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Background and Aims: Image Defined Risk Factors (IDRFs) assess surgical risk in neuroblastoma (NB) and guide neoadjuvant therapy. Despite chemotherapy IDRFs may persist in 70 % of cases. Several studies have suggested that not all IDRFs hold equal significance and that the presence of an IDRF does not inherently signify unresectability. This current study seeks to stratify and assign a score to each IDRF based on its impact on surgical risk., Methods: This collaborative study entailed retrospective collection of patient data from NB operations conducted between 2016 and 2020, together with the computation of a Surgical Complexity Index (SCI) for every patient. The SCI values obtained were correlated with preoperatively identified IDRFs. Mann-Whitney statistical test was employed to assign a relevance score to the association between individual IDRFs and SCI., Results: 14 centers contributed 427 neuroblastoma index cases meeting study inclusion criteria. 303 patients had 1 or more IDRFs. The presence and number of IDRFs in all patients significantly correlated with the SCI value (p < 0.0001). The most frequently encountered IDRF was renal pedicle involvement. There was a significant association observed between clusters of abdominal IDRFs and the occurrence of post-operative complications (p < 0.05), while a weak association link was found with intra-operative complications. A relevance score for individual IDRFs allowed their stratification based on surgical risk. The most relevant IDRFs were extension within two anatomical body compartments, infiltration of the hepato-pancreatic block, encasement of the superior mesenteric artery and coeliac axis, and tumor compressing the trachea., Conclusions: This current study has facilitated the assignment of a relevance score to each IDRF, correlating it with surgical risks. Considering this stratification of surgical risk alongside oncologic risk as defined by the neuroblastoma treatment patient risk grouping should facilitate a more precise definition of surgical objectives and the optimal conditions favoring gross tumor resection., Type of Study: Clinical Research - Study of Diagnostic Test., Level of Evidence: III., Competing Interests: Conflict of interest All authors disclose any financial and personal relationships with other people or organizations that could inappropriately influence or bias their work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Within the Paediatric Rare Tumours Network-European Registry (PARTNER) project, we aimed to evaluate the situation on the registration and management of paediatric patients affected by very rare tumours (VRT) in the European low health expenditure average rates (LHEAR) countries., Methods: A survey regarding infrastructure, organisation, and clinical decision-making information on VRT was designed. This survey was distributed to the representatives of LHEAR countries involved in the activities of the PARTNER Work Package 7., Results: Eighteen answers from 17 countries were collected regarding the national organisation, methods of registration of VRT cases, the availability of medical experts in VRT, the access to updated diagnostic and therapeutic procedures (such as proton therapy, immunotherapy and, targeted therapies), and research on paediatric VRT. A high variability in the registration and management of patients with VRT has been observed with additional wide inequalities in pathology review, uniformity of clinical decisions, availability of selected procedures, and diagnostic and research tools., Conclusion: In the majority of LHEAR countries, no clinical or research structures have been implemented for children and adolescents with VRT. Therefore, VRT still have an orphan status in these countries. These significant differences on the technology access and use between European regions need to be addressed., (© 2024. The Author(s).)

Very rare tumors are usually divided into two groups: One includes tumors that are rare among both children and adults; the other one encompasses tumors that frequently occur in adults but are rarely observed in children. In this review, we focus on adrenocortical tumors, neuroendocrine tumors of the appendix, pheochromocytoma and paraganglioma, pancreatoblastoma and solid pseudopapillary tumors of the pancreas, with special attention to the role of surgery as main curative intervention or as part of the multimodal treatment., (© 2024 Wiley Periodicals LLC.)

