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Asian Journal of Surgery Oct 2023
Topics: Humans; Endodermal Sinus Tumor; Nasal Cavity
PubMed: 37295985
DOI: 10.1016/j.asjsur.2023.05.109 -
Asian Journal of Surgery Oct 2023
Topics: Female; Humans; Mesonephroma; Uterine Cervical Neoplasms; Adenocarcinoma
PubMed: 37230815
DOI: 10.1016/j.asjsur.2023.05.057 -
JNMA; Journal of the Nepal Medical... Feb 2023Yolk sac tumour frequently arises in the gonads as a type of germ cell tumour, though rare is a highly malignant ovarian tumour in children and prompt treatment should...
UNLABELLED
Yolk sac tumour frequently arises in the gonads as a type of germ cell tumour, though rare is a highly malignant ovarian tumour in children and prompt treatment should be done. We hereby report a case of malignant ovarian tumour presenting with an abdominal lump and increased urinary frequency. Different diagnostic modalities were used such as ultrasonography of the whole abdomen, contrast-enhanced computed tomography abdomen pelvis and tumour markers of beta-human chorionic gonadotropin and alpha-fetoprotein. This revealed an 18.2x14.3x10 cm mass likely a neoplastic germ cell tumour with minimal ascites. A tumour mass was found to arise from the left ovary and complete excision of the tumour along the left fallopian tube was done. Adjuvant chemotherapy started immediately. We hereby present a case of a 9-year-old girl with a huge yolk sac tumour of the left ovary which is rare in our setting and is presented here to differentiate any ovarian mass in this age group.
KEYWORDS
children; surgical procedure; yolk sac tumour.
Topics: Female; Humans; Child; Endodermal Sinus Tumor; Yolk Sac; Ovarian Neoplasms; Neoplasms, Germ Cell and Embryonal
PubMed: 37203966
DOI: 10.31729/jnma.8041 -
Molecular Medicine (Cambridge, Mass.) Mar 2023Being the standard-of-care for four decades, cisplatin-based chemotherapy is highly efficient in treating germ cell tumors (GCT). However, often refractory patients...
BACKGROUND
Being the standard-of-care for four decades, cisplatin-based chemotherapy is highly efficient in treating germ cell tumors (GCT). However, often refractory patients present with a remaining (resistant) yolk-sac tumor (YST(-R)) component, resulting in poor prognosis due to lack of novel treatment options besides chemotherapy and surgery. The aim of this study was to identify novel targets for the treatment of YST by deciphering the molecular mechanisms of therapy resistance. Additionally, we screened the cytotoxic efficacy of a novel antibody-drug-conjugate targeting CLDN6 (CLDN6-ADC), as well as pharmacological inhibitors to target specifically YST.
METHODS
Protein and mRNA levels of putative targets were measured by flow cytometry, immunohistochemical stainings, mass spectrometry of formalin-fixed paraffin-embedded tissues, phospho-kinase arrays, or qRT-PCR. Cell viability, apoptosis and cell cycle assays of GCT and non-cancerous cells were performed using XTT cell viability assays or Annexin V / propidium iodide flow cytometry, respectively. Druggable genomic alterations of YST(-R) tissues were identified by the TrueSight Oncology 500 assay.
RESULTS
We demonstrated that treatment with a CLDN6-ADC enhanced apoptosis induction specifically in CLDN6 GCT cells in comparison with non-cancerous controls. In a cell line-dependent manner, either an accumulation in the G2 / M cell cycle phase or a mitotic catastrophe was observed. Based on mutational and proteome profiling, this study identified drugs targeting the FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling pathways as promising approaches to target YST. Further, we identified factors relevant for MAPK signaling, translational initiation and RNA binding, extracellular matrix-related processes as well as oxidative stress and immune response to be involved in therapy resistance.
CONCLUSIONS
In summary, this study offers a novel CLDN6-ADC to target GCT. Additionally, this study presents novel pharmacological inhibitors blocking FGF, VGF, PDGF, mTOR, CHEK1, AURKA, or PARP signaling for the treatment of (refractory) YST patients. Finally, this study shed light on the mechanisms of therapy resistance in YST.
Topics: Humans; Endodermal Sinus Tumor; Neoplasms, Germ Cell and Embryonal; Claudins
PubMed: 36991316
DOI: 10.1186/s10020-023-00636-3 -
Journal of Obstetrics and Gynaecology :... Dec 2023
Topics: Humans; Endodermal Sinus Tumor; Teratoma
PubMed: 36877134
DOI: 10.1080/01443615.2023.2182673 -
Asian Journal of Surgery Jul 2023
Topics: Female; Humans; Uterine Cervical Neoplasms; Mesonephroma; Cervix Uteri; Adenocarcinoma
PubMed: 36841625
DOI: 10.1016/j.asjsur.2023.02.012 -
Postoperative recurrence of mixed extragonadal germ cell tumor in the right shoulder: a case report.Diagnostic Pathology Feb 2023Extragonadal germ cell tumours (EGGCTs) originated in Shoulder are extremely rare, with 1 case described in the literature. We report a case of a patient with a primary...
BACKGROUND
Extragonadal germ cell tumours (EGGCTs) originated in Shoulder are extremely rare, with 1 case described in the literature. We report a case of a patient with a primary Right Shoulder mixed EGGCT.
CASE PRESENTATION
A 36-year-old male patient was hospitalized for 6 months due to progressive right shoulder swelling accompanied by pain. Subsequently, the right shoulder tumor was removed entirely. Gross pathological examination showed that the size of the tumor mass was about 14 × 10 × 6 cm.Mutations were observed in ENPEP (4q25), ZCCHC11, RREB1 (6p24.3), CKAP4 (12q23.3), and other genes were detected by whole exome sequencing. Histology revealed a mixed EGGCT of the Right Shoulder with immature teratoma and yolk sac tumour. The patient went through 6 cycles of chemotherapy. After 7 months of follow-up, the patient is recurrence.
CONCLUSION
The primary MEGCT of the shoulder is an extremely rare condition. However, the recurrence and metastasis rates are high. Therefore, further research is necessary to determine this rare disease's genetic and clinical characteristics to develop an effective treatment plan.
Topics: Male; Humans; Adult; Shoulder; Neoplasms, Germ Cell and Embryonal; Teratoma; Endodermal Sinus Tumor; Mutation
PubMed: 36805679
DOI: 10.1186/s13000-023-01312-0 -
Modern Pathology : An Official Journal... Jan 2023Given the association of mesonephric adenocarcinoma (MA) of the uterine cervix with florid mesonephric hyperplasia, one would expect MAs to rarely arise in other...
Given the association of mesonephric adenocarcinoma (MA) of the uterine cervix with florid mesonephric hyperplasia, one would expect MAs to rarely arise in other anatomical locations that harbor mesonephric remnants. In contrast, mesonephric-like adenocarcinoma (MLA) is thought to arise from Müllerian origin without an association with mesonephric remnants. The current case series characterizes 4 cases of MA arising in the urinary bladder (1 woman and 3 men), 1 case of MA in the perirenal region (woman), and 1 case of MLA in the ureter (woman). All cases displayed morphologic features similar to MA of the uterine cervix and MLA of the ovary and endometrium, characterized by predominant tubular and focal glandular/ductal architecture. Mesonephric remnants in the bladder wall were closely associated with adjacent MA in cases 1 and 4. MLA in case 6 was associated with mesonephric-like proliferations and endometriosis. All cases (6/6) were diffusely positive for Pax8, and all displayed a luminal pattern of CD10 staining, except case 4 for which CD10 immunostain was not available for review. Gata3 was either focally positive (cases 1, 2, and 6), negative (case 3), or diffusely positive (case 5). TTF-1 was diffusely expressed in cases 1 and 3 and negative in cases 2, 5, and 6. Although a KRAS G12C somatic mutation was detected in case 6, hotspot mutations in KRAS, NRAS, and PIK3CA were not present in other tested cases. Our study demonstrates that MAs and MLAs of the urinary tract share similar histopathogenesis, morphology, and immunophenotype to their counterparts in the female genital tract. We propose that, in the urinary tract, MA might be classified as a distinctive tumor that arises from mesonephric remnants or presumed Wolffian origin if they are not related to Müllerian-type precursors. The tumor displaying similar morphology and immunoprofile to MA but associated with Müllerian-type precursors should be classified as MLA.
Topics: Male; Female; Humans; Uterine Cervical Neoplasms; Proto-Oncogene Proteins p21(ras); Adenocarcinoma; Mesonephroma; Urinary Tract
PubMed: 36788068
DOI: 10.1016/j.modpat.2022.100031 -
BMC Pregnancy and Childbirth Jan 2023Approximately 10-15% of 46,XY disorders of sex development (DSDs) have an SRY mutation residing in the high mobility group (HMG) domain. Here, we present a case of 46,XY...
