Neoplasms of the Anus: High-Grade Squamous Intraepithelial Lesions and Cancer

Anatomy

The anal canal starts at the pelvic floor where the rectum enters the puborectalis muscle at the superior most aspect of the sphincter complex and ends where the stratified squamous epithelium becomes continuous with the perianal skin ( Fig. 173.1 ). On digital examination, this corresponds to the palpable anorectal ring superiorly and the intersphincteric groove, the outermost boundary of the internal sphincter inferiorly. It includes columnar epithelium above the dentate line, squamous epithelium below the dentate line, and the anal transition zone (ATZ). The ATZ is a region 1 to 12 mm in length at the dentate line where there is a “transitional urothelium-like” epithelium. This is considered to be a variant of squamous epithelium and includes cloacogenic, transitional, and basaloid epithelium instead of the columnar epithelium of the rectum. The “transformation zone” refers to the squamous metaplasia that can involve the proximal anal canal above the dentate line that is usually lined with columnar epithelium. The average length of the anal canal is longer in men (3 to 6 cm) than in women (2 to 4 cm).

Anal canal lesions cannot be visualized at all or are incompletely visualized with gentle traction placed on the buttocks. The perianus extends from the inferior boundary of the anal canal to approximately a radius of 5 cm around the anus and represents a region and not a distinct anatomic boundary. This region was previously referred to as the anal margin, but under the current accepted nomenclature, lesions of the perianus are referred to as perianal lesions. It is characterized by stratified squamous epithelium as well as skin appendages such as apocrine glands and hair. Perianal lesions are easily visible and are within a 5-cm radius of the anal canal when gentle traction is placed on the buttocks. Finally, skin lesions fall outside of the 5-cm radius of the perianus (see Fig. 173.1 ). This distinction is important to determine the exact location of lesions because the management of anal canal and lesions of the perianus and skin can be different.

The anal canal and perianal region has a diverse number of cell types and therefore a variety of different cancers can originate from this region. The most frequent malignancy is SCC that can be nonkeratinizing or keratinizing. Lesions originating from the ATZ include cloacogenic, transitional, basaloid, and mucoepidermoid carcinomas. These distinctions are not clinically important anymore as they are grouped under SCCs because their treatment and prognosis are similar to anal SCC. The second most common malignancy of the anal canal are adenocarcinomas. Other uncommon malignancies include melanoma, verrucous carcinoma, Paget disease, and BCC.

Anal Squamous Cell Carcinoma

Presentation and Diagnosis

The common presenting symptoms are anal pain, bleeding, anal discharge, irritation, and discomfort. Patients may report anal leakage or soiling and can also develop fecal incontinence and tenesmus if the sphincter complex is involved. In patients with locally advanced disease, there may be signs and symptoms of perianal sepsis and fistulous disease. Patients can also be asymptomatic or be incidentally diagnosed after excision of anal lesions or after hemorrhoid surgery. Due to the nonspecific nature of these presenting symptoms, patients are frequently misdiagnosed as having a benign anorectal pathology. In patients with a nonhealing anal fissure, chronic ulcer, or fistula that is not responsive to therapy, it is important to rule out an underlying malignancy with a tissue diagnosis.

The initial work-up of a patient with anal SCC should include a complete history including assessment of risk factors for anal cancer and a physical examination with emphasis on the inguinal lymph nodes, a digital rectal examination, and anoscopic examination with biopsy. It is important to note the location and size of the lesion, its relationship to the sphincter complex, and evidence of invasion into surrounding structures such as the vagina, urinary bladder/urethra, and pelvic sidewalls. Although this can all be performed with the patient awake in the office, it is usually uncomfortable for the patient. Therefore an exam under anesthesia provides a better opportunity to thoroughly examine the patient, as well as obtain a tissue diagnosis.

Diagnostic Imaging

The clinical assessment of the primary disease and inguinal nodes is helpful in the clinical staging of the disease, whereas radiologic evaluation is more accurate and reliable in determining the nature and extent of local, nodal, and distant disease. Because the definitive treatment for anal cancer is chemoradiation, there are few data to validate the accuracy and reliability of radiologic staging of local and nodal disease, as there is no pathologic correlation or comparable referent stage. The most frequent staging modality used to evaluate metastatic disease is a contrast computed tomography (CT) scan because it can reliably evaluate for distant disease in the liver and lungs, as well as abnormal lymphadenopathy in the inguinal region and the pelvis. For local staging purpose, endorectal ultrasound (ERUS) allows visualization of the anal canal and can accurately assess the depth of tumor penetration and extension to surrounding structures, including sphincter complex involvement. However, ERUS is of limited value in assessing mesorectal and pelvic lymphadenopathy, and therefore its routine use is not recommended. Magnetic resonance imaging (MRI) provides accurate assessment of the primary lesion, in particular the extent and nature of involvement of surrounding organs, and is also more reliable than ERUS in evaluating lymph nodes in the mesorectum and inguinal regions and as a result should be used to complement CT scan findings.

Fluorodeoxyglucose Positron Emission Tomography–Computed Tomography

PET/CT with fluorodeoxyglucose (FDG) has the ability to evaluate lymph node involvement and distant metastases because the majority of these cancers are FDG avid. It can also detect lymph nodes with metastatic disease that have increased uptake but are normal size. In early-stage disease (T size <3 cm) the risk of inguinal node involvement is less than 5%, whereas in clinical stages T3 (>5 cm) and T4 (involvement of adjacent structures such as bladder or vagina) the probability of metastatic lymph node disease is almost 20%. Clinical examination and imaging with CT scans along with fine-needle aspiration is considered the standard to determine nodal involvement. This strategy likely understages a proportion of patients because almost half of involved lymph nodes are less than 5 mm in size and would not be clinically palpable or detected by CT scan, which usually has a size threshold of 8 mm.

Overall, the data would suggest that FDG-PET/CT alters the stage in approximately 20% of cases, with a trend toward upstaging, and results in modification of treatment intent in 3% to 5% of patients. As a result, PET/CT has been advocated to be incorporated into the staging work-up because it may be able to identify positive lymph nodes that may not necessarily be identified by CT scan or physical examination. The current National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) have included PET/CT as a part of the routine diagnostic work-up.

Staging

SCC of the anal canal can spread by (1) direct extension and invasion of adjacent structures such as the vagina in women, the bladder, and urethra; (2) lymphatic spread through the perirectal, pelvic, and inguinal lymph nodes; and (3) hematogenously to distant organs such as the liver and lung. This relatively wide and variable range of spread is due to the unique lymphatic and venous drainage of the anal canal. As a result, metastases can occur to the inguinal and pelvic lymph nodes and to the liver by the portal system or to the lung via the systemic circulation, depending on the location of the SCC. The part of the anal canal above the dentate line drains through the superior rectal vessels to the inferior mesenteric lymph nodes and vein and laterally to the internal iliac lymph nodes. The anal canal below the dentate line, as well as the perianus, drains primarily into the inguinal lymph nodes and the internal iliac vein through the inferior rectal vein but could also involve the inferior and superior rectal lymph nodes.

Tumors of the anus and perianus that are discussed in this chapter are staged according to the unified AJCC/International Union against Cancer (UICC) staging system, eighth edition, which incorporates tumor size (T), lymph node status (N), and distant metastasis. The T stage is based on size of the cancer and extent of involvement of surrounding structures, and the N stage is based on presence or absence of nodal disease ( Table 173.1 ). Mesorectal, superficial and deep inguinal, superior rectal, and external and internal iliac nodes are considered regional lymph nodes, whereas all other nodal groups represent distant metastasis ( Fig. 173.2 ).