Calogero Virgone

Sex cord stromal tumors of the ovary in children: a clinicopathological report from the Italian TREP project.

Ovarian sex‐cord stromal tumors (SCST) are rare in childhood and include a variety of neoplasms with different clinical features and biologic behavior. Aim of the analysis was to report the clinical findings and treatment results of a series of patients with SCST of the ovary, registered in a multi‐institutional Italian network on rare tumors in children and adolescent between 2000 and 2009.

Sex cord-stromal tumors of the testis in children. A clinicopathologic report from the Italian TREP project

PURPOSE Testicular sex cord-stromal tumors (SCSTs) are very rare in children and include a variety of neoplasms with different clinical features and biologic behavior. Aim of the study was to report the clinical findings and results observed in a series of patients with testicular SCST, registered in a multi-institutional Italian network on rare tumors in children and adolescents. MATERIALS AND METHODS The records of 11 patients, enrolled in 6 Italian centers from January 2000 to December 2008, were reviewed. The Childrens Oncology Group (COG) staging system was adopted. Chemotherapy was recommended in patients with incomplete surgery or metastatic disease. RESULTS A testicular mass was the most common symptom. All patients underwent primary removal of the tumor; orchiectomy with high ligation of spermatic cord was performed in 7 and tumor enucleation in 4. At histology, 4 patients had Leydig cell tumors, 4 juvenile granulosa cell tumors, 1 Sertoli cell tumor, 1 incompletely differentiated SCST, and 1 SCST with an intermediate pattern Sertoli cell tumor/mixed form. The histology of 8 of 11 cases was reviewed and investigated through immunohistochemical stains. Ten children were in stage I; 1 patient, who did not undergo hemiscrotectomy after enucleation through a transscrotal access, was considered stage II. All the patients are in first complete remission (mean follow-up, 59 months; range, 8-94). CONCLUSIONS Our experience confirmed the rarity of testicular SCST. They have to be considered in the differential diagnosis of testicular solid masses, taking into account that hormonal signs are present in a minority of cases. All patients were cured with surgery alone. The sparing surgery represented a choice in selected cases.

Appendiceal Neuroendocrine Tumours in Childhood: Italian TREP Project

Background: Neuroendocrine tumours (NETs) of the appendix are slow-growing tumours and, although rare, they are the most common gastrointestinal epithelial tumours in childhood and adolescence. The treatment and the follow-up screenings have not been standardised. In addition to this, although tumour size is considered the main prognostic variable to define the aggressiveness of approach, a precise cutoff needs to be established. Methods: A total of 113 patients younger than 18 years with a diagnosis of appendiceal NETs were registered as of January 1, 2000, until May 30, 2013, within the Rare Tumors in Pediatric Age (TREP) project, an Italian multi-institutional network dedicated to rare tumours in children and adolescents. The recommendations of the Rare Tumors in Pediatric Age study included imaging and laboratory investigations. The treatment after appendectomy was decided on the basis of histology, tumour size, and imaging; primary reexcision (PRE) was not recommended in completely excised tumours, regardless of tumour size and invasiveness. Results: A total of 113 of 113 patients had a diagnosis of well-differentiated NETs; in 108 of 113 the tumour was smaller than 2 cm and in 5, larger than 2 cm. Excision margins were free in 111 of 113 patients. In 3 of 113 a PRE was performed, and in 1 residual tumour was detected. All 113 of 113 patients are alive in complete remission (median follow-up of 41 months). Conclusions: Reported data and our experience showed that no relapse or death occurred in children and adolescents affected by appendiceal NETs. Appendectomy alone should be considered curative for most patients, and a more aggressive surgical approach is warranted in the cases with incompletely excised tumours.

GATA-4 and FOG-2 Expression in Pediatric Ovarian Sex Cord-Stromal Tumors Replicates Embryonal Gonadal Phenotype: Results from the TREP Project

Aim GATA proteins are a family of zinc finger transcription factors regulating gene expression, differentiation and proliferation in various tissues. The expression of GATA-4 and FOG-2, one of its modulators, was studied in pediatric Sex Cord-Stromal tumors of the ovary, in order to evaluate their potential role as diagnostic markers and prognostic factors. Materials and Methods Clinical and histological data of 15 patients, enrolled into the TREP Project since 2000 were evaluated. When available, immunostaines for FOG-2, GATA-4, α-Inhibin, Vimentin and Pancytokeratin were also analyzed. Results In our series there were 6 Juvenile Granulosa Cell Tumors (JGCT), 6 Sertoli-Leydig Cell Tumors (SLCT), 1 Cellular Fibroma, 1 Theca Cell Tumor and 1 Stromal Sclerosing Tumor (SST). Thirteen patients obtained a complete remission (CR), 1 reached a second CR after the removal of a metachronous tumor and 1 died of disease. Inhibin was detectable in 11/15, Vimentin in 13/15, Pancytokeratin in 6/15, GATA-4 in 5/13 and FOG-2 in 11/15. FOG-2 was highly expressed in 5/6 JGCT, while GATA-4 was weakly detectable only in 1 of the cases. SLCT expressed diffusely FOG-2 (4/6) and GATA-4 (3/5). GATA-4 and FOG-2 were detected in fibroma and thecoma but not in the SST. Conclusions Pediatric granulosa tumors appear to express a FOG-2/GATA-4 phenotype in keeping with primordial ovarian follicles. High expression of GATA-4 does not correlate with aggressive behaviour as seen in adults, but it is probably involved in cell proliferation its absence can be associated with the better outcome of JGCT. SLCTs replicate the phenotype of Sertoli cells during embryogenesis in normal testis. In this group, the lack of expression of FOG-2 in tumors in advanced stages might reveal a hypothetical role in inhibiting GATA-4 cell proliferation pathway. In fibroma/thecoma group GATA-4 and FOG-2 point out the abnormal activation of GATA pathway and might be involved in the onset of these tumors.

Epithelial Tumors of the Ovary in Children and Teenagers: A Prospective Study from the Italian TREP Project

STUDY OBJECTIVE To report the clinical findings and treatment results of a series of patients with epithelial tumors of the ovary, registered and treated prospectively in a multi-institutional Italian network (TREP project) on rare tumors in children and adolescent between 2000 and 2014. DESIGN, SETTING, AND PARTICIPANTS Data on 16 patients, aged 22 to 206 months, from 7 centers were reviewed. All patients were grouped on the basis of the results of the first surgical approach, according to the Children Oncology Group staging system. RESULTS The most frequent symptom was abdominal pain; 3 patients were hospitalized for acute pain after ovarian torsion. Initial surgical treatment was complete in 15 of 16, and a biopsy was performed in 1 of 16. The histology examination revealed 8 benign tumors (7 mucinous cystadenomas and 1 serous cystadenoma) and 8 borderline tumors (2 serous and 6 mucinous). Fifteen of 16 patients maintained the complete remission after surgical treatment alone; 1 affected by Proteus syndrome died consequent to the progression of a synchronous Wilms tumor, after a delayed incomplete surgery. CONCLUSION Our analysis documented the rarity of these tumors in children and adolescents. No malignant histologies were found. Surgery alone was effective to cure the majority of patients. Considering the rarity of malignant entities, ovary-sparing surgery may be planned when an epithelial tumor is suspected on the basis of the preoperative work-up and intraoperative findings.

Comparative retrospective study on the modalities of biopsying peripheral neuroblastic tumors: a report from the Italian Pediatric Surgical Oncology Group (GICOP)

Peripheral neuroblastic tumors are the most common extracranial solid neoplasms in children. Early and adequate tissue sampling may speed up the diagnostic process and ensure a prompt start of optimal treatment whenever needed. Different biopsy techniques have been described. The purpose of this multi‐center study is to evaluate the accuracy and safety of the various examined techniques and to determine whether a preferential procedure exists.

Outcome after surgery for solid pseudopapillary pancreatic tumors in children: Report from the TREP project-Italian Rare Tumors Study Group

Solid pseudopapillary pancreatic tumors (SPPT) are an extremely rare entity in pediatric patients. Even if the role of radical surgical resection as primary treatment is well established, data about follow‐up after pancreatic resection in children are scant.

Gastrointestinal tract carcinoma in pediatric and adolescent age: The Italian TREP project experience

Gastrointestinal (GI) carcinomas are very rare in the pediatric and adolescent age range. We report the clinical features, treatment, and outcome of a series of children and adolescents with GI carcinoma prospectively registered in the Italian Tumori Rari in Età Pediatrica (TREP) project.

DAX-1 Expression in Pediatric Rhabdomyosarcomas: Another Immunohistochemical Marker Useful in the Diagnosis of Translocation Positive Alveolar Rhabdomyosarcoma

Objectives The aim of this study was to investigate the expression of DAX-1 in a series of pediatric rhabdomyosarcomas (RMS) with known translocation and compare it to Ap2β, known to be selectively expressed in ARMS. Design We revised a series of 71 alveolar rhabdomyosarcomas (ARMS), enrolled in the Italian Protocols RMS 79 and 96, and 23 embryonal rhabdomyosarcomas (ERMS) as controls. Before investigating Ap2β and DAX-1, ARMS were reviewed and reclassified as 48 ARMS and 23 non-ARMS. Results Translocation positive ARMS showed a characteristic Ap2β/DAX-1+ staining pattern in 78% of cases, while 76% of classic ERMS were negative for both. Ap2β alone was positive in 3.9% of RMS lacking translocation, whereas DAX-1 alone was positive in 25.4%. Conversely, 9% and 6% of translocation positive ARMS were positive only for DAX-1 or Ap2β, respectively. The 23 non-ARMS shared the same phenotype as ERMS but had a higher frequency of DAX-1 expression. Conclusions DAX-1 is less specific than Ap2β, however it is a sensitive marker for translocation positive ARMS and can be helpful in their diagnosis if used in combination with Ap2β.