Defining the Teratoma as a Model for Multi-lineage Human Development.

We propose that the teratoma, a recognized standard for validating pluripotency in stem cells, could be a promising platform for studying human developmental processes. Performing single-cell RNA sequencing (RNA-seq) of 179,632 cells across 23 teratomas from 4 cell lines, we found that teratomas reproducibly contain approximately 20 cell types across all 3 germ layers, that inter-teratoma cell type heterogeneity is comparable with organoid systems, and teratoma gut and brain cell types correspond well to similar fetal cell types. Furthermore, cellular barcoding confirmed that injected stem cells robustly engraft and contribute to all lineages. Using pooled CRISPR-Cas9 knockout screens, we showed that teratomas can enable simultaneous assaying of the effects of genetic perturbations across all germ layers. Additionally, we demonstrated that teratomas can be sculpted molecularly via microRNA (miRNA)-regulated suicide gene expression to enrich for specific tissues. Taken together, teratomas are a promising platform for modeling multi-lineage development, pan-tissue functional genetic screening, and tissue engineering.

Induction of mouse totipotent stem cells by a defined chemical cocktail.

In mice, only the zygotes and blastomeres from 2-cell embryos are authentic totipotent stem cells (TotiSCs) capable of producing all the differentiated cells in both embryonic and extraembryonic tissues and forming an entire organism1. However, it remains unknown whether and how totipotent stem cells can be established in vitro in the absence of germline cells. Here we demonstrate the induction and long-term maintenance of TotiSCs from mouse pluripotent stem cells using a combination of three small molecules: the retinoic acid analogue TTNPB, 1-azakenpaullone and the kinase blocker WS6. The resulting chemically induced totipotent stem cells (ciTotiSCs), resembled mouse totipotent 2-cell embryo cells at the transcriptome, epigenome and metabolome levels. In addition, ciTotiSCs exhibited bidirectional developmental potentials and were able to produce both embryonic and extraembryonic cells in vitro and in teratoma. Furthermore, following injection into 8-cell embryos, ciTotiSCs contributed to both embryonic and extraembryonic lineages with high efficiency. Our chemical approach to totipotent stem cell induction and maintenance provides a defined in vitro system for manipulating and developing understanding of the totipotent state and the development of multicellular organisms from non-germline cells.

Control of embryonic stem cell lineage commitment by core promoter factor, TAF3.

Deciphering the molecular basis of pluripotency is fundamental to our understanding of development and embryonic stem cell function. Here, we report that TAF3, a TBP-associated core promoter factor, is highly enriched in ES cells. In this context, TAF3 is required for endoderm lineage differentiation and prevents premature specification of neuroectoderm and mesoderm. In addition to its role in the core promoter recognition complex TFIID, genome-wide binding studies reveal that TAF3 localizes to a subset of chromosomal regions bound by CTCF/cohesin that are selectively associated with genes upregulated by TAF3. Notably, CTCF directly recruits TAF3 to promoter distal sites and TAF3-dependent DNA looping is observed between the promoter distal sites and core promoters occupied by TAF3/CTCF/cohesin. Together, our findings support a new role of TAF3 in mediating long-range chromatin regulatory interactions that safeguard the finely-balanced transcriptional programs underlying pluripotency.

Decoding the universal human chromatin landscape through teratoma-based profiling.

Teratoma formation is key for evaluating differentiation of human pluripotent stem cells into embryonic germ layers and serves as a model for understanding stem cell differentiation and developmental processes. Its potential for insights into epigenome and transcriptome profiling is significant. This study integrates the analysis of the epigenome and transcriptome of hESC-generated teratomas, comparing transcriptomes between hESCs and teratomas. It employs cell type-specific expression patterns from single-cell data to deconvolve RNA-Seq data and identify cell types within teratomas. Our results provide a catalog of activating and repressive histone modifications, while also elucidating distinctive features of chromatin states. Construction of an epigenetic signature matrix enabled the quantification of diverse cell populations in teratomas and enhanced the ability to unravel the epigenetic landscape in heterogeneous tissue contexts. This study also includes a single cell multiome atlas of expression (scRNA-Seq) and chromatin accessibility (scATAC-Seq) of human teratomas, further revealing the complexity of these tissues. A histology-based digital staining tool further complemented the annotation of cell types in teratomas, enhancing our understanding of their cellular composition. This research is a valuable resource for examining teratoma epigenomic and transcriptomic landscapes and serves as a model for epigenetic data comparison.