BACKGROUND
Approximately 10-15% of 46,XY disorders of sex development (DSDs) have an SRY mutation residing in the high mobility group (HMG) domain. Here, we present a case of 46,XY DSD caused by a novel missense mutation in the HMG region of SRY rapidly progressing to germ cell tumors (GCTs).
CASE PRESENTATION
An adolescent female (15 years old) exhibiting primary amenorrhea was later diagnosed as a 46,XY female with bilateral gonadal dysplasia on the basis of peripheral lymphocyte karyotype 46,XY and a novel missense mutation in SRY (c.281 T > G, p.L94R). The novel missense mutation (c.281 T > G, p.L94R) and its adjacent region were conserved. Protein structure analysis showed that the mutant site was located in the middle of the HMG domain, and the mutant protein had a diminished ability to bind to DNA. Imaging examination revealed an adolescent female with a naive uterus. Laparoscopy and initial pathological examination revealed left gonadal dysplasia and right gonadal dysplasia with gonadoblastoma (GB). Right gonadectomy by laparoscopy was performed upon consent from the patient's parents. Less than 1 year postoperatively, the left gonadal gland deteriorated as observed by the findings of a mass in the left adnexal region by pelvic MRI and serum AFP > 1000 ng/ml by serological tests, and then total hysterectomy and adnexal and left gonadectomy by laparoscopy were performed. The GCT stage was classified as stage Ic according to FIGO. At this time, pathologic examination showed that the left gonad had progressed to yolk sac tumor and dysgerminoma. The patient underwent chemotherapy post-operatively but developed type III myelosuppression and tumor recurrence several months later.
CONCLUSIONS
The patient initially presented with right gonadoblastoma but chose only right gonadectomy by laparoscopy to preserve the female sex characteristics, which resulted in rapid deterioration of the left gonad and poor treatment outcomes. This case demonstrates the importance of early genetic diagnosis and treatment of 46,XY female DSD.
Topics: Adolescent; Female; Humans; Dysgerminoma; Endodermal Sinus Tumor; Gonadoblastoma; Gonads; Mutation, Missense; Neoplasm Recurrence, Local; Ovarian Neoplasms; Sex-Determining Region Y Protein
PubMed: 36694125
DOI: 10.1186/s12884-022-05317-3 -
Cancer Cytopathology Apr 2023In this study, the authors sought to describe the cytologic features of primary gynecologic germ cell tumors and carcinomas exhibiting germ cell differentiation because...
BACKGROUND
In this study, the authors sought to describe the cytologic features of primary gynecologic germ cell tumors and carcinomas exhibiting germ cell differentiation because little information currently exists.
METHODS
An institutional database search was performed to identify histologically confirmed gynecologic germ cell tumors and carcinomas with germ cell tumor differentiation. Available cytologic material was reviewed by three observers, and morphologic features were recorded in addition to patient age at original diagnosis, primary tumor site, site(s) from which the examined cytologic material was obtained, and the type of examined cytologic preparations.
RESULTS
In total, 15 cytologic specimens from 12 women (aged 19-82 years) were identified and included touch preparations of core biopsies from various sites (n = 6), fine-needle biopsies (n = 2), pelvic washings (n = 1), ascitic fluids (n = 4), pelvic cyst fluid (n = 1), and endometrial aspirate (n = 1). Of the 12 patients, seven had primary gynecologic germ cell tumors, four had gynecologic (ovarian and endometrial) tumors exhibiting somatic yolk sac tumor-like differentiation, and the remaining patient had an intestinal-type adenocarcinoma arising within an ovarian teratoma. There was morphologic overlap among many of the cases, although cytoplasmic vacuolation/granular cytoplasm was seen in 75% of primary yolk sac tumors or carcinomas with yolk sac tumor differentiation, and dense/squamoid cytoplasm was seen in 100% of teratomatous elements that were sampled.
CONCLUSIONS
Germ cell tumors and somatic neoplasms exhibiting germ cell tumor differentiation occurring in adult women share some cytologic features and may be difficult to distinguish from one another, although some tumor types showed characteristic cytomorphologic findings.
Topics: Adult; Humans; Female; Endodermal Sinus Tumor; Neoplasms, Germ Cell and Embryonal; Teratoma; Ovarian Neoplasms; Adenocarcinoma
PubMed: 36574209
DOI: 10.1002/cncy.22673