Contrast-Enhanced CT for Differentiation of Ovarian Metastasis from Gastrointestinal Tract Cancer: Stomach Cancer Versus Colon Cancer

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1 CT of Ovarian Metastasis Women s Imaging Clinical Observations WOMEN S IMAGING Hyuck Jae Choi 1 Joo-Hyuk Lee 1 Sokbom Kang 2 Sang-Soo Seo 2 Joon-Il Choi 1 Sun Lee 3 Sang-Yoon Park 2 Choi HJ, Lee JH, Kang S, et al. Keywords: cancer, CT, metastasis, oncologic imaging, ovary, pelvic imaging DOI: /AJR Received June 3, 2005; accepted after revision October 21, Department of Radiology, Research Institute and Hospital, National Cancer Center, 809 Madu 1-dong, Ilsan-gu, Koyang, Kyonggi, Korea. Address correspondence to H. J. Choi. 2 Department of Gynecologic Oncology, Research Institute and Hospital, National Cancer Center, Koyang, Kyonggi, Korea. 3 Department of Pathology, Research Institute and Hospital, National Cancer Center, Koyang, Kyonggi, Korea. AJR 2006; 187: X/06/ American Roentgen Ray Society Contrast-Enhanced CT for Differentiation of Ovarian Metastasis from Gastrointestinal Tract Cancer: Stomach Cancer Versus Colon Cancer OBJECTIVE. The purpose of our study was to determine whether the CT findings of ovarian metastasis from stomach cancer differ from those of ovarian metastasis from colon cancer. CONCLUSION. On contrast-enhanced CT scans, ovarian metastatic lesions from stomach cancer appear more solid than, more frequently have dense enhancement of the solid portion, and are smaller than ovarian metastatic lesions from colon cancer. he ovaries, lungs, and liver are the T organs most frequently involved in metastasis of malignant tumors. Approximately 5 20% of ovarian cancers are metastatic lesions [1 3]. An ovarian mass suspected of being ovarian neoplasia is found to be metastatic disease to the ovary in approximately 6 7% of patients [4]. The origins of these tumors include the stomach, colon, breast, lung, pancreas, bile duct, kidney, and other organs [3 12]. Most of the nongenital cancers that metastasize to the ovaries arise from the gastrointestinal tract. Petru et al. [9] reported that ovarian metastasis precedes detection of the primary site in 38% of cases. For this reason, differentiation between metastatic and primary ovarian tumors is important for patient care. A number of studies have highlighted the CT and MRI findings of Krukenberg tumors [13 19]. Most of these investigations showed that differentiation between metastatic and primary tumors on the basis of imaging findings is almost impossible [17 20]. Some authors, however, reported findings suggestive of Krukenberg tumors [13 16]. CT showed that Krukenberg tumors were solid ovarian tumors containing well-demarcated intramural cysts that have apparently strong contrast enhancement [14]. In a previous study we found that on CT scans, ovarian metastatic lesions from colon cancer had smooth margins and were more cystic than primary malignant ovarian tumors [13]. To our knowledge, however, there has been no CT documentation of differentiation between ovarian metastasis from stomach cancer and that from colon cancer. In this study, we investigated whether CT can be used to differentiate ovarian metastasis from stomach cancer and ovarian metastasis from colon cancer. Materials and Methods Patient Population Between January 2001 and March 2005, eight patients (age range, years; mean age ± SD, 45 ± 10 years) with 13 ovarian metastatic lesions among nine patients with surgically confirmed ovarian metastasis from stomach cancer and 23 patients (age range, years; mean age ± SD, 58 ± 15 years) with 31 ovarian metastatic lesions among 27 patients with surgically confirmed metastasis from colon cancer underwent CT and were included in this study. During this period, 274 patients had surgical confirmation of malignant ovarian tumors. One patient with stomach cancer and four with colon cancer were excluded because they declined CT examination (n = 3) or had already undergone CT with poor image quality (n = 2) at another hospital. Our institutional review board did not require its approval for this study. CT Image Acquisition All CT data were obtained with a 4-MDCT scanner (Mx 8000, Philips Medical Systems). Preoperative CT scans were obtained in a single institution an average of 22 days before surgery (range, 2 50 days). Patients received IV contrast material (iopromide; Ultravist 300, Schering) in an antecubital vein via mechanical injector; 140 ml of the agent was administered at a rate of 2.3 ml/s. Scanning began 70 or 80 seconds after the start of IV injection of contrast material and covered the region AJR:187, September

2 TABLE 1: CT Findings Finding Mass characteristics Size Age Enhancement of solid portion from the diaphragm to the lower pelvis. Scanning parameters included a detector array of mm, beam pitch of 1.35, section thickness of 3.2 mm, and a reconstruction increment of 3 mm. p Stomach Colon Ratio 95% CI % (n) Odds Ratio (Relative Risk) a < b c c b Oval shape 84.6 (11/13) 61.3 (19/31) Bilaterality 62.5 (5/8) 34.8 (8/23) b Lymph node enlargement 25.0 (2/8) 13.0 (3/23) b Peritoneal seeding 37.5 (3/8) 52.2 (12/23) b Amount of ascites b Metastasis 25.0 (2/8) 21.7 (5/23) b Smooth margin (13/13) 96.8 (30/31) 0.7 d b Note CT findings and patient age are presented according to ascending order of p value. Stomach = ovarian metastasis from stomach cancer, Colon = ovarian metastasis from colon cancer, Mass characteristics = degree of solid nature of mass, Size = longest diameter in axial scan. a Likelihood of the presence of the feature in ovarian metastasis from stomach cancer versus ovarian metastasis from colon cancer. b Fisher s exact test. c Independent samples t-test. d Relative risk calculated because odds ratio could not be calculated. Image Interpretation CT images were interpreted retrospectively by consensus of two radiologists unaware of the histologic results. The radiologists had three and four years of experience in gynecologic imaging, including CT. All CT images were randomized before interpretation to decrease selection bias. The following characteristics of each ovarian mass were recorded: laterality, size (longest diameter in axial scan), margin (smooth versus irregular), shape (oval versus nonoval), mass characteristics (cystic; mainly cystic, i.e., more than two-thirds of the mass; mainly solid, i.e., more than two thirds of the mass; solid), enhancement of the solid portion (none; mild, i.e., less than that of the junctional zone of the myometrium; moderate, i.e., equal to or more than that of the outer myometrium; and dense, i.e., equal to or more than that of the outer myometrium), amount of ascites (none; mild, i.e., few collections of fluid and largest dimension generally less than 3 cm; moderate, i.e., multiple collections and smallest dimension more than 3 cm; and severe, i.e., generalized fluid, floating bowel), peritoneal seeding (peritoneal carcinomatosis, including omental, mesenteric, peritoneal, and serosal deposits; perihepatic, perisplenic, gastrohepatic, and gastrosplenic ligaments), abdominal and retroperitoneal lymph node enlargement (> 1 cm in the largest short axis diameter), and presence of metastasis to abdominal solid organs. Statistical Analysis The Fisher s exact test was used to correlate statistical association between binary dependent variables of the pathologic features of the ovarian masses to variables of interest, including laterality, margin, shape, mass characteristics, enhancement of the solid portion, amount of ascites, presence of peritoneal seeding, lymph node enlargement, and presence of metastasis. Odds ratio (or relative risk) and 95% CI were reported for each variable. We used the independent samples t- test to compare tumor sizes and patient ages between the two diseases. A p value less than 0.05 was considered significant. Results Histopathology The histologic types of the primary sites of 13 ovarian metastatic lesions from stomach cancer included signet-ring cell carcinoma (76.9%, 10/13), adenosquamous cell carcinoma (15.4%, 2/13), and tubular adenocarcinoma (7.7%, 1/13). The histologic types of the primary sites of ovarian metastatic lesions from colon cancer were tubular adenocarcinoma (61.3%, 19/31) and mucinous adenocarcinoma (38.7%, 12/31). Imaging Findings The frequencies of imaging findings and their corresponding p values are presented in Table 1. Mass characteristics of the two tumor types were distinct. Ovarian metastatic lesions from stomach cancer (Figs. 1 and 2) were more solid in nature (cystic, 0% [0/13]; mainly cystic, 30.8% [4/13]; mainly solid, 15.4% [2/13]; solid, 53.8% [7/13]) than those from colon cancer (Figs. 3 and 4) (cystic, 6.5% [2/31]; mainly cystic, 83.9% [26/31]; mainly solid, 6.5% [2/31]; solid, 3.2% [1/31]) (p < 0.001). The enhancement patterns of solid portions of the masses were discrete (p = 0.013). Ovarian metastatic lesions from stomach cancer displayed more prominent enhancement (none, 0% [0/13]; mild, 30.8% [4/13]; moderate, 15.4% [2/13]; dense, 53.8% [6/13]) than those from colon cancer (none, 0% [0/29]; mild, 6.9% [2/29]; moderate, 82.8% [24/29]; dense, 10.3% [3/29]) (p = 0.01). Applying the imaging characteristics that masses with a mainly solid or solid nature and dense enhancement of the solid portion were ovarian metastasis from stomach cancer and that masses without these findings were from colon cancer, we accurately differentiated the origin of ovarian metastasis in 32 (72.7%) of 44 cases. The ovarian metastatic lesions from colon cancer were larger than ovarian metastatic lesions from stomach cancer (p = 0.006). In addition, patients in the former group were older than those in the latter group (p = 0.007). No differences were evident between the two patient groups in laterality, shape, margin, amount of ascites, peritoneal seeding, abdominal retroperitoneal lymph node enlargement, and presence of metastasis. Discussion Since Schlagenhaufer [21] established the metastatic nature of most Krukenberg tumors, a number of reports have shown that many carcinomas, including those of the stomach, colon, breast, lung, pancreas, bile duct, and kidney and malignant tumors arising from the female genital tract metastasize to the ovaries [3 12]. The term Krukenberg tumor is used either as a broad designation to cover all metastatic tumors of the ovary or in a narrow sense to describe metastatic tumors from the gastrointestinal tract [9, 10]. Several investigators have suggested that stomach cancer is one the most frequent sources of ovarian metastasis [9, 10], but others have reported colon cancer as the most common source [11, 12]. 742 AJR:187, September 2006

3 CT of Ovarian Metastasis A Fig year-old woman with bilateral ovarian metastasis from stomach cancer. Contrast-enhanced CT scan shows mainly solid, oval, moderately enhancing masses (arrows) with smooth margins. A, Left adnexa. B, Right adnexa. Misinterpretation of a metastatic ovarian tumor as a primary tumor may have adverse consequences for the patient, such as unnecessary surgery or inappropriate chemotherapy or radiation therapy. Therefore whenever adnexal masses are encountered, especially those with bilateral or smooth margins, ovarian metastasis is highly suspected. It has been proposed that an initial search be performed for a primary site in the gastrointestinal tract [13 20]. Accordingly for the management of ovarian neoplasms, differentiation between primary and secondary neoplasms is one of the principal roles of the radiologist. In our study, ovarian metastatic lesions were found without known primary cancer in two (6.5%) of the patients. In addition, although it is easy to find the primary site when the histologic type clearly indicates primary disease, in many instances the pathologic findings are ambiguous. In such cases, clinicians attempt to identify the primary disease according to the order of the likelihood of ovarian metastasis. The results of our study strongly suggest that specific CT findings are useful for differentiation of ovarian metastasis from stomach cancer and from colon cancer. Our CT results showed that mass characteristics, laterality, enhancement pattern of the solid portion, and size are valuable parameters for differentiating ovarian metastasis from stomach cancer and from colon cancer. Specifically, 69.2% of ovarian metastatic lesions from stomach cancer were mainly solid or solid in appearance on CT scans, whereas only 9.7% of ovarian metastatic lesions from colon cancer displayed these patterns. These different imaging findings may arise from variations in primary sites and, consequently, in histologic type. The histologic type of all ovarian metastatic lesions from stomach cancer with a solid or mainly solid appearance was signet ring cell carcinoma, and 90.0% (9/10) of the ovarian metastatic lesions from stomach cancer that were of the signet ring cell type had a solid or mainly solid appearance. Ovarian metastasis from stomach cancer that had a histologic type other than signet ring cell carcinoma (adenosquamous cell carcinoma [n = 2], tubular adenoma [n = 1]) had a mainly cystic appearance. The histologic types of ovarian metastasis from colon cancer included tubular adenocarcinoma (n = 19) B Fig year-old woman with unilateral ovarian metastasis from stomach cancer. Contrast-enhanced CT scan shows mainly solid, oval, moderately enhancing mass with smooth margin in left adnexa. Dense enhancing portions (arrows) are evident in mass. AJR:187, September

