Extensive surgical resections for rare pleural neoplasms: a single-center experience with a yolk sac tumor and synovial sarcoma.

BACKGROUND: Pleural neoplasms are rare and can be subdivided into pleural metastasis and primary pleural neoplasms. Non-mesothelioma primary pleural neoplasms are a diverse group of extremely rare pathologies. CASE PRESENTATION: In this case series, we describe the presentation and management of two rare primary pleural neoplasms. A first case describes a primary pleural yolk sac tumor treated with neoadjuvant chemotherapy, extended pleurectomy decortication, and hyperthermic intrathoracic chemotherapy. In a second case we describe the management of a primary pleural synovial sarcoma by neoadjuvant chemotherapy and extrapleural pneumonectomy. A complete resection was obtained in both cases and the post-operative course was uncomplicated. No signs of tumor recurrence were noted during follow-up in the first patient. In the second patient a local recurrence was diagnosed 6 months after surgery. CONCLUSION: Neo-adjuvant chemotherapy followed by extensive thoracic surgery, including hyperthermic intrathoracic chemotherapy, is a feasible treatment strategy for non-mesothelioma primary pleural neoplasms, but careful follow-up is required.

[Clinical analysis of 12 cases of ovarian yolk sac tumor].

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 µg/L) were significantly higher than normal (<25 µg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

Survival difference among adult and pediatric mediastinal yolk sac tumors cases: A meta-analysis of case reports.

BACKGROUND: Mediastinal Yolk sac tumors (YST) are rare and highly malignant extragonadal germ cell tumors with rapid growth and early metastases. We sought to conduct a meta-analysis of published case reports/case series to compare differences in survival, demographics, and treatment modalities between adult and pediatric patients with YST. METHODS: Ovid Embase, Cochrane, and Ovid Medline databases were searched for primary mediastinal pure YST cases. The primary outcome was overall survival (OS). Log-rank and Cox regression were used. This study is registered on PROSPERO (CRD42022367586). RESULTS: Among 846 studies, 87 met our inclusion criteria including 130 patients (Adults: 90 and Pediatrics: 40). About 41.5% of the patients were from the United States. The median age was 23.0 (Q1-Q3: 17.0-30.0), 88.5% were males, and (32.3%) were Asian. Stage II represented almost 40%. AFP was elevated in 96.9%. Respiratory distress was the presenting symptom in 65.4%. Chemotherapy, radiotherapy, and surgery were utilized in 84.6, 23.1, and 64.7% respectively. Median OS was 24 months (Adults: 23 months, Pediatrics: 25 months, P = 0.89). 3- and 5-year OS were 34.4% and 22.9% in adults and 41.5% and 41.5% in pediatrics, respectively. On multivariate analysis, anterior location of tumors, receipt of chemotherapy, and undergoing surgery were associated with better OS. CONCLUSION: Primary mediastinal YSTs are rare, but lethal neoplasms. Our meta-analysis showed that mediastinal YSTs mimic other non-seminomatous mediastinal GCTs in terms of clinical characteristics and available treatment options. Early diagnosis, neoadjuvant chemotherapy, and surgical resection are the key points for effective management and improved outcomes.

Liver transplantation for advanced-stage primary hepatic yolk sac tumor: A case report and literature review.

RATIONALE: Primary hepatic yolk sac tumors (YSTs) are rare in adults. Liver resection is an acknowledged treatment modality for primary hepatic YST. Liver transplantation may offer a possible cure for unresectable cases. PATIENT CONCERNS: We present a case of a 31-year-old woman with an abdominal mass who had abnormally elevated alpha-fetoprotein (AFP) levels (31,132 ng/mL; normal: 0-7 ng/mL). Contrast-enhanced computed tomography (CT) revealed large tumors located in both lobes of the liver, with arterial enhancement and venous washout. Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT indicated increased 18F-FDG uptake (maximum standardized uptake value, 24.4) in the liver tumors and left middle intra-abdominal nodule. DIAGNOSES: The diagnosis was primary hepatic YST with metastasis to the greater omentum. INTERVENTIONS: The patient underwent orthotopic liver transplantation and intra-abdominal nodule resection after transarterial chemoembolization (TACE) as a bridge. Intraoperatively, an intra-abdominal nodule was confirmed in the greater omentum. Histopathological examination of the liver tumors revealed Schiller-Duval bodies. The tropomyosin receptor kinase (TRK) inhibitor larotrectinib was administered, followed by four cycles of chemotherapy with bleomycin, etoposide, and cisplatin based on the next-generation sequencing results. OUTCOMES: The AFP level decreased to within the normal range. No evidence of tumor collapse was observed during the 34-month follow-up period. LESSONS: This case suggests that multimodal therapy dominated by liver transplantation, including preoperative TACE, postoperative adjuvant chemotherapy, and TRK inhibitors, is an effective treatment modality for unresectable primary hepatic YST.

Administration of a glypican-3 peptide increases the infiltration and cytotoxicity of CD8+ T cells against testicular yolk sac tumor, associated with enhancing the intratumoral cGAS/STING signaling.

BACKGROUND: Glypican-3 (GPC3) is highly expressed in testicular yolk sac tumor (TYST). GPC3 has been evaluated as a cancer vaccine for some types of tumors, but little is known on the effects of GPC3 peptide-based therapy on TYST. Here, we evaluated the antitumor effect of GPC3144-152 on TYST and its potential mechanisms. METHODS: GPC3144-152 -specific CD8+ T cells were induced by vaccine immunization and examined by ELISPOT. The CD8+ T cells were purified for testing their cytotoxicity in vitro against TYST cells by CCK-8 and TUNEL assays and in vivo against tumor growth. The influence of GPC3144-152 loading and/or cGAS silencing on the tumor growth, apoptosis and cGAS/STING signaling was tested by immunohistochemistry, immunofluorescence, flow cytometry, and Western blot. RESULTS: Vaccination with GPC3144-152 induced tumor-specific CD8+ T cells that secreted high levels of IFN-γ and granzyme B, and had potent cytotoxicity against TYST in a dose-dependent manner. Adoptive transfer of CD8+ T cells and treatment with GPC3144-152 significantly inhibited the growth of TYST tumors, but less effective for cGAS-silenced TYST tumors in vivo. Treatment with GPC3144-152 enhanced the infiltration of CD8+ T cells into the tumor environment and their cytotoxicity against TYST tumors in vivo by up-regulating granzyme B and IFN-ß expression, but down-regulating GPC3 expression in the tumors. Co-culture of CD8+ T cells with TYST in the presence of exogenous GPC3144-152 enhanced peptide-specific CD8+ T-cell cytotoxicity in vitro, accompanied by enhancing cGAS, γH2AX, TBK1, and IRF3 phosphorylation in TYST cells, but less effective in cGAS-silenced TYST cells. CONCLUSIONS: These data indicated that GPC3 peptide-specific CD8+ T cells had potent antitumor activity against TYST tumor, particularly for combined treatment with the peptide, which was partially dependent on the intratumoral cGAS/STNG signaling. GPC3 peptide vaccine may be valuable for the combination treatment of TYST.

Retroperitoneal yolk sac tumour encroaching the liver and adrenal gland with tumour thrombus in cavo-atrial region and hepatic veins.

Paediatric germ cell tumours (GCT) are rare tumours and are unique because of varied clinical presentation and locations. Yolk sac tumour is the predominant malignant histology and a serum marker; alpha fetoprotein is used to see treatment response and recurrent disease. It is extremely rare to find a retroperitoneal GCT with tumour thrombus extending up to the cavo-atrial region with involvement of the hepatic veins. We report a case of retroperitoneal yolk sac tumour (RPYST) with extension to the liver and right adrenal gland along with tumour thrombus in the inferior vena cava and in the right and middle hepatic veins. The child was operated after satisfactory response to chemotherapy. Excision of the tumour along with the right adrenal gland and around 5 cm of retro-hepatic caval resection was done. Inferior vena cava resection was tolerated without reconstruction. Currently child is disease-free and symptom-free at 22 months of follow-up with normal serum marker.

Survival outcomes and establishment of a novel risk stratification system in patients with ovarian yolk sac tumors.

OBJECTIVE: To evaluate the survival outcomes and establish a risk stratification system in patients with ovarian yolk sac tumors (OYST). METHODS: The recurrence-free survival (RFS), disease-specific survival (DSS), and prognostic factors were retrospectively evaluated in 151 OYST patients treated in our hospital between 2006 and 2022. A risk stratification system based on the identified prognostic factors was established. RESULTS: The median follow-up time was 5.1 years, with a 5-year RFS and DSS rate of 75.5% and 91.2%, respectively. FIGO stage III-IV and the interval between treatment and normalization of AFP were two prognostic predictors. Significant differences in RFS and DSS (both P < 0.001) were identified between patients who had normalized AFP ≤ 3 and ≥ 4 cycles of chemotherapy, or among patients who had normalized AFP after ≤2, 3-4, and ≥ 5 cycles of chemotherapy. FIGO stage I - II and stage III-IV were scored as 0 and 2, respectively. AFP normalization ≤2, 3, 4, and ≥ 5 cycles of chemotherapy were scored as 0, 1, 2, and 4, respectively. A total score of 0-1, 2-3, and ≥ 4 were stratified patients into low-risk (96 patients), intermediate-risk (35 patients), and high-risk groups (20 patients), respectively. Patients in three risk stratifications manifested significant differences in both RFS and DSS (P < 0.0001). CONCLUSION: This risk stratification system based on tumor stage and the interval between treatment and normalization of AFP may help to guide clinical management by dividing OYST patients into three risk groups.

Clinical characteristics and prognostic models of gonadal and extra-gonadal yolk sac tumors: a population-based analysis in children and adolescents.

PURPOSE: Yolk sac tumors (YST) are a rare and aggressive germ cell tumor. We aimed to conduct a population-based cohort study and develop a nomogram to predict overall survival (OS) in pediatric patients with YST. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all pediatric patients with YST diagnosed between 2000 and 2018. The log-rank test was used to compare survival curves. To examine the impact of each factor on overall survival, a multivariate Cox proportional hazards model was created. Based on the results of the Cox regression model, a nomogram was constructed. RESULTS: A total of 520 YST patients were identified. Overall survival rates for all patients were 92.2% at 3-year and 90.3% at 5-year, respectively. The outcome of Cox proportional hazard regression revealed that age, gender, primary sites, and treatment regimens were important independent predictors in this model. Based on the Cox regression model, we created a nomogram for predicting OS in pediatric YST patients. The chance of death increased with age in patients. Furthermore, patients with extra-gonadal YST have a lower survival rate than those with gonadal YST. CONCLUSIONS: Our study revealed that age, gender, and primary site were found to be the most important predictors of the overall survival of pediatric YST, providing crucial epidemiological information for clinical management.

Primary orbital yolk sac tumor in an infant: A rare entity.

We report a case of pure orbital yolk sac tumor (YST) in an 11-month-old infant, which is a rare entity. The child presented with progressive painless swelling of the right eye and on examination had proptosis, chemosis, and lid edema. Systemic examination was within normal limits. Magnetic resonance imaging (MRI) orbit revealed a lobulated heterogeneously enhancing right retroocular mass extending up to the orbital apex, displacing the optic nerve and eroding the medial orbital wall. Biopsy of the lesion revealed pure YST histology. Serum alpha-fetoprotein (AFP) was markedly raised at 76900 ng/mL. She was started on infant bleomycin etoposide cisplatin (BEP) chemotherapy protocol. There was a good clinical and radiological response. A high index of malignancy is required in young children presenting with orbital proptosis. A multidisciplinary approach and early intervention are essential to save both vision and life.

Yolk Sac Tumour Arising in the Glans Penis an Achondroplasic Child: A Case Report with Summary of Prior Published Cases.

BACKGROUND: Yolk sac tumors (YST) are commonly encountered gonadal germ cell tumors in children, especially in the prepubertal age group. In addition to gonadal primary, it can occur in multiple extragonadal sites, of which sacrococcygeal, retroperitoneum, gastric and mediastinum are the commonest. There are 4 previous reports of primary penile YST. CASE REPORT: We describe a primary penile yolk sac tumor in a child with achondroplasia. CONCLUSION: Yolk sac tumor can occur in the penis during the prepubertal period. Penile yolk sac tumor associated with achondroplasia has not been previously reported, but this could be incidental.

Malignant testicular tumors in children: overview on 10 years of Saudi Cancer Registry.

BACKGROUND/OBJECTIVE: The aim of this study was to identify epidemiological and histopathological patterns of pediatric testicular tumor (TT) in Saudi population over 10 years. METHODS: Retrospective data extracted from the Saudi Cancer Registry for Saudi children diagnosed with TT from 2008 to 2017. The data collected included patient's factors as age, year of diagnosis, survival status, and tumor factors as basis of diagnosis, origin of the tumor, histopathological group and subtype, and tumor behavior, stage, and laterality. RESULTS: A total of 115 patients with a median age of 14 (IQR 1.5-17) were included. The primary tumor site was a normal descended testis in 98.3% (115). Yolk sac tumor was the most common 28.2% (33), followed by embryonal carcinoma in 27.4% (32) and mixed germ-cell tumors in 23.1% (27). Kaplan-Meier analysis revealed significant association between survival and the stage of the tumor (p = 0.002). However, there was a lack of significant association between survival and age groups, histopathological groups, and histopathological subtypes (p = 0.541, p = 0.609, and p = 0.733, respectively). The overall mortality rate of TT 5.2% with all deaths caused by non-seminomatous germ-cell tumor diagnosed with stage 3. CONCLUSIONS: The median age of the patients was 14 years. Yolk sac tumors were the most common while testicular choriocarcinomas were the least in incidence. No increase in the incidence of TT was seen and the mortality rate over the 10-year period was 5.2%. Shorter survival was associated with higher tumor stage.

Primary endodermal sinus tumor originating from the sacral ligament: a case report and review of the literature.

BACKGROUND: Endodermal sinus tumor (EST) is a malignant tumor originating from the ovary or testis. In most case, ultrasound examination shows ovarian mass. But there is a special kind of extra-gonadal endodermal sinus tumor, which occur in organs other than gonads with insidious onset. Here we reported a case of endodermal sinus tumor, which originated from the sacral ligament presenting as an acute lower abdominal pain. CASE PRESENTATION: A 14-year-old girl was admitted to the hospital because of acute lower abdominal pain. The ultrasound showed a mass with 72 mm × 64 mm × 50 mm in Douglas, and there was no abnormality in bilateral ovaries and fallopian tubes. Laparoscopic exploration showed a large amount of blood clots in the pelvic cavity. After removal of the blood, we found rotten fish-like tissue in the left sacral ligament, rapid pathology suggested endodermal sinus tumor. After the operation, we retrospectively examined the value of alpha-fetoprotein (AFP), which was found to be elevated, and post-operative paraffin pathology confirmed the diagnosis. After four cycles of BEP chemotherapy, exploratory laparotomy was performed to remove the visible lesion, but postoperative pathology showed no abnormality. At the one-year follow-up, the patient remained recurrence-free. CONCLUSION: Extra-gonadal germ cell tumors are rarely reported. When young teenagers complain of acute lower abdominal pain with elevated AFP, but there was no lesion in bilateral ovaries and fallopian tubes, we must think about the possibility of endodermal sinus tumors. Accurate diagnosis facilitates complete resection of lesions and improves patient's outcomes.

Detailed characterization of PD-1/PD-L1 and CTLA4 expression and tumor-infiltrating lymphocytes in yolk sac tumors.

BACKGROUND: Immune checkpoint blockade (ICB) is considered as a promising approach for cancer treatment. However, the potency of ICB therapy in yolk sac tumors (YSTs) has not been confirmed, and the comprehensive analysis of tumor immune microenvironment and the expression of PD-1/PD-L1 and CTLA4 were also not thoroughly evaluated. METHODS: Immunohistochemistry was performed in formalin-fixed, paraffin-embedded tumor specimens from 23 YSTs patients to detect the density and distribution of tumor-infiltrating T cells, tertiary lymphoid structures (TLSs), as well as the expression of PD-1/PD-L1 and CTLA4. RESULTS: Overall, more than half (61 %) of all patients exhibited an immune-desert phenotype based on CD3+ T cells. PD-1 expression was identified in five tumor samples (21.7 %), and PD-L1 expression exhibited a different positive rate in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) (39.1 % and 17.4 %). Noteworthily, the rate of positive CTLA4 expression in both TCs and TILs was markedly higher (69.6 % and 56.5 %) than those of PD-1 and PD-L1 expression. Furthermore, TLSs were observed in 21.74 % of all tissues, and samples with TLSs exhibited significantly higher densities of TILs and higher expression of immune checkpoint molecules, particularly PD-1/PD-L1. In addition, tumors located in testes also exhibited a higher density of TILs and higher expression of immune checkpoint molecules. CONCLUSION: Generally a high frequency of CTLA4 expression was found, PD-1/PD-L1 expression, the immune-inflamed phenotype, and TLSs were low frequency in YSTs, however, YSTs in testes showed a higher density of TILs and higher expression of immune checkpoint molecules.

FoxA2 is a reliable marker for the diagnosis of yolk sac tumour postpubertal-type.

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.

First case of endometrial cancer after yolk sac tumor in a patient with Li-Fraumeni syndrome.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease with high penetrance caused by a germline variant of TP53 gene. We report the first case of endometrial cancer after yolk sac tumor with LFS. CASE PRESENTATION: The presented female patient underwent right adnexectomy at age 23 because of a yolk sac tumor of the ovary. At the age of 27, the patient was diagnosed with endometrial adenocarcinoma, received cytoreductive surgery and chemotherapy. Given that her personal cancer history along with a strong family history of cancer, her father passing away from lung cancer at age 48 and her grandmother dying of ovarian cancer at age 50, the patient was referred for genetic counseling and testing. Genetic screening revealed a heterozygous pathogenic TP53 c.844C > T, p.( R282 W) with NM_000546.5 variant, a class 5 (C5) variant. This is the first reported case of a yolk sac tumor accompanied by subsequent endometrial cancer that is associated with LFS. CONCLUSIONS: We reported a first case of an endometrial cancer after yolk sac tumor patient with a tumor family history of harboring the germline TP53 pathogenic variation which expanded types of tumor that can be presented in patients with LFS. This case highlights the importance of genetic testing for patients with malignant tumors, as well as patients with a family history of malignant tumors. And our case highlights the necessity of screening for gynecologic tumor in LFS patients.

Primary Endodermal Sinus Tumor of the Intraspinal Cavity: A Case Report and Review of the Literature.

Endodermal sinus tumor (EST) occurs most frequently in the gonads and is relatively rare in other sites, particularly in the spinal cavity. We report a 19-year-old woman who presented with back pain and weakness of both lower extremities who was found to have an EST in the spinal canal cavity. She had severely elevated serum alpha-fetoprotein (AFP) level at presentation. Magnetic resonance imaging (MRI) revealed the mass in the spinal canal. The tumor was excised. Serum AFP returned to normal after three cycles of chemotherapy. We describe the imaging findings and the macroscopic and microscopic features of this rare tumor. EST is a relatively rare malignant germ cell tumor that usually originates in the gonads and has poor prognosis. This is a rare case of the primary EST in the spinal canal. Radiologists need to be aware of the MRI appearance of extragonadal EST.