Pediatric Blood & Cancer

Loss of heterozygosity does not occur in BRCA1/2 mutant pediatric solid and central nervous system tumors

AbstractUtilization of tumor‐only sequencing has expanded in pediatric cancer patients, which can lead to identification of pathogenic variants in genes that may be germline and/or have uncertain relevance to the tumor in question, such as the homologous recombination (HR) pathway genes BRCA1/2. We identified patients with pathogenic BRCA1/2 mutations from somatic tumor sequencing, and performed additional germline sequencing to assess for the presence of loss of heterozygosity (LOH). Of seven patients identified, four (57.1%) mutations were found in the germline and none had associated LOH. Our data suggest that BRCA1/2 mutations identified in this context are likely incidental findings.

Comprehensive fertility preservation can be offered in a timely manner around gonadotoxic therapy in children and adolescents

AbstractBackgroundTreatment for certain childhood cancers and nonmalignant conditions can lead to future infertility and gonadal failure. The risk of treatment delay must be considered when offering fertility preservation (FP) options. We examined the timeline from FP referral to return to treatment (RTT) in pediatric patients who underwent FP due to iatrogenic risk for infertility.MethodsA retrospective review was performed of patients with FP consultation due to an increased risk of iatrogenic infertility at Ann & Robert H. Lurie Children's Hospital of Chicago from 2018 to 2022. Data on diagnosis, age, treatment characteristics, and procedure were collected.ResultsA total of 337 patients (n = 149 with ovaries, n = 188 with testes) had an FP consultation. Of patients with ovaries, 106 (71.1%) underwent ovarian tissue cryopreservation (OTC), 10 (6.7%) completed ovarian stimulation/egg retrieval (OSER), and 33 (22.1%) declined FP. Of the patients with testes, 98 (52.1%) underwent testicular tissue cryopreservation (TTC), 48 (25.5%) completed sperm banking (SB), and 42 (22.3%) declined FP. Median time from referral to FP consultation was short (ovaries: 2 days, range: 0–6; testes: 1 day, range: 0–5). OSER had a significantly longer RTT versus OTC and no FP (52.5 vs.19.5 vs. 12 days, p = .01). SB had a significantly quicker RTT compared to TTC or no FP (9.0 vs. 21.0 vs. 13.5 days; p = .008). For patients who underwent OTC/TTC and those who declined FP, there was no significant difference in time from consultation to treatment.ConclusionsIt is feasible to promptly offer and complete FP with minimal delay to disease‐directed treatment.

Extracranial germ cell tumours: Mature and immature (1990–2015). First report by the South African Association of Paediatric Haematology Oncology (SAAPHO)

AbstractBackground and objectivesOutcomes of rare paediatric teratomas have not previously been reported nor treatment regimens standardised in low‐ and middle‐income settings. We sought to evaluate treatment outcomes of children and adolescents with histologically confirmed extracranial germ cell tumours, both mature teratomas (MT) and immature teratomas (IT) in preparation for the development of the South African national treatment guideline.MethodsRetrospective data by folder review were collated from nine South African paediatric oncology units. Kaplan–Meier analysis with Cox regression was performed to determine 5‐year overall survival (OS) and prognostic factors.ResultsFrom January 1990 to December 2015, 60 patients were diagnosed with MTs; 14 males (median age 2 months; interquartile range [IQR]: 0–8.75 months) and 46 females (median age 9 months; IQR: 0–88.5 months). Forty patients were diagnosed with ITs; 10 males (median age less than 1 month; IQR: 0–1.75 months) and 30 females (median age 4.5 months; IQR: 1–162 months). There were high rates of upfront surgical resections in patients with MTs (58/60; 96.6%) and ITs (36/40; 90%), and similarly satisfactory rates of complete resection in patients with both MTs (55/60; 91.7%) and ITs (32/40; 80%). The 5‐year OS for the whole group was 85.4%, significantly influenced by stage: Stage I (96.9%), Stage II (100%), Stage III (38.9%) (p < .001 [MT]; p = .013 [IT]). The event‐free survival (EFS) ratio for the whole cohort was 78.7%.ConclusionsFive‐year OS for those with low‐stage disease was excellent, but was poorer for patients with advanced disease. The implementation of a national treatment guideline will facilitate the standardising of surgical approaches, indications for chemotherapy and specifications for follow‐up to improve survival and to collect more robust late effects data.

