Anal squamous cell carcinoma with mucinous microcysts represents anal gland duct differentiation

The subtype of anal cancer known as squamous cell carcinoma with mucinous microcysts (SCC-MM) is recognised to portend a poorer prognosis. However, the clinical significance of identifying this subtype has been downplayed more recently because of the frequent admixture of other SCC subtypes with SCC-MM and subjectivity in diagnosing the latter. This study aimed to immunohistochemically assess an anecdotal observation that SCC-MM morphologically resembles anal gland ducts and to thus determine whether SCC-MM has a unique immunoprofile which could then assist its distinction from differential diagnoses.

Ten immunohistochemical markers were applied to five cases of SCC-MM, three cases each of basaloid SCC and conventional SCC of the anus, as well as physiological anal tissue including anal gland ducts and both transitional and squamous epithelia. Of the latter three, the immunophenotype of SCC-MM most resembled anal gland duct epithelium, whereas the immunophenotype of basaloid SCC most resembled transitional epithelium. SCC-MM differed from basaloid SCC by expressing MUC5AC, expressing GATA3 more diffusely and showing only peripheral p63 positivity.

SCC-MM represents anal gland duct differentiation and can be reliably distinguished from its closest and commonest differential diagnosis, basaloid SCC, by the histological identification of mucin containing cysts and by immunohistochemistry for MUC5AC, GATA3 and p63. This distinction may be clinically important for the prognostication and pathological staging of anal carcinoma in excision specimens.