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ITAL J PEDIATR 2006;32:122-125 CASE REPORT CASO CLINICO Pleuropulmonary blastoma: a differential diagnosis of chronic cough. Long-term survival after multimodal aggressive therapy Blastoma pleuro-polmonare: rara diagnosi differenziale da tosse cronica. Remissione a lungo termine dopo aggressiva terapia multimodale P. D''ANGELO, V. MANZO*, S. VENEZIA*, R. ALAGGIO", E SIRACUSA*, M. LO CURTO* Unità Operativa di Oncoematologia Pediatrica, Ospedale dei Bambini " G . Di Cristina", Palermo; * Dipartimento Materno Infantile, Università di Palermo; ** Istituto di Anatomia Patologica, Università di Padova Summary Pleuropulmonary blastoma (PPB) in childhood is a rare clinicopathologic entity distinct from adult pneumoblastoma. This tumour may originate from the lung, the pleura, or the mediastinum; it can metastasize and is usually associated with a poor outcome. We report the case of a 5-year-old boy who developed PPB manifesting with respiratory distress. At the standard x-ray and magnetic resonance imaging of the chest there was opacity covering the entire right lung. The histological and immunohistological tests led to the diagnosis of blastematous, malignant mesenchymatous PPB with pluridirectional differentiation. Treatment consisted of preoperative chemotherapy to reduce tumour volume, complete surgical resection of the residuai tumour mass, and post-surgical chemotherapy. Following this approach, the child is alive in continuous complete remission 9 years after diagnosis. Riassunto II Blastoma Pleuro-Polmonare (BPP) infantile è un ''entità clinico patologica ben distinta dal Pneumoblastoma dell''adulto. Questo tumore può prendere origine dal polmone, dalla pleura o dal mediastino; può metastatizzare e ha spesso una prognosi infausta. Riportiamo il caso di un bambino di 5 anni, in cui il BPP si manifestò con un distress respiratorio; la radiografia del torace e la Risonanza Magnetica hanno evidenziato una grossa massa che occupava l''emitorace destro. L''esame istopatologico ha permesso di porre diagnosi di BPP. Il paziente è stato trattato con chemioterapia, che ha ridotto il volume della massa, con asportazione del tumore e chemioterapia post-operatoria; tale trattamento ha consentito i''eradicazione della malattia; il paziente è in remissione completa continua a 9 anni dalla diagnosi. Introduction Pleuropulmonary blastoma (PPB) is an extremely rare and aggressive malignancy of childhood. It was originally described as a distinct entity by Manivel et al. ''. Prior to its identification it was reported in the early literature by Spencer as pulmonary blastoma or embryonic sarcoma 2. It is characterized by primitive mesenchymal tissue and epithelial tubular structures resembling the foetal lung. The eponymous PPB defines the paediatric variety of pulmonary blastoma. In PPB, the dysembrionic neoplasm shows blastematous and sarcomatous components and a lack of carcinomatous components (which are instead present in adult pulmonary blastoma), sometimes on previous dysplastic pulmonary conditions 3 . PPB is classified in 3 subtypes: type I (cystic), type II (mixed solid and cystic) and type III (solid)4. Key words Pleuropulmonary blastoma • Childhood lung cancer • Adjuvant chemotherapy Parole chiave Blastoma pleuropolmonare • Tumore polmonare infantile • Chemioterapia post-operatoria Submitted: March 16, 2005 Accepted: July 19, 2005 Correspondence: Prof. Margherita Lo Curto Dipartimento di Pediatria Università di Palermo Istituto Materno Infantile via Cardinale Rampolla 1 Palermo, Italy Tel. +39 091 6555476 E-mail: margheritalocurto@virgilio.it. 122 PLEUROPULMONARY BLASTOMA IN A CHILD The predominant clinical features are cough, tachypnea, fever, respiratory distress; secondary pneumothorax 5 and chest pain have also been reported 6. Since these features are not specific, an infectious disease is often erroneously diagnosed; hence, when eventually detected, the neoplasm is often very large, may even involve an entire hemithorax, and present metastases. Despite the different therapeutic procedures - surgery, chemotherapy and radiotherapy - prognosis is often poor: Indolfi et al. 7 report 42% and Priest et al. 6 45% of event free survival (EFS) at 2 years. Poor prognostic factors are histological subtype II or III6 , a maximum diameter greater than 5 cm 7 , failure to completely remove the mass, extrapulmonary effusion such as pleura or pericardium, metastases 8. We report the case of a five-year-old child who, despite the large tumour