Paraneoplastic neuromyelitis optica spectrum disorder associated with ovarian dysgerminoma: a case report and literature review.

Neuromyelitis optica spectrum disorder (NMOSD) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. We report a case with paraneoplastic NMOSD that improved after immunosuppressive therapy, surgical resection, and chemotherapy. A 48-year-old woman initially presented with gradual binocular visual loss over the course of one week. The patient was evaluated using magnetic resonance imaging (MRI), computed tomography (CT), visual evoked potential (VEP), pathological biopsy, immunohistochemistry, and autoimmune antibody testing. The brain MRI findings were normal. The VEP revealed prolonged P100 latencies in the right eye and an absence of significant waves in the left eye. Positive serum AQP4-IgG antibodies were found. The patient was diagnosed as NMOSD. Then the patient responded well to treatment with methylprednisolone. An ovarian tumor was found in the patient using abdominal MRI and CT. The tumor was surgically resected, and a pathological biopsy revealed that it was ovarian dysgerminoma. The patient received four rounds of chemotherapy after surgery. One month after the final chemotherapy treatment, a positron emission tomography (PET) scan revealed no tumor. The vision of the patient gradually recovered and serum AQP4 was negative. Furthermore, we summarized the characteristics of patients diagnosed with paraneoplastic NMOSD associated with ovarian neoplasms in previous studies. This is a characteristic case of overlapping NMOSD and ovarian dysgerminoma, demonstrating the importance of tumor therapy in cases of paraneoplastic NMOSD.

SRY-positive 45,X/46,XY karyotype in a phenotypically Turner-like Chinese adolescent female with ovarian dysgerminoma and gonadoblastoma.

OBJECTIVES: 45,X/46,XY mosaicism is a rare condition with clinical and genetic heterogeneity and have a greatly increased risk of developing germ cell tumors. We describe a rare 45,X/46,XY Chinese girl with malignant tumors, especially focusing on the molecular genetics of gonadal tumor. CASE PRESENTATION: We report a phenotypically Turner-like Chinese adolescent girl who presented primary amenorrhea and a pelvic mass as the chief complaint, which finally demonstrated dysgerminoma replacing the left gonad and gonadoblastoma arising from right gonad respectively. Her chromosome karyotype was 45,X(4)/46,XY(46); Y-chromosome microdeletions in AZFb regions were found on gonadal DNA rather than peripheral blood lymphocyte (PBL) DNA, while no variants were found in the promoter and coding region of SRY gene in both PBL and gonadal tissues. She underwent bilateral gonadectomy; no recurrence or serious complications were identified after 3 years of follow-up. CONCLUSIONS: This case emphasizes the probable correlation between Y chromosome microdeletions in gonadal tissue and the severity of the phenotype in patients with 45,X/46,XY mosaicism and highlights the importance of clinical genetic testing at the chromosomal and molecular level.

Dysgerminoma Probably Due to a Novel SOHLH1-pathogenic Variant Causing Familial Ovarian Dysgenesis.

Pathogenic variants of the SOHLH1 gene are responsible for an autosomal recessive form of ovarian dysgenesis; this gene encodes a transcription factor expressed early in spermatogonia and oocytes and contributes to folliculogenesis. Previously, four affected women from two unrelated families reported homozygous variants in the SOHLH1 gene, but none had a history of gonadal malignancy or a histologic description. We present two sisters and their paternal great-aunt with a history of primary amenorrhea, pubertal delay, and hypergonadotrophism who came from an inbred Mexican family. The proband was the younger sister who was referred for bilateral dysgerminoma. She had a normal blood karyotype, and whole-exome sequencing analysis revealed a novel homozygous missense variant, c.275C>T, in SOHLH1; several family members were also analyzed. In addition to pure dysgerminoma, histopathological analysis revealed an ovarian cortex with fibrosis and almost total absence of follicles. This work confirms the inheritance of ovarian dysgenesis 5, supports the occurrence of cell loss in mouse models, and suggests that affected women should undergo periodic imaging surveillance due to the likely risk of tumor development.

Study of neoadjuvant chemotherapy in advanced malignant ovarian germ cell tumors at a tertiary center in western India.

