Eur J Cardiothorac Surg 2006;29:236-239
© 2006 Elsevier Science NL
Pulmonary blastoma — a rare tumor with variable presentation
Rajeshwara Krishna Prasad Adluri
*
,
Srikanth Reddy Boddu,
Antonio Martin-Ucar,
John Peter Duffy,
Frederick David Beggs,
William Ellis Morgan
Department of Thoracic Surgery, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, United Kingdom
Received 10 October 2005;
received in revised form 16 November 2005;
accepted 21 November 2005.
* Corresponding author. Tel.: +44 115 969 1169x7479; fax: +44 115 840 2605. (Email: arkrishnap{at}yahoo.com).
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Abstract
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Background: Pulmonary blastoma is a rare primary lung tumor with poor prognosis that commonly presents at a younger age than the non-small cell lung carcinoma (NSCLC). Classically they are large, symptomatic tumors with lymph nodal metastasis and carry poor prognosis. We report our experience of 7 patients with pulmonary blastoma who presented with varying clinical features. Methods: Retrospective analysis of our database revealed seven patients with pulmonary blastoma that were operated between January 1993 and December 2004. During the same time, 889 lung resections were performed for primary NSCLC. Demographic and clinical details were obtained from hospital notes. The histopathology reports were reviewed with the department of pathology and the radiological images were reported. Results: The tumors showed a bimodal pattern in age at incidence being (four patients were less than 49 years and three more than 66 years). All patients were symptomatic and demonstrated variable sized tumors. Lesions were common in lower lobes (lower:other lobes –4:3) and were staged T2N0 pathologically. All of the patients underwent surgical resections and had no chemotherapy/radiotherapy following surgery. Three of the seven patients died during follow-up due to unrelated causes between 24 and 29 months. The longest follow-up was more than 9 years and the survivor continues to do well. Conclusions: Pulmonary blastomas are rare tumors but can present with differing clinical features. Early detection and treatment may improve prognosis. Further larger series are needed to evaluate the characteristics of the tumor.
Key Words: Lung cancer • Blastoma • Pulmonary blastoma • Primary tumors of lung
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1. Introduction
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Pulmonary blastomas (PB) are a rare primary malignant tumor (non-small cell lung carcinoma—NSCLC) of lung comprising immature mesenchyme and epithelium that mimic morphologically an embryological pulmonary structure. Over 200 cases have been reported so far worldwide since the first description of the tumor in 1945 [1]. PB present at a younger age and has been reported to have a poor prognosis despite treatment. We report a series of seven cases of pulmonary blastoma that were presented and treated in our unit and review their clinical, radiological, and pathological variability.
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2. Methods
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A review of all cases of lung cancer treated surgically in our unit between January 1995 and December 2004 identified seven patients with a confirmed diagnosis of pulmonary blastoma. The demographic, clinical, and operative data were obtained by reviewing their clinical notes and the histopathological diagnosis was verified with the department of pathology. Full follow-up was obtained in all cases. The results of clinical presentation, radiological features, and outcomes following treatment were compared to the available literature.
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3. Results
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The male to female ratio was 2:5 and the patients were aged between 39 and 81 years with a median age of 57 years (range 39–85 years) (Table 1
). Mean age at presentation was less in the women when compared to men (49.2 years vs 73.5 years).
All the patients were heavy smokers and presented with symptoms of cough and shortness of breath. Three patients had voice change and chest pain at presentation. Five patients presented with hemoptysis; however, only one of them had a bleeding endobronchial lesion. Other personal histories were not contributory. Four of the seven patients had lesions in lower lobes and three in left upper lobe.
Preoperative bronchoscopy revealed a visible tumor in the bronchial tree in three patients; only one patient had active bleeding from the tumor. On the CT scan, the lesions were reported as non-specific masses in two patients and as bronchogenic cyst in one and as an abscess in one patient (Fig. 1
). In contrast to the solitary lesions in rest of the patients, one patient presented with multiple nodules, which were thought to be ‘metastasis with atypical distribution’.
Fine needle aspiration of the lesions was variably reported as cells suspicious of malignancy, squamous cell carcinoma, and germ cell tumor. The tumor size varied between 3.2 cm to a maximum of 8 cm (average, 5 cm). The tumors were staged as being T2N0 preoperatively.
All seven patients underwent pulmonary excisions, which were considered macroscopically curative (lobectomy in six patients and wedge resection in one patient). Mediastinal lymph nodes were selectively sampled in all cases.
Pathological examination revealed features suggesting pulmonary blastoma, five patients had biphasic tumors with mesenchymal and epithelial components and two patients had well-differentiated fetal adenocarcinoma (WDFA) (Fig. 2
). All tumors were staged as being IB (T2N0) with microscopically clear margins. Postoperatively none of the patients had radiotherapy or chemotherapy. The patient who had wedge resection developed a radiological recurrence after 12 months, which was not operated for medical reasons (aged 84 years with comorbidities). During follow-up, three patients died at 24, 29, and 84 months; however, none of these deaths were related to the primary malignant lesion, or recurrence. The longest follow-up was up to 9 years following surgery. The overall survival at 2 years was 85.7% and at 5 years was 71.4%. Average stay in hospital was 9 days. In hospital, complications included impaired renal function in one patient who recovered with conservative management not requiring dialysis, and one patient developed atrial fibrillation, which was treated medically.
