Synchronous ovarian metastasis from colorectal cancer: A report of two cases

  • Authors:
    • Jiro Shimazaki
    • Takanobu Tabuchi
    • Kiyotaka Nishida
    • Akira Takemura
    • Gyo Motohashi
    • Hideki Kajiyama
    • Shuji Suzuki
  • View Affiliations

  • Published online on: May 11, 2016     https://doi.org/10.3892/ol.2016.4553
  • Pages: 257-261
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Ovarian metastasis of colorectal cancer is relatively rare. The present study reports two cases of synchronous ovarian metastasis from colorectal cancer, which were managed by cytoreductive surgery. In case one, a 60-year-old female patient presented with a multilocular pelvic tumor and ascites. Virtual colonoscopy revealed a mass in the sigmoid colon; however, no tumor cells were identified on histological examination. Ovarian metastasis from sigmoid colon cancer was suspected and adnexectomy was subsequently performed. Histological examination of the excised tumor revealed adenocarcinoma. Immunohistochemical analysis of the resected tumor revealed positive staining for cytokeratin (CK)20 and caudal‑type homeobox 2 (CDX2), and negative staining for CK7, estrogen receptor, progesterone receptor and inhibin. The immunohistological results supported the diagnosis of ovarian metastasis from sigmoid colon cancer. In case two, a 56‑year‑old female patient presented with a multilocular pelvic tumor and ascites. Colonoscopy identified a rectal tumor, and histological examination revealed moderately‑differentiated adenocarcinoma, which was confirmed by cytological analysis of ascites. Subsequently, ovarian metastasis from rectal cancer with peritoneal dissemination was diagnosed, and left ovariectomy and transverse colostomy were performed. Histological examination of the excised tumor revealed moderately‑differentiated adenocarcinoma, and immunohistochemical investigation revealed positive staining for CK20 and CDX2, but negative staining for CK7. These immunohistological results indicated ovarian metastasis from rectal cancer. Both patients recovered well and are currently undergoing regular follow‑up examinations. The observations from the two cases indicate that ovarian metastases of primary colorectal cancer may present as pelvic tumors and, thus, preoperative examination of the gastrointestinal tract is required. Furthermore, even in cases of widespread colorectal cancer metastases, excision of the ovarian tumor is required to establish a histological diagnosis for the selection of appropriate treatments.

Introduction

Common sites for synchronous metastases from colorectal cancer include the liver, lung, peritoneum, bone and brain (1). The frequency of ovarian metastasis from colorectal cancer is 1.6–6.4%, however, this type of metastasis is difficult to distinguish from primary ovarian neoplasms (25). Furthermore, synchronous ovarian metastasis from colorectal cancer is generally poor, and the optimal first-line treatment strategy is debatable (6,7). The present study reports two cases of synchronous ovarian metastasis from colorectal cancer that were managed by cytoreductive surgery.

