Gastrointestinal Metastasis From Primary Lung Cancer: CT Findings and Clinicopathologic Features

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1 Gastrointestinal Imaging Clinical Observations Kim et al. Gastrointestinal Metastasis of Lung Cancer Gastrointestinal Imaging Clinical Observations So Yeon Kim 1,2 Hyun Kwon Ha 1 Sung Won Park 1 Jun Kang 3 Kyoung Won Kim 1 Seung Soo Lee 1 Seong Ho Park 1 h Young Kim 1 Kim SY, Ha HK, Park SW, et al. Keywords: CT, gastrointestinal tract, lung cancer, metastasis DOI: /JR Received October 3, 2008; accepted after revision January 7, Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, san Medical Center, 388-1, Pungnap-2 dong, Songpa-ku, Seoul , Korea. ddress correspondence to H. K. Ha (hkha@amc.seoul.kr). 2 Present address: Department of Radiology, Seoul National University undang Hospital, undang, Korea. 3 Department of Pathology, University of Ulsan College of Medicine, san Medical Center, Seoul, Korea. WE This is a Web exclusive article. JR 2009; 193:W197 W X/09/1933 W197 merican Roentgen Ray Society Gastrointestinal Metastasis From Primary Lung Cancer: CT Findings and Clinicopathologic Features OJECTIVE. The purpose of this study was to evaluate retrospectively the CT findings and clinicopathologic features of gastrointestinal metastasis from lung cancer. CONCLUSION. The most common histologic type of lung cancer among the patients in this study was squamous cell carcinoma (n = 12). The most common clinical presentation was abdominal pain (n = 15). total of 31 lesions were visualized on CT scans, involving the stomach (n = 3), small bowel (n = 26), and colon (n = 2). The metastatic lesions were seen on CT scans as wall thickening in 14 cases, an intraluminal polypoid mass in 14 cases, and an exophytic mass in three cases. The lesions exhibited isoattenuation in 19 cases, hypoattenuation in seven cases, and hyperattenuation in five cases. Complications included intussusception in seven cases, perforation in six cases, and obstruction in four cases. L ung cancer is the most frequent cause of cancer death in the world [1]. The brain, liver, adrenal glands, and bone are the most likely sites of metastatic disease in patients with lung cancer [2]. lthough metastasis to the gastrointestinal (GI) tract is found at as many as 11.9% of autopsies after death of lung cancer [3], the reported incidence of symptomatic GI metastasis is % [4, 5]. GI metastasis has probably been underdiagnosed in living patients because it is frequently regarded as part of generalized metastatic disease or the lesions are considered side effects of chemotherapy, such as ulcers, enteritis, or colitis [6]. ecause the life expectancy of patients with lung cancer is longer than in the past, clinicians attention to the clinical manifestations and management of GI metastasis from lung cancer is increasing [4, 6]. ccurate diagnosis of GI metastasis may prevent unnecessary thoracotomy and its complications [4]. lthough there have been a small number of radiologic reports on metastasis of lung cancer to the GI tract [7, 8], the CT features of GI metastasis [3, 4, 9] have not been well visualized, to our knowledge. ecause CT plays an essential role in oncologic imaging of the GI tract, we believe it is important to characterize the CT findings of GI metastasis. The purpose of our study was to evaluate the CT findings of GI metastasis from lung cancer and correlate them with the clinical and pathologic features. Materials and Methods This retrospective study was approved by our institutional review board, and the requirement for patient informed consent was waived. Study Group computer search of the medical records of our hospital, a tertiary referral center, was performed to identify cases of GI metastasis from lung cancer pathologically confirmed from ugust 1998 to ugust Of the 8,493 patients with new cases of lung cancer diagnosed at our institution during this period, 29 were found to have metastasis involving the GI tract. The incidence of pathologically confirmed GI metastasis was 0.34%. One patient was excluded from the study because CT images and complete clinical data were not available. total of 28 patients (24 men, four women; mean age, 59.1 years; range, years) were included in the study. mong these 28 patients, two patients had been included in our previous study [8]. The specimens used to make the pathologic finding of GI metastasis were obtained at surgical resection in 18 cases and endoscopic biopsy in 10 cases. Clinical Findings The medical records were reviewed by one of the investigators. Clinical data obtained included clinical presentation of GI metastasis, histologic JR:193, September 2009 W197

