Squamous Cell Carcinoma of the Anal Margin

Mendenhall and colleagues provide a useful review of the management of squamous cell carcinoma of the anal margin. Although I generally agree with their conclusions and recommendations for treatment, their paper highlights the continuing difficulties in developing a universally agreed-upon descriptive terminology for the anal region.

Universal Terminology Remains Elusive

Mendenhall et al define a carcinoma of the anal margin as a lesion "originating between the dentate line and the outer limit of the perianal skin, defined to be 5 cm from the anal verge in any direction." This definition is not consistent with the current recommendations of the two major international cancer staging committees, the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC). The AJCC defines the anal canal as "extending from the rectum to the perianal skin," and describes the anal margin as "the junction of the hair-bearing skin and the mucous membrane of the anal canal."[1] Cancers of the anal margin, together with those of the more distal skin, are staged according to the system used to classify skin cancers.

The UICC also describes the anal canal as extending "from the rectum to the perianal skin (to the junction with hair-bearing skin)."[2] Both staging committees list the anal margin and perianal skin in their sections on carcinoma of the skin but do not define the extent of these areas. The anal margin and perianal skin are identified with the skin of the trunk by a single ICD-O topography rubric 173.5, and the anal canal is coded ICD-O 154.2.[2]

Mendenhall and colleagues cite 15 relevant clinical papers in their review. Those papers use no fewer than four different definitions of the anal margin and perianal area! The definition favored by Mendenhall et al is used by only three of the cited papers (the authors' references 5, 18, and 16). The definition recommended by the UICC and AJCC is employed by half (the authors' references 3, 4, 12, 13, 15, 17, and 19), although some use only the term "perianal" as distinct from "anal canal" without referring to the anal margin at all.

A third variant is to ascribe to the anal margin only those cancers that arise below the dentate line and above the junction of the mucocutaneous membrane and the hair-bearing skin (the authors' references 9 and 20). Finally, two papers define the perianal skin as a 6-cm-diameter circle centered on the anal orifice (the authors' references 6 and 14), whereas most authors use the 10-cm diameter area recommended by Beahrs and Wilson (the authors' reference 4).

Are the Inconsistent Anatomical Definitions Important?

In the face of such inconsistency of anatomical definition, it is remarkable that so many of the authors reach similar conclusions regarding treatment, stressing approaches designed to preserve anorectal function. Does this mean that the inconsistency is unimportant? The answer to this question must be no.

In particular, the lymphatic drainage of the anatomical anal canal differs significantly from that of the perianal skin. Whereas the latter drains primarily to the inguinal lymph nodes, the lymphatics of the distal part of the anal canal communicate freely with those of the mid- and proximal canal. Hence, there is a risk that cancers that involve the distal canal, either primarily or secondarily, may spread not only to the inguinal nodes but also to the internal iliac and superior hemorrhoidal lymph node systems.[3] This must be considered in planning treatment.

The spectra of histologic subtypes of cancer encountered in the anal canal and in the perianal skin also differ, although there is some overlap.[4] While reasonable arguments have been presented for each of the various anatomical classifications used, it is clear that the adoption of a more standardized descriptive terminology would be of value.

An Attempt at Standardization

One such attempt at standardization has been proposed by Fenger.[5] He recommended that the anal canal be defined as the terminal part of the gastrointestinal tract extending from the pelvic floor to the anal opening (Figure 1). This definition has the advantage that it is based on palpable borders, there being no clinically visible boundary to the proximal limit of the canal. The upper border is defined by the palpable muscular ring of the anal sphincter and the puborectalis muscle. The distal limit of the canal is the point where the walls of the canal come into contact in their normal resting state. This point may be called the anal verge and approximates to the palpable groove between the lower edge of the internal sphincter and the subcutaneous part of the external sphincter.

The terms "anal verge" and "anal margin" are used interchangeably in many series, a practice that is at least consistent with English usage even if not explicitly sanctioned by the staging committees. (The term "anal orifice" used in earlier versions of the UICC manual was replaced by "anal margin" in the 1987 classification[2]). The definition proposed by Fenger also implies that the anal verge or margin has no width, being only the line at the lowermost point where the walls of the canal come into contact. Effectively, anal cancers would be classified as arising in either the anal canal or the perianal skin. I favor this simple system.

A Reasonable Approach to Treatment

The difficulties presented by the heterogeneity of classification notwithstanding, Mendenhall and coauthors have done well to distill from the papers a reasonable approach to treatment. For superficial well- or moderately differentiated squamous cell cancers up to about 3 to 4 cm in diameter, our practice in Toronto has tended to shift away from radiation therapy toward primary resection by local excision, supplemented with a skin graft when necessary, provided that this surgery is not anticipated to interfere with anal sphincter function. Although severe damage is infrequent following radiation, chronic irritation of the perianal skin and varying degrees of dysfunction of the anal region are common and can prove troublesome.

If local excision is impractical, we agree with the recommendation of combined radiotherapy and chemotherapy. The two randomized trials that have demonstrated the superiority of radiation combined with fluorouracil(Drug information on fluorouracil) and mitomycin(Drug information on mitomycin) (Mutamycin) over radiation alone in terms of local control and colostomy-free survival rates both included patients with cancers arising in the anal canal and anal margin.[6,7] Neither investigative group has yet reported subset analyses according to the site of origin of the cancer, but the results appear likely to favor combined-modality therapy, as was suggested in the nonrandomized studies (the authors' references 3 and 15). The relatively limited information available so far suggests that combined-modality treatment is preferable to radiation alone for all anal cancers more than about 3 cm in size and for the treatment of regional node metastases.

Summary

There are many similarities between squamous cell cancers of the anal canal and of the perianal skin. Nevertheless, their natural history is not identical, and they should be considered separately. The anal margin remains an often poorly defined boundary between the two and is a term best discarded.