Implantation of rectosigmoid cancer in a preexisting anal fissure

Abstract

Colorectal cancer (CRC) rarely spreads by implantation. We report a case of implantation of rectosigmoid cancer in an anal fissure. A 70-year-old woman with a 15-year medical history of anal fissure was referred to our hospital with anal pain of 3-month duration. Colonoscopy revealed a rectosigmoid tumor and a 10-mm submucosal tumor at the anal verge. Biopsy of the rectosigmoid and anal tumors revealed that both were moderately differentiated adenocarcinomas, and abdominoperineal resection (APR) was performed. The anal adenocarcinoma was surrounded by squamous cell epithelium and mainly proliferated in the submucosal and muscular layers. The patient was diagnosed as having rectosigmoid cancer with implantation of cancer in a preexisting anal fissure. The patient remains well 43 months post-surgery with no sign of recurrence. Implantation of CRC in anal fissure is a rare occurrence. Nevertheless, performing adequate anal examination of patients with CRC before surgery and during follow-up is necessary. Further, it is important to perform preoperative large bowel examination of patients with benign anal diseases to prevent implantation of CRC.

Introduction

Colorectal cancer (CRC) can spread via lymphatic, hematogenous, or transperitoneal means or by direct extension. However, CRC spread by implantation is a rare occurrence. CRCs are known to exfoliate cells into the bowel lumen [1]. Implantation of exfoliated cancer cells has been suggested as a mechanism of local recurrence at colorectal anastomosis sites [2]. However, implantation of CRC in benign anal diseases is extremely rare [3]. In this report, we present a rare case of implantation of rectosigmoid cancer in a preexisting anal fissure, which was diagnosed during preoperative examination and required treatment in the form of abdominoperineal resection (APR).

Case report

A 70-year-old woman was referred to Rokuwa Hospital with anal pain of 3-month duration. She underwent surgery for hemorrhoids 35 years ago and had a 15-year medical history of anal fissure. At initial presentation, there were no abnormal findings in the chest or abdomen. A 10-mm hard mass was palpated at the anal verge during digital rectal examination, although active anal fissure was not found. Her laboratory results revealed normal carcinoembryonic antigen and carbohydrate antigen 19–9 levels of 2.7 ng/mL and 3 U/mL, respectively. However, barium enema study revealed a defect, which had an irregular surface and is about 5 cm in length, in the rectosigmoid colon. Colonoscopy confirmed the presence of a tumor with ulceration located 15 cm proximal to the anal verge (Fig. 1a) and a 10-mm submucosal tumor at the anal verge (Fig. 1b, c). Epithelium was not found in biopsy of the anal tumor histologically (Fig. 1d). Biopsy of the rectosigmoid and anal tumors (Fig. 1e) revealed that both tumors were moderately differentiated adenocarcinomas. Computed tomography of the chest and abdomen revealed no abnormalities.

Fig. 1.

Representative colonoscopy images. Colonoscopy showing an ulcerated tumor in the rectosigmoid colon (a) and a 10-mm submucosal tumor at the anal verge (arrow) (b, c). Epithelium was not found in biopsy of the anal tumor histologically (d). Biopsy of the anal tumor revealed that tumor was moderately differentiated adenocarcinoma (e)

The patient was then transferred to Fujita Health University Hospital for the treatment of the rectosigmoid and anal cancers. Because the base of cancer in the anal region was firm widely and it was suspected to be more widespread and deeper compared with a tumor observed in the surface, APR with lateral lymph node dissection was performed 5 weeks after the initial presentation. The resected specimen revealed an ulcerated tumor in the rectosigmoid colon (45 × 50 × 10 mm) and a submucosal tumor with a surface ulcer in the anus (10 × 10 × 5 mm) (Fig. 2a). Macroscopically, the surface mucosa between the two tumors was normal (Fig. 2a), and a scar with epithelial concentration, thought to be formed by the anal fissure, was found at the base of the anal tumor (Fig. 2b). Histological examination of the larger rectosigmoid tumor revealed a moderately differentiated adenocarcinoma similar to the anal tumor (Fig. 3a, b) with serosal invasion but without lymph node metastasis. The final pathological staging of the rectosigmoid cancer was stage IIb (T4a N0 M0) according to the Japanese classification of colorectal carcinoma [4] and stage IIB (T4a N0 M0) according to the tumor–node–metastasis classification. Lymphatic and vascular invasion was evaluated using immunohistochemical analysis with D2-40 and Victoria-blue hematoxylin–eosin staining. There was no lymphangitic (Ly0) or venous invasion (V0) of the rectosigmoid and anal tumors according to the Japanese classification of colorectal carcinoma [4]. Although the anal adenocarcinoma was surrounded by squamous cell epithelium (Fig. 3c, d), adenocarcinoma was found at the squamous defective site, which was present in the oral side of the anal tumor and was observed like a scar macroscopically (Fig. 3d). And adenocarcinoma mainly proli). A foreign body, which was thought to be feces, was found among adenocarcinoma under the squamous defective site (Fig. 3b, d). Based on these findings, the patient was diagnosed as having rectosigmoid cancer with implantation of cancer in a preexisting anal fissure.

Fig. 2.

Macroscopic findings on the resected specimen. The resected specimen showing an ulcerated tumor in the rectosigmoid colon and a submucosal tumor with a surface ulcer in the anus (yellow arrow). The surface mucosa between the two tumors is macroscopically normal (a). A scar with epithelial concentration thought to be formed by the anal fissure is found at the base of the anal tumor (white arrow) in the magnified image of the anal region (b). A white line in b indicates the location which accords in Fig. 3c

Fig. 3.

Examination findings of the rectosigmoid and anal tumors. Histological examination of the larger rectosigmoid tumor (a) showing a moderately differentiated adenocarcinoma similar to the anal tumor (b) (hematoxylin and eosin staining,  × 12.5 magnification). Macroscopic view of the cut surface of the smaller anal lesion (c). Microscopic view of the area in the square shown in c after histopathological examination (d) (hematoxylin and eosin staining,  × 10 magnification). Microscopic view of the area in the square shown in b after histopathological examination (d). The anal adenocarcinoma is surrounded by squamous cell epithelium and mainly proliferated in the submucosal and muscular layers, which are covered by squamous cell epithelium (c, d). Adenocarcinoma was found at the squamous defective site, which was present in the oral side of the anal tumor and was observed like a scar macroscopically (black arrow) (b–d). A foreign body, which was thought to be feces, was found among adenocarcinoma under the squamous defective site (yellow arrow) (b, d)

The postoperative course of the patient was uneventful. No adjuvant chemotherapy was administered to the patient in accordance with the guidelines of the Japanese Society for Cancer of the Colon and Rectum [5]. The patient remains well 43 months post-surgery with no sign of recurrence.

Discussion

In 1907, Charles Ryall first reported implantation metastasis of solid cancers and described this phenomenon as “cancer infection” [6]. This concept of implantation was recently accepted. Although CRCs are known to exfoliate cells into the bowel lumen [1], the exfoliated cancer cells do not implant on normal mucosa or epithelium. In their experimental study on rats, Hubens et al. reported that colonic mucosa is extremely resistant to cancer cell implantation [7]. In general, exfoliated cancer cells can implant on open wounds or ulcerated areas. CRC spread by implantation has been reported in the presence of mucosal or epithelial damage such as that due to colonoscopic biopsy [8], insertion of laparoscopic ports [9] and Lone Star retractors [10], introduction of anastomotic stapler devices [11], hemorrhoidectomy wounds [12], and anal fistulae [13, 14]. However, to our knowledge, this is the first report of implantation of CRC in an anal fissure.

Regarding diagnosis, distinguishing between implantation of CRC in anal fissure and primary anal cancer is difficult. In the case of our patient, although the surface mucosa between the two tumors in the resected specimen was macroscopically normal, histological examination revealed that the rectosigmoid and anal tumors have a similar histology, and most of the anal adenocarcinoma was found to be surrounded by squamous cell epithelium except the squamous defective site which was observed like a scar macroscopically. Further, the anal adenocarcinoma mainly proliferated in the subepithelial and muscular layers. These findings suggest that the anal tumor is related to the rectosigmoid tumor. Microscopic tumor spread via the intestinal wall distal to the inferior edge of a macroscopic tumor is known as distal intramural spread [15]. To date, distal intramural spread is thought to result from direct tumor extension, vessel invasion, or cancer cell implantation [16, 17]. However, in the case of our patient, there was no lymphangitic or venous invasion by the rectosigmoid or anal tumor, and direct extension between the rectosigmoid and anal tumors was not detected on histological examination. Furthermore, adenocarcinoma was found at the squamous defective site, which was present in the oral side of the anal tumor and was observed like a scar caused by the anal fissure macroscopically. And a foreign body, which was thought to be feces, was found among adenocarcinoma under the squamous defective site. It was supposed that a cancer cell which was implanted in the anal fissure with feces proliferated in the subepithelial and muscular layers because surface of anal fissure was covered by epithelium due to the healing. In their review of cases of CRC implantation in anal fistulae, Wakatsuki et al. reported that most primary cancers were located in the sigmoid colon and rectum [14]. They further suggested that exfoliated cancer cells cannot implant on anal fistulae because cell viability decreases in tumors located in the proximal colon [14]. Our patient had a rectosigmoid cancer located 15 cm proximal to the anal verge and a medical history of anal fissure with open wound. Based on these clinical and histological findings, our patient was diagnosed as having rectosigmoid cancer with implantation of cancer in a preexisting anal fissure. Although APR was performed in most reported cases, in some cases, local excision was performed for curative or palliative intent [13, 14]. There was no local recurrence in any of the reported cases, although the follow-up periods were not sufficiently long. Therefore, taking patient quality of life into account, transperitoneal local excision may be considered. However, in our patient, tumor proliferation occurred mainly in the submucosal and muscular layers although the anal tumor was located in the epithelium and had a size of 10 mm. Considering and confirming that anal function preservation surgery is appropriate for each patient is necessary.

In conclusion, implantation of CRC in an anal fissure is an extremely rare occurrence. Nevertheless, performing adequate anal examination of patients with CRC before surgery and during follow-up is necessary. Further, it is considered important to perform preoperative large bowel examination of patients with benign anal diseases to prevent implantation of CRCs as it may lead to better local control and better outcomes in patients with CRC.

Funding

No financial support was received for the work described in this manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

The patient provided informed consent prior to treatment and publication.