Pediatric adrenocortical neoplasms (ACNs) are extremely rare tumors in contrast to their adult counterparts. Distinguishing benign from malignant is challenging based on pure morphologic grounds. Previously, 2 scoring systems were proposed in pediatric ACN, including the Wieneke criteria (WC) and its modified version (modified WC [mWC]). In adults, the reticulin algorithm (RA) has proven inexpensive, reliable, predictive, and reproducible; however, it has been validated only recently in children in a limited number of cases. This study aims to assess the RA utility compared with other scoring systems in a series of 92 pediatric ACNs. All cases were individually scored, and mitotic rate cutoffs were recorded. Reticulin alterations were classified as quantitative and qualitative. Outcome data were available in 59/92. The median age was 5 years (0.1 to 18 y) with an M:F of 0.6. Clinical presentation included virilization (39%), Cushing syndrome (21%), other symptoms (4%), and asymptomatic (36%). The reticulin framework was intact in 27% and altered in 73% of cases, showing qualitative (22%), quantitative (73%), and both (5%) alterations. In patients with favorable outcomes, 59% showed either intact reticulin or qualitative alteration compared with the unfavorable outcome group, where 90% showed quantitative alterations. All scoring systems WC ( P < 0.0001), mWC ( P = 0.0003), and the adult/pediatric RA ( P < 0.0001) had predictive value. The RA is comparable to WC and mWC, easier to apply, and is the most sensitive histopathological approach to identifying aggressive behavior in pediatric ACN. Its integration into the WC might be helpful in ACN of uncertain malignant potential and deserves further investigation., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Primary lung carcinoma is an exceptionally rare childhood tumour, as per definition of the European Cooperative Study Group on Paediatric Rare Tumours (EXPeRT), with an incidence of 0.1-0.2/1,000,000 per year. Little is known about the clinical characteristics of children with primary lung carcinoma, a gap which this joint analysis of the EXPeRT group aimed to fill., Patients and Methods: We performed a retrospective case series of children (aged 0-18 years) with primary lung carcinoma, as collected through the EXPeRT databases between 2000 and 2021. We recorded relevant clinical characteristics including treatment and outcome., Results: Thirty-eight patients were identified with a median age of 12.8 years at diagnosis (range: 0-17). Mucoepidermoid carcinoma (MEC) was the most frequent entity (n = 20), followed by adenocarcinoma (n = 12), squamous cell carcinoma (n = 4), adenosquamous carcinoma (n = 1) and small-cell lung cancer (n = 1). Patients with MEC presented rarely with lymph node metastases (2/20 cases). Overall, 19/20 patients achieved long-lasting remission by surgical resection only. Patients with other histologies often presented in advanced stages (14/18 TNM stage IV). With multimodal treatment, 3-year overall survival was 52% ± 13%. While all patients with squamous cell carcinoma died, the 12 patients with adenocarcinoma had a 3-year overall survival of 64% ± 15%., Conclusions: Primary lung carcinomas rarely occur in children. While the outcome of children with MEC is favourable with surgery alone, patients with other histotypes have a poor prognosis, despite aggressive treatment, highlighting the need to develop new strategies for these children, such as mutation-guided treatment., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Purpose: Pediatric adrenocortical carcinoma (pACC) is a rare disease with poor prognosis. Publications on radiotherapy (RT) are scarce. This review summarizes the current data on RT for pACC and possibly provides first evidence to justify its use in this setting., Materials and Methods: We searched the PubMed and Embase database for manuscripts regarding RT for pACC., Results: We included 17 manuscripts reporting on 76 patients treated with RT, after screening 2961 references and 269 full articles. In addition, we added data of 4 unreported pACC patients treated by co-authors. All reports based on retrospective data. Median age at first diagnosis was 11.1 years (70% female); 78% of patients presented with hormonal activity. RT was mostly performed for curative intent (78%). 88% of RT were administered during primary therapy. The site of RT was predominantly the local tumor bed (76%). Doses of RT ranged from 15 to 62 Gy (median 50 Gy). Information on target volumes or fractionation were lacking. Median follow-up was 6,9 years and 64% of the patients died of disease, with 33% alive without disease. In 16 of 48 patients with available follow-up data after adjuvant RT (33%) no recurrence was reported and in 3 of 9 patients palliative RT seemed to induce some benefit for the patient., Conclusions: Our first systematic review on RT for pACC provides too few data for any general recommendation, but adjuvant RT in patients with high risk might be considered. International collaborative studies are urgently needed to establish better evidence on the role of RT in this rare malignancy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Background: Inguinal hernia containing the uterus in pediatric patients with normal karyotype and phenotype is an extremely rare entity, and no consensus is available concerning diagnosis, surgical management, and follow-up., Methods: A systematic review according to the Synthesis Without Meta-analysis protocol was conducted. Studies including pediatric female patients with inguinal hernia containing the uterus were searched. Keywords and mesh term searches were conducted (Medline, Scopus, and Web of Science). We additionally reviewed our center's clinical records and found 1 patient with an inguinal uterus hernia that was included in the statistical analysis., Results: Thirty-six articles and 73 patients were considered for this analysis. The median gestational age at birth was 36 weeks. The inguinal mass was first noticed at the median age of 1.5 months (0-18 months), on the left side in 61% (on the right in 16, 39%). Sixty percent of patients had no associated symptoms or signs; 37.5% showed symptoms and signs of an incarcerated hernia. Median age at surgery was 2 months (1-72 months). In all patients, one or both adnexa herniated with the uterus. An open approach was more frequently used (56.4%). Contralateral duct exploration and ligation was performed in 7 patients (24.1%). No postoperative complications or recurrence have been described., Conclusions: The data obtained do not allow us to draw univocal conclusions on which is the best management in these patients. It is still unclear if an elective approach in an asymptomatic patient might bear long-term consequences on reproductive functions. No surgical technique proved to be superior to others, but both the open and laparoscopic approaches seem to be effective without postoperative complications or recurrence., (Copyright © 2021. Published by Elsevier Inc.)

