Squamous Cell Carcinoma of the Lung in Association With Sarcoidosis
Shoh Tatebe, MD,
Kuniyuki Oka, MD1,
Joe Toda, MD2,
Maya Watanabe, MD,
Mayumi Shinonaga, MD,
Setsuo Kuraoka, MD
Department of Thoracic and Cardiovascular Surgery
1 Department of Pathology
2 Department of Radiology, Mito Saiseikai General Hospital, Mito City, Japan
Shoh Tatebe, MD, Tel: +81 25 227 2243, Fax: +81 25 227 0780, Email: statebe{at}yahoo.com, Department of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medicine and Dentistry, 757 Ashimachi-Dohri 1, Chuo District, Niigata City, 951-8520, Japan.
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ABSTRACT
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A 76-year-old man who was known to have sarcoidosis, developed a lung tumor. He had previously undergone cardiac and abdominal vascular surgery, at which sarcoidosis was confirmed by lymph node biopsy. A right lower lobectomy was carried out. Postoperative pathology showed limited disease, but cancer recurred 1 year later. Issues regarding the combination of sarcoidosis and a malignant tumor are discussed.
Key Words: Lung Neoplasms • Sarcoidosis • Pulmonary
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INTRODUCTION
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Sarcoidosis is a systemic granulomatous disorder that presents with hilar and mediastinal lymphadenopathy, pulmonary, skin, and eye lesions. There is evidence suggestive of an immunological disorder, of which the etiology remains unknown. There have also been reports of sarcoidosis patients with malignant tumors, and the risk developing cancer is still controversial.1–3 We describe a case of lung cancer with sarcoidosis, with a brief review to this combination.
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CASE REPORT
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A 76-year-old man initially presented with ischemic heart disease and underwent coronary artery bypass grafting. His history included 50 years of smoking half a pack of cigarettes daily (20–70 years of age). Preoperatively, swollen mediastinal lymph nodes were noted on computed tomography (CT). Intraoperatively, the parathymic lymph node was removed for pathological examination, which showed noncaseating epithelioid cell granuloma. Therefore, a diagnosis of sarcoidosis was achieved. Postoperatively, a systemic review was carried out, and all organs except lymph nodes were free from sarcoidosis. One year later, the patient underwent surgery for an abdominal aortic aneurysm, when sarcoidosis was again confirmed by paraaortic lymph node biopsy. The patient remained asymptomatic, but developed an abnormal shadow on chest radiography 2 years later. A CT showed pulmonary emphysema, bullae and a tumor in the basal segment of the right lung, which measured 1.6 x 3.0 cm (Figure 1A
). The mediastinal lymph nodes remained unchanged compared with CT 1 and 3 years previously (Figure 1B). Most serum tumor markers (carcinoembryonic antigen, alpha fetoprotein) were normal, but squamous cell carcinoma-related antigen and cytokeratin-19 fragment were elevated. Serum angiotensin-converting enzyme and Krebs von den Lungen-6 were normal. A diagnosis of squamous cell carcinoma was obtained by needle biopsy of the right lung, with the aid of CT. Further examination showed no distant metastases. The patient underwent a lower lobectomy of the right lung, partial resection of the right upper lobe (bulla), and lymph node dissection. Histopathological findings in the resected specimen included squamous cell carcinoma, moderately differentiated and 3 cm in size (Figure 2A), but no sarcoidosis lesions or scar/fibrosis were found adjacent to the cancer. There was no cancer metastasis, but noncaseating epithelioid cell granuloma was found in the excised lymph nodes (Figure 2B). Considering the limited nature of the cancer, which was confirmed by pathological examination, no postoperative treatment, such as cancer chemotherapy, was undertaken. However, 1 year later, serum tumor markers were found to be elevated (carcinoembryonic antigen, squamous cell carcinoma-related antigen) and CT revealed swollen lymph nodes adjacent to the thymus and in the supraclavicular region. A CT-guided needle biopsy was repeated, and a diagnosis of metastasis of squamous cell carcinoma and sarcoidosis was confirmed. The patient underwent irradiation of the anterior mediastinum and the right supraclavicular region. He is currently well, and tumor markers have decreased.
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Figure 1. Computed tomography showing (A) tumor in the right lower lobe and (B) enlarged mediastinal lymph nodes.
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Figure 2. Histological appearance of the resected specimen. (A) Lung tumor: a moderately differentiated squamous cell carcinoma was found. (B) Lymph node: a noncaseating epithelioid cell granuloma but no cancer metastasis was observed. Hematoxylin-eosin stain, original magnification, x200.
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DISCUSSION
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Despite the pathological examinations showing lung cancer as a limited disease, it recurred early postoperatively in this patient with primary lung cancer associated with sarcoidosis. Several issues were raised through this case.
The association of sarcoidosis with malignancy remains controversial. Lymphoma is the most frequent malignancy, whereas lung cancer is less common, and other form such as gastric, hepatic, and colon cancer are rare.2 Brincker and Wilbek4 reviewed 2,544 patients with sarcoidosis and found a 3-times higher risk of developing lung cancer. According to previous cohort studies to assess the risk of malignancy, sarcoidosis was not suggested to increase the risk of lung cancer5, and the relative risk of developing lung cancer was doubled during the first decade of follow-up.6 There have been 49 cases (26 males and 23 females) of lung cancer with sarcoidosis, including the present case, described in the literature. Ages ranged from 34 to 77 years (mean 62 ±10 years). Lung cancer occurred within 10 years after diagnosis of sarcoidosis in 45 patients, including our case.
Issues concerning the correlation between sarcoidosis and lung cancer are still unclear. Sakula7 presented 3 possibilities: (1) sarcoidosis precedes the development of the bronchial carcinoma, and is in some way causally connected and may even predispose to the malignant change; (2) sarcoidosis develops as a reaction to the bronchial carcinoma; or (3) sarcoidosis precedes the development of the bronchial carcinoma, the occurrence of the latter being entirely coincidental. Sakula’s 1st type is represented by cancer that develops from the postinflammatory scar tissue, namely, scar cancer. The 2nd type is difficult to apply because one can never be certain how long sarcoidosis has been present before it is clinically apparent. In our case, sarcoidosis occurred prior to the development of lung cancer. As there was no scar/fibrosis adjacent to the cancer, this was not a scar cancer. Furthermore, there were no sarcoidosis lesion in the lung suggestive of a positive correlation; therefore, this case might be one where sarcoidosis and lung cancer merely coincided.
Our patient remained asymptomatic and stable after the diagnosis of sarcoidosis, and this was confirmed by repeated CT scans. When lung cancer was confirmed, lymph nodes were also found to be swollen but unchanged. We thought the enlarged lymph nodes were due to sarcoidosis rather than cancer metastases, thus we undertook surgical resection of the lung. However, it should be noted that in 18 of 49 cases reported previously, sarcoidosis was confirmed at the same time of diagnosis or surgical resection of lung cancer. Regarding enlarged lymph nodes on preoperative CT, it is quite difficult to make a distinction between cancer metastasis and sarcoidosis. Lymph node biopsy by mediastinoscopy or thoracoscopic surgery, which was not carried out on our case, could provide a definite diagnosis in such cases.
In addition to the pathogenesis of lung cancer with sarcoidosis, there has been controversy over whether sarcoidosis, as an immunologic disorder, may accelerate cancer growth or recurrence. In a cohort study of 1,411 sarcoidosis patients, Yamaguchi and colleagues8 reported a 3-fold higher mortality rate from lung cancer. However, this conclusion may be weak due to the small number of lung cancer patients (n =3). In 49 cases previously reported, only 2 patients survived >5 years. Particularly, in 20 patients with non-small-cell lung cancer who underwent standard surgery, 2-year survival (Kaplan-Meier method) was 81% ±12%, which was compatible with the life expectancy of lung cancer without sarcoidosis. Despite no definite conclusion, sarcoidosis is suggested to have no influence on the prognosis in such patients.
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REFERENCES
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Asian Cardiovasc Thorac Ann 2009;
17:291-293
© 2009 by SAGE Publications
DOI: 10.1177/0218492309104764
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ABSTRACT
INTRODUCTION