Constitutional balanced translocations involving SMARCB1: A rare cause of rhabdoid tumor predisposition syndrome.

Rhabdoid Tumor Predisposition Syndrome 1 (RTPS1) confers an increased risk of developing rhabdoid tumors and is caused by germline mutations in SMARCB1. RTPS1 should be evaluated in all individuals with rhabdoid tumor and is more likely in those with a young age at presentation (occasionally congenital presentation), multiple primary tumors, or a family history of rhabdoid tumor or RTPS1. Proband genetic testing is the standard method for diagnosing RTPS1. Most known RTPS1-related SMARCB1 gene mutations are copy number variants (CNVs) or single nucleotide variants/indels, but structural variant analysis (SVA) is not usually included in the molecular evaluation. Here, we report two children with RTPS1 presenting with atypical teratoid/rhabdoid tumor (ATRT) who had constitutional testing showing balanced chromosome translocations involving SMARCB1. Patient 1 is a 23-year-old female diagnosed with pineal region ATRT at 7 months who was found to have a de novo, constitutional t(16;22)(p13.3;q11.2). Patient 2 is a 24-month-old male diagnosed with a posterior fossa ATRT at 14 months, with subsequent testing showing a constitutional t(5;22)(q14.1;q11.23). These structural rearrangements have not been previously reported in RTPS1. While rare, these cases suggest that structural variants should be considered in the evaluation of children with rhabdoid tumors to provide more accurate genetic counseling on the risks of developing tumors, the need for surveillance, and the risks of passing the disorder on to future children. Further research is needed to understand the prevalence, clinical features, and tumor risks associated with RTPS1-related constitutional balanced translocations.

Adjunctive Surgery Is Often Without Oncological Benefit at Time of Postchemotherapy Retroperitoneal Lymph Node Dissection.

PURPOSE: Postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for advanced nonseminomatous germ cell tumors (GCTs) aims to resect all remaining metastatic tissue. Resection of adjacent visceral or vascular organs is commonly performed for complete resection. Resection of organs harboring only necrosis results in relevant overtreatment. The study aimed to describe the frequency of metastatic involvement of resected organs with teratoma or viable cancer and to analyze perioperative complications and relapse-free survival. MATERIALS AND METHODS: In a 2-center study, we reviewed a cohort of 1204 patients who underwent PC-RPLND between 2008 and 2021 and identified 242 (20%) cases of adjunctive surgery during PC-RPLND. We analyzed the removed adjacent structures and the pathohistological presence of GCT elements in the resected organs: viable GCT, teratoma, or necrosis/fibrosis. Surgery-associated complications were reported according to the Clavien-Dindo classification. RESULTS: Viable GCT, teratoma, and necrosis were present in 54 (22%), 94 (39%), and 94 (39%), respectively, of all patients with adjunctive resection of adjacent organs. Vascular resections or reconstructions (n = 112; viable: 23%, teratoma: 41%, necrosis: 36%) were performed most frequently, followed by nephrectomies (n = 77; viable: 29%, teratoma: 39%, necrosis: 33%). Perioperative complications of grade ≥ IIIa occurred in 6.6% of all patients, with no difference between the viable GCT and teratoma/necrosis groups (P = .1). A total of 76 patients have been followed without a relapse for at least 36 months. Median follow-up of the whole cohort was 22 months (quartile 7 and 48). Patients with viable GCT/teratoma in the resected specimens had a significantly increased risk of recurrence by 5 years compared to patients with only necrosis (19% vs 59% vs 81%, P < .001). CONCLUSIONS: This study shows that 33% to 40% of all resections of adjacent organs do not harbor teratoma or viable GCT. This highlights the need for better patient selection for these complex patients.

Diffuse infiltrating tumour with the molecular profile of an atypical teratoid rhabdoid tumour (AT/RT SHH-1B) in an adult patient.

We describe a 46-year-old patient with an IDH-wildtype diffusely infiltrating atypical teratoid/rhabdoid tumour (AT/RT), SHH-1B molecular subtype. The unusual histology and subsequent diagnosis in an adult patient will be discussed.

Teratoma-associated and so-called pure Wilms tumour of the ovary represent two separate tumour types with distinct molecular features.

AIMS: Ovarian Wilms tumour (WT)/nephroblastoma is an extremely rare neoplasm that has been reported to occur in pure form or as a component of a teratomatous neoplasm. We hypothesized that teratoma-associated and pure ovarian WT may represent different tumour types with diverging molecular backgrounds. To test this hypothesis, we comprehensively characterized a series of five tumours originally diagnosed as ovarian WT. METHODS AND RESULTS: The five cases comprised three teratoma-associated (two mature and one immature) and two pure WTs. Two of the teratoma-associated WTs consisted of small nodular arrangements of "glandular"/epithelial structures, while the third consisted of both an epithelial and a diffuse spindle cell/blastemal component. The pure WTs consisted of "glandular" structures, which were positive for sex cord markers (including inhibin and SF1) together with a rhabdomyosarcomatous component. The two pure WTs harboured DICER1 pathogenic variants (PVs), while the three associated with teratomas were DICER1 wildtype. Panel-based DNA sequencing of four of the cases did not identify PVs in the other genes investigated. Analysis of the HA19/IGF2 imprinting region showed retention of imprinting in the pure WTs but loss of heterozygosity with hypomethylation of the ICR1 region in two of three teratoma-associated WTs. Furthermore, copy number variation and clustering-based whole-genome DNA methylation analyses identified divergent molecular profiles for pure and teratoma-associated WTs. CONCLUSION: Based on the morphological features, immunophenotype, and molecular findings (DICER1 PVs, copy number, and DNA methylation profiles), we suggest that the two cases diagnosed as pure primary ovarian WT represent moderately to poorly differentiated Sertoli Leydig cell tumours (SLCTs), while the tumours arising in teratomas represent true WTs. It is possible that at least some prior cases reported as pure primary ovarian WT represent SLCTs.

Growing teratoma syndrome in children and adolescents: Prevalence and surgical outcome.

INTRODUCTION: Patients affected by metastatic germ cell tumors may occasionally experience enlargement of masses with concurrent normalization of tumor markers during or after chemotherapy. This phenomenon is described as growing teratoma syndrome (GTS). The aim of the pre sent study is to assess the prevalence of GTS in the pediatric population and its implications in terms of surgical outcome. PATIENTS AND METHODS: The clinical notes of patients diagnosed with stage III and IV malignant germ cell tumors from January 2010 until December 2020 at our Institution were retrospectively reviewed. The prevalence of GTS, treatment strategies, survival, and outcome were analyzed. RESULTS: Thirty-three patients with high-stage malignant germ cell tumors were diagnosed in our institution in the analyzed period. Nine patients (28%) had radiologic evidence of enlargement of persistent masses with normal markers after chemotherapy; these patients were classified as GTS patients. All nine patients underwent resection of metastatic lymph nodes, and six had surgery on visceral metastases. In six patients, radical excision of all metastatic sites was achieved; five patients are alive and in complete remission, while one died because of peri-operative complications. Out of the three patients who could not achieve radical excision of the metastases, two died of progressive disease, and one is alive with progressive disease. CONCLUSIONS: Patients affected by GTS have a risk of progression of chemotherapy-resistant disease and death. Radical surgical excision is essential to achieve disease control and long-term survival.

