BACKGROUND: The fifth edition of World Health Organization classification of urinary and male genital tumours also brought news regarding testicular tumours. In contrast to the previous editions\' radical alterations, the adjustments in the fifth edition are subtle and mostly impact the terminology, categorization of some of the rare tumours and diagnostic criteria.
OBJECTIVE: Acquainting with current terms and tumor classification, which is necessary for good clinical practice.

Malignant germ cell tumours are a group of rare cancers whose incidence peaks in late adolescence and early adulthood. Dysgerminomas of the ovary and seminomas of the testis are analogous diseases, but seminomas have a 10-fold higher incidence. The two tumours are morphologically identical and are only differentiated by surrounding organ-specific tissue or testicular germ cell neoplasia in situ. They share genetic features including KIT and RAS mutations, amplification of chromosome 12p, and expression of pluripotency markers (NANOG (Nanog homeobox), OCT3/4 (Octamer-binding transcription factor 3/4), and SAL4 (Spalt-like trascription factor 4)). Both histologies are exquisitely sensitive to platinum chemotherapy, and the combination of bleomycin, etoposide, and cisplatin (BEP) yields survival rates greater than 90%. However, BEP causes significant, lifelong toxicity (cardiovascular, renal, respiratory, and neurological) in these young patients with an expectation of cure. Here, we comprehensively review the biological features of dysgerminoma and seminoma to demonstrate that they are biologically analogous diseases. We present available clinical trial data supporting de-escalation of chemotherapy treatment. Finally, we propose that future trials should enrol men, women, and children to benefit all patients regardless of age or sex.

Adolescent and young adults (AYA) with germ cell tumours (GCT) have poorer survival rates than children and many older adults with the same cancers. There are several likely contributing factors to this, including the treatment received. The prognostic benefit of intended dose intensity is well documented in GCT from trials comparing regimens. However, evidence specific to AYA is limited by poor recruitment of AYA to trials and dose delivery outside trials not being well examined. We examined the utility of cancer registration data and a clinical trials dataset to investigate the delivery of relative dose intensity (RDI) in routine National Health Service practice in England, compared to within international clinical trials. Linked data from the Cancer Outcomes and Services Dataset (COSD) and the Systemic Anti-Cancer Therapy (SACT) dataset, and data from four international clinical trials were analysed. Survival over time was described using Kaplan-Meier estimation; overall, by age category, International Germ-Cell Cancer Collaborative Group (IGCCCG) classification, stage, tumour subtype, primary site, ethnicity and deprivation. Cox regression models were used to determine the fully adjusted effect of RDI on mortality risk. The quality of both datasets was critically evaluated and clinically enhanced. RDI was found to be well maintained in all datasets with higher RDIs associated with improved survival outcomes. Real-world data demonstrated several strengths, including population coverage and inclusion of sociodemographic variables and comorbidity. It is limited in GCT however, by the poor completion of data items enabling risk classification of patients and a higher proportion of missing data.

OBJECTIVE: Testicular germ cell tumours are the most common solid malignancies in young men of age 14-44 years. It is generally accepted that both seminomas and non-seminomas arise from a common precursor, the germ cell neoplasia in-situ, which itself is the result of a defective (primordial) germ cell development. The stem cell-like population of the non-seminomas, the embryonal carcinoma, is capable of the differentiation of all three germ layers (teratomas) and extra-embryonic tissues (yolk-sac tumours, choriocarcioma) into cells. In contrast, seminomas are thought to have a limited differentiation potential. Nevertheless, several studies have highlighted their ability to undergo reprogramming to an embryonal carcinoma or differentiation into other non-seminomatous entities. Here, we demonstrate that in approximately 5% of seminomas, the yolk-sac tumour driver gene FOXA2 is detectable at the protein level, indicative of an occult yolk-sac tumour subpopulation that putatively arose from seminoma cells, as the presence of other GCT entities could be excluded. The presence of these subpopulations might render the tumour more aggressive and argue for an adjustment of the therapeutic concept. We used our data to update the model of germ cell tumour pathogenesis, especially regarding the developmental potential of seminomas. Additionally, we suggest to include detection of FOXA2 into standard routine diagnosis of seminomas.

