Izindaba

Kulolu daba lwe-Clinical Difficulties, u-Bendu Konneh, BS, kanye nozakwabo bethula icala lendoda eneminyaka engu-21 ubudala enomlando wezinyanga ezingu-4 we-edema ye-testicular eqhubekayo efanele.
Indoda eneminyaka engu-21 ubudala ikhala ngokuvuvuka kwesende elifanele izinyanga ezi-4.I-Ultrasound yembula isisindo esiqinile esingafani nesende elingakwesokudla, izinsolo ze-neoplasm eyingozi.Ukuhlolwa okwengeziwe kwakuhlanganisa i-computed tomography, eyembula i-lymph node ye-retroperitoneal engu-2 cm, kwakungekho zimpawu ze-metastases esifubeni (Fig. 1).Omaka be-serum tumor bakhombise amazinga aphakeme kancane e-alpha-fetoprotein (AFP) namazinga ajwayelekile e-lactate dehydrogenase (LDH) kanye ne-chorionic gonadotropin (hCG) yabantu.
Isiguli senziwa i-radical inguinal orchiectomy engakwesokudla.Ukuhlolwa kwe-pathological kwembula i-teratoma engu-1% enezingxenye eziyingozi zesibili ze-fetus rhabdomyosarcoma kanye ne-chondrosarcoma.Akukho ukuhlasela kwe-lymphovascular okutholakele.Izimpawu zesimila eziphindaphindiwe zibonise amazinga ajwayelekile e-AFP, LDH kanye ne-hCG.Ama-CT scans wokulandelela ngezikhathi ezimfushane aqinisekisa i-lymph node ye-interluminal aortic engu-2 cm evelele ngaphandle kobufakazi bokuma-metastases akude.Lesi siguli senziwe i-retroperitoneal lymphadenectomy, eyayilungile ku-1 kwama-lymph nodes angu-24 ngokunwetshwa kwe-extranodal ye-somatic malignancy efanayo ehlanganisa i-rhabdomyosarcoma, i-chondrosarcoma, ne-spindle cell sarcoma engahlukanisi.I-Immunohistochemistry ibonise ukuthi amaseli wesimila ayelungile ku-myogenin ne-desmin futhi engemihle ku-SALL4 (Umfanekiso 2).
Izimila ze-testicular germ cell (TGCTs) ziyimbangela yezehlakalo eziphezulu zomdlavuza wamasende emadodeni amadala.I-TGCT iyithumba eliqinile elinama-subtypes amaningi e-histological anganikeza ulwazi lokuphathwa komtholampilo.I-1 TGCT ihlukaniswe izigaba ezi-2: i-seminoma ne-non-seminoma.Ama-nonseminomas ahlanganisa i-choriocarcinoma, i-fetus carcinoma, i-yolk sac tumor, ne-teratoma.
I-teratomas ye-testicular ihlukaniswe yaba amafomu we-postpubertal kanye ne-prepubertal.I-teratomas yangaphambi kokuthomba ayisebenzi ngokwezinto eziphilayo futhi ayihlotshaniswa ne-germ cell neoplasia in situ (GCNIS), kodwa i-teratomas yangemva kokuthomba ihlotshaniswa ne-GCNIS futhi iyingozi.2 Ngaphezu kwalokho, ama-teratoma angemva kokuthomba avame ukumetastaze kumasayithi angaphandle kwama-lymph nodes afana ne-retroperitoneal lymph nodes.Akuvamile ukuthi i-postpubertal testicular teratomas ikhule ibe yizifo ezibulalayo futhi imvamisa yelashwa ngokuhlinzwa.
