Case Report
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Feb 21, 2008; 14(7): 1137-1140
Published online Feb 21, 2008. doi: 10.3748/wjg.14.1137
Clear cell adenocarcinoma of the colon: A case report and review of literature
Koichi Soga, Hideyuki Konishi, Natsuko Tatsumi, Chika Konishi, Keimei Nakano, Naoki Wakabayashi, Shoji Mitsufuji, Keisho Kataoka, Takeshi Okanoue, Ken-Ichi Mukaisho, Takanori Hattori
Koichi Soga, Hideyuki Konishi, Natsuko Tatsumi, Chika Konishi, Keimei Nakano, Naoki Wakabayashi, Shoji Mitsufuji, Keisho Kataoka, Takeshi Okanoue, Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
Ken-Ichi Mukaisho, Takanori Hattori, Department of Pathology, Shiga University of Medical Science, Shiga, Japan
Correspondence to: Koichi Soga, MD, Molecular Gastro-enterology and Hepatology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan.
Telephone: +81-75-2515519
Fax: +81-75-2510710
Received: September 10, 2007
Revised: December 11, 2007
Published online: February 21, 2008


A primary clear cell adenocarcinoma of the colon is a rare oncologic entity. We herein report a case of such a tumor of the sigmoid colon in a 71-year-old woman who was successfully treated by an endoscopic polypectomy in our hospital. We also reviewed the published reports regarding cases of primary clear cell tumors in the colon.

Key Words: Adenoma-carcinoma sequence, Clear cell carcinoma, Colonic adenoma, Colon cancer, Endoscopic polypectomy


The first report of primary clear cell adenocarcinoma of the colon was published in 1964[1]. Even though advances have been made in the techniques regarding pathological examinations and immunohistochemistry over the past years, this tumor has been rarely diagnosed in the colon. We report a rare case of a clear cell adenocarcinoma in the colon which was successfully treated by an endoscopic polypectomy.


A 71-year-old Japanese woman presented at our hospital due to symptoms of lower abdominal pain and melena. After further examination, the pain was suspected to be due to ischemic colitis. After the symptoms of the ischemic colitis improved, we performed lower endoscopy to the cecum, which revealed healing ischemic lesions at the descending colon and a 7-mm diameter “berry-like” polyp in the sigmoid colon (Figure 1). The biopsy specimens of the polyp did not disclose a definite adenocarcinoma, but an adenoma instead. Radiologic examinations showed no evidence of a tumor elsewhere in the body, including the kidneys or the gynecologic regions. However, the surface of the polyp had a granular surface pattern and an irregular microcapillary appearance, which seemed to indicate a focal malignancy. Because endoscopic polypectomy alone for early polypoid colonic cancer is highly effective[2], we therefore performed a polypectomy during endoscopy in suspicion of focal malignancy. The resected “berrylike” polyp measured 8 mm × 6 mm in diameter with a granular lesion at the top with a cream colored portion in part.

Figure 1
Figure 1 The 7-mm diameter “berrylike” polyp on the sigmoid colon.

The microscopic examination showed clear cell adenocarcinoma on the top of the polyp and adenoma at the base and body of the polyp. There was no transition between the areas of the usual adenoma and the clear cell adenocarcinoma. Vascular invasion and lymphatic involvement were not found. The cut margin was negative (Figure 2). As shown in Figure 2, we considered the polypectomy was a curative treatment. In PAS staining, the adenoma portion revealed PAS-positive mucin on the superficial layer, while the clear cell adenocarcinoma portion showed mildly PAS-positive mucin. In the Alcian blue staining, the adenoma took up the blue stain, while the clear cell adenocarcinoma did not (Figure 3). For immunochemical staining, the clear cell adenocarcinoma showed positive staining for p53, negative for CK7, weakly positive for CD10, and positive for CK20 (Figure 4), while the adenoma portion showed slightly less positive staining for p53 than did the clear cell carcinoma, and it was negative for CK7, weakly and focally positive for CD10, and positive for CK20. About 70% of the clear cell adenocarcinoma showed Ki67 positive staining, while the adenoma showed about 45% positive staining.