BACKGROUND: Teratomas originating from extra-gonadal account for 15 % of all teratomas, while retroperitoneal site being the least site for teratoma 1-11 %, extremely rare adrenal teratoma is less than 4 % of the retroperitoneal teratomas. Usually, patients are asymptomatic and the tumours are detected incidentally during imaging.
METHODS: A case of a 29 years old female, presented with intractable pain for four weeks. Computed tomography scan study of the abdomen showed an avascular septate cystic lesion measuring 11.6 × 11.4 14.5 cm (cranial-caudal x transverse x anterior-posterior) with central fat density and large punctate calcification in the right suprarenal region displacing the inferior vena-cava laterally, abutting the gall bladder, pancreas and duodenum. Impressions of right adrenal teratoma and less likely adrenal myelipoma were suggested. She remarkably improved one day post operation. During clinic visit a month later, she was completely recovered and resumed her daily activities.
CONCLUSIONS: In adults primary retroperitoneal mature cystic teratoma are uncommon, mostly are secondary tumours and very rare will occur in adrenal gland. Adrenal incidentaloma have been seldom reported mimicking primary mature cystic teratoma. Biochemical and Imaging studies are of great importance in diagnosing and showing relationship of the tumour and other organs. This work has been reported in line with the SCARE criteria (Agha et al., 2018 [1]).
CONCLUSIONS: Primary retroperitoneal tumours are rare and surgery is the main stay of treatment whether it be open or laparoscopic, the latter being best for small lesion for it offers early recovery and complete excision gives excellent prognosis of 100 %.

Chemotherapy for non-seminomatous germ cell tumours (NSGCT) exposes to dose-dependent toxicities. The TGM13-NS protocol (EudraCT 2013-004039-60) aimed to decrease the chemotherapy burden compared to the previous TGM95 protocol while maintaining the 5-year event-free survival (EFS) at 80% or more.
Patients less than 19 years of age with disseminated NSGCT were enrolled (May 2014 to May 2019) and stratified into four groups: two intermediate-risk (IR: localised tumour with low tumour markers [TM]) groups treated with VBP (vinblastine-bleomycin-cisplatin): three courses for IR1 (ovarian tumour any age/testis tumour less than or equal to 10 years) and four courses for IR2 (extragonadal tumour 10 years or less) groups, and two high-risk (HR: metastatic and/or high TM) groups treated with etoposide-cisplatin and either ifosfamide (VIP) or bleomycin (BEP): three courses for HR1 (ovarian tumour any age/testis tumour less than or equal to 10 years and low TM/testis tumour more than 10 years and very low TM) groups and four courses for HR2 (remainder) groups.
One hundred fifteen patients were included: median age of 12.8 years (0.4-18.9); tumour sites: 44 ovaries, 37 testes and 34 extragonadal. The 5-year EFS and overall survival (OS) were 87% (95% CI: 80-92) and 95% (89-98), respectively (median follow-up: 3.5 years, range: 0.2-5.9), similar to those of the TGM95 protocol (5-year EFS 89% (84-93), 5-year OS 93% (89-95), p = .561). The 5-year EFS were 93% (95% CI: 80-98), 88% (71-95) and 79% (62-90) for ovarian, testicular and extragonadal tumours, respectively. The 5-year EFS varied (p = .02) according to the risk groups: 90% (66-97), 64% (30-85), 95% (72-99) and 87% (74-94) for IR1, IR2, HR1 and HR2, respectively. TM decline adjusted to tumour site, and alpha-fetoprotein (AFP) level revealed a prognostic impact of time to normalisation on EFS: HR = 1.03 (1.003-1.007).
Risk-adapted and globally decreased chemotherapy burden maintains excellent outcomes, exclusive of the IR2 group, which warrants more intensive chemotherapy.

Non-germinomatous germ cell tumours (NGGCT) are rare intracranial tumours that account for 1% to 3% of cases. They are usually seen in the pineal and suprasellar regions. NGGCT of the frontal lobe arising from the lateral ventricle with a synchronous pineal lesion is uncommon. We present a case of NGGCT with multifocal lesions in the pineal gland, frontal lobe, and pons treated with chemotherapy followed by craniospinal irradiation (CSI).

The 5th edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours includes some important revisions of the testicular tumour classifications, which are summarized in this article. They concern, for example, the definition of tumours of neuroectodermal and neuroendocrine origin. Furthermore, signet-ring stromal tumours and myoid gonadal stromal tumours are listed as separate entities in the section about sex-cord stromal tumours. Moreover, lymphatic neoplasia as well as soft tissue tumours of the urinary and male genital tract are each combined in a common section.
UNASSIGNED: In der 5. Edition der WHO-Klassifikation für Tumoren der ableitenden Harnwege und des männlichen Genitaltraktes gab es einige Neuerungen der bestehenden Klassifikationen. Sie werden in diesem Artikel zusammengefasst und betreffen u. a. die Bezeichnungen neuroektodermaler und neuroendokriner Tumoren des Hodens. Daneben wurden der siegelringzellige Stromatumor und der myoidale Gonadenstromatumor als eigenständige Entitäten der Gonadenstromatumoren eingeführt. Außerdem wurden jeweils gemeinsame Kapitel für hämatolymphoide Neoplasien sowie Weichgewebstumoren der ableitenden Harnwege und des männlichen Genitaltraktes geschaffen.

The great variety of pathological patterns in germ cell tumours, especially in yolk sac tumours but also the possibility of somatic-type malignancies, can complicate daily diagnosis. For the correct diagnosis, knowledge of morphological aspects and additional immunohistochemical staining can be helpful. Also, rare entities like sex cord stromal tumours, tumours of testicular adnexa or mesenchymal tumours of the spermatic cord can be diagnostically challenging.
UNASSIGNED: Die große Vielfalt der histologischen Muster von Keimzelltumoren, insbesondere beim Dottersacktumor, aber auch das Phänomen der somatischen Malignität können die tägliche Diagnostik komplizieren. Verschiedene morphologische Aspekte und immunhistochemische Zusatzuntersuchungen können bei der Diagnosefindung hilfreich sein. Auch das Spektrum seltener Entitäten wie Gonadenstromatumoren, testikuläre Adnextumoren und Weichgewebstumoren des Samenstrangs können zu einer diagnostischen Herausforderung werden.

Multiple relapsed/refractory germ cell tumor (GCT) patients have extremely poor prognosis. Cisplatin resistant testicular GCTs overexpress aldehyde-dehydrogenase (ALDH) isoforms and inhibition of ALDH activity by disulfiram is associated with reconstitution of cisplatin sensitivity in vitro as well as in animal model. This study aimed to determine the efficacy and toxicity of ALDH inhibitor disulfiram in combination with cisplatin in patients with multiple relapsed/refractory GCTs.
Disulfiram was administered at a dose of 400 mg daily until progression or unacceptable toxicity, cisplatin was administered at dose 50 mg/m2 day 1 and 2, every 3 weeks. Twelve evaluable patients had to be enrolled into the first cohort, and if 0 of 12 patients had treatment response, the study was to be terminated. The results of the first stage of the trial are presented in this report.
Twelve patients with multiple relapsed/refractory GCTs were enrolled in the phase II study from May 2019 to September 2021. Median number of treatment cycles was 2 (range 1-6). None of patients achieved objective response to treatment, therefore the study was terminated in first stage. Median progression-free survival was 1.4 months, 95% CI (0.7-1.5 months), and median overall survival was 2.9 months 95% CI (1.5-4.7 months). Disease stabilization for at least 3 months was observed in 2 (16.7%) patients. Treatment was well tolerated, however, 5 (41.7%) of patients experienced grade 3/4 fatigue, 4 (33.3%) thrombocytopenia, 3 (25.0%) anemia, while 2 (16.7%) experienced neutropenia, nausea and infection.
This study failed to achieve its primary endpoint and our data suggest limited efficacy of disulfiram in restoring sensitivity to cisplatin in multiple relapsed/refractory GCTs.