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Carcinoma of the anal canal is a rare malignancy representing approximately 2.5% of all gastrointestinal malignancies. It is estimated in 2015 that over 7,200 patients will be diagnosed with carcinoma of the anal canal in the United States, resulting in greater than 1,000 deaths (1). The incidence of this disease continues to rise steadily. A practicing oncologist will evaluate and treat less than one such patient per year. The majority of anal carcinoma arises within the mucosa of the anus and is of squamous cell histology (2). Traditionally, 74% to 90% of carcinomas of the anal canal are cured with the combined modalities of chemoradiation, reserving an abdominoperineal resection (APR) for salvage therapy of persistent or recurrent disease (3). This chapter focuses on treatment of squamous cell carcinoma of the anal canal and the potential innovative strategies that lie ahead.


The anal canal is approximately 4 cm wide and is composed of the region extending from the proximal anorectal ring to the distal anal verge (margin) (Fig. 25-1). Because various definitions of the normal anal canal anatomy exist, classifying these tumors by a histologic definition based on the lining mucosa offers a more consistent approach to guide diagnosis and treatment (2).


Anatomy of the anal canal.

Malignancies of the anal margin are treated as primary skin cancers and are often surgically excised. The rectal mucosa adjacent to the anorectal ring is composed of columnar epithelium. A transition zone of both cuboidal and columnar epithelium (6-12 mm in length) extends from the distal rectum to the dentate line. The dentate line separates the columnar epithelium (columns of Morgagni) of the proximal anal canal and the squamous epithelium of the distal canal, which extends to the anal verge. The anal verge is the convergence of squamous epithelium and the anal margin. The anal margin comprises the dermis, located within 5 cm of the anal verge.

The mucosa of the transition zone, formally referred to as the cloacogenic mucosa, represents 66% of the lesions now commonly referred to as nonkeratinizing squamous cell carcinoma (SCC) (Figs. 25-2 and 25-3) (4). Tumors distal to the dentate line are usually keratinizing SCC (Figs. 25-4 and 25-5).


Nonkeratinized squamous cell carcinoma of the anal canal.


Magnified view of nonkeratinized squamous cell carcinoma of the anal canal.


Keratinized squamous cell carcinoma of the anal canal.


Magnified view of keratinized squamous cell carcinoma of the ...

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