Pátá edice WHO klasifikace nádorů varlat z roku 2022 představila v porovnání s předchozí z roku 2016 minimum novinek. Členění germinálních tumorů na tumory odvozené od germinální in situ neoplazie (GCNIS) a tumory vznikající bez souvislosti s GCNIS bylo zcela přejato do WHO klasifikace 2022. Skupina germinálních tumorů odvozená od GCNIS zůstává téměř neměnná, nebyla obohacena o žádnou novou jednotku ani o žádnou nepřišla. Nejvýraznější novinkou je změna terminologie u somatické malignity v rámci postpubertálního teratomu: primitivní neuroektodermální tumor (PNET) byl přejmenován na neuroektodermální tumor embryonálního typu (ENET; embryonic-type neuroectodermal tumor). Drobně změněna byla rovněž diagnostická kritéria pro teratom se somatickým typem malignity. Seminom je nově řazen do skupiny germinomů. Ve skupině germinálních tumorů vznikajících bez souvislosti s GCNIS přibyla jedna nová samostatná jednotka, testikulární neuroendokrinní tumor prepubertálního typu. Od termínu karcinoid bylo, podobně jako v jiných oblastech, upuštěno. Ve skupině sex cord stromálních tumorů přibyly 2 nové jednotky: myoidní gonadální stromální tumor a stromální nádor z prstenčitých buněk. Mírně se upravilo jedno z diagnostických kritérií malignity sex cord stromálních tumorů, nově se již mitotická aktivita hodnotí dle mm2 a nikoliv dle počtu mitóz na pole velkého zvětšení, jako tomu bylo v minulosti. Vzhledem k tomu, že intratubulární hyalinizující velkobuněčná neoplazie ze Sertoliho buněk (intratubular large cell hyalinizing Sertoli cell neoplasia) vzniká pouze v rámci Peutz-Jeghersova syndromu, byl tento tumor přeřazen do nově vzniklé sekce geneticky podmíněných nádorových syndromů urogenitálního traktu a není již samostatnou jednotkou mezi sex cord stromálními tumory. Velkobuněčný kalcifikující nádor ze Sertoliho buněk (large cell calcifying Sertoli cell tumor) se může vyskytovat jednak hereditárně, ve spojitosti s Carneyho komplexem, jednak sporadicky. Tento tumor je proto zařazen do obou sekcí. Změnami v adnexálních testikulárních tumorech je určení dobře diferencovaného papilárního mezoteliálního tumoru jako samostatné jednotky. Naopak, z této skupiny byl vyjmut Sertoliformní cystadenom. Ten je nově subtypem nádorů ze Sertoliho buněk.

Compared to the WHO classification of the male genital tumors in 2016, minimal changes were introduced in the current WHO 2022. Classification of germ cell tumors remains the same as in the previous edition, dividing germ cell tumors into those derived from germ cell neoplasia in situ (GCNIS) and those independent of GCNIS. The group of GCNIS derived germ cell tumors is essentially unchanged. Most remarkable change was made to the chapter teratoma with somatic malignancy. Primitive neuroectodermal tumor (PNET), a particular type of somatic malignancy arising in the setting of teratoma, is currently termed embryonic-type neuroectodermal tumor (ENET). Diagnostic criteria for teratoma with somatic type malignancy have been mildly modified. Seminoma now belongs to the group of germinomas. There is one novel entity in the category of germ cell tumors independent of GCNIS, namely testicular neuroendocrine tumor, prepubertal type. Similar to other organ systems, the term carcinoid is no longer used. Two new entities were introduced in the category of sex cord stromal tumors: myoid gonadal stromal tumor and signet ring stromal tumor. Diagnostic criteria for malignant sex cord stromal tumors were moderately changed. Mitotic activity is now assessed according to mm2 instead of historical assessment according to the number of mitoses per high power fields. There is a new separate chapter named Genetic tumor syndromes. Intratubular large cell hyalinizing Sertoli cell neoplasia which arises exclusively in patients with Peutz-Jeghers syndrome, now belongs here. Large cell calcifying Sertoli cell tumor occurs as a hereditary tumor in patients with Carney complex as well as sporadically. Therefore, it is enlisted both in the chapter on sex cord tumors and as well as in genetic tumor syndromes. Well differentiated papillary mesothelial tumor was added as a new entity to the section of testicular adnexal tumors. Sertoliform cystadenoma, a tumor previously belonging to testicular adnexal tumors, is currently recognized as a subtype of Sertoli cell tumor.

