Lung Cancer 36 (2002) 207– 211
Unexpected response of a pulmonary blastoma on radiotherapy: a case report and review of the literature Veerle F. Surmont a,b,*, Rob J. van Klaveren b, Peter J.C.M. Nowak c, Pieter E. Zondervan d, Henk C. Hoogsteden b, Jan P. van Meerbeeck b a
Department of Pulmonology, Respiratory Oncology Unit, Uni6ersity Hospital Gasthuisberg, Herestraat 49, B-3000 Leu6en, Belgium b Department of Pulmonology, Uni6ersity Hospital Rotterdam, 3015 GD Rotterdam, The Netherlands c Department of Radiotherapy, Uni6ersity Hospital Rotterdam, 3015 GD Rotterdam, The Netherlands d Department of Pathology, Uni6ersity Hospital Rotterdam, 3015 GD Rotterdam, The Netherlands Received 18 September 2001; accepted 1 November 2001
Abstract Pulmonary blastoma (PB) is a rare malignant tumor of the lung. Treatment is primarily surgical, although, combination chemotherapy has been reported to result in objective responses in inoperable tumors or after incomplete resections. To our knowledge, this is the first report of a very radiosensitive PB, which showed major tumor reduction after several fractions of radiotherapy without further tumor regression after additional chemotherapy with cisplatin and etoposide. The literature on the treatment of PB is reviewed. © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Cancer; Pulmonary blastoma; Treatment; Radiotherapy; Case report; Review
1. Introduction Pulmonary blastoma (PB) is a malignant tumor of the lung composed of immature mesenchymal and epithelial cells. It is a very rare tumor, which constitutes 0.5% of all malignant lung tumors . The first published case of PB was described by Barrett and Barnard in 1945 . The tumor was named ‘pulmonary embryoma’ because of its microscopic similarity to the embryonal lung. In 1961 Spencer proposed the term ‘blastoma’ with the then prevailing view that the pathogenesis of the tumor was similar to Wilms tumor or nephroblastoma . In 1988 Manivell and co-workers introduced the term ‘pleuropulmonary blastoma’ (PPB), an embryonal type of pulmonary tumor in the pediatric population, with distinct clinico – pathological features different from the ordinary PB of adulthood . Although, the response of PB on radiotherapy is generally poor [5–7], this case report illustrates that PB * Corresponding author. Tel.: + 32-16-346-802; fax: + 32-16-346803. E-mail address: [email protected]
can be very radiosensitive. The literature on the management of this rare disorder is reviewed.
2. Case history A 49-year-old male presented in May 2000 with a 4-week history of fatigue, cough, left sided chest pain and progressive shortness of breath. His medical history revealed a smoking history of 10 pack-years. Physical examination was unremarkable except for absent breath sounds over the left hemithorax. This was confirmed by a chest radiograph, which showed an opacification of the entire left hemithorax and associated displacement of the mediastinum to the right. Laboratory tests were normal except for lactic dehydrogenase which was 6816 U/l (N B 450 U/l). The erythrocyte sedimentation rate was 84 mm in the first hour. Neuron specific enolase (NSE) was 68 mg/l (NB 12.5 mg/l). Sputum cytology was negative, and the analysis of the pleural fluid showed only a sterile exudate without malignant cells. Bronchoscopy showed extrinsic distortion of the left bronchial tree, with absence of endobronchial abnor-
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V.F. Surmont et al. / Lung Cancer 36 (2002) 207–211
malities. On chest computer tomography (CT) a bulky inhomogeneous mass was seen which occupied the whole left hemithorax, and a shift of the mediastinum to the right (Fig. 1). Transthoracic needle biopsy of the tumor was at first compatible with a diagnosis of small cell lung cancer (SCLC). Staging by bone scintigraphy and CT-scan of the brain, showed no further evidence of metastases. Due to rapid clinical deterioration and the presumed diagnosis of SCLC, treatment with cyclophosphamide (1000 mg/m2, D1), doxorubicine (45 mg/m2, D1) and etoposide (100 mg/m2, D1 – 3) was initiated. During the first course of chemotherapy the results of additional immuno-histochemical stainings became available, which showed both malignant epithelial and mesenchymal structures. Proliferation of epithelial cells with frequent mitosis in a mesenchymal stroma was found, and a diagnosis of PB was made (Fig. 2). Due to the very rapid growth of the tumor despite the initiation of chemotherapy, and the very poor performance (WHO 4) of the patient, we decided to refrain from further chemotherapy. Surgery was also considered impossible. In an attempt to relieve the patient from his dyspnea, 20 Gy of palliative radiotherapy was given on this large tumor in five fractions of 4 Gy. Although, we expected the patient to pass away within a few weeks, 1 month later he presented symptom-free at the outpatient clinic. A CT-scan at this time (1 month after radiotherapy) revealed a 75% tumor reduction (Fig. 3). To achieve further tumor regression treatment with cisplatin (80 mg/m2) and etoposide (100 mg/m2) every 3 weeks was initiated. Evaluation after
two cycles showed only minor additional tumor regression, and after four cycles chemotherapy had to be stopped, because of obvious disease progression. Presently, 1 year after diagnosis, the patient is still alive, but the tumor has grown again and occupies a large part of the left hemithorax. Furthermore, he has a right-sided intrapulmonary metastasis. Since, the tumor proved to be radiosensitive, it was decided to irradiate the primary tumor again with five fractions of 4 Gy, with also this time a good response.
3. Discussion PB are very rare tumors, which occur usually as large and well circumscribed solitary peripheral masses. The peak incidence of PB is in the 4th decade of life and some groups report a male predominance . Although, patients can be asymptomatic (41%), review of cases report that important symptoms are due to bronchial irritation, cough, dyspnea and hemoptysis are frequent. One third of patients have chest pain. Some of them present with weight loss (12%), fever (8%) or recurrent pneumonia (4%) . Chest X-ray at the time of diagnosis shows partial or complete opacification of one hemithorax, associated with mediastinal shift. This is usually confirmed by CT-scan, which shows a large space-occupying mass, which is unilateral in 98% of cases . Pleural effusion occurs in 13% of patients. Some patients present with pneumothorax . Sputum cytology and pleural fluid analyses are of limited value for diagnosis. Abnormalities in laboratory tests are
Fig. 1. CT scan shows a bulky mass with shift of the mediastinum to the right.
V.F. Surmont et al. / Lung Cancer 36 (2002) 207–211
Fig. 2. Proliferation of epithelial cells with frequent mitosis (E) in a mesenchymal stroma (M); diagnosis of PB. (Hematoxylin-eosin stain;original magnification, ×100.)
nonspecific. High levels of LDH have been reported . There are not specific tumor markers for this type of tumor. Siegel et al. reported two cases of PB with increased alpha foeto-protein production . PB is difficult to diagnose non-invasively. For correct diagnosis adequate histological specimens are needed. As illustrated in this case report, it can sometimes be difficult to distinguish PB from more common lung cancers. Microscopically, the tumor resembles to first trimester fetal lung. PB is a bifasic neoplasm, with a mixture of malignant epithelial and stromal cells. The epithelial component consists of tubular adenocarcinoma with glycogenated cytoplasm. The stroma consists of loose undifferentiated mesenchym and may have variable degrees of nuclear atypia. The glandular cells are strongly reactive for keratin, carcinoembryonic antigen and milk fat globulin and often chromogranin. Vimentin, actin and less desmin and myoglobin are mesenchymal markers. Koss et al. detected single p53 mutations in PB cells, which supports the clonal nature of the tumor . The types of p53 mutations are similar to the p53 mutations found in other lung cancers. They also detected adducts of benzpyrene (a product in tobacco smoke) in PB, which suggests that smoking may play a role in the development of these tumors. The hypothesis that PB might have the same pathogenesis as the more common lung cancers, is supported by the fact that 82% of these patients are smokers . The preferred treatment is surgical resection, although, in the majority of the patients the tumor is
unresectable or only incompletely resectable, because of massive tumor involvement [14,15], and in nearly half of all cases, local recurrences occur postoperatively . Overall survival after surgery is dependent on the extent of the resection, with a median survival of 26 months for lobectomies or minor resections, and 9 months for pneumonectomies . The prognosis of patients with PB is generally poor, and comparable with the prognosis of non-SCLC. Two thirds of patients die within 2 years of diagnosis, 16% survive 5 years and only 8% survive 10 years . Numerous case reports have confirmed the effectiveness of combination chemotherapy in inoperable tumors as well as adjuvant therapy after surgery [14–17,19]. Treatment with vincristine, doxorubicine, etoposide, ifosfamide, cyclophosphamide and cisplatin has induced objective responses. Larsen and Sorensen reported 26% overall response rate to first-line chemotherapy (without concurrent radiotherapy) in evaluable patients . Ozkaynak reported two pediatric cases in which combination chemotherapy was used successfully . A recent Italian study confirms these findings; event free survival at 2 years from the time of diagnosis was 45% for all patients, with an overall 2-year survival rate of 72%. . Cutler and Mitchel reported a 7-year remission induced by combination chemotherapy with cisplatin and etoposide after incomplete surgical resection . Since, the disease is so rare, there are no controlled chemotherapy trials available.
V.F. Surmont et al. / Lung Cancer 36 (2002) 207–211
Fig. 3. CT-scan 1 month after 20 Gy (5 ×4 Gy) radiotherapy.
There is disagreement about the role of local radiotherapy for the primary tumor. Some authors have emphasized the poor outcome after radiotherapy [17,5]. Calabria et al. described three patients treated with radiotherapy (4680 cGy during 3 months, 5580 cGy during 2.5 months and 400 cGy in 2 days, respectively) for recurrent disease, without objective response . Priest et al. reported that the survival rate does not differ significantly between patients who received radiotherapy and those who did not (2-year survival rate of 64% vs. 65%) . However, this case report illustrates that PB can be very radiosensitive.
4. Conclusion This case report illustrates that PB can be a very radio-sensitive tumor. Therefore, we should consider to include radiotherapy as part of a combined modality approach or as palliative therapy in the treatment of this rare disease.
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