size at diagnosis and histological subtype II, after a treatment with chemotherapy before and after surgery, is in continuous complete remission (CCR) nine years after the diagnosis. Case report A 5-year-old boy was admitted to our ward for hyporexia, cough, shortness of breath, progressive thinning and pallor in the previous 2 months. The physical examination showed poor clinical conditions, tachydyspnea (R.F. 45/min.), hypophonesis and reduction of the physiologic vescicular murmure of the middle and lower regions of the right lung, meteoric abdomen with the liver margin 5 cm below the right costai margin. The results of the laboratory investigations were Hb 8.5 g/dl, white blood cells 18.800/ul (N 68%, L 22%, M 6%, E 4%), platelets 611.000/u.l, VES (K.I.) 65, CRP 2.4 mg/dl; serum levels of copper 168 ixg/dl, ferritin 292 ng/dl, LDH 1.261 u/1, oc-FP 6.3 u/1. Chest radiographs showed a bulky mass in the right hemithorax displacing the mediastinum leftward and the liver downward (Fig. 1). The thoracic-abdominal ultrasound scan showed a poorly confined voluminous mass, having diameters of 120 x 86 mm, with echogenic-hyperechogenic structure and some hypo-anechogenic areas, arising in right hemithorax and displacing the liver and right kidney downwards. A magnetic resonance imaging (MRI) of the thorax showed a mass involving entirely the right hemitorax, with a centrai hemorrhagic component that displaced the mediastinum and the heart to the left. The patient underwent surgical thoracotomy, which revealed an unencapsulated mass with smooth surface and tense-elastic consistency, entirely covered by pleura, not adherent to the thoracic wall; since the conspicuous extension of the mass did not allow resection, only a biopsy was performed. Microscopically, the biopsy specimen showed a predominantly solid neoplasm with focal cysts. The tumour contained mesenchymal elongated cells arranged in sheets, and more primitive blastematous foci. There Fig. 1. Posterior-anterior chest radiograph at presentation, showing a bulky mass, displacing the mediastinum. was no evidence of typical rhabdomyoblasts or cartilage. Cysts exhibited an epithelial lining, with flattened to columnar cells and an underlying layer of primitive mesenchymal cells. The morphologic appearance was consistent with a diagnosis of PPB type II. Immunostains emphasized the doublé component with a positive staining for cytokeratin (MNF116, pancytokeratin) in the epithelial component and a positive vimentin staining in mesenchymal component. Occasionai spindle cells were positive for desmin; oc-fetoprotein, S-100 protein, CD99, NB84A were negative in both the epithelial and the stremai component. In order to stage the disease the patient underwent total body bone scan with "Tc-MDP, brain and abdominal CT scan, and bone marrow aspirate; no metastatic spread was detected, and a stage III was defined. The child underwent chemotherapy with carboplatinum (CBP) 400 mg/m2 + etoposide (VP16) 150 mg/m2 days 1, 2; vincristine (VCR) 1.5 mg/m2 + actinomycin-D (ACT-D) 1.5 mg/m2 day 21 + ifosfamide (IFO) 1500 mg/m2 days 21-23, for overall 3 cycles; thereafter, 2 cycles were scheduled, including VCR 1.5 mg/m2 + ACTD 1.5 mg/m2 day 1, doxorubicin 40 mg/m2 days 1-2 and IFO 1500 mg/m2 days 1-3. The number of cycles were established according to the features of imaging studies. A chest x-ray survey showed a very good response (Fig. 2) to chemotherapy. Six months after the diagnosis complete resection of the tumour was performed through a right posterior-lateral thoracotomy by the fifth intercostal space. The tumour was capsulated and located between the upper and middle lobe of the right lung, displacing caudally the middle and lower pulmonary lobes. The centrai zone of the mass was composed of hyalinized fibrous stroma nodules and very small fragments of blastomatosous tumoral tissue, at about 2 cm from the resection borders. The neoplasm was almost entirely necrotic. 