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Kulo mbandela we-Clinical Difficulties, u-Bendu Konneh, i-BS, kunye nabalingane babonisa imeko yendoda eneminyaka eyi-21 enembali ye-4 yenyanga ye-progressive right testicular edema.
Indoda eneminyaka engama-21 ubudala yakhalaza ngokudumba okuqhubekayo kwe-testicle efanelekileyo kwiinyanga ezi-4.I-Ultrasound ibonakalise ubunzima obunzima obuqinileyo kwi-testicle elungileyo, ukukrokra kwe-neoplasm enobungozi.Uvavanyo olongezelelweyo lubandakanya i-tomography ye-computed, ebonisa i-2 cm ye-retroperitoneal lymph node, kwakungekho zibonakaliso ze-metastases zesifuba (umzobo 1).Iziphawuli zethumba leSerum zibonise amanqanaba aphezulu kancinane e-alpha-fetoprotein (AFP) kunye namanqanaba aqhelekileyo e-lactate dehydrogenase (LDH) kunye ne-chorionic gonadotropin (hCG).
Isigulana sifumene i-orchiectomy ye-inguinal yecala lasekunene.Uvavanyo lwe-Pathological lubonakalise i-1% ye-teratomas kunye ne-somatic somatic malignant components e-fetal rhabdomyosarcoma kunye ne-chondrosarcoma.Akukho luhlaselo lwe-lymphovascular lufunyenweyo.Iimpawu ze-tumor eziphindaphindiweyo zibonise amanqanaba aqhelekileyo e-AFP, i-LDH kunye ne-hCG.Ukulandelelwa kwe-CT scans ngamaxesha amafutshane kuqinisekisile i-2-cm ye-interluminal aortic lymph node ngaphandle kobungqina be-metastases ekude.Esi sigulana senziwa i-lymphadenectomy ye-retroperitoneal, eyayilungile kwi-1 ye-24 lymph nodes kunye nokwandiswa kwe-extranodal ye-somatic malignancy efana ne-rhabdomyosarcoma, i-chondrosarcoma, kunye ne-spindle cell sarcoma engahlukanisiyo.I-Immunohistochemistry ibonise ukuba iiseli ze-tumor zilungile kwi-myogenin kunye ne-desmin kunye ne-negative ye-SALL4 (Umfanekiso 2).
Amatyhalarha eentsholongwane zeeseli zentsholongwane (TGCTs) anoxanduva lwezehlo eziphezulu zomhlaza wamatyhalarha kumadoda aselula amadala.I-TGCT lithumba eliqinileyo elinee-subtypes ezininzi ze-histological ezinokubonelela ngolwazi kulawulo lweklinikhi.I-1 TGCT ihlukaniswe kwiindidi ze-2: i-seminoma kunye ne-non-seminoma.Iinonseminomas ziquka i-choriocarcinoma, i-fetal carcinoma, i-yolk sac tumor, kunye ne-teratoma.
I-teratomas ye-testicular yahlulahlulwe kwiifom zasemva kunye ne-prepubertal.I-teratomas ye-Prepubertal i-indolent ye-biologically kwaye ayidibanisi ne-germ cell neoplasia in situ (GCNIS), kodwa ii-teratomas zasemva kokuphuncuka zinxulunyaniswa ne-GCNIS kwaye ziyingozi.2 Ukongeza, ii-teratomas zasemva kokuphuncuka zikholisa ukuba ne-metastasize kwiindawo ezingaphaya kwe-extragonadal ezifana ne-retroperitoneal lymph nodes.Kunqabile, i-postpubertal testicular teratomas inokuphuhla ibe yi-somatic malignancies kwaye ihlala inyangwa ngotyando.