Kulo mbiko, sethula ukubonakaliswa kwamangqamuzana ezimweni ezingavamile ze-teratoma enengxenye eyingozi ye-somatic kuma-testes nama-lymph nodes.Ngokomlando, i-TGCT ene-somatic malignancies ayiphenduli kahle emisebeni nasekwelapheni okujwayelekile okusekelwe ku-platinum, ngakho impendulo A ayilungile.3,4 Imizamo yokukhomba ukwelashwa ngamakhemikhali okushintshile i-histology kuma-teratomas e-metastatic ibe nemiphumela exubile, ngocwaningo oluthile olubonisa impendulo eqhubekayo evumayo futhi eminye engabonisi mpendulo.I-5-7 Inothi, u-Alessia C. Donadio, MD, kanye nozakwethu babonise izimpendulo ezigulini ezinomdlavuza ezine-subtype eyodwa ye-histological, kuyilapho sikhomba ama-subtypes angu-3: i-rhabdomyosarcoma, i-chondrosarcoma, ne-spindle cell sarcoma engahlukanisi.Kudingeka ucwaningo olwengeziwe ukuze kuhlolwe impendulo yokwelashwa ngamakhemikhali eqondiswe ku-TGCT kanye ne-somatic malignant histology esimweni se-metastasis, ikakhulukazi ezigulini ezinezinhlobo eziningi ze-histological subtypes.Ngakho-ke, impendulo ethi B ayilungile.
Ukuhlola isimo se-genomic kanye ne-transcriptome yalo mdlavuza futhi sihlonze okungase kube okuhlosiwe kokwelapha, senze ukuhlaziya kwe-whole-transcriptome tumor normal sequencing (NGS) kumasampula aqoqwe ezigulini ezine-aortic lumenal lymph node metastases, kuhlanganiswe nokulandelana kwe-RNA.Ukuhlaziywa kwe-Transcriptome ngokulandelana kwe-RNA kubonise ukuthi i-ERBB3 ukuphela kofuzo oluvezwe ngokweqile.Ufuzo lwe-ERBB3, olutholakala ku-chromosome 12, amakhodi e-HER3, isamukeli se-tyrosine kinase ngokuvamile esivezwa kulwelwesi lwamaseli e-epithelial.Ukuguqulwa kwe-Somatic ku-ERBB3 kuye kwabikwa kwamanye ama-carcinoma amathumbu kanye ne-urothelial.ayisishiyagalombili
Ukuhlolwa okusekelwe ku-NGS kuqukethe iphaneli eqondiwe (iphaneli ye-xT 648) yezakhi zofuzo ezingama-648 ngokuvamile ezihlotshaniswa nomdlavuza oqinile nowegazi.Iphaneli ye-xT 648 ayizange iveze okuhlukile komugqa wegciwane le-pathogenic.Kodwa-ke, okuhlukile kwe-KRAS missense (p.G12C) ku-exon 2 kukhonjwe njengokuwukuphela kokuguqulwa kwe-somatic okunokwabelana okuhlukile kwe-allele okungu-59.7%.Isakhi sofuzo se-KRAS singelinye lamalungu amathathu omndeni we-oncogene we-RAS onesibopho sokulamula izinqubo eziningi zamaselula ezihambisana nokukhula nokuhlukaniswa ngokusayina kwe-GTPase.9
Nakuba ukuguqulwa kwe-KRAS G12C kuvame kakhulu kumdlavuza wamaphaphu ongewona omncane (NSCLC) kanye nomdlavuza we-colorectal, ukuguqulwa kwe-KRAS kuye kwabikwa kuma-TGCT ama-codon ahlukahlukene.10,11 Iqiniso lokuthi i-KRAS G12C ukuphela koguquko olutholakala kuleli qembu liphakamisa ukuthi lokhu kuguqulwa kungase kube amandla aqhuba inqubo yoshintsho olubi.Ukwengeza, le mininingwane inikeza umzila ongaba khona wokwelashwa kwe-TGCTs engamelana neplatinamu njengama-teratomas.Muva nje, i-sotorasib (Lumacras) ibe inhibitor yokuqala ye-KRAS G12C ukukhomba izimila eziguqukayo ze-KRAS G12C.Ngo-2021, i-FDA igunyaze i-sotorasib yokwelapha umdlavuza wamaphaphu ongewona omncane.Abukho ubufakazi obusekela ukusetshenziswa kwe-adjuvant translational histological targeted therapy ye-TGCT nge-somatic malignant component.Kudingeka izifundo ezengeziwe ukuze kuhlolwe impendulo ye-histology yokuhumusha ekwelashweni okuqondiwe.Ngakho-ke, impendulo C ayilungile.Kodwa-ke, uma iziguli zithola ukuphindaphinda okufanayo kwezingxenye zomzimba, ukwelashwa kokulondoloza nge-sotorasib kungase kunikelwe ngamandla okuhlola.
