Clear cell adenocarcinoma of the colon: A case report and review of literature

Abstract

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

INTRODUCTION

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.

CASE REPORT

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 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 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 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 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.

DISCUSSION

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[4–6], 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.

References	Age (yr)	Sex	Location	Treatment
Rubio[15]	68	M	Splenic flexure	Left hemicolectomy
Hellstrom and fisher[1]	67	M	Rectum	Abdominoperineal resection
Suzuki et al[24]	62	M	Descending colon	Polypectomy
Jewell et al[23]	26	F	Descending colon	Polypectomy
	75	M	38 cm from anus	Polypectomy
	56	F	Sigmoid colon	Sigmoidectomy
	61	F	Sigmoid colon	Polypectomy
Domoto et al[3]	54	M	Sigmoid colon	Polypectomy
	45	M	Transverse colon	Polypectomy
	44	M	Sigmoid colon	Polypectomy
McCluggage et al[9]	65	M	Rectosigmoid colon	Anterior resection
Braumann et al[25]	89	M	Transverse colon	Segmental resection
Current case	71	F	Sigmoid colon	Polypectomy

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[16–21] 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.