Primary Testicular Tumor Research Articles

Imaging Diagnosis of Testicular Lymphoma in Young Male Patient: Incidental Finding in Ultrasonography

BACKGROUND: Ultrasonography is a common diagnostic procedure in patients with testicular abnormalities. Primary testicular lymphoma (PTL) is rarely discovered and is more common among elderly populations. CASE PRESENTATION: This case describes a young male patient with a history of painless testicular enlargement. Ultrasonography reveals an incidental finding of hypoechoic echo structural mass and increased vascularity using color Doppler ultrasonography. The further pathological examination discovered the findings indicative of a non-Hodgkin, diffuse, and large B-cell lymphoma. These distinctive features should be helpful in suggesting a diagnosis of PTL on imaging. CONCLUSION: PTL is a rare and aggressive extranodal NHL. Despite its low incidence, it is an extremely rare testicular cancer at a young age. Careful ultrasound imaging examination should be applied in patients with testicular enlargement. The presence of hypoechoic echostructural and an increase in vascularity should be considered for the possibility of a diagnosis of primary testicular tumor.

Non-choriocarcinomatous trophoblastic tumors of testis in postchemotherapy retroperitoneal lymph node dissections.

Non-choriocarcinomatous trophoblastic tumors (NCTTs) are seldomly diagnosed in male genital tract. As they have been recently described among the testicular germ cell tumor (TGCT) variants, pathologists' familiarity with their morphology is limited. We searched our electronic hospital records covering the years 2000-2017 for post-chemotherapy retroperitoneal TGCT metastectomies. Slides of all cases with viable tumor were retrieved from the archives and reviewed. Cases suspected of N-CTT morphologies were subjected to immunohistochemistry. Twelve NCTTs were identified, 9 of which were unseen or misdiagnosed by the original pathologists: Cystic trophoblastic tumor (CTT) (n = 5), placental site trophoblastic tumor (n = 2), epithelioid trophoblastic tumor (ETT) (n = 4), and coinciding PSTT + ETT (n = 1). Eight of these were associated with mature teratoma components, and one case (ETT) contained embryonal carcinoma and yolk sac tumor in addition to teratoma. Ten patients were clinically N1 at the time of primary tumor detection and orchiectomy. One patient had burned-out primary testicular tumor. Six patients were clinical M1a at presentation, while one male was cM1b. Six patients had mildly elevated β-HCG (≤ 410 mIU/ml) just prior to retroperitoneal lymph node dissections (RPLND), while the others had normal β-HCG levels. All patients had follow-ups ranging from 8 to 118months (mean 42.3months). Three patients died of disease-related and two of unrelated causes. In conclusion, because NCTTs are rare and newly described tumor types, their diagnosis is difficult and most of them are missed in post-chemotherapy RPLNDs. The majority of patients exhibit normal or slightly elevated β-HCG levels. N-CTTs are usually accompanied by other components of TGCT, the most common being teratoma. Despite the high survival rate of the patients, our study points to the unpredictable evolution of NCTT cases, which may concur with a high-stage or progressive disease.

PSAT048 Management of a Unilateral Testicular Tumor in a Patient with Congenital Adrenal Hyperplasia – Malignancy or Testicular Adrenal Rest Tumor?

