Ain D48.5

• Recently, a clinical classification of perianal intraepithelial neoplasia has been proposed that is based on the classification of other intraepithelial neoplasias:
• bowenoid AIN
• erythroplaque AIN
• leukoplakic AIN
• ...crazy AIN.
• Classification by stadiums:
• AIN I, more likely the lower third of the anoderma.
• AIN II: Lower two thirds of the anoderm
• AIN III: Complete infection of the anoderma.

• Increased incidence of:
• HIV infection
• diminished CD4 cell count
• Smoking
• receptive anal sex
• positive history of genital warts, perianal warts, condylomata, CIN or vulvar intraepithelial neoplasia
• High risk groups:
• Homosexual or bisexual men, especially those with HIV infection
• Drug-using HIV-infected people.

• HPV infection is considered the leading cause of AIN. Anal intraepithelial neoplasias are associated with human papilloma virus infections. As in cervical carcinoma, high-risk HPV types 16 and 18 are the most frequently detected.
• HPV association:
• Low-risk types: HPV 6, 11, 42, 43, 44 (responsible for the development of condyloma acuminata).
• High-risk types: HPV 16, 18, 31, 33, 35, 39, 45, 50, 51, 53, 55, 56, 58, 59, 68 (responsible for anal, cervical, penile and vulvar carcinomas).

• Clinically, AIN is often described in international literature as scaly, whitish, erythematous, eczematous, papillomatous, papular, pigmented or fissured plaques. Induration and ulceration may indicate invasion.
• The significantly more frequent and often asymptomatic intraanal localized dysplasias can often only be detected by high resolution anoscopy (HRA). While the normal mucosa appears slightly shiny pink, granular, slightly fragile, differently keratinized or leukoplakic areas are suspicious for the presence of anal dysplasia. Typical HPV-associated, HSIL-suspects, vascular changes visible in the HRA are called "punctation" and "mosaiscism" in the English literature. While homogeneous terminal capillaries (in HRA) are typically found in condyloma acuminata, neovascularization with caliber fluctuations or vessel ruptures are indicative of dysplasia or invasive growth.

• The gold standard is high-resolution anoscopy with a conventional colposcope used in gynaecology. This is used for clinical inspection of the perianal region, anal canal, linea dentata (transformation zone) and distal rectum at 30x magnification.
• The analytical cytology is analogous to the cervical cytology, smears are stained according to Papanicolaou and classified according to the Bethesda classification into:
• ASCUS (atypical squamous cells of unknown significance)
• LSIL (low-grade squamous intraepithelial lesion)
• HSIL (high-grade squamous intraepithelial lesion).
• Cave! The material obtained by anal Papanicolaou smears or the grading based on it correlates relatively poorly with histologically confirmed lesions, depending on the cytologist. Suspicious areas must be biopsied, histopathological processing is considered the gold standard!

The differential diagnosis must include psoriasis inversa, lichen simplex chronicus, nummular eczema, epidermal naevi, flat condyloma acuminata and possibly also basal cell carcinoma, extramammary Paget's disease and malignant melanoma.

• Extensive lesions / high-grade AIN: excision with primary closure, possibly split skin grafts. However, this often leads to severe postoperative complications.
• Small lesions: cauterisation, erbium YAG or CO ₂ laser ablation, cryosurgery, podophyllotoxin, imiquimod.
• Cave! The less radical the therapy, the higher the risk of recurrence.
• In case of intraanal localisation, the indication for surgical intervention with the aim of complete removal should be given early (either electrocaustically or by excision). These measures should only be carried out in priority facilities set up for this purpose.
• Regular applications of Imiquimod cream (3 times/week for 16 weeks) seem to bring about a significant clinical improvement in homosexual men according to the study results (reduction of the HPV viral load and number of oncogenic HPV virus types).
• See below: 3 times vaccination with a quadrivalent HPV vaccine effectively reduced AIN morbidity in a larger study.

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