Teratoma with a malignant somatic component in pediatric patients: the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience.

BACKGROUND: Teratoma with a malignant somatic component (TMSC) is rare but described in adults, whereas information on pediatric presentation is sparse. PROCEDURE: The Associazione Italiana Ematologia Oncologia Pediatrica identified 14 cases of TMSC. Clinical files and pathology specimens were reviewed. RESULTS: The series (9 female, 5 male) showed the following disease: testis (2), sacrococcygeal (3), ovary (3), retroperitoneum (3), mediastinum (2), and foot soft tissue (1). Distribution of the somatic component was: carcinoma (4), pancreatic neuroendocrine tumor (1), neuroblastoma (3), rhabdomyosarcoma (3), rhabdomyosarcoma plus liposarcoma, chondrosarcoma, neurogenic sarcoma (1), chondrosarcoma plus neuroectodermal sarcoma (1), malignant peripheral nerve sheath tumor (1). Three patients were in stage I, four in stage II, three in stage III, and four in stage IV. All but one patient underwent surgery and only females showed carcinoma components. Nine patients relapsed or progressed and eight died. Six patients are alive and disease-free. Two patients underwent complete resection and four were treated based on transformed histologies. Relapse-free and overall survival rates were 35.7% and 42.8%, respectively (median follow-up, 31 months). CONCLUSIONS: Prognosis for germ cell tumors (GCTs) containing MSC is worse than that for GCTs. The pediatric disease appears to be more heterogeneous in tumor site distribution and MSC histology than in adults. Our series suggests no effects of age, histology, or gender on outcome. Surgery has an essential role in localized disease, with complete resection highly desirable. Chemotherapy optimized for histology should include reagents directed to the somatic malignancy, if chemosensitive. Malignant GCT warrants GCT-directed chemotherapy.

The correlation of functional pain and psychological distress: a study in Italian school students.

BACKGROUND: Functional Pain (not detectable organic cause) is often associated with psychological problems and, according to literature, it can lead to severe manifestations. The purpose of the study was to investigate the correlation between functional pain and psychological disagreement, in a series of school students. METHODS: An observational questionnaire-based study was performed. A questionnaire was given to a group of students of primary school; the following data were collected in the questionnaire: a) sex and age; b) functional pain; c) relation with relatives, teachers and schoolfellows: d) school failure. STATISTICAL METHODS: P-value of concordance test and P-value of correlation have been performed with MINITAB 15.1 software. RESULTS: Eight hundred nine students, 354 females, 455 males, median age 14 years, participated to the study. Functional Pain was referred from 537/809 students (66%): 265 Females, 272 males: p = 0.155. The difference between the number of pain episodes in females vs. males was statistically significant (p = 0,511), as pain intensity vs. the number of episodes in females (p = 0.001). The most frequent location of pain was abdomen in females, limbs in males. Psychological disagreement was referred from 513/809 students (63%) (260 females; 253 males: p = 0,150). Psychological disagreement was reported with parents (19); siblings (22); other relatives (18); teachers: 42, schoolfellows: 366, relatives as well as school fellows: 46. The correlation between disagreement and functional pain in all the students included in the study was statistically significant (p < 0.001). CONCLUSIONS: most students reported psychological disagreement and pain. The most frequent cause of disagreement was schoolfellows' behaviour. The study shows a student's lack of discussing of their problems with parents, teachers, peer. According to literature, confiance would be a useful treatment for avoiding psychological disagreements and functional pain.

Bax mutation and overexpression inversely correlate with immature phenotype and prognosis of childhood germ cell tumors.

Primary childhood germ cell tumors (GCTs) represent a rare and heterogeneous group of tumors that varies in histologic differentiation, age of presentation and clinical outcome. In malignant neoplasms, apoptosis is a prognostic marker and a predictive factor of response to therapy. Therefore, the study of the expression and mutation of molecules involved in the regulation of apoptosis could be useful in order to both predict the clinical outcome and design self-tailored therapeutic approaches. We retrospectively analysed tissue samples of 54 childhood GCTs. The expression of p53 and BAX protein was assessed by immunohistochemistry (IHC). Moreover, we investigated the presence of mutations in the BAX and p53 genes SSCP-PCR and direct sequencing. IHC analysis of BAX protein expression showed that 14 out of 54 tumors (26%) had no BAX protein expression, in the remaining 40 patients (74%) the intensity of BAX was low in 20 patients (37%) and high/intermediate in 20 (37%). BAX was mutated in 6 patients. p53 was expressed in 43 patients (79.6%), was not detectable in the remaining 11 (20.4%) and mutated in only 3 patients. p53 mutational status and expression were not correlated to the overall survival (OS). On the other hand, both IHC score and mutations for BAX were correlated to sacrococcygeal primary localization. BAX mutations were inversely correlated with OS (p=0.0419) while BAX IHC intensity was directly correlated with OS (p=0.0376). The stratification for histotype showed a direct correlation between BAX IHC and OS in both immature teratoma (p=0.045) and mixed malignant GCT (p=0.010) while the correlation was lost in mature teratoma (p=0.300). These results indicate that both mutations and BAX protein levels are useful molecular biological markers for prognosis and clinical management of pediatric GCT.

Mature and immature teratomas: results of the first paediatric Italian study.

Teratoma is the most common germ cell tumour in childhood; mature (MT) and immature teratomas (IT) are benign tumours, but if they recur, they can be in some cases malignant. The aim of this paper is to evaluate Italian patients with MT and IT enrolled from 1991 to 2001, in a prospective multicentric study. One hundred and eighty-three patients, observed in 15 Italian Centers of Paediatric Oncology and three Paediatric Surgical Units were enrolled. Clinical data, treatment and results were all analysed. Initial evaluation and subsequent follow up included clinical examination, tumour markers and imaging procedures. Surgical resection was recommended for all the tumours. Histology was centrally reviewed and IT was classified as grading 1-3. Chemotherapy (CT) with Vinblastine, D: -actinomycin and cyclophosphamide was indicated for extra-testicular IT grade 2 or 3. MT was diagnosed in 127 patients (93 F and 34 M, age 1-192 months, median 24): 58 patients had gonadic tumour (23 testicular, 35 ovaric), 69 extragonadic (45 sacrococcygeal, 11 mediastinic, 7 retroperitoneal, 6 in other sites). A complete resection was performed in 117 patients, a partial resection in eight patients and biopsy in one. IT was diagnosed in 56 patients (34 F, 22 M, age 1-168 months, median 7). The T grading was 1 in 14 cases, 2 in 26, 3 in 16; 28 had gonadic T (17 ovary, 11 testis), 28 extragonadic (sacrococcygeal 19, mediastinic 3, retroperitoneal 2, other sites 4). CT was administered in eight patients; 15/182 patients relapsed (1 in a metastatic site) and in 5/15 the relapse showed malignant histology. Seven MT (5.5%) relapsed (five sacrococcygeal, one retroperitoneal, one mediastinic): surgery at diagnosis had been complete in five and with residual in two; the relapse was malignant in two patients with sacrococcygeal (sc) tumours, who had a complete resection and a partial resection respectively. Eight IT (14.2%) relapsed (four ovary, three sc, one retroperitoneal). The initial surgical resection had been complete in one, with residual in six, and a biopsy had been performed in one. A malignant recurrence occurred in two patients with sc tumours (after partial resection in one and after biopsy + CT in one) and in one patient with ovarian IT after a partial resection. All the patients underwent surgical excision of the recurred mass; CT according to Protocol for Malignant GCT was administered to those who had malignant recurrence; 122/126 patients with MT and 53/56 with IT are alive without disease with a follow up of 8-144 months (median 56). Two patients with malignant relapse (one with sc MT, one with sc IT) died because of the progression of the disease. Another two died due to severe malformations (one MT, one IT) and three were lost to follow up (two MT, one IT). The overall survival (OS) at 10 years is 98% (95% CI 93.9-99.4); the event free survival (EFS) is 90.4% (95 CI 84.8-94.0). At Cox analysis no significant difference in EFS was found regarding age and site of the primary tumour, while females (P = 0.011), patients with grade 1-3 histology (P = 0.025) and patients with incomplete resection appeared at higher risk of death or relapse (P < 0.001), with a seven, three and eightfold increase in risk, respectively. Our data showed that incomplete resection and female gender are important risk factors for relapse or death, more so than IT histology. The number of patients treated with CT is not sufficient to evaluate the efficacy of CT in avoiding malignant relapse.

Perlman syndrome: clinical report and nine-year follow-up.

We present the clinical and follow-up data of a female infant with Perlman syndrome from birth to the age of 9 years. Main features of Perlman syndrome include polyhydramnios, fetal overgrowth, neonatal macrosomia, macrocephaly, dysmorphic facial features, visceromegaly, nephroblastomatosis, and a predisposition for Wilm's tumor. In our patient, the nephromegaly with nephroblastomatosis was not present at birth or during the neonatal period; it became evident in the first months of postnatal life. A Wilm's tumor was diagnosed when she was about 1 year old. Long term follow-up documents the natural history of Perlman syndrome and allows us to establish the long-term prognosis of the affected individuals.

Malignant germ cell tumors in childhood: results of the first Italian cooperative study "TCG 91".

BACKGROUND AND AIMS: About 20% of patients with germ cell tumor (GCT) are still resistant to therapy. To investigate which features are present in resistant patients, a multicenter study on GCT in children was undertaken to correlate clinical and laboratory parameters with the outcome. METHODS: Patients aged less than 16 years, with histologically proven extracranial GCT were included. RESULTS: Ninety-five patients (median age 33 months, 45 males) were eligible. The site of the primary tumor was gonadal in 59, extragonadal in 36. The stage was I in 39; II in 5; IIIa (microscopic residue) in 7; IIIb (macroscopic residue) in 16; IIIc (unresectable) in 13; IV in 15. The treatment was surgery alone in 31; surgery plus radiotherapy in 1; chemotherapy +/- surgery in 63. Post-chemotherapy resection in 19 (10 complete, 9 partial). The chemotherapy regimen was carboplatin 400 mg/m2/day on days 1, 2; etoposide 150 mg/m2/day on days 1, 2; ifosfamide 1,500 mg/m2/day on days 21, 22; dactinomycin 1.5 mg/m2/day on day 21; vincristine 1.5 mg/m2/day on day 21. Three patients died because of toxicity and two non-responders (to primary chemotherapy), died of progression; among the remaining 90 patients 20 relapsed, 9 are in second remission, 2 are alive with disease, and 9 died of disease progression (one from progression and intracranial hemorrhage). Overall survival was 82.7% and event-free survival: 71.5%. Survival according to: (a) site: testis: 100%; ovary: 88%; sacrococcyx: 69.6%; other sites: 33.3% (P < 0.001); (b) stage: I and II: 100%; IIIa: 83.3%; IIIb: 84.6%; IIIc: 60.6%; IV: 53.2% (P < 0.001); (c) AFP levels: normal: 85.5%; 42-9,470 ng/ml: 84.6%; >/=10,000 ng/ml: 58.7% (P = 0.02). All the pts who had complete resection of the primary tumor at diagnosis or at delayed surgery, remained in remission. CONCLUSIONS: Multivariate analysis showed that the primary site of tumor was the only independent prognostic factor for survival and EFS.