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Anal Cancer

Anal Cancer. Seema Izfar, MD 3/21/12. New Anatomic Considerations. 5290 new cases of anal cancer in 2009 classification published by American Joint Committee on Cancer Staging Manual three regions: anal canal, perianal skin, skin. Anatomy.

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Anal Cancer

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  1. Anal Cancer • Seema Izfar, MD • 3/21/12

  2. New Anatomic Considerations • 5290 new cases of anal cancer in 2009 • classification published by American Joint Committee on Cancer Staging Manual • three regions: anal canal, perianal skin, skin

  3. Anatomy • anal canal lesions cannot be visualized at all or incompletely visualized • perianal lesions are completely visible and fall within 5 cm radius of the anus • skin lesions fall outside of the 5cm radius • transition zone - 0-12mm from dentate line, transition “urothelium-like” epithelium, squamous metaplasia, columnar mucosa - can extend up 10cm • area susceptible HPV (HPV16)

  4. Lymphatic Drainage • above dentate line - superior rectal lympatics to inferior mesenteric lymph nodes and laterally to internal iliac nodes • below dentate line - inguinal nodes, may involve inf or super rectal lymph nodes

  5. Etiology and Pathogenesis of Anal Dysplasia and Anal Squamous Cell Carcinoma • HPV necessary but not sufficient for development of SCC and SIL • malignant potential serotypes 16, 18, 31, 33, 35 • virus pools at base of penis/scrotum and from vagina to anus - transmission only prevented from abstinence • anal intercourse associated with increased transmission to intra-anal diseases though no necessary

  6. Etiology and Pathogenesis of Anal Dysplasia and Anal Squamous Cell Carcinoma • disruption of normal mucosal barrier - anal intercourse, prolapse/hemorrhiods, STDS, anorectal trauma - can encourage extension into basal and parabasal cells • transitional zone cells are “immature” and susceptible without trauma

  7. Etiology and Pathogenesis of Anal Dysplasia and Anal Squamous Cell Carcinoma • cell-mediated immunity - prevent chronic infection • decreased IL-2 and helper T function seen in cervical dysplasia • increased anal CA risk noted in transplant and HIV pts

  8. Oncogenetics • accumulation of genetic errors needed for cancer transformation • E6 (early virus gene) binds p53 to E6AP and leads to degradation and unblocks p53 • E2 protein allows HPV to avoid intracellular detection • E7 binds Rb tumor suppressor • genetic errors --> accumulate, proliferate

  9. SIL detection • visible with acetic acid and Lugol’s solution - targeted destruction may decrease anal CA incidence • cost-effectiveness of anal cytology screening in HIV positive and homosexual men demonstrated • recommend screening every 2-3 yrs in HIV neg gay males and annually for HIV positive males

  10. HIV and anal CA • HAART suggest association with HIV and anal CA • HIV+ more likely to have HSIL, more likely to progress fro LSIL to HSIL, increased in pts with CD4 ct < 200

  11. Epidemiology • incidence of SCC in US rising over last 30 yrs • most alarming age-adjusted risk in SF: white men 40- 64 with 3.7/100000 in ‘70s to 20.6/100000 in ‘90s • in women, also increased risk of cervical CA • risk factors: HIV, high-risk genotypes 16, 18, 31, 33, 35, cigarette smoking, anal intercourse, immunosuppression

  12. High-Grade Squamous Intraepithelial Lesions • formerly known as Bowen’s disease • in immunocompetent pts, <10% progress to cancer • recommend treatment except in advanced AIDS • no associated with other visceral malignancies

  13. High-Grade Squamous Intraepithelial Lesions • Treatment - old recommendation: random biopsies at 1cm intervals starting at dentate line - wide local excision with 1cm margins if HSIL positive • good local control, did no present recurrence • recurrence as high as 23% • 11% incontinence or stenosis

  14. High-Grade Squamous Intraepithelial Lesions • less radical approach: high-resolustion anoscopy • microscope, lugol’s, acetic acid - still with high-recurrence but less morbid • other less studied techniques: 5-FU cream, Imiquimod, photodynamic therapy, laser, radiation

  15. Perianal SCC (Anal Margin) • resemble SCC of other areas of the skin • present in 7th decade, equal M/F • often misdiagnosed - can resemble pruritus ani, eczema, fissure, hemorrhioes, etc

  16. Perianal SCC (Anal Margin) • Staging based on tumor size and lymph node involvement • distant visceral mets rare but should be evaluated with CT A/P, CXR • Treatment: wide local excision, APR for larger tumors

  17. Perianal SCC (Anal Margin) • wide local excision with high recurrence (18-63%) • radiation use increasing - T3/T4, perineal or inguinal lymph nodes • local control with radiation: T1: 50-100%, T2: 60-100%, T3: 37-100% • recurrence after radiation treated with salvage excision • chemoradiation not well-examined - some show superior

  18. Squamous Cell Carcinoma of the Anal Canal • 5x more common than perianal SCC • terms epidermoid, cloacogenic, and mucoepidermoid • most common symptom: bleeding, anal pain • staging with CT/MRI, U/S +/- FNA, CXR, sigmoidoscopy • need HIV testing

  19. Squamous Cell Carcinoma of the Anal Canal • staging based on size of tumor and lymph node mets • inguinal mets in 10-30% of pts at time of diagnosis • lymphatics - above dentate to superior rectals, at dentate to obturator, internal iliac and internal pudendal, below to inguinal, femoral, and external iliac • distant visceral mets 10-17% - liver, lung, bone subQ

  20. Squamous Cell Carcinoma of the Anal Canal • historically treatment with APR • local recurrence 27-47%, 5-yr survival 40-70%

  21. Squamous Cell Carcinoma of the Anal Canal • Radiation: dose-dependent response with best tumor eradication at 54Gy - benefit lost if split-course • local control in 70-90% with 60-70% retained sphincter function • comp: anal necrosis/stenosis, ulceration, diarrhea, urgency, incontinence, cystitis, SBO, urethral stenosis

  22. Squamous Cell Carcinoma of the Anal Canal • Chemoradiation: Nigro 1974 - originally 30Gy external beam radiation with 5-FU and mitomycin C with complete response in 81% • cisplatin gaining favor over mitomycin C - less myelosuppressive, fewer toxicities (may have higher rate of colostomy though) • lymph node mets: radiation vs. chemorads vs LN dissection • subclinical nodes: chemorads 30-34 Gys

  23. Squamous Cell Carcinoma of the Anal Canal • follow up every 3 mos x 2 yrs and every 6 mos x 5 yrs • recurrent or persistent disease: re-stage, MRI vs CT, salvage surgery with APR • distant mets treated with systemic chemo (5-FU or cisplatin) • isolated liver and lung mets, consider excision

  24. Uncommon Anal Canal Neoplasm • Adenocarcinoma - 3 types: • transitional zone (indistinguishable from rectal adenoCA), • mucin-secreting columnar (base of anal glands), • develop from chronic anal fissure • wide-local excision vs APR, poss better survival with chemorads

  25. Uncommon Anal Canal Neoplasm • Melanoma- anorectal bleeding most common symptom - also anal pain, tenesmus, change in bowel habits • anorectum most common site for GI malignancy but only 0.5-5% malignancies of anorectum • recommend APR if bulky tumor or depth >4mm • some advocate local excision as anal melanoma largely fatal and APR morbid

  26. Uncommon Anal Canal Neoplasm • GIST - only 17 cases reported in literature • CD34 and CD117 positive • 5th-7th decade of life, male predominant • treatment with WLE for tumors <2cm and APR for lesion >5cm, high mitotic counts, pleomorphism, infiltration • success of Gleevac in treating other GISTS may translate

  27. Uncommon Anal Canal Neoplasm • Paget’s Disease - 2 groups, mammary and extramammary • represents intraepithelial adenocarcinoma • rare - fewer than 200 cases reported • lesions appear erythematous and eczematous • histology - hyperchromic nuclei, vacuolated cytoplasm, positive acid-Sciff stain

  28. Uncommon Anal Canal Neoplasm • Pagets: incidence of associated visceral malignancy 30-50% • treatment with WLE for noninvasive lesions • map with random biopsies, within 1cm of lesion, 4 quadrant • pts with invasive component consider for APR

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