Teratomatous Components Research Articles

Incidence and Pitfalls of Intratesticular Adipose Tissue Encountered in Orchiectomy Specimens.

Based on the eighth edition of the American Joint Committee on Cancer staging system, postpubertal germ cell tumors (GCT) and malignant sex cord-stromal tumors (SCST) of the testis invading hilar soft tissue are of pathologic stage pT2. Adipose tissue is typically used as an anatomical landmark by pathologists for determining hilar soft tissue invasion. Herein, we evaluated for the presence, location, and extent of intratesticular fat in a multi-institutional cohort of orchiectomies. Consecutive orchiectomies from 3 academic institutions were reviewed (n = 605), including both benign and malignant specimens. Intratesticular fat was identified by hematoxylin and eosin (H&E) evaluation in 11/605 (1.8%) orchiectomies, including the following diagnoses: mixed non-teratomatous GCT (n = 1), mixed GCT with a teratoma component (n = 2), pure teratoma (n = 2), Leydig cell hyperplasia (n = 1), regressed GCT (n = 1), hormone therapy effect (n = 1), atrophic changes (n = 1), fibrosis (n = 1), infarction (n = 1). Adipose tissue was located within the rete testis stroma (n = 2), just below the rete testis (n = 4), within nodules of Leydig hyperplasia between the seminiferous tubules (n = 1), or within the confines of testicular parenchyma (n = 4). Among the 4 specimens containing admixed neoplastic (teratomatous) fat, the extent of adipose tissue ranged from 3.0 to 11.0 mm (mean 6.8 mm). Among the 7 specimens with non-neoplastic adipose tissue within/near the rete, the extent ranged from 0.1 to 12.7 mm (mean 2.3 mm). Although uncommon, intratesticular fat can be found in orchiectomy specimens, which may represent a staging pitfall in GCT and SCST especially when located at the interface between the testicular parenchyma and hilum.

Síndrome de Teratoma Creciente como Masa Retroperitoneal: Reporte de Caso

Growing Teratoma Syndrome (GTS) is characterized by the enlargement of tumors during or after chemotherapy for nonseminomatous germ cell tumors accompanied by the normalization of previously elevated tumor marker levels and the presence of mature teratoma components upon histological examination. We present a case involving a 25-year-old male diagnosed with a Mixed Germ Cell Tumor. The patient underwent surgery and chemotherapy. However, a year later he was diagnosed with Growing Teratoma Syndrome (GTS) due to the presence of a retroperitoneal mass that failed to respond to a second regimen of chemotherapy.

Embryoid Bodies and Related Proliferations in Ovarian Germ Cell Tumors.

We investigated the frequency and associated pathology of embryoid bodies in ovarian tumors by evaluating neoplasms in which they are known to occur: 100 immature teratomas, 125 malignant mixed germ cell tumors, and 6 polyembryomas. Three immature teratomas contained a single relatively well-formed embryoid body, whereas these and 11 others showed foci we categorized as embryoid body remnants consisting of microscopic aggregates of embryonal or yolk sac-type epithelium associated with spaces consistent with yolk sac or amniotic cavity but lacking a classic embryoid body structure. Teratomas with these foci were all high grade. A well-formed embryoid body was found in only 1 malignant mixed tumor, but embryoid body remnants were present in 25%, invariably associated with foci of immature teratoma (100%) and often with yolk sac tumor (97%), embryonal carcinoma (35%), or both (32%). These foci usually took the form of round to oval aggregates, often well-circumscribed, for which the term "polyembryoma background" has been proposed. The polyembryomas were typically grossly hemorrhagic and occurred in patients from 9 to 43 years of age. The embryoid bodies in them generally grew in lobules within an edematous to occasionally myxoid stroma. Four tumors contained liver-like cells, 4 numerous glands likely recapitulating the allantois, 3 syncytiotrophoblast cells, 2 prominent cysts, and 2 striking vascular proliferations. This study indicates that (1) typical embryoid bodies are rare in immature teratomas but about 14% of them have embryoid body remnants. (2) Embryoid body remnants are seen in 25% of malignant mixed germ cell tumors with a teratomatous component and often proliferate to form yolk sac tumor and embryonal carcinoma. (3) Well-formed embryoid bodies growing in a confluent manner (polyembryoma) are rare, and minor foci of teratoma, yolk sac tumor, or embryonal carcinoma are almost always present, indicating that these are fundamentally malignant mixed germ cell tumors but the polyembryoma component is dominant and distinctive which, in our opinion, justifies its own nomenclature. (4) Embryoid bodies are not a feature of other germ cell tumors.