High‐grade ovarian adenosarcoma with heterologous elements arising from recurrence of benign mucinous cystadenoma in a child

Risk for Unplanned Pregnancy Among Survivors of Childhood Cancer

ABSTRACTThe purpose of this study was to identify factors associated with risk for unplanned pregnancy in sexually active female survivors using self‐report survey data. Risk for unplanned pregnancy was defined as using less effective/no contraception while also not desiring pregnancy. Of N = 160 participants (age 24.0 ± 3.1 years), 33.1% were at‐risk for unplanned pregnancy. On multivariable analysis, participants were less likely to be categorized at‐risk for unplanned pregnancy if they reported diagnosis of ovarian failure/premature menopause (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.02–0.72, p = 0.032), greater concerns about fertility (OR 0.59, 95%CI 0.43–0.80, p = 0.001), and religious identity of agnostic/atheist (compared with Christian, OR 0.10, 95%CI 0.01–0.41, p = 0.005).

Choriocarcinoma in neonates and infants: A severe but curable disease

Abstract Choriocarcinoma in neonates and infants (N‐CC) is an extremely rare, but aggressive cancer, frequently observed with concomitant maternal disease. A retrospective, bi‐national study of patients treated in France and Poland for infantile choriocarcinoma analysed eight cases of N‐CC, median age of 6 weeks. All tumours were diffuse. Six patients received a platinum‐based regimen, and five had delayed surgery on residual distant tumour sites. At the end of follow‐up, four patients were in complete remission and four had died of the disease. In all but two cases, mothers had simultaneous metastatic choriocarcinoma. Even if the outcome remains poor, patients could be cured with multimodal therapy.

Thoracic Sertoli–Leydig cell tumor: An alternative type of pleuropulmonary blastoma associated with DICER1 variation

AbstractA 2‐year‐old boy presented with a large cystic and solid chest mass arising from the lung, radiographically consistent with pleuropulmonary blastoma (PPB). He underwent right lower lobectomy with resection of a well‐circumscribed, mixed solid and cystic mass. The solid areas were composed of cords and nests of tumor cells in the myxoid stroma and retiform foci whose pathologic and immunophenotypic findings were consistent with a sex cord‐stromal tumor with features of a Sertoli–Leydig cell tumor. Tumor testing showed a pathogenic variant in the DICER1 RNase IIIb hotspot domain. Family history was suggestive of DICER1 germline pathogenic DICER1 variation in absence of a detectable germline variant. He received 12 cycles of chemotherapy with ifosfamide, vincristine, dactinomycin and doxorubicin (IVADo) and surgery with complete response. One year after completion of chemotherapy, imaging studies showed concern for recurrence confirmed by thorascopic biopsy of a pleural‐based mass. He is currently receiving cisplatin‐based chemotherapy with reduction in tumor size. Review of the literature showed no similar cases; however, review of our pathology files revealed a single similar case of anterior mediastinal Sertoli cell tumor in a 3‐year‐old girl.

Immature teratoma of the ovary associated with Cowden syndrome

Prevalence of metachronous contralateral mature ovarian teratoma: A systematic review

AbstractThere is increasing recognition that contralateral metachronous tumor may occur following treatment of unilateral mature ovarian teratoma. We aimed to define this risk to guide appropriate surveillance strategies. We undertook a systematic review of three large medical databases (Ovid Medline, Embase, and Cochrane Controlled Trials Register) to April 2020 using a defined search strategy. From 1831 articles retrieved, 23 were included, reporting 1101 girls with unilateral mature ovarian teratomas. The intensity and duration of follow‐up varied between studies, with only five reporting close surveillance. Overall prevalence of metachronous contralateral mature teratoma was 2.1%, with a prevalence per study of 0%–23% (median 0%). Prevalence was higher (7%) among studies with more robust surveillance. These data suggest a small but real risk of metachronous contralateral tumors. Surveillance ultrasonography is proportionate and indicated alongside further prospective data collection to record the natural history and impact of surveillance in greater detail.

