-
Communications Biology Sep 2020To elucidate the molecular pathogenesis of pediatric germ cell tumors (GCTs), we performed DNA methylation array analysis, whole transcriptome sequencing, targeted...
To elucidate the molecular pathogenesis of pediatric germ cell tumors (GCTs), we performed DNA methylation array analysis, whole transcriptome sequencing, targeted capture sequencing, and single-nucleotide polymorphism array analysis using 51 GCT samples (25 female, 26 male), including 6 germinomas, 2 embryonal carcinomas, 4 immature teratomas, 3 mature teratomas, 30 yolk sac tumors, and 6 mixed germ cell tumors. Among the 51 samples, 11 were from infants, 23 were from young children, and 17 were from those aged ≥10 years. Sixteen of the 51 samples developed in the extragonadal regions. Germinomas showed upregulation of pluripotent genes and global hypomethylation. Pluripotent genes were also highly expressed in embryonal carcinomas. These genes may play essential roles in embryonal carcinomas given that their binding sites are hypomethylated. Yolk sac tumors exhibited overexpression of endodermal genes, such as GATA6 and FOXA2, the binding sites of which were hypomethylated. Interestingly, infant yolk sac tumors had different DNA methylation patterns from those observed in older children. Teratomas had higher expression of ectodermal genes, suggesting a tridermal nature. Based on our results, we suggest that KIT, TNFRSF8, and ERBB4 may be suitable targets for the treatment of germinoma, embryonal carcinomas, and yolk sac tumors, respectively.
Topics: Carcinoma, Embryonal; Child; Child, Preschool; DNA Copy Number Variations; DNA Methylation; Endodermal Sinus Tumor; Female; Germinoma; Humans; Infant; Male; Neoplasms, Germ Cell and Embryonal; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Teratoma; Exome Sequencing
PubMed: 32999426
DOI: 10.1038/s42003-020-01267-8 -
The Malaysian Journal of Pathology Aug 2020Yolk sac tumour (YST) or endodermal sinus tumour is rare and typically seen in gonads.
INTRODUCTION
Yolk sac tumour (YST) or endodermal sinus tumour is rare and typically seen in gonads.
CASE REPORT
We described a case of extragonadal vaginal YST in a one year and seven months old girl who presented with vaginal discharge and bleeding, and discuss its differential diagnosis and potential pitfalls in immunohistochemistry. She was found to have a suprapubic mass on examination. The serum alpha fetoprotein was 11919.4 ng/mL. Computed tomography of the pelvis revealed a large 6.4 cm heterogenous pelvic mass. Colposcopic examination of the pelvis showed a fungating vaginal mass that was subsequently confirmed as a yolk sac tumour. Immunohistochemically, the malignant cells were positive toward CKAE1/AE3, AFP and glypican-3, as well as CD117.
DISCUSSION
Solid pattern extragonadal vaginal YST may morphologically resemble dysgerminoma that is also CD117 positive, while the glandular pattern YST may have clear cytoplasm and is positive for cytokeratin; hence, may resemble clear cell carcinoma. Being mindful of these potential diagnostic caveats is necessary to prevent misdiagnosis.
Topics: Biomarkers, Tumor; Diagnosis, Differential; Dysgerminoma; Endodermal Sinus Tumor; Female; Humans; Immunohistochemistry; Infant; Proto-Oncogene Proteins c-kit; Sarcoma, Clear Cell; Vagina; Vaginal Neoplasms
PubMed: 32860387
DOI: No ID Found -
Diagnostic Pathology Jul 2020Mesonephric-like adenocarcinoma (M-LAC) is a rare, recently described tumor occurring in the uterine corpus and ovary, which shares the same morphological and...
BACKGROUND
Mesonephric-like adenocarcinoma (M-LAC) is a rare, recently described tumor occurring in the uterine corpus and ovary, which shares the same morphological and immunohistochemical features with the more common mesonephric adenocarcinoma (MAC), which mostly arises the uterine cervix. Despite the similarities between these tumors, the histogenesis of M-LAC is still disputable.
CASE PRESENTATION
Sixty-one-year-old woman presented with an advanced tumor of the left ovary with intraabdominal spread and liver metastases. After receiving 5 cycles of neoadjuvant chemotherapy, she underwent a hysterectomy with bilateral salpingo-oophorectomy, and resection of the liver metastasis, omentum, and appendix. Histologically, the ovarian tumor consisted of two components, whose morphology and immunohistochemical results were typical of either a serous borderline tumor (immunohistochemical positivity for PAX8, WT1, ER and PR) or a mesonephric-like carcinoma (immunohistochemical positivity for PAX8, TTF1 and GATA3). Only the component of the mesonephric-like adenocarcinoma metastasized to the omentum and liver. A molecular analysis with a panel of 271 genes (size 1020 kbp) was performed separately on samples from the borderline tumor, primary ovarian mesonephric-like adenocarcinoma, and liver metastasis. The results showed the clonal origin of all samples, which shared the same KRAS (NM_004985.3:c.34G > T, p.(G12C)) and PIK3CA (NM_006218.2:c.1633G > A, p.(E545K)) somatic mutations. Moreover, in the sample from the primary mesonephric-like carcinoma and its liver metastasis a likely pathogenic somatic MYCN mutation (NM_005378.4:c.131C > T, p.(P44L) was found. In all samples, the deletion of exons 9-10 in the CHEK2 gene was present, which is in concordance with the previously performed genetic testing of the blood specimen which revealed the hereditary CHEK2 mutation in this patient.
CONCLUSIONS
Our result support the theory that at least some mesonephric-like ovarian adenocarcinomas are of Müllerian origin. The serous borderline tumor seems to be a precursor of mesonephric-like adenocarcinoma, which has been proven in our case by both tumors sharing the same mutations, and the presence of cumulative molecular aberrations in the mesonephric-like adenocarcinoma.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cystadenoma, Serous; Female; Humans; Mesonephroma; Middle Aged; Ovarian Neoplasms; Ovary; Precancerous Conditions; Uterine Neoplasms
PubMed: 32693840
DOI: 10.1186/s13000-020-01012-z -
Indian Journal of Cancer 2020Extragonadal germ cell tumors (GCTs) of head and neck region account for 5% of all benign and malignant GCTs. Orbit is an uncommon site for occurrence of extragonadal...
Extragonadal germ cell tumors (GCTs) of head and neck region account for 5% of all benign and malignant GCTs. Orbit is an uncommon site for occurrence of extragonadal GCTs. Pure yolk sac tumor (YST) of orbit is a rare neoplasm and only a few cases are reported in the literature. An 18-month-old boy presented with right eye proptosis of 2 months duration. Because of rapid clinical course and magnetic resonance imaging (MRI) findings, neoplastic lesion was suspected. Histopathological examination of the biopsy revealed neoplasm with possibility of GCT. Raised serum alpha-feto-protein levels suggested YST component. Positivity for immunohistochemical markers Glypican-3 and SALL4 confirmed pure YST nature of the tumor. The child received six cycles of cisplatin-based chemotherapy with significant reduction in size of the tumor, followed by exenteration of the orbit. This case is reported for its rarity as well as for highlighting diagnostic characteristics and management of orbital YST.
Topics: Endodermal Sinus Tumor; Humans; Infant; Male; Orbit; Orbital Neoplasms
PubMed: 32594074
DOI: 10.4103/ijc.IJC_595_18 -
Nagoya Journal of Medical Science May 2020Environmental endocrine disruptors (EEDs) are natural or synthetic chemical compounds that interfere with normal endocrine function in both wildlife and humans. Previous...
Environmental endocrine disruptors (EEDs) are natural or synthetic chemical compounds that interfere with normal endocrine function in both wildlife and humans. Previous studies have indicated that EEDs may contribute to oncogenesis. This study explores the relationship between EEDs and pediatric germ cell tumors (GCTs). A case-control study was conducted in 84 pediatric patients from 2014 to 2017, including 42 subjects with immature teratoma, yolk sac tumor, or germinoma, and 42 controls who experienced pneumonia or trauma. Serum PFASs, including PFBS, PFHpA, PFHxS, PFOA, PFOS, PFNA, PFDA, PFUA, PFOSA, and PFDoA, were measured in each subject, and their history of possible EED exposure was reviewed. Six of the 10 measured PFASs were significantly increased in the GCT group relative to the control group. With respect to lifestyle history, only PFHxS levels were statistically significantly associated with GCTs as determined by logistic regression analysis. The odds ratio for a 1 ng/L increase in PFHxS was 19.47 (95% CI: 4.20-90.26). Furthermore, in the GCT and control groups, both parental consumption of barbecued foods and hair dye use among parents were significantly correlated with elevated serum PFHxS levels (ρ = 0.383, 0.325 in the patient group and ρ = 0.370, 0.339 in the control group; < 0.05). Our study confirmed that children with GCTs from our institute had relatively high serum levels of PFASs relative to those of tumor-free pediatric patients. Serum PFHxS levels were independently associated with germ cell tumor occurrence.
Topics: Case-Control Studies; Child, Preschool; Endocrine Disruptors; Endodermal Sinus Tumor; Environmental Exposure; Female; Fluorocarbons; Germinoma; Humans; Infant; Male; Maternal Exposure; Neoplasms, Germ Cell and Embryonal; Pregnancy; Prenatal Exposure Delayed Effects; Teratoma
PubMed: 32581411
DOI: 10.18999/nagjms.82.2.315 -
Modern Pathology : An Official Journal... Nov 2020Hepatocyte Nuclear Factor 1 beta (HNF1β) is a transcription factor which plays an important role during early organogenesis, especially of the pancreato-biliary and...
Hepatocyte Nuclear Factor 1 beta (HNF1β) is a transcription factor which plays an important role during early organogenesis, especially of the pancreato-biliary and urogenital tract. Furthermore, HNF1β is an established marker in the differential diagnosis of ovarian cancer and shows a distinct nuclear expression in the clear cell carcinoma subtype. Recently, it has been described in yolk sac tumor, which represents a common component in many non-seminomatous germ cell tumors. Due to its broad histologic diversity, the diagnosis may be challenging and additional tools are very helpful in the workup of germ cell tumors. Immunohistochemistry was used to study HNF1β expression in a tissue microarray (TMA) of 601 testicular germ cell tumors including seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, germ cell neoplasia in situ (GCNIS), and normal tissue. The expression pattern was compared to glypican 3 (GPC3) and α-fetoprotein (AFP), two markers currently in use for the detection of yolk sac tumor. HNF1β showed a distinct nuclear staining in comparison to the cytoplasmic pattern of GPC3 and AFP. The sensitivity and specificity of HNF1β were 85.4% and 96.5%, of GPC3 83.3% and 90.7%, of AFP 62.5% and 97.7%. We conclude that HNF1β allows a reliable distinction of yolk sac tumor from other germ cell tumor components. Therefore, we propose HNF1β as a novel and robust marker in the immunohistochemical workup of testicular germ cell tumors.
Topics: Adult; Biomarkers, Tumor; Carcinoma, Embryonal; Choriocarcinoma; Diagnosis, Differential; Endodermal Sinus Tumor; Hepatocyte Nuclear Factor 1-beta; Humans; Immunohistochemistry; Male; Seminoma; Sensitivity and Specificity; Teratoma; Testicular Neoplasms; Testis; Tissue Array Analysis
PubMed: 32561848
DOI: 10.1038/s41379-020-0597-x -
Diagnostic Pathology Jun 2020Yolk sac tumor (YST) is a germ cell neoplasm that arises predominantly in the gonads, but can also derive from somatic neoplasms in extragonadal locations. These latter...
BACKGROUND
Yolk sac tumor (YST) is a germ cell neoplasm that arises predominantly in the gonads, but can also derive from somatic neoplasms in extragonadal locations. These latter cases have been documented in several organs, although reports from the urinary tract are limited. To our knowledge, this is the first report of a bladder urothelial carcinoma with a predominant component of YST differentiation.
CASE PRESENTATION
We present a unique case of a 76-year-old man with a recurrent urinary bladder tumor, initially interpreted as a high grade urothelial carcinoma with glandular differentiation. In the recurrent tumor, diverse histological patterns were identified, including glandular, hepatoid and sarcomatoid. This tumor showed positivity for AFP, GLP3 and SALL4, and negativity for CK7 and EMA. Fluorescent in situ hybridization study showed a polysomic pattern of chromosome 12. All these findings led to the final diagnosis of a YST derived from urothelial carcinoma.
CONCLUSIONS
YST differentiation should be considered in the differential diagnosis of a high grade urothelial carcinoma, particularly when glandular and other unusual patterns are observed.
Topics: Aged; Carcinoma, Transitional Cell; Diagnosis, Differential; Endodermal Sinus Tumor; Humans; Male; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms
PubMed: 32493368
DOI: 10.1186/s13000-020-00983-3 -
Modern Pathology : An Official Journal... Oct 2020Ovarian germ cell tumors, including yolk sac tumors, are most commonly diagnosed in children and young women. Most so-called yolk sac tumors reported in women >35 years...
Ovarian germ cell tumors, including yolk sac tumors, are most commonly diagnosed in children and young women. Most so-called yolk sac tumors reported in women >35 years old have been associated with an epithelial proliferation (endometriosis or carcinoma). Here, we describe eight cases clinically diagnosed as uterine or ovarian germ cell tumors in women >35 years old. In addition to routine morphologic examination and immunohistochemical evaluation, we present data from targeted next-generation sequencing (NGS) and isochromosome (12p) fluorescence in situ hybridization (FISH). We identified two groups of tumors with mixed germ cell and epithelial features: (1) tumors with background endometriosis and endometrioid carcinoma-like mutations (PTEN, PIK3CA, FGFR2, and CTNNB1), and (2) high-grade morphology, presumptive presence of isochromosome (12p) by FISH, and TP53 or PIK3CA mutations. These findings support the notion that the "germ cell tumor" component of these tumors is often somatically derived. Two tumors in our cohort were from premenopausal women; one showed no detectable mutations by NGS (suggestive of germ cell derivation), whereas the other showed PIK3CA, PTEN, and CTNNB1 mutations (suggestive of somatic derivation). Accurate classification of these tumors is likely important for selection of appropriate chemotherapy.
Topics: Adult; Aged; Carcinoma, Endometrioid; Endodermal Sinus Tumor; Female; Humans; Middle Aged; Neoplasms, Complex and Mixed; Ovarian Neoplasms; Uterine Neoplasms
PubMed: 32404953
DOI: 10.1038/s41379-020-0548-6 -
Ultrasound in Obstetrics & Gynecology :... Aug 2020To describe the clinical and sonographic characteristics of malignant ovarian yolk sac tumors (YSTs).
OBJECTIVE
To describe the clinical and sonographic characteristics of malignant ovarian yolk sac tumors (YSTs).
METHODS
In this retrospective multicenter study, we included 21 patients with a histological diagnosis of ovarian YST and available transvaginal ultrasound images and/or videoclips and/or a detailed ultrasound report. Ten patients identified from the International Ovarian Tumor Analysis (IOTA) studies had undergone a standardized preoperative ultrasound examination, by an experienced ultrasound examiner, between 1999 and 2016. A further 11 patients were identified through medical files, for whom ultrasound images were retrieved from local image workstations and picture archiving and communication systems. All tumors were described using IOTA terminology. The collected ultrasound images and videoclips were used by two observers for additional characterization of the tumors.
RESULTS
All cases were pure YSTs, except for one that was a mixed tumor (80% YST and 20% embryonal carcinoma). Median age at diagnosis was 25 (interquartile range (IQR), 19.5-30.5) years. Seventy-six percent (16/21) of women had an International Federation of Gynecology and Obstetrics (FIGO) Stage I-II tumor at diagnosis. Fifty-eight percent (11/19) of women felt pain during the ultrasound examination and one presented with ovarian torsion. Median serum α-fetoprotein (S-AFP) level was 4755 (IQR, 1071-25 303) µg/L and median serum CA 125 level was 126 (IQR, 35-227) kU/L. On ultrasound assessment, 95% (20/21) of tumors were unilateral. The median maximum tumor diameter was 157 (IQR, 107-181) mm and the largest solid component was 110 (IQR, 66-159) mm. Tumors were classified as either multilocular-solid (10/21; 48%) or solid (11/21; 52%). Papillary projections were found in 10% (2/21) of cases. Most (20/21; 95%) tumors were well vascularized (color score, 3-4) and none had acoustic shadowing. Malignancy was suspected in all cases, except in the patient with ovarian torsion, who presented a tumor with a color score of 1, which was classified as probably benign. Image and videoclip quality was considered as adequate in 18/21 cases. On review of the images and videoclips, we found that all tumors contained both solid components and cystic spaces, and that 89% (16/18) had irregular, still fine-textured and slightly hyperechoic solid tissue, giving them a characteristic appearance.
CONCLUSION
Malignant ovarian YSTs are often detected at an early stage, in young women usually in the second or third decade of life, presenting with pain and markedly elevated S-AFP. On ultrasound, malignant ovarian YSTs are mostly unilateral, large and multilocular-solid or solid, with fine-textured slightly hyperechoic solid tissue and rich vascularization. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology..
Topics: Adult; Early Detection of Cancer; Endodermal Sinus Tumor; Female; Humans; Ovarian Neoplasms; Ovary; Retrospective Studies; Ultrasonography; Vagina; Young Adult
PubMed: 32119168
DOI: 10.1002/uog.22002 -
The Pan African Medical Journal 2019Clear cell carcinoma (CCC) can simulate yolk sac tumor if the location is ovarian. In this case, the morphological distinction between these tumors is often difficult,...
Clear cell carcinoma (CCC) can simulate yolk sac tumor if the location is ovarian. In this case, the morphological distinction between these tumors is often difficult, but immunohistochemistry, the determination of CA125, of alpha fetoprotein (AFP) and the response to chemotherapy are particularly useful for solving this differential diagnosis problem. Endometrial and vaginal localization is even rare and appears to be related to distilbene uptake for vaginal localization. Whatever the gynecological location, CCC seems to have a poor prognosis. We report 5 cases of gynecological CCC including 1 case of vaginal carcinoma, 1 case of endometrial carcinoma and 3 cases of ovarian carcinoma. The definitive pathological examination concluded with the CCC diagnosis for all cases. Our purpose is to report these rare cases, their diagnosis, prognosis and therapeutic management.
Topics: Adenocarcinoma, Clear Cell; Adult; Aged, 80 and over; CA-125 Antigen; Diagnosis, Differential; Endodermal Sinus Tumor; Female; Genital Neoplasms, Female; Humans; Middle Aged; Prognosis; Retrospective Studies; Young Adult; alpha-Fetoproteins
PubMed: 31934230
DOI: 10.11604/pamj.2019.34.87.18505