Neuroendocrine Lesions Arising From Mediastinal Teratoma-A Case Report and Literature Review.

Background. Neuroendocrine lesions arising from mediastinal teratomas are rare tumors with only small number of patients reported in literature. The behavior of these lesions appears to be different from traditional neuroendocrine neoplasms. A comprehensive review will be valuable for histologic assessment and treatment planning for similar cases. Case presentation. We present an example of a 57-year-old man who presented with cough. Subsequent work-up revealed an anterior mediastinal mass of 2.1 cm on computed tomography. The patient underwent robot-assisted thoracoscopic thymectomy. Histological examination revealed a mature cystic teratoma with a neuroendocrine component consisting of clusters of tumor cells with round to oval nuclei and a "salt-and-pepper" chromatin pattern. The tumor cells were immunoreactive to cytokeratin, synaptophysin, chromogranin, and INSM1, with a Ki-67 proliferative index of 4%. A histological diagnosis was mature teratoma with well-differentiated low-grade neuroendocrine tumor (carcinoid) was made. The patient was well and without disease after complete surgical excision at 10 months. Literature review. Literature reviewed yielded 13 examples of neuroendocrine lesions arising from mediastinal teratomas. No disease-related mortality was reported, even in lesions with high-grade neuroendocrine, carcinomatous, or immature teratomatous components. Conclusions. Surgical removal is the mainstay of treatment of these lesions, and the presence of a neuroendocrine component does not appear to negatively affect prognosis.

46, XX disorder of sexual development associated with mixed germ cell tumor of the prostate: a rare case report

BackgroundExtragonadal germ cell tumors originating from the prostate are exceptionally rare. To the best of our knowledge, there have been no reported cases of mixed germ cell tumors in individuals with 46 XX disorder of sex development. In this study, we conducted a comprehensive analysis using whole genome sequencing to investigate the clinicopathological and molecular genetic characteristics of a submitted case, with the objective of elucidating its underlying pathogenesis.Case presentationA 40-year-old male patient was diagnosed with a combination of 46, XX disorder of sex development and a primary prostate mixed germ cell tumor with yolk sac tumor and teratoma components. Whole-genome sequencing revealed that the tumor cells had a high somatic mutational load. Analysis of genomic structural variations and copy number variants confirmed the patient's karyotype as 46, XX (SRY +). Additionally, the patient exhibited short stature, small bilateral testes, slightly enlarged breasts, elevated serum alpha-fetoprotein concentrations, elevated follicle-stimulating hormone and luteinizing hormone levels, and low testosterone levels.DiscussionA case of 46, XX disorder of sex development, along with a primary prostatic mixed germ cell tumor, was diagnosed. This diagnosis has contributed to advancing our understanding of the genetic and phenotypic profile of the disease and may provide some insights for its treatment.

Identification of a panel of microRNA biomarkers for the management of patients with refractory germ cell tumor of the testis.

521 Background: In 1946, nearly 90% of patients diagnosed with metastatic Testicular Germ Cell Tumor (TGCT) succumbed to the disease within a year. In the present day, over 90% of such patients are successfully cured. However, there is a remaining 10% of patients have tumors that consist of chemotherapy-resistant forms of TGCT, such as yolk sac tumors and teratomas. This underlines the need for developing biomarkers that can guide the choice between additional chemotherapy and surgical intervention. MicroRNAs (miRNAs), non-coding RNA molecules that control post-transcriptional modifications, have shown promise in identifying TGCTs. Research has particularly highlighted the overexpression of miR-371a-3p and miR-375-3p in TGCTs. Nevertheless, these miRNAs are not effective in distinguishing between teratomas and other TGCT types. The Cancer Genome Atlas (TCGA), a publicly accessible database, offers clinical and miRNA data on various tumors, including TGCTs. Our objective is to leverage TCGA to identify miRNAs that can be used to classify TGCTs containing teratomas from those that do not. Methods: Between 2001 and 2013, TCGA gathered a total of 135 primary TGCT samples. We group these tumors into those without teratomas and those with any teratomatous components. We used EdgeR, a Bioconductor package designed for differential expression analysis of RNA that accounts for both biological and technical variation. A false discovery rate of less than 1e-8 was applied. A heatmap was generated to display the hierarchical clustering of differentially expressed miRNAs. Results: Based on the above cut-off, a panel of 50 miRNAs of differentially expressed miRNA were used to generate a hierarchical clustering that showed clear clustering between the two groups. Notably, tumor suppressor miRNAs such as hsa-mir-203a, hsa-mir-199, and hsa-mir-152, which are usually downregulated in non-teratoma TCGT, are overexpressed in teratomas. Other miRNA including hsa-mir-146a and hsa-mir-3607, which are downregulated tumor suppressors for non-TCGT are also downregulated in teratomas but not in teratoma-free TGCT. Conclusions: Despite the high cure rate for TGCTs, tumors containing chemotherapy-resistant teratomas still contribute to elevated mortality rates. Utilizing TCGA data, we identified a set of miRNAs that are effective in distinguishing between teratoma-containing and teratoma-free TGCTs. This miRNA panel has the potential to inform decisions related to surgical treatment plans and provide further insight into the biology of the disease.

Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma.

Sinonasal teratocarcinosarcoma (TCS) is a rare tumor that displays a variable histology with admixtures of epithelial, mesenchymal, neuroendocrine and germ cell elements. Facing a very poor prognosis, patients with TCS are in need of new options for treatment. Recently identified recurrent mutations in SMARCA4 may serve as target for modern therapies with EZH1/2 and CDK4/6 inhibitors. Here, we present the first in vitro cell line TCS627, established from a previously untreated primary TCS originating in the ethmoid sinus with invasion into the brain. The cultured cells expressed immunohistochemical markers, indicating differentiation of epithelial, neuroepithelial, sarcomatous and teratomatous components. Whole-exome sequencing revealed 99 somatic mutations including SMARCA4, ARID2, TET2, CDKN2A, WNT7A, NOTCH3 and STAG2, all present both in the primary tumor and in the cell line. Focusing on mutated SMARCA4 as the therapeutic target, growth inhibition assays showed a strong response to the CDK4/6 inhibitor palbociclib, but much less to the EZH1/2 inhibitor valemetostat. In conclusion, cell line TCS627 carries both histologic and genetic features characteristic of TCS and is a valuable model for both basic research and preclinical testing of new therapeutic options for treatment of TCS patients.

Endocrine tumors of the female reproductive tract

Endocrine cells responsible for hormone secretion are found in virtually every organ system. The diverse neoplasms arising from endocrine cells in the female reproductive tract are not well recognized as a distinct component of endocrine oncology. Here, we integrate cellular origins with native anatomical residence to help classify neoplasms of this system. The neoplasms include steroidogenic tumors that arise usually in ovarian stroma, neuroendocrine neoplasms that can arise from normal neuroendocrine cells throughout the female reproductive tract or in ovarian germ cell tumors, and thyroid follicular cell proliferations that are exclusively a component of an ovarian teratoma and may be malignant. The neuroendocrine neoplasms run the full spectrum from indolent neuroendocrine tumors to aggressive poorly differentiated neuroendocrine carcinomas. While many of these lesions are identified as incidental findings in surgically resected tissues, others present with inappropriate hormone excess. An important consideration is the distinction of primary disease from metastatic malignancy. Genetic disorders including those caused by germline mutations of the FOXL2, GNAS, DICER1, STK11 and MEN1 genes can present with primary endocrine neoplasms of the female reproductive tract.

Treatment Course and Outcomes of Intracranial Teratomas in Pediatric Patients: A Retrospective 15-Year Case Series Study

Introduction: There is no standard treatment paradigm for intracranial teratomas, a rare subset of primary intracranial non-germinomatous germ cell tumors (NGGCT), which comprise less than 1% of pediatric brain tumors. This case series retrospectively analyzes treatment and outcomes of pediatric intracranial teratomas from a single institution. Methods: Authors reviewed a comprehensive pathology database at Stanford’s Lucile Packard Children’s Hospital for intracranial teratomas in pediatric patients treated from 2006 to 2021; their demographics, treatment, and clinical course were analyzed. Results: Among 14 patients, median follow-up time was 4.6 years and mean age at diagnosis was 10.5 years. Ten had elevated tumor markers and underwent chemotherapy as initial treatment for NGGCT. Ultimately, these patients all required surgery for progressive or residual disease. Two patients did not undergo radiation. After biopsy or resection, 8 patients had pure mature teratoma, five had mixed germ cell tumor with teratoma component, and one had immature teratoma. The patient with immature teratoma died during chemotherapy from septic shock. No patients experienced recurrence. Common sequelae were endocrine (42.8%) and eye movement (50.0%) abnormalities. Discussion/Conclusion: We highlight the variable treatment course and outcome for pediatric patients with intracranial teratomas. Elevated tumor markers at presentation, along with imaging findings, favor chemotherapy initiation for presumed NGGCT. Resection of residual tumor is recommended even if tumor markers return to normal. Prognosis remains excellent; no patients had recurrence with a median follow-up of 4.6 years.

Non-invasive differential diagnosis of teratomas from other intracranial germ cell tumours using MRI-based fractal and radiomic analyses.

The histologic subtype of intracranial germ cell tumours (IGCTs) is an important factor in deciding the treatment strategy, especially for teratomas. In this study, we aimed to non-invasively diagnose teratomas based on fractal and radiomic features. This retrospective study included 330 IGCT patients, including a discovery set (n = 296) and an independent validation set (n = 34). Fractal and radiomic features were extracted from T1-weighted, T2-weighted, and post-contrast T1-weighted images. Five classifiers, including logistic regression, random forests, support vector machines, K-nearest neighbours, and XGBoost, were compared for our task. Based on the optimal classifier, we compared the performance of clinical, fractal, and radiomic models and the model combining these features in predicting teratomas. Among the diagnostic models, the fractal and radiomic models performed better than the clinical model. The final model that combined all the features showed the best performance, with an area under the curve, precision, sensitivity, and specificity of 0.946 [95% confidence interval (CI): 0.882-0.994], 95.65% (95% CI: 88.64-100%), 88.00% (95% CI: 77.78-96.36%), and 91.67% (95% CI: 78.26-100%), respectively, in the test set of the discovery set, and 0.944 (95% CI: 0.855-1.000), 85.71% (95% CI: 68.18-100%), 94.74% (95% CI: 83.33-100%), and 80.00% (95% CI: 58.33-100%), respectively, in the independent validation set. SHapley Additive exPlanations indicated that two fractal features, two radiomic features, and age were the top five features highly associated with the presence of teratomas. The predictive model including image and clinical features could help guide treatment strategies for IGCTs. Our machine learning model including image and clinical features can non-invasively predict teratoma components, which could help guide treatment strategies for intracranial germ cell tumours (IGCT). • Fractals and radiomics can quantitatively evaluate imaging characteristics of intracranial germ cell tumours. • Model combing imaging and clinical features had the best predictive performance. • The diagnostic model could guide treatment strategies for intracranial germ cell tumours.

Improved Management of the Advanced Nonseminomatous Testis Cancer

With the VAB-6 program about 90% (54/59) of patients with stage III and bulky stage II disease achieved complete remission and eighty percent remain free of disease. Patients with minimal metastatic disease can usually be treated successfully with chemotherapy alone, while patients with advanced disease frequently required combined treatment with chemotherapy and surgery in order to achieve complete remission. Most patients without a teratomatous component in the testis tumor will achieve complete remission with chemotherapy alone, whereas patients with a teratomatous componente are more likely to require the combined approach of chemotherapy and surgery to achieve disease free status. Pure seminoma was apparently the most responsive and pure choriocarcinoma the least responsive histologic type of testis tumor to the combination chemotherapy. The incidence of a residual mature teratoma in the resected specimem has increased with the improved efficacy of chemotherapy. High complete remission rates and a short duration of treatment ensure rapid return of afflicted individuals to productive life, thus, fulfilling a most importante goal of treatment.

Fortuitously detected primary ovarian carcinoid tumor: A case report.

Carcinoid tumors, derived from the cells of the disseminated neuroendocrine system, are rare, slow-growing neuroendocrine neoplasms that display a relatively indolent disease course. The majority of carcinoids are found within the gastrointestinal tract and bronchopulmonary system. Primary ovarian carcinoids are rare and account for merely 1% of all carcinoid tumors. We describe our experience of a rare case of primary ovarian carcinoid, presenting as chronic constipation, with no other carcinoid symptoms such as flushing, diarrhea, and wheezing. A 51-year-old postmenopausal woman with chronic constipation visited the clinic for routine check-up of her preexisting uterine fibroids. She had undergone hemorrhoidectomy 3 years ago. Physical examination revealed a soft abdomen without direct or rebound tenderness. Transvaginal ultrasonography revealed two subserosal fibroids, which had increased in size compared with previous ultrasonographic findings. A 3 cm hyperechoic mass was also detected in the right ovary. Her blood and urine tests were unremarkable, with no ascites in the pelvic cavity. She had a normal CA-125 level of 5.5 units/mL. The patient underwent a robot-assisted hysterectomy and right salpingo-oophorectomy because of enlarging fibroids and the right ovarian mass. Subsequently, based on the pathological and immunohistochemical findings, she was diagnosed with a primary ovarian carcinoid. The mass consisted of the insular and trabecular types of tumor cells. It was positive for pan-cytokeratin and synaptophysin, and the Ki-67 proliferation index was less than 1%. A follow-up positron emission tomography-computed tomography revealed no distant metastasis. Six months postoperatively, the patient was doing well without any signs of recurrence. Primary ovarian carcinoids without teratoma components are rare. It is crucial to make an accurate diagnosis based on the immunohistochemical staining results. Diagnosis in the early stages of the disease are associated with a favorable prognosis, but regular follow-up is mandatory.

Malignant Teratoma Arising From Mediastinal Non-Seminomatous Germ Cell Tumor: A Rare Case Report

Introduction: Primary mediastinal non-seminomatous germ cell tumors (NSGCT) have a worse prognosis than gonadal germ cell tumors (GCTs). Malignant transformation of teratomatous components of GCT to a somatic malignancy is rare.
 Materials and methods: A case of primary mediastinal NSGCT with malignant transformation of a teratoma was seen in a 23 years old male. Resected tumor specimen was received. Tissue processing was done and sections were prepared for Histo Pathological Examination.
 Results: Histopathology confirmed NSGCT with yolk sac and teratomatous components. Chemotherapy for GCT transiently normalized serum tumor markers with little effect on the mediastinal mass. Incomplete resection of the residual tumor revealed intermediate grade chondosarcoma. Here we discuss this rare case.
 Conclusion: malignant transformation to chondrosarcoma is a rare possibility which needs to be considered while managing the patient of Primary Mediastinal Germ Cell Tumors (PMGCT)

Abstract #1398490: The Enigma of Malignant Struma Ovarii

Struma ovarii is a rare form of ovarian germ cell tumor with at least 50% of mature thyroid tissue. Most of them are benign with malignant transformation occurring in only < 5% of tumors. Malignant struma ovarii presenting with follicular-type carcinoma is extremely rare. We present an interesting case of malignant struma ovarii with follicular carcinoma. 66-year-old female was referred with a diagnosis of malignant struma ovarii. She was previously evaluated at emergency room when she presented with right lower quadrant abdominal pain. CT scan done at that time revealed 6.5 cm right adnexal lesion which increased from 3.9 cm from 13 years ago. She subsequently underwent total abdominal hysterectomy with bilateral salpingo-oopherectomy with pathology showing 10.5 cm poorly differentiated follicular thyroid carcinoma with in struma ovarii component of an ovarian teratoma. There was capsular and focal angioinvasion. PET/CT done later was negative for malignancy and the thyroid ultrasound showed no thyroid nodules or neck adenopathy. Laboratory examination revealed TSH and free T4 levels within normal range. She underwent total thyroidectomy and then underwent recombinant human thyrotropin stimulated radioactive iodine treatment with 150 mCi of I-131. Post therapy whole body scan showed increased radiotracer activity in the left pelvic region for which additional SPECT-CT was performed which confirmed that the increased radiotracer activity along the anterior aspect of the left superior iliac bone was misregistered bowel and there was no destructive osseous lesion involving the left iliac bone on the corresponding CT. There is no other evidence of focal iodide activity to suggest extra-thyroidal disease. She is being continued on levothyroxine 100 mcg. Post treatment stimulated thyroglobulin levels were 0.7 ng/mL with negative thyroglobulin antibodies. Because of its rarity and absence of consensus on diagnosis and treatment, there are no established guidelines for management of malignant struma ovarii. The decision to perform thyroidectomy and administer radioiodine after oophorectomy are based on the reports from case series and depends on the presence of metastatic disease and the risk of recurrence. In our patient, large size of the tumor and presence of poorly differentiated follicular carcinoma indicated higher risk of recurrence warranting total thyroidectomy and radioiodine treatment. As she had good treatment response, goal of levothyroxine therapy is to maintain between 0.1-0.5 mU/L. Monitoring of serum stimulated thyroglobulin annually is recommended for 2 years after surgery and, if negative, unstimulated levels annually thereafter.