Unusual ovarian leukemic relapse in a girl with history of B‐cell lymphoblastic leukemia

Extracranial germ cell tumours in children and adolescents: Results from the French TGM13 protocol

AbstractBackgroundChemotherapy for non‐seminomatous germ cell tumours (NSGCT) exposes to dose‐dependent toxicities. The TGM13‐NS protocol (EudraCT 2013‐004039‐60) aimed to decrease the chemotherapy burden compared to the previous TGM95 protocol while maintaining the 5‐year event‐free survival (EFS) at 80% or more.ProcedurePatients less than 19 years of age with disseminated NSGCT were enrolled (May 2014 to May 2019) and stratified into four groups: two intermediate‐risk (IR: localised tumour with low tumour markers [TM]) groups treated with VBP (vinblastine–bleomycin–cisplatin): three courses for IR1 (ovarian tumour any age/testis tumour less than or equal to 10 years) and four courses for IR2 (extragonadal tumour 10 years or less) groups, and two high‐risk (HR: metastatic and/or high TM) groups treated with etoposide–cisplatin and either ifosfamide (VIP) or bleomycin (BEP): three courses for HR1 (ovarian tumour any age/testis tumour less than or equal to 10 years and low TM/testis tumour more than 10 years and very low TM) groups and four courses for HR2 (remainder) groups.ResultsOne hundred fifteen patients were included: median age of 12.8 years (0.4–18.9); tumour sites: 44 ovaries, 37 testes and 34 extragonadal. The 5‐year EFS and overall survival (OS) were 87% (95% CI: 80–92) and 95% (89–98), respectively (median follow‐up: 3.5 years, range: 0.2–5.9), similar to those of the TGM95 protocol (5‐year EFS 89% (84–93), 5‐year OS 93% (89–95), p = .561). The 5‐year EFS were 93% (95% CI: 80–98), 88% (71–95) and 79% (62–90) for ovarian, testicular and extragonadal tumours, respectively. The 5‐year EFS varied (p = .02) according to the risk groups: 90% (66–97), 64% (30–85), 95% (72–99) and 87% (74–94) for IR1, IR2, HR1 and HR2, respectively. TM decline adjusted to tumour site, and alpha‐fetoprotein (AFP) level revealed a prognostic impact of time to normalisation on EFS: HR = 1.03 (1.003–1.007).ConclusionRisk‐adapted and globally decreased chemotherapy burden maintains excellent outcomes, exclusive of the IR2 group, which warrants more intensive chemotherapy.

Imaging of pediatric ovarian tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper

AbstractOvarian tumors in children are uncommon. Like those arising in the adult population, they may be broadly divided into germ cell, sex cord, and surface epithelium subtypes; however, germ cell tumors comprise the majority of lesions in children, whereas tumors of surface epithelial origin predominate in adults. Diagnostic workup, including the use of imaging, requires an approach that often differs from that required in an adult. This paper offers consensus recommendations for imaging of pediatric patients with a known or suspected primary ovarian malignancy at diagnosis and during follow‐up.

Bilateral testicular juvenile granulosa cell tumor: Tumor control with conservative, antihormonal therapy

Rhabdomyosarcoma of the female genitourinary tract: Primary and relapsed disease in infants and older children. Treatment results of five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry

AbstractBackgroundRhabdomyosarcoma (RMS) of the female genitourinary tract (FGU‐RMS) located at the vagina or uterus is one of the most favorable RMS sites. Little is known about treatment and outcome in infants and relapsed disease (RD).MethodsCharacteristics, treatment, and outcome of 71 children with FGU‐RMS registered within five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry (1981‐2019) were evaluated.ResultsFGU‐RMS was diagnosed in 67 patients with localized disease (LD) at a median age of 2.89 years (0.09‐18.08). Multimodal treatment consisted of chemotherapy (CHT) (n = 66), secondary surgery (n = 32), and radiotherapy (n = 11). Age at diagnosis ≤12 months was the only significant negative prognostic factor influencing the event‐free survival (EFS). Ten‐year EFS and overall survival (OS) for infants ≤12 months were 50% and 81%, respectively. In contrast, children with LD >1 year and ≤10 years had a 10‐year EFS and OS of 78% and 94% (P = .038), and >10 years of 82% and 88%, respectively (P = .53). Metastatic disease was observed in four patients of which three are alive. RD occurred in five of 12 infants ≤1 year and 10/55 children at a median of 1.38 years (0.53‐2.97) after initial diagnosis. Treatment of patients with RD consisted of multimodal treatment (n = 13) or resection only (n = 2). Nine patients (60%) were alive in clinical remission at a median of 7.02 years (1.23‐16.72) after diagnosis of RD.ConclusionInfants with FGU‐RMS have a higher relapse rate than older children with FGU‐RMS, but prognosis is fair.

