ARTICLE IN PRESS Respiratory Medicine (2006) 100, 1174–1179
Survival of biphasic pulmonary blastoma Serife Tuba Limana,, Tamer Altinokb, Salih Topcua, Abdullah Irfan Tastepeb, Ali Uzarc, Sedat Demircand, Funda Demirage a
Thoracic Surgery Department, The Faculty of Medicine, Kocaeli University, Kocaeli, Turkey Thoracic Surgery Department, Ataturk Chest Disease and Thoracic Surgery Center, Ankara, Turkey c Thoracic Surgery Department, Alanya State Hospital, Antalya, Turkey d Thoracic Surgery Department, The Faculty of Medicine, Gazi University, Ankara, Turkey e Pathology Department, Ataturk Chest Disease and Thoracic Surgery Center, Ankara, Turkey b
Received 8 June 2005; accepted 25 October 2005
It was presented at the 14th European Respiratory Society Annual Congress in Glasgow, UK, September 4–8, 2004.
KEYWORDS Pulmonary blastoma; Thoracic surgery; Survival
Summary Pulmonary blastoma is a rare malignant lung tumor with a poor prognosis. It is composed of immature mesenchymal and epithelial components that resemble fetal lung tissue. We aimed to share our treatment results in biphasic pulmonary blastoma. In Ataturk Chest Disease and Thoracic Surgery Center, five patients with biphasic pulmonary blastoma (four men, one woman, aged between 27 and 61—mean 39.4) were treated between 1987 and 2000 (0.3% of operated NSCC). Hemoptysis, cough, chest pain and dyspnea were the symptoms. Anemia and high erythrocyte sedimentation rate were determined in two patients. Radiological examinations revealed a mass in four patients and massive pleural effusion in one. None of the patients were diagnosed preoperatively and hence all patients underwent exploratory thoracotomy. Three lobectomy, one pneumonectomy and one wedge resection were performed. Histopathological examinations revealed biphasic pulmonary blastoma in all the patients. Pathological stagings were as follows: 1 patient in T1N0M0 and 1 patient in T2N0M0 (198 and 112 months survival, respectively), three patients in T2N1M0 (9,10,17 months survival). In follow up period, prostate carcinoma and rectum carcinoma were detected as second primary tumors in the patient in stage T2N0M0. In patients who have small size tumors without nodal involvement, long-term survival can be obtained with radical surgery; even in biphasic pulmonary blastomas.
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E-mail address: [email protected]
(S.T. Liman). 0954-6111/$ - see front matter & 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmed.2005.10.026
ARTICLE IN PRESS Pulmonary blastoma
1175 According to our limited experiences, N1 nodal involvement shows very poor prognosis. & 2005 Elsevier Ltd. All rights reserved.
Introduction Pulmonary blastomas (PB) are malignant tumors of uncertain histogenesis that histologically resembles the developing in early fetal life. It was hypotesized that it originated from immature pulmonary ‘‘blastema’’ pleuropotential tissue capable of differentiating into both mesenchymal and epithelial portions of the peripheral lungs.1 There are seen very rarely, 0.5% of all primary lung tumors.2 PB are divided into three sub-groups: biphasic pulmonary blastoma (PB), well differentiated fetal adenocarcinoma (WDFA) and pleuropulmonary blastoma (PPB). WDFA are tumors which contains epithelial malignant component without mesenchymal malignancy. PPB indicates tumors with mesenchymal malignancy but without epithelial malignant component. PB are chacterized by a dual or biphasic immature cellular component both are malignant (epithelial and mesenchymal). Here we presented five biphasic pulmonary blastoma and the results of our treatment.
Patients Between 1987 and 2000, we operated 1411 cases with NSCLC in Ataturk Chest Disease and Thoracic Surgery Center. Five of them were biphasic PB (0.3%). There was a male predominance in the patients with PB. Their ages ranged between 27 and 61 years. Three of them were smokers. Patients’ characteristics were summarized in Table 1. The most frequently seen complaints were cough, hemoptysis and chest pain. Anemia and high erythrocyte sedimentation rates were detected in two patients with big tumors. Chest X-ray and thorax tomography were performed in all patients (Figs. 1 and 2). In four patients, radiological examinations revealed solitary pulmonary mass. In one patient, first examinations showed massive pleural effusion and empyema was detected via thoracentesis. After chest tube drainage, solitary big pulmonary mass was observed in his chest X-ray. Tumors were located in lower lobes in three patients, in upper lobe in one and in middle lobe in one patient.
Bronchoscopy was performed in all patients and endobronchial tumor was observed in three. But bronchoscopic biopsy was not diagnostic in those patients. Diagnosis could not be obtained in all of the patients preoperatively and they all underwent thoracotomy. Wedge resection was performed in one patient, lobectomy in three and pneumonectomy in one patient. Wedge resection was performed since frozen section examination could not be performed. He was advised to have a second operation, but he refused. When recurrences was detected in his 3 months follow up after surgery, he accepted the operation and lobectomy was performed. Staging was defined in accordance with the lung cancer staging system. Survivals were measured from the time of diagnosis.
Results All patients were diagnosed as biphasic pulmonary blastoma after histopathological examination of the specimens. Lymph node involvement were detected in three cases with larger tumors (Table 1). There were one patient in T1N0M0, one pateint in T2N0M0 and three patients in T2N1M0. Bronchopleural fistula was occured in the patient who underwent pnemonectomy (T2N1M0). Thoracomyoplasty was performed as a second operation in that case. In his follow up period local recurrence was developed. Esophageal and cardiac involvement were detected. He had 4000 rad radiotherapy. But treatment was unsuccessful and he died in his 9th month of follow up period. In two patients (T2N1M0) systemic metastasis were detected in follow up and chemotherapy was given. But there was no response to chemotherapy and they died. Survivals of those patients were were 10, 17 months. Two patients with tumors 3 cm (T1N0M0) and 3.6 cm (T2N0M0) in size had long-term survivals, 198 and 112, respectively. First patient is still alive. Two different carcinoma were occurred in the second patient while follow up. He was given treatment for prostate carcinoma and
28, m Cough, chest pain 27, f Cough, chest pain, hemoptysis
54, m Hemoptysis
No positive finding
Diminished respiratory sounds
No positive finding
Anemia, high ERS, leucocytosis, empyema
Right lower lobe, — 6.5 cm
Right middle lobe, 17 cm
No positive Left lower lobe, + finding 3 cm Anemia, high ERS Right upper lobe, — 6 cm
No positive finding No positive finding
Endobronchial Operation lesion
Right lower lobe, + 3.6 cm
No positive finding
No positive finding
Vincristine+cyclophosphamide, 3 — cures
4000 rad RT
17 died Bone, liver, brain metastatis (nasocomial pneumonia) 9 died (local recurrence, esophagial and cardiac involvement) 10 died (bone metastasis)
Prostat ca, 112 died dilated rectal cardiomyopathia carcinoma — 198 alive
Vincristine+Cyclophosphamide, 3 — cures, I˙fosphamid+Etoposite, 2 cures
M: male, F: female, ERS: erythrocyte sedimentation rate, RLL: right lower lobectomy, LLL: left lower lobectomy, RUL: right upper lobectomy, RP: right pneumonectomy, TMP: thoracomyoplastia.
27, m Cough, hemoptysis, fever, dyspnea
61, m Cough, chest pain
Characteristics of the patients.
Number Age, sex
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Figure 1 Posteroanterior and CT scan appearance of lobulated circumscribed large mass with heterogenous enhancement in the middle lobe of the right lung.
rectal carcinoma and he died because of the complications of chemotherapy for rectal carcinoma in his 112th months.