71P Survival outcomes of patients with recurrent malignant ovarian germ cell tumors: A retrospective analysis from a tertiary cancer center

Treatment of recurrent malignant ovarian germ cell tumors (MOGCT) are complex and challenging. There is limited data on outomes of these patientsafter salvage therapy in real world setting. This is a retrospective study of all patients diagnosed with recurrent MOGCT at our center between 2013-2017. Out of 43 patients 12 patients were excluded as they have not followed up after first visit. Clinico-pathological and treatment details of 31 patients were extracted from electronic medical records and were included in the analysis. Table: 71PVARIABLEPATIENTS (%)STAGE AT BASELINEIAICIII/IVUnknown11 (35%)5 (16%)5/3 (16%/9%)7 (22%)HISTOLOGYDysgerminomaYolk sacTeratomaMixed GCT8 (26%)6 (19%)10 (32%)7 (22%)ADEQUACY OF TREATMENT AT BASELINEAdequateInadequateMissing22 (71%)8 (26%)1 (3%)SITES OF RECURRENCEPeritoneum+ pelvis-20 (65%)Lymph node- 8 (25%)Liver+ lung- 3 (9%) Open table in a new tab Baseline characteristics initial stage, adequacy of treatment, sites of recurrence and treatment were in tabular form. Salvage chemotherapy was given in all patients. Ten (33%) patients who were inadequately treated upfront at outside recieved BEP/ EP as salvage regimen in our centre. Other regimens used were VeIP 8 (25%), TIP 6 (19%) and VIP 4 (13%) Others 3 (10%). After salvage chemotherapy 19 (61%) patients underwent second surgery, R0 resection was achieved in 13 (42%) patients. After median follow up of 66 months, 21 patients were alive (18-with no disease, and 3 were alive with stable teratoma component) after salvage therapy, and 10 patients were dead. Out of 13 patients with yolk sac histology (Pure yolk sac -6; Mixed GCT-7) only 6 could be salvaged. Those who could not be salvaged had effusions or extensive liver disease. Two patients out of 8 reccurent dysgerminoma had bulky multi station lymph nodal relapse could not be salvaged. The median PFS was after relapse was 26 months and median OS was 33 months post relapse. Adequate treatment at initial diagnosis is of paramount importance along with active surveillance to minimize default rates especially in low middle-Income countries. 67% of our recurrent cases were effectively salvaged. If managed at experienced centres with multidisciplinary approach using salvage chemotherapy and surgery, majority of recurrences can result in long term cure.

Non-choriocarcinomatous trophoblastic tumors of testis in postchemotherapy retroperitoneal lymph node dissections.

Non-choriocarcinomatous trophoblastic tumors (NCTTs) are seldomly diagnosed in male genital tract. As they have been recently described among the testicular germ cell tumor (TGCT) variants, pathologists' familiarity with their morphology is limited. We searched our electronic hospital records covering the years 2000-2017 for post-chemotherapy retroperitoneal TGCT metastectomies. Slides of all cases with viable tumor were retrieved from the archives and reviewed. Cases suspected of N-CTT morphologies were subjected to immunohistochemistry. Twelve NCTTs were identified, 9 of which were unseen or misdiagnosed by the original pathologists: Cystic trophoblastic tumor (CTT) (n = 5), placental site trophoblastic tumor (n = 2), epithelioid trophoblastic tumor (ETT) (n = 4), and coinciding PSTT + ETT (n = 1). Eight of these were associated with mature teratoma components, and one case (ETT) contained embryonal carcinoma and yolk sac tumor in addition to teratoma. Ten patients were clinically N1 at the time of primary tumor detection and orchiectomy. One patient had burned-out primary testicular tumor. Six patients were clinical M1a at presentation, while one male was cM1b. Six patients had mildly elevated β-HCG (≤ 410 mIU/ml) just prior to retroperitoneal lymph node dissections (RPLND), while the others had normal β-HCG levels. All patients had follow-ups ranging from 8 to 118months (mean 42.3months). Three patients died of disease-related and two of unrelated causes. In conclusion, because NCTTs are rare and newly described tumor types, their diagnosis is difficult and most of them are missed in post-chemotherapy RPLNDs. The majority of patients exhibit normal or slightly elevated β-HCG levels. N-CTTs are usually accompanied by other components of TGCT, the most common being teratoma. Despite the high survival rate of the patients, our study points to the unpredictable evolution of NCTT cases, which may concur with a high-stage or progressive disease.