123 P. D''ANGELO ET AL. Fig. 2. Posterior-anterior chest radiograph, after chemotherapy, before surgical excision. After surgery the patient underwent 2 more cycles of chemotherapy with CBP 400 mg/m2 + VP 16 150 mg/m2/day x 2 days. There was clinical and imaging evidence of a progressive normalisation of lung morphology and function. The patient was monitored with clinical and radiological investigations according to the following schedule: chest radiograms every 3 months the first year, every 6 months the second and third year, every 12 months for the 4t h, 5l h and 6* year; MRI at 1 and 3 years after withdrawal of therapy. Nine years after the diagnosis, the child is in continuous complete remission. Discussion PPB in childhood is very rare. Our patient, as most of those reported in the literature 5 8 , presented unspecific respiratory symptoms; the x-ray revealed a large intrathoracic mass, suggesting the need for further imaging studies. It is important to emphasize the role of an early imaging examination (x-ray, ultrasound scan, CT or MRI) to detect as soon as possible the mass, in order to proceed to more specific investigations to elucidate the nature and staging of this malignant tumour. Radiographic findings of pleuropulmonary blastoma are not specific, especially when most of the neoplasm is cystic, resembling the radiographic features of teratoma. In this respect we note that PPB may initially manifest with clinical and radiologie signs and symptoms of pneumothorax 5 and may arise from other dysplastic conditions; as a matter of fact, cystic pulmonary adenomatoid malformation (CPAM) can be associated with PPB, which is also described in association with some congenital dysembriogenic abnormalities as cystic nephroma 3 . The clinical and radiological presentation in our patient showed mediastinal involvement; the mass was not excisable at the first surgical look because the neoplasm involved the pleura and was very large. The histopathologic diagnosis was consistent with type II PPB. The features described usually correlate with a poor prognosis 6 8 . The patient was submitted to intensive multiagent neoadiuvant chemotherapy, which reduced the tumour mass, making the complete surgical resection feasible, and allowing eradication of the malignancy. Such intensive multiagent chemotherapy is in most cases necessary for the reduction and complete excision of the tumor, which represents the most favourable factor for long term survival. In a recent report describing 11 patients 7 , two underwent total excision of the tumour at diagnosis, and were both alive without disease at 23 and 132 months respectively, with no adjuvant chemotherapy administered in the latter; another 3 patients remained disease free, two after macroscopic total resection and polychemotherapy and one after polychemotherapy and delayed complete surgery. The effectiveness of chemotherapy has also been reported by other Authors 8 1°. The choice of the antiblastic agents used in our patients was due to their known effectiveness on mesenchymal and epithelial tumors n. Our patient was not treated with radiotherapy, which has proven to be effective in few patients 1. In conclusion, this case suggests that PPB may be taken in consideration for the differential diagnosis in respiratory distress. According to our experience and to other literature reports, total remission of this condition may be achieved with complete surgical excision (primary or delayed) and intensive chemotherapy. References 1 Manivel JC, Priest JR, Watterson J, Steiner M, Woods WG, Wick MR. Pleuropulmonary blastoma: the so called pulmonary blastoma of childhood. Cancer 1988;62:1516-26. 2 Spencer H. Pulmonary blastoma. J Pathol Bacteriol 1961 ;82:161-5. 3 Priest JR, Watterson J, Woods WG, Brid RI. Pleuropulmonary blastoma: a marker forfamilial disease. J Pediatr 1996;128:220-4. 4 Dehner LP. Watterson J, Priest J. Pleuropulmonaiy blastoma. A unique intrathoracìc-pulmonary neoplasm of childhood. In: Askin FB, Langston C, Rosemberg HS, eds. Pulmonary disease: perspectives in pediatrie pathology. Basel: Karger 1995, p. 214-26. 5 Guler E, Kutluk MT, Yalcin B, Cila A, Kale G, Buyukpamukcu M. Pleuropulmonary blastoma in a child presenting with pneumothorax. Tumori 2001;87:340-2. 6 Priest JR, McDermott MB, Bathia S, Watterson J, Manivel JC, Dehner LP. Pleuropulmonary blastoma. A clinic-pathologic study ofSOcases. Cancer 1997;80:146-61. 7 Indolfi P, Casale F, Carli M, Bisogno G, Ninfo V, Cecchetto G, et al. Pleuropulmonary blastoma: management and prognosis of 11 cases. Cancer 2000;89:1396-401. 8 Romeo C, Impellizzeri P, Grosso M, Vitarelli E, Gentile C. Pleu- 124 PLEUROPULMONARY BLASTOMA IN A CHILD ropulmonary blastoma: long-term survival and literature review. Med Pediatr Oncol 1999;33:372-6. Parsons SK, Fishman SJ, Hoorntje LE, Jaramillo D, Marcus KC, Perez-Atayde AR, et al. Aggressive multimodal treatment of pleuropulmonary blastoma. Ann Thorac Surg 2001;72:939-42. Ozkajnak MF, Ortega JA, Laug W, Gilsanz V, Isaacs H Jr. Role of chemotherapy in pediatrie pulmonary blastoma. Med Pediatr Oncol 1990;18:53-6. 125

