EP497 - SMILE! You're On Camera (Via High-Resolution Anoscopy)

Purpose/Background: SMILE (stratified mucin-producing squamous lesions) is a very rare finding in the anal canal, and is considered a variant of adenocarcinoma in situ by the World Health Organization. Thus far, six cases of anal SMILE have been described and the current case is the first report of SMILE discovered during an office-based High Resolution Anoscopy (HRA).

Methods/Interventions: A 67 year old HIV+ MSM (well-controlled, CD4 1,090, undetectable viral load) was referred to the Anal Cancer Screening Clinic for evaluation of low-grade squamous intraepithelial lesion (LSIL) on anal cytology. HPV status was unknown. He had undergone two clinic-based HRA procedures in the past, revealing a combination of both low- and high-grade dysplasia. During his recent HRA, the exam revealed thickened pink mucosa and glandular islands with acetowhitening, minimal Lugol's uptake and diffuse punctation at the anal transition zone (ATZ), extending somewhat proximally into the distal rectum. The ATZ was irregular and difficult to define. The morphologic appearance of these lesions appeared consistent with high-grade dysplasia, and the lesions were thoroughly ablated following pinch biopsy.

Results/Outcomes: The pathologic diagnosis revealed AIN-3 admixed with stratified mucin-producing squamous lesions (SMILE) in two of three biopsied locations. The patient had an uneventful recovery and is currently asymptomatic, denying anorectal pain, itchiness, bleeding per anus, change in bowel pattern, fatigue, loss of appetite or weight loss. Special immunohistochemical stains were utilized to document the current diagnosis. P40 highlighted the dysplastic squamous cells, demonstrating nuclear positivity in squamous cells but p40 was negative in the mucin-producing cells. Mucicarmine stain was positive in the mucin-containing cells, highlighting the intracytoplasmic mucin vacuoles. P16 showed block-like diffuse positivity in the dysplastic epithelium.

Conclusion/Discussion: SMILE is an HPV-driven intraepithelial proliferation which is well documented in the uterine cervix but has been identified in the anus in only 6 cases. SMILE often coexists with other preinvasive lesions, and these types of cells can transdifferentiate throughout the carcinogenic process. SMILE shows a morphologic overlap with both squamous intraepithelial lesions (SIL) and adenocarcinoma in situ (AIS), indicating phenotype ambiguity and instability. There is no documented consensus on how to manage SMILE, although cervical SMILE is generally managed as an adenocarcinoma in situ. For patients found to have SMILE on cervical biopsy, surgical excision of a precursor lesion (area of biopsy-confirmed dysplasia) is recommended to clear the area of preinvasive disease and to ensure there is no evidence of invasive carcinoma. In prior reports of patients found to have anal SMILE, there was typically a visible polyp, mass or lesion which could be resected or removed. No distinct precursor lesions or polyps were seen during this HRA, making further treatment difficult. All visible abnormal lesions were ablated via HRA. Close surveillance and prompt intervention is crucial for prevention of progression to invasive carcinoma. For this patient, colonoscopy and short-interval HRA was recommended. Additional research is needed to determine how to identify and treat cases of anal SMILE.

Microscopic features of a stratified mucin-producing intraepithelial lesion (SMILE) of the anus
(A) H&E stain shows multilayered squamous epithelium resembling a squamous intraepithelial lesion (SIL), but with prominent intracytoplasmic mucin extending through the epithelial thickness. (B) Mucicarmine stain highlights the intracytoplasmic mucin vacuoles (magenta). (C) p40 immunostain demonstrates nuclear positivity in squamous cells, but is negative in the mucin-producing cells. (D) p16 immunostain reveals block-like diffuse positivity.

Original magnification, ×400.