Anal Cancer

Anatomy

LoadMedia.ashx.jpeg
  • 3 to 4 cm in length
  • Posterior wall being longer than the anterior
  • The superior margin —> puborectalis muscle of the anorectal ring
    • At this level, the rectal lumen narrows suddenly, and the anal canal passes inferiorly and posteriorly to its external opening, the anus.
  • The distal end —> Anal verge
    • where walls of the anal canal come into contact with true skin
  • Anatomical anal canal:
    • From anal verge to pectinate line
  • Surgical anal canal:
    • From anal verge to puborectalis m.
  • White line of Hilton: intersphinct. groove
    • Between levator ani m. and internal sphincter m.
  • Dentate line (pectinate line)
    • Ectodermal anal pit meet the endodermal anorectal canal
    • Dentate (pectinate) line is the juncture
  • Anal tumours:
    • Carcinomas at or above dentate line
  • Anal margin tumours:
    • Tumours lying below dentate line
  • Perianal carcinomas:
    • Cancers arising from the skin within a 5-cm radius of the anal verge

Histology:

  • Perianal skin:
    • Similar to hair-bearing skin elsewhere
  • At the anal verge
    • Modified squamous epithelium
    • No hair or glandular structures
  • Dentate or pectinate line:
    • A transitional epithelium that incorporates features of:
      • Rectal
      • Urothelial
      • Squamous epithelium

Lymphatic:

  • Intramural system links the anal LN to rectal LN
  • The perianal skin, the anal verge, and the canal distal to the dentate line
    • —> superficial inguinal nodes
    • Some communications to:
      • Femoral nodes
      • External iliac systems
    • Also inferior mesenteric
      • Peri-rectal
      • Sup hemorrhoidal LN
  • Above the dentate line:
    • Internal iliac
      • Internal pudendal
      • Hypogastric
      • Obturator nodes

The veins of the anal canal connect with both the systemic and the portal venous systems. Venous plexuses, which lie in and surround the mucosal and muscular structures of the anal wall, anastomose around the junction of the anal verge and distal canal. The veins draining the inferior parts of these plexuses communicate with the systemic venous system via the internal pudendal and internal veins, and those from the superior canal flow predominately to the inferior mesenteric vein and then to the portal system (50).

Anorectal continence is mediated by both cerebrospinal nerves and the autonomic system. The smooth muscle of the internal sphincter is supplied by parasympathetic fibers from the second, third, and fourth sacral segments as well as sympathetic fibers from the hypogastric plexus. The upper canal has selective sensitivity for intraluminal differences in pressure, and the autonomic nerves mediate both the inhibitor and facilitator reflexes of the internal sphincter. The striated muscle of the external sphincter is under voluntary control and innervated by the internal rectal nerve, a branch of the pudendal nerve arising from the second, third, and fourth sacral nerves. The internal rectal nerve also transmits pain, touch, and other sensations from the anal lining below the dentate line and from the perianal skin (50).

Pathology

  • Squamous Cell Carcinoma
    • large-cell keratinizing
    • large-cell nonkeratinizing
    • basaloid
    • Tumours arise from anal transitional zone= Cloacogenic Carcinoma
      • Mucoepidermoid
        • NOT similar to mucoepidermoid of salivary gland
      • transitional cell carcinoma
      • basaloid
  • Adenocarcinoma
    • Mostly distal rectal ca.
  • Small Cell Carcinoma
  • Undifferentiated Carcinoma
  • Primary anal melanoma
    • rare
    • African
    • distant spread
    • treatment
      • wide local excision or abdominoperineal resection
    • outcome:
      • 5yr survival —> 10%

Epidemiology

  • not very common
    • one-tenth as common as rectal ca
  • F > M
    • This difference is decreasing
  • Perianal cancers —> F=M
  • Median age at diagnosis is from 60 to 65 years.

Risk Factors

  • Most significant —>
    • Sexually transmissible viruses
      • HPV
        • Linked to cancer and precancerous lesions in the anogenital epithelium
      • Type 16 in particular
      • Lesser extent:
        • Types 18, 31, 33, 35
      • Have been found in about 85% of anal squamous cancers
    • Immunosuppression
    • Tobacco smoking

Other risk factors:

  • History of multiple sexual partners
    • Homosexual or heterosexual relationships
    • Unprotected anal intercourse in males and in females
      • In females —> before the age of 30

==> increased risk of AIN and invasive anal cancer

  • Incidence of anal ca in male homosexual population: 30 times more
    • ~20 per 100,000

Associated with:

  • HIV infection
    • Rate of HPV-associated cancers and precursors is increased in HIV-infected persons for all anogenital sites compared with the general population.
  • Iatrogenic suppression of immunity in organ transplant
    • 10-fold excess risk

Suppression of cell mediated immunity

  • Increased rates of HPV infection
  • Higher progression rates from normal epithelium to AIN
  • Lower rates of clearance of HPV and regression from abnormal to normal epithelium
  • Fistula, fissure IBD ARE NOT risk factors.

