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.

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.

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.