Clinical Imaging 36 (2012) 24 – 28
Ileal adenocarcinoma in Crohn's disease: magnetic resonance enterography features Vinciane Placé a , Lora Hristova a , Xavier Dray b , Anne Lavergne-Slove c , Mourad Boudiaf a , Philippe Soyer a,⁎ a
Department of Abdominal Imaging, Hôpital Lariboisière-Assistance Publique-Hôpitaux de Paris and Université Diderot-Paris 7, 2, rue Ambroise Paré, 75010 Paris, France b Department of Digestive Diseases, Hôpital Lariboisière-Assistance Publique-Hôpitaux de Paris and Université Diderot-Paris 7, 2, rue Ambroise Paré, 75010 Paris, France c Department of Pathology, Hôpital Lariboisière-Assistance Publique-Hôpitaux de Paris and Université Diderot-Paris 7, 2, rue Ambroise Paré, 75010 Paris, France Received 14 March 2011; accepted 22 March 2011
Abstract Patients with Crohn's disease are at increased risk for small bowel adenocarcinoma. We report herein two cases of Crohn's disease-related ileal adenocarcinoma, which were investigated by means of magnetic resonance (MR)-enterography. Two different patterns were observed. In one case, the tumor presented as long circumferential, asymmetric and heterogeneous thickening of the ileum with visible nodule on free induction echo stimulated acquisition images. In the other case, the malignant lesion presented as a tumor mass of the terminal ileum, extending onto the cecum, and showed restricted diffusion on diffusion-weighted MR imaging. In both cases, the tumors were diagnosed preoperatively. Histopathological analysis after surgical resection confirmed T4N1 poorly differentiated mucinous adenocarcinoma of the ileum in association with findings consistent with active in one case and inactive Crohn's disease in the other case. Our observations suggest that MR-enterography may be a useful imaging test for the detection of small bowel adenocarcinoma in patients with Crohn's disease. © 2012 Elsevier Inc. All rights reserved. Keywords: Adenocarcinoma; Intestinal neoplasm; Crohn's disease; Imaging; Magnetic resonance imaging
1. Introduction Crohn's disease is a chronic inflammatory bowel disease, which can involve virtually any portion of the gastrointestinal tract [1]. Patients with Crohn's disease are at increased risk for both colon and small bowel adenocarcinoma [2,3]. Identification of increased colorectal cancer risks in individual patients with Crohn's disease has led to well-established surveillance guidelines [3]. Con⁎ Corresponding author. Tel.: +33 149 958 484; fax: +33 149 958 546. E-mail addresses:
[email protected] (V. Placé),
[email protected] (L. Hristova),
[email protected] (X. Dray),
[email protected] (A. Lavergne-Slove),
[email protected] (M. Boudiaf),
[email protected] (P. Soyer). 0899-7071/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.clinimag.2011.03.006
versely, although the increased risk for small bowel adenocarcinoma has been identified, no specific screening recommendations exist. As a consequence, imaging may play a critical role for the detection and the characterization of this rare but severe complication. The multiple patterns of presentation of Crohn's disease have been described extensively, and the imaging features of this disease as observed on magnetic resonance (MR) imaging are well known [4–6]. Conversely, little attention has been given to the imaging appearance of Crohn's disease-related small bowel adenocarcinoma. In addition, reported studies described findings obtained with barium studies [7,8] or computed tomography (CT) [9,10]. To our knowledge, the imaging appearance of Crohn's diseaserelated small bowel adenocarcinomas using MR imaging have never been reported.