Atypical cartilage in type II germ cell tumors of the mediastinum show significantly different patterns of IDH1/2 mutations from conventional chondrosarcoma

AbstractNeoplastic cartilage is a common component of teratomas in type II germ cell tumors. Although IDH1/2 mutations have been well-described in somatic cartilaginous tumors, ranging from benign enchondromas to highly aggressive dedifferentiated chondrosarcomas, the presence of IDH1/2 mutations in cartilaginous neoplasms arising from germ cell tumors has not been previously investigated. To better understand the relationship between these tumors and their bone/soft tissue counterpart, we studied the IDH1/2 mutational status of 20 cases of primary mediastinal mixed germ cell tumors with areas of readily identifiable cartilaginous differentiation. Our study found that cartilaginous lesions arising in germ cell tumors have a different frequency and distribution of IDH1/2 mutations compared to those at somatic sites. We identified IDH1/2 mutations in only 15% (3/20) of cases, compared to a frequency in the literature among differentiated chondroid tumors of bone and soft tissue of 54%, a highly significant decreased frequency (p = 0.0011; chi-square test). Furthermore, they were exclusively IDH2 R172 mutations that occurred at a non-significant, increased frequency in the germ cell tumor group compared to conventional chondrosarcoma (15% vs. 5%, respectively, p > 0.05, chi-square test). The unexpected finding, therefore, was entirely attributable to the absence of IDH1 R132 mutation in chondroid neoplasia of germ cell origin (p < 0.00001, Fisher exact test). Our results suggest that a subset of cartilaginous lesions arising within type II germ cell tumors have a similar oncogenic mechanism to their bone/soft tissue counterpart but that the majority form using different oncogenic mechanisms compared to their somatic counterparts.

Long-term consequences of residual lesions after chemoradiotherapy in patients with germinoma at onset.

In patients with intracranial germ cell tumors, residual lesions are sometimes observed after completion of primary chemoradiotherapy. Although salvage resection of these end-of-treatment residual lesions is recommended for patients with nongerminomatous germ cell tumors, the necessity of early salvage resection for those with germinoma is not clear. The aim of this study was to investigate the frequency of residual germinoma lesions after primary chemoradiotherapy, as well as their management, long-term consequences, and prognosis. The authors retrospectively reviewed patients who were primarily treated for germinoma between 2002 and 2021. Residual lesions were evaluated with MRI with and without contrast enhancement within 2 weeks after chemoradiotherapy. The decision to perform salvage resection of residual lesions was at the discretion of the treating physicians. The change in appearance of residual lesions was assessed with serial MRI. Overall survival (OS), progression-free survival (PFS), and recurrence pattern were also investigated. Sixty-nine patients were treated with chemoradiotherapy for germinoma, with a mean follow-up period of 108 months. Residual lesions were radiologically observed in 30 patients (43.5%). Among these, 5 patients (3 with pineal lesions and 2 with basal ganglia lesions) underwent salvage resection. Pathological examination revealed teratomatous components in 3 patients, whereas no tumoral components were identified in 2 patients. One patient with a basal ganglia lesion showed worsening of hemiparesis postoperatively. The remaining 25 patients received watchful observation without surgical intervention. Chronological periodic radiological change in residual lesions was evaluated in 21 patients. One year after primary treatment, the size of the residual lesions was stable and had decreased in 10 and 11 patients, respectively. None of the lesions increased in size. The 10-year PFS and OS rates were 96.7% and 97.3% in patients without residual lesions (n = 39), and 87.1% and 100% in patients with residual lesions (n = 30), respectively. Presence of residual lesions had no significant effect on PFS or OS. All recurrences occurred at distant sites or via dissemination without progression of the primary tumor site, regardless of the presence of residual lesion. End-of-treatment residual lesions are not rare in patients with germinoma, and these residual lesions seldom show progression. Because of the potential risk of surgical complications, the indication for early salvage surgery for residual lesions should be carefully determined. Watchful observation is recommended for the majority of these cases.