Figure 2
Figure 2 A: Polypectomy specimen containing adenoma and partial clear cell carcinoma. The cut margin was showed on the bottom side; B: There was no transition between the areas of the usual adenoma on right top of the figure and the clear cell adenocarcinoma on left bottom of the figure; C: The cut margin was showed normal colonic mucosa, indicating that this polypectomy was curative treatment. Each bar indicates 200 &mgr;m.
Figure 3
Figure 3 HE staining shows clear cell carcinoma with clear cytoplasm in a normal colonic adenoma (Two top figures). PAS staining shows purple staining on the adenoma on right of the figure, and mild purple staining on the clear cell carcinoma on left of the figure. Alcian blue staining shows granular mucin on the adenoma on right of the figure, and there are no staining on the clear cell carcinoma on left of the figure. Each bar indicates 200 &mgr;m.
Figure 4
Figure 4 Ki67 is about 70% positive, p53 is positive, CK7 is negative, CK20 is positive, and CD10 is weakly positive on immunochemical staining. Each bar indicates 200 &mgr;m.

The presence of clear cell change in colorectal adenoma and adenocarcinoma is extremely unusual. The incidence of a clear cell change in the colorectal adenomas has been reported to be 0.086% out of 3486 cases[3]. In 1964, Hellstrom and Fischer described the first case of adenocarcinoma of the sigmoid colon, composed of neoplastic clear cells which resembled the physaliferous (clear) cells of chordoma tumors[1]. A clear cell adenocarcinoma generally develops in the kidneys[46], ovaries[7], extraovarian endometriosis[89], uterine cervix[1011], upper vagina, or lower genital tract[12]. These organs originate from the mullerian system, which may explain the occurrence of clear cell adenocarcinoma in these systems[13]. Therefore, an isolated clear cell adenocarcinoma of the colon is a rare malignancy and its ontogeny remains unclear.

Regarding the clinical characteristics, more male patients with a clear cell adenocarcinoma of the colon have been reported, and the tumor tends to be located on the left side. Almost all cases in Table 1 were reported as an adenoma situated next to a clear cell adenocarcinoma, as well as a clear cell adenocarcinoma situated next to an adenoma. This supports the concept that the adenoma-carcinoma sequence of colorectal carcinogenesis is also valid for the clear cell adenocarcinoma. In our case, a clear cell adenocarcinoma is also presented adjacent to an adenoma.

Table 1 A review of primary clear cell adenoma and carcinomas of the colon.
ReferencesAge (yr)SexLocationTreatment
Rubio[15]68MSplenic flexureLeft hemicolectomy
Hellstrom and fisher[1]67MRectumAbdominoperineal resection
Suzuki et al[24]62MDescending colonPolypectomy
Jewell et al[23]26FDescending colonPolypectomy
75M38 cm from anusPolypectomy
56FSigmoid colonSigmoidectomy
61FSigmoid colonPolypectomy
Domoto et al[3]54MSigmoid colonPolypectomy
45MTransverse colonPolypectomy
44MSigmoid colonPolypectomy
McCluggage et al[9]65MRectosigmoid colonAnterior resection
Braumann et al[25]89MTransverse colonSegmental resection
Current case71FSigmoid colonPolypectomy

Most reported cases of clear cell adenocarcinoma in the colon have been identified as a metastatic focus from other organs, including renal clear cell malignancies or those arising from an ovarian malignancy[14]. A rare combination of primary malignancies in both clear cell renal carcinoma and clear cell carcinoma of the colon has been reported in two patients[4]. In many cases, the differential diagnosis between advanced colonic clear cell adenocarcinoma and metastatic clear cell renal adenocarcinoma seems to be complicated. The similar histologic structure makes it difficult to distinguish between primary colonic clear cell adenocarcinoma and metastases[15]. Our case revealed no other tumors except for the original clear cell adenocarcinoma in the colon. In addition, the clear cell carcinoma occurring next to a normal colonic adenoma also supports the premise that it is the original (primary) tumor. We performed endoscopic polypectomy in this case, and pathological examination showed focal adenocarcinoma with clear cell change on the top of the polyp and common colonic adenoma on the body and base of the polyp. Vascular invasion and lymphatic involvement was not found. The cut margin was negative. As shown in Figure 2, this polypectomy was considered a curative treatment.

