What are the diagnosis and treatment options for an anal mass?

Diagnosis and Treatment of Anal Mass

An anal mass requires histological confirmation through proctoscopy and biopsy, ideally performed under anesthesia, with subsequent management determined by whether it represents benign disease, anal intraepithelial neoplasia, or invasive squamous cell carcinoma—for which combined chemoradiation with 5-fluorouracil and mitomycin C is the standard of care rather than primary surgery. 1

Initial Diagnostic Approach

Clinical Evaluation

• Document a detailed history focusing on specific symptoms: rectal bleeding, pain, non-healing ulcers, itching, discharge, and fecal incontinence 1
• Elicit predisposing factors including HPV exposure, HIV status, immunosuppression (transplant recipients), history of men who have sex with men, and prior malignancies (gynecological, lung, bladder, vulva, vagina, breast) 1
• Perform digital rectal examination (DRE) and vaginal examination in women to assess tumor size, location, and nodal involvement 1

Mandatory Diagnostic Procedures

• Proctoscopy with examination under anesthesia is essential to facilitate adequate biopsy and clarify anatomical relationships to surrounding structures 1
• Histological confirmation is mandatory before any treatment decisions 1
• Small early cancers may be discovered incidentally after removal of anal tags, but this does not obviate the need for proper staging 1

Differential Diagnosis Considerations

The anal mass differential includes:

• Squamous cell carcinoma (most common malignancy): presents as mass, ulcer, or bleeding lesion 1
• Anal intraepithelial neoplasia (AIN): precursor lesion present in 30-40% of men who have sex with men, with progression risk higher in immunosuppressed patients 1
• Giant condyloma (Buschke-Lowenstein tumor): slow-growing verrucous mass that may harbor invasive carcinoma and typically requires surgical excision 2
• Metastatic disease: rare but reported from rectal adenocarcinoma, breast lobular carcinoma, or other primaries 3, 4
• Benign lesions: hemorrhoids, fissures, abscesses (though these do not predispose to anal cancer) 1

Staging Workup Once Malignancy Confirmed

Local Staging

• MRI of the pelvis is the modality of choice for assessing locoregional disease and determining tumor size, depth of invasion, and relationship to sphincter complex 1
• Physical examination under general anesthesia provides the most definitive assessment and complements imaging 1
• Careful clinical assessment of inguinal nodes is critical, as nodal involvement differs between anal canal and anal margin tumors 1

Distant Metastasis Assessment

• CT thorax and abdomen to evaluate for distant metastases 1
• PET-CT has insufficient evidence for routine use in initial staging or follow-up 1

Additional Testing

• HIV testing recommended in any patient with risk factors 1
• Assessment of cervix and vulva in female patients due to common HPV etiology 1
• Screen for other malignancies given increased risk of synchronous/metachronous tumors 1
• Assess performance status, renal function, and comorbidities before treatment 1

Treatment Algorithm

For Small Well-Differentiated Anal Margin Tumors (T1N0)

• Local excision is appropriate ONLY for tumors <2 cm, well-differentiated, without nodal spread or sphincter involvement 1, 5
• This represents a narrow indication; most anal masses require chemoradiation 1, 5

For All Other Anal Canal Tumors and Advanced Anal Margin Tumors

Combined modality chemoradiation is the standard first-line treatment 1, 5:

• Radiation dose: at least 45-50 Gy for T1-2N0 tumors; 50.4 Gy or higher for T3-4 or N1 tumors 1
• Chemotherapy: 5-fluorouracil and mitomycin C combined with radiotherapy 1
• Capecitabine can possibly be used as alternative to 5-FU in combination with mitomycin C and RT 1
• Uninterrupted treatment without gaps is radiobiologically most effective 1
• IMRT, VMAT, or 3D conformal RT are recommended techniques 1

Inguinal Node Treatment

• Inguinal nodes should be included in radiation fields in most cases, even without demonstrable involvement 1
• Risk of inguinal involvement is at least 20% in T3 disease and higher for tumors below the dentate line or near the anal orifice 1

Role of Primary Surgery (Very Limited)

Primary abdominoperineal resection may be considered ONLY in uncommon scenarios 1:

• Previous pelvic radiotherapy precluding curative RT 1
• Anal adenocarcinoma or adenosquamous carcinoma (less responsive to RT than squamous cell) 1
• Transplant patients on immunosuppressants where completion of CRT is uncertain 1
• Patient refusal of chemoradiation 1

Local excision of early-stage anal canal cancers is contraindicated due to high margin-positive rates and increased morbidity if followed by CRT 1

Adjunctive Surgical Considerations

• Pre-treatment colostomy indicated for: anorectal pain, fecal incontinence, anticipated incontinence during CRT, or rectovaginal fistula 1
• Patients should be counseled that pre-treatment colostomy will likely be permanent 1
• Seton placement for perianal fistulas (present in up to 25% of patients) should be performed before CRT to prevent sepsis and treatment gaps 1

Neoadjuvant/Adjuvant Chemotherapy

• Not recommended outside clinical trials, as it has not improved locoregional or distant control 1

Response Assessment and Follow-Up

Timing of Assessment

• Optimal timepoint to assess tumor response is 26 weeks (approximately 6 months) after completion of CRT 1
• Clinical assessment must be undertaken pre- and post-treatment 1
• Side-by-side comparison of baseline and post-treatment MRI scans enables accurate response assessment 1

Salvage Surgery for Persistent/Recurrent Disease

Patients with locally residual or recurrent disease after CRT should be considered for salvage surgery 1, 5:

• Histological confirmation of residual/recurrent tumor is mandatory before proceeding to radical surgery 1, 5
• MRI in conjunction with specialist multidisciplinary team assessment is essential to optimize surgical cure 1, 5
• Extra-levator abdominoperineal excision (APE) is the mainstay of salvage surgery 1, 5
• More radical exenterative operations may be needed to achieve R0 resection when anal sphincter complex is involved 1
• Perineal plastic reconstruction with musculocutaneous flaps should be considered in almost all cases 1
• Salvage surgery achieves local pelvic control in approximately 60% of cases with 5-year survival rates of 30-60% 5
• Patients should be warned that long-term morbidity after salvage surgery is high 1

Persistent Inguinal Disease

• Radical groin dissection should be considered for persistent/progressive inguinal lymph node disease 5
• Pre- or post-operative irradiation may be considered depending on prior RT dose distribution 5

Critical Pitfalls to Avoid

• Never perform piecemeal resections as this renders assessment of resection margins impossible 1
• Do not perform local excision of anal canal cancers (even early stage) due to high margin-positive rates and subsequent morbidity 1
• Avoid treatment gaps during chemoradiation as this compromises radiobiological effectiveness 1
• Do not proceed to salvage surgery without histological confirmation of recurrence 1, 5
• Do not overlook perianal fistulas before starting CRT, as they risk sepsis and treatment interruption 1
• Recognize that giant condylomas may harbor invasive carcinoma requiring complete surgical excision with negative margins 2

Multidisciplinary Team Approach

All patients with anal tumors should be referred and discussed in a multidisciplinary team meeting with pre-specified interest in anal cancer 1. The anal cancer surgeon should provide input from the outset for most patients, even though 80% are initially treated with CRT 1.