Case Report
271
Pleuropulmonary Blastoma C. Granata1, C. Gambini2, C. Carlini1, P. Repetto1, M. Torre1, C. Mazzola1, G. Mattioli1, V. Jasonni1 Department of Paediatric Surgery, Giannina Gaslini Institute, Genova, Italy 2 Department of Pathology, Giannina Gaslini Institute, Genova, Italy
Summary
Resumen
We report a rare case of pleuropulmonary blastoma arising in a 3-year-old boy and involving the middle and upper lobes of the right lung. Radical resection of the mass was achieved by a bilobectomy. Microscopic examination of the histologic sections showed the typical findings of blastemal and mesenchymal areas with focal zones of rhabdomyoblastic and liposarcomatous differentiation. Monthly cycles of chemotherapy consisting of ifosfamide, vincristine and actinomycin D were given for 10 months after surgical resection. Our patient is presently alive and disease-free two years after diagnosis. As complete tumour ablation is essential to prevent local recurrence and allow any chance of survival, the favourable outcome of our patient is probably due to the radical resection of the neoplasm.
Presentamos un raro caso de blastoma pleuropulmonar aparecido en un niæo de 3 aæos de edad que afectaba a los lóbulos superior y medio del pulmón derecho. La resección radical de la masa requirió una bilobectomía. El examen histológico mostró hallazgos típicos de zonas blastematosas y mesenquimatosas con zonas focales de diferenciación rabdomioblµstica y liposarcomatosa. Se administraron ciclos mensuales de quimioterapia con ciclofosfamida, vincristina y actinomicina D durante 10 meses tras la resección. Nuestro paciente estµ vivo y libre de enfermedad 2 aæos despuØs del diagnóstico. Dado que la extirpación completa del tumor es esencial para evitar recidivas locales y permitir alguna posibilidad de sobrevivencia, el resultado favorable de nuestro paciente debe atribuirse a la resección radical.
n Key words: Pleuropulmonary blastoma ± Child
n Palabras clave: Blastoma pleuropulmonar ± Niæo
RØsumØ
Zusammenfassung
Les auteurs rapportent un cas de blastome pleuropulmonaire chez un enfant âgØ de 3 ans. Les lobes moyen et supØrieur du poumon droit Øtaient concernØs. La rØsection radicale de la masse a ØtØ rØalisØe par une bilobectomie. L Øtude histologique a montrØ des aspects typiques de zones blastØmateuses et mØsenchymateuses avec des zones de diffØrenciation rhabdomyoblastiques et liposarcomateuses. Des cures mensuelles de chimiothØrapie associant ifosfamide, vincristine et actinomycine D ont ØtØ administrØes pendant 10 mois aprs la rØsection chirurgicale. L enfant est aujourd hui vivant et sans maladie, deux ans aprs le diagnostic. Puisque l ablation complte de la tumeur est essentielle pour prØvenir la rØcidive locale et permettre la survie, l Øvolution favorable de notre patient est probablement due à la rØsection radicale de la tumeur.
Ein dreijähriger Knabe mit einem pleuropulmonalen Blastom im mittleren und oberen rechten Lungenlappen wird vorgestellt. Die Histologie ergab fokale Veränderungen mit rhabdomyoblastischer und liposarkomatöser Differenzierung neben blastemalen und mesenchymalen Anteilen. Postoperativ wurden 10 monatliche Zyklen, bestehend aus Ifosfamid, Vincristin und Actinomycin D gegeben. Zwei Jahre später ist das Kind klinisch unauffällig. Entscheidend in der Therapie der pulmonalen Blastome ist die lokale, vollständige Exzision. Die Chemotherapie wird vorgestellt und eine Literaturübersicht gegeben. n Schlüsselwörter: Pleuropulmonales Blastom ± Kindesalter
n Mots-clØs: Blastome pleuropulmonaire ± Enfant
Eur J Pediatr Surg 2001; 11: 271 – 273 Georg Thieme Verlag Stuttgart, New York · Masson Editeur Paris ISSN 0939-7248
Received: December 4, 1999
Accepted after Revision: May 28, 2000
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Eur J Pediatr Surg 2001; 11
Granata C et al
Introduction Pleuropulmonary blastoma (PPB) is an uncommon neoplasm which arises in the lung, mediastinum or pleura of children and is characterised by a primitive blastema and malignant mesenchymal stroma that may show multidirectional differentiation (2). Initially classified together with the ordinary pulmonary blastoma of adulthood, PPB was first recognised as a distinctive intrathoracic lung tumour of childhood by Manivel in 1988 (4). Since then about 50 cases have been reported (6). Despite a multimodal therapy, including surgery, chemotherapy and sometimes radiotherapy, PPB often has a poor prognosis. Because of the rarity of this tumour, we describe the clinical and pathological features of a case of PPB arising in a 3-year-old boy who is presently alive and diseasefree two years after diagnosis.
Case Report A previously healthy boy aged 3 years 2 months was referred to our institute with a two-month history of recurrent pneumonia and chest x-ray evidence of a dense lesion in the right middle lobe, associated with pleural effusion. On the day of admission, he appeared in good general condition. Familiar history and physical examination were unremarkable. Routine laboratory tests detected abnormal ESR (22 at 1 hour) and elevated WBC (12700). A computed tomography scan showed the presence of a non-homogeneous solid lesion in the middle lobe of the right lung. No enlargement of mediastinal, hilar, or peribronchial lymph nodes was observed. These findings prompted the temporary diagnosis of a dysontogenetic lesion and the patient underwent right thoracotomy. A large mass occupying the middle lobe and involving to some extent the upper lobe was found. A bilobectomy was performed with macroscopically complete resection of the mass which appeared to be encapsulated. A 7 6 4.5 cm solid, lobulated and partly necrotic mass was present in the resected lobes. Microscopic examination of the histologic sections revealed areas with blastemal and mesenchymal patterns characterised by cells with large pleomorphic nuclei (Fig. 1). Mitotic activity was variable, ranging from 5 to 15 per high-power fields. Rhabdomyoblastic differentiation was present along with focal zones of liposarcomatous differentiation (Figs. 2, 3). Epithelial differentiation was not found in any of the sections studied, but some glands were observed entrapped in a loose mesenchymal stroma with blastemal cells (Fig. 4). Focal areas of cartilage were not found. According to Dehner s classification (3), these findings were typical of a type III pleuropulmonary blastoma. The postoperative course was uneventful. Monthly cycles of chemotherapy consisting of ifosfamide (6 g/m2), vincristine (1.5 mg/m2) and actinomycin-D (1.5 mg/m2) were given for 10 months. The patient did not receive radiotherapy. A further evaluation 24 months after resection and 12 months after stopping chemotherapy failed to identify residual or recurrent disease.
Fig. 1 Alternating foci of compact cells and loose cells arranged in a myxoid matrix. (Original magnification: 200).
Fig. 2 Area of rhabdomyoblastic differentiation. (Original magnification: 400)
Fig. 3 Area of liposarcomatous differentiation. (Original magnification: 400)
Discussion PPB is a very rare childhood tumour and it is quite different from the pulmonary blastoma (PB) of adults, which is so called because of its resemblance to stages in fetal lung development. PPB is usually large, it often occupies the entire hemithorax and may involve both lung parenchyma and pleura, whereas
adult PB lesions are usually small, solitary and peripheral. In contrast to adult blastomas, no epithelial differentiation is seen in PPB although glandular structures or mesothelial islands may be found entrapped in the mesenchymal stroma (1, 2). Differential diagnosis of PPB includes other pulmonary
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Eur J Pediatr Surg 2001; 11 273 observed within 12 months from diagnosis, the not infrequent occurrence of late relapse well after 3 years from diagnosis prompts to close and prolonged follow-up.
sarcomas of childhood such as rhabdomyosarcoma and leiomyosarcoma. However, only myogenous differentiation is present in these neoplasms, whereas PPB is characterised by a multidirectional differentiation. Nevertheless, some reported cases of pleuropulmonary rhabdomyosarcoma may indeed represent variants of PPB (1, 2). PPB has been classified by Dehner et al in three subtypes according to histopathological features (3). Type 1 is characterised by cystic lesions lined by a well differentiated epithelium with small tumour cells underneath resembling a cambium layer. Type 3 lesions are mostly solid and characterised by blastematous islands in a loose mesenchyme, in which nodules of cartilage, rhabdomyoblasts and liposarcomatous areas can be found. Type 2 includes cysts and solid nodules showing the same histopathologic features as Type 1 and Type 3 lesions. Although some cases of PPB appeared to originate within congenital cysts that probably harboured primitive cells undergoing malignant change, in other cases the cystic lesions observed were likely to be an intrinsic feature of the tumour rather than a predisposing condition (8). Mean age at onset is 2.5 years with a male predominance (2 : 1) (1, 7). Principal signs and symptoms at diagnosis are respiratory distress, fever, chest or abdominal pain, cough and anorexia (6). Priest et al recently observed a striking familial occurrence of other childhood neoplasms such as brain sarcoma, rhabdomyosarcoma, Wilms tumour and ALL, in siblings, cousins, aunts and uncles of children affected by PPB (6). Therefore, an inheritable and constitutional predisposition may be involved in the onset of PPB, although an underlying genetic abnormality has not been clearly identified so far. In a recent review of 50 cases previously described by different surgical teams, Priest (6) reported that the overall survival at 2 years was 63% (80 % for Type 1, 73 % for Type 2, and 48% for Type 3) and 45% at 5 years. Recurrences occurred in 25 out of 50 patients. Local recurrence, with or without distant metastases, were observed in 19 cases. The thorax was the only site of relapse in 10 cases. Two further cases had recurrences in the contralateral chest area. Metastases in the brain or spinal cord occurred in 11 patients; two of them had the brain as the only site of recurrence. Bone metastases occurred in six patients. Single cases of metastases in the adrenal glands, liver and ovary were also observed. Although the majority of relapses were
References 1
2
3
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Allan BT, Day DL, Dehner LP. Primary pulmonary rhabdomyosarcoma of the lung in children. Cancer 1987; 59: 1005 – 1011 Baranija J, Desai S, Kane S, Kurkure P, Nair C, Deshpande R, Borges A. Pleuropulmonary blastoma. Med Ped Oncol 1999; 32: 52 – 56 Dehner LP, Watterson J, Priest J. Pleuropulmonary blastoma: A unique intrathoracic-pulmonary neoplasm of childhood. Perspect Pediatr Pathol 1995; 18: 214 – 226 Manivel JC, Priest R, Watterson J. Pleuropulmonary blastoma: The so-called pulmonary blastoma of childhood. Cancer 1988; 62: 1516 – 1526 Merriman TE, Beasley SW, Chow CW, Smith PJ, Robertson CF. A rare tumour masquerading as an empyema: pleuropulmonary blastoma. Pediatr Pulmonol 1996; 22: 408 – 411 Priest JR, McDermott MB, Bhatia S, Manivel JC, Dehner LP. Pleuropulmonary blastoma. A clinicopathologic study of 50 cases. Cancer 1997; 80: 147 – 161 Seballos RM, Klein RL. Pulmonary blastoma in children. Report of two cases and review of the literature. J Pediatr Surg 1994; 29: 1553 – 1556 Senac Jr MO, Wood BP, Isaacs H, Weller M. Pulmonary blastoma: a rare childhood malignancy. Radiology 1991; 179: 743 – 746
Claudio Granata, M. D. Divisione di Chirurgia Pediatrica Istituto G. Gaslini 16147 Genova-Quarto Italy E-mail:
[email protected]
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Fig. 4 A gland entrapped in loose mesenchymal stroma with blastemal cells. (Original magnification: 400).
As complete tumour ablation is essential to prevent local recurrence and allow any chance of survival (5), the favourable outcome of our patient is probably at least in part due to the radical resection of the neoplasm. The worst prognosis, usually associated with Type 3 PPB, prompted us to administer chemotherapy as adjuvant therapy despite the gross complete resection of the tumour. Chemotherapy (single agents such as vincristine, adriamycin, actinomycin D, cyclofosfamide, ifosfamide or combinations of them) and, in some instances, radiotherapy have been employed in the treatment of PPB. However the rarity of PPB has not permitted the identification of the most active agents or combination of them as no definite improvement of outcome was observed with any therapeutic scheme (6). Therefore it is evident that the most appropriate protocol for PPB treatment has yet to be defined.
