Nūhou

Ma kēia pukana o Clinical Difficulties, ʻo Bendu Konneh, BS, a me nā hoa hana e hōʻike i ka hihia o kahi kanaka 21 makahiki me kahi moʻolelo 4-malama o ka edema testicular akau holomua.
Ua hoʻopiʻi kekahi kanaka 21 makahiki i ka pehu ʻana o ka ʻāʻī kūpono no 4 mau mahina.Ua hōʻike ʻia ka Ultrasound i kahi nuipa paʻa heterogeneous i ka testicle ʻākau, kahi kānalua o kahi neoplasm malignant.ʻO ka nānā hou aʻe i komo i ka computed tomography, i hōʻike ʻia he 2 cm retroperitoneal lymph node, ʻaʻohe hōʻailona o ka metastases o ka umauma (Fig. 1).Ua hōʻike ʻia nā mea hōʻailona tumo serum i nā pae kiʻekiʻe o ka alpha-fetoprotein (AFP) a me nā pae maʻamau o ka lactate dehydrogenase (LDH) a me ka gonadotropin chorionic kanaka (hCG).
Ua loaʻa ka mea maʻi i ka ʻaoʻao ʻākau radical inguinal orchiectomy.Hōʻike ka loiloi pathological i ka 1% teratomas me ka nui o nā mea maʻi somatic lua o ka rhabdomyosarcoma fetal a me chondrosarcoma.ʻAʻole i ʻike ʻia kahi hōʻeha lymphovascular.Hōʻike ʻia nā hōʻailona maʻi maʻamau o AFP, LDH a me hCG.Hoʻopaʻa ʻia ka nānā ʻana i ka CT ma nā manawa pōkole he 2-cm interluminal aortic lymph node me ka loaʻa ʻole o nā metastases mamao.Ua loaʻa kēia mea maʻi i ka lymphadenectomy retroperitoneal, i maikaʻi ma 1 o 24 lymph nodes me ka extranodal extension o kahi malignancy somatic like me ka rhabdomyosarcoma, chondrosarcoma, a me ka sarcoma pūnaewele spindle undifferentiated.Ua hōʻike ʻo Immunohistochemistry i ka maikaʻi o nā cell tumor no myogenin a me desmin a maikaʻi ʻole no SALL4 (Figure 2).
ʻO nā maʻi maʻi maʻi maʻi testicular (TGCTs) ke kuleana no ka piʻi nui loa o ka maʻi kanesa testicular i nā kāne ʻōpio makua.ʻO TGCT kahi maʻi maʻi paʻa me nā subtypes histological he nui i hiki ke hāʻawi i ka ʻike no ka hoʻokele lapaʻau.Hoʻokaʻawale ʻia ʻo 1 TGCT i 2 mau ʻāpana: seminoma a me non-seminoma.ʻO nā nonseminomas e pili ana i ka choriocarcinoma, ka maʻi maʻi hānai, ka ʻōpū ʻeke yolk, a me ka teratoma.
Hoʻokaʻawale ʻia nā teratoma testicular i nā ʻano postpubertal a me nā ʻano prepubertal.ʻO nā teratoma prepubertal he molowa ola a ʻaʻole pili me ka germ cell neoplasia in situ (GCNIS), akā pili nā teratoma postpubertal me GCNIS a he ʻino.2 Eia kekahi, hiki i nā teratoma postpubertal ke hoʻonui i ka metastasis i nā wahi extragonadal e like me ka retroperitoneal lymph nodes.Kakaʻikahi, hiki i ka postpubertal testicular teratomas ke ulu a lilo i mau maʻi maʻi somatic a mālama pinepine ʻia me ka ʻokiʻoki.
I loko o kēia hōʻike, hōʻike mākou i ka molecular characterization o nā hihia kakaikahi o teratoma me kahi mea maʻi maʻi somatic i loko o ka testes a me nā lymph nodes.Ma ka mōʻaukala, ua pane maikaʻi ʻo TGCT me nā maʻi maʻi somatic i ka radiation a me ka maʻamau platinum-based chemotherapy, no laila ʻaʻole pololei ka pane A.3,4 ʻO ka hoʻāʻo ʻana i ka chemotherapy e huli ana i ka histology i hoʻololi ʻia i nā teratoma metastatic ua loaʻa nā hopena like ʻole, me kekahi mau haʻawina e hōʻike ana i kahi pane maikaʻi mau a me nā mea ʻē aʻe ʻaʻohe pane.5-7 O ka moʻolelo, ua hōʻike ʻo Alessia C. Donadio, MD, a me nā hoa hana i nā pane i ka poʻe maʻi maʻi maʻi me hoʻokahi subtype histological, ʻoiai mākou i ʻike i nā subtypes 3: rhabdomyosarcoma, chondrosarcoma, a me undifferentiated spindle cell sarcoma.Pono nā haʻawina hou e loiloi i ka pane ʻana i ka chemotherapy i kuhikuhi ʻia ma TGCT a me ka somatic malignant histology i ka hoʻonohonoho ʻana o ka metastasis, ʻoi loa i nā maʻi me nā subtypes histological he nui.No laila, ʻaʻole pololei ka pane B.
