To establish and identify induced pluripotent stem cells (iPSCs) derived from patients with Aicardi-Goutières syndrome (AGS) with TREX1 gene 667G>A mutation, and obtain a specific induced pluripotent stem cell model for Aicardi-Goutières syndrome (AGS-iPSCs). A 3-year-old male child with Aicardi-Goutieres syndrome was admitted to Zhongshan People's Hospital in December 2020. After obtaining the informed consent of the patient's family members, 5 ml peripheral blood samples from the patient were collected, and mononuclear cells were isolated. Then,the peripheral blood mononuclear cells(PBMCs) were transduced with OCT3/4, SOX2, c-Myc and Klf4 by using Sendai virus, and PBMCs were reprogrammed into iPSCs. The pluripotency and differentiation ability of the cells were identified by cellular morphological analysis, real-time PCR, alkaline phosphatase staining (AP), immunofluorescence, teratoma formation experiments in mice. The results showed that the induced pluripotent stem cell line of Aicardi-Goutieres syndrome was successfully constructed and showed typical embryonic stem-like morphology after stable passage, RT-PCR showed mRNA expression of stem cell markers, AP staining was positive, OCT4, SOX2, NANOG, SSEA4, TRA-1-81 and TRA-1-60 pluripotency marker proteins were strongly expressed. In vivo teratoma formation experiments showed that iPSCs differentiate into the ectoderm (neural tube like tissue), mesoderm (vascular wall tissue) and endoderm (glandular tissue). Karyotype analysis also confirmed that iPSCs still maintained the original karyotype (46, XY). In conclusion, induced pluripotent stem cell line for Aicardi-Goutières syndrome was successfully established using Sendai virus, which provided an important model platform for studying the pathogenesis of the disease and for drug screening.
Animals ; Male ; Mice ; Cell Differentiation ; Induced Pluripotent Stem Cells/pathology* ; Leukocytes, Mononuclear ; Teratoma/pathology* ; Child, Preschool

Objective: To investigate the morphology and immunohistochemical (IHC) expression of pseudostratified ependymal tubules in ovarian mature teratoma (MT). Methods: Five cases of ovarian MT with pseudostratified ependymal tubules were collected from Shenzhen Hospital(Futian) of Guangzhou University of Chinese Medicine and the Eighth Affiliated Hospital of Sun Yat-sen University from March 2019 to March 2022. In addition, 15 cases of ovarian MT with monolayer ependymal epithelium from Shenzhen Hospital (Futian) of Guangzhou University of Chinese medicine and seven cases of immature teratoma (IMT) from Hainan Provincial People's Hospital from March 2019 to March 2022 were collected as control. The morphologic characteristics and immunophenotypes of pseudostratified ependymal tubules, monolayer ependymal epithelium, and primitive neural epithelial tubules were observed and compared by H&E stain and IHC expression pattern of genes related to the differentiation status of neuroepithelium, namely SALL4, Glypican3, nestin, SOX2, Foxj1, and Ki-67. Results: Mean age of the five patients of ovarian MT with pseudostratified ependymal tubules was 26 years (range from 19 to 31 years). Two tumors were located in the left ovary and three in the right. All five cases were excised, and clinical follow-up was available (mean follow-up 1.5 years; range 0.5 to 3 years). No recurrence was noted in any cases. The pseudostratified ependymal tubules of ovarian MT, which were lined with columnar or oval epithelia up to 4-6 layers, were morphologically similar to the primitive neuroepithelial tubules of IMT and different from monolayer ependymal epithelium of ovarian MT. By immunohistochemistry, SALL4 and Glypican3 were negative, Foxj1 was positive and Ki-67 index was lower in the pseudostratified ependymal tubules and the monolayer ependymal epithelium of ovarian MT. However, the primitive neuroepithelial tubules of IMT showed variably expression of SALL4 and Glypican3, were negative for Foxj1 and high Ki-67 index. All the above three groups expressed nestin and SOX2. Conclusions: The pseudostratified ependymal tubules of ovarian MT, which have morphological similarities to the primitive neuroepithelial tubules of IMT, are similar to the monolayer ependymal epithelia of the MT in immunophenotype. IHC assessment of Foxj1 and Ki-67 is helpful to differentiate the pseudostratified ependymal tubules of ovarian MT from the primitive neuroepithelial tubules of IMT.
Female ; Humans ; Young Adult ; Adult ; Nestin ; Ki-67 Antigen ; Immunohistochemistry ; Ovarian Neoplasms/pathology* ; Teratoma/pathology*

Female ; Humans ; Teratoma/pathology* ; Ovarian Neoplasms/pathology* ; Carcinoma, Small Cell/surgery* ; Carcinoma, Squamous Cell/pathology* ; Carcinoma, Neuroendocrine/surgery*

Female ; Humans ; Melanoma/surgery* ; Neoplasms, Multiple Primary/pathology* ; Ovarian Neoplasms/pathology* ; Skin Neoplasms ; Teratoma/surgery*

Endodermal Sinus Tumor ; Female ; Humans ; Mixed Tumor, Malignant ; Neoplasms, Germ Cell and Embryonal ; Teratoma/pathology* ; Uterus/pathology*

Adult ; Humans ; Rhabdoid Tumor/surgery* ; Teratoma/pathology* ; Medulloblastoma ; Central Nervous System Neoplasms ; Cerebellar Neoplasms ; Brain Neoplasms/pathology*

ObjectiveTo study the pathological morphology, immunohistochemical characteristics, and molecular changes of type Ⅱ testicular germ cell tumors (TGCT) and investigate the possible value of immunohistochemistry and fluorescence in situ hybridization (FISH) in the diagnosis of TGCT.

METHODSWe collected for this study 97 cases of TGCT, including 75 cases of seminoma, 17 cases of embryonal carcinoma, 11 cases of yolk sac tumor, 16 cases of mature teratoma, 3 cases of immature teratoma, and 1 case of epidermoid cyst, in which normal testicular tissue was found in 20 and non-TGCT in 6. We detected the expressions of different antibodies in various subtypes of TGCT by immunohistochemistry and determined the rate of chromosome 12p abnormality using FISH.

RESULTSThe immunophenotypes varied with different subtypes of TGCT. SALL4 and PLAP exhibited high sensitivity in all histological subtypes. CD117 and OCT4 showed strongly positive expressions in invasive seminoma and germ cell neoplasia in situ (GCNIS) but not in normal seminiferous tubules. GPC3 was significantly expressed in the yolk sac tumor, superior to GATA3 and AFP in both range and intensity. CKpan, OCT4, and CD30 were extensively expressed in embryonal carcinoma, while HCG expressed in choriocarcinoma. The positivity rate of isochromosome 12p and 12p amplification in TGCT was 96.7% (29/30).

CONCLUSIONSThe majority of TGCT can be diagnosed by histological observation, but immunohistochemical staining is crucial for more accurate subtypes and valuable for selection of individualized treatment options and evaluation of prognosis. Chromosome 12p abnormality is a specific molecular alteration in type Ⅱ TGCT, which is useful for ruling out other lesions.

Biomarkers, Tumor ; metabolism ; Carcinoma, Embryonal ; diagnosis ; genetics ; metabolism ; pathology ; Chromosome Aberrations ; Chromosomes, Human, Pair 12 ; Endodermal Sinus Tumor ; diagnosis ; genetics ; metabolism ; pathology ; Genetic Markers ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Neoplasms, Germ Cell and Embryonal ; diagnosis ; genetics ; metabolism ; pathology ; Prognosis ; Seminiferous Tubules ; metabolism ; Seminoma ; diagnosis ; genetics ; metabolism ; pathology ; Teratoma ; diagnosis ; genetics ; metabolism ; pathology ; Testicular Neoplasms ; diagnosis ; genetics ; metabolism ; pathology

OBJECTIVETo investigate different treatment methods for stage-Is testicular mixed germ cell tumors (TMGCTs).

METHODSWe retrospectively analyzed the clinical data about 3'cases of stage-Is TMGCTs (aged 26-39 years) treated in the 175th Hospital of PLA, reviewed relevant literature, and explored the clinical characteristics of TMGCTs.

RESULTSOf the 3 patients, 1 was treated by radical orchiectomy, 1 by radical orchiectomy + retroperitoneal lymph node dissection + BEP chemotherapy scheme, and the other by radical orchiectomy + radiotherapy. The pathological components of TMGCTs were immature teratoma, seminoma, spermatocytoma, chorioepithelioma, embryonal carcinoma, and yolk sac tumor. No recurrence or distant metastasis was found during the 24-month follow-up after surgery.