Case report

Case one

A 60-year-old female patient presented to Katsuta Hospital (Katsuta, Japan) in June 2014 with progressive abdominal distension and lower abdominal pain. The following day the patient was referred to Ibaraki Medical Center, Tokyo Medical University (Ami, Japan) with a suspected diagnosis of pelvic tumor. The patient's medical history was otherwise unremarkable. Physical examination revealed lower abdominal tenderness with a palpable mass. Laboratory data revealed slight hypoalbuminemia (albumin, 3.5 g/dl; normal range, >4.0 g/dl), and carcinoembryonic antigen (CEA; 11.1 ng/ml; normal range, <5.0 ng/ml) and carbohydrate antigen (CA) 125 (743.7 U/ml; normal range, <37.0 U/ml) levels were increased. Abdominal computed tomography (CT; Somatom Sensation Cardiac; Siemens, AG, Munich, Germany) revealed a multilocular cystic pelvic mass with a solid component measuring 17 cm in diameter and an irregular mass located in the sigmoid colon (Fig. 1). Extensive ascites were also present. Virtual colonoscopy (Synapse VINCENT; Fujifilm Corporatio, Tokyo, Japan) revealed stenosis with a mass in the sigmoid colon (Fig. 2), which was confirmed by traditional colonoscopy. However, no tumor cells were identified in the biopsy specimen (which was obtained during colonoscopy) on hematoxylin and eosin histological examination. Ovarian metastasis from sigmoid colon cancer was suspected, therefore, adnexectomy was performed in July 2014. Intraoperatively, a disseminated tumor in the pelvic cavity was identified and cytology of the ascites using Papanicolaou staining revealed clusters of atypical cells exhibiting anisokaryosis, hyperchromasia and enlarged nuclei, yielding a diagnosis of adenocarcinoma. The resected tumor measured 17×14×8 cm, and macroscopic examination revealed multicystic walls and septa composed of solid and necrotic components (Fig. 3A). Hematoxylin and eosin histological examination of the formalin-fixed and paraffin-embedded excised tumor revealed moderately-differentiated adenocarcinoma forming in the septa with infiltration of the cystic wall (Fig. 3B). Immunohistochemical analysis of the tumor revealed positive staining for cytokeratin (CK)20 (mouse monoclonal; dilution 1:50; M7019; Dako, Glostrup Denmark) and caudal-type homeobox 2 (CDX2; rabbit monoclonal; dilution 1:1; 418011; Nichirei Biosciences, Inc., Tokyo, Japan), and negative staining for CK7 (mouse monoclonal; dilution 1:100; M7018; Dako), estrogen receptor (rabbit monoclonal; dilution 1:1; 107925; Roche Diagnostics, Basel, Switzerland), progesterone receptor (rabbit monoclonal; dilution 1:1; 109431; Roche Diagnostics) and inhibin (mouse monoclonal; dilution 1:50; M3609; Dako) (Fig. 4). These immunohistological results supported the diagnosis of ovarian metastasis originating from colon cancer of the sigmoid. Recovery was uneventful and the patient was discharged 12 days after surgery. From October 2014, the patient was administered modified FOLFOX6 [oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and fluorouracil (5-FU; 400 mg/m2) intravenous infusion on day 1, followed by 2,400 mg/m2 intravenous infusion of 5-FU over 46 h every 2 weeks] plus anti-vascular endothelial growth factor monoclonal antibody (bevacizumab; 5 mg/kg every 2 weeks) for primary sigmoid colon cancer with peritoneal dissemination. At present, the patient is regularly followed up every 2 weeks at the outpatient clinic of Ibaraki Medical Center, Tokyo Medical University, and her condition remains stable at the time of writing the present manuscript, in April 2016.

Case two

A 56-year-old female patient presented to Ryugasaki Saiseikai Hospital (Ryugasaki, Japan) in September 2014 with progressive abdominal distension. The following day the patient was referred to Ibaraki Medical Center, Tokyo Medical University, with a suspected ovarian tumor. The patient's medical history was otherwise unremarkable. Physical examination revealed abdominal distention with fluctuation, indicating abundant ascites. Laboratory data revealed increased lactate dehydrogenase (2,473 IU/l, normal range, 120–240 IU/l), CEA (93.9 ng/ml) and CA 125 (274.4 U/ml) levels. Abdominal CT (Somatom Sensation Cardiac) revealed a multilocular cystic pelvic mass with a solid component, measuring 12 cm in diameter, and ascites (Fig. 5). Cytology of abdominocentesis fluid using Papanicolau staining revealed clusters of atypical cells exhibiting anisokaryosis, hyperchromasia and enlarged nuclei, thus confirming adenocarcinoma, while colonoscopy revealed an elevated tumor with a central depression in the rectum, which did not involve the tumor. Biopsy of the tumor specimen indicated moderately-differentiated adenocarcinoma. A diagnosis of ovarian metastasis from rectal carcinoma with peritoneal dissemination was established; therefore, left ovariectomy and transverse colostomy were performed in November 2014. The resected tumor measured 12×11×8 cm, and macroscopic examination revealed multicystic walls and septa composed of a solid component with hemorrhage (Fig. 6). Hematoxylin and eosin histological examination of the formalin-fixed and paraffin-embedded excised tumor revealed moderately-differentiated adenocarcinoma (Fig. 7A), and immunohistochemical analysis identified positive staining for CK20 and CDX2, and negative staining for CK7 (Fig. 7B–D). These immunohistological results confirmed the diagnosis of ovarian metastasis from rectal cancer. Recovery was uneventful and the patient was discharged 13 days postoperatively. From December 2014, the patient was administered modified FOLFOX plus bevacizumab for primary rectal cancer with peritoneal dissemination. At present, the patient is undergoing regular follow-up examinations every 2 weeks at the outpatient clinic of Ibaraki Medical Center, Tokyo Medical University, and her condition was stable at the time of writing.

Discussion

Metastatic ovarian tumors account for ~21.5% of all malignant ovarian tumors and 3.7–7.4% of the cases metastasize from colorectal cancer (810). However, the process by which colorectal cancer metastasizes to the ovary remains unclear. Graffner et al (9) and Birnkrant et al (11) have postulated that, as there is no lymph flow between the colon and the ovaries, both hematogenous and disseminated peritoneal metastasis present possible metastatic pathways. In the two present cases, peritoneal dissemination was confirmed intraoperatively. Clinically, it is difficult to distinguish between primary and metastatic cancer of the ovary, which results in diagnostic problems for clinicians, radiologists and pathologists. Regarding radiological examination, Cho and Gold (12) reported that a mixed cystic and solid ovarian mass observed by CT scan must be regarded as a metastatic tumor in patients with a history of colonic or gastric carcinoma. In the present cases, the ovarian tumor presented as a multilocular cystic pelvic mass with a solid component. In addition, the patient in case two was preoperatively diagnosed with advanced rectal carcinoma with peritoneal dissemination. Regarding histological examination, Lee and Young (2) reported that bilaterality, microscopic surface involvement of epithelial cells and an infiltrative pattern of stromal invasion were strong indicators of metastatic ovarian carcinoma. In case one, histological examination of the sigmoid colon tumor did not reveal carcinoma cells, although virtual colonoscopy identified stenosis with a mass. However, resection of the ovarian tumor revealed moderately-differentiated adenocarcinoma, and immunohistochemical analysis of the tumor cells revealed positive staining for CK20 and CDX2, and negative staining for CK7, estrogen receptor, progesterone receptor and inhibin. In the majority of cases, primary ovarian neoplasms exhibit positive staining for CK7 and negative staining for CK20. By contrast, colorectal carcinomas most frequently exhibit negative staining for CK7 and positive staining for CK20 (13,14). CDX2 is a homeobox gene encoding the CDX2 protein, which serves as a transcription factor that is expressed in the nuclei of intestinal epithelial cells (15). CDX2 is a useful marker for adenocarcinoma of the gastrointestinal tract, and for distinguishing between primary and metastatic carcinomas of the ovary (1618). According to immunohistological examination, the results of case one support the diagnosis of metastatic ovarian carcinoma from sigmoid colon carcinoma.

The optimal first-line treatment strategy for synchronous ovarian metastasis from colorectal cancer remains controversial. The Japanese guidelines for colorectal cancer treatment recommend surgery for metastatic lesions if the primary colorectal and metastatic lesions are completely resectable, and if the patient is able to tolerate resection of the metastatic lesions (1). In the present two cases, tumor dissemination was intraoperatively detected in the pelvic cavity, however, complete resection was not possible for all lesions. Only excision of ovarian metastases was performed for the following reasons: i) Patients presented with progressive abdominal distension and excision of ovarian metastasis may have alleviated the symptoms (19); ii) it is difficult to distinguish between primary and metastatic cancer of the ovary by diagnostic imaging alone, thus, a definitive histological diagnosis was required to identify appropriate treatment, particularly in case one (preoperative histological examination of the sigmoid colon tumor did not lead to a diagnosis); and iii) cytoreductive surgery is associated with improvement of overall survival in patients with widespread metastases of colorectal cancer (20). A number of cases of synchronous ovarian metastasis from colorectal cancer also exhibit distant metastasis and/or peritoneal dissemination (6,7), therefore, the prognosis is generally poor. Jiang et al (21) reported that the median survival in patients with residual disease after metastasectomy is 10 months. However, as a result of marked improvement in systemic chemotherapy treatment for advanced colorectal cancer, it has been estimated that the median survival time of the patients may improve to >20 months following the administration of FOLFOX or 5-FU, leucovorin and irinotecan combination chemotherapy plus bevacizumab or anti-epidermal growth factor receptor monoclonal antibody (2225).

In conclusion, ovarian metastases from primary colorectal cancer may present as pelvic tumors, thus, preoperative examination of the gastrointestinal tract and excision of the ovarian tumor are required to establish a histological diagnosis for the selection of appropriate treatment strategies.

Acknowledgements

The authors would like to thank Enago (www.enago.jp) for reviewing the English language of the present study.

References

1 

Watanabe T, Itabashi M, Shimada Y, Tanaka S, Ito Y, Ajioka Y, Hamaguchi T, Hyodo I, Igarashi M, Ishida H, et al: Japanese Society for Cancer of the Colon and Rectum: Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer. Int J Clin Oncol. 17:1–29. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Lee KR and Young RH: The distinction between primary and metastatic mucinous carcinomas of the ovary: Gross and histologic findings in 50 cases. Am J Surg Pathol. 27:281–292. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Shiono S, Saito T, Fujii H, Arakawa A, Nakamura T and Yao T: A case of Krukenberg carcinoma metastasized from colon cancer resembling mucinous cystadenocarcinoma of the ovary. Int J Clin Exp Pathol. 7:394–401. 2013.PubMed/NCBI

4 

Aiyer R, Sweetman K, Larsen-Disney P and Fish A: A colorectal carcinoma imitating a primary ovarian carcinoma in a postpartum woman. BMJ Case Rep. 2013:pii: bcr2013201055. 2013.PubMed/NCBI

5 

Hata T, Yoshioka S, Asukai K, Mizumoto S, Nakanishi M, Hamano R, Maekawa T, Hama N, Kashiwazaki M, Taniguchi M, et al: Two cases of ovarian metastasis of colon cancer. Gan To Kagaku Ryoho. 38:2286–2288. 2011.(In Japanese). PubMed/NCBI

6 

Chung TS, Chang HJ, Jung KH, Park SY, Lim SB, Choi HS and Jeong SY: Role of surgery in the treatment of ovarian metastases from colorectal cancer. J Surg Oncol. 100:570–574. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Rayson D, Bouttell E, Whiston F and Stitt L: Outcome after ovarian/adnexal metastectomy in metastatic colorectal carcinoma. J Surg Oncol. 75:186–192. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Ayhan A, Tuncer ZS and Bükülmez O: Malignant tumors metastatic to the ovaries. J Surg Oncol. 60:268–276. 1995. View Article : Google Scholar : PubMed/NCBI

9 

Graffner HO, Alm PO and Oscarson JE: Prophylactic oophorectomy in colorectal carcinoma. Am J Surg. 146:233–235. 1983. View Article : Google Scholar : PubMed/NCBI

10 

MacKeigan JM and Ferguson JA: Prophylactic oophorectomy and colorectal cancer in premenopausal patients. Dis Colon Rectum. 22:401–405. 1979. View Article : Google Scholar : PubMed/NCBI

11 

Birnkrant A, Sampson J and Sugarbaker PH: Ovarian metastasis from colorectal cancer. Dis Colon Rectum. 29:767–771. 1986. View Article : Google Scholar : PubMed/NCBI

12 

Cho KC and Gold BM: Computed tomography of Krukenberg tumors. AJR Am J Roentgenol. 145:285–288. 1985. View Article : Google Scholar : PubMed/NCBI

13 

Wauters CC, Smedts F, Gerrits LG, Bosman FT and Ramaekers FC: Keratins 7 and 20 as diagnostic markers of carcinomas metastatic to the ovary. Hum Pathol. 26:852–855. 1995. View Article : Google Scholar : PubMed/NCBI

14 

Berezowski K, Stastny JF and Kornstein MJ: Cytokeratins 7 and 20 and carcinoembryonic antigen in ovarian and colonic carcinoma. Mod Pathol. 9:426–429. 1996.PubMed/NCBI

15 

German MS, Wang J, Fernald AA, Espinosa R III, Le Beau MM and Bell GI: Localization of the genes encoding two transcription factors, LMX1 and CDX3, regulating insulin gene expression to human chromosomes 1 and 13. Genomics. 24:403–404. 1994. View Article : Google Scholar : PubMed/NCBI

16 

Mutoh H, Sakurai S, Satoh K, Tamada K, Kita H, Osawa H, Tomiyama T, Sato Y, Yamamoto H, Isoda N, et al: Development of gastric carcinoma from intestinal metaplasia in Cdx2-trasgenic mice. Cancer Res. 64:7740–7747. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Li MK and Folpe AL: CDX-2, a new marker for adenocarcinoma of gastrointestinal origin. Adv Anat Pathol. 11:101–105. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Guo RJ, Suh ER and Lynch JP: The role of Cdx proteins in intestinal development and cancer. Cancer Biol Ther. 3:593–601. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Kato R, Murata K, Okamura S, Wada Y, Makino S, Nishigaki T, Owada Y, Murakami M, Okada K, Ebisui C, et al: Resection of ovarian metastasis of colon cancer to improve quality of life. Gan To Kagaku Ryoho. 39:2278–2279. 2012.(In Japanese). PubMed/NCBI

20 

McCormick CC, Giuntoli RL II, Gardner GJ, Schulick RD, Judson K, Ronnett BM, Vang R and Bristow RE: The role of cytoreductive surgery for colon cancer metastatic to the ovary. Gynecol Oncol. 105:791–795. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Jiang R, Tang J, Cheng X and Zang RY: Surgical treatment for patients with different origins of Krukenberg tumors: Outcomes and prognostic factors. Eur J Surg Oncol. 35:92–97. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, et al: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: A randomized phase III study. J Clin Oncol. 26:2013–2019. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Fuchs CS, Marshall J and Barrueco J: Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: Updated results from the BICC-C study. J Clin Oncol. 26:689–690. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, et al: Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study. J Clin Oncol. 28:4697–4705. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Köhne CH, Hofheinz R, Mineur L, Letocha H, Greil R, Thaler J, Fernebro E, Gamelin E, Decosta L and Karthaus M: First-line panitumumab plus irinotecan/5-fluorouracil/leucovorin treatment in patients with metastatic colorectal cancer. J Cancer Res Clin Oncol. 138:65–72. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

July-2016
Volume 12 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Shimazaki J, Tabuchi T, Nishida K, Takemura A, Motohashi G, Kajiyama H and Suzuki S: Synchronous ovarian metastasis from colorectal cancer: A report of two cases. Oncol Lett 12: 257-261, 2016
APA
Shimazaki, J., Tabuchi, T., Nishida, K., Takemura, A., Motohashi, G., Kajiyama, H., & Suzuki, S. (2016). Synchronous ovarian metastasis from colorectal cancer: A report of two cases. Oncology Letters, 12, 257-261. https://doi.org/10.3892/ol.2016.4553
MLA
Shimazaki, J., Tabuchi, T., Nishida, K., Takemura, A., Motohashi, G., Kajiyama, H., Suzuki, S."Synchronous ovarian metastasis from colorectal cancer: A report of two cases". Oncology Letters 12.1 (2016): 257-261.
Chicago
Shimazaki, J., Tabuchi, T., Nishida, K., Takemura, A., Motohashi, G., Kajiyama, H., Suzuki, S."Synchronous ovarian metastasis from colorectal cancer: A report of two cases". Oncology Letters 12, no. 1 (2016): 257-261. https://doi.org/10.3892/ol.2016.4553