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We report herein two cases of small bowel adenocarcinomas that occurred in patients with Crohn's disease, which were investigated by means of MR-enterography. 2. MR imaging protocol MR-enterography examinations were obtained at 1.5 T with two different MR units [Magnetom Avanto (Siemens Healthcare, Erlangen, Germany) or Signa Excite HDX (General Electric Healthcare, Milwaukee, WI)] equipped with a high-performance gradient system (gradient strength, 33–45 mT/m; slew rate, 120–200 mT m−1 ms−1). A circular polarized phase-array surface coil was used for signal detection. MR-enterography studies were obtained after ingestion of 1.5 L of a 2.5% water mannitol solution. T2-weighted MR images (HASTE or SSFSE) (repetition time [TR]=900–1000 ms; echo time [TE]=70–90 ms) were obtained with a single-shot fast (or turbo) spin-echo sequence in the axial and coronal plane with 3- to 4-mm slice thickness, using parallel imaging. Steady-state twodimensional (2D) MR images, with a very short TR (3.5– 4.2 ms) and a very short TE (1.7–2.1 ms) resulting in a hybrid T2/T1 tissue contrast (TrueFISP or FIESTA), were obtained in the axial and coronal planes at 4- to 6-mm thickness. Fat-suppressed three-dimensional T1-weighted fast-spoiled gradient echo images (VIBE or LAVA) (TR=4.2–7 ms; TE=2–4 ms; flip angle=15°–40°) were obtained in the coronal plane. All acquisitions were performed during suspended respiration at end expiration. In addition, for one patient, diffusion-weighted (DW) MR imaging was obtained with a fat-suppressed single-shot spin-echo echo-planar DW technique in the axial plane with three gradient factors (b values=0, 500 and 1000 s/mm2), using parallel imaging (GRAPPA) with an acceleration factor (or reduction factor) of 2. The other parameters were as follows: repetition time/ echo time, 3900 ms/91 ms; echo spacing, 0.83 ms; section thickness, 5 mm; intersection gap, 1 mm; voxel size, 2.1×2.0×5.0 mm; echo-planar imaging factor, 182; 25 axial sections acquired; acquisition time, 120 s. 3. Patients 3.1. Case 1 The patient was a 64-year-old Caucasian male with a 15year history of ileal Crohn's disease. He had no prior bowel resection or endoscopic procedure and was receiving steroids and mesalazine. He was referred to our hospital for persistent hematochezia, abdominal cramping and weight loss. Clinically, an abdominal mass was palpable in the right iliac fossa. Blood tests showed moderate anemia (hemoglobin, 10.8 g/dl) and elevated C-reactive protein. The serum carcinoembryonic antigen was elevated (100 ng/ml; normal value b2.5 ng/ml). Colonoscopy with retrograde ileoscopy
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showed terminal ileitis with aphthous ulcerations and marked stenosis that could not be bypassed by the endoscope. Endoscopic biopsies were obtained, and active Crohn's disease was considered at histopathological analysis, with mucosal ulcerations and transmural inflammation and superimposed ileal adenocarcinoma. On T1- and T2weighted images, MR-enterography showed a circumferential, asymmetric and heterogeneous thickening of the terminal ileum, extending 7 cm away from the ileocecal valve, with luminal narrowing and stranding of the surrounding mesenteric fat. On FIESTA MR images, a relatively hyperintense nodule was visible in the thickened ileal loop (Fig. 1). Surgical resection was performed. Histopathological analysis of resected specimen showed poorly differentiated mucinous adenocarcinoma that contained signet ring cell and findings consistent with active Crohn's disease. The tumor infiltrated the mesenteric fat and involved lymph nodes were present. The tumor was classified T4N1M0. 3.2. Case 2 The patient was a 54-year-old Caucasian female with a 20-year history of ileal Crohn's disease. She had no prior bowel surgery or endoscopic intervention and was receiving steroids and mesalazine. She had no risk factors for the occurrence of gastrointestinal carcinoma except Crohn's disease. She was referred from another institution for abdominal cramping and hematochezia. Clinical examination was unremarkable. Blood tests showed moderate anemia (hemoglobin, 10.2 g/dl) and elevated C-reactive protein. The serum carcinoembryonic antigen was normal (b2.5 ng/ml). Colonoscopy with retrograde ileoscopy showed ileal tumor spreading to the ileocecal valve and cecum. No findings consistent with inflammation were present. Histopathological analysis of biopsy specimens showed moderately differentiated adenocarcinoma. MR-enterography demonstrated a tumor mass of the terminal ileum, involving the ileocecal valve and the medial aspect of the cecum (Fig. 2). DW MR images showed restricted diffusion of the mass. Surgical exploration confirmed ileal tumor involving the cecum. No peritoneal dissemination and no hepatic metastasis were present. After surgical resection of the terminal ileum and descending colon, histopathological analysis of resected specimen showed poorly differentiated mucinous adenocarcinoma and findings consistent with underlying quiescent Crohn's disease. No signet ring cells were present. The tumor infiltrated the mesenteric fat, and metastatic lymph nodes were present. The tumor was classified T4N1M0. 4. Discussion We have reported the MR-enterography imaging findings in two patients with Crohn's disease-related adenocarcinoma of the small bowel. The two tumors displayed different features at MR imaging. In one case, the tumor presented as
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Fig. 1. A 64-year-old man with Crohn's disease and adenocarcinoma of the terminal ileum. (A) Steady-state 2D MR image (FIESTA; TR/TE=4.2 ms/ 2.1 ms) in the axial plane shows irregular and asymmetric thickening of the terminal ileum. Stranding of the adjacent mesenteric fat is present (arrows). Small hyperintense nodule (arrowhead) is visible. (B) At a different level, steady-state 2D MR image shows extensive and irregular thickening of the ileum (arrow) (Courtesy of Marc Zins, MD, Paris, France). (C) Microphotograph from histopathological analysis (hematoxylin and eosin stain, original magnification ×20) shows diffuse infiltration by poorly differentiated adenocarcinoma arising from ileal mucosa.
Fig. 2. A 56-year-old woman with Crohn's disease and adenocarcinoma of the terminal ileum. (A) T2-weighted MR image (HASTE; TR/TE=1000 ms/ 90 ms) in the axial plane shows large tumor mass of the ileocecal area (arrow). (B) In the coronal plane, T2-weighted MR image shows that the tumor (arrow) originates from terminal ileum and spreads to cecum. (C) Axial DW MR image obtained with b=1000 s/mm2 and black and white reversed contrast show dark and well-defined area that corresponds to ileal mass (arrow). Dark signal on reversed contrast image indicates restricted diffusion.
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long circumferential, asymmetric and heterogeneous thickening of the ileum with visible nodule, whereas in the other case, the malignant lesion presented as a tumor mass of the terminal ileum, extending onto the cecum. Most cancers in patients with Crohn's disease are small bowel adenocarcinomas, which are usually located in the jejunum and the terminal ileum [2,3]. By contrast, small bowel adenocarcinomas in the general population (i.e., de novo) are predominantly located in the duodenum. In patients with Crohn's disease, the distribution of adenocarcinoma mirrors that of inflammation. Therefore, adenocarcinoma more frequently occurs in the distal ileum, as it was the cases in the two cases presented herein. Studies have showed an increased risk for developing adenocarcinoma in the small bowel in patients with Crohn's disease, with a relative risk 15 to 50 times greater than that of the general population [2,3,11]. The cumulative risk has been reported as 0.2% at 10 years and 2.2% at 25 years after the onset of the disease [12]. Multiple risk factors have been identified, including extended duration of the disease, male sex, young age at the time of diagnosis and surgically created nonfunctional small bowel loops [3]. Adenocarcinomas often develop in strictured small bowel segments, in chronic anorectal, enteroenteric or enterocutaneous fistulas [3,7]. A few cases of adenocarcinomas that developed in strictured segments after strictureplasty have been reported [3], as well as cases occurring on ileocolic anastomosis [7]. Our two cases of adenocarcinomas developed in ileal segments involved by Crohn's disease, and no cases were associated with neither fistulous track nor prior ileocolic anastomosis. The median age at diagnosis of Crohn's disease-related small bowel adenocarcinoma is 49 years, which is less than the average age of 64 years for sporadic small bowel adenocarcinoma [2,3]. Duration of Crohn's disease until the diagnosis of carcinoma is over 15 years in most cases [7]. In our two cases, the mean duration of Crohn's disease until the discovery of adenocarcinoma was 15 and 20 years, which is within the range of reported values. Clinically, similarities between the presentations of Crohn's disease-related small bowel adenocarcinoma and that of exacerbation of Crohn's disease exist, thus creating major difficulties in diagnosis. One reason is that the most common clinical presentation of small bowel adenocarcinoma is intestinal obstruction [2,3,7]. In addition, the other presenting symptoms include positive fecal blood test, chronic iron deficiency anemia, weight loss, diarrhea and fistulas [7], which all are also frequently observed in patients with Crohn's disease. As a consequence, the diagnosis of small bowel adenocarcinoma is often difficult and delayed. In this regard, adenocarcinoma is found incidentally at surgery in more than 90% of cases [13]. Adenocarcinoma in Crohn's disease is a poorly differentiated neoplasm in more than 50% of the cases, as observed in our two cases. This condition is associated with a worse prognosis than de novo small bowel adenocarcinoma [3,12].
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Therapy is limited, and surgery when feasible is the only hope for cure, but survival is poor with a 5-year survival rate less than 30% [2,3]. One reason may be that small bowel adenocarcinomas in patients with Crohn's disease are discovered late at an advanced stage. In this regard, in our patients, the tumors were classified T4 according to the TNM classification. The diagnosis of small bowel adenocarcinoma remains difficult. Small bowel obstruction in patients with longstanding Crohn's disease is most likely to be due to a benign complication of the disease, but the diagnosis of adenocarcinoma should be considered in a patient with a long period of quiescent activity [7]. Similarly, persisting fistula track without evidence of healing despite apparently appropriate therapy should raise the possibility of adenocarcinoma [7]. Surgery should be considered when the stricture or the fistula cannot be adequately assessed endoscopically or by imaging examination. The imaging features of small bowel adenocarcinoma in patients with Crohn's disease have rarely been reported. In addition, reported studies described findings obtained with barium studies [7,8] or CT [9,10]. On small bowel barium studies, the lesions often present as smooth strictures, ulcerations, shouldering and mucosal destruction, similar to sporadic small bowel adenocarcinoma [7,8]. However, the tumor may present like a benign, inflammatory stricture, making the diagnosis difficult [14]. It has been suggested that the best discriminating finding is the presence of a solitary, protruding mass within a strictured small bowel loop [8]. On CT, the majority of sporadic small bowel adenocarcinomas present as annular lesion, a nodular mass or an ulcerated lesion [15–17]. In patients with Crohn's disease, adenocarcinoma may present as a sacculated loop, with asymmetric thickening [9], or as a short stenosis mimicking benign fibrostenosis [15,16]. MR imaging using enteral contrast agent has a wellestablished value for determining the phenotype of Crohn's disease (i.e., active vs. nonactive). [4–6,18], and the various features of Crohn's disease are well known [4–6]. Conversely, to the best of our knowledge, the MR imaging features of small bowel adenocarcinoma in patients with Crohn's disease have never been reported. One reason may be the rarity of this specific complication. In our two cases, MR imaging helped diagnose ileal tumor. Among the different MR sequences available for the study of the small bowel, steady-state 2D MR imaging (TrueFISP or FIESTA) has proven effective [19]. Of interest, in one of our patient, this sequence showed tumor nodules within thickened ileal wall, suggesting that this sequence may be performed when small bowel adenocarcinoma is suspected in Crohn's disease patient. The MR imaging features of de novo adenocarcinomas of the small bowel have been already described in the literature. In this regard, Van Weyenberg et al. reported five cases of de novo adenocarcinoma that were investigated using MR imaging [20]. All five tumors were located either in the
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duodenum (n=3) or in the jejunum (n=2). All tumors presented with a predominantly intraluminal growth pattern, in association with circumferential thickening, and infiltration of the surrounding mesenteric fat [20]. This presentation is different from that observed in our two cases with respect to tumor location and morphologic features. One of our patients had DW MR imaging. In that case, DW MR imaging using high b value showed increased signal intensity on DW MR images indicating restricted diffusion at the level of the ileocecal mass. DW MR imaging has already been used for the detection of primary colorectal cancer. This technique is a highly sensitive tool for that task, with reported sensitivities up to 100% in some studies [21,22]. Ichikawa et al. [23], who had three false-negative cases in a series of 33 colorectal cancers including 14 rectal cancers, reported a slightly lower but still acceptable sensitivity of 91% for the diagnosis of colorectal cancer with DW MR imaging. As a limitation, active Crohn's disease shows increased signal too [24], so that this technique might not be appropriate to differentiate between active disease and tumor using DW MR images and apparent diffusion coefficient calculation only. However, it may be useful to detect cancer in patient with quiescent or inactive Crohn's disease. This suggests that further studies should be done to confirm this hypothesis. The progression of dysplastic foci to small bowel adenocarcinoma in patients with Crohn's disease is incompletely understood. Because no definite and clear risk factors are emerging and no screening recommendations exist, the radiologist is on the main front for suggesting the possibility of small bowel adenocarcinoma in patients with Crohn's disease. As a consequence, the radiologist should be aware of this rare but serious complication to alert the referring gastroenterologist. Our observations suggest that MR-enterography may be a useful imaging test for the detection of small bowel adenocarcinoma in patients with Crohn's disease. References [1] Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002;347: 417–28. [2] Dossett LA, White LM, Welch DC, Herline AJ, Muldoon RL, Schwartz DA, et al. Small bowel adenocarcinoma complicating Crohn's disease: case series and review of the literature. Am Surg 2007;73:1181–7. [3] Feldstein RC, Sood S, Katz S. Small bowel adenocarcinoma in Crohn's disease. Inflamm Bowel Dis 2008;14:1154–7. [4] Knuesel PR, Kubik RA, Crook DW, Eigenmann F, Froehlich JM. Assessment of dynamic contrast enhancement of the small bowel in active Crohn's disease using 3D MR enterography. Eur J Radiol 2010; 73:607–13. [5] Ippolito D, Invernizzi F, Galimberti S, Panelli MR, Sironi S. MR enterography with polyethylene glycol as oral contrast medium in the follow-up of patients with Crohn disease: comparison with CT enterography. Abdom Imaging 2010;35:563–70. [6] Malagò R, Manfredi R, Benini L, D'Alpaos G, Mucelli RP. Assessment of Crohn's disease activity in the small bowel with MRenteroclysis: clinico-radiological correlations. Abdom Imaging 2008; 33:669–75.
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