|Year : 2011 | Volume
| Issue : 2 | Page : 198-200
Radiation-induced sarcoma in bronchial stump after thoracic radiation therapy for small-cell lung cancer
Hong Zhu1, XiaoGe Zhou2, ChangSheng Wang3
1 Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Republic of China
2 Department of Cardiothoracic Surgery, Beijing Friendship Hospital, Capital Medical University, Republic of China
3 Department of Radiation Oncology, Beijing Friendship Hospital, Capital Medical University, Republic of China
|Date of Web Publication||12-Jul-2011|
Department of Pathology, Beijing Friendship Hospital, No. 95, Yong'an Road, Xuanwu District, Beijing 100050
Republic of China
Source of Support: None, Conflict of Interest: None
We report a rare case of radiation-induced sarcoma (RIS) that arose in the right bronchial stump, 8 years after right pneumonectomy followed by adjuvant chemotherapy and thoracic radiotherapy for a localized small-cell lung cancer. The patient was treated in 2002 with 6 MV X-ray irradiation in a total dose of 60 Gy. Eight years after the end of radiotherapy, he presented with an undifferentiated high-grade pleomorphic sarcoma. Although an increased rate of soft tissue sarcoma has been reported after radiotherapy for some solid cancers or lymphomas, to our knowledge, this is the first report of RIS related to small-cell lung cancer.
Keywords: Pleomorphic sarcomas, radiation-induced neoplasms, small-cell lung cancer
|How to cite this article:|
Zhu H, Zhou X, Wang C. Radiation-induced sarcoma in bronchial stump after thoracic radiation therapy for small-cell lung cancer. J Can Res Ther 2011;7:198-200
|How to cite this URL:|
Zhu H, Zhou X, Wang C. Radiation-induced sarcoma in bronchial stump after thoracic radiation therapy for small-cell lung cancer. J Can Res Ther [serial online] 2011 [cited 2020 Sep 22];7:198-200. Available from: http://www.cancerjournal.net/text.asp?2011/7/2/198/82924
| > Introduction|| |
When radiotherapy and chemotherapy are used as adjuvant therapies of surgery, the possibility of the appearance of a sarcoma within the irradiated field should be considered. Radiation-induced sarcomas (RISs) have been reported after radiotherapy for tumors such as breast cancer, prostate cancer and lymphoma. , To the best of our knowledge, there is only one report of RIS related to curative chemoradiotherapy for non-small-cell lung cancer (NSCLC),  while not being related to small-cell lung cancer (SCLC). Until now, RISs have been considered very rare. This case report may help the clinician to be aware of the existence of such rare complications, which may impact the length of long-term follow-up of patients and the design of future clinical treatment.
| > Case Report|| |
A 51-year-old male initially presented in August 2001 with a 2-month history of cough and right chest pain. Computed tomography (CT) scan revealed a 4-cm central type lung mass in the right lung, and the tumor mass was seen obstructing the right mainstem bronchus on bronchoscopy. The patient underwent thoracotomy, which showed a mass in the root of right upper lobe involving right main pulmonary artery and middle lobar bronchus. A right-sided pneumonectomy was performed. The pathological examination revealed SCLC with a negative surgical margin. Bone scan as well as head and abdominal CT scan were negative for metastases, and the patient was considered to have T3N2M0 disease. Four months after surgery, adjuvant chemotherapy was started, which consisted of carboplatin (CBP), teniposide (Vm-26), etoposide (VP-16) and paclitaxel (PTX). Chemotherapy ended in August 2003 and lasted 20 months for a total of 12 cycles. After the third cycle from March to April 2002, the patient received normofractionated thoracic radiotherapy delivered by a linear accelerator with 6 MV X-rays. The total dose was 60 Gy in 30 fractions, with a dose of 2 Gy daily for 3-5 days each week. The treatment fields encompassed the bronchial stump, bilateral hilum, mediastinum and ipsilateral supraclavicular fossa. By the end of chemotherapy, the patient had no immediate complication and had been followed up for about 8 years without signs for recurrence on his chest X-ray examination.
In January 2010, after approximately 3 months of cough, chest CT was performed which showed no significant abnormalities. Bronchoscopy revealed polypoidal protuberance in the right bronchial stump with 3-mm orificium fistulae. The initial differential diagnosis included recurrent SCLC, a second primary NSCLC and SCLC. The patient underwent bronchoscope biopsy and the histologic examination revealed discontinuous normal mucosal lining with underlined malignant mesenchymal neoplasm. The tumor was moderately to highly cellular and was composed of large, irregular, spindle-shaped to plump elongated cells arranged in short fascicles with focal vague storiform patterns and having foci of necrosis [Figure 1]. The lesion was predominately diffuse with no evidence of epithelial differentiation as previously diagnostic SCLC in 2001 [Figure 2]. The nuclei were large and pleomorphic with shapes including vesicular, elongated, spindled and occasionally multinucleate giant cells [Figure 3]. Approximately six to eight mitoses per 10 high-power fields (HPF) were present. Immunohistochemical staining of the tumor cells showed 100% vimentin [Figure 4] and 40% CD163 positivity, while there was negative staining with pancytokeratin, p63 and CK7, which did not support a diagnosis of recurrent SCLC or newly occurring epithelial tumor. Additional diagnoses which were not supported by immunohistochemical staining included leiomyosarcoma (desmin and SMA negativity), rhabdomyosarcoma (myoglobin negativity), malignant neurofibroma (S-100 negativity), angiosarcoma (CD31 and CD34 negativity) and melanoma (Melan-A/MART-1 and HMB45 negativity). Sixty percent of tumor cells showed MIB-1 positivity. According to the morphologic and immunohistochemical reactivity, a diagnosis of undifferentiated high-grade pleomorphic sarcoma was established.