No ka ʻimi ʻana i ka ʻāina genomic a me ka transcriptome o kēia maʻi maʻi a ʻike i nā pahuhopu therapeutic hiki, ua hana mākou i ka whole-transcriptome tumor normal sequencing (NGS) anana i nā specimens i hōʻiliʻili ʻia mai nā mea maʻi me ka aortic lumenal lymph node metastases, i hui pū me ka RNA sequencing.Ua hōʻike ʻia ka loiloi transcriptome e RNA sequencing ʻo ERBB3 wale nō ka gene i hoʻohālikelike ʻia.ʻO ka gene ERBB3, aia ma ka chromosome 12, nā code no HER3, kahi mea loaʻa tyrosine kinase i hōʻike mau ʻia i loko o ka membrane o nā cell epithelial.Ua hōʻike ʻia nā hoʻololi somatic ma ERBB3 i kekahi mau maʻi maʻi gastrointestinal a me urothelial carcinomas.ʻewalu
ʻO ka ho'āʻo e pili ana i ka NGS he papa kuhikuhi (xT panel 648) o 648 mau genes e pili pū ana me nā maʻi maʻi paʻa a me ke koko.ʻAʻole hōʻike ka Panel xT 648 i nā ʻano ʻano germline pathogenic.Eia naʻe, ʻo ka KRAS missense variant (p.G12C) ma exon 2 i ʻike ʻia ʻo ia wale nō ka somatic mutation me kahi ʻano allele share o 59.7%.ʻO ka gene KRAS kekahi o nā lālā ʻekolu o ka ʻohana oncogene RAS ke kuleana no ka hoʻoponopono ʻana i nā kaʻina kelepona lehulehu e pili ana i ka ulu a me ka ʻokoʻa ma o ka hōʻailona GTPase.9
ʻOiai he mea maʻamau ka hoʻololi ʻana o KRAS G12C i ka maʻi maʻi ʻaʻai liʻiliʻi liʻiliʻi (NSCLC) a me ka maʻi maʻi colorectal, ua hōʻike pū ʻia nā hoʻololi KRAS ma nā TGCT o nā codons like ʻole.10,11 ʻO ka ʻoiaʻiʻo ʻo KRAS G12C wale nō ka hoʻololi ʻana i loaʻa i loko o kēia pūʻulu e hōʻike ana ʻo kēia hoʻololi ʻana paha ke kumu hoʻokele ma hope o ke kaʻina hana hoʻololi kino.Eia kekahi, hāʻawi kēia kikoʻī i kahi ala kūpono no ka mālama ʻana i nā TGCT pale-platinum e like me teratomas.ʻO ka mea hou aku nei, ua lilo ʻo sotorasib (Lumacras) i mea hoʻopiʻi mua KRAS G12C e hoʻopaʻa i nā maʻi mutant KRAS G12C.I ka makahiki 2021, ua ʻae ka FDA i ka sotorasib no ka mālama ʻana i ka maʻi maʻi pūpū liʻiliʻi liʻiliʻi.ʻAʻohe mea hōʻike e kākoʻo i ka hoʻohana ʻana i ka adjuvant translational histological targeted therapy no TGCT me kahi ʻāpana malignant somatic.Pono nā haʻawina hou aʻe e loiloi i ka pane ʻana o ka histology unuhi i ka lāʻau lapaʻau.No laila, hewa ka pane C.Eia nō naʻe, inā ʻike ka poʻe maʻi i ka hoʻihoʻi hou ʻana o nā ʻāpana kino, hiki ke hāʻawi ʻia ka salvage therapy me sotorasib me ka hiki ke ʻimi.