A rare case of retroperitoneal teratoma with evidence of papillary thyroid carcinoma: a case report.

BACKGROUND: Teratomas are germ cell tumors composed of somatic tissues from up to three germ layers. Primary retroperitoneal teratomas usually develop during childhood and are uncommon in adults and in the retroperitoneal space. While there are only a few cases of retroperitoneal thyroid tissue, we report a unique case of a retroperitoneal papillary thyroid carcinoma. CASE PRESENTATION: A 41-year-old woman presented in our institution due to intermitted unspecific abdominal pain. Magnetic resonance imaging detected a multi-cystic solid retroperitoneal mass ventral to the psoas muscle and the left iliac artery. After surgical removal of the retroperitoneal mass, histology sections of the specimen indicated evidence of papillary thyroid carcinoma cells. A staging computed tomography scan of the body showed no further manifestations. To reduce the risk of recurrence, total thyroidectomy was performed followed by radioiodine therapy with lifelong hormone substitution. CONCLUSIONS: Primary retroperitoneal teratoma with evidence of papillary thyroid carcinoma is a rare condition. Preoperative diagnosis is difficult due to its non-specific clinical manifestation and lack of specific radiologic findings. Histopathology analysis is necessary for diagnosis. Although surgery is considered the first line treatment, there is still discussion about the extent of resection and the need for total thyroidectomy with adjuvant radioiodine therapy.

Pulsatile giant sacrococcygeal teratoma appearing like 2nd head.

Sacrococcygeal teratoma is a congenital tumor of early infancy. Eighty percent are present in the first month of life. It is considered to be an extragonadal germ cell tumor that can be diagnosed in utero. It is considered to be a rare tumor in infancy and childhood. Incidences in girls are more common as compared to boys. Association with other congenital abnormalities of the gastrointestinal system, cardiovascular system, and urological manifestations may be present. Association with spinal dysraphism may be present. A complete systemic evaluation needs to be done before any surgical intervention. We hereby present you a case of a 5-day-old male child, born from a non-consanguineous marriage, who presented to us with a large swelling at the coccygeal region. The mass had a variegated consistency with an ear-like appendage over it with associated hair, bones, and necrotic tissue in it. The patient was evaluated with imaging (MRI) which revealed a heterogeneously enhancing mass at the sacrococcygeal region with mild extension into the pre-sacral space suggesting sacrococcygeal teratoma. After a complete evaluation for congenital abnormal abnormalities of other sites, gross total excision of the mass was performed. The post-operative condition of the baby was uneventful. A biopsy of the mass revealed a mature cystic teratoma. The baby is under follow-up at present.

Management strategy for children with ovarian immature teratoma: results from a tertiary pediatric oncology center.

OBJECTIVES: We present an Egyptian study on pediatric ovarian immature teratomas (ITs), aiming to clarify our treatment strategy selection. METHODS: A retrospective review of all children with pure ovarian ITs who were treated at our institution between 2008 and 2023. The analysis included clinical characteristics, tumor staging according to Children's Oncology Group (COG), grading based on the Norris system, management, and outcomes. RESULTS: Thirty-two patients were included, with a median age of 9 years. All patients underwent primary surgery. Unilateral salpingo-oophorectomy was performed in 31 patients. Surgical staging was completed in all patients. Based on COG staging, there were 28 patients (87.5%) stage I, 1 (3%) stage II, and 3 (9.5%) stage III. According to Norris classification, 16 patients (50%) were classified as grade I, 9 (28%) grade II, and 7 (22%) grade III. All patients in stage I were treated using surgery-alone approach, whereas the remaining four (12.5%) received adjuvant chemotherapy. Five patients in stage I had gliomatosis peritonei (GP), and none of them underwent extensive surgery. At a median follow-up of 86 months, two patients had events. The first patient (stage III/grade I) developed IT relapse on the operative bed, and the second (stage I/grade I) had a metachronous IT on the contralateral ovary. Both patients were successfully managed with surgery followed by second-line chemotherapy. Five-year overall survival and event-free survival for all patients were 100% and 93.4%, respectively. CONCLUSIONS: Surgery-alone strategy with close follow-up achieves excellent outcomes for localized ovarian ITs in children, irrespective of the Norris grading or the presence of GP. However, adjuvant chemotherapy is questionable for patients with incompletely resected or locally advanced tumors, and its role requires further evaluation through prospective multicentric studies with a larger sample size.

Investigation of extragonadal teratomas in two Poecilia wingei.

Teratoma is a rare tumour in fish consisting of tissues from more than one germ layer, that may be located in either the gonads or extragonadal sites. Teratomas in many fish species remain poorly understood. In this work, we performed the first histological examinations of extragonadal teratomas in Poecilia wingei and also examined the influence of a large teratoma on male sexual activity. The studied teratomas shared general organizational features, but they also had variations in both external and internal features. In teratomas, the most common and highly differentiated tissues were striated muscle and nervous tissue. Despite the tumour, the male P. wingei exhibited normal mating behaviour and retained the ability for successful copulation. The structural features of extragonadal teratomas in guppy fish indicate a possible connection between these tumours and a failure of conserved processes operating in the embryonic germline.

Genetic Profiling of Sebaceous Carcinoma Arising from an Ovarian Mature Teratoma: A Case Report.

Ovarian mature teratomas (OMTs) originate from post-meiotic germ cells. Malignant transformation occurs in approximately 1-2% of OMTs; however, sebaceous carcinoma arising from OMTs is rare. This is the first report of a detailed genomic analysis of sebaceous carcinoma arising from an OMT. A 36-year-old woman underwent evaluation for abdominal tumors and subsequent hysterectomy and salpingo-oophorectomy. Pathologically, a diagnosis of stage IA sebaceous carcinoma arising from an OMT was established. Eight months post-surgery, the patient was alive without recurrence. Immunohistochemically, the tumor was negative for mismatch repair proteins. A nonsense mutation in TP53 (p.R306*) and a deletion in PIK3R1 were identified. Single nucleotide polymorphisms across all chromosomes displayed a high degree of homozygosity, suggestive of uniparental disomy. Herein, the OMT resulting from the endoreduplication of oocytes underwent a malignant transformation to sebaceous carcinoma via TP53 as an early event and PIK3R1 as a late event.

Assessment of Molecular Markers in Pediatric Ovarian Tumors: Romanian Single-Center Experience.

Pediatric ovarian tumors exhibit unique diagnostic and therapeutic challenges. This study evaluates the expression of SALL4 and OCT3/4 biomarkers in pediatric ovarian tumors and their associations with tumor subtype, stage, and clinical outcome. A retrospective analysis was conducted on 64 patients under 18 years old, examining demographic data, tumor characteristics, immunohistochemical staining, and clinical outcomes. Our results show that SALL4 was significantly expressed in adenocarcinoma, dysgerminoma (DSG), mixed germ cell tumors (GCTs), and immature teratoma, while OCT3/4 was highly expressed in DSG and mixed GCTs. Both markers are associated with a higher tumor grade and stage, indicating a more aggressive disease. The SALL4 positivity expression was correlated with high alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) levels, while OCT3/4 positivity significantly predicted the risk of subsequent metastasis. The mean progression-free survival (PFS) was notably shorter in patients with positive markers. These findings underscore the diagnostic and prognostic value of SALL4 and OCT3/4 in pediatric ovarian tumors, aligning with previous research and supporting their use in clinical practice for better disease management and patient outcomes.

Ovarian teratoma in a Swiss mountain dog.

A Swiss mountain dog, ~3 y old, was brought to a veterinary clinic because of a progressive enlargement of the abdomen. Upon clinical examination, a large mass was detected. After surgical extraction, the mass was confirmed to be a large ovarian teratoma. The weight of the tumor was > 16% of the dog's overall body weight. The dog recovered fully after surgery. The observations from this case suggest that, although teratomas are rare, prompt and accurate diagnosis is necessary to prevent further growth of these masses and to ensure positive outcomes.

Tératome ovarien chez un chien de montage suisse. Un chien de montagne suisse âgé d'environ 3 ans a été présenté dans une clinique vétérinaire en raison d'une augmentation de volume progressive de l'abdomen. Lors de l'examen clinique, une grosse masse a été détectée. À la suite du retrait chirurgical, la masse a été confirmée comme étant un large tératome ovarien. Le poids de la masse tumorale était > 16 % du poids total du chien. Le chien a récupéré complètement après la chirurgie. Les observations à partir de ce cas suggèrent, bien que les tératomes soient rares, un diagnostic rapide et exact est nécessaire pour prévenir une croissance ultérieure de ces masses et assurer une issue positive.(Traduit par Dr Serge Messier).

Testicular Mixed Teratoma and Yolk Sac Tumor, Prepubertal Type: A Case Report with Summary of Prior Published Cases.

BACKGROUND: Testicular mixed germ cell tumor is common in the post-pubertal age, less so in prepuberty. There are only 3 reports of prepubertal mixed teratoma and yolk sac tumor. Two of these cases had immature teratoma component and were in the neonatal age group. The third case in a toddler had a mature teratoma component. CASE REPORT: An 18-month-old boy presented with a testicular mass. Serum AFP was elevated (2200 ng/ml). The orchidectomy specimen contained a yolk-sac tumor and a small epidermoid cyst, indicating a mature teratomatous component. CONCLUSION: We report a testicular mixed teratoma and yolk sac tumor, prepubertal type along with summary of prior published cases. There is only one report describing this combination of mature teratoma with yolk sac tumor in the prepubertal testis.

Congenital Gastric Teratoma Presenting with Gastrointestinal Bleeding: Case Report and Review of Literature.

BACKGROUND: Gastric teratoma is an extremely rare tumor, representing <1% of all pediatric teratomas, and commonly manifests as a palpable abdominal mass. Upper gastrointestinal tract bleeding in newborns and infants is rare and is mostly caused by a benign lesion. CASE REPORT: We present a 3-month-old boy who presented with recurrent attacks of hematemesis, vomiting, and melena which on work up revealed a gastric teratoma. DISCUSSION/CONCLUSION: Owing to the unique characteristics and the extreme rarity of this entity, accurate preoperative diagnosis has remained elusive.

Ruptured Ovarian Cystic Teratoma: A Rare Diagnosis, Easily to Be Confused with Peritoneal Carcinomatosis.

Although ovarian cystic teratoma is the most common ovarian tumor, complications are quite rare. However, it is important to be recognized by the radiologist in order to avoid inaccurately diagnosing them as malignant lesions. This case report describes a 61-year-old postmenopausal woman, who presented to the emergency room with abdominal pain following a minor blunt abdominal trauma. In this context, a CT scan was performed, which showed the presence of round, hypodense masses randomly distributed in the peritoneum, with coexisting ascites in moderate amount; ovarian carcinoma with peritoneal carcinomatosis was suspected. The patient was hospitalized and an MRI of the abdomen and pelvis was recommended for a more detailed lesion characterization. Following this examination, the patient was diagnosed with mature cystic ovarian teratoma complicated by rupture. Surgery was performed, and the outcome was favorable. The cases of ruptured cystic teratomas are rare, and to our knowledge, this is the first occurrence described in literature. Special attention must be paid when confronting with such a case in medical practice, since it can easily misdiagnosed as peritoneal carcinomatosis.

Congenital orofacial teratoma in a 22-week foetus.

No abstract available.