Search

Background and Objectives : Seminoma is the most common solid malignant tumour in young men. Clear-cell kidney carcinoma is the most common malignancy of the genitourinary tract. However, the synchronous occurrence of both of these tumours is rare. Case presentation: We present the case of a 36-year-old patient who presented to a medical facility at the end of 2019 with an enlarged right testicle. A unilateral orchofuniculectomy was performed, and a mass measuring 30 cm was removed. During histological examination, testicular seminoma pT2, R0, was diagnosed. An abdominal computed tomography (CT) scan showed a 6.4 cm × 6.8 cm × 6.7 cm tumour in the right kidney and a metastatic-like lesion in the right adrenal gland. A right nephrectomy and an adrenalectomy and paraaortic and paracaval lymphadenectomies were performed. A histological evaluation confirmed the presence of clear-cell renal carcinoma pT2aR0 G2, adrenal hyperplasia, and seminoma metastases in the removed lymph node. Chemotherapy with a Bleomycin, Etoposide, and Cisplatin (BEP) regimen was carried out. Three years after the last cycle of chemotherapy, a follow-up CT scan showed metastases in the left kidney, the right ischium, and the right lung. A well-differentiated clear-cell carcinoma G1 of the left kidney and metastasis of clear-cell carcinoma G2 in the right ischium were confirmed after the biopsy, and no tumour lesions were found in the lung tissue specimen. Treatment with targeted therapy with Sunitinib was started because the risk was favourable according to the Heng criteria. Genetic testing was performed, and the following genes were analysed: VHL , BAP1 , CHEK2 , FH , MET , MUTYH , APC , and STK11. The testing did not reveal any pathogenic or potentially pathogenic mutations or sequence changes of unknown clinical significance in the genes analysed. Conclusions : According to the authors, the occurrence of synchronous primary tumours is linked to one's genetic predisposition. DNA sequencing of tumour tissue could provide more information on the corresponding aetiopathogenesis.

The authors describe a case of bilateral diffuse paraneoplastic orbital myositis induced by a stage IA left testicular pure seminoma. The patient presented with findings typical of thyroid-associated orbitopathy (TAO) and was thought to have TAO until discovery of the malignancy. Treatment included an urgent orchiectomy, as well as 7 weeks of therapeutic plasma exchange. This is the fifth reported case of seminoma-associated orbitopathy, and the second to occur while cancer was in the occult phase. Although seminoma-associated orbitopathy is exceedingly rare, it can masquerade as TAO and should be considered in the differential diagnosis of any young male with atypical TAO findings.

Koi(Cyprinus carpio) is an ornamental variety of common carp frequently kept as pets. Given their long lifespan, neoplasia, albeit uncommon, may occur in these animals, and only a few studies have faced their cytological diagnosis. In the present case, a koi carp was referred to the clinicians due to coelomic swelling. The carp underwent surgery, which revealed an enlargement of both testes. Testicular samples were cytologically and histologically examined. The lesion was diagnosed as a seminoma since it was composed of round, large, atypical, and often multinucleated cells with round central nuclei and moderate cytoplasm. These tumors had the same appearance as seminomas in mammals and should be considered among differential diagnoses when coelomic swelling occurs in koi carp. Seminomas in koi carp are diagnosed histologically, but cytology, a rapid and cheap exam executable in all veterinary clinical facilities, could be a relevant preliminary diagnostic tool that may influence the entire diagnostic process., (© 2024. The Author(s).)

Introduction: In testicular cancer, the positive effect of early diagnosis on survival has been known for many years. In this study, we aimed to determine the diagnostic features of testicular cancer patients, to examine the effect of duration of diagnosis delay (DD) on tumor size, tumor stage, and serum tumor markers, and to reveal the possible benefits of early diagnosis., Methods: A total of 71 patients who underwent inguinal orchiectomy due to suspicion of testicular cancer and whose pathology was found to be the germ cell tumor were included in the study. The relationship between the duration of diagnosis delay and tumor size, level of tumor markers, TNM stage, presence of LAP, and presence of metastasis were examined., Results: Seminoma was detected in 39 (54.9%) patients and non-seminoma tumor was detected in 32 (45.1%) patients. In the correlation analysis between the markers, a significant and positive correlation was found between DD and radiological tumor size, pathological tumor size, retroperitoneal LAP detection rate, LDH and AFP levels, and N stage (respectively; r=0.345 p=0.003, r=0.324 p=0.006, r=0.244 p=0.041, r=0.286 p=0.015, r=0.244 p=0.040, r=0.238 p=0.046). It was determined that a 1-day increase in DD caused an increase of 0.431mm in the pathological size of the tumor., Conclusion: Duration of diagnosis delay is an issue that still keeps its importance for testicular tumors. Delay in diagnosis not only leads to an increase in tumor size but also negatively affects tumor stage and prognostic factors., (Copyright © 2023 AEU. Published by Elsevier España, S.L.U. All rights reserved.)

Persistent Müllerian duct syndrome (PMDS) is a rare sexual development disorder. It is even more rarely associated with transverse testicular ectopia (TTE), a rare form of testicular ectopia, in which both testes descend through a single inguinal canal and are present in the same hemiscrotum. PMDS with TTE is associated with 18%-33% malignant transformation. Here we report the case of a 48-year-old man who presented with a large right inguinoscrotal swelling and on evaluation was found to have a large right testicular mass with complete right inguinal hernia, undescended left testis and a central abdominal mass. On evaluation with contrast-enhanced computed tomography abdomen and pelvis and image-guided biopsy he was diagnosed with mixed germ cell tumour of the right testis (predominantly a seminoma) with a retroperitoneal nodal mass and absent left testis, for which he received chemotherapy. Post-chemotherapy he underwent surgery and was diagnosed intraoperatively with PMDS along with TTE and testicular malignancy arising from the ectopic left testis. Postoperative recovery and follow-up were uneventful. Most cases of PMDS are diagnosed early in life. They present clinically with unilateral or bilateral undescended testis with inguinal hernia. In adults, PMDS is usually associated with male infertility. However, TTE is associated with an increased risk of testicular tumours if undiagnosed until adulthood. In adults PMDS with TTE is usually an intraoperative finding and is commonly associated with malignancy in the ectopic/undescended testis.

Introduction . This study aims to review the morphological and immunohistochemical features of testicular tumors and compare them with prognostic parameters. Methods . Testicular tumors diagnosed between January 2011 and September 2021 were reviewed. Patient age, tumor subtype, size, spread, lateralization, number of foci, and immunohistochemical results were recorded. Results . A total of 121 tumors were detected, of which 108 (89%) were germ cell tumors (GCTs). Of the germ cell tumors, 70 (65%) were found to be pure type, and 38 (35%) were mixed germ cell tumors. The ratio of pure seminoma among GCTs was 56/108 (52%). Lymphatic/vascular invasion (LVI) was detected in 48/121 (40%), rete testis invasion in 32/121 (26%), hilar soft tissue invasion in 10/121 (8%), epididymal invasion in 5/121 (4%), and spermatic cord invasion in 5/121 (4%) patients. Lymphatic/vascular invasion was observed in 6 (22%) of 27 germ cell tumors smaller than 3 cm in size, and rete testis invasion was observed in 2 (7%), while in 40 (55%) of the 73 germ cell tumors of 3 cm and above, lymphatic/vascular invasion was seen, and 26 (36%) of them had rete testis invasion. Immunohistochemical results contributed significantly to the determination of tumor components and rates, especially in mixed germ cell tumors. Conclusion . Most of the tumors were germ cell tumors, and the majority were seminomas. Lymphatic/vascular invasion and rete testis invasion rates increase as the tumor diameter increases, which is more evident when the 3 cm cut-off value is taken into account ( P  < 0.005)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Declaration of interests We declare no competing interests.

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.

Objectives: We tested the hypothesis that the free-β subunit (βhCG) is diagnostically more sensitive with total hCG assays (hCGt) not detecting all tumours secreting βhCG. The effects of sex, age, and renal failure were investigated as secondary objectives., Methods: We compared βhCG 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 βhCG in 14 (6.9 %) patients. Primary hypogonadism was the most common cause of isolated hCGt increases. After therapeutic interventions βhCG 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 βhCG's were documented in serial samples., Conclusions: The similar false negative rates did not support the hypothesis that βhCG will detect more patients with testicular cancer than hCGt. In contrast to hCGt, βhCG was unaffected by primary hypogonadism which is a predictably frequent complication in testicular cancer patients. We therefore recommend βhCG as the preferred biomarker in testicular cancer., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

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.

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 (β-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, β-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 β-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 β-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 β-HCG of 66.7%. In GCT/seminomas, M371-Test had a sensitivity of 85%, AFP of 5%, LDH of 30% and β-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., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., Competing Interests: Declaration of interests All the authors present in this article declare no conflict of interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Seminomas are most commonly diagnosed in clinical stage I (CSI). After orchiectomy, approximately 15% of patients in this stage have subclinical metastases. Adjuvant radiotherapy (ART) delivered to the retroperitoneum and ipsilateral pelvic lymph nodes has been the mainstay of treatment for many years. Although highly efficient, with long-term cancer-specific survival (CSS) rates approaching almost 100%, ART is associated with considerable long-term consequences, particularly cardiovascular toxicity and increased risk of secondary malignancies (SMN). Therefore, active surveillance (AS) and adjuvant chemotherapy (ACT) were developed as alternative treatment options. While AS prevents patient overtreatment, it is associated with strict follow-up regimens and increased radiation exposure due to repeated imaging. Due to equivalent CSS rates to ART, and lower toxicity, one course of adjuvant carboplatin presents the cornerstone of chemotherapy for CSI patients. CSS is almost 100% for patients with CSI seminoma, regardless of the chosen treatment option. Therefore, a personalized approach in treatment selection is preferred. Currently, routine radiotherapy for CSI seminoma patients is no longer recommended. Instead, it should be reserved for patients who are unfit or unwilling for AS or ACT. Identification of prognostic factors for disease relapse allowed for the development of risk-adapted treatment strategy and stratification of patients in low-risk and high-risk groups. Although risk-adapted policy needs further validation, surveillance is currently recommended in low-risk patients, while ACT is reserved for patients with a higher risk of relapse., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2022 Bumbasirevic et al.)

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 (8 th 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., Competing Interests: Funding There are no sources of funding to report., (Copyright © 2022. Published by Elsevier Inc.)

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.

Background: Seminoma is a testicular tumor type, routinely diagnosed after orchidectomy. As cfDNA represents a source of minimally invasive seminoma patient management, this study aimed to investigate whether cfDNA methylation of six genes from liquid biopsies, have potential as novel seminoma biomarkers. Materials & methods: cfDNA methylation from liquid biopsies was assessed by pyrosequencing and compared with healthy volunteers' samples. Results: Detailed analysis revealed specific CpGs as possible seminoma biomarkers, but receiver operating characteristic curve analysis showed modest diagnostic performance. In an analysis of panels of statistically significant CpGs, two DNA methylation panels emerged as potential seminoma screening panels, one in blood CpG8/CpG9/CpG10 ( KITLG ) and the other in seminal plasma CpG1( MAGEC2 )/CpG1( OCT3/4 ). Conclusion: The presented data promote the development of liquid biopsy epigenetic biomarkers in the screening of seminoma patients.