Kule ngxelo, sibonisa i-molecular characterization yeemeko ezinqabileyo ze-teratoma kunye ne-somatic malignant component kwi-testes kunye ne-lymph nodes.Ngokwembali, i-TGCT ene-somatic malignancies iphendule kakubi kwi-radiation kunye ne-chemotherapy yesiqhelo esekwe kwiplatinam, ngoko ke impendulo A ayichanekanga.I-3,4 Iinzame zokujolisa ichemotherapy kwi-histology kwi-metastatic teratomas zineziphumo ezixubileyo, kunye nophononongo oluthile olubonisa impendulo eqinisekileyo ezinzileyo kwaye ezinye zingabonisi mpendulo.I-5-7 yenqaku, u-Alessia C. Donadio, MD, kunye noogxa babonisa iimpendulo kwizigulane zomhlaza nge-subtype enye ye-histological, ngelixa sichonga i-3 subtypes: i-rhabdomyosarcoma, i-chondrosarcoma, kunye ne-spindle cell sarcoma engahlukanisiyo.Uphononongo olongezelelweyo luyafuneka ukuvavanya impendulo kwi-chemotherapy ejoliswe kwi-TGCT kunye ne-somatic malignant histology kwimeko ye-metastasis, ngakumbi kwizigulane ezine-histological subtypes ezininzi.Ngoko ke, impendulo B ayichanekanga.
Ukuphonononga i-genomic kunye ne-transcriptome landscape yalo mhlaza kunye nokuchonga okujoliswe kuko konyango okunokubakho, senze uhlalutyo lwe-transcriptome tumor normal sequencing (NGS) kwisampulu eqokelelwe kwizigulana ezine-aortic lumenal lymph node metastases, ngokudityaniswa nolandelelwano lwe-RNA.Uhlalutyo lwe-Transcriptome ngokulandelelana kwe-RNA lubonise ukuba i-ERBB3 yayikuphela kofuzo olugqithisekileyo.I-gene ye-ERBB3, efumaneka kwi-chromosome 12, iikhowudi ze-HER3, i-tyrosine kinase receptor ngokuqhelekileyo ibonakaliswe kwi-membrane yeeseli ze-epithelial.Ukuguqulwa kweSomatic kwi-ERBB3 kuye kwabikwa kwezinye i-gastrointestinal kunye ne-urothelial carcinomas.Sibhozo
Uvavanyo olusekwe kwi-NGS lubandakanya ipaneli ekujoliswe kuyo (iphaneli ye-xT 648) yama-648 yofuzo edla ngokunxulunyaniswa nomhlaza wegazi oqinileyo.Iphaneli ye-xT 648 ayizange ibonise i-pathogenic germline variants.Nangona kunjalo, umahluko we-KRAS we-missense (p.G12C) kwi-exon 2 ichongiwe njengekuphela kwenguqu ye-somatic enesabelo esahlukileyo se-allele esingama-59.7%.I-gene ye-KRAS lelinye lamalungu amathathu osapho lwe-RAS oncogene olunoxanduva lokulamla iinkqubo ezininzi zeselula ezinxulumene nokukhula kunye nokwahlula ngophawu lwe-GTPase.9
Nangona iinguqu ze-KRAS G12C zixhaphake kakhulu kumhlaza wemiphunga we-cell (NSCLC) kunye nomhlaza we-colorectal, ukuguqulwa kwe-KRAS kuye kwabikwa kwii-TGCTs zeecodon ezahlukeneyo.10,11 Inyaniso yokuba i-KRAS G12C kuphela kwenguqu efunyenwe kweli qela ibonisa ukuba olu tshintsho lunokuba luqhubela phambili kwinkqubo yenguqu enobungozi.Ukongeza, le nkcukacha ibonelela ngendlela enokwenzeka yonyango lwe-TGCTs enganyangekiyo ngeplatinam njenge-teratomas.Kutshanje, i-sotorasib (i-Lumacras) ibe yeyokuqala inhibitor ye-KRAS G12C ukujolisa kwi-KRAS G12C ye-mutant tumors.Ngo-2021, i-FDA yavuma i-sotorasib kunyango lomhlaza wemiphunga ongeyonxalenye encinci.Akukho bungqina bokuxhasa ukusetyenziswa kwe-adjuvant translational histological targeting therapy ye-TGCT kunye necandelo elibi le-somatic.Uphononongo olongezelelweyo luyafuneka ukuvavanya impendulo ye-histology yoguqulelo kunyango olujoliswe kuyo.Ngoko ke, impendulo C ayilunganga.Nangona kunjalo, ukuba izigulana zifumana ukuphindaphinda okufanayo kwamalungu omzimba, unyango lokuhlangula kunye ne-sotorasib lunokunikwa amandla okuhlola.