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Fig. 2. Photomicrograph showing pulmonary blastoma with a characteristic biphasic picture with well-differentiated tubular glands and cellular stroma composed of small oval to spindle cells.
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4. Discussion
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Pulmonary blastomas (PB), designated ‘embryomas’ by Barnard [2], are a specific form of carcinosarcoma, which were defined by Spencer [3]. These are biphasic tumours in which both the epithelial and mesenchymal components are immature or embryonal in appearance (Fig. 2). Pulmonary blastomas comprise between 0.25 and 0.5% of all primary malignant lung tumours [4,5].
Over 200 cases have been reported world over. Patients traditionally present at a younger age than non-small cell lung carcinoma (NSCLC). In our report, four patients were aged less than 48 years, which is similar to previous series [4,6]. However, the other three patients were aged more than 65 years (with two of them in 80s), which may suggest a bimodal age distribution in incidence. Another feature of these tumors is that they are more common in females [7] than in males (current series F:M = 5:2).
PB present as large and well-demarcated masses (Koss et al. [6] reported an average size of 10.1 cm and Jacobson et al. [5] have reported an average size of 6.9 cm), and owing to their bulkiness they are usually symptomatic. The average size of the tumors in our series is 5.0 cm, smaller than those reported in previous studies (Fig. 3
). In the current series, the largest tumor was 8 cm (as compared to 27 cm in the series reported by Koss et al. [6]); however, the size of tumor at presentation has been reducing over the years with recent tumors being less than 6 cm. The possible explanation for this reduction in size could be improvement in awareness and easy availability of investigations.
Pulmonary blastomas are usually solitary, large, peripheral tumors, which macroscopically appear pale and fleshy with foci of cystic change and hemorrhage [8,9].
PB are seen as a well-demarcated mass, usually located in the upper lobes on chest radiographs (Fig. 3) and CT scans. In our current series, the incidence was more common in the lower lobes than in the upper [7,10] (upper:lower = 3:4). Rarely PB can present as multiple nodules [10], as seen in one of the patients in the current series, which could be mistaken for metastasis.
Microscopically, the epithelial component corresponds to low-grade adenocarcinoma of fetal lung type (L-FLAC)/well-differentiated adenocarcinoma (WDFA), which characteristically exhibits complex ‘endometrioid’ glands, which resemble fetal lung and squamoid morules with biotin-rich optically, clear nuclei.
The mesenchymal component may be embryonic or blastemal and may differentiate toward striated muscle, smooth muscle, cartilage or a combination of these.
Recent studies have demonstrated gene mutations in PB with aberrant nuclear/cytoplasmic localization of beta-catenin, which can be, detected immumohistochemically in both the epithelial and mesenchymal components [9]. By contrast, most conventional lung carcinomas show membranous localization of beta-catenin with no mutations in the gene. A similar pattern is seen in blastomatoid variants of carcinosarcoma, which had previously been grouped with PB. The final histology showed that five patients had biphasic tumor and two had fetal adenocarcinoma-type tumors.
Inspite of having characteristic features a preoperative cytology and FNAC for PB are usually nonspecific [8] and final histogical confirmation is after excision and with immunochemical techniques.
Bronchoscopy may or may not reveal an endobronchial lesion as majority of the lesions are placed peripherally. In our series, three patients had lesions that were visible endobronchially and another patient had a bleeding lesion; however, the preoperative biopsies were inconclusive.
PB often metastasize to the local lymph nodes, which are usually involved at presentation. In one of the recent series, four of the five patients reported had N2 disease on final histology [8]. However, in the current series none of the patients had any nodal disease. In the series that reported metastasis, the metastatic lesions did not reproduce the biphasic primary tumor architecture but showed evenly distributed monotype or mixed histologies [4].
Chemotherapy and radiotherapy have been tried for advanced tumors. Chemotherapy agents similar to that used in germ cell tumors were used, which included Cisplatin, VP-16, Uromitexan, Ifosfamide [7]. Radiotherapy with upto a total of 64 Gy in 32 fractions over 7 weeks has been used in prior studies [7]. In our series owing to the early stage of tumor none of the patients received either chemotherapy or radiotherapy. In cases with locally advanced tumors, mediastinal lymph node involvement, or metastasis chemotherapy/radiotherapy can be attempted.
Pulmonary blastomas are fast growing tumors with poor prognosis. In a Danish survey of 83 patients, following surgery the average survival was 33 months; in a recent series the median survival was approximately one year [8]. However, in the current series two patients died around 2 years following surgery and the other patient at 84 months. One of the patients continues to do well after 9 years follow-up. Owing to their early stage at presentation and surgically clear margins, none of the patients had either chemotherapy or radiotherapy following surgery. The average survival was 49.7 months (survival at 2 years was 85.7% and at 5 years was 71.4%). Improved survival could be the result of early stage of the disease in all patients (presenting at T2N0M0).
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5. Conclusion
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Traditionally, pulmonary blastomas have been reported to be tumors affecting younger patients and carry poor prognosis. In contrast to previous studies, our series of patients presented with variable features—older patients, smaller tumors with varying appearances on imaging, early stage of tumors (T2N0), and better survival following surgery alone. The improved survival in our series may be due to the fact that the tumors were small and hence could be resected completely. Whether early detection and intervention carries good prognosis and longer survival with surgery alone needs to be studied.
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References
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Abstract
1. Introduction