CONCLUSIONThe diagnosis of TMGCTs primarily depends on physical examination, ultrasonography, MRI, and measurement of serum tumor markers, while its confirmation necessitates pathological examination, and its treatment is basically radical orchiectomy.

Adult ; Carcinoma, Embryonal ; pathology ; Endodermal Sinus Tumor ; pathology ; Humans ; Lymph Node Excision ; Male ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplasms, Germ Cell and Embryonal ; pathology ; surgery ; Orchiectomy ; Retrospective Studies ; Seminoma ; pathology ; Teratoma ; pathology ; Testicular Neoplasms ; pathology ; surgery

We aimed to evaluate the histologic components of primary mediastinal mixed germ cell tumors. A total of 221 patients diagnosed with a mediastinal germ cell tumor (GCT) were retrospectively reviewed. Among them, 14 patients underwent surgical resection after chemotherapy and 8 patients were diagnosed with mixed GCT, who were then selected for further evaluation. Clinical chart review and histologic review of biopsy and surgical specimens of 8 patients were performed. All 8 patients were young males and showed a mature teratoma or a mature teratoma with a focal immature teratoma in the resected specimens. Serum alpha-feto protein was variably elevated. Seven patients experienced an increase in tumor size after the chemotherapy. In 5 patients, a variable amount of vasculoconnective tissue was found along with the mature teratoma occupying average 66.3% of resected mass, and 3 of them showed an identical vasculoconnective component on biopsy before chemotherapy. We suggest that vasculoconnective tissue might be the intrinsic component of primary mediastinal mixed GCT. When vasculoconnective tissue is obtained on small biopsy of an anterior mediastinal mass of a young male, the possibility of underlying mixed GCT should be considered and further clinical work up should be performed.
Adolescent ; Adult ; Blood Vessels/*pathology ; Connective Tissue/*pathology ; Diagnosis, Differential ; Humans ; Male ; Mediastinal Neoplasms/*pathology ; Middle Aged ; Neoplasms, Germ Cell and Embryonal/*pathology ; Teratoma/*pathology ; Young Adult

OBJECTIVETo improve the diagnosis and treatment of testicular teratoma in children by analysis of clinical data.

METHODSWe retrospectively analyzed the clinical data about 64 cases of testicular teratoma treated in the Children's Hospital of Chongqing Medical University from 1995 to 2014.

RESULTSSixty-one of the cases presented painless scrotal mass with a sense of bearing down and the other 3 cases were confirmed because of empty scrotum diagnosed as cryptorchidism. The level of serum alpha fetal protein ( AFP) was obviously increased in 46 cases but normal in the other 18 preoperatively. Ultrasonography manifested abnormal inhomogeneous echo zones with calcification or necrosis. X-ray examination presented patchy or curvilinear high-density shadows in 28 cases. Forty-one of the patients underwent testis-sparing surgery (TSS) , 20 received high inguinal orchiectomy, and 3 refused surgical treatment. Pathological examination revealed 3 mature germinal layers in the 49 cases of mature teratoma and immature germinal tissue, including the original neural tube, and 11 cases of immature teratoma. The mature cases were exempted from chemotherapy, while the immature cases received the combination of cisplatin, etoposide, and bleomycin (PEB). The patients were followed up for 2 years postoperatively, which revealed no recurrence or metastasis.

CONCLUSIONMost children with testicular teratoma presented painless scrotal mass with a sense of bearing down and with abnormal serum AFP in most cases. Ultrasonography and plain radiography of the scrotum contribute to the diagnosis of the tumor. TSS is the main treatment option and intraoperative frozen-section can help the surgeons decide on the surgical mode. Postoperative chemotherapy is necessitated for immature teratoma but not for mature cases.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; administration & dosage ; Child ; Cisplatin ; administration & dosage ; Cryptorchidism ; diagnosis ; Etoposide ; administration & dosage ; Gonadal Dysgenesis, 46,XY ; diagnosis ; Humans ; Male ; Orchiectomy ; methods ; Retrospective Studies ; Scrotum ; Teratoma ; blood ; diagnosis ; pathology ; therapy ; Testicular Neoplasms ; blood ; diagnosis ; pathology ; therapy ; Testis ; abnormalities ; alpha-Fetoproteins ; analysis