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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 -
Journal of Cellular and Molecular... Feb 2021Yolk-sac tumours (YSTs), a germ cell tumour subtype, occur in newborns and infants as well as in young adults of age 14-44 years. In clinics, adult patients with YSTs...
Yolk-sac tumours (YSTs), a germ cell tumour subtype, occur in newborns and infants as well as in young adults of age 14-44 years. In clinics, adult patients with YSTs face a poor prognosis, as these tumours are often therapy-resistant and count for many germ cell tumour related deaths. So far, the molecular and (epi)genetic mechanisms that control development of YST are far from being understood. We deciphered the molecular and (epi)genetic mechanisms regulating YST formation by meta-analysing high-throughput data of gene and microRNA expression, DNA methylation and mutational burden. We validated our findings by qRT-PCR and immunohistochemical analyses of paediatric and adult YSTs. On a molecular level, paediatric and adult YSTs were nearly indistinguishable, but were considerably different from embryonal carcinomas, the stem cell precursor of YSTs. We identified FOXA2 as a putative key driver of YST formation, subsequently inducing AFP, GPC3, APOA1/APOB, ALB and GATA3/4/6 expression. In YSTs, WNT-, BMP- and MAPK signalling-related genes were up-regulated, while pluripotency- and (primordial) germ cell-associated genes were down-regulated. Expression of FOXA2 and related key factors seems to be regulated by DNA methylation, histone methylation / acetylation and microRNAs. Additionally, our results highlight FOXA2 as a promising new biomarker for paediatric and adult YSTs.
Topics: Age Factors; Biomarkers, Tumor; Cell Line, Tumor; DNA Methylation; Disease Susceptibility; Endodermal Sinus Tumor; Hepatocyte Nuclear Factor 3-beta; Humans; Immunohistochemistry; Models, Biological; Oncogene Proteins
PubMed: 33448076
DOI: 10.1111/jcmm.16222 -
Medicine Jul 2022Ovarian yolk sac tumor (YST) is a very rare malignant tumor in young women. This study aimed to explore the clinicopathological prognostic characteristics and... (Review)
Review
Clinicopathological features, prognosis, and fertility outcomes in Chinese Han women treated for ovarian yolk sac tumor: A retrospective case series study from two tertiary-care academic medical centers.
OBJECTIVE
Ovarian yolk sac tumor (YST) is a very rare malignant tumor in young women. This study aimed to explore the clinicopathological prognostic characteristics and reproductive outcomes of Chinese Han patients.
METHODS
To describe a case series study, we reviewed the clinicopathological data of 50 YST patients treated from 2 tertiary medical academic medical centers from January 2009 to December 2019. The Akaike information criterion was used to select variables. The influence of relevant characteristics on prognosis factors was analyzed by the Cox proportional hazard model.
RESULTS
The median follow-up time was 64.5 months (range from 3 to 124 months). The median age was 22.7 years (3 to 34 years). Abdominal pain (54.0%) or mass (42.0%) were the most common clinical symptoms in the early stage of diagnosis. The tumors were located bilaterally in 4 cases. 27 patients, 7 patients, 13 patients, and 3 patients were in stage I, II, III, and IV, respectively. Twenty-one stage I patients and 12 stage II to IV patients underwent fertility-preserving surgery. Of the 50 patients who received postoperative chemotherapy, 49 received the BEP regimen. At the last follow-up, 92% of the patients were still alive. The overall survival rate and disease-free survival rate were 91.6% and 90.6%, respectively. Recurrence occurred in 7 (14%) patients with a median survival time of 16.7 months (range from 3 to 50 months). Six patients had recurrence in the abdominal space. The percentage of Ki67 (P = .01) and tumor size (P = .03) were 2 important prognostic factors in multivariate analysis. In terms of survival outcomes, fertility-preserving surgery can be equivalent to radical surgery. Sixteen patients tried to conceive, and 6 patients with advanced-stage succeeded in 10 pregnancies. Of these, 6 patients successfully gave birth to 6 healthy babies.
CONCLUSIONS
The diagnosis of YST of childbearing age is very rare. Because the failure of primary treatment is related to the residual disease after salvage surgery, the fertility and survival results of patients undergoing fertility-preserving surgery are promising.
Topics: Academic Medical Centers; Adult; China; Endodermal Sinus Tumor; Female; Fertility; Humans; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Pregnancy; Prognosis; Retrospective Studies; Young Adult
PubMed: 35866762
DOI: 10.1097/MD.0000000000029868 -
Medicine Jul 2022Testicular neoplasms are not commonly found in children and are a formidable threat if treated inappropriately. However, there is no consensus regarding its management....
Testicular neoplasms are not commonly found in children and are a formidable threat if treated inappropriately. However, there is no consensus regarding its management. This study aimed to create a holistic picture of the interprofessional team in the management of malignant testicular tumors. Seventeen patients had mixed germ cell tumors, 15 had pure yolk sac tumors, 2 had immature teratomas, 2 had teratocarcinomas, and 1 had a sex cord stromal tumor. Five lesions were diagnosed as nongerm cell tumors: 2 embryonal rhabdomyosarcomas, 2 lymphomas, and 1 acute myeloid leukemia. At initial presentation, retroperitoneal (n = 2), bone marrow (n =1), and mediastinal (n = 1) metastases were identified in 4 (10%) patients. The operative interventions performed included radical inguinal orchiectomy (n = 5), scrotal orchiectomy (n = 31), and testicular biopsy or testis-sparing enucleation of the tumor (n = 6). Postoperatively, 18 patients received either adjuvant chemotherapy (n = 14) or chemoradiation (n = 5). Five patients with mixed germ cell tumors (n = 2), group IV paratesticular rhabdomyosarcoma (n = 2), and acute myeloid leukemia with myeloid sarcoma (n =1) died of disease progression. Thirty-six patients remained alive and disease-free at the last visit. Malignant testicular tumors in children deserve proper diagnostic support from a therapeutic perspective. Any concern or suspicion of a testicular tumor warrants an inguinal approach to avoid scrotal violation.
Topics: Child; Endodermal Sinus Tumor; Humans; Male; Neoplasms, Germ Cell and Embryonal; Orchiectomy; Teratoma; Testicular Neoplasms
PubMed: 35866814
DOI: 10.1097/MD.0000000000029735 -
Medicine Sep 2021Mesonephric adenocarcinoma (MNAC) is a very rare tumor that originates from mesonephric duct remnants of the female genital tract. Only a few cases were reported in the...
Mesonephric adenocarcinoma (MNAC) is a very rare tumor that originates from mesonephric duct remnants of the female genital tract. Only a few cases were reported in the literature, and most of them occurred in the cervix, extremely rare in the uterine body and ovary. MNAC was rarely reported to arise in the uterine corpus, but never was reported in the ovary. Mesonephric-like adenocarcinomas are recently suggested to describe these neoplasms arising from the uterine corpus and ovary. Due to the rareness of the disease, little is known regarding clinical characteristics, pathological diagnosis, prognosis, and optimal management strategy of MNAC in the female reproductive system. We report a series of MNACs arising from the vagina, cervix, uterine corpus, ovary, and fallopian tube, to summarize the clinical characteristics, pathological diagnosis, treatment, and prognosis.We retrospectively analyzed all MNACs in the female genital tract derived from our institute from January 2010 till January 2020. Patients' clinical details and follow-up were obtained from hospital records and scans were obtained from picture archiving and communication system.A total of 11 patients were included. The median age of onset of symptoms was 52 years. All patients underwent total hysterectomy and bilateral salpingo-oophorectomy, and lymph node dissections were performed in 7/11 (63.6%) patients. Two/eleven (18.2%) received neoadjuvant chemotherapy before surgery and 7/11 (63.6%) received adjuvant chemotherapy after primary surgery. Of the 11 patients, only 1 patient received adjuvant radiation therapy. One patient died at the end point of this study, 9 patients (81.8%) survived and 1 patient was lost to follow-up. The mean follow-up duration was 33.5 months.Although there is no consensus for the optimal treatment of this rare disease, radical surgery is considered to be the initial choice for localized lesion. Given the high malignancy, the majority of MNAC or mesonephric-like adenocarcinoma patients who underwent adjuvant chemotherapy received 4 to 8 cycles of carboplatin/paclitaxel as a first-line treatment after primary surgery with a median progression-free survival of 12 months. Treatment for recurrent disease in these patients included gemcitabine, carboplatin, and paclitaxel. Radiation was very limited in the treatment of the disease.
Topics: Adenocarcinoma; Adult; Aged; China; Female; Genital Neoplasms, Female; Genitalia, Female; Humans; Mesonephroma; Middle Aged; Retrospective Studies
PubMed: 34477176
DOI: 10.1097/MD.0000000000027174 -
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 -
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 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Dec 2019Primary mediastinal yolk sac tumor, which is also known as endodermal sinus tumor, is a rare but lethal neoplasm and its prognosis is very dismal. The current treatment...
OBJECTIVE
Primary mediastinal yolk sac tumor, which is also known as endodermal sinus tumor, is a rare but lethal neoplasm and its prognosis is very dismal. The current treatment for this tumor is controversial, and chemotherapy combined with resection of residual lesions is adopted sometimes. We summarized the experience of seven primary mediastinal yolk sac tumors treated with platinum-based chemotherapy and extended resection in Peking University First Hospital.
METHODS
Clinicopathological data of the patients with primary mediastinal yolk sac tumor who received operation in Peking University First Hospital between August 2014 and August 2018 were collected and analyzed retrospectively.
RESULTS
We experienced seven primary mediastinal yolk sac tumors during this period. Computed tomography scan revealed an anterior mediastinal tumor in all the patients and all of them had markedly raised alphafetoprotein (AFP) and normal β-human chorion gonadotropin (β-HCG). Five patients underwent needle core biopsy before treatment, which showed a mediastinal yolk sac tumor. All of these patients received preoperative platinum-based chemotherapy and they all presented partial response according to computed tomography. Two other patients did not receive preoperative biopsy, so they directly underwent extended resection. All of the seven patients underwent operation successfully and two of them experienced postoperative complications, including one with pneumonia and the other with atelectasis. R0 resection was achieved in six patients and R1 resection was achieved in the other patient. According to postoperative pathology, there were one microcyst subtype, one adenoid subtye, one giant capsule subtype and two hybrid subtypes. Surprisingly, there were no yolk sac tumor tissue in the other two patients after preoperative chemotherapy. All the patients received postoperative chemotherapy, excluded one patient who was unable to tolerate chemotherapy after operation. Three patients experienced postoperative pulmonary metastases within one year and two of them died soon. The other patient received chemotherapy and immunotherapy after recurrence and he was alive at the time of writing. Four other patients were alive without recurrence and metastasis.
CONCLUSION
Primary mediastinal yolk sac tumor is rare and its prognosis is poor. A multimodality approach including adjuvant chemotherapy and resection of residual lesions is the optimal treatment and it may lead to long-term survival.
Topics: Endodermal Sinus Tumor; Humans; Male; Mediastinal Neoplasms; Mediastinum; Neoplasm Recurrence, Local; Retrospective Studies
PubMed: 31848510
DOI: 10.19723/j.issn.1671-167X.2019.06.020 -
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 -
Frontiers in Public Health 2022Testicular yolk sac tumor (TYST) is a rare malignant germ cell tumor that mainly occurs in young men. Due to the low incidence of yolk sac tumors, there is a lack of... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Testicular yolk sac tumor (TYST) is a rare malignant germ cell tumor that mainly occurs in young men. Due to the low incidence of yolk sac tumors, there is a lack of prospective cohort studies with large samples. We aimed to develop a nomogram to predict cancer-specific survival (CSS) in patients with TYST.
MATERIALS AND METHODS
Patient information was downloaded from the Surveillance, Epidemiology and End Results (SEER) database. We enrolled all patients with TYST from 2000 to 2018, and all patients were randomly divided into a training set and a validation set. Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors for patients. We constructed a nomogram based on the multivariate Cox regression model to predict 1-, 3-, and 5-year CSS in patients with TYST. We used a series of validation methods to test the accuracy and reliability of the model, including the concordance index (C-index), calibration curve and the area under the receiver operating characteristic curve (AUC).
RESULTS
619 patients with TYST were enrolled in the study. Univariate and multivariate Cox regression analysis showed that age, T stage, M stage and chemotherapy were independent risk factors for CSS. A nomogram was constructed to predict the patient's CSS. The C-index of the training set and the validation set were 0.901 (95%CI: 0.859-0.847) and 0.855 (95%CI: 0.865-0.845), respectively, indicating that the model had excellent discrimination. The AUC showed the same results. The calibration curve also indicated that the model had good accuracy.
CONCLUSIONS
In this study, we constructed the nomogram for the first time to predict the CSS of patients with TYST, which has good accuracy and reliability and can help doctors and patients make clinical decisions.
Topics: Male; Humans; Nomograms; Endodermal Sinus Tumor; SEER Program; Neoplasm Staging; Reproducibility of Results
PubMed: 36324443
DOI: 10.3389/fpubh.2022.1038502