sensitivity and specificity for germ cell tumors, lactate dehydrogenase has weak sensitivity and specificity. We explored the utility of lactate dehydrogenase in identifying relapse among stage I seminomatous and nonseminomatous germ cell tumors on surveillance. MATERIALS AND METHODS: Patients with a history of stage I testicular germ cell tumors were identified from a prospectively maintained database at the Princess Margaret Cancer Centre from December 1980 to May 2021 and surveyed according to established institutional algorithm guidelines. The utility of lactate dehydrogenase elevation to independently detect germ cell tumor relapse was examined. RESULTS: Among 1,014 seminoma and 676 nonseminomatous germ cell tumor patients, 176 and 176 patients relapsed with a median time to relapse of 13.6 and 8.9 months, respectively. Imaging alone was the most common mode of relapse detection in 144 and 74 of seminoma and nonseminomatous germ cell tumor patients, respectively. Lactate dehydrogenase was elevated in 49 cases of seminoma and 38 cases of nonseminomatous germ cell tumors at relapse, but was never the sole relapse indicator. Among 350 seminoma and 311 nonseminomatous germ cell tumor patients who never relapsed, 210 and 233, respectively, had at least 1 elevated lactate dehydrogenase value. CONCLUSIONS: Lactate dehydrogenase alone did not independently contribute to early relapse detection in stage I seminoma or nonseminomatous germ cell tumor. Elevated lactate dehydrogenase values were documented in a high proportion of nonrelapsing seminoma and nonseminomatous germ cell tumor cases.

Widespread metastasis of a spermatocytic seminoma with concomitant hepatic peliosis in a Southern African hedgehog (Atelerix frontalis).

ABSTRACT: A six-year-old intact male Southern African hedgehog (Atelerix frontalis) presented with a history of chronic mild to moderate weight loss, and sub-acute hind limb ataxia that progressed to complete paralysis, at which point the hedgehog was euthanised. At autopsy, a large multinodular pale mass had completely replaced the left testicle and transcoelomically metastasised to the diaphragm and the peri-renal area, from where it then invaded the vertebral column and spinal cord. Multifocal, irregular to round, well-demarcated, blood-filled, proliferative lesions were also present in the hepatic parenchyma. Histological analysis of both the testis and metastatic lesions revealed diffuse sheets of neoplastic cells with moderate pale cytoplasm, large irregular to round nuclei and mostly one prominent magenta nucleolus, consistent with metastatic seminoma. The neoplastic cells were negative for periodic acid-Schiff (PAS) stain and positive for CD117 by immunohistochemistry (IHC). Taken together with the morphology of the neoplastic cells and the advanced age of the animal, this is suggestive of a spermatocytic seminoma. Histological analysis of the liver revealed multifocal lesions consisting of large anastomosing blood-filled spaces bordered by compressed hepatocytes, consistent with hepatic peliosis. This is the first report of a neoplasm in the Southern African hedgehog (Atelerix frontalis), the first report of a metastatic seminoma in a hedgehog, together with diagnosis of spermatocytic subtype, and the first report of a hedgehog with concomitant hepatic peliosis.

Total embedding of spermatic cord and hilar soft tissue in orchiectomy for seminoma: does the extensive sampling improve pathologic risk factors?

Pure seminomas represent the majority of testicular germ cell tumors and accurate diagnosis and staging require an accurate sampling of radical orchiectomy specimens. The aim of our study is to find the most informative gross sampling method for orchiectomy specimens. We performed the extensive sampling of 88 radical orchiectomy specimens embedding in their entirety testicular hilum, rete testis, hilar soft tissue, and spermatic cord. We examined the impact of this procedure on tumor stage, prognostic parameters (lymphovascular invasion and infiltration of rete testis, epididymis, tunica vaginalis, and spermatic cord), and their relationship with recurrence. Eighty-eight seminomas from 88 radical orchiectomies were sampled. Seventy-seven cases (87.5%) presented as clinical stage I and 11 cases (12.5%) as clinical stage II. The follow-up period range was 18-54 months and 82 patients (93.2%) had a minimum of 2-year follow-up. Tumor size ranged from 0.4 to 16 cm (mean 3.6) requiring a mean of 7.1 sections for entire tumoral sampling. Epididymis required 2 to 8 sections (mean 3.3), and hilum and hilar soft tissues 2 to 9 sections (mean 3.4). Epididymal infiltration and lymphovascular invasion resulted significant at multivariate analysis generating a receiver operating characteristic (ROC) curve with area under curve of 0.778. All the other parameters (except for pagetoid rete testis infiltration) were significant to predict metastasis only at univariate analysis. Extensive sampling of radical orchiectomy specimens does not improve the accuracy of staging in pure seminomas. Lymphovascular invasion and epididymal infiltration are useful to predict metastasis.

Paraneoplastic Demyelinating Inflammatory Neuropathy Revealing Metastatic Seminoma: A Case Report.