4 Fig year-old woman with unilateral ovarian metastasis from colon cancer. Contrast-enhanced CT scan shows cystic, oval ovarian masses with smooth margins. Thin septation (arrows) is evident within mass. and mucinous adenocarcinoma (n = 12), 84.2% (16/19) and 96.7% (11/12) of the lesions displayed a cystic or mainly cystic appearance. Histopathologically, metastatic colorectal cancer often simulates primary adenocarcinoma of the ovary [4, 22 25]. Metastatic colorectal adenocarcinoma forms large, complex glands and cysts that contain necrotic debris [25]. Although it is characteristic of metastatic colorectal adenocarcinoma, extensive necrosis also can occur in primary ovarian carcinoma [4]. We postulate that the more cystic nature of ovarian metastatic lesions from colon cancer compared with lesions from stomach cancer is attributable to this pathologic feature. This finding is consistent with our previous results [13]. Furthermore, the cystic nature of metastatic lesions from colon cancer may interfere with correct differentiation of primary malignant tumors and metastatic ovarian tumors from colon cancer. Thus, on the basis of the data obtained, we suggest that thorough preoperative examination of the stomach is required when ovarian masses display a mainly solid or solid appearance on CT scans. The sensitivity and specificity for differentiation were 69% and 90%. Although there is large overlap between the characteristics of these two tumors, we propose that this finding can serve supplementary roles. Dense enhancement of the solid portion on a CT scan was present in 46.2% (6/13) of ovarian metastatic lesions from stomach cancer compared with only 10.3% (3/29) of ovarian metastatic lesions from colon cancer. Unfortunately, radiologic pathologic correlation of the solid portion with dense enhancement was not performed because of the retrospective nature of the study. Although there is overlap for this finding, we propose that these parameters serve a supplementary role in differentiation of subtypes of ovarian metastatic lesions from stomach and colon cancers. Ovarian metastatic lesions from stomach cancer were larger (5.6 ± 2.1 cm) than those from colon cancer (9.1 ± 4.6 cm) (p = 0.007). We postulate that the more cystic nature is partly responsible for the larger size of ovarian metastatic lesions from colon cancer. In our study, patients with ovarian metastasis from colon cancer were older than those with metastasis from stomach cancer. Specifically, 37.5% (3/8) of the patients with ovarian metastasis from stomach cancer were younger than 40 years, whereas none of the patients in the other group were younger than 40 years. This finding may be attributable to an increase in the percentage of young patients with stomach cancer and the more aggressive nature of this disease in younger patients [26, 27]. There were limitations to our study. First, the number of cases was not large. The rare incidence of the disease entity provides little opportunity for comprehensive observation. Furthermore, ovarian metastasis is often viewed as a late presentation of cancer, and patients often are treated with palliative measures, which frequently do not include comprehensive assessment of disease extension. A second limitation was that although they were unaware of the pathologic features of the ovarian masses, the radiologists who reviewed the images may have deduced the pathologic characteristics of the mass on the Fig year-old woman with unilateral ovarian metastasis from colon cancer. Contrast-enhanced CT scan shows mainly cystic ovarian mass with smooth margin in right lower portion of abdomen. Septation (arrows) in mass and moderately enhancing solid portions (arrowheads) are evident. basis of clues such as evidence of stomach or colon resection or the presence of a mass. In our study, ovarian metastasis and primary cancer were found simultaneously in 17 (54.8%) of the patients, and ovarian metastasis was found after operations for primary cancer in 12 (38.7%) of the patients. The primary cancer or clues of a previous operation were detected on the CT scans of 27 (93.5%) of the patients. Finally, primary malignant tumors of the ovary were not included in this study. This factor might have given rise to selection bias. In conclusion, our findings imply that CT is useful in differentiation between ovarian metastasis from stomach cancer and ovarian metastasis from colon cancer. Mass characteristics, dense enhancement of the solid portion, and size are valuable CT parameters for differentiation. References 1. Yada-Hashimoto N, Yamamoto T, Kamiura S, et al. Metastatic ovarian tumors: a review of 64 cases. Gynecol Oncol 2003; 89: Young RH, Scully RE. Metastatic tumors in the ovary: a problem-oriented approach and review of the recent literature. 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