CT Differentiation of Mucinous and Nonmucinous Colorectal Carcinoma

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1 CT of Colorectal Carcinoma Gastrointestinal Imaging Original Research Eun Young Ko 1,2 Hyun Kwon Ha 1 Ah Young Kim 1 Kwon Ha Yoon 3 Chang Sick Yoo 4 Hee Cheol Kim 4 Jin Cheon Kim 4 Ko EY, Ha HK, Kim AY, et al. Keywords: cancer, colon, CT DOI: /AJR Received April 4, 2006; accepted after revision August 18, Department of Diagnostic Radiology, Asan Medical Center, University of Ulsan College of Medicine, Poongnap-dong, Songpa-gu, Seoul , Korea. Address correspondence to H. K. Ha (hkha@amc.seoul.kr). 2 Present address: Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 3 Department of Radiology, Hospital of Wonkwang University, Iksan, Jeonbuk, Korea. 4 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. AJR 2007; 188: X/07/ American Roentgen Ray Society CT Differentiation of Mucinous and Nonmucinous Colorectal Carcinoma OBJECTIVE. The purpose of this study was to evaluate the CT findings that can help differentiate mucinous from nonmucinous colorectal carcinoma. MATERIALS AND METHODS. CT scans of 86 patients with pathologically proven mucinous colorectal carcinoma were analyzed, and 105 consecutive patients with nonmucinous colorectal carcinoma were also included as a control group. CT findings were compared between the two groups with regard to the bowel involvement patterns; patterns of contrast enhancement; and presence or absence of bowel obstruction, intratumoral calcification, pericolic fat infiltration, and local tumor extension to adjacent organs. Statistical analyses were performed using the Student s t test and Pearson s chi-square test. RESULTS. Compared with nonmucinous carcinoma, mucinous carcinoma showed more severe (2.41 ± 1.19 cm vs 1.94 ± 0.92 cm) (p = 0.004) and more eccentric (22% vs 8%) (p = 0.025) bowel-wall thickening. Heterogeneous contrast enhancement was more common in mucinous than in nonmucinous carcinoma (83% vs 53%) (p = 0.001). Mucinous carcinoma showed more areas with hypoattenuation (p = 0.001), and the solid portion of mucinous carcinoma showed less enhancement than that of nonmucinous carcinoma (p = 0.001). Presence of intratumoral calcification was more frequent in mucinous carcinoma (21% vs 5%) (p = 0.001). Heterogeneous enhancement showed the highest sensitivity (82.6%) but moderate specificity (55.9%) in diagnosing mucinous carcinoma. Tumors with four or more CT findings with a statistically significant difference were mostly mucinous carcinoma, and the specificity was 87%. CONCLUSION. CT is useful in the differentiation of mucinous from nonmucinous colorectal carcinoma. ucinous colorectal carcinoma is a M histologic subtype of adenocarcinoma characterized by abundant extracellular mucin production [1, 2]. Although clearly not established yet, some variations exist in the amount of extracellular mucin for the definition of mucinous colorectal carcinoma, which range between 50% and 80% [3 8]. Compared with nonmucinous carcinoma, mucinous carcinoma has been known to have a propensity for higher incidence of lymph node metastasis, venous and lymphatic invasions, local recurrence, and distant metastasis. Consequently, the prognosis is worse [5 10]. Therefore, mucinous carcinomas require more aggressive surgical excision, with wide margins, extensive lymph node dissection, and complete dissection of tumor extending into adjacent structures, than do nonmucinous carcinomas [11, 12]. In standard daily practice, a biopsy is required to determine mucinous or nonmucinous tumors, and CT or MRI is usually performed for tumor staging. Because mucinous carcinomas have somewhat different tumor behaviors from the nonmucinous type, imaging interpretation with knowledge of the tumor type may improve tumor staging. Despite the importance of biopsy to determine tumor type, sometimes pathologic reports on biopsy specimens lack an exact description of the tumor type in colorectal carcinomas, although after resection these tumors may be proved to be mucinous. In other words, imaging diagnosis can be more useful than biopsy in certain instances to determine the tumor type. In fact, there have been some efforts to differentiate mucinous from nonmucinous carcinoma with MRI [3, 4]. On T2-weighted images, mucinous colorectal carcinomas show high signal intensity due to the presence of abundant extracellular mucin. Although MRI appears to be useful for the differentiation of both types of carcinomas, in general CT is much more widely used as the initial technique AJR:188, March

2 TABLE 1: CT Findings of Mucinous and Nonmucinous Colorectal Carcinomas Variable Mucinous Tumors (n = 86) Nonmucinous Tumors (n = 105) p Colon site Rectosigmoid Cecum 10 5 Ascending 10 6 Transverse or descending Morphologic type Annular wall thickening 73 (84.9) 99 (94.3) Mass-forming 13 (15.1) 6 (5.7) Length of involved segment (cm) Mean thickness of wall (cm) 2.41 (± 1.19) 1.94 (± 0.92) Size of polypoid lesion (cm) Pattern of wall thickening Concentric even 23/73 (31.5) 43/99 (43.4) Concentric uneven 34/73 (46.6) 48/99 (48.5) Eccentric 16/73 (21.9) 8/99 (8.0) Enhancement pattern Homogeneous 15 (17.4) 49 (46.7) Heterogeneous 71 (82.6) 56 (53.3) Degree of enhancement a Greater 13 (15.1) 39 (37.1) Equal 39 (45.3) 43 (41.0) Lesser 34 (39.5) 23 (21.9) Extent of low attenuation < 1/3 of tumor 31 (36.0) 72 (68.6) 1/3 2/3 of tumor 23 (26.7) 16 (15.2) > 2/3 of tumor 32 (37.2) 17 (16.2) Intratumoral calcification 18 (20.9) 5 (4.8) Note Numbers in parentheses are percentages except where noted otherwise. a Measured in solid portion of tumor and compared with that of adjacent normal bowel wall. of choice for patients with colorectal cancer in many institutions. Unfortunately, to our knowledge, there has been no report regarding CT differentiation between colorectal mucinous and nonmucinous carcinoma. Thus, the aim of this study is to differentiate mucinous from nonmucinous colorectal carcinoma on CT. Materials and Methods Ninety-one patients with mucinous adenocarcinoma of the colon and rectum were selected at two institutions (Ulsan University Hospital and Hospital of Wonkwang University) during an 8-year period; and as a control group, 171 consecutive patients with nonmucinous adenocarcinoma of the colon and rectum during a 3-month period in one institution (Ulsan University Hospital) were included in this retrospective study. CT was performed in 87 patients with mucinous and 122 patients with nonmucinous carcinomas. We excluded 18 patients who showed negative CT findings due to small sizes of the tumors (one case of mucinous and 14 cases of nonmucinous carcinoma) and who underwent CT without enhancement (three cases of nonmucinous carcinoma). Therefore, a total of 86 cases of mucinous and 105 cases of nonmucinous colorectal carcinomas constituted the basis of our study. All patients were pathologically confirmed by surgery (n = 173) or colonoscopic biopsy (n = 18). The study population (n = 191) consisted of 116 men and 75 women, and the mean age was 58 years with an age range of years. The pathologic diagnosis of mucinous carcinoma was made according to the criteria that at least 50% of the tumor was composed of extracellular mucin. CT examinations were performed with a Somatom Plus-S scanner (Siemens Medical Solutions), HiSpeed CT/i (GE Healthcare), or LightSpeed QX/i (GE Healthcare). Images were obtained with a helical acquisition from the top of the diaphragm to the anal verge in a craniocaudal direction by using 7- to 8-mm collimation, mm/s table speed during a single breath-hold, and a 7- to 8-mm reconstruction interval. Conventional IV contrast enhancement was performed with scanning 60 seconds after injection of ml of nonionic contrast material (iopromide [Ultravist 370, Schering]) through the antecubital vein at a rate of 3 ml/s at the first institution and with scanning at seconds after injection of ml of nonionic contrast agent (iopamidol [Iopamiro 300, Bracco]) at a rate of ml/s with 10-mm slice thickness at the second institution. Retrospective review of CT images was performed in consensus by two radiologists who were blinded to the pathologic results. Site and length of involved segment; types of morphologic features (bowel-wall thickening or protruding mass); size of the mass or thickness of involved bowel wall; patterns of bowel-wall thickening (even or uneven, concentric or eccentric); patterns of contrast enhancement (homogeneous or heterogeneous) of the lesion; the degree of pericolic fat infiltration; the presence or absence of intratumoral calcification, bowel obstruction, and regional lymphadenopathy; and direct invasion of adjacent organs were evaluated. The degree of contrast enhancement in the solid portion of the tumor was compared with that of the normal bowel wall. In cases with a heterogeneous mass, the