Anus & perianal area

• Rare adenocarcinoma that primarily involves the anal canal (not rectal adenocarcinomas with downward spread)

• Also known as perianal adenocarcinoma or perianal gland adenocarcinoma
• The term anal duct adenocarcinoma is not recommended

• 5% of anorectal malignancies (JCO Oncol Pract 2020;16:635)
• Slightly more common in white men (Cancer Med 2019;8:3855)

• Anus (by definition)

• May arise from anal glands, from congenital anorectal duplications or along a fistula tract (Dis Colon Rectum 1998;41:992)
• May demonstrate HPV 18 DNA but not HPV 16 DNA (Mod Pathol 1991;4:58)
• Accordingly, rare cases are linked to HPV infection and are positive for p16 (Mod Pathol 2020;33:944, Int J Surg Pathol 2021;29:672, Br J Cancer 2018;118:1302)
• Rare nonanal gland type, nonfistula associated anal carcinomas have recently been recognized (Pathol Int 2021;71:715)

• Proposed etiologic associations include chronic fistula, anal Crohn's disease and anal sexual intercourse (Semin Surg Oncol 1994;10:235)

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• May present in fistula tract or as a vaginal cyst
• Often a long history of perianal fistulas, abscesses, surgery
• Indolent course with gradual progression

• Poor prognosis associated with advanced T and N category disease and higher histologic grade (Int J Radiat Oncol Biol Phys 2003;56:1274)

• 42 year old man with anal tenderness (Medicine (Baltimore) 2021;100:e27083)
• 70 year old man with firm perianal nodule (BMJ Open Gastroenterol 2021;8:e000661)
• 72 year old man with Crohn's disease and perianal fistula (Cureus 2022;14:e31339)
• 84 year old man with adenocarcinoma arising from an anal gland (Int J Surg Case Rep 2014;5:234)

• Standard treatment includes abdominoperineal resection; adding chemotherapy and radiation improves outcome (Int J Radiat Oncol Biol Phys 2003;56:1274)

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• Anal canal tumors are nodular, ulcerated, 3 - 4 cm or more, invade deeply into wall and spread proximally and distally into submucosa of distal rectum and proximal anus

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• Adenocarcinomas with an intestinal type appearance involving the anus are likely of rectal origin and should be regarded as such
• True anal gland adenocarcinomas form haphazardly dispersed small glands with scant mucin production that invade the wall of the anorectal area without an intraluminal component (Cancer 2001;92:2045)
• Fistula associated adenocarcinomas are often mucinous (> 50% of tumor volume consists of mucin); granulomatous reaction to mucin may be present
• May contain melanin pigment, perhaps due to tumor cell phagocytosis of melanin from melanocytes (Am J Surg Pathol 1981;5:711)
• Single neoplastic cells may colonize the overlying and adjacent squamous mucosa (Paget disease)
• HPV related cases show papillary or villiform structures lined by columnar cells that often contain abundant mucin (Mod Pathol 2020;33:944)

Contributed by Raul S. Gonzalez, M.D.

• CK7, MUC5AC (Cancer 2001;92:2045, Med Mol Morphol 2007;40:50, Hum Pathol 2012;43:216)

• Stanford University: Adenocarcinoma of the Anus [Accessed 8 March 2023], WHO Classification of Tumours Editorial Board: Digestive System Tumours, 5th Edition, 2019

Which of the following is true about primary anal adenocarcinoma?

1. Advanced stage cases paradoxically have a better prognosis
2. It can arise in a fistula tract
3. It is more common in women
4. It is more common than secondary involvement by rectal carcinoma

B. It can arise in a fistula tract. This may occur in patients with Crohn's disease. Overall, anal adenocarcinoma is more common in men and advanced stage indicates poor prognosis. It is rare and secondary anal involvement by rectal carcinoma is more common.

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Reference: Anal adenocarcinoma

Primary anal adenocarcinoma is usually positive for which of the following immunohistochemical stains?

1. CDX2
2. CK7
3. CK20
4. p16

B. CK7. Only rare cases of anal adenocarcinoma are positive for p16. Rectal carcinoma involving the anus is positive for CDX2 and CK20.

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Reference: Anal adenocarcinoma