OBJECTIVE: To study clinical characters and outcomes in patients of malignant ovarian germ cell tumor (MOGCT) undergoing surgery following neoadjuvant chemotherapy (NACT). METHODS: Retrospective study of patients undergoing surgery following NACT for MOGCT at our institute. Platinum based chemotherapy was given in all patients in NACT. RESULTS: Between March 2013 and February 2023, 30 patients had surgery after NACT. Patient's median age was 22 years (range, 12 to 35 years) and median follow up 42months (range, 6 to 132 months). Majority had endodermal sinus tumor (n=12), dysgerminoma (n=9) and mixed GCT (n=7). All had either International Federation of Gynecology and Obstetrics (FIGO) stage 3 (n=19) or FIGO stage 4 disease (n=11). Complete response to NACT seen in 5 patients and 23 patients had partial response. Fertility sparing surgery in 18 patients and complete surgery in 12 patients. Suboptimal surgery was seen in 4 patients. Currently, 20 of 30 patients are alive and disease free, 3 lost for follow up and 7 patients had progression after adjuvant therapy. Five patients had mortality-4 with progression and 1 with bleomycin toxicity. Fifteen of 17 eligible patients have resumed menstruation and one had successful pregnancy. Prognostic factors noted in study are stage, optimal surgery and viable tumor in histopathology. Dysgerminoma had better outcome than other histology. CONCLUSION: NACT may be a reasonable option in patients with extensive unresectable disease or in whom fertility sparing is not possible or in the poor general condition. Fertility sparing surgery can be attempted post neoadjuvant chemotherapy without adversely affecting prognosis.

Prevalence, distribution, and risk markers for the development of gonadal germ cell tumors in patients with certain types of disorders of sexual differentiation with Y chromosome - A retrospective study.

PURPOSE: To study the prevalence, subtypes, and risk markers for the development of gonadal germ cell tumors (GCT's) among disorders of sexual differentiation (DSD) patients with the Y chromosome. MATERIALS AND METHOD: Design: A retrospective review of the patient's case records from 2010 to 2020 in Government Medical College, Thiruvananthapuram, India was studied. The study participants included 54 subjects with DSD containing the Y chromosome. Demographic data, external masculinization scoring, associated congenital anomalies, karyotyping, intraoperative findings such as gonadal location and internal genital ducts, histopathology of the resected gonads, and its immunohistochemistry were collected. The prevalence of gonadal GCT's was estimated from paraffin-embedded gonadectomy samples (S = 82). RESULTS: The median age of occurrence of gonadal GCT's was 18 years. The prevalence of malignant gonadal GCT's was highest among the PAIS group (19.2%) followed by gonadal dysgenesis (15.8% each in MGD and CGD) and least among CAIS (7.7%) (p < 0.01). The most common type of malignant gonadal GCT's in the descending order of frequency was dysgerminoma, seminoma, mixed GCT, and yolk sac tumor. Multivariance logistic analysis showed post-puberty and the presence of congenital anomalies were associated with the occurrence of gonadal GCT's ( P < 0.01). CONCLUSION: The overall prevalence of gonadal GCT's (malignant and premalignant) among DSD with Y chromosomes is nearly 25%. Dysgerminoma is the most common malignant gonadal GCT's. Age at or above 18 years and the presence of congenital anomalies like renal agenesis, retroperitoneal vascular defects, and congenital diaphragmatic hernia were independent risk markers for the development of gonadal GCT's.

A Perplexing Case of a Germ Cell Tumor: A Case Report.

Germ cell tumors (GCTs) are associated with pure gonadal dysgenesis or Swyer syndrome. Swyer syndrome usually presents with primary amenorrhea, streak ovaries, and mixed GCT. However, our patient presented with secondary amenorrhea, normal female external genitalia, and a mixed GCT. Constitutional karyotype was suggestive of 46,XY. Management comprised chemotherapy, followed by surgery. Histopathology was suggestive of dysgerminoma complicating a gonadoblastoma. The purpose of reporting this case is its rarity and the importance of diagnosing an XY karyotype, as the incidence of GCTs is higher in these patients.

Clinical and ultrasonographic findings of ovarian tumours in bitches: A retrospective study.