Paraneoplastic neurological syndrome (PNS) is uncommon and not well known. PNS can reveal cancer, but its role in seminomas has not been described explicitly. We report the case of a 36-year-old man with unremarkable medical history and no comorbidities who was diagnosed with a retroperitoneal metastatic seminoma. The patient's general condition deteriorated, and he developed progressive neurological palsy without other clinical anomalies. Electromyography revealed demyelinating, non-lengthy neuropathy. Guillain-Barré syndrome was initially suspected. However, a positron emission tomography scan revealed a retroperitoneal mass, and blood markers revealed increased human chorionic gonadotropin. The patient was diagnosed with PNS, and a computed tomography-guided biopsy revealed a metastatic seminoma without a primary tumor. No circulating neural antibodies were detected. Human polyvalent immunoglobulin was simultaneously administered with chemotherapy. After three cycles of a cisplatin-etoposide-bleomycin, a complete biological and metabolic response rate was observed, and his neurological symptoms rapidly improved. Four years later, the patient responded completely, without any neurological complaints. Paraneoplastic demyelinating inflammatory neuropathy can lead to advanced seminoma diagnosis. Prompt management of seminomas with cisplatin-based regimens provides the best chance of cure for both advanced seminoma and paraneoplastic syndrome.

Primary seminoma of prostate in a patient with Klinefelter syndrome: A case report.

RATIONALE: Klinefelter syndrome (KS) is a sex differentiation syndrome that occurs in men and is characterized by the 47XXY genotype. An association between KS and cancer has also been reported. The occurrence of seminoma of the prostate in KS has not been reported in the literature to date. Primary seminoma should be included in the differential diagnosis of prostate neoplasms in patients with KS. PATIENT CONCERNS: A 39-year-old man presenting with urinary retention was admitted to our hospital. Physical examination revealed sparse pubic hairs, atrophic testes, and an underdeveloped penis. Hormonal examination revealed significantly lowered serum testosterone levels and markedly higher follicle-stimulating hormone levels. A chromosomal examination was performed. Computed tomography and magnetic resonance imaging imaging showed a neoplasm in the left lobe of the prostate, and immunohistochemical examination of a transrectal needle biopsy of the prostate was performed. DIAGNOSES: Chromosomal examination was exhibited a 47 XXY genotype. Histopathology and of Immunohistochemistry of the transrectal needle biopsy specimen confirmed a seminoma. No other neoplasm was found on systemic examination; therefore, the patient was diagnosed with primary prostate seminoma and Klinefelter syndrome. INTERVENTIONS: The patient refused any treatment except catheterization because of religious reason. OUTCOMES: The patient died 2 years later. LESSONS: Primary seminoma should be included in the differential diagnosis of neoplasms of the prostate in patients with KS. Transrectal ultrasound-guided prostate needle biopsy is essential for the diagnosis of prostate neoplasms, and cisplatin-based chemotherapy remains the primary treatment for seminoma.

Testis Cancer Care in North Carolina: Implications for Real-World Evidence and Cancer Surveillance.

INTRODUCTION: Contemporary testis cancer management requires fastidious adherence to clinical guidelines and care principles, especially for those pursuing active surveillance (AS). However, real-world testis cancer care remains largely undescribed. Accordingly, we sought to assess the rigor of evaluation and monitoring among men with testis cancer. PATIENTS AND METHODS: Using North Carolina Central Cancer Registry data linked to insurance claims, we selected adult males diagnosed with primary testis cancer from 2003 to 2013. After identifying demographics, care setting, histology, stage, and index management, we evaluated the receipt of tumor markers, imaging, and clinic visits during initial evaluation and subsequent monitoring with respect to contemporaneous clinical guidelines. Care patterns were compared using chi-squared testing and multivariable logistic regression. RESULTS: Of 2526 men with primary testis cancer, we assembled a cohort of 487 with seminoma (59.3%) or nonseminoma (40.7%), losing most to a lack of insurance or continuous coverage. The cohort was predominantly white (92.4%) and had stage I disease (87.9%). Overall, 18.9% had complete tumor markers, staging imaging, and visits with 2 relevant specialists as recommended during their initial evaluation. For subsequent monitoring, 17.5% of patients with seminoma on active surveillance met minimal thresholds for recommended testing and follow-up during the first year vs. 21.9% and 34.9% of patients with seminoma treated with adjuvant radiation and chemotherapy, respectively. For nonseminoma, 10.1% of men on active surveillance met the minimal thresholds for recommended monitoring compared with 60.4% and 62.0% of those treated with surgery and chemotherapy, respectively. Recommended monitoring also differed by academic vs. community setting and receipt of recommended evaluation (P < .05). CONCLUSIONS: From real-world data, the evaluation and monitoring of patients with testis cancer appears substandard. Ongoing data and quality gaps highlight potential challenges with generating real-world evidence and ensuring adequate surveillance in this population.