Xov xwm

Hauv qhov teeb meem ntawm Kev Kho Mob Nyuaj Siab, Bendu Konneh, BS, thiab cov npoj yaig nthuav tawm rooj plaub ntawm tus txiv neej hnub nyoog 21 xyoo uas muaj 4-hli keeb kwm ntawm kev loj hlob ntawm txoj cai testicular edema.
Ib tug txiv neej muaj hnub nyoog 21 xyoos yws yws ntawm qhov mob o ntawm cov noob qes txoj cai rau 4 lub hlis.Ultrasound qhia ib tug heterogeneous khoom loj nyob rau hauv txoj cai testicle, ib tug suspicion ntawm ib tug malignant neoplasm.Kev soj ntsuam ntxiv suav nrog suav tomography, uas qhia txog 2 cm retroperitoneal lymph node, tsis muaj cov tsos mob ntawm lub hauv siab metastases (Daim duab 1).Cov kab mob qog ntshav hauv cov ntshav tau pom me ntsis nce qib ntawm alpha-fetoprotein (AFP) thiab qib qis ntawm lactate dehydrogenase (LDH) thiab tib neeg chorionic gonadotropin (hCG).
Tus neeg mob tau txais txoj cai sab xis radical inguinal orchiectomy.Kev ntsuam xyuas kab mob tau qhia txog 1% teratomas nrog cov kab mob sib kis loj heev ntawm cov fetal rhabdomyosarcoma thiab chondrosarcoma.Tsis pom muaj lymphovascular ntxeem tau.Rov ua cov cim qog nqaij hlav pom cov qib ib txwm muaj ntawm AFP, LDH thiab hCG.Kev soj ntsuam xyuas CT ntawm lub sijhawm luv luv tau lees paub qhov tseem ceeb ntawm 2-cm interluminal aortic lymph node uas tsis muaj pov thawj ntawm cov metastases nyob deb.Tus neeg mob no tau txais kev kho mob retroperitoneal lymphadenectomy, uas yog qhov zoo hauv 1 ntawm 24 cov qog nqaij hlav nrog extranodal txuas ntxiv ntawm qhov zoo sib xws ntawm somatic malignancy suav nrog rhabdomyosarcoma, chondrosarcoma, thiab undifferentiated spindle cell sarcoma.Immunohistochemistry pom tias cov qog hlwb tau zoo rau myogenin thiab desmin thiab tsis zoo rau SALL4 (Daim duab 2).
Testicular germ cell hlav (TGCTs) yog lub luag haujlwm rau qhov tshwm sim ntau tshaj plaws ntawm qog nqaij hlav qog nqaij hlav hauv cov txiv neej hluas.TGCT yog cov qog nqaij hlav uas muaj ntau hom kab mob histological uas tuaj yeem muab cov ntaub ntawv rau kev tswj xyuas kev kho mob.1 TGCT muab faib ua 2 pawg: seminoma thiab non-seminoma.Nonseminomas muaj xws li choriocarcinoma, fetal carcinoma, yolk sac qog, thiab teratoma.
Testicular teratomas muab faib ua postpubertal thiab prepubertal cov ntaub ntawv.Prepubertal teratomas yog lom lom thiab tsis cuam tshuam nrog cov kab mob ntawm tes neoplasia hauv situ (GCNIS), tab sis postpubertal teratomas yog txuam nrog GCNIS thiab yog malignant.2 Tsis tas li ntawd, postpubertal teratomas zoo li metastasize rau extragonadal chaw xws li retroperitoneal lymph nodes.Tsis tshua muaj, postpubertal testicular teratomas tuaj yeem txhim kho mus rau hauv kev mob qog noj ntshav thiab feem ntau kho nrog kev phais.
Hauv tsab ntawv tshaj tawm no, peb nthuav tawm cov yam ntxwv ntawm cov molecular yam tsis tshua muaj tshwm sim ntawm teratoma nrog cov tshuaj somatic malignant hauv cov qog ntshav thiab cov qog ntshav.Keeb kwm, TGCT nrog cov kab mob qog noj ntshav tau teb tsis zoo rau hluav taws xob thiab cov tshuaj siv tshuaj platinum raws li kev kho mob, yog li teb A tsis raug.3,4 Kev sim ntawm chemotherapy aiming transformed histology nyob rau hauv metastatic teratomas tau sib xyaw ua ke, nrog rau qee cov kev tshawb fawb qhia cov lus teb zoo thiab lwm tus tsis pom cov lus teb.5-7 Ntawm kev ceeb toom, Alessia C. Donadio, MD, thiab cov npoj yaig tau pom cov lus teb hauv cov neeg mob qog noj ntshav nrog ib hom kab mob histological, thaum peb tau txheeb xyuas 3 hom subtypes: rhabdomyosarcoma, chondrosarcoma, thiab undifferentiated spindle cell sarcoma.Cov kev tshawb fawb ntxiv yog xav tau los soj ntsuam cov lus teb rau cov tshuaj kho mob qhia ntawm TGCT thiab somatic malignant histology nyob rau hauv qhov chaw ntawm metastasis, tshwj xeeb tshaj yog nyob rau hauv cov neeg mob uas muaj ntau yam histological subtypes.Yog li, teb B tsis raug.
Txhawm rau tshawb nrhiav genomic thiab transcriptome toj roob hauv pes ntawm cov qog nqaij hlav no thiab txheeb xyuas cov hom phiaj kho mob, peb tau ua tag nrho-transcriptome qog ib txwm sib luag (NGS) kev tshuaj ntsuam ntawm cov qauv sau los ntawm cov neeg mob aortic lumenal lymph node metastases, ua ke nrog RNA sequencing.Kev txheeb xyuas cov ntaub ntawv los ntawm RNA sequencing qhia tias ERBB3 tsuas yog cov noob tshaj tawm.ERBB3 noob, nyob rau ntawm chromosome 12, codes rau HER3, ib tug tyrosine kinase receptor ib txwm qhia nyob rau hauv daim nyias nyias ntawm epithelial hlwb.Somatic kev hloov pauv hauv ERBB3 tau tshaj tawm hauv qee qhov mob plab hnyuv thiab urothelial carcinomas.yim
NGS-raws li kev soj ntsuam muaj lub hom phiaj vaj huam sib luag (xT vaj huam sib luag 648) ntawm 648 cov noob feem ntau cuam tshuam nrog cov khoom thiab cov qog ntshav.Vaj Huam Sib Luag xT 648 tsis tau nthuav tawm cov kab mob germline variants.Txawm li cas los xij, KRAS missense variant (p.G12C) hauv exon 2 tau txheeb xyuas tias tsuas yog kev hloov pauv ntawm somatic nrog qhov sib txawv ntawm allele feem ntawm 59.7%.KRAS gene yog ib qho ntawm peb tus tswv cuab ntawm RAS oncogene tsev neeg lub luag haujlwm rau kev sib kho ntau cov txheej txheem ntawm tes cuam tshuam nrog kev loj hlob thiab kev sib txawv los ntawm GTPase signaling.9
Txawm hais tias KRAS G12C kev hloov pauv feem ntau tshwm sim hauv cov qog nqaij hlav tsis me me (NSCLC) thiab mob qog noj ntshav, KRAS kev hloov pauv kuj tau tshaj tawm hauv TGCTs ntawm ntau codons.10,11 Qhov tseeb tias KRAS G12C yog qhov kev hloov pauv tsuas yog pom hauv pab pawg no qhia tias qhov kev hloov pauv no yuav yog lub zog tsav tom qab cov txheej txheem hloov pauv tsis zoo.Tsis tas li ntawd, qhov nthuav dav no muab txoj hauv kev ua tau rau kev kho mob ntawm platinum-resistant TGCTs xws li teratomas.Tsis ntev los no, sotorasib (Lumacras) tau los ua thawj KRAS G12C inhibitor rau phiaj KRAS G12C mutant qog.Hauv xyoo 2021, FDA pom zoo sotorasib rau kev kho mob ntawm cov qog nqaij hlav tsis me me.Tsis muaj pov thawj los txhawb kev siv adjuvant translational histological tsom txoj kev kho rau TGCT nrog cov tshuaj somatic malignant.Cov kev tshawb fawb ntxiv yog xav tau los ntsuas cov lus teb ntawm translational histology rau kev kho mob.Yog li ntawd, teb C tsis yog lawm.Txawm li cas los xij, yog tias cov neeg mob muaj qhov tshwm sim zoo sib xws ntawm cov khoom hauv lub cev, kev kho kom zoo nrog sotorasib tuaj yeem muab nrog kev tshawb nrhiav.
Nyob rau hauv cov nqe lus ntawm immunotherapy markers, microsatellite ruaj khov (MSS) qog pom qhov hloov pauv (TMB) ntawm 3.7 m / MB (50 feem pua).Muab hais tias TGCT tsis muaj TMB siab, nws tsis yog qhov xav tsis thoob tias qhov xwm txheej no nyob hauv 50 feem pua ​​​​piv rau lwm cov qog.12 Raws li qhov qis TMB thiab MSS ntawm cov qog, qhov tshwm sim ntawm kev ua rau lub cev tiv thaiv kab mob raug txo;Cov qog tuaj yeem tsis teb rau kev tiv thaiv kab mob tiv thaiv kab mob.13,14 Yog li ntawd, teb E yog tsis raug.
Serum qog markers (STMs) yog qhov tseem ceeb rau kev kuaj mob ntawm TGCT;lawv muab cov ntaub ntawv rau staging thiab pheej hmoo stratification.Feem ntau STMs tam sim no siv rau kev kuaj mob xws li AFP, hCG, thiab LDH.Hmoov tsis zoo, qhov ua tau zoo ntawm peb cov cim no tsuas yog txwv rau qee qhov TGCT subtypes, suav nrog teratoma thiab seminoma.15 Tsis ntev los no, ntau lub microRNAs (miRNAs) tau muab tso ua ke ua cov cim biomarkers rau qee yam TGCT subtypes.MiR-371a-3p tau pom tias muaj peev xwm txhim kho kom pom ntau TGCT isoforms nrog rhiab heev thiab qhov tshwj xeeb muaj nuj nqis xws li 80% txog 90% hauv qee qhov kev tshaj tawm.16 Txawm hais tias cov txiaj ntsig no tau cog lus tseg, miR-371a-3p feem ntau tsis yog nce siab hauv cov xwm txheej ntawm teratoma.Kev tshawb fawb ntau qhov chaw los ntawm Klaus-Peter Dieckmann, MD, thiab cov npoj yaig tau pom tias hauv ib pawg ntawm 258 tus txiv neej, miP-371a-3p qhia tau qis tshaj hauv cov neeg mob uas muaj teratoma ntshiab.17 Txawm hais tias miR-371a-3p ua haujlwm tsis zoo hauv cov teratomas, cov ntsiab lus ntawm kev hloov pauv tsis zoo nyob rau hauv cov xwm txheej no qhia tias kev tshawb nrhiav muaj peev xwm.Kev soj ntsuam MiRNA tau ua tiav ntawm cov ntshav los ntawm cov neeg mob ua ntej thiab tom qab lymphadenectomy.Lub hom phiaj miR-371a-3p thiab miR-30b-5p siv cov noob tau suav nrog hauv kev tshuaj xyuas.MiP-371a-3p qhia tau raug ntsuas los ntawm qhov rov qab hloov pauv cov tshuaj polymerase saw cov tshuaj tiv thaiv.Cov txiaj ntsig tau pom tias miP-371a-3p tau pom muaj tsawg kawg hauv cov qauv kuaj ua ntej thiab tom qab phais, qhia tias nws tsis tau siv los ua tus cim qog hauv tus neeg mob no.Qhov nruab nrab lub voj voog suav ntawm cov qauv ua ntej yog 36.56, thiab miP-371a-3p tsis tau kuaj pom hauv cov qauv tom qab phais.
Tus neeg mob tsis tau txais kev kho mob ntxiv.Cov neeg mob tau xaiv qhov kev soj ntsuam zoo nrog kev ntsuas lub hauv siab, plab, thiab lub plab mog raws li kev pom zoo thiab STM.Yog li, cov lus teb raug yog D. Ib xyoos tom qab tshem tawm cov qog retroperitoneal, tsis muaj cov tsos mob ntawm tus kab mob rov qab.
Kev Tshaj Tawm: Tus neeg sau tsis muaj kev txaus siab txog nyiaj txiag lossis lwm yam kev sib raug zoo nrog cov chaw tsim khoom ntawm cov khoom lag luam uas tau hais hauv tsab xov xwm no lossis nrog ib tus neeg muab kev pabcuam.
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, and Aditya Bagrodia, MD1.31 Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX