Diagnostic Utility of a Modified Reticulin Algorithm in Pediatric Adrenocortical Neoplasms.

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.

Localized vaginal/uterine rhabdomyosarcoma-results of a pooled analysis from four international cooperative groups.

BACKGROUND: Vaginal/uterine rhabdomyosarcoma (VU RMS) is one of the most favorable RMS sites. To determine the optimal therapy, the experience of four cooperative groups (Children's Oncology Group [COG], International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Group [MMT], Italian Cooperative Soft Tissue Sarcoma Group [ICG], and European pediatric Soft tissue sarcoma Study Group [EpSSG]) was analyzed. PROCEDURE: From 1981 to 2009, 237 patients were identified. Median age (years) at diagnosis differed by tumor location; it was 1.9 for vagina (n = 160), 2.7 for uterus corpus (n = 26), and 13.5 for uterus cervix (n = 51). Twenty-eight percent of patients received radiation therapy (RT) as part of primary therapy (23% COG, 27% MMT, 46% ICG, and 42% EpSSG), with significant differences in the use of brachytherapy between the cooperative groups (23% COG, 76% MMT, 64% ICG, and 88% EpSSG). RESULTS: Ten-year event-free (EFS) and overall survival (OS) were 74% (95% CI, 67-79%) and 92% (95% CI, 88-96%), respectively. In univariate analysis, OS was inferior for patients with uterine RMS and for those with regional lymph node involvement. Although EFS was slightly lower in patients without initial RT (71% without RT vs. 81% with RT; P = 0.08), there was no difference in OS (94% without RT vs. 89% with RT; P = 0.18). Local control using brachytherapy was excellent (93%). Fifty-one (51.5%) of the 99 survivors with known primary therapy and treatment for relapse were cured with chemotherapy with or without conservative surgery. CONCLUSIONS: About half of all patients with VU RMS can be cured without systematic RT or radical surgery. When RT is indicated, modalities that limit sequelae should be considered, such as brachytherapy.

Pancreatic tumors in children and adolescents: the Italian TREP project experience.

INTRODUCTION: Malignant pancreatic tumors are exceedingly rare in pediatric age and their clinical features and treatment usually go unappreciated by most pediatric oncologists and surgeons. METHODS: From January 2000 to July 2009, 21 patients <18 years old with pancreatic tumors were prospectively registered in the Italian cooperative TREP project dedicated to very rare pediatric tumors. RESULTS: Tumor types were 4 pancreatoblastomas, 2 pancreatic carcinomas, 3 neoplasms of the endocrine pancreas, and 12 solid pseudopapillary tumors. Three of the four patients with pancreatoblastoma had advanced disease at diagnosis and were given chemotherapy; at the time of this report, three patients were alive in first remission, while one died due to treatment toxicity. Both the cases of pancreatic carcinoma had the acinar cell subtype and successfully underwent pancreaticoduodenectomy with complete tumor resection, remaining without evidence of disease at the time of this analysis. The histological diagnoses of the three endocrine tumors were a malignant islet cell tumor, a gastrinoma, and a well-differentiated tumor. All 12 patients with solid pseudopapillary tumors underwent complete tumor resection and were given no adjuvant treatment; 11 were alive in first remission, while one experienced a local and distant relapse 5 years after diagnosis. CONCLUSIONS: Surgery remains the keystone of treatment for pancreatic tumors in pediatric age as in adults. The TREP project shows that prospective cooperative studies are feasible even for such very rare tumors as these and may serve as a model for developing international cooperative schemes.

Prognostic factors in pleuro-pulmonary blastoma.

PURPOSE: To evaluate the prognostic factors in a series of children affected by pleuropulmonary blastoma (PPB). PATIENTS AND METHODS: Clinicopathological findings, treatment, and outcome of 22 PPB cases observed in 13 Italian Associations for Pediatric Hematology and Oncology centers are reported. Clinical data, surgical notes, pathologic findings, and summaries of treatment were taken from the charts and correlated with outcome by standard statistical methods. RESULTS: The series included 22 patients (14 males) with a median age of 30.5 months followed up for a median of 22 months (range 2-176 months). In nine patients the PPB developed with lung involvement only. Congenital lung cysts were recorded in five cases. Nine patients had recurrences. Gender, side, tumor size, pre-existing lung cysts, and extent of surgical resection at diagnosis did not significantly affect survival by univariate analysis. Achieving total resection of the tumor at any time of treatment resulted in a significantly better prognosis (P = 0.01), whereas extrapulmonary involvement at diagnosis resulted in a significantly worse prognosis (P = 0.01). Estimated 15-year event-free and overall survival rates were 44 and 49% for all patients, respectively. CONCLUSIONS: PPB is an aggressive neoplasm. Total resection of PPB performed at any time of treatment appears to provide a better outcome, whereas extrapulmonary involvement at diagnosis worsens the prognosis.