2 Kim et al. type of lung cancer, stage of lung cancer at initial diagnosis, presence of concomitant extrathoracic metastasis at diagnosis of GI metastasis, interval between diagnosis of lung cancer and detection of GI metastasis, and therapy before detection of GI metastasis. One investigator reviewed the surgical, endoscopic, and pathologic reports and correlated the findings with the CT findings. CT and Imaging Evaluation ll patients underwent contrast-enhanced abdominal CT with a single-detector or MDCT scanner (Somatom Plus 4, Siemens Healthcare; Light- Speed plus, GE Healthcare; Somatom Sensation 16, Siemens Healthcare). ecause of the long interval over which the cases were collected, the CT protocols varied. Each patient received ml of iopromide (Ultravist 300 or Ultravist 370, ayer Schering Pharma) administered at a rate of 3.0 ml/s through an antecubital vein. Venous phase images were obtained from the dome of the diaphragm to the pubic symphysis seconds after initiation of the IV contrast injection. t our institution, positive oral contrast medium, that is, barium sulfate solution (1.5 Easy CT Solution, Taejoon Pharmaceutical), usually was given to the oncologic patients for opacification of the small intestine. If, however, the presence of bowel obstruction, perforation, bleeding, inflammatory bowel disease, or biliary stone disease was suspected, use of a positive oral contrast agent was prohibited. CT parameters for imaging with a single-detector helical scanner were detector collimation, 5 mm; pitch, ; 120 kvp; 200 ms; slice thickness, 5 mm; reconstruction interval, 5 mm. CT parameters for imaging with a 4-MDCT scanner were detector collimation, 4 5 mm; table feed, 15 mm per gantry rotation; 120 kvp; effective tube current time product, 200 ms; slice thickness, 5 mm; interval, 5 mm. The CT parameters for a 16-MDCT scanner were detector collimation, mm; table feed, 24 mm per gantry rotation; 120 kvp; maximal effective tube current time product, 200 ms with automatic dose adaptation technique (CareDose, Siemens Healthcare); slice thickness, 5 mm; interval, 5 mm. CT scans were retrospectively reviewed by two GI radiologists each with more than 5 years experience in evaluating abdominal CT images. They conducted a consensus reading. ll images were reviewed with DICOM image viewing software. On CT scans, the involved bowel sites and lesion multiplicity were assessed, and the bowel wall involvement patterns, including the morphologic appearance and the contrast enhancement pattern of the lesions, were analyzed. The morphologic appearance of a lesion was subjectively categorized as an intraluminal polypoid or exophytic mass or as bowel wall thickening. The maximum lesion dimension in cases of polypoid lesion or exophytic mass and the thickness and length of involvement in cases of wall thickening also were measured. The contrast enhancement of GI lesions was compared with that of normal adjacent segments of bowel wall. The images were evaluated for the presence or absence of bowel obstruction, intussusception, and perforation. The presence of lymphadenopathy adjacent to the lesion and metastasis to other abdominal organs was assessed. The size criterion for lymphadenopathy was a lymph node with a dimension of 1 cm in the shortest axis. Lymphadenopathy was classified as bulky or nonbulky. ulky lymphadenopathy was considered present when the lesion was massive and conglomerate. Nonbulky lymphadenopathy was considered present when minimally enlarged and separable lymph nodes were found. The presence of ascites was assessed. Statistical nalysis In cases of perforation, Fisher s exact test was used to ascertain whether the incidence of perforation among patients who underwent chemotherapy differed from that of patients who did not. Significance was indicated at two-tailed p < Statistical analyses were performed with commercially available statistical software (SPSS version 12.0, SPSS). Results Clinical and Pathologic Findings The most common clinical presentation of GI metastasis was abdominal pain in 15 of 28 patients. Six patients had an initial finding of GI bleeding. Other clinical presentations included vomiting, anemia, jaundice, and bowel habit change, each in one patient. The other three patients had no symptoms. The most common histologic type of lung cancer was squamous cell carcinoma (n = 12, 42.9%), followed by adenocarcinoma (n = 6, 21.4%), small cell carcinoma (n = 3, 10.7%), sarcomatoid carcinoma (n = 3, 10.7%), large cell carcinoma (n = 2, 7.1%), and other (n = 2, 7.1%). The stage of lung cancer at its initial presentation was Ib in one patient, IIb in five, IIIa in three, IIIb in six, and IV in 13 patients. Common sites of simultaneous extrathoracic metastasis at the diagnosis of GI metastasis were abdominal lymph nodes (n = 10), liver (n = 8), bone (n = 7), adrenal gland (n = 6), brain (n = 4), muscle (n = 3), pancreas (n = 2), and skin (n = 1). Twelve patients had more than two sites of metastasis. The mean number of concomitant extrathoracic metastatic sites other than the GI tract was 1.4 (range, 0 3). In seven patients (25.0%), the GI tract was the only extrathoracic site of metastasis. The mean time between the diagnosis of lung cancer and detection of GI metastasis was 8.1 months (range, 0 37 months; median, 4 months). In 11 patients (39.3%), GI metastasis was found at the time of diagnosis of lung cancer. Six patients underwent lobectomy or pneumonectomy before GI metastasis was detected. djunctive treatment before the detection of GI metastasis was radiation therapy alone for three patients and both chemotherapy and radiation therapy for nine patients. ecause perforation of the GI tract occurred in 22.2% (2/9) of the patients who underwent chemotherapy and 21.1% (4/19) of the patients who did not undergo chemotherapy, the incidences of perforation did not differ significantly between those two groups (p > 0.99). CT Findings total of 31 lesions were found on CT scans of 26 patients (22 men; four women; mean age, 59.1 years; range, years) among 43 pathologically confirmed lesions in 28 patients; that is, 12 lesions were not visualized with CT. Five of 26 patients had two lesions, and the other 21 patients each had only one lesion. The sites of the 31 lesions were the stomach (n = 3), duodenum (n = 5), jejunum (n = 13), ileum (n = 8), and colon (n = 2). The shape of the 31 metastatic GI lesions varied on CT scans, manifesting as wall thickening in 14 cases and an intraluminal polypoid mass in 14 cases (Figs. 1 and 2). The other three lesions had the appearance of an exophytic mass (Fig. 3). The mean maximal dimension of the polypoid lesions was 25.0 ± 14.0 (SD) mm and that of the exophytic lesions was 29.8 ± 17.4 mm. Wall-thickening lesions were 15.3 ± 5.9 mm thick, and the involved length was 44.1 ± 14.5 mm. In five patients with two simultaneous lesions, the individual lesions had the same morphologic features (Fig. 1). allooning or focal bulging of the involved segment was seen in five lesions (Fig. 3). The contrast enhancement patterns of the lesions were highly variable, predominantly isoattenuation in 19 lesions, hypoattenuation in seven, and hyperattenuation in five lesions. Intussusception was associated with seven lesions, all of which were polypoid (Fig. 1); bowel obstruction accompanied four lesions associated with intussusception. owel per- W198 JR:193, September 2009

3 Gastrointestinal Metastasis of Lung Cancer foration was associated with six lesions (Fig. 4); five of these lesions were of the wallthickening type and one was polypoid. In the cases of 10 lesions, lymphadenopathy was present in the adjacent mesentery (Fig. 5); paraaortic lymphadenopathy also was associated with three lesions. Lymphadenopathy was nonbulky in the cases of seven lesions and bulky in the cases of three. scites was found in six patients, although the amount of fluid was small and accumulation was limited to the pelvic cavity or the GI lesions. Discussion We found that on CT scans GI metastasis of lung cancer manifested itself as an intraluminal polypoid mass or wall thickening with variable contrast enhancement patterns, predominantly isoattenuation. The most common site of involvement was the small intestine, consistent with the results of previous studies [3, 6]. The lesions were frequently associated with nonbulky regional mesenteric lymphadenopathy. The most common presenting symptom in our study was abdominal pain. ecause the symptoms do not relay specific information in this clinical setting, CT may have an important role in identifying the exact cause of abdominal pain in patients with lung cancer [6]. In contrast to previous belief, our study showed that GI metastasis may occur early in D Fig year-old man with abdominal pain 1 month after diagnosis of pleomorphic carcinoma of lung. and, xial CT scans show small polypoid lesion (arrowheads, ) in distal ileum and small-bowel obstruction (asterisks, ) caused by intussusception (curved arrows, ). C, xial CT scan shows another well-enhanced polypoid mass (arrows) in pelvic ileal loop as leading point of intussusception. Small ascites is evident. D, Photograph of surgical specimen shows two polypoid masses (arrowheads and arrows) in concordance with CT findings. E, Low-power-field microphotograph shows polypoid mass (arrowheads) involving mucosa (m) and submucosa (sm). pm = muscularis propria, s = serosa. (H and E, 12) Fig year-old man with gastrointestinal bleeding 3 months after diagnosis of squamous cell carcinoma of lung., xial CT scan shows heterogeneous wall thickening (arrows) in distal ileum without obstruction in proximal bowel loop., Photograph of surgical specimen shows concentric mass in involved segment. Fig year-old man with abdominal pain. and, xial CT scans show exophytic mass (arrows) with large central ulceration (asterisk, ) communicating with proximal jejunum. E C JR:193, September 2009 W199

4 Kim et al. Fig year-old man with abdominal pain 12 months after diagnosis of squamous cell carcinoma of lung., xial CT scan shows wall thickening (straight arrows) in jejunum. rrowheads indicate extraluminal air bubbles with perienteric fluid and infiltration, representing bowel perforation. Curved arrow indicates defect in jejunum., Photograph of surgical specimen shows ill-defined, firm mass (arrows) with perforation (asterisk). Fig year-old man with abdominal pain 10 days after diagnosis of malignant fibrous histiocytoma of lung. xial CT scan shows wall thickening (arrows) in second portion of mildly dilated duodenum and multiple adjacent metastatic lymph nodes (arrowheads). the course of lung cancer and even as the initial manifestation [4, 6]. GI metastasis of lung cancer can cause serious complications, such as perforation, obstruction, intussusception, and GI hemorrhage [4]. It appears that small-bowel perforation more frequently results from metastatic lesions of lung cancer than from other primary malignant tumors [10]. Contrary to previous speculation about the relation between chemotherapy-induced necrosis and perforation, in our study many perforations occurred in patients who had not undergone chemotherapy [10]. Instead, the morphologic appearance of lesions seemed more likely to be related to the type of complication. In our study, all but one case of perforation were associated with wall-thickening lesions. Our study showed that intestinal obstruction did not occur unless intussusception was present. In 21.4% (6/28) of the patients in whom the initial symptom was GI bleeding, CT did not depict active bleeding because our CT protocol was not optimized to detect GI bleeding and the bleeding was not massive. lthough a neutral contrast agent is generally used for evaluation of the GI tract because of the advantages in bowel-wall enhancement, use of a positive oral contrast agent may improve lesion detection during CT of patients with a history of primary lung cancer. In many instances, metastatic lesions exhibit isoattenuation with normal-appearing bowel wall. ecause the morphologic features and the contrast enhancement patterns of GI metastasis on CT scans varied in our study, differential diagnosis from primary GI tract tumors, including primary adenocarcinoma, GI