Clin J Gastroenterol (2009) 2:89–95 DOI 10.1007/s12328-008-0053-9
Colonic metastasis from primary carcinoma of the lung: report of a case and review of Japanese literature Hiromi Ono Æ Mihiro Okabe Æ Takashi Kimura Æ Masato Kawakami Æ Kenji Nakamura Æ Yasushi Danjo Æ Hidero Takasugi Æ Hiroshi Nishihara
Received: 19 July 2008 / Accepted: 27 November 2008 / Published online: 7 January 2009 Ó Springer 2008
Abstract We report a rare case of colonic metastasis from primary carcinoma of the lung. A 59-year-old man who underwent pulmonary surgery for lung cancer was referred to our hospital in June 2007. The patient complained of abdominal pain, and barium enema examination at another hospital had demonstrated a descending colon tumor. Postoperative histopathological and immunohistochemical findings indicated that the tumor was a colonic metastasis of lung cancer. Three months postoperatively, the cancer had metastasized to the brain, and the patient underwent radiotherapy. He survived for more than 1 year after colonic surgery. Clinically apparent metastases from lung cancer to the colon are rare, and in the 50 Japanese cases retrospectively investigated here, the prognosis was poor. Keywords Colonic metastasis Cytokeratin 7 (CK7) Cytokeratin 20 (CK20) Lung cancer Thyroid transcription factor-1 (TTF-1)
H. Ono (&) M. Okabe T. Kimura M. Kawakami Department of Internal Medicine, Seiwa Memorial Hospital, 1-5-1-1 Kotoni, Nishi-ku, Sapporo 063-0811, Japan e-mail: [email protected]
K. Nakamura Y. Danjo Department of Surgery, Seiwa Memorial Hospital, Sapporo, Japan H. Takasugi Department of Internal Medicine, Ohguro Gastroenterology Hospital, Sapporo, Japan H. Nishihara Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Introduction Colonic metastasis from primary lung cancer is rare. Approximately half of all patients with lung cancer have metastatic disease at the initial diagnosis, and the brain, liver, adrenal glands, bones, and lymph nodes are the most commonly involved sites [1, 2]. A search of Ichushi Web, a Japanese medical database, showed that only 50 Japanese cases of colonic metastases from primary lung cancer were reported between 1983 and 2007 (Table 1). Median survival after abdominal surgery in 14 of these 50 cases was 90.5 days (range 12–300 days). We report the case of a patient with a primary lung cancer demonstrating a solitary colonic metastasis that was successfully resected.
Case report A 59-year-old man with a history of lung cancer (Fig. 1) was referred to our hospital in June 2007 for colonic tumor. Ten days before admission, he had consulted another hospital with complaints of left lower abdominal pain. Barium enema examination revealed a submucosal tumor (SMT), which was diagnosed as a descending colonic tumor (Fig. 2). He was 168 cm tall and weighed 55 kg. He had been smoking 20 cigarettes daily for 38 years. Right upper lobectomy of the lung was performed on 5 October 2006, and the tumor was staged as pT1N0M0 (pStage IA). His vital signs were stable. Physical examination demonstrated left lower abdominal pain and abdominal fullness. Results of hematological and biochemical investigations were normal. Tumor markers, carcinoembryonic antigen, and carbohydrate antigen 19–9 were below the detection range. Computed tomography (CT) scanning showed a mass measuring 3 9 3 cm at the fifth lumbar level (Fig. 3).
Clin J Gastroenterol (2009) 2:89–95
Table 1 Japanese cases of colonic metastases from the lung cancer between 1983 and 2007 (based on a search of Ichushi Web)
Table 1 continued Prognosis
M 43, F 6, U 1
Abdominal surgery (median 90.5 survival days; range 12-300)
70.5 ± 8.7 years (37–85 years)
Non-abdominal surgery (median 45.0 survival days; range 17-96)
Abdominal surgery (over 1 year alive)
Chief complaint Abdominal pain
3 (6%) 2 (4%)
M male, F female, U unknown, SCC squamous cell carcinoma, Adeno adenocarcinoma, large large cell carcinoma, small small cell carcinoma, p pathological, c clinical
Serious complications with abdominal pain undergoing emergency surgery (13 cases) Obstruction (ileus: eight cases, invagination: 9 one case) Perforation
Staging of the lung cancer on admission Lobectomy (U: 11 cases); non-lobectomy (U: 20 cases) pI
Sites of metastases other than colon Small intestine
Type of surgery Colonic resection
Small intestinal resection None
1 (2.0%) 7 (14.0%)
Fig. 1 Chest CT scan showing a high-density mass in the right upper lung region (arrow)
Colonoscopic examination showed a SMT in the descending colon; however, we could not pass the colonoscope through the region due to intense abdominal pain and hence could not examine the whole of the descending colon (Fig. 4). Biopsy specimens of the colonic mucosa did not demonstrate any malignancy. Surgery was performed on 22 June 2007, after informed consent was obtained from the patient. The tumor was located in the descending colon, and descending colectomy was performed. The tumor and lymph nodes appeared to be completely resected. The tumor measured 4 9 3 cm, invaded the submucosa, and had clear margins; in addition, a small ulcer had formed on the intraluminal side (Fig. 5). Macroscopic examination demonstrated a tumor extending from the submucosal to the subserosal layer of the colonic wall (Fig. 6). Microscopic examination demonstrated chiefly tubular adenocarcinoma and lymph node metastasis. The tumor was initially diagnosed as primary colonic cancer and was staged as pT3N1M0 (pStage III), but it was mainly located in the submucosal layer of the colonic wall. Therefore, immunohistochemical staining for cytokeratin 7 (CK7), cytokeratin 20 (CK20), and thyroid transcription factor-1 (TTF-1) was performed. The tumor
Clin J Gastroenterol (2009) 2:89–95
Fig. 4 Colonoscopic view showing a submucosal tumor in the descending colon (arrow)
colonic tumor was finally diagnosed as a metastasis from lung carcinoma. One month postoperatively, we initiated chemotherapy. Three months postoperatively, the patient underwent magnetic resonance imaging after reporting a headache, and brain metastasis was discovered, for which irradiation was performed. He has survived for more than 1 year since the abdominal surgery. Fig. 2 Barium enema showing stenosis due to external pressure in the descending colon (arrow)
Fig. 3 Abdominal CT scan showing a ringed high-density mass with a central low-density area at the fifth lumbar level (arrow)
stained for CK7 and TTF-1, but not CK20 (Fig. 7). Microscopic examination of primary lung cancer cells was suggestive of papillary adenocarcinoma, and these cells stained for CK7 and TTF-1, but not CK20 (Fig. 8). The
Colonic metastases account for 0.1–1% of the overall incidence of colonic tumors , but those originating from lung cancer are rare [4–6]. Only 50 Japanese cases of colonic metastases from lung cancer were reported between 1983 and 2007 according to a search of Ichushi Web (Table 1). The most common sites of metastasis from lung carcinoma are the brain, liver, adrenal glands, bones, and lymph nodes [1, 2]. A total of 350 patients with nonsmall-cell lung cancer (NSCLC) underwent whole-body 18 fluorodeoxyglucose positron emission tomography (FDG-PET)/CT imaging, and in 350 patients, 37 solitary metastases were located in bone, brain, liver, and adrenal and abdominal lymph nodes, but none in the colorectum . This report indicates that colonic metastases from lung cancer are very rare. Antler et al.  reported that largeand small-cell carcinomas lead to gastrointestinal metastases more often than the other histological types. In contrast, squamous cell carcinoma and adenocarcinoma were the most frequent histological types in the 50 Japanese patients with colonic metastases included in our retrospective investigation (Table 1).
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Fig. 5 Macroscopic examination of the descending colonic tumor showing its invasion at the mucosal level (a small intraluminal ulcer can also be seen) (a) and at the serosal level (b). The tumor after formalin fixation is shown in c
Fig. 6 Loupe findings of specimens stained with hematoxylin and eosin (HE). The tumor measured 40 9 30 9 30 mm. Histologically, the tumor extended from the submucosal to the subserosal layer. The mucosa was intact
Abdominal pain, hemorrhage, and anemia were the most frequent chief complaints presenting as clinical symptoms of colonic metastases in these patients (Table 1); these metastases were diagnosed by barium enema or endoscopic examination. Early detection of colonic metastases is thought to be difficult for the following reasons: (1) physicians have limited awareness of this clinically rare type of metastasis, (2) non-specific symptoms may be considered a side effect of chemotherapy, (3) patients do not undergo colonoscopic examination unless specific abdominal symptoms arise, and (4) conventional CT scanning may have low sensitivity for the early detection of colonic tumors . Recently, FDG-PET scanning has begun to be used in screening for unsuspected distant metastases from lung cancer. It has better sensitivity than CT for the detection of distant metastases in patients with lung cancer . In
patients with clinical stage III disease, PET scanning detected extrathoracic metastases in *25% of patients . In fact, a solitary colonic metastasis from lung cancer has been previously detected by PET scanning , but since this imaging tool also demonstrates increased FDG uptake in other colonic lesions, e.g., abscesses, adenomatous polyps, and hamartomatous adenomas, colonoscopic examinations need to be performed for differential diagnosis . In a recent retrospective review of patients with NSCLC, solitary extrapulmonary lesions were detected on PET/CT imaging in 21% of patients, and 46% of the lesions were either another malignancy, a benign tumor, or an inflammatory condition . When there are similar histological findings in both colorectal and pulmonary lesions, the question is whether both lesions are primary cancers or the colorectal lesions are metastases from lung cancer. Microscopic examination of a conventional pathological section is not sufficient to make this determination . Because primary colonic cancer shows a CK7(-)/CK20(?) cytokeratin pattern, whereas adenocarcinoma of the lung shows a CK7(?)/ CK20(-) pattern, Kummar et al.  used immunohistochemical staining for effective differential diagnosis; lung and colorectal adenocarcinomas were identified in 95% of cases based on the CK7/CK20 pattern, suggesting that cytokeratin staining is a cost-effective screening tool. Yatabe et al.  reported the use of TTF-1 to distinguish between primary and metastatic lung adenocarcinomas. TTF-1, a common thyroid and peripheral lung antigen, stains positively in primary lung and thyroid adenocarcinoma cells, but not in primary colorectal adenocarcinoma cells. Pathological examination in our case showed that the pulmonary and colonic lesions were papillary and tubular adenocarcinomas, respectively. Staging of the lung cancer was pT1N0M0 (pStage IA), so at first it was thought that the colonic tumor did not metastasize from the lung.
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Fig. 7 Loupe and microscopic findings of the colonic metastasis. HE staining (a), immunohistochemical staining of the tumor for cytokeratin 7 (CK7) (b), absence of staining for cytokeratin 20 (CK20) (9200) (c), and staining for thyroid transcription factor 1 (TTF-1) (9400) (d)
Fig. 8 Loupe and microscopic findings of the primary lung cancer. HE staining (a), immunohistochemical staining of the tumor for CK 7 (b), absence of staining for CK20 (9200) (c), and staining for TTF-1 (9400) (d)
Therefore, immunohistochemical staining was performed for CK7, CK20, and TTF-1 to distinguish between primary and metastatic colon adenocarcinoma. We found that adenocarcinoma of the colon showed a CK7(?)/CK20(-)/ TTF-1(?) pattern, and the colonic tumor was diagnosed as a metastasis from lung carcinoma.
The prognosis of patients with a solitary colonic metastasis detected on PET scanning, barium enema, or endoscopic examinations is unclear. A proportion of patients with solitary brain or adrenal gland metastasis may achieve prolonged survival with resection of both the primary and solitary metastatic lesions [17, 18]. However, whether long-
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Table 2 Characteristics of three patients with colonic metastases from lung cancer who are alive more than 1 year after abdominal surgery Reporter (year)
Region of lung cancer
Staging of lung cancer
Region of colon metastases
Sites of metastases except colon
Appe, C, A
Right hemi-colectomy, partial jejunoileectomy
IIIA Machida (2006)
Our case (2008)
IA M male, p pathological, U unknown, scc squamous cell carcinoma, adeno adenocarcinoma, A ascending colon, Appe appendix, C cecum, D descending colon
term survival is possible with resection of the primary lung cancer and solitary colonic metastasis is unknown. Among the 50 Japanese cases that we investigated retrospectively, median survival after abdominal surgery in 14 cases was 90.5 ± 83.4 days (range 12–300 days) and that without surgery in 5 was 45.0 ± 27.0 days (range 17–96 days). These figures indicate poor prognoses. Stage III and IV disease accounted for 68.4% of all stages in 19 cases, and metastases to other sites, such as small intestine, brain, liver, bone, and adrenal gland, typically tended to occur in the end stages of a widespread disease. They also tended to be multiple. Colonic metastases eventually resulted in serious complications such as obstruction or perforation (Table 1). Morris et al.  reported that the survival time averaged less than 60 days after patients with lung cancer complained of abdominal symptoms. However, of the 50 Japanese patients surveyed, three including the present one have survived more than 1 year after surgery (Table 2). It is difficult to determine surgical indications from three cases. These patients had metastases in sites such as bone, kidney, small intestine, and brain. It is thought that patients may survive more than 1 year after colonic surgery if surgery or radiation therapy can control the lung cancer and metastases. In conclusion, it remains controversial whether abdominal surgery should be performed for colonic metastases, because in the 50 Japanese cases assessed here, median survival after abdominal surgery was 90.5 days and that without was 45.0 days, a difference that was not significant (P = 0.054). However, emergent surgery should be performed for patients with serious complications such as obstruction or perforation.
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