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Muchinyorwa ichi cheClinical Difficulties, Bendu Konneh, BS, uye vaanoshanda navo vanopa nyaya yemurume ane makore 21 ane 4-mwedzi nhoroondo yekufambira mberi yakarurama testicular edema.
Murume ane makore 21 okuberekwa akanyunyuta nekuzvimba zvishoma nezvishoma kwechete chaiyo kwemwedzi mina.Ultrasound yakaratidza heterogeneous yakasimba misa muchetura chaimo, fungidziro yeakaipa neoplasm.Kumwe kuongorora kwaisanganisira computed tomography, iyo yakaratidza 2 cm retroperitoneal lymph node, pakanga pasina zviratidzo zvechipfuva metastases (Fig. 1).Serum tumor markers yakaratidza yakakwira zvishoma mazinga ealpha-fetoprotein (AFP) uye akajairwa mazinga elactate dehydrogenase (LDH) uye chorionic gonadotropin (hCG) yevanhu.
Murwere akavhiyiwa kurudyi-side radical inguinal orchiectomy.Pathological evaluation yakaratidza 1% teratomas ine yakakura yechipiri somatic malignant zvikamu zve fetal rhabdomyosarcoma uye chondrosarcoma.Hapana lymphovascular invasion yakawanikwa.Akadzokororwa bundu mamaki airatidza akajairwa mazinga eAFP, LDH uye hCG.Kutevera CT scans munguva pfupi yakasimbisa 2-cm interluminal aortic lymph node pasina humbowo hwematastases ari kure.Murwere uyu akaita retroperitoneal lymphadenectomy, iyo yaive yakanaka mu1 ye24 lymph nodes ine extranodal kuwedzera kweiyo yakafanana somatic malignancy inosanganisira rhabdomyosarcoma, chondrosarcoma, uye undifferentiated spindle cell sarcoma.Immunohistochemistry yakaratidza kuti masero ebundu aive akanaka kune myogenin uye desmin uye asina kunaka kune SALL4 (Mufananidzo 2).
Testicular germ cell tumors (TGCTs) inokonzera chiitiko chepamusoro chegomarara re testicular muvarume vechidiki vakuru.TGCT ibundu rakasimba rine akawanda histological subtypes ayo anogona kupa ruzivo rwekuchipatara manejimendi.1 TGCT yakakamurwa muzvikamu zviviri: seminoma uye isiri-seminoma.Nonseminomas inosanganisira choriocarcinoma, fetal carcinoma, yolk sac tumor, uye teratoma.
Testicular teratomas yakakamurwa kuita postpubertal uye prepubertal mafomu.Prepubertal teratomas ndeye biologically indolent uye haina hukama negerm cell neoplasia in situ (GCNIS), asi postpubertal teratomas yakabatana neGCNIS uye yakaipa.2 Mukuwedzera, postpubertal teratomas inowanzoita metastasize kune extragonadal nzvimbo dzakadai seretroperitoneal lymph nodes.Kashoma, postpubertal testicular teratomas inogona kukura kuita somatic malignancies uye kazhinji inorapwa nekuvhiyiwa.
Mumushumo uyu, tinopa mamolecular maitiro ezviitiko zvisingawanzoitiki zveteratoma ine somatic malignant chikamu mumates uye lymph nodes.Nhoroondo, TGCT ine somatic malignancies yapindura zvisina kunaka kune radiation uye yakajairika platinum-based chemotherapy, saka mhinduro A haina kururama.3,4 Kuedza chemotherapy kunangwa kwakashandura histology mu metastatic teratomas kwakave nemhedzisiro yakasanganiswa, nedzimwe ongororo dzichiratidza mhinduro yakanaka uye dzimwe dzisingaratidzi mhinduro.5-7 Yechinyorwa, Alessia C. Donadio, MD, uye vaaishanda navo vakaratidza mhinduro muvarwere vekenza vane imwe histological subtype, apo takaona 3 subtypes: rhabdomyosarcoma, chondrosarcoma, uye undifferentiated spindle cell sarcoma.Zvimwe zvidzidzo zvinodiwa kuti uongorore mhinduro kune chemotherapy inotungamirirwa kuTGCT uye somatic malignant histology mukugadzirisa metastasis, kunyanya kune varwere vane multiple histological subtypes.Naizvozvo mhinduro B haina kururama.
Kuti tiongorore genomic uye transcriptome landscape yegomarara iri uye kuona zvingangonangwa pakurapa, takaita yakazara-transcriptome tumor yakajairwa sequencing (NGS) inoongorora pane zvienzaniso zvakaunganidzwa kubva kuvarwere vane aortic lumenal lymph node metastases, pamwe chete neRNA kutevedzana.Ongororo yeTranscriptome neRNA sequencing yakaratidza kuti ERBB3 ndiyo yega gene rakanyanyisa.Iyo ERBB3 gene, iri pachromosome 12, makodhi eHER3, a tyrosine kinase receptor anowanzo kuratidzwa mu membrane ye epithelial masero.Somatic mutations muERBB3 yakataurwa mune mamwe gastrointestinal uye urothelial carcinomas.sere
Iyo NGS-yakavakirwa assay ine inonangwa pani (xT pani 648) ye648 majini anowanzo sangana neakasimba uye eropa gomarara.Panel xT 648 haina kuratidza pathogenic germline variants.Nekudaro, iyo KRAS missense variant (p.G12C) mu exon 2 yakaonekwa seyo chete somatic mutation ine akasiyana allele share ye59.7%.Iyo KRAS gene ndeimwe yenhengo nhatu dzeRAS oncogene mhuri ine mutoro wekuyananisa akawanda cellular maitiro ane chekuita nekukura uye kusiyanisa kuburikidza neGTPase kusaina.9
Kunyangwe kuchinja kweKRAS G12C kunonyanya kuwanda mukenza isiri-diki yekenza yemapapu (NSCLC) uye colorectal cancer, KRAS shanduko dzakataurwawo muTGCTs dzemacodon akasiyana.10,11 Icho chokwadi chekuti KRAS G12C ndiyo yega shanduko inowanikwa muboka iri inoratidza kuti shanduko iyi inogona kunge iri simba rekufambisa kuseri kwekuchinja kwakashata.Mukuwedzera, iyi tsanangudzo inopa nzira inogoneka yekurapa kweplatinamu-resistant TGCTs senge teratomas.Munguva pfupi yapfuura, sotorasib (Lumacras) yakava yekutanga KRAS G12C inhibitor kunanga KRAS G12C mutant tumors.Muna 2021, iyo FDA yakabvumidza sotorasib kurapwa kweiyo isiri-diki cell cancer yemapapu.Hapana humbowo hunotsigira kushandiswa kweadjuvant translational histological targeted therapy yeTGCT ine somatic malignant component.Zvimwe zvidzidzo zvinodikanwa kuongorora mhinduro yeshanduro histology kune yakanangwa kurapa.Naizvozvo, mhinduro C haina kururama.Zvisinei, kana varwere vakawana kudzokorora kwakafanana kwezvikamu zvemuviri, salvage therapy ne sotorasib inogona kupiwa ine simba rekuongorora.
Panyaya ye immunotherapy markers, microsatellite stable (MSS) tumors yakaratidza mutation load (TMB) ye3.7 m / MB (50th percentile).Tichifunga kuti TGCT haina TMB yakakwirira, hazvishamisi kuti nyaya iyi iri mu50th percentile kana ichienzaniswa nemamwe mamota.12 Tichifunga nezve yakaderera TMB uye MSS mamiriro emamota, mukana wekukonzeresa mhinduro yekudzivirira kwemuviri unoderedzwa;tumors inogona kusapindura kune immune checkpoint inhibitor therapy.13, 14 Naizvozvo mhinduro E haina kururama.
Serum tumor markers (STMs) inokosha pakuongororwa kweTGCT;ivo vanopa ruzivo rwekuita uye njodzi stratification.Zvakajairwa STMs parizvino anoshandiswa pakuongororwa kwekiriniki anosanganisira AFP, hCG, uye LDH.Nehurombo, kushanda kweaya mamaki matatu kunogumira mune mamwe TGCT subtypes, kusanganisira teratoma uye seminoma.15 Munguva pfupi yapfuura, akati wandei mamicroRNAs (miRNAs) akaiswa seanogona biomarker kune mamwe TGCT subtypes.MiR-371a-3p yakaratidza kuve nekwaniso yakakwidziridzwa yekuona akawanda TGCT isoforms ane sensitivity uye hunhu hunokosha kubva pa80% kusvika 90% mune zvimwe zvinyorwa.16 Kunyangwe izvi zvabuda zvichivimbisa, miR-371a-3p haiwanzo kukwidziridzwa mumamiriro ezvinhu eteratoma.Chidzidzo chakasiyana-siyana chakaitwa naKlaus-Peter Dieckmann, MD, uye vashandi pamwe navo vakaratidza kuti muboka revarume ve258, miP-371a-3p kutaura kwaive kwakaderera kune varwere vane teratoma yakachena.17 Kunyangwe miR-371a-3p ichiita zvisina kunaka muteratomas yakachena, zvinhu zvekuchinja kwakashata pasi pemamiriro aya zvinoratidza kuti kuferefetwa kunogoneka.MiRNA ongororo yakaitwa paserum yakatorwa kubva kuvarwere isati yasvika uye mushure me lymphadenectomy.Iyo miR-371a-3p chinangwa uye miR-30b-5p referensi gene yakabatanidzwa mukuongorora.MiP-371a-3p kutaura kwakaverengerwa nereverse transcription polymerase chain reaction.Mhedzisiro yacho yakaratidza kuti miP-371a-3p yakawanikwa mune shoma shoma mune preoperative uye postoperative serum samples, zvichiratidza kuti haina kushandiswa sebundu marker mumurwere uyu.Izvo zvinoreva kutenderera kuverengera kwe preoperative samples yaive 36.56, uye miP-371a-3p haina kuwonekwa mune postoperative samples.
Murwere haana kugamuchira adjuvant therapy.Varwere vakasarudza kuongorora kunoshanda nekufungidzira kwechipfuva, dumbu, uye pelvis sezvakakurudzirwa uye STM.Nokudaro, mhinduro yakarurama ndeye D. Gore mushure mekubviswa kwe retroperitoneal lymph nodes, pakanga pasina zviratidzo zvekudzokazve kwechirwere.
Kuzivisa: Munyori haana zvinhu zvekufarira mari kana humwe hukama nemugadziri wechero chigadzirwa chataurwa muchinyorwa chino kana chero chero mupi webasa.
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, uye Aditya Bagrodia, MD1.31 Dhipatimendi reUrology, University of Texas Southwestern Medical Center, Dallas, TX