stromal tumor, carcinoid, and lymphoma, was challenging [9]. In contrast to primary adenocarcinoma, which has a tendency to obstruct the bowel lumen because of abundant desmoplastic reaction, our study showed that bowel obstruction did not occur unless intussusception developed [11]. This finding may have occurred because in our study, only 21.5% of patients had adenocarcinoma as a pathologic subtype of lung cancer. Even in the patients with adenocarcinoma, however, obstruction did not occur without intussusception. Lack of calcification or spiculated mesenteric masses is helpful in differentiating GI metastasis of lung cancer from carcinoid tumor [11]. The high frequency of associated mesenteric lymphadenopathy and the rarity of exophytic morphologic features may help to differentiate GI metastatic lesions of lung cancer from GI stromal tumor [9]. Lymph node enlargement was not as bulky or extensive as in typical -cell lymphoma [11]. Compared with peripheral T-cell lymphoma, the involved segment was shorter, multifocality was less common, and the lymphadenopathy was less diffuse in GI metastasis [3, 12]. GI metastasis from lung cancer and that from melanoma have many features in common, such as hematogenous metastasis, the most common site of involvement, and imaging features [9]. Our study had limitations. First, it included a small number of patients because of the rarity of GI metastatic tumors. To our knowledge, however, it is one of the largest studies of the radiologic findings of GI metastasis from lung cancer. Second, selection bias was present. ecause we included only patients who had pathologic confirmation and underwent CT of GI metastasis, it was possible that subtle cases of lung cancer existed that did not produce symptoms and may have had a different appearance and not led to surgery. The exact incidence of GI metastasis and the diagnostic accuracy of CT for detecting these lesions were not identified in our study. We conclude that GI metastasis from lung cancer should be considered in the differential diagnosis when CT scans depict short segmental bowel-wall thickening or a polypoid mass in the small intestine in combination with regional lymphadenopathy, perforation, or intussusception. References 1. Parkin DM, ray F, Ferlay J, Pisani P. Global cancer statistics, C Cancer J Clin 2005; 55: Hillers TK, Sauve MD, Guyatt GH. nalysis of published studies on the detection of extrathoracic metastases in patients presumed to have operable non-small cell lung cancer. Thorax 1994; 49: Yoshimoto, Kasahara K, Kawashima. Gastrointestinal metastases from primary lung cancer. Eur J Cancer 2006; 42: erger, Cellier C, Daniel C, et al. Small bowel metastases from primary carcinoma of the lung: clinical findings and outcome. m J Gastroenterol 1999; 94: Kim MS, Kook EH, hn SH, et al. Gastrointestinal metastasis of lung cancer with special emphasis on a long-term survivor after operation. J Can- W200 JR:193, September 2009

5 Gastrointestinal Metastasis of Lung Cancer cer Res Clin Oncol 2009; 135: metastatic tumors to the gastrointestinal tract: CT abdominal malignancy: report of three cases. 6. Rossi G, Marchioni, Romagnani E, et al. Pri- findings with clinicopathologic correlation. JR Surg Today 2001; 31: mary lung cancer presenting with gastrointestinal 2006; 186: Horton KM, Fishman EK. Multidetector-row tract involvement: clinicopathologic and immuno- 9. Maglinte DD, Lappas JC, Sandrasegaran K. Ma- computed tomography and 3-dimensional com- histochemical features in a series of 18 consecu- lignant tumors of the small bowel. In: Gore RM, puted tomography imaging of small bowel neo- tive cases. J Thorac Oncol 2007; 2: Libshitz HI, Lindell MM, Dodd GD. Metastases to the hollow viscera. Radiol Clin North m 1982; 20: Kim SY, Kim KW, Kim Y, et al. loodborne Levine MS, eds. Textbook of gastrointestinal radiology, 3rd ed. Philadelphia, P: Saunders Elsevier, 2008: Ise N, Kotanagi H, Morii M, et al. Small bowel perforation caused by metastasis from an extra- plasms: current concept in diagnosis. J Comput ssist Tomogr 2004; 28: yun JH, Ha HK, Kim Y, et al. CT findings in peripheral T-cell lymphoma involving the gastrointestinal tract. Radiology 2003; 227:59 67 JR:193, September 2009 W201