A retrospective study was carried out to investigate incidence, clinical signs and ultrasonographic findings of ovarian tumours in a population of dogs referred to the Veterinary Teaching Hospital of the University of Perugia (Italy) and Anicura Tyrus Veterinary Clinic (Terni, Italy). The period of study ranged from January 2005 to December 2021. A total of 1910 dogs were affected by neoplasia but only 35 of them (1.8%), of different breeds and ages, were found to have ovarian tumours. Ultrasound of the ovaries was performed based on clinical signs; the diagnosis was achieved after ultrasound findings prompted ovariohysterectomy and ovarian pathologic evaluation In our study, the age of bitches affected by ovarian neoplasia ranged from 3 to 20 years (mean 9.6 ± 3.8). The histopathological findings of ovarian masses identified 16 granulosa cell tumours (GCT) (46%), 7 adenomas (20%), 5 adenocarcinomas (14%), 2 teratomas (6%), 1 leiomyoma (3%), 1 luteoma (3%), 1 tecoma (3%), 1 dysgerminoma (3%), and 1 haemangiosarcoma (3%). In particular, with respect to clinical signs, 69% of bitches showed abnormalities of estrus cycle (short interestral interval, persistent estrus, prolonged interestral interval). The other main clinical signs included abdominal distention, palpable abdominal mass, vulvovaginal discharge, polyuria/polydipsia, mammary masses. When present, the laboratory abnormalities were slight anemia and leucocytosis with neutrophilia. The tumours were ultrasonographically classified as mainly solid: 12/35 (34%) (1 adenoma, 4 adenocarcinomas, 1 dysgerminoma, 1 haemangiosarcoma, 1 leyomioma, 1 luteoma, 1 GCT, 1 tecoma, 1 teratoma); solid with cystic component 13/35 (37%) (9 GCT, 2 Adenomas, 1 adenocarcinoma, 1 teratoma); and mainly cystic 10/35 (29%) (6 GCTs, 4 adenomas). In our study, the ultrasound examination allowed us to suspect ovarian neoplasia in asymptomatic subjects referred for breeding management or for preventive health check. On the basis of our data, we proposed to perform a complete periodic examination of the reproductive system once a year from 6 years. Nevertheless, the presence of ovarian neoplasms found in young subjects, during breeding management, suggest including routine ultrasound examination of the reproductive tract.

Ovarian dysgerminoma: clues to the radiological diagnosis.

Ovarian dysgerminoma (OD) is a rare germ cell tumor accounting for 1%-2% of all malignant ovarian tumors and is generally associated with a good prognosis. The condition is more frequent in young women and can arise in dysgenetic gonads that contain gonadoblastomas. While the definitive diagnosis of OD is only possible histologically, certain radiological features can provide facilitating clues. A large, unilateral, solid, lobulated ovarian tumor with markedly enhancing septa should raise the suspicion of OD in young women. Serum lactate dehydrogenase is characteristically elevated in this tumor type and can complement its diagnosis and postoperative follow-up; however, it is a nonspecific marker. Moreover, knowing the mimickers of OD is essential to optimizing the radiological image interpretation and allowing for adequate management and timely treatment. Therefore, in this article, the radiological and clinical-pathologic features of ODs were reviewed to allow radiologists to become familiarized with them and narrow the diagnostic possibilities when facing this type of tumor.

Germ Cell Tumors of the Ovary: A Review.

Ovarian germ cell tumors are a diverse group of benign and malignant neoplasms that occur in a wide age range, but with a predilection for younger age group. The majority are represented by the frequently encountered mature cystic teratomas. Malignant germ cell tumors are uncommon, and in some cases have a characteristic clinical presentation. However, from a histologic standpoint these tumors can sometimes be challenging to diagnose due to overlapping morphology with epithelial, and in some cases sex cord tumors. In these cases, a panel of immunohistochemical stains often facilitates the correct diagnosis. This review article discusses the clinicopathologic findings and pertinent ancillary studies of both common and uncommon germ cell tumors of the ovary.

Metastatic germ cell tumour in effusion cytology.

BACKGROUND: Germ cell tumours infrequently metastasise to body cavities, where early detection on fluid samples is possible and can spearhead early treatment and survival. MATERIALS AND METHODS: A total of seven cases of metastatic germ cell tumours were retrieved out of 7500 effusion samples received for cytopathological examination from 2015 to 2021. Detailed cytological features of metastatic germ cell tumours in effusion samples were studied, along with a correlation between clinical, radiological, and histopathological features. RESULTS: A total of seven cases of metastatic germ cell tumours were analysed in effusion samples which included dysgerminoma (2), immature teratoma (2), yolk sac tumour (1), embryonal carcinoma (1), and mixed germ cell tumour (1). The smears showed predominantly discrete or loose clusters of cells. The cells with round nuclei and prominent nucleoli were helpful in detecting dysgerminoma and yolk sac tumours. Immature teratoma showed tiny groups of small cells and mature squamous cells. Serum tumour markers were raised in the majority of cases. CONCLUSION: Metastatic germ cell tumours in effusion are uncommon, but detailed clinical history, including serum markers and characteristic cytological features, are helpful in their diagnosis.

Long-Term Outcomes and Factors Related to the Prognosis of Pure Ovarian Dysgerminoma: A Retrospective Study of 107 Cases.

OBJECTIVE: The aim of this study was to evaluate the long-term outcomes and the factors related to patient prognosis. MATERIALS AND METHODS: We retrospectively analyzed patients treated at the Department of Gynecology, Sun Yat-sen University Cancer Center, between January 1, 1968, and December 12, 2018. RESULTS: A total of 107 patients were identified. Of all patients, 79 (73.8%) presented with stage I disease, 14 (13.1%) stage II, 13 (12.2%) stage III, and 1 (0.9%) stage IV. All patients received surgery, with 70 (65.4%) undergoing fertility-sparing surgery (FS) and 37 (34.6%) nonfertility-sparing surgery (NFS). Ninety patients received postoperative chemotherapy. Nine of the 43 cases with a lymphadenectomy had metastasis (20.9%). The median follow-up time was 132 months (range, 1-536 months). The overall 5-year and 10-year survival was 95.1% and 91.7%, respectively. The 10-year survival rate for stage I and II-IV patients was 96.1% and 79.1%, respectively (p = 0.008). For the patients undergoing FS and NFS, the 10-year disease-free survival rate was 82.3% and 88.0%, respectively (p = 0.403). The 10-year disease-free survival rate for patients with or without lymphadenectomy was 95.1% and 78.4%, respectively (p = 0.040), and it was 92.5% and 76.0%, respectively (p = 0.041), for those with or without omentectomy. Fifteen patients relapsed, and 4 of them (26.7%) had recurrence in the lymph nodes. Eleven of the 15 relapsed patients (73.3%) had been successfully salvaged. LIMITATIONS: As a study of a rare disease, our analysis was limited by its small sample size and the deemed disadvantage of a retrospective study. CONCLUSION: Excellent treatment results can be achieved in dysgerminoma patients who received proper treatment. Lymphadenectomy may improve patient survival. Relapsed patients can also be successfully salvaged.

Ovarian dysgerminoma with pseudo-Meigs syndrome: A case report.

RATIONALE: Dysgerminoma is a rare malignant tumor of the ovary, more frequently occurring in young women. The main signs of pseudo-Meigs syndrome (PMS) are ascites and hydrothorax accompanying benign or malignant ovarian tumors (no fibroma or fibroma-like tumor). PATIENT CONCERNS: A 19-year-old woman with fever and chest tightness for 2 days. DIAGNOSES: Pectoral-abdominal computed tomography (CT) scan and contrast-enhanced magnetic resonance imaging revealed a large amount of right pleural effusion, a small amount of ascites, and a huge abdominopelvic mass measuring about 29.2cm × 11.8cm × 8.4 cm in the left ovary. The result of hydrothorax examination was consistent with the diagnosis of exudative pleural effusion. In addition, Rivalta-test showed a positive result and lactate dehydrogenase was elevated. The histopathological diagnosis was a giant germ cell tumor, which was consistent with dysgerminoma in terms of both morphology and immunophenotype. Based on these findings, a diagnosis of malignant ovarian neoplasm with PMS was made. INTERVENTIONS: Surgical resection of the tumor was performed. OUTCOMES: The patient recovered well after operation, and the pleural effusion and abdominal ascites vanished. No recurrence was observed during the 1-year follow-up period. LESSONS: Ovarian dysgerminoma with PMS is a rare malignant tumor of the ovary, which often occurs in young women. It should be considered in differential diagnosis of patients with a pelvic mass, ascites and pleural effusion. Early diagnosis and surgical treatment are beneficial to prolonged survival.

Comparison of immunohistochemical profiles of ovarian germ cells in dysgerminomas of a captive maned wolf and domestic dogs.

We characterized the immunohistochemical expression profiles of dysgerminomas from a 16-y-old maned wolf and 13 domestic dogs using the following biomarkers: Sal-like protein 4 (SALL4), octamer-binding transcription factor 3/4 (OCT3/4), placental alkaline phosphatase (PLAP), c-kit, and vimentin. The maned wolf had nonspecific and long-standing clinical signs of lethargy, anorexia, and weight loss, and was euthanized because of poor prognosis. At autopsy, the left ovary was effaced by a 12 × 8 × 6 cm mass, comprised of anaplastic cells with a mitotic count of 20 mitoses in 10 high power fields. Dysgerminomas from 7 of 13 domestic dogs had nuclear expression of SALL4. Dysgerminomas from the maned wolf and 2 domestic dogs had both nuclear and cytoplasmic expression of SALL4. Cytoplasmic expression of PLAP and OCT3/4 was present in dysgerminomas from the maned wolf and 3 (PLAP) or 4 (OCT3/4) domestic dogs. All dysgerminomas expressed vimentin. Membranous c-kit expression was rare in the dysgerminoma from the maned wolf, and variable in dysgerminomas from 4 domestic dogs. A dysgerminoma from a domestic dog had cytoplasmic expression of c-kit. SALL4 is a useful marker to confirm germ cell origin of dysgerminoma in canids.

Dysgerminoma of the Ovary: An Analysis of 140 Cases Emphasizing Unusual Microscopic Findings and Resultant Diagnostic Problems.

One-hundred fourty pure dysgerminomas were evaluated with particular focus on the microscopic features as seen in 125 cases with available slides. The patients ranged from 8 to 59 years of age (mean, 24.1 y). The tumors, bilateral in 4% of the cases and with a mean tumor diameter of 13 cm, were typically soft, lobulated, homogeneous, and creamy white to tan to yellow but necrosis was found in 13%, hemorrhage in 20%, and focal cystic change in 15%. On microscopic examination, the patterns and other notable features encountered, including their frequency, were as follows: an alveolar pattern resulting from delicate fibrovascular septa (51%), diffuse (33%), macronodular (14%), insular (26%), cords (28%), solid tubular (17%), microspaces (sometimes simulating glands) (12%), follicle-like spaces (5%), prominent fibrous bands (65%), stromal edema (56%), stromal luteinization (9%), granulomatous infiltrate (46%), lymphocytic infiltrate (100%), Langhans cell type giant cells (35%), syncytiotrophoblast giant cells (6%), prominent population of cells with pale to clear cytoplasm (73%), cells with amphophilic to eosinophilic cytoplasm (53%) and vacuolated occasionally signet ring-like cells (7%). Various constellations of the above findings often resulted in an appearance different from that usually portrayed in the literature and certain tumors of very different nature being in the differential such as undifferentiated carcinoma not otherwise specified, small cell carcinoma of hypercalcemic type, and malignant lymphoma. The correct diagnosis can be arrived at by considering the usual relative youth of the patient, often rather characteristic gross features, and most crucially careful attention to the microscopic features and awareness of variant morphologic findings. Those that are particularly problematic based on this study are diffuse growth with inconspicuous fibrovascular septa, macronodules, cords, solid tubular formations, spaces ranging from small to large, and mimicking glands or follicles, prominent fibrous to edematous stroma, and cells with amphophilic to eosinophilic cytoplasm. According to the degree of difficulty and confidence of the interpreter, well-known immunohistochemical features of dysgerminoma, which largely differ from those of other neoplasms in the differential, will aid if felt indicated.

Extraovarian dysgerminoma in a pregnant woman: an extremely rare finding.

Extraovarian germ cell tumors are very rare and their occurrence during pregnancy is exceptional. In this case report an abdominal mass was shown by ultrasonography, during a routine monitoring of a 26-year-old pregnant woman. The patient was left under radiological control in the following months in order to bring the pregnancy to term. A few months after the delivery, the patient underwent surgery and a diagnosis of extraovarian (abdominal) dysgerminoma was made. To the best of our knowledge, there are only 3 other case reports describing an extra-gonadal dysgerminoma occurring during pregnancy. The aim of this study was to report an extremely rare tumor, whose management can be challenging first because this neoplasm has some differences from its ovarian and testicular counterparts. Furthermore, the occurrence during pregnancy makes the multidisciplinary approach mandatory since 3 distinct but not independent entities are involved (tumor, mother and fetus).

Ovarian Dysgerminoma: A Tertiary Center Experience.

Purpose: The aim of this study is to evaluate the oncologic outcome in patients with pure ovarian dysgerminomas treated and followed-up in our hospital. Methods: This study included 18 ovarian dysgerminoma patients with unilateral and/or bilateral salpingo-oophorectomy (BSO) ± hysterectomy+omentectomy+bilateral pelvic ± para-aortic lymphadenectomy+peritoneal cytologic sampling. Results: Four (22%) patients underwent definitive surgery, including type I hysterectomy and BSO. Only one of the remaining 14 patients underwent BSO because of bilateral streak gonad presence during intraoperative examination. Thirteen patients (72%) had conservative surgeries. In addition, staging surgeries were performed to all patients except for one patient with 16 weeks of pregnancy (patient #3) in the study group. Retroperitoneal lymphadenectomy was part of the staging procedure except for this pregnant patient. Lymph node metastasis was positive in four (22%) patients. Three (16%) patients recurred and none of them died because of disease during follow-up period. Two of the relapsed patients were treated with combination of surgery and chemotherapy, whereas the third patient received only chemotherapy for treatment. Conclusions: Fertility sparing surgery should be the choice of treatment in patients with pure ovarian dysgerminoma. In addition, staging surgery, including retroperitoneal lymph node dissection is obligatory for determining stage IA patients who are exempt from adjuvant chemotherapy. Close surveillance policy enables early detection of patients with recurrences in whom salvage therapy is highly curable.

Malignant Mixed Germ Cell Tumors of the Ovary: An Analysis of 100 Cases Emphasizing the Frequency and Interrelationships of Their Tumor Types.

One hundred malignant mixed germ cell tumors of the ovary that occurred in patients 3 to 55 years (mean: 20 y) of age are described. The clinical presentation was usually that of any highly malignant tumor of the ovary (abdominal pain and distension), but rarely (3 cases) endocrine manifestations were present. The tumors were usually unilateral (96%), ranged from 4 to 38 cm (mean: 16 cm), and were uniformly solid or, more often, solid and cystic; occasionally the typical appearance of dysgerminoma could be appreciated. The most common tumor type was yolk sac tumor (91%), followed by dysgerminoma (61%), immature teratoma (58%), embryonal carcinoma (38%), and choriocarcinoma (11%). A variety of admixtures were encountered; dysgerminoma and yolk sac tumor was the most common combination (25% of the tumors) with the 2 components often being sharply demarcated. Immature teratoma and yolk sac tumor was the next most common pairing (20%) followed by yolk sac tumor and embryonal carcinoma, with or without immature teratoma (16%). Tumors with a choriocarcinoma component had the most varied combinations of tumor types. Embryoid bodies were seen in 21% of the tumors, most often as fragmented forms arranged in a nodular manner with yolk sac tumor and/or embryonal carcinoma; uncommonly they occurred singly or in clusters. Numerous confluent well-formed embryoid bodies (polyembryoma) were prominent in 2 tumors. Three tumors had a focal diffuse embryoma pattern. The specific tumor types showed the known diverse spectrum of microscopic appearances, but the frequent haphazard arrangement of 2 or more subtypes often resulted in complex morphology. Overgrowth of another neoplastic component, most often primitive neuroectodermal tumor, occurred in 10% of the tumors further complicating the histologic picture. This is the largest series of ovarian malignant mixed germ cell tumors reported and details their characteristics including associations of their subtypes and the frequent apparent role of embryoid bodies in giving rise to yolk sac tumor and embryonal carcinoma components.

An aggressive systemic mastocytosis preceded by ovarian dysgerminoma.

BACKGROUND: Aggressive systemic mastocytosis (ASM) is a rare malignant disease characterized by disordered mast cell accumulation in various organs. We here describe a female ASM patient with a previous history of ovarian dysgerminoma. METHODS: Molecular cytogenomic analyses were performed to elucidate an etiological link between the ASM and dysgerminoma of the patient. RESULTS: This patient was affected by ovarian dysgerminoma which was treated by chemotherapy and surgical resection. Having subsequently been in complete remission for 2 years, she developed symptoms of ASM. A somatic D816A mutation in the KIT gene was detected in her bone marrow, which facilitated the diagnosis of ASM. Unexpectedly, this KIT D816A variant was also detected in the prior ovarian dysgerminoma sample. Whole-exome sequencing allowed us to identify a somatic nonsense mutation of the TP53 gene in the bone marrow, but not in the dysgerminoma. Microarray analysis of the patient's bone marrow revealed a copy-number-neutral loss of heterozygosity at the TP53 locus, suggestive of the homozygous nonsense mutation in the TP53 gene. In addition, the loss of heterozygosity at the TP53 locus was also detected in the dysgerminoma. CONCLUSIONS: These results indicated that either the mast cells causing the ASM in this case had originated from the preceding ovarian dysgerminoma as a clonal evolution of a residual tumor cell, which acquired the TP53 mutation, or that both tumors developed from a common cancer stem cell carrying the KIT D816A variation.

Need for risk-adapted therapy for malignant ovarian germ cell tumors: A large multicenter analysis of germ cell tumors' patients from French TMRG network.

BACKGROUND: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. PATIENTS AND METHODS: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. RESULTS: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. CONCLUSION: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging.