Primary Pulmonary Rhabdomyosarcoma Arising Within Cystic Adenomatoid Malformation: A Case Report and Review of the Literature ¨ zcan, Ahmet C¸elik, Zeliha Ural, Ali Veral, Gu¨ls¸en Kandilog˘lu, and Erol Balık By Cos¸kun O Bornova-I˙zmir, Turkey
The current report describes a 13-month-old boy with primary pulmonary rhabdomyosarcoma (RMS) that originated within a congenital cystic adenomatoid malformation (CCAM). To the best of our knowledge, he is the youngest patient of all primary pulmonary RMS cases reported in the English-language literature. The tumor, localized in left upper lobe, was removed completely, and histologic examination showed embryonal subtype. Postoperative systemic chemotherapy was carried out. Recent evaluation 15 months after resection has not identified any residual or recurrent
disease. Primary pulmonary RMS, although very rare in the pediatric age group, should be considered in young patients with solitary pulmonary masses and associated cystic lesions. J Pediatr Surg 36:1062-1065. Copyright © 2001 by W.B. Saunders Company.
RIMARY PULMONARY neoplasms are very rare, and primary pulmonary rhabdomyosarcoma (RMS) is one of the rarest, accounting for only 0.5% of childhood RMS and for 4.4% of childhood pulmonary neoplasms.1 The current study describes the clinical, radiographic, and morphologic features of primary pulmonary RMS of the lung in a child and reviews the literature.
The cut surfaces of the tumor had extensive solid areas of necrosis and some mixed areas of small cysts. Microscopically, cystic areas were lined by pseudostratified respiratory epithelium. Blastematous cells composed of oval and small nuclei and pleomorphic, large, eosinophilic rhabdomyoblasts with cytoplasmic striations were seen in the solid areas. Rhabdomyoblasts showed cambium layer effect into the wall of some of the surrounding cysts (Fig 4) and strong immune reactivity against desmin. No evidence of lymphatic or pleural involvement was noted.
A 13-month old boy with a 3-month history of persistent cough, fever, and dyspnea was admitted to a pediatric surgical center for a left pleural effusion (Fig 1). There he had been treated with antibiotherapy and tube thoracostomy with a misdiagnosis of empyma. Chest radiograph after completion of treatment showed an air cyst together with a large mass in the left hemithorax (Fig 2), and he was referred to our department for further evaluation and treatment. Computerized tomography showed a large cyst with multiple septations in the left upper lobe and collapse of the rest of the lung with contralateral deviation of the mediastinum (Fig 3). Results of additional diagnostic investigations were negative. The child underwent surgery that found multicystic mass (10 ⫻ 8 cm) that originated from the anterior segment of the left upper lobe without local invasion; segmentectomy with complete removal of the tumor and pleural and mediastinal lymph node biopsies then were performed. Pathologic examination showed pulmonary RMS, arising in cystic adenomatoid malformation and no local invasion. The child has been on systemic chemotherapy for 8 weeks with vincristine, Adriamycin, and ifosfamide. Recent evaluation 15 months after resection has not identified any residual or recurrent disease.
From Ege University Faculty of Medicine and the Departments of Pediatric Surgery and Pathology, Bornova-I˙zmir, Turkey. ¨ zcan, Ege University, Faculty Address reprint requests to Cos¸kun O of Medicine, Department of Pediatric Surgery, 35100 Bornova-I˙zmir, Turkey. Copyright © 2001 by W.B. Saunders Company 0022-3468/01/3607-0021$35.00/0 doi:10.1053/jpsu.2001.24747
Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and occurs commonly in the head, neck, and urogenital organs. Primary pulmonary neoplasms are unusual in the pediatric age group, and RMS of the lung is one of the rarest. It accounts only 0.5% of childhood RMS2, and for 4.4% of childhood pulmonary neoplasms.1 Only 3 of 2,747 children included in the Intergroup Rhabdomyosarcoma Study had a primary pulmonary lesion.2-4 In review of the English-language literature, we found 29 (including our own) cases of primary pulmonary RMS so far1-21 (Table 1). Noda et al5 reported 4 cases in the Japanese literature in 1995.5 The most common symptoms at onset are cough, fever, and dyspnea especially in patients with cystic lesions as a result of spontaneous pneumothorax. In 26 cases in which the sex was documented, 11 were boys, and 15 were girls. Bilateral cases are not reported; 14 lesions were on the left, and 13 lesions were on the right. In 21 cases in which the pathologic subtype was documented, 16 were embryonal, 2 were alveolar, and 3 were undifferentiated. Fifteen cases arose in a preexisting pulmonary cystic malformation, 7 of which (including our own) were in CCAM, 2 were in bronchogenic cysts, and 6 were in nonspeci-
Journal of Pediatric Surgery, Vol 36, No 7 (July), 2001: pp 1062-1065
INDEX WORDS: Rhabdomyosarcoma, lung, lung cysts, congenital cystic adenomatoid malformation.
Initial chest radiograph shows a left pleural effusion.
fied cysts. Our case is the seventh case arising in CCAM, and he is the youngest patient of all reported primary pulmonary RMS cases. According to the follow-up data (3 months to 12 years) for the 28 reported cases, 19 patients were alive. In 10 of 28 patients, metastatic disease developed in the brain or ipsilateral lung and cavity, but only 3 patients are alive. Noda et al5 reported that serum neuron-specific enolase levels in these cases might be helpful in diagnosis of metastasis and recurrence. Among 15 patients with associated cystic lesions, 11 (73%) are disease free, 3 (20%) are dead of disease and 1 is alive with disease, whereas in the 13 cases without detectable lung cysts, 6 patients (46%) are free of disease, 5 (38%) are dead of disease, 1 is alive with disease, and 1 is lost to follow-up. Some investigators recommend that primary pulmonary RMS can be divided into
Fig 2. Chest radiograph after completion of treatment with thoracostomy shows complete resolution of pleural effusion, and an air-filled cyst together with a large solid mass in the left hemithorax became apparent.
Fig 3. Computerized tomography scan shows a large solid mass in the left upper lobe and collapse of the rest of the lung with contralateral deviation of the mediastinum
2 main groups: tumor in the normal lung and tumor in the cystic lesion of the lung.5 Although large series with long-term results are required to make objective comments, the prognosis in cases associated with cystic lesions seems to be more favorable than the ones without. The occurrence of malignant degeneration in congenital cystic malformations of the lung has been controversial. Although the etiologic factors of the pulmonary RMS are unknown, pulmonary developmental abnormalities may play a pathogenic role. Hartman and Shochat6 reported that only 4% of pulmonary tumors were associated with congenital cystic malformations. The tumors developing within these malformations included various sarcomas, pulmonary blastoma, bronchogenic carcinoma, and mesenchymoma.1,6 Two main hypotheses regarding the origin of RMS in CCAM have been suggested. Some investigators argued
Fig 4. Rhabdomyoblasts (r) beneath the cystic spaces (cs) lined by respiratory epithelium (H&E, original magnification ⴛ 100).
¨ ZCAN ET AL O
Table 1. Primary Pulmonary Rhabdomyosarcoma: Review of the Literature Study Grosfeld et al18 Fallonetal14 Ueda et al9
Sex/age (mo) Not reported F/72 M/18
Associated Lung Cyst
Outcome / Follow-Up (mo)
Right bronchus LUL
AWD / 33 DF / 36
Thomas et al21 Krous and Sexauer16 Christ et al,2 Andrassy et al,3 Maurer et al4 Hartman and Shochat6
Fever Fever, croup, dyspnea Cough Cough, fever
Lobectomy Lobectomy with residue Biopsy
DF / 60 DOD / 6 (Brain and local relapse after 6 mo) DOD / 16 (Local relapse)
DF / 72
M/84 M/122 F/156
Not reported Cough, fever Cough, chest pain
No No No
LUL Left bronchus Right lung
Lobectomy Left PNMT Right PNMT
Undifferentiated Undifferentiated Embryonal
S⫹CT⫹RT S⫹CT⫹RT S⫹CT⫹RT
Williams17 Allan et al8
M/21 F/21 F/30
Dyspnea Dyspnea-PTX Dyspnea-PTX
CCAM Cyst Cyst
RLL LLL RLL
Lobectomy Lobectomy Lobectomy
Embryonal Not specified Not specified
S⫹CT S⫹CT S⫹CT
Shariff et al7 Hendlund et al20 Murphy et al13 McDermott et al15
F/15 F/22 F/18 F/24 F/36 M/42 M/36 F/24
CCAM Cyst Cyst BC CCAM CCAM Cyst No
LLL RLL LUL RLL RLL-RML LLL RLL Left lung
Lobectomy Lobectomy Lobectomy Wedge resection Lobectomy Lobectomy Resection Resection
Not specified Not specified Embryonal Embryonal Embryonal Not specified Embryonal Embryonal
S S⫹CT S⫹CT S⫹CT S⫹CT S⫹CT S⫹CT S⫹CT
Hancock et al1 Bogers et al12 Doval et al19 Noda et al5
?/24 ?/18 M/10 yr M/22
Cough, fever Dyspnea-PTX Croup Dyspnea-PTX Dyspnea-PTX Fever, cough Cough, pyrexia Wheezing, dyspnea Not reported Dyspnea Cough, chest pain Wheezing, fever
LTF / 10 DF / 24 DF / 72 (Brain relapse after 48 mo) DF / 24 DF / 48 AWD / 11 (Local relapse 5th and 11th mo) DF / 3 DF / 9 DF / 144 DF / 12 DF / 3 DF / 6 DOD (Brain relapse) DOD / 5 (Brain relapse)
No LE No No
LLL LUL Left lung RUL
Lobectomy Local resection Broncoscopy - biopsy Lobectomy
Not reported Not reported Embryonal Alveolar
S⫹CT S⫹CT CT⫹RT S⫹CT⫹RT
Schiavetti et al11 d’Agustine et al10
Cough Cough, fever, dyspnea Wheezing, cough, dyspnea Cough, fever, dyspnea
DOD DOD / 24 (Local relapse) DF* / 36 DF / 38 (Brain relapse after 6 mo, local relapse 11th and 24th mo) DOD / 14 (Brain relapse) DOD / 3 (Local relapse after 2 mo) DF / 72
DF / 15
F/22 Current case
Abbreviations: S, surgery; CT, chemotherapy; RT, radiotherapy; PTX, pneumothorax; CCAM, congenital cystic adenomatoid malformation; BC, broncogenic cyst; LE, localized emphysema; LUL, left upper lobe; RLL, right lower lobe; RML, right middle lobe; LLL, left lower lobe; RUL, right upper lobe; PNMT, pneumonectomy; DF, disease free; DOD, dead of disease; AWD, alive with disease; LTF, lost to follow-up, ?, not reported. *Exitus in traffic accident, autopsy: disease free.
that RMS arises from well-differentiated but poorly organized skeletal muscle fibers present in some subtype of CCAM,22,23 whereas the others favor a hypotheses of rabdomyoblastic differentiation of the cambium layer.7-9,24 Primary pulmonary RMS, although very rare, should be considered in the differential diagnosis of childhood
lung masses, and the simultaneous presence of cystic lesions could be considered a favorable prognostic feature. Although multimodal therapy remains inevitable, total removal of the tumor should be stressed in operative management so that the recurrence and metastasis can be controlled.
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