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Histopathology Sep 2023Yolk sac tumour postpubertal-type (YSTpt) shows a wide range of histological patterns and is challenging to diagnose. Recently, forkhead box transcription factor A2...
AIMS
Yolk sac tumour postpubertal-type (YSTpt) shows a wide range of histological patterns and is challenging to diagnose. Recently, forkhead box transcription factor A2 (FoxA2) emerged as a driver of YSTpt formation and a promising marker for diagnosing YSTpt. However, FoxA2 has not been tested in the different patterns of YSTpt. This study aimed to assess the staining pattern of FoxA2 in te different patterns of YSTpt and other germ cell tumours of the testis (GCTT), comparing it with glypican-3 (GPC3) and α-fetoprotein (AFP).
METHODS AND RESULTS
FOXA2, GPC3 and AFP immunohistochemistry was performed on 24 YSTpt (24 microcystic/reticular, 10 myxoid, two macrocystic, five glandular/alveolar, two endodermal sinus/perivascular, four solid, two polyembryoma/embryoid body and two polyvesicular vitelline) and 81 other GCTT. The percentage of positive cells (0, 1+, 2+, 3+) and the intensity (0, 1, 2, 3) were evaluated regardless of and within each YSTpt pattern. FoxA2 was positive in all YSTpt (24 of 24) and all but one (23 of 24) exhibited 2+/3+ stain, with higher intensity [median value (mv): 2.6] than AFP (1.8) and GPC3 (2.5). Both FoxA2 and GPC3 were positive in all microcystic/reticular (24 of 24), myxoid (10 of 10), macrocystic (two of two), endodermal sinus/perivascular (four of four) and polyembryoma/embryoid body (two of two) patterns. Nevertheless, only FoxA2 was positive in all glandular/alveolar (five of five), solid (four of four) and polyvesicular vitelline (two of two) patterns. The intensity of FoxA2 was higher than AFP and GPC3 in almost all YST patterns. In the other GCTT, FoxA2 was positive only in teratoma postpubertal-type (Tpt) [13 of 20 (65%)], with staining almost exclusively confined to the mature gastrointestinal/respiratory tract epithelium.
CONCLUSIONS
FoxA2 is a highly sensitive and specific biomarker that supports the diagnosis of YSTpt. FoxA2 is superior to GPC3 and AFP, especially in rare and difficult-to-diagnose histological patterns of YSTpt, but mature glands of Tpt could represent a potential diagnostic pitfall.
Topics: Male; Humans; Female; alpha-Fetoproteins; Biomarkers, Tumor; Endodermal Sinus Tumor; Testicular Neoplasms; Cysts; Ovarian Neoplasms; Glypicans
PubMed: 37317674
DOI: 10.1111/his.14968 -
Asian Journal of Surgery Oct 2023
Topics: Humans; Endodermal Sinus Tumor; Nasal Cavity
PubMed: 37295985
DOI: 10.1016/j.asjsur.2023.05.109 -
BMJ Case Reports May 2023We present a rare case of an extragonadal retroperitoneal yolk sac tumour in an adult male, who presented with severe abdominal pain to his local hospital. Imaging...
We present a rare case of an extragonadal retroperitoneal yolk sac tumour in an adult male, who presented with severe abdominal pain to his local hospital. Imaging revealed a large retroperitoneal soft tissue mass with no evidence of metastases. Initial biopsy demonstrated poorly differentiated carcinoma, favoured to be renal cell carcinoma. The patient underwent surgical resection following re-presentation with severe abdominal pain and significant interval enlargement of the mass. Laparotomy revealed a renal tumour that had ruptured through the left mesocolon into the peritoneal cavity. Postoperative histopathological examination revealed a yolk sac tumour involving the kidney, perinephric fat, renal sinus fat, renal hilar lymph node and colonic mesentery. Immunohistochemical staining for alpha-fetoprotein and glypican 3 was positive in the tumour cells without evidence of other germ cell elements, confirming the diagnosis of a pure yolk sac tumour. To our knowledge, this is an extremely rare case of a primary pure yolk sac tumour arising from the kidney in an adult.
Topics: Humans; Male; Adult; Endodermal Sinus Tumor; Kidney Neoplasms; Carcinoma, Renal Cell; Kidney Pelvis; Abdominal Pain
PubMed: 37236676
DOI: 10.1136/bcr-2022-254024 -
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 -
The Journal of Surgical Research Aug 2023The purpose of this study was to perform a population-based investigation to assess the disease characteristics and prognosis of children and adolescents with malignant...
Clinical Features and Survival Outcomes in Children and Adolescents With Malignant Mediastinal Germ Cell Tumors Based on Surveillance, Epidemiology, and End Results Database Analysis.
INTRODUCTION
The purpose of this study was to perform a population-based investigation to assess the disease characteristics and prognosis of children and adolescents with malignant mediastinal germ cell tumors (MMGCT).
METHODS
Data on the demographics, treatment, and survival outcomes of children and adolescents with MMGCT from January 1, 2000 to December 31, 2018 were obtained. To compare survival curves, the log-rank test was employed. The generation of survival curves based on different parameters was done using Kaplan-Meier estimations. Cox proportional hazards regression was performed to determine the variables linked to disease-specific survival.
RESULTS
The selection criteria were met by 152 MMGCT patients, 130 of whom were male. Fifty three cases of mixed germ cell tumors (GCTs), 41 cases of malignant teratomas, 26 cases of yolk sac tumors, 14 cases of seminoma, 13 cases of choriocarcinomas, and five cases of embryonal carcinoma were reported. Overall survival at 3 and 5 y for all patients was 63.1% and 61.2%, respectively. Malignant teratoma, yolk sac tumors, and mixed GCTs in children and adolescents had comparable survival rates, while those with choriocarcinoma and embryonal carcinoma showed the worst prognosis. Embryonal carcinoma, malignant teratoma, mixed GCTs, and choriocarcinoma were found as risk factors by multivariate Cox proportional hazards analysis. In contrast, surgery and younger age were protective factors. However, chemotherapy alone showed no survival benefits.
CONCLUSIONS
Our population-based evidence showed that MMGCT had worse prognosis in older children and adolescents. Choriocarcinomas and embryonal carcinomas had the worst prognosis. Surgery can prolong survival time. Chemotherapy and radiotherapy were not associated with improved prognosis.
Topics: Pregnancy; Female; Humans; Male; Child; Adolescent; Carcinoma, Embryonal; Endodermal Sinus Tumor; Neoplasms, Germ Cell and Embryonal; Teratoma; Mediastinal Neoplasms; Choriocarcinoma; Testicular Neoplasms
PubMed: 37062232
DOI: 10.1016/j.jss.2023.03.018 -
The American Journal of Surgical... Jun 2023Extrauterine mesonephric-like carcinoma (ExUMLC) shares histologic, immunohistochemical (IHC), and molecular (MOL) features with endometrial mesonephric-like carcinoma...
Extrauterine mesonephric-like carcinoma (ExUMLC) shares histologic, immunohistochemical (IHC), and molecular (MOL) features with endometrial mesonephric-like carcinoma (EnMLC). Its rarity and histologic overlap with Mullerian carcinomas contribute to underrecognition of ExUMLC. Aggressive behavior of EnMLC is well-documented; behavior of ExUMLC is yet to be characterized. This study presents the clinicopathologic, IHC, and MOL features of 33 ExUMLC identified over a 20-year time period (2002-2022) and compares the behavior of this cohort to more common upper gynecologic Mullerian carcinomas (low-grade endometrioid, LGEC; clear cell, CCC; high-grade serous, HGSC) and EnMLC diagnosed over the same time period. ExUMLC patients ranged from 37 to 74 years old (median=59 y); 13 presented with advanced stage (FIGO III/IV) disease. Most ExUMLC had the characteristic mixture of architectural patterns and cytologic features, as previously described. Two ExUMLC had sarcomatous differentiation, 1 with heterologous rhabdomyosarcoma. Twenty-one ExUMLC (63%) had associated endometriosis, and 7 (21%) arose in a borderline tumor. In 14 (42%) cases, ExUMLC was part of a mixed carcinoma representing >50% of the tumor in 12. Twenty-six cases (79%) were incorrectly classified as follows: LGEC or HGEC (12); adenocarcinoma, not otherwise specified (3); HGSC (3); LGSC (2); mixed carcinoma (1); carcinosarcoma, Mullerian type (2); seromucinous carcinoma (1); transitional pattern of HGSC (1); and female adnexal tumor of probable Wolffian origin (1). Three patients had occult synchronous endometrial LGEC. IHC facilitated diagnosis in all cases with an expression of GATA-3 and/or TTF-1 in conjunction with decreased hormone receptor expression in most tumors. MOL testing (n=20) identified a variety of mutations, most frequently: KRAS (15); TP53 (4); SPOP (4); and PIK3CA (4). ExUMLC and CCC were more likely to be associated with endometriosis ( P <0.0001). ExUMLC and HGSC had more recurrences compared with CCC and LGEC ( P <0.0001). Histologic subtype was associated with longer disease-free survival for LGEC and CCC versus HGSC and ExUMLC ( P <0.001). ExUMLC trended towards a similar poor overall survival as HGSC compared with LGEC and CCC, and EnMLC trended to shorter survival compared with ExUMLC. Neither finding reached significance. No differences were seen between EnMLC and ExUMLC with respect to presenting stage or recurrence. Staging, histotype, and endometriosis were associated with disease-free survival, but on multivariate analysis, only stage remained as an independent predictor of outcome. The tendency of ExUMLC to present at an advanced stage and have distant recurrence points to more aggressive behavior compared with LGEC with which it is most frequently confused, underscoring the importance of an accurate diagnosis.
Topics: Adult; Aged; Female; Humans; Middle Aged; Adenocarcinoma; Carcinoma; Carcinoma, Endometrioid; Disease-Free Survival; Endometrial Neoplasms; Endometriosis; Mesonephroma; Nuclear Proteins; Ovarian Neoplasms; Repressor Proteins
PubMed: 37026792
DOI: 10.1097/PAS.0000000000002039 -
International Journal of Surgical... Dec 2023Yolk sac tumor is a malignant germ cell tumor, which typically occurs in the gonads with elevated serum alpha-fetoprotein (AFP). Among extragonadal sites, the liver is...
Yolk sac tumor is a malignant germ cell tumor, which typically occurs in the gonads with elevated serum alpha-fetoprotein (AFP). Among extragonadal sites, the liver is an uncommon location for primary pediatric yolk sac tumors. Other common hepatic tumors in this age group presenting with elevated serum AFP like hepatoblastoma and hepatocellular carcinoma must be differentiated from yolk sac tumors for initiating appropriate treatment and accurate prognostication. Lung metastasis with refractoriness to chemotherapy is an extraordinary presentation that has never been documented in the literature. We report our experience with a 2-year-old female child initially misdiagnosed as hepatoblastoma. It was found that LIN28 positivity by immunohistochemistry aided in confirmation of the histopathological diagnosis of primary yolk sac tumor of the liver.
Topics: Child; Child, Preschool; Female; Humans; alpha-Fetoproteins; Endodermal Sinus Tumor; Hepatoblastoma; Immunohistochemistry; Liver; Lung Neoplasms
PubMed: 37013352
DOI: 10.1177/10668969231157777 -
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 -
Virchows Archiv : An International... May 2023Vasculogenic mesenchymal tumor (VMT), a primitive mesenchymal neoplasm enriched by various-sized atypical vessels, is a new entity that develops in mediastinal germ cell...
Vasculogenic mesenchymal tumor (VMT), a primitive mesenchymal neoplasm enriched by various-sized atypical vessels, is a new entity that develops in mediastinal germ cell tumors (GCTs) with yolk sac tumor (YST) components after chemotherapy. Notably, patients with VMT in the residual GCT have increased risk of developing sarcomas or hematopoietic malignancies. Here, we report a late-teenage male patient with residual teratoma and high-grade VMT after chemotherapy for a mediastinal mixed GCT, including YST. Whole-exome sequencing revealed biallelic inactivation of TP53 and extensive copy number alterations that suggested whole-genome doubling. The biopsy tissue of the mixed GCT before chemotherapy exhibited overlapping genetic alterations to those in the VMT. Immunohistochemical analyses of the VMT showed that the abnormal vessels were positive for cytokeratin, glypican 3, EZH2, and IMP3. The findings that VMT inherits the genetic alterations of pre-existing mixed GCT and exhibits a partly YST-like immunophenotype might contribute to its clinical aggressiveness.
Topics: Adolescent; Humans; Male; Mediastinum; Exome Sequencing; Neoplasms, Germ Cell and Embryonal; Teratoma; Mediastinal Neoplasms; Endodermal Sinus Tumor; Testicular Neoplasms
PubMed: 36943470
DOI: 10.1007/s00428-023-03529-2