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: Disclosures The authors have no financial disclosures or conflicts of interest to report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: An increasing number of incidental testicular tumors are diagnosed in patients during infertility workup. The aim of this study was to evaluate the accuracy of frozen section examination (FSE) for the management of these tumors., Methods: We retrospectively studied a series of 46 testicular tumors diagnosed during exploration for infertility from 2000 to 2019 and submitted for FSE., Results: A diagnosis of malignancy was made in 23 cases on both gross examination (yellow-white or cream-colored nodules for seminomas) and FSE, then confirmed on final diagnosis in 22 of the cases. One seminoma reported on FSE was revised as being a Leydig cell tumor. The 23 other lesions were diagnosed as benign on FSE, including 11 Leydig cell tumors (yellow-brown nodules), 2 Leydig cell hyperplasias, and 10 whitish fibrous lesions. All Leydig cell lesions were confirmed except 1, which was reclassified as a Sertoli cell tumor. Of the 10 cases of fibrous lesions, 6 were associated with malignancy., Conclusions: The high incidence of Leydig cell tumors and the accuracy of FSE for these lesions demonstrate the interest in FSE. In contrast, FSE is not reliable for fibrous lesions, and surgeons should be aware that a fibrosis result often corresponds with regressed tumors., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The accurate identification of different components in testicular germ cell tumors (GCT) is essential for tailoring treatment and informing the clinical prognosis. PRAME (preferentially expressed antigen in melanoma), a member in the family of cancer testis antigens, plays critical roles in regulating pluripotency and suppressing somatic/germ cell differentiation in seminomas (SEM). To investigate the potential diagnostic value of PRAME in testicular GCT, here we comparatively examined the expression patterns of PRAME and SOX17 by immunohistochemistry in both pure and mixed GCT. Tissue microarrays constructed from 66 pure or mixed GCT were examined, including 25 seminomas (13 pure and 12 mixed), 35 embryonal carcinomas (EC; 7 pure and 28 mixed), 23 teratomas (TER; 10 pure and 13 mixed), 15 yolk sac tumors (YST; 1 pure and 14 mixed), and 5 choriocarcinomas (CC; 1 pure and 4 mixed), with 11 germ cell neoplasia in situ (GCNIS) and 6 normal testicular tissue as controls. The expression levels of PRAME or SOX17 were evaluated by a scoring system counting for intensity and extent of staining. PRAME nuclear expression was present in 92% (23/25) of SEM, including all 13 pure SEM, and 10 out of 12 seminomatous component of mixed GCT. In contrast, all EC and TER were completely negative for PRAME, and focal expression was demonstrated in 33.3% of YST and 20% of CC. As for SOX17, 96% of SEM and 73% of YST stained positively, whereas EC and CC were negative. Focal nuclear positivity was identified in the epithelial cell component of 17.4% (4/23) of TER. We found the sensitivity of PRAME to detect SEM to be comparable to SOX17, although SOX17 staining is more diffuse and stronger in the majority of cases. The specificity of PRAME for SEM appeared to be superior to that of SOX17 (92% versus 81%). In conclusion, PRAME is preferentially expressed in SEM or within the seminomatous component of mixed GCT with only focal variable expression in YST and CC, but shows no expression in EC and TER. These findings suggest that PRAME can be explored as a diagnostic marker for SEM., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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.

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., (Copyright© Authors.)