Gli Autori presentano i risultati del Secondo Studio Cooperativo Italiano sui Tumori a Cellulle Germinali Maligni del bambino, esito del Proytocollo Nazionale TCG 98.

Analysis of treatment and results of the patientsenrolled in the Italian TCG-98 Study, still open and comparison of data with those of the previous Studt TCG-91

The aim of the Study: To analyze the outcome of patirnts with extragonadal (eg) GCT teated with TCG 91/98 Protocols. 45 pts were enrolled: 34 were females, 11 males; median age 17 months (range: 1-137 months)

CIRCA IL 20% DEI PAZIENTI CON TUMORI A CELLULE GERMINALI (tcg) SONO RESISTENTI AL TRATTAMENTO. GLI aUTORI HANNO EFFETTUATO UNO STUDIO POLICENTRICO AL FINE DI RILEVARE CORRELAZIONI TRA PARAMETRI CLINOCO/LABORATORISTICI E LA PROGNOSI

Platinum based chemptherapy improves the cure rate of patients with MGCT to over 80 poer cent, but tumour recurrence is associated with an unfavourable prognosis. We sought to identify factors predicitive of poor outcome following relapse.

The role of autologous bone marrow transplantation (ABMT) in childhood ALL after an isolated extramedullary (IE) relapse is controversial. Between December 1984 and November 1995, 52 children underwent ABMT because of an IE relapse. The data were stored in the AIEOP-BMT Registry. Thirty four children were transplanted in 2nd CR; eighteen > 2nd CR. The median duration of 1st CR was 24 (range 3-69) and 18 (range 3-59) months, respectively. The median interval from last CR to ABMT was 6 (range 1-28) and 3 (range 1-81) months, respectively. The 5 year EFS for patients transplanted in 2nd CR was 67.7%, while the 3 year EFS for patients in > 2nd CR was 16.7%. In conclusion, ABMT was an effective treatment in early IE relapse only if performed in 2nd CR

Tha Authors report a retrospective Study carried out because of the rarity of Primary Testicular Tumors (PTT) in childhood. The aim was to revise the surgical treatment performed in 60 Pz affected by PTT during a 10 year period.

Gli Autori presentano il progetto del Protocollo Nazionale di disgnosi e cura dei Tumori a Cellule germinali (TCG) con gli obiettivi di costituire una casistica nazionale, approfondire la storia naturale dei TCG, promuovere un trattametno uniforme nazionale. vengono presentati i primi dati.

Gli Autori riportano i risultati del Protocollo AIEOP-91 presentando igli 88 casi registrati in 15 Centro AIEOP dal gGennaio 1991 al Dicembre 193

In età pediatrica la Sindrome da INtestino Corto (SIC), il più delle volte conseguenza di un intervento chirurgico di resezione intestinale massiva, è la più frequente causa di Insufficienza Intestinale (ID). L'esigenza di conoscere la realtà delle SIC ha promosso uno Studio Nazionale Multicentrico retrospettivo ("SIC 91" ) per valutare i casi di SIC osservati dal 1991 al 2001, avvalendosi inoltre dei dati del Network Italiano "Insufficienza Intestinale in Età Pediatrica". I dati preliminari sono già stati presenatti e pubblicati in altra sede ed hanno permesso di esprimere alcune considerazioni iniziali. Gli obiettivi di questo Studio sono quelli di valutare l'outcome dei pazienti in relazione alla durata della Nutrizione Parenterale.

GCT account for about 3% of all solidi Neoplasms in children. Because of the confusion as to their classification, diagnostic apporoach and treatment, a multi-istitutional study was carried and a National Protocol for Diagnosis and treatment of CGT (TCG-91), approved by AIEOP, straded in January 1991.

Authors analyze the preliminary results of the first multicentric cooperative study on Germ Celkl Tumors in childhood (TCG 91). The Authors discuss the role of primary surgical procedure on the treatment of benign forms and of resectable malignant tumors.

Gli Autori eseminano tutti gli aspetti del ruolo della chirurgia nel trattamento di queste neoplasie, valutandone le applicazioni per tipo di tumore, benigno o maligno, e per sede interessata.

Gli studi embriologici ed anatomopatologici hanno chiarito le origini dei Tumori a cellule germinali e di classificarli in diversi tipi istologici, benigni e maligni, riconducibili al momento differenziativo durante il quale la cellula primordiale viene colpita da un imput o proliferativo o neoplastico. Viene esaminato ogni aspetto clinico con la migliore forma di terapia.

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.

Gli Autori riportano un caso di tumore primitivo del testicolo (Yolk Sac Tumor) e metastasi gigante retroperitoneale e sindrome virilizzante associata

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.

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

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.

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.

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

Malignant Germ Cell Tumours (MGCT) account approximately 3% of all malignancies in the paediatric age group. Although many of them are curable, their natural history, staging, systems and optimal treatment still need to be better defined. Tha data of an Italian co-operative study are reported here

I Teratomi Immatuti sono tumori costituiti da tessuto non maligno ma con potenzialità evolutiva maligna. Gli Autori presentano i dati dello Studio Cooperativo "TCG-91".

Germ Cell Tumors (GCT) are rare in childhood, accounting for 2-4% of all solid neoplasms. Teratoma is the most frequent histological type (50%) of GCT and the most important neonatal tumors.. Authors analyze the results of the first Italian Multicentric Cooperative Study on GCTs in childhood (TCG 91). The role of surgical radical excision of the mass with thw coccyx in sacrococcygeal forms is streassed.

The incidence of acute and chronic liver damage and its relation to hepatitis B virus (HBV) infection was evaluated in 164 consecutive children with acute leukemia seen in ten Italian hemato-pediatric units. Thirteen out of 164 children (7.9%) had acute hepatitis (AH) during treatment, while 8/90 (8.8%) showed an acute exacerbation of liver damage within 6 months after therapy withdrawal. Seven of the 13 children with AH while on therapy were HBsAg positive. In 12/13 cases, liver disease progressed to chronicity. Five of eight children who developed AH after completion of treatment were HBsAg positive. Eighty-nine patients (54.2%) developed biochemical evidence of chronic hepatitis during therapy; 48/89 were followed after cessation of treatment and 33 of them showed persisting evidence of liver cell necrosis. Thirty-three out of 133 children (24.8%) tested for serum HBsAg were found positive: 26 (78.7%) of them developed chronic hepatitis. Sixty-four out of 133 patients were evaluated after cessation of treatment: Chronic hepatitis persisted in 16/22 HBsAg-positive (72.7%) and in 17/42 HBsAg-negative (40.4%) children during follow-up. The outcome of these liver diseases after treatment withdrawal did not differ significantly in relation to HBV serology, suggesting that viral rather than toxic agents were responsible for liver damage also in most HBsAg-negative patients. The high incidence of chronic HBV infection in children with leukemia found in this multicentric study could suggest a need for active immunization with HBV vaccine, but the efficacy of such approach in this clinical setting is still to be validated.

Thirty-four infants under 1 year of age with Wilms’ tumor were diagnosed and treated in 14 Italian pediatric oncology units during 1970-79. The 3-year survival rates decreased with higher group unilateral tumors: 95% in group I Wilms’ tumor, 75% in group II and 20% in group III. The survival rates for children with group I and II Wilms’ tumor were similar for those who were treated with surgery and chemotherapy and those who also received postoperative radiotherapy. During 1975-79 fewer patients with group I Wilms’ tumor received radiotherapy (1 of 11) than during 1970-74 (4 of 6, p < 0.05). All these children are alive at this writing.

Gli Autori presentano i dati relativi ad uno studio retrospettivo su 25 casi di Teratoma sacrococcigeo, osservati tra il 1980 ed il 1988.