Primary Anal Canal Syphilis in Men: The Clinicopathologic Spectrum of an Easily Overlooked Diagnosis

Context The incidence of syphilis is on the rise, particularly in male patients who are human immunodeficiency virus (HIV) positive, and men who have sex with men. Objective To describe 4 cases of primary syphilis presenting in the anal canal to increase awareness of its presentation and morphology in this location, as the diagnosis can be easily overlooked clinically and by the pathologist. Design Clinical presentation, hematoxylin-eosin–stained sections, and Treponema pallidum immunohistochemical staining were reviewed in detail in all 4 cases. Results Three patients presented with anal canal ulcers; one presented with an ulcerated anal mass. All 4 patients were male, of whom 2 were HIV positive. Syphilis was clinically suspected in only 1 case; in 2 cases, confirmatory evaluation and treatment were prompted by pathologic diagnosis. In the fourth case, syphilis was diagnosed serologically at time of biopsy; however, the patient had an anal mass, and malignancy was clinically suspected. All 4 cases had bandlike chronic plasma cell–rich inflammation at the squamous epithelium and lamina propria junction; 2 cases had poorly formed granulomas. One case had concomitant rectal biopsy specimens with proctitis. Treponema pallidum immunohistochemistry highlighted homing of organisms in a perivascular pattern and at the junction of squamous epithelium and lamina propria. Conclusions Syphilis should be considered in the differential diagnosis of anal canal ulcers, anorectal inflammatory masses, and proctitis. Detailed knowledge of clinical history and recognition of the characteristic pattern of inflammation by the pathologist is important. Treponema pallidum immunohistochemical staining can help avoid a missed diagnosis of syphilis, which, if left unrecognized, can progress to late-stage disease with serious complications.