Conclusion Pulmonary blastomas (PB) are rarely seen tumors. They are composed of both mesenchymal and epithelial components which resemble fetal lung tissue morphologically with a frequency of only 0.5% of all primary lung tumors.2 It has been shown that the tumor arises from the endodermal tissue or that it originates in pleuropotential stem cells.3,4 Some authors consider pulmonary blastoma to represent a variant of carcinosarcoma.5 There were three types of PB. Biphasic PB have two malignant components; epithelial and mesenchymal. The prognosis of biphasic blastoma is much worse than the others.
Figure 2 Posteroanterior and CT scan appearance of a solitary mass in the right lower lobe.
The etiology and predisposing factors are not still fully understood. In the literature, there is strong evidence showing the correlation between cigarette smoking and PB.6,7 They may occur at all ages but predominantly common in adults (the peak incidence in the fourth decade of life). There is a male predominance.2 When compared to the operated nonsmall cell lung carcinomas, PB are rare, large and symptomatic tumors which affect younger age groups and have poor prognosis.8 Approximately 60% of the patients are symptomatic.9–11 All of our patients were symptomatic. We detected anemia in two patients who had larger tumors and nodal involvements. Biphasic blastomas are usually located in the periphery of the lung.12 Only 25% exhibit endobronchial growth.13,14 Three of our patients had endobronchial tumor but bronchoscopic biopsies
ARTICLE IN PRESS 1178 were not diagnostic. Pleural effusions occur in a minority of cases. It sometimes may be infected causing empyema like in one of our patients. Considerable immunoreactivity for alpha-fetoprotein (AFP) was reported in the literature.15,16 It was pointed out that the epithelial cells of PB might occasionally de-differentiate into cells functionally resembling fetal hepatic, foregut and yolk sac cells expressing AFP.15 Unfortunately AFP levels were not measured in our patients. In radiological examinations, PB manifest as a solitary pulmonary nodule or mass with a smooth margin because of the desmoplastic change surrounding the mass. Generally, the tumor has massive necrosis.17 The tumor rarely appear to be cavitated, calcified or multiple. Despite bronchoscopy, mediastinoscopy, thoracoscopy, percutaneous and transbronchial biopsies, PB cannot be diagnosed preoperatively due to the lack of cellular material and extensive necrosis of the lesions.18 We also could not diagnose pulmonary blastoma preoperatively. The best treatment of pulmonary blastoma is surgery in the early stages of the disease. Adjunctive therapy is still controversial because of lack of data. Rare cases, which have good responds to chemotherapy and radiotherapy, have been reported in the literature whereas in the majority of cases recurrences are seen.19–21 Cutler et al. treated and reviewed the chemotherapy literature for PB and recommended cisplatin and etoposide treatment as effective regimes.15 Neoadjuvant chemotherapy for downstaging advanced tumors can be used before surgical resections.7 Recurrences are mostly seen with the incidence of 43%, 1–11 months after surgery.18 Recurrences most commonly occur in the brain, mediastinum, pleura, liver, diaphragm, heart and soft tissues of extremities.18 Nodal involvement is almost always associated with the tumor size and also poor prognosis in biphasic PB.6 Based on our limited experience, resection of small tumors, which do not have any lymph node involvement, can provide better survival without any additional treatment. Wedge resection should not be performed in PB. In one of our patient, there was a recurrence due to the inadequate surgical procedure (wedge resection). That patient underwent second operation, he did not have any nodal involvement and he has the best survival time in this small serie. In our cases adjuvant chemotherapies were not effective. Finally, in the patients with small size tumors, which do not have nodal involvement, long-term survival can be obtained with surgery even if it is
S.T. Liman et al. biphasic pulmonary blastoma. According to our limited experiences, N1 nodal involvement shows very poor prognosis even tumor is resected completely. Unfortunately, we still do not know the efficiency of the adjuvant chemotherapy and radiotherapy treatment. Multi-institutional treatment protocols in a sufficient number of patients should be performed.
References 1. Spencer H. Pulmonary blastoma. J Pathol 1961;82:161. 2. Larsen H, Sorensen JB. Pulmonary blastoma: a review with special emphasis on prognosis and treatment. Cancer Treat Rev 1996;22:145–60. 3. Berean K, Truong LD, Dudley AW, Cagle PT. Immunohistochemical characterization of pulmonary blastoma. Am J Clin Pathol 1988;89:773–7. 4. Korbi S, M’Boyo A, Dusmet M, Spiliopoulos A. Pulmonary blastoma. Immunohistochemical and ultrastructural studies of a case. Histopathology 1987;11:753–60. 5. Roth JA, Elguezabal A. Pulmonary blastoma evolving into carcinosarcoma. A case study. Am J Surg Pathol 1978;2(4):407–13. 6. Koss MN, Hochholzer L, O’Leary T. Pulmonary blastomas. Cancer 1991;67:2368–81. 7. Zaidi A, Zamvar V, Macbeth F, Gibbs AR, Kulatilake N, Butchart EG. Pulmonary blastoma: medium-term results from a regional center. Ann Thorac Surg 2002;73:1572–5. 8. Robert J, Pache JC, Seium Y, de Perrot M, Spiliopoulos A. Pulmonary blastoma: report of five cases and identification of clinical features suggestive of the disease. Eur J Cardiothorac Surg 2002;22(5):708–11. 9. LeMense GP, Reed CE, Silvestri GA. Pulmonary blastoma: a rare lung malignancy. Lung Cancer 1996;15:233–7. 10. Di Lieto E, Baldi A, Vicidomini G, Di Marino MP, Baldi F. Pulmonary blastoma in adults. Minerva Chir 1997;52: 839–46. 11. Dogan R, Gungen Y, Ucanok K, Cetin G. Pulmonary blastoma. Hacettepe Medical Journal 1989;22:235–9. 12. Majid OA, Rajendran U, Baker LT. Pulmonary blastoma. Ann Thorac Cardiovasc Surg 1998;4:47–52. 13. Berho M, Moran CA, Suster S. Malignant mixed epithelial/ mesenchymal neoplasms of the lung. Semin Diagn Pathol 1995;12:123–39. 14. Jacobsen M, Francis D. Pulmonary blastoma. A clinicopathological study of eleven cases. Acta Pathol Microbiol Scand 1980;88:151–60. 15. Inoue H, Kasai K, Shinada J, Yoshimura H, Kameya T. Pulmonary blastoma. Comparison between its epithelial components and fetal bronchial epithelium. Acta Pathol Jpn 1992;42:884–92. 16. Kasuga I, Miyamoto D, Ichinose Y, et al. Alpha-fetoprotein producing pulmonary blastoma in a patient with systemic sclerosis: pathogenetic analysis. Eur Respir J 1998;11:1185–7. 17. Lee HJ, Goo JM, Kim KW, Im JG, Kim JH. Pulmonary blastoma radiologic findings in five patients. Clin Imag 2004;28:113–8. 18. Novotny JE, Hurias CM. Resection and adjuvant chemotherapy of pulmonary blastoma: a case report. Cancer 1995;76:1537–9.
ARTICLE IN PRESS Pulmonary blastoma 19. Cutler CS, Michel RP, Yassa M, Langleben A. Pulmonary blastoma: case report of a patient with a 7-year remission and review of chemotherapy experience in the world literature. Cancer 1998;82:462–7. 20. Surmont VF, van Klaveren RJ, Nowak PJ, Zondevan PE, Hoogsteden HC, van Meerbeeck JP. Unexpected response of
1179 a pulmonary blastoma on radiotherapy: a case report and review of the literature. Lung Cancer 2002;36: 207–11. 21. Hasturk S, Erdogan Y, Cakiroglu E, Teke Y. Pulmoner Blastoma (bir olgu nedeniyle). Turk Hematol Onkol Derg 1993;3:116–20.