Background: The aim was to assess the success of a three-drug regimen, consisting of cefazoline, metronidazole and gentamicine, for the antimicrobial treatment of complicated appendicitis and to investigate predictors of failure., Methods: This retrospective study included patients who had undergone appendectomy for complicated appendicitis from 2013 to 2018. The shift to second-line antibiotics was considered a failure. The choice was based upon clinical deterioration. Patients were grouped into 2 groups: localized complicated appendicitis (LCA) and extensively complicated appendicitis (ECA) for the study purpose. Univariate and multivariate analysis were performed to identify predictors of failure., Results: Ninety patients (65.2%) with LCA and 48 patients (35%) with ECA were included. Three-drug regimen failed in 50 patients (36%) with a higher rate in the ECA group (50%, p=0.017). In a multivariate analysis, this failure was found to be associated with ECA (adjusted OR 3.00 [1.2-7.4], p=0.041). Children with ECA experienced a longer hospital stay (median length 8 days, p &lt; 0.001) and antimicrobial therapy (median length 8 days, p &lt; 0.001). However, no difference in the rate of surgical site infections was found (p=0.514)., Conclusions: The institutional antibiotic stewardship program highlighted a high failure rate for the old threedrug regimen. A new protocol should be recommended, especially for the patients affected by ECA.

Pancreatoblastoma (PB) is a tumor typically seen in childhood. Despite its rarity, there are some internationally agreed recommendations for its first-line treatment, but very little is known about the management of relapse. We reviewed the literature on the treatment and outcome of children with progressing/recurrent PB, and the role of high-dose chemotherapy (HD-CT) or liver transplantation in difficult cases. A first analysis concerned 15 patients: liver metastases were the most frequent cause of first-line treatment failure. Eight patients underwent surgery, only 3 were irradiated. Various second-line chemotherapy regimens were adopted, with evidence of response in 8 children. The most often-used combinations included etoposide, cyclophosphamide/ifosfamide, and cisplatin/carboplatin. Overall, 7 patients are alive with a median follow-up of 24 months (range, 3 to 88 mo). In a separate analysis, considering patients in first-line or second-line treatment, we found 5 of 6 patients alive after HD-CT and 3 of 3 after liver transplantation. Our review shows that the outcome for patients with recurrent PB is not always dismal, especially when surgery is possible. Different chemotherapy combinations can be used, and HD-CT or liver transplantation may be considered in selected cases., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Adrenocortical tumours (ACTs) are rare during childhood. A complete surgical resection provides the best chance of cure, but the role and efficacy of the adjuvant therapy are still controversial. Various histologic criteria of malignancy for ACTs adopted in children do not facilitate comparative studies and are not completely shared. Therefore, a sharp demarcation between benign and malignant lesions has not been recognised, making it difficult to identify who potentially needs perioperative therapy. This manuscript presents the internationally harmonised recommendations for the diagnosis and treatment of ACTs in children and adolescents, established by the European Cooperative Study Group for Paediatric Rare Tumours (EXPeRT) group within the EU-funded project PARTNER (Paediatric Rare Tumours Network - European Registry)., (© 2021 Wiley Periodicals LLC.)

Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm that affects typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological confirmation is mandatory. The mainstay of the treatment is a complete surgical resection. Unresectable and/or metastatic PBL may become amenable to complete delayed surgery after neoadjuvant chemotherapy. This manuscript presents the international consensus recommendations for the diagnosis and treatment of children with PBL, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER (Paediatric Rare Tumors Network - European Registry) project., (© 2021 Wiley Periodicals LLC.)

Thymic tumors are epithelial tumors arising from the anterior mediastinum and constitute 0.2-1.5% of all adult malignancies but are exceptional in pediatric population. Thymic epithelial tumors (TETs) encompass a variety of histologic subtypes associated with different clinical outcomes. Due to its rarity in children, TETs' management requires a multidisciplinary approach. However, prognosis remains still poor, especially among patients with thymic carcinoma. This study presents the internationally recognized recommendations for the diagnosis and treatment of thymic tumors in children and adolescents, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) group within the EU-funded project Paediatric Rare Tumours Network - European Registry (PARTNER)., (© 2021 Wiley Periodicals LLC.)

It has become increasingly clear in recent years that we need to develop ad hoc strategies to combat very rare tumors (VRT) of pediatric age. In 2008, several schemes being run in different countries were pooled together to create the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) project: a cooperative study group that aimed to promote research in the relatively uncharted territory of rare tumors of pediatric age. EXPeRT members were able to activate different levels of cooperation to achieve their goals, and to obtain dedicated funding by participating in EU-financed projects. Their experiences emphasize the merits of networking, seeking new partnerships, joining forces, and pooling resources to extend the reach of research efforts, and ultimately improve the quality of patient care. Between 2018 and 2021, the EXPeRT has been active in establishing the Pediatric Rare Tumors Network - European Registry (PARTNER). This project had the main purposes of building a European common registry of pediatric VRT, but also the major task of developing diagnostic and treatment guidelines for VRT (or at least part of them). These clinical recommendations are the subject of a series of papers on Pediatric Blood and Cancer., (© 2021 Wiley Periodicals LLC.)

Background: Extra-appendicular neuroendocrine tumors (NETs) are very rare tumors. While diagnostic and therapeutic guidelines are well established for adults, data on children and adolescents are lacking., Patients and Methods: Patients with a diagnosis of extra-appendicular NET registered on the Tumori Rari in Età Pediatrica - Rare Tumors in Pediatric Age (TREP) from 2000 to 2020 were analyzed. Clinical characteristics including patients' presentation, tumor features, treatment, and outcome were reviewed., Results: Twenty-seven patients with extra-appendicular NET registered on TREP with a median age of 173 months. The primary site was the pancreas (12) or bronchi (10) in the majority of cases. Other primary sites included the thymus, Meckel's diverticulum, and liver. Thirteen (48%) of tumors extended beyond the organ of origin: four invaded neighboring organs and/or regional nodes and nine involved distant metastases. The 3-year event-free survival (EFS) for those with localized disease was superior to those with metastatic disease (66.6% 95% CI 5-95% vs 33% 95% CI 5-68%, respectively; P = .005). A complete resection was feasible in 17 patients. The 3-year EFS in these patients was superior to those with no or incomplete resection (R0 vs R1/R2, respectively; P = .007). Overall, 16 children had no evidence of disease at follow-up, and one is alive with disease; five died, and five were lost to follow-up., Conclusions: Data from our experience demonstrated a wide heterogeneity of presentation and outcome of these tumors. Localized disease and complete surgical resection were the main prognostic factors of good outcome. Other therapies may have a role in prolonging survival in metastatic disease., (© 2021 Wiley Periodicals LLC.)

Pediatric adrenocortical tumors (ACT) are rare and sometimes aggressive malignancies, but there is no consensus on the outcome predictors in children. A systematic search of MEDLINE, SCOPUS, Web of Science, and the Cochrane Library for studies from 1994 to 2020 about pediatric ACT was performed. In 42 studies, 1006 patients, aged 0-18 years, were included. The meta-analyses resulted in the following predictors of better outcome: age <4 years (P < .00001), nonsecreting tumors (P = .004), complete surgical resection (P < .00001), tumor volume (P < .0001), tumor weight (P < .00001), tumor maximum diameter (P = .0009), and Stage I disease (P < .00001). Moreover, patients affected by Cushing syndrome showed a worse outcome (P < .0001). International prospective studies should be implemented to standardize clinical prognostic factors evaluation, together with pathological scores, in the stratification of pediatric ACT., (© 2020 Wiley Periodicals LLC.)

Background: A unique Case of metachronous contralateral cystadenoma diagnosed 2 years after a juvenile granulosa cell tumor (JGCT) of the ovary is reported., Case: One year after a left ovariectomy for JGCT, a 7 year-old girl was found to have, during her standard ultrasound follow-up, a 18-mm cyst in the right ovary, which was initially considered to be a follicular cyst. Six months later, the mass appeared to be increased and characterized by multivacuolar features, and inhibin A was mildly elevated. A laparoscopic-assisted cystectomy was performed, sparing healthy ovarian tissue around. The pathology report showed a benign mucinous cystadenoma., (Copyright © 2021 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

The diagnosis of balanitis xerotica obliterans (BXO) in children may be challenging, since clinical examination only could lead to an underestimation of its incidence. The aim of this retrospective and single-centre study is to assess the diagnostic performance of clinical examination, together with clinical history, in identifying BXO. Ninety-seven children underwent circumcision for phimosis from 2015 to 2019. Histology was routinely performed. Cohen's kappa coefficient, sensitivity, specificity, predictive values, likelihood ratios and accuracy of macroscopic appearance of the foreskin, steroid administration and past medical history were estimated. Forty-eight patients (50%) were affected by BXO; 31 of them (69%) presented with suggestive clinical signs. A strictured or whitish urethral meatus was detected during surgery in nine cases (19%); this was associated to allergic or immune diseases (p = 0.046). Foreskin appearance alone mildly correlated with histology (k = 0.494; p < 0.001) and it showed a diagnostic accuracy of 75%. The specificity and positive predictive value of abnormal macroscopic findings at examination, together with a positive clinical history for other allergic or immune diseases, and/or for balanitis, were 100% and the positive likelihood ratio was greater than 10. Conversely, sensitivity decreased to 4.5% (95% CI 0-11%).Conclusion: Foreskin appearance together with clinical history could predict BXO with certainty. However, since the absence of a positive medical history could not exclude the diagnosis, foreskin histology is still highly recommended. What is Known: • Occurrence of balanitis xerotica obliterans may be underestimated in children and it could lead to long-term complications. • The diagnostic accuracy of clinical examination is controversial. What is New: • Clinical signs together with patients' medical history present high specificity and positive predictive values but low sensitivity. • When suggestive clinical aspects are present, patient should be referred to surgery avoiding prolonged conservative treatment; and preputial histology is highly recommended.

Gastrostomy placement is crucial in neurologically impaired (NI) children to ensure an adequate food intake and a safe route for drugs administration and to reduce the risk of primary aspiration. NI patents are more prone to gastroesophageal reflux. The association with fundoplication is deemed to reduce reflux-related respiratory complications. However, long-term benefits of this approach are not clear. We therefore aimed to compare long-term reflux-related respiratory complications of gastrostomy only (GO) to gastrostomy with fundoplication (GF). We retrospectively reviewed 145 consecutive NI children managed from 2008 to 2018. As long-term outcomes, we analyzed number and length of hospital admissions (Reflux-Related-Hospitalization, RRH) and emergency department accesses (Reflux-Related-Accesses, RRA) due to respiratory problems. Results were analyzed with appropriate statistical method. Median age at referral and at gastrostomy placement were 2.2 and 3.4 years (SD 5.6), respectively. Median follow-up was four years (range 1-12). Anti-reflux procedures were performed in 26/145 patients (18%); tracheotomy in 23/145 (16%). RRH following surgery showed lower number of admissions/year (0.32 vs. 1 for GO vs. GF, p < 0.005) and days hospitalization/year (3 vs. 13, p = 0.08) in GO compared to GF; RRA was similar (0.60 vs. 0.65, p = 0.43). Gastrostomy placement alone appeared not to be inferior to gastrostomy plus fundoplication with respect to long-term respiratory-related outcomes for NI children in our center.

Introduction: Very little is known about the characteristics of mesothelial tumours in the paediatric population. In adults with malignant mesothelioma, the pemetrexed-based regimen with cytoreductive surgery (CRS) is a standard of care in limited tumours, but long-term survival is uncommon., Material and Methods: The European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT) retrospectively reviewed children, adolescents and young adults (≤21 year) diagnosed with mesothelial tumours treated between 1987 and 2018., Results: Thirty-three patients were identified, 15 male and 18 female patients. One patient's exposure to asbestos was documented. Primary tumour was mainly in the peritoneum (23 patients). Histology was multicystic mesothelioma of the peritoneum (MCM) (six patients) or malignant mesothelioma (MM) (27 patients). Among MM, the first-line treatment comprised preoperative chemotherapy (14 cases), surgery only (three cases), chemotherapy only (five cases), adjuvant chemotherapy (three cases) or palliative treatment (two cases). The response rate to cisplatin-pemetrexed was 50% (6/12 cases). CRS with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) was performed in 19 patients (upfront in three, after neoadjuvant therapy in 12, or after tumour progression in six patients, including three twice). After a median follow-up of 6.7 years (range, 0-20), five-year overall and event-free survivals were 82.3% (95% CI, confidential interval ((CI), 67.8-99.9) and 45.1% (95% CI, 28.4-71.7), respectively. All patients with MCM are alive after surgery (five patients) and CRS-HIPEC (one patient)., Conclusions: Paediatric mesothelioma is exceptional and seems to be different from its adult counterpart with few asbestos exposures, more peritoneal primary, and a better outcome. The cisplatin-pemetrexed regimen showed promising efficacy. Relapses could be salvaged with active therapy including CRS-HIPEC., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Pheochromocytomas (PCs) are neuroendocrine tumors arising from the chromaffin cells of the adrenal gland, and paragangliomas (PGLs) are their extra-adrenal counterparts arising from ganglia along the sympathetic/parasympathetic chain. Surgery is the cornerstone of treatment. A sporatic or inherited germline mutation is commonly associated., Materials and Methods: Among over 1000 patients registered into the Tumori Rari in Età Pediatrica-rare tumors in pediatric age project-from 2000 to 2019, 50 were affected by PC/PGL. All clinical and therapeutic data were evaluated., Results: Twenty-eight patients had PC and 22 had PGL. Age at diagnosis ranged between 5 and 17 years. Thirty-five patients had symptoms related to catecholamine hypersecretion; in 7 of 50 patients, diagnosis was incidental or done during assessment of a familial syndrome. In all cases, conventional imaging was effective to assess the presence of a tumor. In addition, 18 of 38 functional imaging studies were positive (61%). Forty-eight patients were eligible for surgery: a complete resection was more frequently achieved in PC than in PGL (26/28 vs 11/22). All relapses were treated with surgery alone, surgery plus medical treatment, or chemotherapy alone; one PC with metastasis at diagnosis received radiotherapy only. Forty-four patients were in the first, second, or third complete remission (10/50 recurred; 8/10 carried a germline mutation). Five of 50 patients were alive with disease. One patient died of disease., Conclusions: Surgery can be curative in most tumors but it may not be always effective in removing PGLs. Severe postsurgical sequelae may affect these patients. Genetic tests should always be considered in individuals affected, and genetic counseling should be offered to their families., (© 2020 Wiley Periodicals, Inc.)