Pulmonary blastoma in children: Report of two cases and review of the literature

Pulmonary blastoma in children: Report of two cases and review of the literature

Pulmonary Blastqma in Children: Report of Two Cases and Review of the Literature ByRaymond M. Seballos &-id Robert L. Klein Youngstown, Ohio and A...

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Pulmonary Blastqma in Children: Report of Two Cases and Review of the Literature ByRaymond

M. Seballos

&-id Robert

L. Klein

Youngstown, Ohio and Akron, Ohio 0 Pulmonary blastoma is a rare primary neoplasm of the lung. Approximately 25% of the reported cases have occurred in pediitric patients. The authors found 45 cases of these tumors in children aged ~16 years, and report two more cases of pulmonary blastoma-ih a 3W-year-old boy and a 22-month-old girl. Because these tumors are considered malignant, surgical excision is recommended. Copyright Q 1991 by W.B. Saundars Company INDEX WORDS:

Pulmonary blastoma, pediatric.

I

N 1945, Barrett and Barnard described this rare malignant pulmonary tumor,l which was named an embryoma of the lung by Barnard in 1952.* In 1961, Spencer called the tumor a pulmonary blastoma and suggested that it arose from mesodermal blastema because of its similarities to nephroblastoma.3 Histologically, most tumors contain a mixture of immature mesenchymal and epithelial elements.4-6 We describe two new cases and provide a brief review of the literature. CASE REPORTS

Case 1 A 31/2-year-old boy presented with abdominal pain, difficulty in breathing, and a productive nonbloody cough. During the physical examination he was found to be afebrile. He had a respiratory rate of 60 breaths per minute. decreased breath sounds on the left, and dullness to percussion on the left. A chest x-ray showed complete opacification of the left lung field, with massive rightward shift of the trachea, mediastinum, and heart, secondary to an effusion and possibly a mass (Fig 1). A computed tomography (CT) scan of the chest showed a large effusion on the left, associated with a mass within the left base. The patient undetwent a left thoracotomy for complete excision of a necrotic tumor approximately 20 cm in diameter. Histologically, the tumor was necrotic, with reactive mesothelial cells and large bizarre cells having hyperchromatic nuclei. Malignant cartilaginous cells with fibrosarcomatous cells were seen in the pathological specimen (Fig 2). The result of a bone marrow biopsy was negative. The lung tumor was evaluated for multiple antigens including cytokeratins, placental alkaline phosphatase, human chorionic gonadotropin (HCG), desmin, and muscle cell action; all results were negative. Recurrence in the left hemithorax required surgical excision 12 months later (Fig 3). The histological examination showed recurrence of pulmonary blastoma, with epithelial and sarcomatous changes. After the first operation the child received the initial dose of chemotherapy (1.0 mg of vincristine, 21 mg of melphalan). A follow-up chest CT scan 1 month postoperatively showed pleural thickening and a mass in the left hemithorax, suggestive of tumor. In each of the five separate hospitalizations over the next 11 months, he received vincristine (1.0 to 1.1 mg), actinomycin (0.275 to 0.28 mgid for 5 days), cyclophosphamide (1.54 to 1.60 mg), and mesna (315 to 340 mg). On two separate occasions he also received Journa/ofPediatriCSurgery, Vol29,No12(December),1994:pp1553-1556

vim&tine (1.0 to 1.1 mg). After 6 months of this regimen, the tumor size had reduced to 1.5 x 0.7 cm. However, 6 months later (12 months after the initial surgery), the tumor had increased to 3.0 x 2.4 cm, despite chemotherapy. The patient again underwent thoracotomy for tumor debulking and exploration. During this operation, pericardial effusion was seen, along vvith metastases to the pleura, lung, and pericardium. Over the next 10 months, on three separate hospitalizations, the child received1 chemotherapy of vincristine (2 mg), actinomycin (20 mg/d for 2 days), mesna (270 mg [eight doses] in 2 days), and cyclophosphamidk (450 mg/d for 2 days). Between treatments he received etoposide (75 mg/d for 5 days), ifosfamide (350 mg/d for 5 days), and me&a (270 mg [eight doses] over 5 days). Despite use of aggressive chemotherapy and radiation, the child’s condition slowly deteriorated, with brain metastasis and severe ascites. He died 22 months after the initial operation.

Case 2 The second patient, a 22-month-old girl, presented with tachypnea and moderate respiratory distress. During the physical examination she was found to be afebrile, with a respiratory rate in the 40s. Breath sounds were decreased on the right lung fields. A chest radiograph showed opacification of the right hemithorax. A chest CT scan showed a solid cystic tumor of the right chest region, which compressed the barely identifiable lung pqenchyma (Fig 4). A large, lobulated, soft, tan-colored tumor, arising from the middle lobe and measuring 17 x 10 x 5 cm, was removed along with the medial aspect of the middle lobe (Fig 5). There was no gross evidence of lymph node metastasis at the time of thoracotomy. The tumor had solid and cystic components that were: filled with air and fluid. The right lung expanded well after removal of the tumor. Microscopic examination showed mesenchymal and blastematous tissue elements. The cystic areas were consistent with congenital cystic adenomatous malformation. Although the margins were clear, the capsule was ruptured at the time of surgery. The prognosis for long-term survival was estimated to be 25% to 50% by the pathological report. This child initially received vincristine (0.75 rng) and melphalan (2.0 mg [five doses]) on two separate occasions. On six different hospitalizations over a lo-month period, her regimen consisted of vincristine (0.75 mg) actinomycin (0.17 mg/d for 2 days), cyclophosphamide (1,000 mg), and mesna (225 to 250 mg [four to five doses] over 2 days). Although the tumor was as large as that of case 1, there has been no evidence of recurrence throughout the 20 months since her surgery. The results of her chest CT scans and

From the Department of Surgery, St Elizabeth Hospital Medical Center, Youngstown, OH, and the Department of Surgery, Northeastem Ohio Universities College of Medicine, Children S Hospital Medical Center, Akron, OH. Address reprint requests to Raymond M. Seballas, MD, c/o Vincent W. Vanek, MD, Director of Research, Depanment of Surgery, St Elizabeth Hospital Medical Center, 1044 Belmont Ave, PO Box 1790, Youngstown, OH 44501-I 790. Copyright o 1994 by WB. Saunders Company 0022-346819412912-OOI7$03.OOlO 1553

SEBALLOS AND KLEIN

Fig 2.

Fig 1. Chest x-ray shows opacification of the left hemithorax, with shift of the mediastinum to the right.

x-rays are normal. She continues to have follow-up in the hematology clinic and is doing well at this time (20 months after surgery). DISCUSSION

In the literature there had been 45 cases of pediatric pulmonary blastoma, a rare primary malignant tumor of the lung.5,7-10The two patients described herein presented with respiratory symptoms, underwent thoracotomy for tumor excision, and received chemotherapy. Surgical excision is the treatment of choice. Although authors of previous reports question the effectiveness of chemotherapy and radiation,4,7-9J1 some advocate chemotherapy in certain situations.12 Pulmonary blastoma is more common in adults,4J1 but 25% of the reported cases have occurred in pediatric patients I 15 years of age.13 Most often the condition occurs in the fourth or fifth decades of life (median age, 39). lo The mean ages of presentation are 45 (males) and 36 (females).14 The age range at presentation for the pediatric population is 2 months to 15 years.5,7-10The male:female ratio is approximately 2:1.i5 Pulmonary blastoma has not been noted to have any familial patterns.6 Although it has not been mentioned in relation to any syndromes, it has

Malignant cartilaginous cells with fibrosarcomatous

cells.

been associated with cystic lung disease.6-16 Case 2 represents this association. Most patients present with breathlessness, chest pain, and multiple chest infections,8 and some with spontaneous pneumothorax.17 Our patients presented with tachypnea. Patients also may present with infiltrate (noted on a chest radiograph) pneumonia and fever, dyspnea, cough, hemoptysis, and, occasionally, neurological symptoms.6 Clinically it is difficult to distinguish pulmonary blastoma from other pulmonary tumors. The differential diagnosis includes epidermoid carcinoma with a spindle-cell component,

Fii 3. CT scan of the chest shows tumor recurrence in the posterolateral aspect of the left hemithorax, at the level of the carina.

PULMONARY BLASTOMA

Fig 4. CT scan of the chest shows a large tumor almost completely occupying the right hemithorax.

mixed bronchial mucosa gland tumor, teratoma, mesothelioma, hemartoma, and carcinosarcoma.6 Controversy remains regarding the histogenesis of pulmonary blastoma. Han et al described a resemblance to nephroblastoma and suggested that the tumor originated from mesenchymal blastema.18 Some confusion exists when distinguishing pulmonary blastoma from rhabdosarcoma. Some investigators believe that the pulmonary blastoma differentiates into mesenchymal and epithelial tissue.‘Jl’ Histologically, pulmonary blastoma can be differentiated from rhabdosarcoma by its blastomatous, epithelial, and stroma1 components. 6~17~19 The tumor usually lacks bronchial connections and arises peripherally, in contrast to carcinosarcoma, which arises centrally, with bronchial connections.10J8,20 Pulmonary blastoma is similar to the fetal lung at 3 months’ gestation.6J0J4Ji-25 There may be a spindle cell orientation as well as epithelial components associated with atypical cells and ciliated epithelium and cartilage.26-28 Childhood pulmonary blastoma is differentiated by a variable

Fig 5. Surgical specimen lobulated).

after complete

excision (smooth

and

anatomic location, primitive embryonic-like blastema and stroma, absence of carcinosarcomatous features, and potential for sarcomatous differentiation.9 Cystic and solid characteristics may be seen on chest x-rays, as in our cases. The existing lung parenchyma may be almost completely obliterated or compressed by the tumor. A chest CT scan will show the solid and/or cystic tumor. There is a slight predilection for location in the upper lobes.10.26Aspiration cytology, bronchoscopy, and needle biopsy are not needed for making a definitive diagnosis4,29; thoracotomy and surgical excision are required for cure. The gross specimen may be necrotic or hemorrhagic. Some tumors glisten and are mucoid to grayish-white17)25; some are gelatinaus, gritty, or hard.6.7,25,26 The cystic component is more common in pediatric cases than in adult cases.?’ The prognosis for this condition is poor; half the patients die within 3 to 12 months after diagnosis. Cases with the poorest prognosis are those that recur, have metastases, are larger than 5 cm, or have thoracic adenopathy. 4.7~19,30 In both cases described herein, the tumors were larger than 5 cm. The 5-year survival rate is reportedly 5% to 16%.“J” However, there are some long-term survivors. Gibbons et al described a patient who had pulmonary blastoma diagnosed at age 7 years, who was alive and well at age 31.15Two thirds of the patients die within 2 years of diagnosis.30 Metastases and recurrence usually occur within 1 year of resection. This was the case with patient 1. The chance of survival is not influenced significantly by the patient’s age, sex, or tumor location.6 According to our experience, the prognosis is poor if recurrence is noted within 1 year or if the tumor enlarges despite chemotherapy. Surgical excision, ranging from wedge excision to pneumonectomy, is the treatment of choice.4~8~10~11~ 24,28.31 In the two present cases, complete gross excision was performed along with wedge resection of the involved lobe. It is possible that pneumonectomy could have prevented recurrence in the first patient because the tumor was noted at the staple line. However, the tumor’s aggressiveness was apparent by its recurrence within 2 months and its spread to the mediastinum, diaphragm, and pericardium. Chemotherapy using vincristine, actinomycin, and cyclophosphamide has been employed by some oncologists.” Kummet and Doll recommend surgery alone for lesions smaller than 5 cm. Patients whose condition is inoperable and those with tumor recurrence should receive chemotherapy, as described above.” Some clinicians question the effectiveness of chemotherapy. We used actinomycin, vincristine, mesna, and cyclo-

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phosphamide as part of the rhabdosarcoma protocol at Akron Children’s Hospital. The first child had an initial response but later was overcome by the illness. The second child has had a much better response, with no evidence of recurrence. Time will tell whether the child will continue to do well and whether prolonged remission will be attained. We believe the best prognosis is determined by a good response to chemotherapy and the absence of recurrence after 1 year of close follow-up. Radiotherapy’s role in treatment remains uncertain.4*7-9J1 It was not used in the second child because the current chemotherapeutic regimen was sufficient.

The tumors in the two present cases arose from a single lobe. In such cases, the tumor should be removed along with the involved lobe. Whether pneumonectomy is beneficial is debatable. This procedure most likely would not be used unless tumor-free margins could not be attained through lobectomy alone. The recommended surgical procedure is thoracotomy with complete gross removal of the tumor and the involved lobe. ACKNOWLEDGMENT The authors acknowledge Carole F. Klingler for editorial and secretarial assistance.

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17. Allan BT, Day DL, Dehner LP: Primary pulmonary rhabdomyosarcoma of the lung in children. Cancer 59:1005-loll,1987 18. Han SS, Wills JS, Allen OS: Pulmonary blastoma: Case report and literature review. AJR 127:1048-1049, 1976 19. Iverson RE, Straehley CT: Pulmonary blastoma; Long-term survival of juvenile patient. Chest 63:436-440,1973 20. Valderrama E, Saluja G, Shende A, et al: Pulmonary blastoma: Report of two cases in children. Am J Surg Pathol 2:415-422,1978 21. Fung CH, Lo JW, Yonan TN, et al: Pulmonary blastoma: An ultrastructural study with a brief review of literature and a discussion of pathogenesis. Cancer 39:153-163,1977 22. Ionescu J, Eskenasy A: Pulmonary blastoma. Morphol Embryo1 25:157-161,1979 23. Kodaira Y, Akiyama H, Morikawa M, et al: Pulmonary blastoma in a child. J Pediatr Surg 11:239-241, 1976 24. Martinez JC, Pecero FC, Gutierrez de la Pena C, et al: Pulmonary blastoma: Report of a case. J Pediatr Surg 13193-94, 1978 25. Roth JA, Elguezabal A: Pulmonary blastoma evolving into carcinosarcoma: A case study. Am J Surg Pathol2:407-413,1978 26. Ashworth TG: Pulmonary blastoma, a true congenital neoplasm. Histopathology 7:585-594,1983 27. Solomon A, Rubinstein ZJ, Rogoff M, et al: Pulmonary blastoma. Pediatr Radio1 12:148-149,1982 28. Holland-Moritz RM, Heyn RM: Pulmonary blastoma associated with cystic lesions in children. Med Pediatr Oncol 12:85-88, 1984 29. Sumner TE, Phelps CR III, Crowe JE, et al: Pulmonary blastoma in a child. AJR 133:147-148, 1979 30. Koss MN, Hochholzer L, O’Leary T: Pulmonary blastomas. Cancer 67236%2381,199l 31. Nazari A, Amir-Mokri E, Sarram A, et al: Pulmonary blastoma. Chest 60:187-189,197l