Ngokwamaka we-immunotherapy, izimila ezizinzile ze-microsatellite (MSS) zibonise umthwalo oguqukayo (TMB) we-3.7 m/MB (amaphesenti angama-50).Njengoba kunikezwe ukuthi i-TGCT ayinayo i-TMB ephezulu, akumangazi ukuthi leli cala liku-50th percentile uma kuqhathaniswa nezinye izimila.12 Uma kubhekwa isimo esiphansi se-TMB kanye ne-MSS yamathumba, amathuba okuvusa ukusabela komzimba ayancipha;amathumba angase angaphenduli ekwelashweni kwe-immune checkpoint inhibitor.13,14 Ngakho-ke, impendulo E ayilungile.
Izimpawu ze-serum tumor (STMs) zibalulekile ekuxilongweni kwe-TGCT;bahlinzeka ngolwazi lwesiteji kanye nokuhlukaniswa kwengozi.Ama-STM avamile okwamanje asetshenziselwa ukuxilongwa komtholampilo ahlanganisa i-AFP, i-hCG, ne-LDH.Ngeshwa, ukusebenza kahle kwalaba maka abathathu kunomkhawulo kwezinye izinhlobo ezincane ze-TGCT, okuhlanganisa i-teratoma ne-seminoma.15 Muva nje, ama-microRNAs (miRNA) amaningana afakwe njengama-biomarker angaba khona wezinhlobo ezithile ze-TGCT.I-MiR-371a-3p iboniswe inekhono elithuthukisiwe lokuthola ama-isoform amaningi e-TGCT anokuzwela kanye namanani akhethekile asuka ku-80% kuya ku-90% kwezinye izincwadi.16 Nakuba le miphumela ithembisa, i-miR-371a-3p ngokuvamile ayiphakamisi ezimweni ezivamile ze-teratoma.Ucwaningo lwe-multicenter olwenziwa u-Klaus-Peter Dieckmann, MD, nozakwabo lubonise ukuthi eqenjini lamadoda angu-258, inkulumo ye-miP-371a-3p yayiphansi kakhulu ezigulini ezine-teratoma ehlanzekile.17 Nakuba i-miR-371a-3p ingasebenzi kahle kuma-teratomas amsulwa, izici zoshintsho oluyingozi ngaphansi kwalezi zimo ziphakamisa ukuthi uphenyo lungenzeka.Ukuhlaziywa kwe-MiRNA kwenziwa ku-serum ethathwe ezigulini ngaphambi nangemuva kwe-lymphadenectomy.Ithagethi ye-miR-371a-3p kanye nofuzo lwereferensi ye-miR-30b-5p kufakiwe ekuhlaziyeni.Isisho se-MiP-371a-3p silinganiswa ngokusabela okuhlanekezelwe kwe-polymerase chain reaction.Imiphumela yabonisa ukuthi i-miP-371a-3p itholwe ngamanani amancane kumasampula e-serum yangaphambi kokuhlinzwa nangemuva kokuhlinzwa, ebonisa ukuthi ayizange isetshenziswe njengomaka wesimila kulesi siguli.Isilinganiso somjikelezo wesibalo samasampuli wangaphambi kokuhlinzwa sasingu-36.56, futhi i-miP-371a-3p ayizange itholwe kumasampuli angemva kokuhlinzwa.
Isiguli asizange sithole ukwelashwa kwe-adjuvant.Iziguli zakhetha ukugadwa okusebenzayo ngokuthwebula isifuba, isisu, ne-pelvis njengoba kunconyiwe kanye ne-STM.Ngakho-ke, impendulo efanele ingu-D. Ngonyaka ngemva kokukhishwa kwama-lymph nodes e-retroperitoneal, kwakungekho zimpawu zokubuyela emuva kwalesi sifo.
Ukudalula: Umbhali akanalo intshisekelo yezezimali noma obunye ubudlelwano nomkhiqizi wanoma yimuphi umkhiqizo oshiwo kulesi sihloko noma nanoma yimuphi umhlinzeki wesevisi.
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, kanye no-Aditya Bagrodia, MD1.31 Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX