Ain D48.5

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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anal dysplasia; anal M. Bowen

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Acronym for "Anal Intraepithelial Neoplasia". AIN are incipient precursor lesions for squamous cell carcinomas of the anus. S.a.u. anal carcinoma, spinocellular carcinoma. S.a. CIN, PIN, KIN.

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  • 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.

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  • 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.

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  • 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).

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The main localization of anal intraepithelial neoplasia is the linea dentata (transformation zone), i.e. the transition from squamous to cylindrical epithelium. This zone is particularly vulnerable to infections with human papillomavirus.

Clinical features
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  • 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.

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Loss of normal skin stratification. Frequently nuclear polymorphisms, hyperchromatinization and koilocytosis. Barely inflammatory infiltrates. Basement membrane intact. S.a. Tab.

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  • 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!

Differential diagnosis
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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.

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  • 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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It has been shown that quadrivalent HPV vaccination (HPV6, 11, 16, 18) can effectively prevent HPV infections in men.

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Histological description


mild dysplasia

small cellular atypias, often koilocytes with enlarged irregular nuclei and halo


Moderate dysplasia

Replacement of up to 50% of the anode epithelium by narrow basaloid cells with increased nuclear plasma ratio


Severe dysplasia/carcinoma in situ

Replacement of > 50% of the anode epithelium by narrow basaloid cells with increased nuclear plasma ratio

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For HIV-patients: At least once a year anal inspection or proctoscopy; for patients with AIN II and AIN III regular follow-ups every 3 months. Biopsy controls!

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  1. Bontkes et al (1999) Immune responses against human papillomavirus (HPV) type 16 virus-like particles in a cohort study of women with cervical intraepithelial neoplasia. II Systemic but not local IgA responses correlate with clearance of HPV-16 J Gene Virol 80: 409-417
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  3. Daling JR et al (1987) Sexual practices, sexually transmitted diseases, and the incidence of anal cancer. N Engl J Med 317: 973-977
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  7. Giuliano
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  10. Holly EA (1989) Anal cancer incidence: genital warts, anal fissure or fistula, hemorrhoids, and smoking. J Natl Cancer Inst 81: 1726-1731
  11. Kreuter A et al (2005) Clinical spectrum and virologic characteristics of anal intraepithelial neoplasia in HIV infection. J Am Acad Dermatol 52: 603-608
  12. Kreuter A et al (2007) p16ink4a expression decreases during imiquimod treatment of anal intraepithelial neoplasia in human immunodeficiency virus-infected men and correlates with the decline of lesional high-risk human papillomavirus DNA load. Br J Dermatol 157: 523-530
  13. Kreuter A et al (2008) Imiquimod Leads to a Decrease of Human Papillomavirus DNA and to a Sustained Clearance of Anal Intraepithelial Neoplasia in HIV-Infected Men. J Invest Dermatol. 2008 Feb 14 [Epub ahead of print]
  14. Litle et al (2000) Angiogenesis, proliferation and apoptosis in anal high-grade squamous intraepithelial lesions. Dis Colon Rectum 43: 346-352
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  17. Palefsky JM et al (2011) HPV vaccine against anal HPV infection and anal intraepithelial neoplasia. N Engl J Med 365:1576-1585
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  19. Wieland U et al (2006) Imiquimod treatment of anal intraepithelial neoplasia in HIV-positive men. Arch Dermatol 142: 1438-1444


Please ask your physician for a reliable diagnosis. This website is only meant as a reference.


Last updated on: 29.10.2020