|Figure 1: H&E staining of the sarcoma, low-power view: sheets of cells arranged in short fascicles with focal vague storiform patterns, with no evidence of epithelial differentiation|
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|Figure 2: H&E staining of the small-cell lung cancer, low-power view: densely packed tumor cells having a round to fusiform shape, scant cytoplasm, and fi nely granular chromatin|
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|Figure 3: H&E staining of the sarcoma, high-power view: marked nuclear pleomorphism and a number of multinucleated cells|
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|Figure 4: Positive immunochemical staining for vimentin (EliVision ×400)|
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Instead of a surgery because of the impossible radical resection and fear of a postoperative fistula, bronchial stent-graft implantation was used to seal the bronchial stump fistula. The patient was not given postoperative chemotherapy due to the general condition and the relative ineffectiveness of the tumor. Three months later, the patient presented with dyspnea, chest pain and pleural effusion indicative of a recurrent fistula. He received a reirradiation therapy by 3-dimensional conformal radiotherapy (3DCRT) to relieve symptoms. The patient still has the above symptoms in a 6-month follow-up, without further therapy.
| > Discussion|| |
RIS is an uncommon but well-documented long-term complication of radiotherapy, with an incidence ranging from 0.03% to 0.80%. , Common primary cancers were breast (26%), lymphoma (25%), and cervix (14%) in the large series of 160 RISs reported from MSKCC.  Most series agree in showing osteosarcoma and malignant fibrous histiocytoma as the most common histologic types. ,, In 1948, Cahan et al. established a set of diagnostic criteria that are still cited by most of the studies today: previous radiotherapy treatment; a minimum latency period of 4-5 years; appearance of the sarcoma in an irradiated area; and the different histology of the second neoplasm by pathologic review.  The current knowledge does not allow us to distinguish morphologically the RISs from spontaneous tumors in the same area. However, the sarcomas that match with the Cahan criteria are usually considered as RISs.
Compared with NSCLC, SCLC is a rapidly growing tumor with a median survival of only 6-10 months.  To the best of our knowledge, there is no report of RIS related to radiotherapy for SCLC. RIS is a later complication, thus the current patients' survival have not been long enough to observe a large number of long-time, radiation-induced second neoplasms. Nevertheless, given the high incidence of lung cancer, the earlier stage at diagnosis and the relatively long survival achieved with therapeutic advances, an increase in the number of patients at risk for this complication is to be expected in the near future.
Radiation dose may be a factor in the development of RIS. There are some suggestions that 40 Gy is the threshold dose for tumorigenic effects and the risk increases further with a total dose of 55 Gy or above. , Development of RIS also is influenced by other factors, including genetic tendency and chemotherapeutic agents. Cytogenetic analysis using G-banding showed a striking variety of chromosome rearrangements, although no distinctive cytogenetic aberrations are known to be specific for NISs. 
Despite the rare incidence, RISs' biological behavior is more aggressive than that of spontaneous tumors. In the relatively large unselected groups with various RIS, the median survival was 12-23 months. , Also, the 5-year survival was 39% for patients treated with surgery, while it was only 10% for those treated with chemotherapy.  Surgery seems to be the only effective treatment but adequate resection is sometimes difficult or impossible because of the previously delivered treatment. Given the rarity of this complication and the relatively poor prognosis of lung cancer, the decision regarding the treatment of radiotherapy should not be dependent on the possibility of the occurrence of a RIS. However, vigilant serial examinations of patients who have received radiation are therefore encouraged. The present case highlights the importance of being aware of this unusual complication.
| > References|| |
|1.||Brady MS, Gaynor JJ, Brennan MF. Radiation-associated sarcoma of bone and soft tissue. Arch Surg 1992;127:1379-85. |
|2.||Mark RJ, Poen J, Tran LM, Fu YS, Selch MT, Parker RG. Postirradiation sarcomas. A single-institution study and review of the literature. Cancer 1994;73:2653-62. |
|3.||Stinchcombe TE, Walters R, Khandani AH, Socinski MA. Radiation-induced sarcoma after high-dose thoracic radiation therapy in non-small-cell lung cancer. J Clin Oncol 2007;25:1621-3. |
|4.||Sale KA, Wallace DI, Girod DA, Tsue TT. Radiation-induced malignancy of the head and neck. Otolaryngol Head Neck Surg 2004;131:643-5. |
|5.||Amendola BE, Amendola MA, McClatchey KD, Miller CH Jr. Radiation-associated sarcoma: A review of 23 patients with postradiation sarcoma over a 50-year period. Am J Clin Oncol 1989;12:411-5. |
|6.||Lagrange JL, Ramaioli A, Chateau MC, Marchal C, Resbeut M, Richaud P, et al. Sarcoma after radiation therapy: Retrospective multiinstitutional study of 80 histologically confirmed cases. Radiology 2000;216:197-205. |
|7.||Cahan WG, Woodard HQ, Higinbotham NL, Stewart FW, Coley BL. Sarcoma arising in irradiated bone: report of eleven cases. 1948. Cancer 1998;82:8-34. |
|8.||Beadsmoore CJ, Screaton NJ. Classification, staging and prognosis of lung cancer. Eur J Radiol 2003;45:8-17. |
|9.||Prevost JB, Bossi A, Sciot R, Debiec-Rychter M. Post-irradiation sarcoma after external beam radiation therapy for localized adenocarcinoma of the prostate. Tumori 2004;90:618-21. |
|10.||Huvos AG, Woodard HQ, Cahan WG, Higinbotham NL, Stewart FW, Butler A, et al. Postradiation osteogenic sarcoma of bone and soft tissues. A clinicopathologic study of 66 patients. Cancer 1985;55:1244-55. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]