Dysplasia of the Anus

Definition

• Non-invasive neoplastic changes of anal mucosa

Alternate/Historical names:

• Low grade squamous intraepithelial lesion (LSIL):
• Low grade dysplasia
• Anal intraepithelial neoplasia grade I (AIN I)
• Anal squamous intraepithelial lesion grade I (ASIL I)
• High grade squamous intraepithelial lesion (HSIL):
• AIN II or III
• ASIL II or III
• Bowen disease
• Carcinoma in situ
• High grade or severe dysplasia
• Moderate dysplasia

Covered separately

• Condyloma acuminatum

Diagnostic Criteria

• Superficial, non-invasive lesion of squamous mucosa or skin
  • May be flat or occur within a condyloma acuminatum
• Low grade squamous intraepithelial lesion (LSIL)
  • Frequently limited to superficial koilocytosis
    • Perinuclear clearing
    • Hyperchromatic “raisinoid” nuclei
      • Irregular nuclear membrane
      • May be binucleate
  • Orderly maturation
  • Low nucleus/cytoplasm ratio < 1:1
  • Mitotic figures basal unless inflamed
    • No atypical mitotic figures
  • Dyskeratosis may be present
• High grade squamous intraepithelial lesion (HSIL)
  • Includes both moderate and severe dysplasia, AIN2 and AIN3
  • We require the following
    • Full thickness atypia
      • Disorderly maturation
      • Nucleus/cytoplasm ratio ≥ 1:1
    • Mitotic figures in upper levels
      • Atypical mitotic figures may be present
• The usual condyloma demonstrates low grade squamous intra-epithelial lesion (LSIL)
  • Koilocytes are, by definition, at least LSIL
  • High grade squamous intra-epithelial lesion (HSIL) may also be seen
• Invasive carcinoma may be associated with HSIL
• Incidence reported to be 5-25%

Original posting/updates : 10/7/10

Supplemental studies

Immunohistochemistry

• Staining for p16 is a useful surrogate for the presence of high risk HPV
  • 82% sensitive
  • 100% specific vs. hyperplasia and reactive atypia
  • Does not distinguish low from high grade lesions
    • More often seen in high than low grade lesions, but
    • Low grade lesions containing high risk HPV will be positive
      • Significance of this is not known
  • Positive reaction requires strong, band-like staining
    • Both nucleus and cytoplasm usually stained

Genetic analysis

• Human papilloma virus (HPV) can be demonstrated by PCR
  • Low grade lesions including condyloma acuminatum usually HPV 6 and 11
  • High risk HPV is present in virtually all HSIL and invasive anal squamous carcinomas
    • May be absent in some poorly differentiated invasive carcinomas
  • Frequently HPV 16

Differential Diagnosis

• Reactive atypia
• Extramammary paget disease
• Bowenoid papulosis
• Condyloma with podophyllin effect

• Condyloma with podophyllin effect should be distinguished from HSIL
• Podophyllin does not produce:
• Cytologic dysplasia
• Disturbance of maturation
• Dyskeratosis
• Early podophyllin effects (≤48 hours post application)
• Intra- and intercellular edema
• Necrotic keratinocytes in lower half of epithelium
• Numerous mitotic figures in lower half of epithelium
• Changes resolving by 72 hours
• Necrotic keratinocytes now in upper half of epithelium
• Fewer mitotic figures
• Changes entirely resolved by one week

Clinical

• Patients at high risk of developing dysplasia or carcinoma include those with:
  • Immunosuppression
    • HIV seropositivity and low CD4 counts
    • Solid organ allografts
  • History of lower genital tract neoplasia
  • Persistent high-risk HPV genotype infection or infection with multiple HPV genotypes
  • Heavy cigarette smoking
  • Frequent anoreceptive intercourse
  • Radiation
    
• HSIL is generally treated by local excision
  • Frequently recurs (30% in 5 years)
  • We consider HSIL or the presence of high risk HPV to be an indication for high resolution mapping and targeted ablation or resection
  • We consider LSIL in high risk patients to justify topical therapy with surveillance

Grading / Staging / Report

Grading

Staging

• HSIL is staged as Tis

Report

• Should offer alternative terminology for the level of dysplasia if required by the submitting physicians
• If the dysplasia is present within a condyloma acuminatum the diagnosis should reflect the level present, e.g.:
  • Condyloma acuminatum (LSIL), or
  • Condyloma acuminatum, no evidence of high grade dysplasia

Classification / Lists

Anal Tumors and Neoplasms

• Adenocarcinoma
• Condyloma
• Dysplasia / HSIL / LSIL
• Extramammary Paget disease
• Fibroepithelial polyp / skin tag
• Melanoma
• Squamous carcinoma
• Verrucous carcinoma

Extension from rectal lesions must be ruled out

Bibliography

• Hamilton SR, Aaltonen LA eds. Pathology and genetics of tumours of the digestive system. World Health Organization classification of tumours, Vol. 2. Lyon: IARC Press 2000.
• Longacre TA, Kong CS, Welton ML. Diagnostic problems in anus pathology. Adv Anat Pathol. 2008 Sep;15(5):263-78.
• Wade TR, Ackerman AB. The effects of resin of podophyllin on condyloma acuminatum. Am J Dermatopathol. 1984 Apr;6(2):109-22.
• Kong CS, Balzer BL, Troxell ML, Patterson BK, Longacre TA. p16INK4A immunohistochemistry is superior to HPV in situ hybridization for the detection of high-risk HPV in atypical squamous metaplasia. Am J Surg Pathol. 2007 Jan;31(1):33-43.
• Sarmiento JM, Wolff BG, Burgart LJ, Frizelle FA, Ilstrup DM. Perianus Bowen's disease: associated tumors, human papillomavirus, surgery, and other controversies. Dis Colon Rectum. 1997 Aug;40(8):912-8.
• Rüdlinger R, Buchmann P. HPV 16-positive bowenoid papulosis and squamous-cell carcinoma of the anus in an HIV-positive man. Dis Colon Rectum. 1989 Dec;32(12):1042-5.