• Keywords
• WHO klasifikace 2022,
• MeSH
• Humans MeSH
• Testicular Neoplasms * classification   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Review MeSH

STUDY QUESTION: What is the prevalence of malignant testicular germ cell tumors (TGCT) and its precursors, (pre-) germ cell neoplasia in situ (GCNIS), in late teenagers and adults who have androgen insensitivity syndrome (AIS) and the impact of an individual's genetic susceptibility to development of TGCT? SUMMARY ANSWER: No GCNIS or TGCT was diagnosed, but pre-GCNIS was identified in 14 and 10% of complete and partial AIS patients, respectively, and was associated with a higher genetic susceptibility score (GSS), with special attention for KITLG (rs995030) and ATFZIP (rs2900333). WHAT IS KNOWN ALREADY: Many adult women with AIS decline prophylactic gonadectomy, while data regarding the incidence, pathophysiology and outcomes of TGCT in postpubertal individuals with AIS are lacking. The relevance of genetic factors, such as single nucleotide polymorphisms (SNPs), in predisposing AIS individuals to TGCT is unknown. STUDY DESIGN, SIZE, DURATION: This multicenter collaborative study on prophylactically removed gonadal tissue was conducted in a pathology lab specialized in germ cell tumor biology. PARTICIPANTS/MATERIALS, SETTING, METHODS: Material from 52 postpubertal individuals with molecularly confirmed AIS (97 gonadal samples) was included; the median age at surgery was 17.5 (14-54) years. Immunohistochemical studies and high-throughput profiling of 14 TGCT-associated SNPs were performed. The main outcome measures were the prevalence of pre-GCNIS, GCNIS and TGCT, and its correlation with a GSS, developed based on the results of recent genome-wide association studies. MAIN RESULTS AND ROLE OF CHANCE: The earliest recognizable change preceding GCNIS, referred to as pre-GCNIS, was present in 14% of individuals with complete and 10% of those with partial AIS at a median age of 16 years. No GCNIS or invasive TGCT were found. The median GSS was significantly greater for those with, compared to those without, pre-GCNIS (P = 0.01), with an overlap between groups. Our data suggest important roles for risk alleles G at KITLG (rs995030) and C at ATFZIP (rs2900333), among the 14 studied TGCT-associated SNPs. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: A limited number of cases were included. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that the prevalence of pre-GCNIS in individuals with AIS beyond puberty is around 15%. Genetic susceptibility likely contributes to pre-GCNIS development in AIS but factors related to malignant progression remain unclear. Although data in older patients remain scarce, malignant progression appears to be a rare event, although the natural history of the premalignant lesion remains unknown. Therefore, the practice of routine prophylactic gonadectomy in adults with AIS appears questionable and the patient's preference, after having been fully informed, should be decisive in this matter. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by research grants from the Research Foundation Flanders (FWO) (to M.C.), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq G0D6713N) (to B.B.M. and M.C.) and the European Society for Pediatric Endocrinology (ESPE), granted by Novo Nordisk AB (to J.K.). There are no competing interests.

• MeSH
• Alleles MeSH
• Genome-Wide Association Study MeSH
• Adult MeSH
• Phenotype MeSH
• Genetic Predisposition to Disease MeSH
• Neoplasms, Germ Cell and Embryonal complications   diagnosis   epidemiology   genetics   MeSH
• Polymorphism, Single Nucleotide * MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Sexual Maturation MeSH
• Prevalence MeSH
• Stem Cell Factor genetics   MeSH
• Androgen-Insensitivity Syndrome complications   diagnosis   epidemiology   genetics   MeSH
• Testicular Neoplasms complications   diagnosis   epidemiology   genetics   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH