Current outstanding challenges in germ cell tumors.

PURPOSE OF REVIEW: Despite the remarkable advances in the treatment of germ cell tumors (GCT), several challenges remain. This review aims to highlight some of these challenges and provide guidance on how to navigate through them. RECENT FINDINGS: Patients with International Germ Cell Cancer Collaborative Group poor risk disease have worse prognosis and investigating novel therapeutic interventions are warranted in this population. Patients with brain metastases require a multidisciplinary approach by a group of clinicians experienced in the management of germ cell tumors. Patients with platinum refractory disease have poor prognosis and development of novel treatment options is urgently needed. Conventional tumor markers including alpha fetoprotein and human chorionic gonadotropin remain standard. Development of novel biomarkers to detect minimal residual disease or teratoma is needed. SUMMARY: Management of patients with GCT requires a multidisciplinary approach. Patients should preferably be evaluated at tertiary care centers with expertise in the management of this disease.

Impact of teratoma on survival probabilities of patients with metastatic non-seminomatous germ cell cancer: Results from the IGCCCG Update Consortium.

AIMS: To resolve the ongoing controversy surrounding the impact of teratoma (TER) in the primary among patients with metastatic testicular non-seminomatous germ-cell tumours (NSGCT). PATIENTS AND METHODS: Using the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium database, we compared the survival probabilities of patients with metastatic testicular GCT with TER (TER) or without TER (NTER) in their primaries corrected for known prognostic factors. Progression-free survival (5y-PFS) and overall survival at 5 years (5y-OS) were estimated by the Kaplan-Meier method. RESULTS: Among 6792 patients with metastatic testicular NSGCT, 3224 (47%) had TER in their primary, and 3568 (53%) did not. In the IGCCCG good prognosis group, the 5y-PFS was 87.8% in TER versus 92.0% in NTER patients (p = 0.0001), the respective 5y-OS were 94.5% versus 96.5% (p = 0.0032). The corresponding figures in the intermediate prognosis group were 5y-PFS 76.9% versus 81.6% (p = 0.0432) in TER and NTER and 5y-OS 90.4% versus 90.9% (p = 0.8514), respectively. In the poor prognosis group, there was no difference, neither in 5y-PFS [54.3% in TER patients versus 55.4% (p = 0.7472) in NTER], nor in 5y-OS [69.4% versus 67.7% (p = 0.3841)]. NSGCT patients with TER had more residual masses (65.3% versus 51.7%, p < 0.0001), and therefore received post-chemotherapy surgery more frequently than NTER patients (46.8% versus 32.0%, p < 0.0001). CONCLUSION: Teratoma in the primary tumour of patients with metastatic NSGCT negatively impacts on survival in the good and intermediate, but not in the poor IGCCCG prognostic groups.

A basaloid carcinoma with multilocular thymic cyst mimicking a mediastinal teratoma.

This case report details a rare thymic basaloid carcinoma initially misinterpreted as a mediastinal teratoma, underscoring the diagnostic challenges posed by such tumors. A 71-year-old female presented with an asymptomatic anterior mediastinal tumor discovered incidentally during a routine health examination. Surgical intervention, followed by pathological and immunohistochemical analysis including CK-pan, p63, p40, and CD117 molecules, led to a definitive diagnosis of basaloid carcinoma of the thymus. This case highlights the critical importance of differential diagnosis in mediastinal lesions, especially those presenting with multilocular thymic cysts on chest CT. The subxiphoid video-assisted thoracoscopic surgery enabled complete tumor resection with minimal trauma and favorable postoperative outcomes. The patient opted against further radiotherapy or chemotherapy and she has survived for over eight months without recurrence. This case report contributes to the growing understanding of thymic basaloid carcinoma, a rare and potentially aggressive thymic carcinoma subtype. It emphasizes the necessity for precise surgical techniques and enhanced diagnostic acumen among cardiothoracic surgeons and oncologists.

Fertility-sparing approach in concurrent gliomatosis peritonei and growing teratoma syndrome in a young woman.

Gliomatosis peritonei (GP) and Growing Teratoma Syndrome (GTS) are rare and clinically significant conditions often associated with ovarian teratomas. GP involves the development of benign glial implants on the peritoneal surface, while GTS is characterised by the growth of benign, yet enlarging peritoneal implants following chemotherapy for malignant germ cell tumours. These implants are typically histologically mature teratomas devoid of malignancy. Our report documents a unique case where both GP and GTS manifested in a patient undergoing treatment for an immature ovarian teratoma. This dual occurrence is scarcely reported in the existing literature. The patient, a nulliparous woman in her 20s, developed a tumour indicative of GTS immediately after completing three cycles of bleomycin, etoposide and cisplatin therapy. This chemotherapy regimen followed fertility-sparing surgery for a stage IIIb ovarian immature teratoma. Given that total tumour resection is pivotal in positively influencing the prognosis of GTS, early minimally invasive surgical intervention before significant tumour growth is essential. This approach is particularly crucial considering that ovarian germ cell tumours are commonly present in younger patients, necessitating a focus on fertility preservation in most cases.

Congenital brain tumour in a neonate: a therapeutic challenge.

A term neonate with history of ventriculomegaly in the fetal period was diagnosed with a central nervous system tumour after radiological investigations. It was confirmed as an immature teratoma after histopathological examination. He underwent left frontal craniotomy with tumour excision. Intraoperatively, massive haemorrhage (venous bleed) occurred due to the high vascularity of the tumour and led to haemodynamic instability. A massive transfusion protocol was initiated. Despite multiple transfusions and shock management, he succumbed at 2 weeks of life. This case report highlights the importance of antenatal diagnosis and fetal MRI in prognostication and also the possible role of neoadjuvant chemotherapy in reducing tumour vascularity and, hence, bleeding.

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.

Mature solid teratoma of the uterine cervix: A rare case report and review of the literature.

RATIONALE: Most of the mature teratomas are found in the ovaries. Extragonadal teratomas are extremely rare. To date, there are only a handful of reports of uterine cervical teratomas documented in the English literature. PATIENT CONCERNS: Herein we describe a rare case of a 40-year-old patient who was presented to our hospital for a cervical polypoid mass, which was finally confirmed to be mature solid teratoma in uterine cervix. DIAGNOSES: Histological examination of the polypoid mass was found to consist of ciliated pseudostratified columnar respiratory epithelium, intestinal epithelium and smooth muscle tissue, adipose tissue and mature glial component, epidermis, and skin adnexa. Meanwhile, no history of abortion, dilatation, and curettage was present in this patient, so implantation of fetal tissue was excluded. Therefore, we make a diagnosis of uterine cervical mature teratoma. INTERVENTIONS: Tumorectomy was performed after discovering the cervical polypoid mass. OUTCOMES: The patient had been followed-up for next 3 months after surgery and no recurrence was documented until now. LESSONS: Though teratomas of the uterine cervix are extremely rare, more attention should be paid on this rare but possible tumor for appropriate treatment in these patients.

Squamous cell carcinoma malignant transformation in mature cystic teratoma of the ovary: a case report and review of the literature.

BACKGROUND: Mature cystic teratoma of the ovary is classified among the benign ovarian germ cell neoplasms, and its malignant transformation occurs very rarely (in about 2%). As a result of nonspecific signs and symptoms, preoperative diagnosis of theses malignancies is a challenge to clinicians, resulting in delayed diagnosis (in advanced stages) and poor outcomes. CASE PRESENTATION: We report the case of a 43-year-old Iranian woman with progressive distension of the abdomen and hypogastric pain, who was diagnosed with squamous cell carcinoma transformation in a mature cystic teratoma of the ovary confirmed by histopathology examination. Total abdominal hysterectomy, bilateral salpingooophorectomy, and comprehensive staging surgery were performed for the patient, and she was scheduled for chemotherapy after the surgery. She responded well to the treatment and is currently continuing her chemotherapy process. CONCLUSION: There are a great number of reports in the literature regarding mature cystic teratoma of the ovary transformation into malignancy, so these neoplasms must be considered as a possible differential diagnosis and should be evaluated in older individuals with abdominal pain and palpable mass, or those with considerable tumor diameter and raised serum tumor markers.

Gastric Teratoma in Children: A Report of Two Cases and Review of Literature.

ABSTRACT: Gastric teratomas are very rare tumours. They present with upper abdomen distension which can easily be confused with other common conditions with mass per abdomen in the paediatric age group. Surgical excision is curative for gastric teratomas. The diagnosis is confirmed by radiological evaluation followed by histopathological analysis of excised specimen. We are reporting two such cases of gastric teratomas who presented with complaints of upper abdomen distension. They were evaluated with radiological imaging and successfully managed by surgical excision.

Elevated chorionic gonadotropic hormone in transgenic mice induces parthenogenetic activation and ovarian teratomas.

Both male and female reproductive functions are impacted by altered gonadotrophin secretion and action, which may also influence the development of endocrine tumours. To ascertain if chronic hypersecretion of human chorionic gonadotropin (hCG) contributes to the development of gonadal tumours, double transgenic (TG) mice that overexpress hCGα- and ß-subunits were analysed. By the age of two months, ovarian tumours with characteristics of teratomas developed with 100% penetrance. Teratomas were also seen in wild-type ovaries orthotopically transplanted into TG mice, demonstrating an endocrine/paracrine mechanism for the hCG-induced ovarian tumorigenesis. Both in vitro and in vivo experiments showed oocyte parthenogenetic activation in TG females. In addition, ovaries showed reduced ovulatory gene expression, inhibited ERK1/2 phosphorylation, and impaired cumulus cell expansion. Hence, persistently high endocrine hCG activity causes parthenogenetic activation and development of ovarian teratomas, along with altered follicle development and impaired ERK1/2 signalling, offering a novel mechanism associated with the molecular pathogenesis of ovarian teratomas.

Clinical features and treatment options for pediatric adrenal incidentalomas: a retrospective single center study.

BACKGROUND: The aim of this study was to investigate the clinical features and treatment options for pediatric adrenal incidentalomas(AIs) to guide the diagnosis and treatment of these tumors. METHODS: The clinical data of AI patients admitted to our hospital between December 2016 and December 2022 were collected and retrospectively analyzed. All patients were divided into neonatal and nonneonatal groups according to their age at the time of the initial consultation. RESULTS: In the neonatal group, 13 patients were observed and followed up, and the masses completely disappeared in 8 patients and were significantly reduced in size in 5 patients compared with the previous findings. Four patients ultimately underwent surgery, and the postoperative pathological diagnosis was neuroblastoma in three patients and teratoma in one patient. In the nonneonatal group, there were 18 cases of benign tumors, including 9 cases of ganglioneuroma, 2 cases of adrenocortical adenoma, 2 cases of adrenal cyst, 2 cases of teratoma, 1 case of pheochromocytoma, 1 case of nerve sheath tumor, and 1 case of adrenal hemorrhage; and 20 cases of malignant tumors, including 10 cases of neuroblastoma, 9 cases of ganglioneuroblastoma, and 1 case of adrenocortical carcinoma. CONCLUSIONS: Neuroblastoma is the most common type of nonneonatal AI, and detailed laboratory investigations and imaging studies are recommended for aggressive evaluation and treatment in this population. The rate of spontaneous regression of AI is high in neonates, and close observation is feasible if the tumor is small, confined to the adrenal gland and has no distant metastasis.

A rare case of tumor-to-tumor metastasis from thymic carcinoma to an ovarian mature teratoma.

Metastasis from one neoplasm to another is referred to as tumor-to-tumor metastasis (TTM). TTM is rarely observed. Here, we present a patient with TTM from a thymic carcinoma to an ovarian mature teratoma. A 25-year-old woman, diagnosed with unresectable thymic carcinoma, presented with a cyst with a solid tumor component in her right ovary. Laparoscopic cystectomy of the right ovary revealed that the solid tumor was a distant metastasis of the thymic carcinoma in an ovarian mature teratoma. The possibility of malignant transformation of the ovarian mature teratoma was ruled out, enabling accurate staging of the thymic carcinoma. This case emphasizes the need for clinicians to consider TTM and the importance of pathological confirmation of TTM when investigating potential distant metastases.

Simultaneous spine extradural and intradural teratomas in a pediatric patient: A rare presentation with insights in the flawed migration of germ cells theory.

Spinal teratomas are infrequent lesions in the pediatric population. These lesions can be extradural, intradural or intramedullary. We present a case of an 8-month-old boy that was assessed for underdevelopment of motor milestones. The neurologic examination revealed hyporeflexia, decreased sensation and flaccid paraplegia. MRI of the spine revealed two simultaneous and independent lesions in the extradural and intradural compartment. A laminectomy was performed for the T4-T7 vertebrae with total resection of both lesions. The histopathological analysis confirmed both lesions to be mature cystic teratomas. At the 1-year follow-up, the patient remained with no recovery of neurological function. A debate takes place regarding the etiology of formation of these lesions in the spine. The simultaneous presentation of two independent lesions in this patient could contribute to define the flawed migration of germ cells theory as the etiology for formation of teratomatous lesions in the spine.

Astrocitoma de bajo grado en un teratoma retroperitoneal: reporte de caso / Low-grade astrocytoma within a retroperitoneal teratoma: Case report

Los teratomas son neoplasias que se originan de las células germinales, algunos pueden sufrir una transformación maligna. La Organización Mundial de la Salud (OMS) los clasificó como teratomas con malignidad de tipo somático, los cuales son poco comunes, siendo los sarcomas el tipo histológico con mayor incidencia. Es importante diferenciar esté tipo de tumores ya que influye en el pronóstico y en la supervivencia del paciente. A continuación se presenta el caso de un masculino de 5 meses de edad, que inició su padecimiento al mes de vida con la presencia de estreñimiento y aumento del perímetro abdominal, los estudios de imagen revelaron una lesión abdominal. Se inició tratamiento con quimioterapia y se realizó tumorectomía retroperitoneal. El reporte histopatológico reportó teratoma inmaduro grado I con foco de tejido nervioso que muestra características de astrocitoma de bajo grado. (AU)

Teratomas are neoplasms originate from germ cells and can undergo malignant transformation, the World Health Organization (WHO) classified them as teratoma with somatic-type malignancy which is uncommon and sarcomas are the histological type with the highest incidence. It is important to identify this type of tumors because influences the prognosis and survival of the patient. We present the case of a 5-month-old male, who began his condition at one month-old with constipation and increase of the abdominal circumference, imaging studies revealed an abdominal lesion, he was treated with chemotherapy and surgery. The histopathological report was immature teratoma, grade 1, with a focus of nervous tissue showing characteristics of low-grade astrocytoma. (AU)

A rare germline BMP15 missense mutation causes hereditary ovarian immature teratoma in human.

Ovarian immature teratomas (OITs) are malignant tumors originating from the ovarian germ cells that mainly occur during the first 30 y of a female's life. Early age of onset strongly suggests the presence of susceptibility gene mutations for the disease yet to be discovered. Whole exon sequencing was used to screen pathogenic mutations from pedigrees with OITs. A rare missense germline mutation (C262T) in the first exon of the BMP15 gene was identified. In silico calculation suggested that the mutation could impair the formation of mature peptides. In vitro experiments on cell lines confirmed that the mutation caused an 84.7% reduction in the secretion of mature BMP15. Clinical samples from OIT patients also showed a similar pattern of decrease in the BMP15 expression. In the transgenic mouse model, the spontaneous parthenogenetic activation significantly increased in oocytes carrying the T allele. Remarkably, a mouse carrying the T allele developed the phenotype of OIT. Oocyte-specific RNA sequencing revealed that abnormal activation of the H-Ras/MAPK pathway might contribute to the development of OIT. BMP15 was identified as a pathogenic gene for OIT which improved our understanding of the etiology of OIT and provided a potential biomarker for genetic screening of this disorder.

[Paraneoplastic Anti-N-methyl-D-aspartate Receptor Encephalitis Associated with Anterior Mediastinal Mature Teratoma].

We report a 27 years-old previously healthy male admitted to a psychiatric hospital because of abnormal behavior. He was suspected meningoencephalitis with fever, abnormal sweating, muscle tone, confusion, and introduced to the neurology department of our hospital. After admission, increasing convulsions and apnea attack required mechanical ventilation therapy. Anti-N-methyl-D-aspartate( NMDA) - receptor encephalitis was diagnosed based on positive (20-fold) anti-NMDA antibody in cerebrospinal fluid examination. An enhanced chest computed tomography (CT) showed a 43 mm cystic mass with calcification of the anterior mediastinum. He underwent the tumor resection under median sternotomy on the 18th hospital day. The plasmapheresis and steroid therapies were treated after the operation. The consciousness level gradually improved, the patient was withdrawn from the respirator on the post operative day( POD) 35, and transferred to a rehabilitation hospital on POD 60. The pathological result was mature teratoma. However, no specific findings such as inflammatory cell infiltration into nerve components were observed. Anti-NMDA receptor encephalitis was established by Dalmau in 2007 as encephalitis associated with ovarian teratoma. It presents mainly in young adult women with psychiatric symptoms, and requires mechanical ventilation management due to disturbance of consciousness, convulsions, and central hypoventilation in a short period of time. It presents severe symptoms in the acute phase and shows a unique clinical finding with a good prognosis even though it shows a protracted course. Treatment requires prompt tumor detection and early resection, as well as methylprednisolone (mPSL) pulse, plasmapheresis, and high-dose gamma globulin therapy. It is a neurological disease that requires emergency response, and the understanding and prompt response of related departments is important.

Astrocitoma de bajo grado en un teratoma retroperitoneal: reporte de caso / Low-grade astrocytoma within a retroperitoneal teratoma: Case report

Los teratomas son neoplasias que se originan de las células germinales, algunos pueden sufrir una transformación maligna. La Organización Mundial de la Salud (OMS) los clasificó como teratomas con malignidad de tipo somático, los cuales son poco comunes, siendo los sarcomas el tipo histológico con mayor incidencia. Es importante diferenciar esté tipo de tumores ya que influye en el pronóstico y en la supervivencia del paciente. A continuación se presenta el caso de un masculino de 5 meses de edad, que inició su padecimiento al mes de vida con la presencia de estreñimiento y aumento del perímetro abdominal, los estudios de imagen revelaron una lesión abdominal. Se inició tratamiento con quimioterapia y se realizó tumorectomía retroperitoneal. El reporte histopatológico reportó teratoma inmaduro grado I con foco de tejido nervioso que muestra características de astrocitoma de bajo grado. (AU)

Teratomas are neoplasms originate from germ cells and can undergo malignant transformation, the World Health Organization (WHO) classified them as teratoma with somatic-type malignancy which is uncommon and sarcomas are the histological type with the highest incidence. It is important to identify this type of tumors because influences the prognosis and survival of the patient. We present the case of a 5-month-old male, who began his condition at one month-old with constipation and increase of the abdominal circumference, imaging studies revealed an abdominal lesion, he was treated with chemotherapy and surgery. The histopathological report was immature teratoma, grade 1, with a focus of nervous tissue showing characteristics of low-grade astrocytoma. (AU)

MR diagnosis of SCC arising within ovarian cystic teratomas: analysis of mural nodule characteristics.

PURPOSE: This study aims to evaluate and identify magnetic resonance (MR) findings of mural nodules to detect squamous cell carcinoma arising from ovarian mature cystic teratoma (SCC-MCT). METHODS: This retrospective study examined 135 patients (SCC-MCTs, n = 12; and benign MCTs, n = 123) with confirmed diagnoses across five different institutions between January 2010 and June 2022. Preoperative MR images for each patient were independently assessed by two experienced radiologists and analyzed following previously reported findings (PRFs): age, tumor size, presence of mural nodules, size of mural nodule, and the angle between mural nodule and cyst wall (acute or obtuse). Furthermore, this study evaluated four mural nodule features-diffusion restriction, fat intensity, Palm tree appearance, and calcification-and the presence of transmural extension. RESULTS: There were significant differences between the SCC-MCT and benign MCT groups in terms of all PRFs and all mural nodule findings (p < 0.01). Among the PRFs, "tumor size" demonstrated the highest diagnostic performance, with a sensitivity of 83.3% and a specificity of 88.6%. A combination of the aforementioned four mural nodule findings showed a sensitivity and specificity of 83.3% and 97.6%, respectively, for the diagnosis of SCC-MCT. Regarding diagnosis based on a combination of four mural nodule findings, the specificity was significantly higher than the diagnosis based on tumor size (p = 0.021). Based on these mural nodule findings, three SCC-MCT patients without transmural invasion could be diagnosed. CONCLUSION: Mural nodule MR findings had a higher diagnostic performance than PRFs for SCC-MCT and can potentially allow early detection of SCC-MCTs.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy to Treat Pseudomyxoma Peritonei of Ovarian Origin: A Retrospective French RENAPE Group Study.

BACKGROUND: Ovarian pseudomyxoma peritonei (OPMP) are rare, without well-defined therapeutic guidelines. We aimed to evaluate cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat OPMP. METHODS: Patients from the French National Network for Rare Peritoneal Tumors (RENAPE) database with proven OPMP treated by CRS/HIPEC and with histologically normal appendix and digestive endoscopy were retrospectively included. Clinical and follow-up data were collected. Histopathological and immunohistochemical features were reviewed. RESULTS: Fifteen patients with a median age of 56 years were included. The median Peritoneal Cancer Index was 16. Following CRS, the completeness of cytoreduction (CC) score was CC-0 for 9/15 (60%) patients, CC-1 for 5/15 (33.3%) patients, and CC-2 for 1/15 (6.7%) patients. The median tumor size was 22.5 cm. After pathological review and immunohistochemical studies, tumors were classified as Group 1 (mucinous ovarian epithelial neoplasms) in 3/15 (20%) patients; Group 2 (mucinous neoplasm in ovarian teratoma) in 4/15 (26.7%) patients; Group 3 (mucinous neoplasm probably arising in ovarian teratoma) in 5/15 (33.3%) patients; and Group 4 (non-specific group) in 3/15 (20%) patients. Peritoneal lesions were OPMP pM1a/acellular, pM1b/grade 1 (hypocellular) and pM1b/grade 3 (signet-ring cells) in 13/15 (86.7%), 1/15 (6.7%) and 1/15 (6.7%) patients, respectively. Disease-free survival analysis showed a difference (p = 0.0463) between OPMP with teratoma/likely-teratoma origin (groups 2 and 3; 100% at 1, 5, and 10 years), and other groups (groups 1 and 4; 100%, 66.6%, and 50% at 1, 5, and 10 years, respectively). CONCLUSION: These results suggested that a primary therapeutic strategy using complete CRS/HIPEC for patients with OPMP led to favorable long-term outcomes.