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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: Disclosure JO received honoraria for advisory boards for Bristol Myers Squibb (BMS), Merck Sharp & Dohme (MSD), Pfizer, Roche, Astellas, AstraZeneca, Bayer, Ipsen and Janssen-Cilag and undertaken institutional research as coordinating project lead for BMS, MSD and Sanofi; DMB received institutional research grants from Orchid and PCUK; CB received honoraria for advisory boards for Merck Serono, Bayer Health Care, Sanofi Aventis, AstraZeneca, MSD, BMS, GSO Research Organisation, Janssen-Cilag, Berlin-Chemie and Novartis and invited speaker fees from Roche Pharma, AOK Germany and med update europe; MAC received honoraria for advisory boards and invited speaker fees for Roche, BMS, EUSA, Pfizer, Sanofi, Janssen, Astellas, Merck, Ipsen and MSD and as a representative for the Spanish Germinal Tumours Group; GD received honoraria for advisory boards for Janssen, Astellas, Bayer, MSD, BMS and reports institutional research roles as coordinating project lead for BMS, Roche and MSD; JAG received institutional research grants from Roche, Siemens and AbbVie; UDeG received honoraria for advisory boards for Pfizer, BMS, MSD, PharmaMar, Astellas, Bayer, Ipsen, Novartis, invited speaker fees for Roche, BMS, Sanofi, AstraZeneca and institutional research grants from AstraZeneca, Sanofi and Roche; RH received honoraria for advisory boards for Roche, Nektar Therapeutics, BMS, MSD, Astellas, expert testimony from National Institute of Clinical Excellence, other honoraria from the Cancer Centre London, institutional royalties from Janssen, institutional research grants from MSD, Roche and local project lead patient funding from Janssen, MSD, Nektar Therapeutics, Basilea Pharmaceutica, Astellas and Cancer Research UK; RL received honoraria for advisory board for MSD and Janssen and resources training support from Astellas and MSD; AS received honoraria for invited speaker fees from Pfizer and leadership role for the International Cancer Imaging Society; SG received personal honoraria for participation in advisory boards for Sanofi, Orion, Roche, Amgen, MSD and Aranda, other honoraria from RSI (Televisione Svizzera Italiana), invited speaker for ESMO, Swiss Group for Clinical Cancer Research (SAKK), Swiss Academy of Multidisciplinary Oncology (SAMO), China Anti-Cancer Association Genitourinary Oncology Committee (CACA-GU), ORIKATA Academy research group and, speaker’s bureau for Janssen Cilag, travel grant from ProteoMEdiX, institutional honoraria for advisory boards for Bayer, Janssen Cilag, Roche, AAA International including Independent Data Monitoring Committee and Steering Committee member for Amgen, Menarini Silicon Biosystems, Astellas Pharma, Tolero Pharmaceuticals, MSD, Pfizer, Telixpharma, BMS and Orion, patent royalties and other intellectual property for a research method for biomarker WO2009138392; TP received research funding from Merck Serono, MSD, Roche, BMS, AstraZeneca, Astellas, Novartis, Johnson & Johnson, Seattle Genetics, Pfizer, Exelixis and Eisai and honoraria from Merck Serono, MSD, Roche, BMS, AstraZeneca, Astellas, Novartis, Johnson & Johnson, Seattle Genetics, Pfizer, Exelixis and Eisai. HSH has declared no conflicts of interest.

Aim: To evaluate disease presentation, treatment practices, and outcomes of patients with germ cell tumor (GCT) treated in a high-volume cancer center in Australia., Methods: This is a retrospective analysis of 609 patients diagnosed with GCT in the Sydney West Cancer Network between 1990 and 2013. Cause and date of death, and second malignancy information was sourced from The Centre for Health Record Linkage., Results: The median age was 33 years (range, 14-85). Primary site was testis in 590 (96.9%), mediastinum in nine (1.5%), and retroperitoneum in nine (1.5%). History of undescended testis was present in 48 (7.9%). Pure seminoma was seen in 334 (54.8%), with 274 (82.0%) being stage I. There was a decline in use of adjuvant radiotherapy from 83% in 1990-1997 to 29% in 2006-2013. Nonseminoma GCT (NSGCT) was diagnosed in 275 (45.2%), with 162 (58.9%) being stage 1. Active surveillance has increased as the initial treatment, from 58% between 1990 and 1997 to 89% between 2006 and 2013. Metastatic disease at presentation was seen in 162 (26.6%): 55 (34.0%) seminoma and 107 (66.0%) NSGCT. With median of 15-year follow-up, 18 (3.0%) have died from GCT and 70 (11.5%) from all causes. Ten-year overall survival was 93% and GCT-specific survival was 97%. Forty patients developed a secondary malignancy, with 38 receiving chemotherapy, radiotherapy, or both., Conclusions: This large Australian series illustrates a changing pattern of care and outcomes and compares them favorably with other series. This serves as a basis for future comparison of outcomes for this malignancy., (© 2021 John Wiley & Sons Australia, Ltd.)

A 40-year-old, male, Japanese patient presented with the complaint of painless, right testicular swelling. Tumor markers for testicular cancer were normal. He underwent radical orchiectomy with the clinical diagnosis of stage I seminoma. Pathological examination revealed seminoma and coexisting neuroendocrine tumor (NET). Germ cell neoplasia in situ (GCNIS) was present in the vicinity of seminoma, but there was no continuity between NET and seminoma. Tumor cells of both lesions displayed amplification of 12p and isochromosome 12p on fluorescence in situ hybridization, suggesting that both tumors originated from GCNIS. The present report is the first to describe a case of primary testicular NET coexisting with seminoma in an ipsilateral testis.

Both Hodgkin's lymphoma and testicular cancers can present in young men; however, concurrent Hodgkin's lymphoma with seminoma is very rare. When they do coexist, careful consideration must be made to avoid missing new cancer by assuming the presence of primary metastatic disease when lymphadenopathy presents. Here we present a rare case of coexistence of seminoma and Hodgkin's lymphoma and the staging and treatment challenges associated with a 2-cancer diagnosis., (©Copyright 2021 by University Health Partners of Hawai‘i (UHP Hawai‘i).)

Aims: Spermatocytic tumour (ST) is a rare testicular germ cell neoplasm with few confirmatory biomarkers that can be challenging to diagnose. Like normal spermatogonia, STs are known to express SSX proteins. Recently, a novel SSX antibody directed against a conserved C-terminal region of SSX1, SSX2 and SSX4 (SSX&#95;CT) has emerged as a reliable biomarker for these SSX proteins and synovial sarcoma. However, SSX&#95;CT immunostaining has not been demonstrated in ST. The aim of this study was to assess the diagnostic utility of SSX&#95;CT immunohistochemistry in ST and other tumours in the differential diagnosis with ST., Methods and Results: SSX&#95;CT, OCT3/4 and c-KIT immunohistochemistry was performed on 15 STs, 38 seminomas, 13 embryonal carcinomas, 12 yolk sac tumours, six choriocarcinomas, four teratomas, seven Sertoli cell tumours, and six lymphomas. Staining was scored as negative, rare, focal, or diffuse. SSX&#95;CT was positive in all (15/15) STs, and diffusely positive in 14 of 15 (93%). SSX&#95;CT was positive in 22 of 38 (58%) seminomas; however, only two cases showed diffuse expression. SSX&#95;CT was negative in all other tumours. OCT3/4 was negative in all STs, but positive in all seminomas and embryonal carcinomas. c-KIT was frequently positive in both STs (12/15; 80%) and seminomas (33/38; 87%). OCT3/4 and c-KIT were negative in all other tumours., Conclusions: SSX&#95;CT is a valuable and highly sensitive biomarker that supports the diagnosis of ST. Diffuse expression of SSX-CT in STs is also highly specific for ST. Nevertheless, SSX&#95;CT is best used in combination with OCT3/4 when ST is in the differential diagnosis., (© 2021 John Wiley & Sons Ltd.)

The "burned out" or "burnt out" testicular cancer (BTC) indicates the spontaneous and complete regression of a testicular germ cell tumor in the presence of distant metastases at the diagnosis. As this condition was never reviewed systematically, a scoping review was conducted to scrutinize the available literature on clinical and histological features of BTC patients. Medline was searched from inception to 19 April 2020. A virtual cohort of 68 BTC patients was generated. Our findings highlighted some inconsistencies: BTC was diagnosed in 5,9% of patients not showing distant metastases and in 2,9% of patients who did not undergo an orchiectomy. Besides, evidence of residual tumor was found in 22,7% of testis specimens, recognized as seminoma in 40% of cases. The emerged inconsistencies may derive from the lack of an unequivocal definition of BTC. Larger collaborative studies are needed to define the best diagnostic workup and treatment for BTC patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Primary mediastinal germ tumours (PMGCT) constitute, a mere 3-4% of all germ cell tumours (GCT). Although they account for approximately 16% of mediastinal tumours in adults and 19-25% in children as per western literature, there is hardly any large series on PMGCT reported from the Indian subcontinent., Design: We have retrospectively analysed clinicopathological features of 98 cases of PMGCT diagnosed over 10 years (2010-2019) from a tertiary-care oncology centre., Results: The study group (n = 98) comprised predominantly of males (n = 92) (M:F ratio-15:1), with an age range between 3 months to 57 years (median: 25 years). The tumours were predominantly located in the anterior mediastinum (n = 96). Broadly, Non-seminomatous germ cell tumours (NSGCT) were more common (n = 73, 74%) compared to pure seminoma (n = 25, 26%). Mixed NSGCT was the most common histological subtype (n = 30) followed by pure mature teratoma (n = 18), pure Yolk sac tumour (n = 13), mixed seminoma and NSGCT (n = 5), pure immature teratoma (n = 3) and GCT; NOS (n = 4). Interestingly, all female patients had exclusive teratomas. Nine cases revealed secondary somatic malignancy (5 carcinomas and 4 sarcomas). The majority of patients received neoadjuvant chemotherapy (n = 71). Surgical excision was performed in 60 patients. Follow up was available in 68 patients. NSGCT showed a poor prognosis as compared to seminoma (p value = 0.03) and tumours with somatic malignancies had a more aggressive clinical course., Conclusion: PMGCT was seen predominantly in young adult males and somatic malignancies were noted in as high as 9% of cases. Patient with somatic malignancy have aggressive clinical course, hence, extensive sampling and careful histopathological evaluation are recommended for the identification and definitive characterization., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Clinical guidelines do not recommend further investigation for occult malignancy in the scenario of unprovoked venous thromboembolism in the absence of additional clinical features suggestive of malignancy. We present the case of a young gentleman with pulmonary embolism who was diagnosed with testicular seminoma despite lack of symptoms or signs suggestive of malignancy. This is a unique case describing a scenario not well documented in existing literature where contravention of clinical guidelines had a potentially advantageous outcome for the patient., Case Presentation: A 37-year-old white male presented with seemingly unprovoked acute pulmonary embolism with right heart strain. He did not have any predisposing factors for venous thromboembolism and did not have any symptoms or signs suggestive of malignancy. Clinical guidelines do not recommend further investigation to screen for malignancy in this scenario. Despite this, our young, otherwise healthy patient proceeded to computed tomography scanning, resulting in the diagnosis of localized testicular seminoma. Testicular ultrasound described normal-sized testes (despite a discrete lesion in the right testis), suggesting this was not detectable by the patient or clinician on routine examination. The patient was anticoagulated and had an inferior vena cava filter inserted to facilitate orchidectomy followed by adjuvant radiotherapy., Conclusions: This case highlights the importance of considering malignancy in seemingly unprovoked venous thromboembolism and the availability of guidelines to direct further investigation. Our patient's treatment was not in line with clinical guidelines and was considered a "lucky find.", (© 2021. The Author(s).)

Abstract: A 45-year-old man with a history of testicular seminoma treated 8 years earlier presented with chronic progressive truncal and limb ataxia, progressive sensorineural hearing loss, and episodic vertigo. Eye movement and neuro-otology examinations showed localizing abnormalities to the bilateral cerebellar flocculus, vermis, and bilateral cerebellar hemispheres. Audiometric testing showed bilateral symmetric sensorineural hearing loss. There was a normal MRI of the brain. Cerebrospinal fluid (CSF) showed modest lymphocytic pleocytosis, and there was an elevated serum choriogonadotrophic hormone. An abdominal CT scan showed a solitary, large retroperitoneal lymph node, and histopathologic examination of the node biopsy showed granulomatous inflammation without microorganisms; eventually, immunohistochemical markers confirmed the diagnosis of metastatic seminoma. Although normal neuroimaging and inflammatory CSF reaction suggested a paraneoplastic etiology, the initial paraneoplastic antibody testing was negative. Subsequent investigation identified a positive kelch-11 protein antibody, thus confirming the paraneoplastic connection between the metastatic seminoma and the subacute neurologic-cochleovestibular syndrome., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

Background: Adjuvant carboplatin reduces relapse risk in clinical stage 1 (CS1) seminoma, though there is a paucity of long-term safety data., Aim: Our objective was to report long-term outcomes of two cycles of adjuvant carboplatin dosed at area under the time-concentration curve (AUC) of 7., Methods and Results: We performed a retrospective analysis on treatment and outcomes of patients with CS1 seminoma who received adjuvant carboplatin from 2000 to 2016 at our centres in the Midland Region, New Zealand. Of 159 patients, median age 39 years, 153 received two cycles of carboplatin: 147 dosed at AUC7 and 6 at AUC6. Six patients had one cycle of carboplatin AUC7. One patient relapsed at 22 months and died of bleomycin pneumonitis 2 months after achieving a complete response with BEP chemotherapy. Neither RTI (present in 21.3%) nor tumor size >4 cm (in 43.3%) was predictive of relapse. Median follow-up was 106 months. At 15 years, outcomes were: relapse-free survival 99.4%, overall survival 91.4%, disease-specific survival 100%, subsequent malignant neoplasm rate 7.6%, and second testicular germ cell tumor rate 3.85%. One patient had persistent grade 1 thrombocytopenia at 46 months., Conclusions: These data add to the body of evidence that two cycles of carboplatin AUC7 is safe and effective adjuvant treatment for CS1 seminoma., (© 2020 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Objective: Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed., Methods: The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT., Results: Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality., Conclusion: Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups., (Copyright © 2021 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Objective: To characterize the presentation and management of spermatocytic seminoma (SS) compared to classic seminoma in adults utilizing a large cancer registry., Methods: Patients >18 years of age in the National Cancer Database from 2006 to 2016 who underwent orchiectomy for testicular tumors were identified. Demographics, oncologic characteristics, and treatment patterns were compared between patients with SS and classic seminoma., Results: Of 53,481 adults receiving orchiectomy, 29,208 were diagnosed with classic seminoma and 299 (1%) with SS. Compared to patients with classic seminoma, SS patients were older (57 vs 39 years) and more likely to be African-American (odds ratio (OR) 1.8) and insured by Medicare (OR 2.0; all P <.05). SS patients had larger tumors on presentation (3-6 cm: OR 1.8; >6 cm: OR 1.8), but were less likely to have ≥pT2 stage (OR 0.5), regional nodal involvement (Clinical Stage II: OR 0.3), or distant metastatic disease (Clinical Stage III: OR 0.1; all P <.01). For postorchiectomy management, 73.6% of SS patients underwent surveillance while 24.5% had active treatment (retroperitoneal lymph node dissection, chemotherapy, radiation, or a combination). When stratified by year, there was an increasing trend toward surveillance compared to active treatment., Conclusion: SS is a rare germ cell tumor that typically presents as a larger tumor in older patients. Although these tumors are less likely to be characterized by advanced disease compared to classic seminoma, many patients have undergone aggressive postorchiectomy treatment in the past. Importantly, treatment trends have shifted toward surveillance in recent years with adjuvant therapy limited primarily to higher stage tumors., (Copyright © 2020 Elsevier Inc. All rights reserved.)