Genetic diagnosis of pseudomyxoma peritonei originating from mucinous borderline tumor inside an ovarian teratoma

BackgroundPseudomyxoma peritonei is a rare disease condition mainly caused by primary mucinous tumors from the appendix and rarely from the ovary, such as when mucinous ovarian tumors arise from within a teratoma. Molecular analyses of pseudomyxoma from the appendix showed that KRAS and GNAS pathogenic variants are common genetic features of pseudomyxoma peritonei. However, the origin of the tumors is difficult to be identified via genetic variants alone. This study presents a case of pseudomyxoma peritonei of ovarian origin, which was diagnosed by comprehensive genomic profiling with ploidy analysis in a series of primary, recurrent, and autopsy tumor specimens.Case presentationA 40-year-old woman was diagnosed with Stage IC2 mucinous ovarian tumor of borderline malignancy with mature cystic teratoma, upon clinical pathology. Immunohistochemical analysis suggested that the mucinous tumor was derived from the intestinal component of an ovarian teratoma. Three years later, intraperitoneal recurrence was detected, which subsequently progressed to pseudomyxoma peritonei. Genomic analysis detected KRAS (G12D), GNAS (R201C), and FBXW7 (R367*) variants in the primary tumor. In addition, the tumor showed aneuploidy with loss of heterozygosity (LOH) in all its chromosomes, which suggested that the primary ovarian tumor was derived from germ cells. Existence of one Barr body suggested the existence of uniparental disomy of the tumors throughout the genome, instead of a haploid genotype. All three pathogenic variants remained positive in the initial recurrent tumor, as well as in the paired DNA from the whole blood in pseudomyxoma peritonei. The pathogenic variant of KRAS (G12D) was also identified in the autopsy specimen of the appendix by droplet digital polymerase chain reaction.ConclusionsThis study pathologically and genetically confirmed that the primary ovarian borderline tumor was derived from the intestinal component of an ovarian teratoma, and that the subsequent pseudomyxoma peritonei progressed from the primary ovarian tumor. Integrative genomic analysis was useful to identify cellular origin of tumors, as well as to precisely interpret the process of disease progression.

Mediastinal germ cell tumors: a narrative review of their traits and aggressiveness features.

Mediastinal extragonadal germ-cell tumors (MEGCTs) are rare neoplasms with a multifaceted clinical behavior. This paper is devoted to review their main characteristics, including histological patterns and different factors of aggressiveness in MEGCTs. Proper understanding of the latter can help to better stratify patients' prognoses and improve clinical management. Different theories exist on the origin of MEGCTs, including primordial germ cells deposition during embryogenesis. MEGCTs predominantly affects young males and aggressiveness follows the ability of local and systemic spread of each germ-cell neoplasia subtype, as well as their distinct responsiveness to therapy. Indeed, non-seminomatous MEGCTs have a worse prognosis. Unfortunately, they are also more frequent than seminomas in the mediastinum. Regardless of histological type, local aggressiveness can follow tumoral expansion with compression on or infiltration of mediastinal structures. Chemotherapy can be effective in reducing neoplastic volume, but different levels of sensitivity can be found in different MGCTs. In particular, a chemo-resistant teratoma component of a mixed MEGCTs can undergo a paradoxical enlargement after chemotherapy, while other components of the tumor regress. This is reflected by a concomitant normalization of serum tumoral markers and cardiopulmonary deterioration due to compression. Such clinical phenomenon, called growing-teratoma syndrome (GTS), requires a prompt surgical approach. A literature research of pertinent epidemiological, pathological and clinical articles was conducted. The mediastinum can harbor different kinds of neoplasia, including GCTs. The full spectrum of MEGCTs includes a variety of tumors with different clinical behaviors. Aggressiveness follows the inherent ability of local and systemic spread of each neoplastic type, as well as their distinct responsiveness to therapy.