Abstract Male patients with Congenital Adrenal Hyperplasia (CAH) are at risk of developing testicular adrenal rest tumors (TART). Late presentations are rare and often misdiagnosed as primary testicular germ cell tumors or other more common benign testicular lesions. We describe the case of a patient with CAH and a unilateral testicular tumor with regression in size after initiation of dexamethasone. A 24-year-old male with salt-wasting form of 21-hydroxylase deficiency underwent testicular U/S for evaluation of TART. While aware of a painless firm nodule on the latero-posterior aspect of his left testicle, his main concern was new onset infertility as he had conceived previously. He denied personal or family history of malignancy. Testicular U/S showed a 1.1×0.7×0.8 cm ill-defined, heterogeneously hypoechoic lesion with scattered calcifications and internal vascularity. He was referred to urology to undergo evaluation for possible for testicular cancer. CT abdomen/pelvis showed no evidence of metastatic disease. AFP was less than 2.5 ng/mL (reference range < 9.0 ng/mL), hCG was less than 1.0 mIU/mL (reference range<5.0 mIU/mL), and LDH was 221 U/L (reference range 140-271 U/L). The patient declined surgical intervention at this point and requested medical management. After discussion with the patient, we opted to trial dexamethasone to help suppress the nocturnal surge of ACTH in addition to his physiological dose of prednisone and fludrocortisone for CAH. He was started on 0.25 mg of dexamethasone followed closely with serial imaging and labs. Prior to initiation of dexamethasone, ACTH was 90.3 pg/mL (reference range 7.2–63.3 pg/mL). Two months after initiation of dexamethasone, ACTH decreased to 10.0 pg/mL. LH after initiation of dexamethasone was 8.58 mIU/mL (reference range 1.24–8.62 mIU/mL), FSH was 11.90 (reference range 1.27–19.26 mIU/mL), and testosterone level was 177 ng/dL (reference range 259-818 ng/dL). Testicular U/S six months after starting dexamethasone showed a 50% reduction in size of the heterogeneous hypoechoic left testicular lesion measuring 0.5×0.5×0.4 cm consistent with TART. However, he continued to have concerns regarding infertility, with work-up currently underway. TARTs are thought to arise from aberrant adrenal cells that may descend with the testes during embryogenesis. High ACTH levels in CAH due to lack of negative feedback can cause proliferation of these undifferentiated adrenal cells. Infertility is a predominant symptom due to local mass effect on the testes. Treatment of TART to prevent infertility requires elucidating an optimal steroid regimen that suppresses ACTH production, without suppression of LH and FSH. Moreover, most of the TARTs (around 80%) are bilateral and never malignant. Our patient's testicular tumor poses a diagnostic challenge given the late and atypical presentation of a unilateral tumor. The response to dexamethasone is very reassuring but continued surveillance is warranted. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

A rare case report: testicular leydig cell tumor with gynecomastia

Gynecomastia is the most common definition of breast tissue growth. It is common in urology due to androgen blockade used in prostate cancers. Clinically insignificant gynecomastia is present in 50% of men and there is no proliferation of breast tissue in ductus epithelium. Gynecomastia is rarely seen in primary testicular tumors such as Leydig Cell Tumors (LCT). Leyındg Cell Tumors are one of the rare sex cord stromal cell tumors of the testis . Although it is usually with endocrine changes, it is a painless mass or incidentally occurring tumor in the testis. In this case report, we examined the left testicle cell tumor of the gynecomastia at the age of 43 years. He had been admitted to our clinic for gynecomastia and breast pain for 6 years. The patient was followed-up by endocrinology due to the aforementioned complaints. The patient was suspected of prolactinoma. Physical examination revealed no MRI. MRI, heterogenous hyperintense in T2A with mild lobulated contoured T2A with a hypointense capsule in T2A with well limited T2A in the left intratesticular area, and heterogeneous isohaphy hyperintense internal T1A in the form of a nodular lesion (testicular tumor) showing intense and heterogeneous contrast enhancement commented. The patient underwent left inguinal orchiectomy and the pathology report was negative for the leyding cell tumor and surgical margin.
 Leydig cell tumors are the most common spermatic cord / stromal tumors. About 30% of patients present with gynecomastia. Ultrasonography is accepted as the first research method for the diagnosis of leydic cell tumor, but MRI is superior to ultrasonography in diagnosis. The gold standard treatment option is radical inguinal orchiectomy. The mechanism of hormonal disorders may be an overproduction of testosterone and estrogens by the tumor. As in our case, it is necessary to consider the possibility of LCT which is rarely seen in patients with gynecomastia and to provide differential diagnosis by performing the tests in this direction.

Testicular Germ Cell Tumours-The Role of Conventional Ultrasound.

Simple SummaryTesticular tumours are the most common cancer found in young men, and germ cell tumours account for the majority. This article describes the use of conventional ultrasound in germ cell tumours and how to perform the ultrasound, including how to improve patient position and scanning technique. The classification of germ cell tumours is also provided, and the salient features of different types of tumour are described. Some pitfalls and difficulties of ultrasound are discussed, as well as other uses of ultrasound in this group of patients.Testicular tumours are the most common tumours found in young males and germ cell tumours account for 95% of testicular tumours. Ultrasound is the first-line radiological investigation for imaging of the testis. This article outlines how to undertake an ultrasound examination, including optimal patient position, scanning technique and imaging parameters. Classification of germ cell tumours is provided, and salient imaging features of different tumours are described. Difficulties and pitfalls of ultrasound are described, including tumours found after a trauma presentation, orchitis causing diagnostic difficulties and imaging of small testicular lesions. Other uses of ultrasound are outlined, including looking for a primary testicular tumour following the discovery of retroperitoneal lymph nodes, imaging when tumour-makers increase, local recurrence in the scrotum, and for solid organ biopsy in metastatic disease. Conclusion: Ultrasound remains the first-line of investigation for imaging of the testis, and conventional ultrasound still plays a large role in imaging. On ultrasound alone, accurate morphological characterisation of tumours remains a challenge, despite the imaging features that can be seen in different tumour types. Therefore, histology following orchidectomy of a germ cell tumour remains the gold standard for accurate tumour characterisation.

Burned-Out Testicular Germ Cell Tumor Presenting as Retroperitoneal Lymphadenopathy in a Patient With Cryptorchidism: A Case Report & Review of Literature

Testicular germ cell tumors are the most common malignancy in young and middle-aged men. Spontaneous primary testicular tumor regression, or testicular tumor burn-out, is a rare clinical phenomenon where extragonadal metastatic lesions are observed concurrently with the spontaneous regression of the primary testicular germ cell tumors. Here, we describe the case of a 36-year-old male who presented to our hospital with left-sided abdominal pain and testicular swelling and was found to have significant retroperitoneal lymphadenopathy on his abdominopelvic CT scan. His testicular ultrasound showed multiple echogenic calcifications through the right testicle consistent with microlithiasis. Biopsy of the retroperitoneal lesion revealed a mixed germ cell tumor of testicular origin composed of embryonal carcinoma and teratoma. The patient received four cycles of bleomycin, etoposide, and cisplatin, followed by retroperitoneal lymph node dissection (RPLND) and radical right testicular orchiectomy. Here, we report the second case of burned-out testicular tumor in a patient with ipsilateral cryptorchidism. Furthermore, we elucidate the etiology, clinical presentation, and diagnostic modalities in burned-out testicular germ cell tumors.

PD51-03 MOLECULAR CHARACTERISTICS OF METASTATIC TERATOMAS AND MATCHED PRIMARY TESTICULAR GERM CELL TUMORS

You have accessJournal of UrologyCME1 May 2022PD51-03 MOLECULAR CHARACTERISTICS OF METASTATIC TERATOMAS AND MATCHED PRIMARY TESTICULAR GERM CELL TUMORS Anna Savelyeva, Feng Wang, Lei Guo, John Lafin, Liwei Jia, Kirill Medvedev, Cheryl Lewis, Payal Kapur, Vitaly Margulis, Solomon Woldu, Xiaosong Meng, Nick Grishin, James Amatruda, Lin Xu, and Aditya Bagrodia Anna SavelyevaAnna Savelyeva More articles by this author , Feng WangFeng Wang More articles by this author , Lei GuoLei Guo More articles by this author , John LafinJohn Lafin More articles by this author , Liwei JiaLiwei Jia More articles by this author , Kirill MedvedevKirill Medvedev More articles by this author , Cheryl LewisCheryl Lewis More articles by this author , Payal KapurPayal Kapur More articles by this author , Vitaly MargulisVitaly Margulis More articles by this author , Solomon WolduSolomon Woldu More articles by this author , Xiaosong MengXiaosong Meng More articles by this author , Nick GrishinNick Grishin More articles by this author , James AmatrudaJames Amatruda More articles by this author , Lin XuLin Xu More articles by this author , and Aditya BagrodiaAditya Bagrodia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002622.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Metastatic teratoma (MT) is a subtype of germ cell tumor (GCT) characterized by resistance to platinum-based chemotherapy. MT is treated via complete surgical excision, using retroperitoneal lymph node dissection (RPLND), following chemotherapy. Molecular characterization of post-chemotherapy MTs along with pre-chemotherapy testicular primary tumors could reveal 1) the mechanisms of MT development and differentiation, 2) molecular changes associated with platinum-resistance, 3) novel therapeutic options for patients with unresectable MTs. METHODS: We performed whole exome and transcriptome sequencing for 16 primary germ cell tumors and 18 metastatic teratomas, 11 were matched tumor/metastasis pairs. All MTs in our cohort were collected after induction platinum-based chemotherapy. We used VarScan for SNV analysis and PennCNV to detect genomic copy-number variations (CNVs). Metastatic Teratomas were compared to matched primary tumors and primary teratomas characterized by TCGA. RESULTS: Our analysis revealed that metastatic teratomas as well as their tumors of origin had low tumor mutation burden (0.65 and 0.47 accordingly). Amongst 583 SNVs detected in the study cohort, only two (KRAS p.Gly12Asp and KRAS p.Gly12Val) were previously described as oncogenic. Analysis of SNVs in proteins playing key roles in oncogenic signaling showed that TP53 and Ras pathways were the most affected in metastatic teratomas. The majority of metastatic teratomas possess gain of 3p11.1 and loss of 10q26.3, 16p11.2, 19p13.2, 19q12 and 22q12.3 loci. Within 3p11.1 we did not identify any well-known oncodrivers. However, 5 chromosomal loci with lost heterozygosity contained 16 previously annotated tumor suppressor genes: HTRA1, EBF3, FUS, PRKCB, NUPR1, PYCARD, ZNF668, ARMC5, YPEL3, DNMT1, DNAJB1, SMARCA4, GADD45GIP1, MIR199A1, TIMP3, TMPRSS6. Amongst those, GADD45GIP1 inhibition (growth arrest and DNA-damage-inducible, gamma interacting protein 1) is associated with cisplatin resistance development through mechanism of cellular senescence. CONCLUSIONS: Metastatic teratoma in our cohort is characterized by low tumor mutational burden and several recurring copy number changes. Molecular insight of metastatic teratoma may inform disease biology and treatment. Source of Funding: Dedman Scholar Award © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e843 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Anna Savelyeva More articles by this author Feng Wang More articles by this author Lei Guo More articles by this author John Lafin More articles by this author Liwei Jia More articles by this author Kirill Medvedev More articles by this author Cheryl Lewis More articles by this author Payal Kapur More articles by this author Vitaly Margulis More articles by this author Solomon Woldu More articles by this author Xiaosong Meng More articles by this author Nick Grishin More articles by this author James Amatruda More articles by this author Lin Xu More articles by this author Aditya Bagrodia More articles by this author Expand All Advertisement PDF DownloadLoading ...

Intratesticular Rhabdomyosarcoma- A Rare Childhood Tumour

Primary malignant of tumours of the testis are rare in children. Tumours of germ cell origin account for 60-77% of primary testicular tumors. Intrascrotal tumours of nongerm cell origin are rare. Rhabdomyosarcomas (RMS) are the commonest tumours among nongerm cell tumours. RMS are more commonly seen in paratesticular region. Pure testicular RMS are rare. A 16 yr boy was evaluated right sided testicular mass. Histopathology and immunohistochemistry confirmed it to be an anaplastic embryonal rhabdomyosarcoma. Here we report this case with a brief review of literature.

Molecular analysis of primary testicular germ cell tumor and matched metastatic teratomas.

425 Background: Metastastic teratoma (MT) is a unique germ cell tumor (GCT) subhistology characterized by resistance to platinum-based chemotherapy. Metastatic teratoma requires complete surgical excision, usually via retroperitoneal lymph node dissection (RPLND), following chemotherapy as a part of multidisciplinary GCT care. Molecular characterization of post-chemotherapy metastatic teratoma along with companion pre-chemotherapy testicular primary tumors could inform 1) the origin and differentiation site of metastatic teratomas, 2) mechanisms of platinum-resistance, 3) novel therapeutic options for patients with unresectable teratomas. Methods: We performed integrated molecular analysis for 16 primary germ cell tumors and 18 metastatic teratomas, 11 were matched tumor/metastasis pairs. All teratomas in our cohort were collected after induction platinum-based chemotherapy. In addition to SNV analysis, we conducted a chromosomal copy number gain and loss analysis for selected teratomas, matched primary tumors and primary teratomas from the TCGA. Results: Metastatic teratomas as well as their tumors of origin had low tumor mutation burden (0.65 and 0.47 accordingly). Amongst 583 SNVs detected in the study cohort, only two (KRAS p.Gly12Asp and KRAS p.Gly12Val) were previously described as oncogenic. Analysis of SNVs in proteins playing key roles in oncogenic signaling [1] showed that TP53 and Ras pathways were the most affected in metastatic teratomas. The majority of metastatic teratomas possess gain of 3p11.1 and loss of 10q26.3, 16p11.2, 19p13.2, 19q12 and 22q12.3 loci. Within 3p11.1 we did not identify any previously described oncodrivers. However, 5 chromosomal loci with lost heterozygosity contained 16 previously annotated tumor suppressor genes (15 protein coding and 1 microRNA, MIR199A1). Amongst those, GADD45GIP1 inhibition (growth arrest and DNA-damage-inducible, gamma interacting protein 1) is known for playing a role in cisplatin resistance through mechanism of cellular senescence [2]. Conclusions: Metastatic teratoma in our cohort is characterized by low tumor mutational burden, recurring copy number changes, and lack of recurring SNVs. Molecular insight of teratoma may inform disease biology and treatment.

Cystic retroperitoneal metastasis from testicular seminoma, radiologically mimicking as lymphangioma

BackgroundRetroperitoneal nodal metastasis in a primary testicular tumor is not uncommon and usually presents as solid or solid-cystic nodal masses. A completely cystic appearance with fluid attenuation or fluid signal intensity on computed tomography (CT) and magnetic resonance imaging (MRI), respectively, is an uncommon presentation. There are many case reports of different types of cystic retroperitoneal masses; however, to our knowledge, metastatic retroperitoneal cystic masses showing fluid attenuation/fluid signal intensity on CT/ MRI secondary to primary testicular seminoma masquerading as cystic lymphangioma has been rarely reported in the medical literature. Our case report reports a case of a metastatic retroperitoneal cystic mass in a known case of testicular seminoma patient, which was misdiagnosed as cystic lymphangioma initially based on imaging.Case presentationA 55-year-old—patient presented to our hospital with abdominal pain, which was on and off in character. The patient underwent routine ultrasound abdomen, CT and MRI, which revealed multiple cystic lesions in the retroperitoneum. Initially, a provisional diagnosis of cystic lymphangioma was made based on the utterly cystic nature of the lesion and the presence of calcification. However, fine-needle aspiration cytology (FNAC) confirmed the metastatic origin of the lesion and was strengthened by the previous clinical history of orchidectomy.ConclusionThe treatment strategy for cystic retroperitoneal masses varies depending on the cause and its nature, so differentiation between the cystic masses is essential. Metastasis should also be kept in the differentials in all cystic retroperitoneal masses. Moreover, clinical history and FNAC can assist in making the correct diagnosis.

Iso-chromosome 12p Analysis by Fluorescent In-Situ Hybridization: An Academic Institutional Experience

Abstract Introduction/Objective Chromosome 12 abnormalities like iso-chromosome 12p (i12p) and amplification of 12p are seen in majority (89%) of the primary and metastatic testicular germ cell tumors (TGCTs). i12p can be detected by karyotyping, fluorescent in-situ hybridization (FISH) or reverse transcriptase polymerase chain reaction. The aim of this study was to review i12p FISH data at our institution and assess the clinical utility. Methods/Case Report Laboratory information system was queried over a period of 15 years to search for cases where i12p FISH test was requested. FISH test was performed using TelVysion 12p telomeric probe and CEP 12 centromere probe on paraffin-embedded tissue or cell blocks. A ratio of 12ptel/CEP12 signal of 1.4 or greater was considered as positive. Patient demographics, clinical presentation, pathologic findings, and follow-up data were documented and correlated. Results (if a Case Study enter NA) Total 58 cases were identified with an age range of 14 to 76 years. Majority were male (M=52, F=6). Of these cases, 15 were testicular and 43 extra-testicular cases that included resection (n=35), biopsy (n=20) and cell-blocks (n=3). i12p was detected in 8 out of 15 testicular cases while i12p was detected in 16 out of the 43 extra-testicular cases. The extra- testicular cases included 17 retroperitoneal lesions, 8 lesions from the mediastinum, 6 lymph nodes from other sites and 12 miscellaneous lesions. Using pathology diagnosis with immunohistochemistry as gold standard, overall sensitivity was 60% and specificity was 86%. There were 3 false positive cases [Benign testicular parenchyma (n=1), suspicious for germ cell neoplasia in-situ (n=1) and undifferentiated epithelioid neoplasm (n=1)]. Conclusion Our results show that although the sensitivity was limited, FISH test for i12p demonstrated high specificity(86%) for diagnosis of primary or metastatic TGCTs. As an adjunct test, i12p FISH can help identify and further characterize a significant number of GCTs with unusual morphology or clinical presentation.

Primary testicular carcinoid tumor with marked lymphovascular invasion.

Testicular carcinoid tumors are very rare, accounting for less than 1% of all testicular tumors. We report a rare case of a testicular carcinoid tumor with extensive lymphatic invasion. A 42-year-old man presented with a painless, enlarged right testicular mass. There was no history of injury or discomfort in this region. Right radical orchiectomy was performed, which showed a well-defined, non-encapsulated solid white mass with calcification (7.0 × 4.5 × 3.5 cm) and absence of cystic components. Microscopic examination using hematoxylin and eosin staining of the tumor sections identified organoid, trabecular, and solid patterns with rosette formation. Extensive multifocal lymphatic invasion was observed. Immunohistochemistry was positive for synaptophysin, chromogranin, and CD56. Testicular carcinoid tumors usually show good prognoses; however, there was extensive lymphovascular invasion in this case. Thus, in the case of unusual presentation of the disease, close follow-up is necessary.