Reply to “Comment on: Standardizing the surgical management of benign ovarian tumours in children and adolescents: A best practice Delphi consensus statement”

Standardizing the surgical management of benign ovarian tumors in children and adolescents: A best practice Delphi consensus statement

AbstractAimNo widely agreed consensus protocols exist for the management of benign ovarian tumors (BOT) in children. This presents a substantial risk for suboptimal management. We aimed to generate multispecialty consensus guidance to standardize surgical management and provide a clear follow‐up protocol for children with BOTs.MethodsProspective two‐round confidential e‐Delphi consensus survey distributed among multispecialty expert panel; concluded by two semistructured videoconferences.Main resultsConsensus was generated on these core outcome sets: preoperative/intraoperative management; follow‐up; adolescent gynecology referral. (1) Children with BOTs should receive the same management as other patients with potentially neoplastic lesions: Preoperative discussion at a pediatric oncology multidisciplinary meeting to risk stratify tumors, and management by health professionals with expertise in ovarian‐sparing surgery and laparoscopy. (2) Ovarian‐sparing surgery for BOTs should be performed wherever possible to maximize fertility preservation. (3) Ovarian masses detected during emergency laparoscopy/laparotomy should be left in situ wherever feasible and investigated appropriately (imaging/tumor markers) before resection. (4) Follow‐up should be undertaken for all patients after BOT resection. Patients should be offered referral to adolescent gynecology to discuss fertility implications.ConclusionThis best practice Delphi consensus statement emphasizes the importance of managing children with BOTs through a well‐defined oncological MDT strategy, in order to optimize risk stratification and allow fertility preservation by ovarian‐sparing surgery wherever possible.

General cancer screening practices among adult survivors of retinoblastoma: Results from the Retinoblastoma Survivor Study

AbstractWe assessed breast, cervical, and colorectal cancer screening practices in adult retinoblastoma (Rb) survivors and non‐Rb controls. We found that most Rb survivors adhered to general population cancer screening recommendations. Rates did not differ among Rb survivors and non‐Rb controls, or among survivors by laterality, even though bilateral survivors reported higher levels of concern about future health and cancer risk. Older age, being overweight/obese, and lack of recent contact with medical personnel were independently associated with decreased utilization of Pap smear among female Rb survivors. Future studies are warranted to determine whether these associations might provide an opportunity for intervention.

The Evolving Spectrum of Paediatric Ovarian Malignancies From Childhood to Adulthood: A Multicentre Experience

ABSTRACT Background/Objectives Ovarian malignancies in children and young women exhibit distinct clinical characteristics and may be managed by either paediatric surgeons or gynaecologists, depending on patient age and institutional protocols. This multicentre retrospective study aims to evaluate similarities and differences in the management and outcomes of ovarian malignancies treated by different surgical teams. Design/Methods A multicentre retrospective review was conducted, including patients who underwent surgery for ovarian malignancies from 2013 to the present. Data were collected from two paediatric surgical departments and one adult gynaecological department. Patients were categorized into two groups according to the surgical team: Group A (paediatric surgeons) and Group B (gynaecologists). Clinical, diagnostic, surgical and oncological data were analysed. Results A total of 52 patients were included: 29 in Group A (median age 10 years, range 3–15) and 23 in Group B (median age 31 years, range 23–39). The most common tumour types were immature teratomas in Group A (45%) and borderline tumours in Group B (43.5%). Group A commonly underwent transabdominal ultrasound (87%) and MRI (31%), whereas Group B received transvaginal ultrasound (100%) and CT scans (78.2%). In Group A, 62% of girls underwent laparotomy, whereas 83.4% of women (Group B) underwent laparoscopy ( p  < 0.01). Oophorectomy was performed in 90% of cases across both groups. Patients in Group A presented more frequently with early‐stage disease (93% vs. 30%, p  < 0.05). During follow‐up, relapse occurred in three paediatric and four adult patients, and two patients (one from each group) died due to disease progression. Conclusions Despite variations in preoperative assessment and surgical approaches, postoperative oncological treatment and long‐term outcomes, including disease‐free and overall survival, were comparable between the groups. Integrating the strengths of both paediatric and gynaecological approaches may further optimize the management of ovarian malignancies in young patients.

Standard‐Dose Versus High‐Dose Cisplatin for Intermediate/Poor‐Risk Extracranial Malignant Germ Cell Tumors: Re‐Analysis of Pediatric Oncology Group 9049 and Children's Cancer Group 8882 Trial Using Updated MaGIC Risk Stratification

ABSTRACTBackgroundCisplatin, etoposide, and bleomycin (PEb) have been the standard of care for patients with germ cell tumors (GCT). In the 1990s, an intergroup trial (POG9049/CCG8882) randomized patients with high‐risk GCT, as defined by the 1990 criteria, to high‐dose (HDPEb) versus standard‐dose PEb. HDPEb resulted in improved event‐free survival (EFS), but no difference in overall survival (OS), thus standard‐dose PEb has remained the standard of care. Subsequently, the Malignant Germ Cell International Consortium (MaGIC) updated the risk stratification for pediatric and adolescent patients with GCT. Currently, patients are categorized as intermediate or poor risk if they are ≥11 years of age with Stage IV ovarian GCT, or testicular, mediastinal, or retroperitoneal GCT with intermediate or poor prognosis using the International Germ Cell Consensus Classification criteria.MethodsWe re‐analyzed data from the POG9049/CCG8882 trial using the updated MaGIC risk stratification to determine whether HDPEb improved outcomes over PEb in patients with intermediate/poor‐risk GCTs.ResultsAmong 299 patients in the trial, 57 patients (48 males, nine females) met the inclusion criteria for this analysis. There were no statistically significant differences in 5‐year EFS (0.72 vs. 0.70, p‐value = 0.82) or OS (0.76 vs. 0.74, p‐value = 0.91) among patients treated with HDPEb versus PEb, respectively. Also, of note patients with mediastinal primaries had significantly worse 5‐year EFS (0.51 vs. 0.83, p‐value = 0.0062) and OS (0.49 vs. 0.89, p‐value = 0.0013) compared to other sites, with no difference in outcome between HDPEb and PEb.ConclusionsTreatment with HDPEb did not improve outcomes for intermediate/poor‐risk GCT patients compared to standard‐dose PEb.

Oncofertility care for children, adolescents, and young adults at risk for treatment‐related fertility loss

AbstractAs therapy for childhood malignancies becomes more sophisticated and survival has improved, long‐term therapy‐related sequelae have emerged. Loss of reproductive potential among childhood cancer survivors is one such concern that has become increasingly recognized among patients, families, and healthcare providers. The risk status for infertility based upon therapy received, state of current reproductive technology and outcomes, and an emphasis on adequate referral and counseling for fertility preservation options are reviewed. Contributing factors to infertility are discussed, and options for female and male preservation based upon age and pubertal status are summarized. This article highlights the current state of fertility opportunities for children and adolescents undergoing therapy for cancer. Providers caring for these young patients should be familiar with such options and should routinely initiate evaluations for eligibility of fertility preservation.

Current surgical approach: Extracranial malignant germ cell tumors

AbstractGerm cell tumors (GCT) are a complex, heterogeneous collection of tumors that may present in either gonadal or extragonadal sites. They consist of a variety of benign and malignant histologies that can occur at several locations throughout the body. An important component of treatment is surgical resection, and while the key components of resection are site specific, the universal goals of GCT resection include the complete resection of tumor without violating the tumor capsule, while preserving function of surrounding organs, minimizing morbidity, and assessing for regional spread.

Clear Cell Adenocarcinoma of the Uterine Cervix and Vagina in Children Without Exposure to Diethylstilbestrol

ABSTRACTAimClear cell adenocarcinoma of the uterine cervix (CCAC) or vagina (CCAV) is rare and usually presents in postmenopausal women. Paediatric cases are rare, and have historically been associated with intrauterine exposure to diethylstilbestrol (DES). We aimed to summarise outcomes of CCAC and CCAV in children with no history of DES exposure.MethodsSystematic review of the Pubmed/Medline/Ovid databases from inception to 2024 according to PRISMA guidelines. The initial search identified 127 articles, and 29 articles were included in the final analysis.Main ResultsForty‐three cases of paediatric CCAC and CCAV were described. Median age at presentation was 10 years [interquartile range (IQR): 8–14 years]. Most patients presented with stage I tumours and symptoms of prolonged vaginal bleeding. Staging assessment included CT or MRI abdomen/pelvis and vaginoscopy with biopsy in most cases. Treatments consisted of variable combinations of chemotherapy, radiotherapy (external beam or brachytherapy) and surgery. Surgical procedures included localised resection only, radical trachelectomy or radical hysterectomy with pelvic lymph node clearance. Follow‐up information was available for 88% patients and was overall very heterogeneous. Median duration of follow‐up was 24 months [IQR: 14–82.5]. There were seven reported deaths, and two additional patients experienced recurrence during follow‐up.ConclusionThis is the first systematic review on the management and outcomes of children with CCAC and CCAV. The cases identified were few and heterogeneous, with limited information on longer term outcomes. Current evidence does not allow for the generation of paediatric‐specific treatment guidelines. A cautious approach to the management of this rare and aggressive disease is essential, carefully balancing the desire of fertility preservation with the need for cure from disease.

Paraneoplastic juvenile idiopathic arthritis as a manifestation of a benign teratoma in a 5‐year‐old female

von Hippel–Lindau syndrome and steroid cell tumor of the ovary: A case report

Novel Findings in Pediatric and Adolescent Patients With Cancer and a Germline SMARCA4 Variant

ABSTRACTIntroductionSMARCA4 is a known susceptibility gene for malignant rhabdoid tumors (MRT) in children and small cell carcinoma of the ovary hypercalcemic type (SCCOHT) in young females and women. Recently, a novel association between germline SMARCA4 variants and predisposition to neuroblastoma was proposed.MethodsWe present a single‐center study summarizing the clinical and genetic data of pediatric and adolescent cancer patients with a germline SMARCA4 variant diagnosed with and/or treated for an MRT, SCCOHT, or neuroblastoma.ResultsWe identified nine patients with germline SMARCA4 variants, including one patient with an MRT, four patients with a SCCOHT, and four patients with a neuroblastoma. We observed two novel pathogenic SMARCA4 variants that were initially missed using diagnostic testing: a low‐mosaic pathogenic SMARCA4 variant in the patient with an MRT, and a germline SMARCA4 partial gene deletion, encompassing the promoter region, in a patient with a SCCOHT. The patients with neuroblastoma in our cohort had a strikingly old age at diagnosis (range: 10–22 years old). In three of four patients with neuroblastoma, the germline SMARCA4 variant was a variant of unknown significance (VUS). In two of their neuroblastomas, we observed loss of heterozygosity at the SMARCA4 locus, and loss of BRG1 expression was found in one of these.ConclusionsThis study highlights that awareness is needed for easy‐to‐miss germline variants in SMARCA4 and that knowledge about variant types, cancer spectrum, and cancer penetrance in individuals with a germline SMARCA4 variant is still evolving.

Pediatric pseudo‐Meigs syndrome with ovarian dysgerminoma

Reproductive late effects after hematopoietic stem cell transplant in pediatric, adolescent, and young adult cancer survivors

AbstractReproductive late effects after hematopoietic stem cell transplant can have a significant impact on cancer survivors’ quality of life. Potential late effects include gonadal insufficiency, genital graft‐versus‐host disease, uterine injury, psychosexual dysfunction, and an increased risk of breast and cervical cancer in patients treated with total body irradiation. Despite guidelines, screening and treatment are not standardized among at‐risk patients. Provider barriers include lack of knowledge of at‐risk therapies and evidenced‐based guidelines. Patient barriers include a reluctance to report symptoms and lack of awareness of treatment options. System barriers include inefficient implementation of screening tools and poor dissemination of guidelines to providers who serve as the medical home for survivors. This review guides the clinician in identifying and managing reproductive late effects after hematopoietic stem cell transplant to improve outcomes.

Outcome and late effects of patients treated for childhood vaginal malignant germ cell tumors

AbstractPurposeVaginal malignant germ cell tumors (MGCT) are rare, occurring in children less than 2 years old and raise the question of the optimal local treatment.MethodsWe included children treated for vaginal MGCT according to the French TGM‐95/2013 regimen. Patients were classified as standard risk (SR: localized disease and alpha‐fetoprotein (AFP) < 10,000 ng/mL) or high risk (HiR: metastatic and/or AFP > 10,000 ng/mL) and were treated, respectively, with three to five VBP (vinblastine–bleomycin–cisplatin) or four to six VIP (etoposide–ifosfamide–cisplatin), followed by conservative surgery and/or brachytherapy in case of post‐chemotherapy residuum.ResultsFourteen patients were included (median age = 12 months), of which six (43%) were classified as HiR. AFP levels were normalized after first‐line chemotherapy in all cases but one. A vaginal post‐chemotherapy residuum (median size = 8 mm, range: 1–24 mm) was observed in 13/14 patients, treated by complete resection in seven of 13 (viable cells in three of seven), incomplete resection in four of 13 (viable cells in two of four), with adjuvant brachytherapy in two of 13, and exclusive brachytherapy in two of 13 (viable cells in one of six). Among the six patients with viable disease, four patients received adjuvant chemotherapy. One patient (SR) experienced immediate postoperative relapse despite presenting no viable residual cells and was treated with four VIP cycles and brachytherapy. At last follow‐up (median = 4.6 years, range: 0.5–16), all patients were alive in complete remission. Five patients suffered from vaginal sequelae with synechiae and/or stenosis (of whom four had undergone brachytherapy).ConclusionChildhood vaginal MGCTs show a highly favorable prognosis with risk‐adapted chemotherapy and local treatment of post‐chemotherapy residuum (preferably by conservative surgery with partial vaginectomy). Brachytherapy could be an alternative when conservative surgery is not deemed possible or in cases of incomplete resection with residual viable cells.

Pediatric ovarian Sertoli‐Leydig cell tumors with heterologous rhabdomyosarcoma elements: Clinical case series and review of the literature

AbstractSertoli‐Leydig cell tumors (SLCTs) are rare ovarian neoplasms in pediatric patients. More exceedingly rare are SLCTs that also contain heterologous rhabdomyosarcoma (RMS) elements. For these patients, there is no standardized treatment. We report four cases of pediatric SLCT with heterologous RMS elements that were successfully treated with surgical resection and adjuvant chemotherapy. All four patients are alive and remain in remission.

Disorder of sex development with germ cell tumors: Which is uncovered first?

AbstractBackgroundDisorders of sex development (DSD) are rare conditions. Although they are known to predispose to germ cell tumors (GCT), there is a paucity of information regarding the circumstances of DSD discovery.Design/methodsAll patients with DSD registered in two French pediatric GCT protocols (TGM95 and 13) were analyzed.ResultsSixteen patients were identified among 276 ovarian, 160 testicular, and 24 mediastinal GCT. Eleven phenotypic females (median age 15 years) exhibited gonadal GCT, including 10 with a 46,XY karyotype and gonadal dysgenesis and one with 46XX,45X0 mosaicism. None had genital anomalies, seven had spontaneous pubertal changes, and one had spontaneous menarche. The tumors were bilateral in four cases. DSD was diagnosed after the GCT diagnosis in seven cases. The reasons for karyotyping were bilateral tumors (3), gonadoblastoma/streak gonad/absence of egg follicles (3), or systematic for GCT (1). The karyotyping was performed before the GCT diagnosis in four cases: for polymalformative syndrome (2) or primary amenorrhea (2). Four males (median age 14 years) exhibited mediastinal GCT (metastatic in two cases) indicative of Klinefelter syndrome, despite typical phenotypes in all cases. The remaining patient had severe hypospadias, leading to the discovery of 46,XY/45,X0 mosaicism before the diagnosis of testicular nonseminomatous GCT at 16 years of age.ConclusionDSD are often uncovered at the time of GCT diagnosis (11/16 cases). This should prompt oncologists to rule out a DSD in patients with GCT, even in case of pubertal development. Earlier recognition of Klinefelter syndrome could potentially lead to GCT detection at an earlier stage.

Pure pediatric ovarian immature teratomas: The French experience

AbstractObjectiveTo describe characteristics and outcome of pediatric ovarian immature teratomas (IT) to better define the place of chemotherapy.MethodsChildren with ovarian IT enrolled in TGM95 and TGM2013 studies were analyzed. Norris grading and International Federation of Gynecology and Obstetrics staging system were used.ResultsThirty‐six cases were identified with a median age of 11 years (range = 1‐18): 35 of 36 stage I (17 stage IA, 13 stage IC, and 5 stage IX), including seven patients with gliomatosis peritonei (GP), and 1 stage IIIB (IT peritoneal implants). Centrally reviewed Norris grading was performed in 31 cases: 14 grade I and 17 grade II/III tumors. All patients underwent upfront surgery: 19 unilateral oophorectomy, 14 unilateral adnexectomy, 2 unilateral cystectomy, and 1 bilateral cystectomy. No extensive GP surgery was performed. Six patients received adjuvant vinblastin, bleomycin, and cisplatinum because of tumor rupture (n = 5, including two patients with GP) or stage III (n = 1). After a median follow‐up of 39.5 months (range = 6‐238), two events occurred 10 and 11 months after diagnosis: one bilateralization (initial stage IX, grade I) and one IT peritoneal relapse (initial stage IA, grade II), respectively. Both were successfully rescued by platinum‐based chemotherapy and delayed surgery. No stage IC patients treated without adjuvant chemotherapy relapsed (four grade I and three grade III). None of the seven patients with GP progressed. Five‐year event‐free survival and overall survival were 94% (95% CI = 81‐98%) and 100%.ConclusionsThe current series confirms the excellent prognosis of pediatric ovarian IT, arguing for conservative surgical approach in GP and against systematic adjuvant chemotherapy, even in ruptured tumors.

Comment on: Standardizing the surgical management of benign ovarian tumors in children and adolescents: A best practice Delphi consensus statement

Oncological and endocrinological outcomes for children and adolescents with testicular and ovarian sex cord‐stromal tumors. Results of the TGM13 National Registry

Abstract Rationale Sex cord‐stromal tumors (SCST) are hormonally active and rare. The aim was to describe their endocrinological presentation and outcomes. Method Patients (< 19 years) registered in the TGM13 registry between 2014 and 2021 for SCST were selected. Results Sixty‐three ovarian SCST (juvenile granulosa tumor (JGT) n  = 34, Sertoli‐Leydig cell tumor (SLCT) n  = 17, other SCST n  = 12) were included. Median age was 13.1 years (0.4‐17.4). Germline DICER1 pathogenic variant was present in 9/17 SLCT. Sixty‐one were FIGO stage I (IC n  = 14). Adjuvant chemotherapy was administered for 15. Seven had recurrence (FIGO IA n  = 3, IX n  = 2, III n  = 2), leading to one death. With a median follow‐up of 42 months (2.5‐92), the 3‐year progression‐free survival (PFS) was 89% (95% CI 76%‐95%). Median age was 6.4 years (0.1‐12.9) among the 15 testicular SCST (Leydig cell tumor n  = 6, JGT n  = 5, Sertoli cell tumor n  = 3, mixed SCST n  = 1). Tumor‐nodes‐metastases (TNM) stage was pSI in 14. Eight underwent a tumorectomy, 7 an orchiectomy. None experienced recurrence. Endocrinological data were reviewed for 41 patients (18 prepubescent). Endocrine symptoms were present at diagnosis in 29/34 females and 2/7 males (gynecomastia). After a median follow‐up of 11 months, 15 patients had persistent endocrine abnormalities: gynecomastia/breast growth (2 males, 1 prepubescent female), precocious/advanced puberty (4 prepubescent females), and hirsutism/menstruation disorders/voice hoarseness/hot flashes (8 pubescent females). The mean height at the last follow‐up was within normal ranges (+0.3 standard deviation). Conclusions SCSTs have a favorable prognosis. Tumorectomy appears safe with testicular primary. Endocrinological disorders, common at diagnosis, may persist warranting endocrinological follow‐up.