| Summary: | Background: Squamous cell carcinoma of the anus (SCCA) is increasing in incidence. High-grade squamous intraepithelial lesion (HSIL), its immediate precursor, arises in the mucosa or perianal skin. SCCA without mucosal involvement is rare and diagnostically challenging. This phenomenon has been described in the cervix after HSIL treatment. We describe six cases of submucosal SCCA. Methods: All patients with SCCA seen in our practice from February 2014 through February 2018 were included in this study. We described all six who presented without mucosal involvement. Results: Six patients developed submucosal SCCA. The first case occurred in 2009 and all subsequent cases occurred within the past three years. The median age at diagnosis was 58 (range 41–83) years, 4 were male, 5 were HIV+, and none had inflammatory bowel disease. Five patients had a prior or concurrent HSIL discrete from the SCCA.Two HIV+ patients (TJ and JG) developed SCCA within fistula tracts three years after initial abscess drainage. Two (JE and YW) developed submucosal SCCA after multiple HSIL ablations. Two HIV+ patients (LR and JP) developed submucosal SCCA remote from prior HSIL. LR was diagnosed with SCCA in a submucosal rectal nodule after hemorrhoid rubber band ligation and JP developed SCCA deep to the mucosa within an anal canal sinus tract diagnosed by PET/CT. Conclusions: We described 6 cases of SCCA without apparent mucosal involvement. One must maintain a high index of suspicion in high risk individuals with submucosal nodules or recurrent abscesses/fistulae. Previous anal procedures may increase risk for submucosal variant SCCA.
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