Challenging and newly emerging neoplastic diseases in anal canal and their mimics

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The anal canal is comprised of heterogenous elements, including colorectal epithelium in the upper portion, transitional epithelium in the middle portion, and squamous epithelium in the lower portion. This gives rise to a wide range of entities. The benign tumor/tumor-like conditions include hemorrhoids, hidradenoma papilliferum, and fibroepithelial polyps. The anal canal is also susceptible to dysplastic lesions associated with human papillomavirus (HPV) ranging from low-grade squamous intraepithelial lesions/condyloma acuminatum to high-grade squamous intraepithelial lesions. The latter being more commonly associated with high-risk HPV (HPV-16 and HPV-18). Buschke-Lowenstein tumors (BLT), a unique locally aggressive HPV associated neoplasm, are characterized by a pushing endophytic border with morphologic similarities to condylomas. These precursor HPV lesions can give rise to squamous cell carcinoma, the most common malignant neoplasm in the anus. Squamous cell carcinomas of the anal region have a wide morphologic spectrum including keratinization and basaloid appearance. A well-differentiated variant of squamous cell carcinoma, verrucous carcinoma, is locally aggressive and has a pushing border, similar to BLT. However, verrucous carcinomas are not associated with HPV. Other malignant neoplasms of the anus include adenocarcinoma, either primary to the anal glands, colorectal epithelium of the upper anus, or HPV-associated anogenital-type adenocarcinoma. A small subset of primary adenocarcinomas of the anus can give rise to Paget's disease, although Paget's disease can also arise as a primary neoplasm in the anal canal or spread from carcinoma of nearby anatomic sites. Overall, the morphologic pattern and immunohistochemical pattern of these entities can help distinguish between them.

Original languageEnglish
Article number300649
JournalHuman Pathology Reports
StatePublished - Jun 2022


  • Buschke-Lowenstein tumors
  • HPV-associated anogenital-type adenocarcinoma
  • Human papillomavirus
  • Paget's disease of the anal canal
  • Squamous cell carcinoma
  • Squamous intraepithelial lesion
  • Verrucous carcinoma


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