Natural History

  • HPV infection is an initiating event
  • Loss of heterozygosity at 11q23
    • Appears to be independent of HIV status
  • Invasive Ca develop from high grade AIN ( Anal Intraepithelial Neoplasia )
    • Only 1% of AIN
      • Less than cervical intraepithelial neoplasia
HIV+ HIV-
Trigger for progression toward invasive cancer microsatellite instability allele losses at chromosome regions harboring tumor suppressor genes

Pathways of tumour spread

  • Direct extension
    • Into sphincter muscles
    • Perianal connective tissue spaces
    • Vaginal involvement is more likely than prostate involvement.
      • Anovaginal fistula —> <5%
  • Lymphatic
    • Occurs early
    • ~25% at diagnosis
    • Superior hemorrhoidal nodes
    • External iliac
    • Obturator
    • Hypogastric
    • Inguinal —> 20%(clinical)
    • Chance of LN+
      • If tumour extends through sphincter —> 60%
      • If confined to anal canal —> 30%
  • Hematogenous is less common
    • <10% at time of diagnosis
    • May occur via:
      • Portal system
      • Systemic venous systems
      • Lymphatics
      • Liver and lungs

Overall 5-year cause-specific survival rates usually exceed 80%.

Overall 5-year survival rates are of the order of 55% to 65%.

  • Mostly locoregional (30%)
  • Extrapelvic (20%)

Clinical Presentation

  • Duration of symptoms: more than 6 months in a third of patients
  • Bleeding
  • Anal discomfort
  • Awareness of an anal mass
  • Pruritus
  • Anal discharge
  • Pain is uncommon but may be severe
  • Alteration in bowel habits

Small carcinomas are often nodular or plaquelike, but larger tumors are more typically ulcerated and infiltrative.

Ph/E:

  • General
    • Cachetia
    • Uncomfortable when sitting
    • Jaundice
    • Anemia/Pale
    • Performance status
  • Lymphadenopathy
    • Cervical
    • Supraclavicular
      • Virchow node
    • Axillary
    • Inguinal
  • Abdominal mass/pain/tenderness
  • Examinal of anogenital area:
  • Coexisting benign conditions
    • Anogenital warts
    • Hemorrhoids
    • Anal fissures
  • Anal sphincter tone
    • Usually preserved and may be increased by painful spasm
    • Gross fecal incontinence resulting from sphincter destruction—> < 5%
      • Some fecal soiling is common
  • Vaginal fistulas
    • Uncommon
  • BIOPSY
  • Exam under anesthesia
  • Proctoscopy
  • Sigmo-colonoscopy
    • R/O another malignancy
  • Investigations:
    • CBC
    • Blood Chemistry
      • Lytes
      • KFT
      • LFT
      • If high risk patient
        • HIV test
      • If young female
        • Pregnancy test
    • CT Abdo/Pelvis
      • R/O liver mets
      • Any pelvic/Abdo lymph node
        • Suspicious LN —> biopsy
      • Localize kidneys
        • R/O Pelvic horseshoe kidney
    • MRI Pelvis
    • CXR or CT chest
    • Transanorectal ultrasonography
      • Depth of tumor penetration into the anal wall
      • Presence of enlarged perirectal lymph nodes

Prognostic Factors

  • Most adverse factor for survival —> extrapelvic metastasis
  • For non-emtastatic disease:
    • Size of primary tumor
      • Most useful predictor for local control
      • Preservation of anorectal function and survival

Involvement of regional lymph nodes is an adverse factor for survival but not for control of the primary tumor

Other prognostic factors:

  • Women have a better prognosis
  • Hemoglobin levels ≤10 g/L at presentation
    • Correlation with poor local control and survival rates
  • Poor prognostic factors for local tumour control and survival and poor tolerance of treatment in HIV-positive patients:
    • High viral load
    • Low lymphocyte CD4+ counts
    • AIDS

Management of Anal Cancer