Primary Mediastinal and Testicular Germ Cell Tumors in Adolescents and Adults: A Comparison of Genomic Alterations and Clinical Implications.

Simple SummaryThe germ cell tumors (GCTs) family is a heterogeneous group of neoplasms that includes tumors affecting testis (TGCTs) and rarer cases occurring in extragonadal sites. Mediastinal germ cell tumors (MGCTs) are more aggressive and have poorer prognosis. Due to their rarity of MGCTs, few molecular and clinical studies are reported. MGCTs share biological similarities with TGCT, and international guidelines recommend use of the same therapies validated for TGCT. However, while high response rate is achieved in TGCT, MGCT tend to be resistant to therapy. This review resumes all molecular findings reported in MGCTs, summarizing molecular characteristics common with TGCT and highlighting the different molecular alterations that characterize mediastinal tumors. A deeper understanding of the MGCT biology will help in clinical management of these patients.Mediastinal germ cell tumors (MGCTs) share histologic, molecular and biomarkers features with testicular GCTs; however, nonseminomatous MGCTs are usually more aggressive and have poorer prognosis than nonseminomatous TGCTs. Most nonseminomatous MGCT cases show early resistance to platinum-based therapies and seldom have been associated with the onset of one or more concomitant somatic malignancies, in particular myeloid neoplasms with recent findings supporting a common, shared genetic precursor with the primary MGCT. Genomic, transcriptomic and epigenetic features of testicular GCTs have been extensively studied, allowing for the understanding of GCT development and transformation of seminomatous and nonseminomatous histologies. However, MGCTs are still lacking proper multi-omics analysis and only few data are reported in the literature. Understanding of the mechanism involved in the development, in the progression and in their higher resistance to common therapies is still poorly understood. With this review, we aim to collect all molecular findings reported in this rare disease, resuming the similarities and disparities with the gonadal counterparts.

Burned-out testicular tumor: Two case reports

Spontaneous regression of a testicular tumor or burned-out testicular tumor is a rare phenomenon in patients with testicular germ cell tumors. The condition is characterized by tumor metastases, suspicious findings of the testicular tumor on ultrasound imaging, and partial or total histological regression of the primary testicular tumor after orchiectomy without treatment. Clinically, patients present with a disseminated tumor with symptoms related to the metastatic site without a palpable testicular tumor. Patients may also present with elevated levels of tumor biomarkers, depending on the histology. The etiopathogenesis of this phenomenon remains unclear and may involve immunologic factors as well as necrosis due to tumor growth beyond the available blood supply. We report here two clinical cases of patients treated at our center, both presenting with symptoms caused by retroperitoneal lymph node dissemination but different histologiesas well as a different clinical course. Keywords: germ cell tumor; testicular cancer; spontaneous regression.

Impact of Testicular Germ Cell Tumor Laterality on Recurrence-Free Survival in the Mexican Population.

BackgroundTo date, the prognostic value of laterality for testicular germ cell tumors remains unknown. Herein, we describe this prognostic factor in the Mexican population.MethodsA retrospective single-center study that included 37 patients with primary testicular germ cell tumors was conducted. Primary outcome was recurrence-free survival (RFS) at 2 years. Secondary outcomes were RFS by histology, progression-free survival by laterality, and 2-year overall survival.ResultsThirty-seven patients were included, of which five showed relapses. By laterality, the 2-year RFS rate was 100% for left tumors and 77.3% for right tumors, with a trend toward statistical significance (P = 0.058). By histology, the RFS rate was higher for seminomas than non-seminomas (89% vs. 83%, respectively) without this difference being statistically significant. Progression-free survival was higher for right tumors than left tumors (91% vs. 80%, respectively) but without reaching statistical significance. The overall survival rate for the entire cohort was 94.5%.ConclusionsOur study shows that patients with primary germ cell tumors of the right testicle have a higher risk of recurrence than those with primary germ cell tumors of the left testicle, with a trend toward statistical significance.

A presumed extragonadal germ cell tumor that turned out to be a gastric cancer—a case report

A solely retroperitoneal mass in males in combination with elevated serum Alpha-Fetoprotein (AFP) and beta-human choriogonadotropin (β-HCG) levels is highly indicative of a metastatic testicular cancer. Although testicular cancers are rare, they represent the most common diagnosed cancer in males between 14 and 40 years. However, in cases without evidence of a primary testicular tumor, the rare diagnosis of a retroperitoneal extragonadal germ cell tumor (EGCT) must be assumed. Here, we describe the first published case of a 66-year-old man presenting with this typical clinical picture and the diagnosis of an AFP and β-HCG producing advanced gastric cancer with retroperitoneal lymph node metastases mimicking a primary retroperitoneal EGCT. The final diagnosis was only made by gastroscopy performed after a CT-guided retroperitoneal lymph node biopsy revealed an adenocarcinoma, suggesting an upper gastrointestinal tract primary origin. However, a specific initial anamnesis and also in the primary staging, including a full-body CT-scan there was no hint for another primary tumor. Only the slightly unusual extension of the retroperitoneal mass up to the ligamentum hepatoduodenale and the pylorus, as well as the atypical age made us question our initial diagnosis. This extraordinary case is of special clinical interest to all practising physicians and once again highlights the importance of keeping rare differential diagnosis such as AFP-producing gastrointestinal tumors in mind.

Differential methylation EPIC analysis discloses cisplatin-resistance related hypermethylation and tumor-specific heterogeneity within matched primary and metastatic testicular germ cell tumor patient tissue samples

Testicular germ cell tumors (TGCTs) are among the most common solid malignancies in young-adult men, and currently most mortality is due to metastatic disease and emergence of resistance to cisplatin. There is some evidence that increased methylation is one mechanism behind this resistance, stemming from individual studies, but approaches based on matched primary and metastatic patient samples are lacking. Herein, we provide an EPIC array-based study of matched primary and metastatic TGCT samples. Histology was the major determinant of overall methylation pattern, but some clustering of samples related to response to cisplatin was observed. Further differential analysis of patients with the same histological subtype (embryonal carcinoma) disclosed a remarkable increase in net methylation levels (at both promoter and CpG site level) in the patient with cisplatin-resistant disease and poor outcome compared to the patient with complete response to chemotherapy. This further confirms the recent results of another study performed on isogenic clones of sensitive and resistant TGCT cell lines. Differentially methylated promoters among groups of samples were mostly not shared, disclosing heterogeneity in patient tissue samples. Finally, gene ontology analysis of cisplatin-resistant samples indicated enrichment of differentially hypermethylated promoters on pathways related to regulation of immune microenvironment, and enrichment of differentially hypomethylated promoters on pathways related to DNA/chromatin binding and regulation. This data supports not only the use of hypomethylating agents for targeting cisplatin-resistant disease, but also their use in combination with immunotherapies and chromatin remodelers.

Comprehensive genomic profiling (CGP) in patients with relapsed/refractory germ cell tumors (GCT).

388 Background: Understanding the genetic alterations in patients with relapsed/refractory GCT (rrGCT) could delineate the pathogenesis of cisplatin resistance. Our study uses CGP to characterize genomic alterations (GA) in refractory GCT and correlate with clinical outcomes. Methods: 432 patients with rrGCT were seen at Indiana University between Jan 2016 to Sep 2019 of whom 52 patients underwent CGP using a hybrid-capture based commercial assay to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and reported as mutations/Mb and microsatellite instability (MSI) was determined on 114 loci. PDL1 expression was determined by IHC (DAKO 22C3 antibody). Results: All patients relapsed after first-line cisplatin-based combination chemotherapy. Median age at diagnosis was 33 (range 15-68). Primary site of GCT was testicular in 85% and mediastinum in 8%. 6 patients had pure seminoma and 46 had non-seminoma. Platinum refractory disease, defined as serologic or radiographic progression within 4 weeks of first-line chemotherapy comprised 23% of patients. The primary tumor was used for sequencing in 6 cases (12%) and non-primary tumor metastatic site (lymph node, lung, liver, brain, omentum) in 46 cases (88%). The most common GA in the entire cohort were FGF6 (27%), FGF23 (27%), KDM5A (27%), CCND2 (27%), KRAS (18%), TP53 (14%), KIT (8%), APC (8%), ZNF217 (6%), MUTYH (6%), AURKA (6%), NRAS (6%), EGFR (6%), CTNNB1 (6%), GNAS (6%). Most common alterations for testicular primary tumors were FGF6, FGF23, KDM5A, CCND2, KRAS, TP53, KIT. For non-testicular primary GCT, most common GA were APC, TP53, EGFR. Most common GA for non-seminoma were FGF6, FGF23, KDM5A, CCND2, KRAS, TP53, APC. Most common GA for pure seminoma was KIT. Potentially targetable genomic alterations were found in 17 patients (33%). 10 of 17 patients (59%) tested had PDL1 score ≥1% and 3 patients had PDL1 ≥50%. Median TMB was 3.5 mutations/MB. There were 4 patients (8%) with TMB ≥ 10 mutations/Mb and 2 patients (4%) with TMB ≥ 20 mutations/Mb. 1 of 48 patients (2%) evaluated for MSI had MSI-High status. Isochromosome 12p was detected in the majority of samples where it was tested. Outcomes with GA-directed therapy will be presented at the conference. Conclusions: CGP can reveal potential therapeutic targets in patients with rrGCT including EGFR, ERBB3, KIT, and MET. Consistent with reported clinical trials in rrGCT, biomarkers predicting response to immune checkpoint blockade are uncommon with most patients having low TMB, absence of MSI-H status, and low expression of PDL1.

TERT Gene Fusions Characterize a Subset of Metastatic Leydig Cell Tumors.

Metastatic Leydig cell tumors (LCT) are rare, difficult-to-treat malignancies without known underlying molecular-genetic events. An index case of metastatic LCT showed an LDLR-TERT gene fusion upon routine genetic profiling for detection of therapeutic targets, which was then followed by an investigation into a cohort of additional LCTs. Twenty-nine LCT (27 male and 2 female patients) were profiled using next-generation sequencing and immunohistochemistry. TERT gene fusions were detected only in testicular metastatic LCTs, in 3 of 7 successfully analyzed cases (RMST:TERT, LDLR:TERT, and B4GALT5:TERT). TOP1 and CCND3 amplifications were identified in the case with a B4GALT5:TERT fusion. A TP53 mutation was detected in 1 metastatic tumor without a TERT fusion. Five primary (4 testicular and 1 ovarian) LCTs showed multiple gene amplifications, without a consistent pattern. A single metastatic ovarian LCT showed BAP1 mutation and copy number amplifications affecting the NPM1, PCM1, and SS18 genes. At the protein level, 4 of 7 metastatic and 6 of 10 primary testicular LCTs overexpressed Topo1. Androgen receptor was overexpressed in 10 of 13 primary testicular tumors and 2 of 5 metastatic testicular LCTs (without detectable ARv7 messenger RNA or ARv7 protein). Only 1 metastatic testicular LCT exhibited a high tumor mutational burden; all tested cases were microsatellite instability stable and did not express programmed cell death ligand 1. Our study for the first time identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in metastatic LCTs. Topo1 and androgen receptor may guide decisions on chemotherapy and/or hormone therapy for selected individual patients.

Complete remission of Cdx-2 positive primary testicular carcinoid tumor: 10-years follow-up and literature review

BackgroundThe neuroendocrine cells can cause a variety of malignancies throughout the human body known as the neuroendocrine tumors (NETs) or carcinoid tumors. The primary testicular carcinoid tumor (PTCT) accounts for less than 1% of the testicular neoplasms and for only 0.2% of all carcinoid tumors representing already a very rare neoplastic entity. Here, we present a patient with a history of an exceptionally rare primary testicular carcinoid tumor, staining positive for Cdx-2 along with a literature review.Case presentationA 44-year old patient without significant past medical history was diagnosed in September 2009 with primary testicular carcinoid tumor, which was surprisingly staining positively for Cdx-2, too. At the time of the initial diagnosis the tumor was already showing histopathological infiltration of veins. DOTA-TATE-PET/CT imaging and endoscopy studies did not show any signs of distant metastases and in particular no gastrointestinal manifestation following no further medical indication for systemic chemotherapy. The continuous and close follow-up of the patient has reached a total of over 10 years at the time of publication remaining in complete remission.ConclusionThe diagnosis of primary testicular carcinoid is based on histopathology. The detailed histopathologic assessment of biomarkers based on immunohistochemistry is very important for the classification and the prognosis of the primary testicular carcinoid tumor. Primary testicular carcinoid tumor with Cdx-2 positive stain outlines an exceptionally rare neoplastic entity without a consensus about general follow-up guidelines, requiring close clinical and imaging aftercare and consideration in Cdx-2 positive metastatic tumor of unknown origin.