Cytokeratins (CK) are a family of at least 20 structural proteins found in the cytoskeletons of epithelial cells. Certain epithelia exhibit characteristic patterns of CK expression depending on the type, location, and differentiation of the epithelium. CK7, essentially, is not expressed in the normal epithelium of the gastrointestinal tract, whereas CK20 is expressed in the intestinal epithelium, the gastric foveolar epithelium, and the endocrine cells in the upper portions of the pyloric glands. On immunochemical staining, it was negative for CK7 and positive for CK20, also indicating that this tumor originated from the colonic mucosa, but not from the mullerian system.

To our knowledge, the proliferative activity among clear cells in adenomas has been rarely discussed. Immunohistochemical staining using antibodies against the Ki67 antigen is recognized to be a useful way to evaluate the proliferative activity of tumors. The increased Ki67 labeling index in the clear cell portion supported a high proliferative activity of the present tumor. The expression of the p53 protein is a well known and frequent abnormality in colorectal cancer, and it is involved in the progression of an adenoma to an adenocarcinoma. In our case, the p53 positivity tended to be higher in the clear cell portion than in the other portions, which supported the high malignant potential of the clear cells. On the other hand, a p53 overexpression has been described in 0%-40% of renal cell carcinomas[1621] and ovarian clear cell carcinoma, and a p53 overexpression in 7% of other tumors[22]. The p53 immunostaining in this case also supports the evidence for a colonic origin of this colon tumor.

As shown in Table 1, prognosis was not described in most of the cases undergoing polypectomy. One patient was alive for 12 mo without any troubles[24]. This indicates that prognosis of clear cell carcinoma is still unclear. Further reports are necessary for elucidation of this tumor.

In conclusion, we herein reported a rare case of clear cell carcinoma in the colon which was successfully resected by an endoscopic polypectomy.


Peer reviewer: Alessandro Fichera, MD, FACS, FASCRS, Assistant Professor, Department of Surgery-University of Chicago, 5841 S. Maryland Ave, MC 5031, Chicago, IL 60637, United States

1.  Hellstrom HR, Fisher ER. Physaliferous Variant of carcinoma of colon. Cancer. 1964;17:259-263.  [PubMed]  [DOI]
2.  Williams CB, Saunders BP, Talbot IC. Endoscopic management of polypoid early colon cancer. World J Surg. 2000;24:1047-1051.  [PubMed]  [DOI]
3.  Domoto H, Terahata S, Senoh A, Sato K, Aida S, Tamai S. Clear cell change in colorectal adenomas: its incidence and histological characteristics. Histopathology. 1999;34:250-256.  [PubMed]  [DOI]
4.  D'Amato A, Nigri G, Pronio A, Montesani C, Ferrazza G, Rusignolo A, Solinas S, Ribotta G. The use of autotransfusion in general surgery. Ann Ital Chir. 2000;71:643-647; discussion 647-648.  [PubMed]  [DOI]
5.  Tokonabe S, Sugimoto M, Komine Y, Horii H, Matsukuma S. Solitary colonic metastasis of renal cell carcinoma seven years after nephrectomy: a case report. Int J Urol. 1996;3:501-503.  [PubMed]  [DOI]
6.  Zerbib F, Becouarn Y, Stockle E, Ravaud A, Brunet R. Colonic metastasis of a renal carcinoma. A case report. Tumori. 1992;78:219-220.  [PubMed]  [DOI]
7.  Kim SJ, Kimoto Y, Nakamura H, Taguchi T, Tanji Y, Izukura M, Shiba E, Takai S. Ovarian carcinoma with fistula formation to the sigmoid colon and ileum: report of a case. Surg Today. 1999;29:449-452.  [PubMed]  [DOI]
8.  Hitti IF, Glasberg SS, Lubicz S. Clear cell carcinoma arising in extraovarian endometriosis: report of three cases and review of the literature. Gynecol Oncol. 1990;39:314-320.  [PubMed]  [DOI]
9.  McCluggage WG, Desai V, Toner PG, Calvert CH. Clear cell adenocarcinoma of the colon arising in endometriosis: a rare variant of primary colonic adenocarcinoma. J Clin Pathol. 2001;54:76-77.  [PubMed]  [DOI]
10.  Jones WB, Koulos JP, Saigo PE, Lewis JL Jr. Clear-cell adenocarcinoma of the lower genital tract: Memorial Hospital 1974-1984. Obstet Gynecol. 1987;70:573-577.  [PubMed]  [DOI]
11.  Zhang WH. Adenocarcinoma of the uterine cervix. An analysis of 121 cases. Zhonghua Zhongliu Zazhi. 1993;15:61-64.  [PubMed]  [DOI]
12.  Rovinescu I, Rousseau E. Multiple primary urinary cancers triple cancers. Union Med Can. 1976;105:1351-1353.  [PubMed]  [DOI]
13.  Evans H, Yates WA, Palmer WE, Cartwright RL, Antemann RW. Clear cell carcinoma of the sigmoid mesocolon: a tumor of the secondary mullerian system. Am J Obstet Gynecol. 1990;162:161-163.  [PubMed]  [DOI]
14.  Medina Perez M, Valero Puerta JA, Valpuesta Fernandez I, Perez Fernandez D, Sanchez Gonzalez M. Renal carcinoma with intranuclear inclusions associated with colon carcinoma. Arch Esp Urol. 2000;53:79–81.  [PubMed]  [DOI]
15.  Rubio CA. Clear cell adenocarcinoma of the colon. J Clin Pathol. 1995;48:1142-1144.  [PubMed]  [DOI]
16.  Vasavada SP, Novick AC, Williams BR. P53, bcl-2, and Bax expression in renal cell carcinoma. Urology. 1998;51:1057-1061.  [PubMed]  [DOI]
17.  Sejima T, Miyagawa I. Expression of bcl-2, p53 oncoprotein, and proliferating cell nuclear antigen in renal cell carcinoma. Eur Urol. 1999;35:242-248.  [PubMed]  [DOI]
18.  Uchida T, Gao JP, Wang C, Jiang SX, Muramoto M, Satoh T, Minei S, Shimura S, Irie A, Kameya T. Clinical significance of p53, mdm2, and bcl-2 proteins in renal cell carcinoma. Urology. 2002;59:615-620.  [PubMed]  [DOI]
19.  Haitel A, Wiener HG, Blaschitz U, Marberger M, Susani M. Biologic behavior of and p53 overexpression in multifocal renal cell carcinoma of clear cell type: an immunohistochemical study correlating grading, staging, and proliferation markers. Cancer. 1999;85:1593-1598.  [PubMed]  [DOI]
20.  Shiina H, Igawa M, Urakami S, Shirakawa H, Ishibe T, Kawanishi M. Clinical significance of immunohistochemically detectable p53 protein in renal cell carcinoma. Eur Urol. 1997;31:73-80.  [PubMed]  [DOI]
21.  Zhang XH, Takenaka I, Sato C, Sakamoto H. p53 and HER-2 alterations in renal cell carcinoma. Urology. 1997;50:636-642.  [PubMed]  [DOI]
22.  Skirnisdottir I, Seidal T, Sorbe B. A new prognostic model comprising p53, EGFR, and tumor grade in early stage epithelial ovarian carcinoma and avoiding the problem of inaccurate surgical staging. Int J Gynecol Cancer. 2004;14:259-270.  [PubMed]  [DOI]
23.  Jewell LD, Barr JR, McCaughey WT, Nguyen GK, Owen DA. Clear-cell epithelial neoplasms of the large intestine. Arch Pathol Lab Med. 1988;112:197-199.  [PubMed]  [DOI]
24.  Suzuki H, Ohta S, Tokuchi S, Moriya J, Fujioka Y, Nagashima K. Adenoma with clear cell change of the large intestine. J Surg Oncol. 1998;67:182-185.  [PubMed]  [DOI]
25.  Braumann C, Schwabe M, Ordemann J, Jacobi CA. The clear cell adenocarcinoma of the colon: case report and review of the literature. Int J Colorectal Dis. 2004;19:264-267.  [PubMed]  [DOI]