extent of hypoattenuated area within the tumor was graded into three groups: less than one third, equal to or greater than one third but less than two thirds, and equal to or greater than two thirds of the tumor. Pericolic fat infiltration was graded according to the extent of infiltration: less than 1 cm around the tumor, grade 1; equal to or greater than 1 cm and less than 3 cm, grade 2; and equal to or greater than 3 cm, grade 3. We used the Student s t test and Pearson s chisquare test for statistical analyses. We also investigated the usefulness of CT findings that had a statistically significant difference between the two types of tumor by evaluating the sensitivities, specificities, and diagnostic accuracies for each CT parameter. Institutional review board approval and informed consent were not required for this retrospective study. Results Comparison of CT findings between mucinous and nonmucinous carcinomas is shown in Table 1. Both tumor types involved the rectosigmoid area most frequently. There was no difference in the involved sites between mucinous and nonmucinous carcinomas. Compared with nonmucinous carcinomas, mucinous carcinomas involved the cecum and ascending colon to some extent, but the involvement was statistically not significant (p = 0.117). In morphologic features, the annular wall-thickening type was more frequently seen than the mass-forming type in both mucinous and nonmucinous carci- 786 AJR:188, March 2007

3 CT of Colorectal Carcinoma Fig year-old woman with mucinous carcinoma in rectum. CT scan shows severe rectal wall thickening with large areas of low attenuation (arrow). Fig year-old woman with mucinous carcinoma in cecum and proximal ascending colon. CT scan shows eccentric bowel-wall thickening along with evidence of exophytic tumor growth posteriorly (asterisk). Large metastatic lymph node (arrow) is noted in medial side of tumor. nomas. The length of the involved segment in the annular wall-thickening type was similar in both mucinous and nonmucinous carcinomas. The size of the masses in the mass-forming type of mucinous carcinoma was larger than in nonmucinous carcinoma, but there was no statistically significant difference (p = 0.943). However, mucinous carcinomas showed more severe (p = 0.004) (Figs. 1 and 2) and more eccentric (p=0.025) (Figs. 3 and 4) bowel-wall thickening. Atypical morphologic features, such as a large polypoid lesion with a broad base, combined annular wall thickening and a partial polypoid lesion, a large exophytic mass, or eccentric wall thickening without narrowing of the bowel lumen, were more commonly seen in mucinous carcinomas (n =6) than in nonmucinous carcinomas (n =1) (Fig. 5). Heterogeneous contrast enhancement of the tumor was much more commonly seen in mucinous carcinomas than in nonmucinous carcinomas (p = 0.001). A statistically significant Fig year-old woman with nonmucinous carcinoma in rectum. CT scan shows mild rectal wall thickening with homogeneous enhancement (arrow). Fig year-old woman with nonmucinous carcinoma in distal ascending colon near hepatic flexure. CT scan shows concentric bowel-wall thickening (arrows). difference was also noted in the extent of hypoattenuated areas within tumors (p = 0.001). Nonmucinous carcinomas usually showed a hypoattenuated area of less than one third of the tumor, whereas mucinous carcinomas showed a hypoattenuated area equal to or greater than two thirds of the tumor (Figs. 6 and 7). The degree of contrast enhancement in the solid portion of the tumor was equal to or greater than that of the normal bowel wall in nonmucinous carcinomas, but it was less than AJR:188, March

4 Fig year-old woman with mucinous carcinoma in rectum. A, CT scan shows broad base of tumor in upper rectum. B, Lower portion of tumor forms large polypoid endoluminal mass. Fig year-old woman with mucinous carcinoma in proximal transverse colon. A, CT scan shows large mass with heterogeneous enhancement. B, Hypoattenuated area is greater than two thirds of tumor (asterisk), and enhancement in solid portion of tumor is less than that of normal bowel wall (arrow). A A that of the normal bowel wall in mucinous carcinomas (p = 0.001) (Figs. 6 and 7). The presence of intratumoral calcification was more frequently seen in mucinous carcinomas (21% vs 5%); most calcifications were small and punctate (Fig. 8). Peritoneal seeding was more frequent in mucinous carcinomas (7/86) than nonmucinous carcinomas (1/105) (p =0.014). However, the presence of bowel obstruction (8/86 vs 12/105) (p = 0.203), peritumoral fat infiltrations more than 1 cm (29/86 vs 37/105) (p = 0.609), lymph node metastasis (34/86 vs 50/105) (p = 0.457), and direct invasion of adjacent organs (4/86 vs 7/105) (p = 0.313) were not significantly different between mucinous and nonmucinous carcinomas. In the differential diagnosis on CT, the sensitivities, specificities, and diagnostic accuracies of CT findings that showed a statistically significant difference between mucinous and nonmucinous carcinomas are listed on Table 2. Heterogeneous contrast enhancement of the tumor showed the highest sensitivity (82.6%) with 55.9% specificity, and the presence of intratumoral calcification showed the highest specificity (78.2%) with 20.9% sensitivity. Diagnostic accuracies of CT parameters, such as bowel-wall thickening greater than 2 cm, eccentric bowel-wall thickening, heterogeneous contrast enhancement of the tumor, poor contrast enhancement of the solid component of the tumor, a large area of hypoattenuation within tumor, and intratumoral calcification, ranged between 58.2% and 62.8%. When the presence of any findings that were shown to be statistically significant in the current study was considered diagnostic of mucinous carcinoma, the sensitivity of CT was 93% (80/86), whereas spec- B B 788 AJR:188, March 2007

5 CT of Colorectal Carcinoma Fig year-old woman with nonmucinous carcinoma in proximal ascending colon. CT scan shows bowel-wall thickening is relatively homogeneous and greater than that of normal bowel wall. Hypoattenuated area is less than one third of tumor. Pericolic fat infiltrations with small regional lymph nodes are also noted (arrows). Fig year-old woman with mucinous carcinoma in rectum. A and B, CT scans show small intratumoral calcification (arrow, A) within hypoattenuated area of eccentric bowelwall thickening. ificity was 50.6%. When the cases with four or more of these CT findings were diagnosed as mucinous tumor, the specificity was increased to 87% (20/23), whereas sensitivity decreased to 23.3% (20/86). Discussion There have been a few reports about the MRI findings of mucinous colorectal carcinoma [3, 4, 13 16]. Studies for MRI findings of colorectal mucinous carcinoma, including in vitro A B study, revealed that signal intensity of colorectal tumors varied depending on the histologic components of the tumor, and mucinous colorectal carcinomas showed high signal intensity on T2- weighted images due to the presence of abundant extracellular mucin. The proportion of the high signal intensity within the tumor correlated well with the amount of intratumoral mucin pools [3, 4, 14, 15]. In addition, colorectal mucinous carcinomas showed either peripheral or heterogeneous enhancement on MR images, as has been seen in mucinous tumors at other sites [3, 13]. Some investigators considered MRI superior to CT because of its ability to differentiate mucinous from fibrotic components of tumors; both components showed hypoattenuation on CT scans [4]. But MRI is not routinely performed as an initial diagnostic evaluation of colorectal carcinoma in most institutions. CT is widely accepted as a basic and accurate method for preoperative evaluation of colorectal carcinoma. However, to our knowledge, no investigation has been made regarding the CT findings of colorectal mucinous carcinoma in comparison with nonmucinous carcinoma. In fact, there have been some reports about the radiologic findings of mucinous carcinoma in sites other than the colorectum, such as mucinproducing hepatobiliary, pancreatic, and gastric carcinomas or metastatic tumors of the liver or ovary from mucinous colon cancer [17 19]. According to our results, the presence of CT findings, such as bowel-wall thickening greater than 2 cm, eccentric bowel wall thickening, heterogeneous contrast enhancement of the tumor with poor enhancement of the solid portion, a large area of hypoattenuation, and intratumoral calcification, indicates the high likelihood of the mucinous type of colorectal carcinoma. Diagnostic accuracies of these CT parameters in differentiating mucinous from nonmucinous carcinomas ranged between 58.2% and 62.8%. Depending on the number of these parameters, the sensitivity of CT ranged from 23.3% to 93% with 50.6% to 87% specificity. Both heterogeneous enhancement patterns and large areas (greater than two thirds of the tumor) of hypoattenuation were more frequently seen in mucinous colorectal carcinomas, as has been seen in mucinous carcinomas of other sites. A hypoattenuated area on a single-phase CT scan can also be caused by necrotic tissue of the tumor, fibrous stroma, or abundant extracellular mucin components. Delayed enhanced CT scans obtained more than 5 minutes after contrast injection can be helpful in differentiation of the areas of extracellular mucin components from fibrous lesions, but large areas of necrosis AJR:188, March

6 TABLE 2: Sensitivity, Specificity, and Diagnostic Accuracy of CT Findings in Differentiating Mucinous from Nonmucinous Colorectal Carcinomas Variable Sensitivity (%) Specificity (%) Accuracy (%) Bowel wall thickening > 2 cm Eccentric wall thickening Heterogeneous enhancement of the tumor Poor contrast enhancement of solid component in tumor Large area of hypoattenuation (> 2/3 of tumor) Intratumoral calcification in poorly differentiated nonmucinous carcinoma are still difficult to differentiate [4, 19, 20]. In contrast with the previous report [3] in which the difference of mucinous and nonmucinous colorectal carcinoma on MRI was only in the peripheral contrast enhancement pattern but the tumor-to-tissue contrast-enhancement ratio was not useful, our study results showed a statistically significant difference between the degree of contrast enhancement in the solid portion of mucinous and nonmucinous carcinoma. The solid portion of mucinous carcinoma was enhanced less than that of the normal bowel wall, whereas the solid portion of nonmucinous carcinoma was enhanced equal to or greater than that of the normal bowel wall. The exact reason for this discrepancy of results [3] is not clear, but it is probably caused by the different mechanisms of enhancement between CT and MR contrast agents. Similar to the MRI findings [3], on CT scans, mucinous colorectal carcinomas showed a thicker colonic wall than did nonmucinous carcinomas, and the thickened wall appeared to be more uneven and eccentric. Calcifications were more frequently seen in mucinous carcinomas than in nonmucinous carcinomas in about one fifth of mucinous carcinomas but in only one in 20 nonmucinous carcinomas. Because unenhanced scans were not obtained in most CT studies of patients with colorectal carcinoma, the frequency of intratumoral calcifications in mucinous carcinomas is expected to be higher than our result. Although not statistically significant, atypical morphologic features, such as a broad-based polypoid lesion, combined partially polypoid and partially wall-thickening pattern, or a large eccentric mass without significant narrowing of bowel lumen, were more commonly seen in mucinous carcinomas. Our observation was in accordance with the results of other investigators in which the macroscopic characteristics of mucinous colorectal carcinoma tended to be exophytic, partially polypoid lesions with a broad base, and not pedunculated [1]. In fact, there has been no sufficient explanation for these unusual gross features of mucinous carcinomas in the literature. Histopathologically, nonmucinous carcinomas usually consist of glands combined with solid sheets of malignant cells, but mucinous carcinomas chiefly consist of large pools of extracellular mucin lined with columns of malignant cells, cords, and vessels that give rise to a typical meshlike internal structure [3, 21]. Furthermore, in contrast to nonmucinous carcinomas, mucinous carcinomas frequently lack an inflammatory response around the mucus deposits, have scanty desmoplastic reaction, and sometimes have various sizes of pericolic tumor nodules of gelatinous components even larger than the primary tumor or a small mucosal tumor with extensive submucosal and muscular spread. We presume that such different histopathologic features might be the primary causes of the high incidence of atypical CT findings. One limitation of this study is that the images were acquired using 7- to 10-mm collimation helical CT, and improvements in technology with thinner-slice MDCT will improve visualization, characterization, and differentiation of colorectal carcinoma. We conclude that CT is highly useful in the differentiation of mucinous from nonmucinous colorectal carcinoma. References 1. Symonds DA, Vickery AL. Mucinous carcinoma of the colon and rectum. 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