Ma ke ʻano o nā hōʻailona immunotherapy, hōʻike ʻia nā ʻōpū microsatellite stable (MSS) i kahi mutation load (TMB) o 3.7 m/MB (50th percentile).Ma muli o ka loaʻa ʻole o ka TMB kiʻekiʻe o TGCT, ʻaʻole ia he mea kupanaha no kēia hihia i ka 50th percentile i hoʻohālikelike ʻia me nā maʻi ʻē aʻe.12 Hāʻawi ʻia i ke kūlana TMB a me MSS haʻahaʻa o nā maʻi ʻaʻai, ua hoʻemi ʻia ka hiki ke hoʻoulu i kahi pane immune;ʻAʻole hiki i nā maʻi koko ke pane i ka hoʻomaʻamaʻa hoʻopaʻa hoʻopaʻa kino.13,14 No laila, ʻaʻole pololei ka pane E.
He mea koʻikoʻi nā hōʻailona tumo serum (STM) i ka hōʻailona o TGCT;hāʻawi lākou i ka ʻike no ka hoʻonohonoho ʻana a me ka stratification pilikia.ʻO nā STM maʻamau i hoʻohana ʻia i kēia manawa no ka maʻi lapaʻau e pili ana i AFP, hCG, a me LDH.ʻO ka mea pōʻino, ua kaupalena ka maikaʻi o kēia mau māka ʻekolu i kekahi mau subtypes TGCT, me ka teratoma a me ka seminoma.15 I kēia mau lā, ua hoʻopaʻa ʻia kekahi mau microRNAs (miRNAs) ma ke ʻano he biomarkers kūpono no kekahi mau subtypes TGCT.Ua hōʻike ʻia ʻo MiR-371a-3p i ka hiki ke ʻike i nā isoforms TGCT he nui me ka naʻau a me nā waiwai kikoʻī mai 80% a 90% i kekahi mau paʻi.16 ʻOiai he manaʻo maikaʻi kēia mau hopena, ʻaʻole i hoʻokiʻekiʻe ʻia ka miR-371a-3p i nā hihia maʻamau o ka teratoma.Ua hōʻike ʻia kahi haʻawina multicenter e Klaus-Peter Dieckmann, MD, a me nā hoa hana i loko o kahi hui o 258 mau kāne, haʻahaʻa loa ka hōʻike miP-371a-3p i nā maʻi me ka teratoma maʻemaʻe.17 ʻOiai he maikaʻi ʻole ka hana ʻana o ka miR-371a-3p i nā teratoma maʻemaʻe, ʻo nā ʻano o ka hoʻololi ʻino ma lalo o kēia mau kūlana e hōʻike ana he hiki ke hoʻokolokolo.Ua hana ʻia nā loiloi MiRNA ma ka serum i lawe ʻia mai nā maʻi ma mua a ma hope o ka lymphadenectomy.ʻO ka miR-371a-3p target a me ka miR-30b-5p reference gene i hoʻokomo ʻia i ka nānā ʻana.Ua helu ʻia ka ʻōlelo MiP-371a-3p e ka hoʻohuli ʻana i ke kaulahao polymerase transcription.Ua hōʻike nā hualoaʻa ua loaʻa ka miP-371a-3p i nā helu liʻiliʻi i nā hōʻailona serum preoperative a me ka postoperative, e hōʻike ana ʻaʻole i hoʻohana ʻia ma ke ʻano he hōʻailona tumo i kēia maʻi.ʻO 36.56 ka helu pōʻaiapili o nā laʻana preoperative, a ʻaʻole i ʻike ʻia ka miP-371a-3p i nā laʻana postoperative.
ʻAʻole i loaʻa i ka mea maʻi ka adjuvant therapy.Ua koho ka poʻe maʻi i ka nānā ʻana me ke kiʻi kiʻi o ka umauma, ka ʻōpū, a me ke pelvis e like me ka mea i ʻōlelo ʻia a me STM.No laila,ʻo ka pane pololeiʻo D. He makahiki ma hope o ka weheʻiaʻana o nā lymph nodes retroperitoneal,ʻaʻohe hōʻailona o ka hoʻi houʻana o ka maʻi.
Hōʻike: ʻAʻohe kuleana kālā a ka mea kākau a i ʻole pili ʻē aʻe me ka mea hana i kekahi huahana i ʻōlelo ʻia ma kēia ʻatikala a i ʻole kekahi mea lawelawe.
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, a me Aditya Bagrodia, MD1.31 Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX