Squamous Carcinoma of the Anus

Differential Diagnosis

Squamous Carcinoma of the Anus	Colorectal Squamous Carcinoma
Must involve anal canal	Must not involve the anal squamous mucosa

Some require that colorectal SCC be at least 5-7 cm from the anus

Squamous Carcinoma of the Anus	Perianal Squamous Carcinoma
Must involve anal canal	≤5 cm from anal verge and entirely visible outside the anal canal on clinical examination

Perianal carcinomas have a better prognosis of 85-90% 5 year survival vs. 65-80% for anal squamous carcinomas

High risk HPV may be seen in both

Squamous Carcinoma of the Anus, Predominantly Basaloid	Basal Cell Carcinoma of Perianal Skin
Involves anal canal	Extremely rarely involves anal canal
May have adjacent squamous carcinoma in situ	No relationship to carcinoma in situ
Frequent necrosis	Necrosis infrequent
BerEp4 and smooth muscle actin negative	BerEp4 and smooth muscle actin positive reported up to 100%
AE1, CK22, CEA, EMA positive 80-100%	AE1, CK22, CEA, EMA negative

Squamous Carcinoma of the Anus, Predominantly Basaloid	Adenocarcinoma of the Anus, Poorly Differentiated
CK5/6 and p63 virtually always positive	CK5/6 and p63 negative
CK20 negative	CK20 positive if rectal type; negative if perianal gland type

High risk HPV may be seen in both

Verrucous Carcinoma of the Anus	Usual Squamous Carcinoma of the Anus
Only blunt pushing invasion	Jagged invasion
No more than mild dysplasia	Usually significant dysplasia
Mitotic figures confined to basal layer unless inflamed	Mitotic figures may be present at all levels
No vascular or perineural invasion	May have vascular or perineural invasion
Does not metastasize	May metastasize

Note that usual squamous carcinoma can develop in verrucous carcinoma

Squamous Carcinoma of the Anus	Poorly Differentiated Neuroendocrine Carcinoma, Small Cell (Undifferentiated) Type
CK5/6 and p63 virtually always positive	CK5/6 and p63 negative
CK7 variably positive	CK7 negative

Squamous Carcinoma of the Anus	Poorly Differentiated Neuroendocrine Carcinoma, Large Cell Type
CK5/6 and p63 virtually always positive	CK5/6 and p63 negative
At most, scattered neuroendocrine marker positivity	Synaptophysin, chromogranin or CD56 extensively positive
Nests of cells with peripheral palisading	At least focal trabeculae, rosettes and/or stippled chromatin