Ngokweempawu ze-immunotherapy, i-microsatellite stable (MSS) i-tumor ibonise umthwalo oguqukayo (TMB) we-3.7 m / MB (i-50th percentile).Ngenxa yokuba i-TGCT ayinayo i-TMB ephezulu, akumangalisi ukuba eli tyala likwipesenti ze-50 xa kuthelekiswa namanye amathumba.I-12 Ukunikezelwa kwe-TMB ephantsi kunye ne-MSS isimo se-tumor, ithuba lokuqalisa impendulo yokuzivikela komzimba liyancipha;amathumba asenokungaphenduli kunyango lwe-immune checkpoint inhibitor.13,14 Ngoko ke, impendulo E ayichanekanga.
Iimpawu ze-Serum tumors (STMs) zibaluleke kakhulu ekuxilongweni kwe-TGCT;zibonelela ngolwazi lweqonga kunye nokuhlelwa komngcipheko.Ii-STM eziqhelekileyo ezisetyenziselwa ukuxilongwa kwekliniki ziquka i-AFP, i-hCG, kunye ne-LDH.Ngelishwa, ukusebenza kwaba bamakishi bathathu kulinganiselwe kwezinye ii-subtypes ze-TGCT, kubandakanywa i-teratoma kunye ne-seminoma.15 Kutshanje, ii-microRNAs (miRNAs) ezininzi ziye zabekwa njengee-biomarkers ezinokubakho kwii-TGCT subtypes ezithile.I-MiR-371a-3p ibonakaliswe ukuba inamandla aphuculweyo okubona ii-isoforms ezininzi ze-TGCT ezinovakalelo kunye namaxabiso athile ukusuka kwi-80% ukuya kwi-90% kwezinye iimpapasho.16 Nangona ezi ziphumo zithembisa, i-miR-371a-3p ayidli ngokuphakanyiswa kwiimeko eziqhelekileyo ze-teratoma.Uphando lwe-multicenter olwenziwe nguKlaus-Peter Dieckmann, MD, kunye noogxa babonisa ukuba kwiqela lamadoda angama-258, i-miP-371a-3p ibonakaliso yayiphantsi kakhulu kwizigulane ezine-teratoma ecocekileyo.17 Nangona i-miR-371a-3p iqhuba kakubi kwi-teratomas esulungekileyo, iimpawu zenguqu enobungozi phantsi kwezi meko zibonisa ukuba uphando lunokwenzeka.Uhlalutyo lwe-MiRNA lwenziwa kwiserum ethathwe kwizigulana ngaphambi nasemva kwe-lymphadenectomy.Ithagethi ye-miR-371a-3p kunye ne-miR-30b-5p ye-reference gene yafakwa kuhlalutyo.Ukuchazwa kwe-MiP-371a-3p kulinganiswe nge-reverse transcription polymerase chain reaction.Iziphumo zibonise ukuba i-miP-371a-3p ifunyenwe kwixabiso elincinci kwiisampulu ze-serum zangaphambi kokuhlinzwa kunye ne-postoperative, ebonisa ukuba ayizange isetyenziswe njengophawu lwethumba kwesi sigulana.Ubungakanani bomjikelezo oqhelekileyo weesampuli zangaphambili ze-36.56, kwaye i-miP-371a-3p ayizange ibonwe kwiisampuli ze-postoperative.
Isigulane asizange sifumane unyango lwe-adjuvant.Izigulana zikhethe ukucupha okusebenzayo kunye nemifanekiso yesifuba, isisu, kunye ne-pelvis njengoko kucetyiswa kunye ne-STM.Ngoko ke, impendulo echanekileyo nguD. Unyaka emva kokususwa kwe-lymph nodes ye-retroperitoneal, kwakungekho zibonakaliso zokubuyela kwesi sifo.
Ukubhengezwa: Umbhali akanalo umdla wemali okanye obunye ubudlelwane kunye nomvelisi wayo nayiphi na imveliso ekhankanywe kweli nqaku okanye nawuphi na umboneleli wenkonzo.
Corresponding author: Aditya Bagrodia, Associate Professor, MDA, Department of Urology UC San Diego Suite 1-200, 9400 Campus Point DriveLa Jolla, CA 92037Bagrodia@health.ucsd.edu
Ben DuConnell, BS1.2, Austin J. Leonard, BA3, John T. Ruffin, PhD1, Jia Liwei, MD, PhD4, kunye no-Aditya Bagrodia, MD1.31 iSebe le-Urology, iYunivesithi yaseTexas Southwestern Medical Centre, Dallas, TX