This document provides information on anal malignancies, including: - Anal cancer is uncommon but incidence has increased, making up 4% of anorectal malignancies. - The anal canal anatomy and blood supply are described. Risk factors for anal cancer include human papillomavirus infection, HIV/AIDS, immunosuppression, and smoking. - Symptoms typically include rectal bleeding, pain, or masses. Evaluation involves examination, imaging, and biopsy. Treatment is usually chemoradiation, while surgery is reserved for residual or recurrent disease. Prognosis depends on stage and response to treatment.

1. ANAL MALIGNANCIES
BY
Dr Franklyn Bagenda
3rd Year General Surgery Resident

2. INTRODUCTION
• Anal cancer is uncommon
• Incidence of anal cancer in the general population has
increased over the last 30 years
• makes up to 4% of all anorectal malignancies
• 1.5% of gastrointestinal malignancies.

4. ANATOMY

5. ANATOMY
• Anal canal is the caudal segment of large intestine
• Anal canal is approximately 4 cm in length and extends distally
to the point referred to as anal verge.
• Upper anal canal is lined by columnar tissue that transitions
into squamous epithelium at the dentate line
• Dentate line, identified by the termination of the anal columns,
lies 1 to 2 cm above the anal verge
• Squamous epithelium of anal canal is devoid of epidermal
appendages such as hair follicles, apocrine glands and sweat
glands.

6. CONT….
• Transformation Zone
• 0-12 mm in length
• Beginning at the dentate line
• Transitional urothelium-like epithelium in rectal
mucosa instead of columnar mucosa
• Squamous metaplasia may be found overlying
the normal columnar mucosa involving up to 10 cm
or more of distal rectal mucosa

7. • Arterial supply of the anus is
derived
• from branches of the superior
rectal artery,
• the inferior rectal branch of the
pudendal artery,
• branches of the median sacral
artery.

8. • Venous drainage of the anal
canal is divided into two
patterns
• Above the dentate line,
through the terminal
branches of the superior
rectal vein into the inferior
mesenteric vein and portal
system
• Below the dentate line via
the inferior rectal vein into
the pudendal vein which
itself drains into the internal
iliac vein

9. • Lymphatic drainage of anal cancers is
dependent upon the location of the lesion
with respect to the dentate line.
• Cancers arising proximal to dentate line
drain to perirectal and paravertabral
lymph nodes
• cancers distal to dentate line drain to
inguinal and femoral nodes.
• Lymph node involvement at diagnosis is
observed in 30%–40%
• systemic spread is uncommon with distant
extra-pelvic metastases 5%–8% at onset.

10. 4 distinct categories of tumors arise in the anal
region
Tumors that develop from any of the three types of mucosa
Tumors arising in the transitional or squamous mucosa are squamous cell
cancers
 Nonkeratinizing types of SCC
• Tumors arising within the anal canal distal to the pectinate (dentate) line are
often
Adenocarcinomas arising from glandular elements within the anal canal are
rare
Tumors arising within the hair-bearing skin at or distal to the squamous
mucocutaneous junction have been referred to as anal margin cancers

11. FACTS…
• The anal and cervical canal share embryologic, histologic, and
pathologic characteristics.
• Both develop from the embryonic cloacal membrane, and are sites
of fusions of endodermal and ectodermal tissue to form a
squamocolumnar epithelial junction.
• The pathology, risk factors, clinical manifestations, screening,
prevention, and treatment of anal squamous intraepithelial lesions
• biologic consequences of anal SIL are considered analogous to
those of cervical SIL.

13. RISK FACTORS
• Human papilloma virus infection
• HIV infection
• Chronic immunosuppression not due to HIV
• Multiple sexual partners
• Receptive anal intercourse
• Female gender
• History of cervical, vulvar, or vaginal carcinoma
• Smoking
• Crohn’s disease

14. HPV
• Human papillomavirus (HPV) is the most common sexually
transmitted
• HPV genotypes’ association with cancer risk .
• High-risk – This includes HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56,
58, 59, and 68
• Low-risk – 6, 11, 40, 42, 43, 44, 53, 54, 61, 72, 73, and 81
• Types 16 and 18 are the most commonly isolated HPV types

15. HPV PATHOGENESIS
• HPV DNA is commonly present in anogenital precancer and invasive
cancers, as well as oropharyngeal cancers
• Expression of the viral oncogenes E6 and E7 is consistently
demonstrated in lesional tissue
• The E6 and E7 gene products have transforming properties by their
interaction with growth-regulating host cell proteins
• Continued E6 and E7 expression is necessary to maintain the
malignant phenotype

16. • The two most important HPV proteins in the pathogenesis of
malignant disease are E6 and E7
• Following E6 binding of p53, p53 is degraded in the presence of
E6-associated protein
• allows unchecked cellular cycling, and has an anti-apoptotic
effect, permitting the accumulation of chromosomal mutations
without DNA repair
• E7 interacts with Rb protein via an E2F/Rb protein complex.
• The interaction of E7 with Rb may permit cells with damaged DNA
to bypass the G1 growth arrest

17. HIV infection
The effects of immunosuppression
 Promotes the persistence of HPV infection
Co-infection with human immunodeficiency virus (HIV)
may directly promote HPV-associated oncogenesis at the
molecular level

18. Sexual activity
• FEMALES
• 10 or more lifetime sexual partners
(RR 4.5)
• a history of anal warts (RR 11.7),
• genital warts (RR 4.6),
• gonorrhea (RR 3.3),
• cervical dysplasia (RR 2.3),
• sexual partners with a history of a
sexually transmitted disease (RR 2.4).
• MALES
• 10 or more lifetime sexual partners
(RR 2.5),
• a history of anal warts (RR 4.9),
• a history of syphilis

19. Chronic immunosuppression not due to HIV
• such as solid organ transplantation
• Among renal transplant recipients the risk of anogenital cancer may
be increased as much as 100-fold
• Chronic glucocorticoid therapy for the treatment of autoimmune
disease

20. Cigarette smoking
• Noted a statistically significant risk of anal cancer in
smokers, especially current smokers
• Significantly increased risk of anal cancer (RR 1.9 for
20 pack-years, RR 5.2 for 50 pack-years)
• Act as a cocarcinogen

21. Bowens disease
• SCCA in situ and HSIL
• Is frequently found as an incidental histologic finding after
surgery for an unrelated problem, often hemorrhoids
• Clinically unapparent but histologically reveals SCC in situ
• May present with complaints of perianal burning, pruritus, or
pain
• Physical examination may reveal scaly, discrete, erythematous,
or pigmented lesions
• In the immunocompetent , lt will progress to cancer

22. Bowen disease cont…
• Standard recommendation for lesions found
after hemorrhoidectomy is to return the patient to the OR for
random biopsies taken at 1-cm intervals starting at the dentate line
and around the anus in a clock-like manner
• Frozen sections establish the presence of Bowens disease and these
areas are widely locally excised with 1-cm margins
• A less radical approach involves taking patients to the OR and using
an operating microscope, acetic acid, and Lugols solution to
visualize and target for electrocautery destruction
• May also simply be locally excised
• The deep margin is kept equally close because wide local excision
seems of limited benefit and increases morbidity

23. CLINICAL FEATURES
 Rectal bleeding is the most common initial symptom 45
percent
Anorectal pain or the sensation of a rectal mass is present
in 30 percent
Bleeding from a mass
history of anorectal condyloma is present in approximately
50 percent of homosexual men
pruritus ani
bleeding erythematous eczematoid plaque

26. • At initial presentation, most patients have a T1 or T2 lesion and
fewer than 20 percent are node-positive. In a series of 270 patients
with anal canal SCC, the distribution of stage at diagnosis was as
follows
• T1 — 9 percent
• T2 — 51 percent
• T3 — 30 percent
• T4 — 10 percent
• Node-positive — 13 percent

27. PROGNOSIS
• 5 y survival-
• T1 — 86 percent
• T2 — 86 percent
• T3 — 60 percent
• T4 — 45 percent
• N0 — 76 percent
• N+ — 54 percent

28. Molecular prognostic factors
• High expression of p53 associated with decreased
DFS.
• Also local control rates are lower with increased p53
expression.
• High level of Ki 67 – longer DFS.

29. Evaluation
• PE should include a complete anorectal examination with
external inspection of the anoderm,
digital examination,
anoscopy
proctoscopy
exam of inguinal areas
• Notation should be made of size, location, and mobility of the
mass, associated perirectal lymphadenopathy

30. •In women, a pelvic exam should be done to look for any
associated lesions or invasion of tumor into the vagina
•Additional workup should include
an endoanal/endorectal ultrasound to assess
the depth of the tumor,
presence of perirectal lymph nodes,
invasion of adjacent organs as an adjunct to the physical
examination

31. • Enlarged lymph nodes can be reactive to
secondary inflammation and should be biopsied with
direct FNA or ultrasound-guided FNA
• Studies of sentinel lymph node biopsy may result in more
accurate staging but the actual impact on initial and subsequent
management remains unclear
• CT scan or MRI of the A/P can add to locoregional staging as
well as evaluating for liver metastasis
• CXR is used as a screening tool for lung lesions and, if
suspicious, a chest CT should be performed.

32. • Positron emission tomography (PET) scans are useful for assessing
persistent or residual disease after treatment
• Colonoscopy can exclude any associated lesions proximal to the
anal canal
• HIV test should be performed for those at higher risk
HIV-positive patients with CD4 counts lt200 need better
monitoring of opportunistic infections,

33. TREATMENT
• Traditionally consisted of surgical resection with wide
local excision for smaller-sized tumors and APR for
larger, invasive tumors
• Wide local excision alone results in high locoregional
recurrence rates
• Should be reserved for those lesions that can
be excised with a 1-cm margin, are Tis or T1, and
do not involve enough sphincter to
compromise function

34. Radiation Therapy
• Quite effective because this tumor is extremely radiosensitive
• Can be given as external beam radiation, brachytherapy, or in
combination
• Response is dose dependent--best chance of tumor eradication
with at least 54 Gy of external beam radiation
• When tumors are gt5 cm or lymph nodes are involved, the cure
rate decreases to 50%
• Better results with higher doses of radiation must be exchanged
with increased radiation-induced complications (when gt40 Gy
is administered)

36. Chemoradiation Therapy
•Introduction of by Nigro et al. in 1974 revolutionized the
treatment of anal canal SCC.
•Described using 30-Gy external beam radiation with 5-FU and
mitomycin C
•has become the standard therapy for SCC of the anal cancer.
•Operative treatment for anal canal SCC was largely
abandoned and reserved for those patients with persistent or
recurrent disease after chemoradiation

39. Treatment of Residual or Recurrent Disease
• Patients need to be restaged with a CT of the chest, abdomen,
and pelvis
• MRI may be useful to assess resectability of pelvic recurrence
• PET may help differentiate tumor from radiation-induced tissue
changes or other undetectable metastases
• APR can be performed for tumor localized to the pelvis with a 5-
year survival of 2447
• Positive margins, nodal disease at salvage, and persistent
disease after chemoradiation have poorer outcomes
• If the metastases are isolated in the liver or lung and the primary
disease is controlled, resection can be considered

40. SALVAGE SURGERY
• Locoregional failure in 30%
• ½ recurrence, ½ progression
• Salvage APR is associated with five- year survival rates from
24 to 58%
• Salvage Surge types:
APR = abdominoperineal resection
Pelvic exenteration = multiviseral resection
• WITH Urinary and fecal diversion

41. Prognostic variables
 Node positivity
Size of the resected tumor
Status of resection margins
An analysis of the pathologic data from patients
show
• lateral excision margin free of cancer
 > 1 mm - recurrence occurred in 25%
 < 1mm - recurrence occurred in

42. RECURRENCES
• Strictly, all local recurrences are due to residual
cancer.
• Salvage surgery offers a potential for long-term local
control and survival in roughly one third to one half of
the patients fit for surgery who do not have clearly
unresectable cancer or known extrapelvic disease.
• Need reconstructive surgery to close defects in
irradiated pelvic tissues should be considered.

43. ADENOCARCINOMA OF THE ANAL CANAL
• Adenocarcinoma arises from the columnar epithelium of the anal
canal and its incidence is low accounting for less than 5 % of all
anal malignancies.
• Extension of rectal cancer into the anal canal is the more common
presentation. Occasionally, adenocarcinoma may occur in patients
with ulcerative colitis or Crohn disease who have ileal pouch-anal
anastomosis.
• APR should be offered for early-stage disease.
• For locally advanced disease (T3 or any T with N + ), a
multimodality approach should be considered. Patients treated
with APR had significantly improved 5-year OS than those treated
with radiation alone.

44. MELANOMA OF THE ANORECTAL REGION
• Anorectal melanoma is rare and accounts for less than 3 % of all
malignant melanomas and less than 1 % of all anal canal tumors.
• The 5 -year OS rate is generally less than 20 % . The initial stage at
presentation largely determines OS.
• Local recurrence was lower in the APR group (29 % for APR; 5 8 %
for local excision) . However, there was no difference in OS
between the two groups ( 19 . 5 months for APR; 18 .9 months for
local resection ) .
• Most authors recommend local excision of anorectal melanoma if
adequate margins could be achieved.

46. THE END