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Anal Neoplasms- Dysplasia to Cancer Paul A. Lucha Jr., D.O., FACOS, FAOCPr VAMC Salisbury, NC Introduction lHistology lMuscles of the anorectal region lAnorectal spaces lVascular anatomy lLymphatic drainage Anatomy lSurgical Anal Canal differs from anatomists description 4 cm length arises from anorectal junction terminates at anal verge lAnatomists Anal Canal l2-3 cm in length lbegins at the pectinate line lterminates at the anal verge Anatomy Anatomy lAnal Margin area caudal to anal canal Intersphinceric groove to approximately 5 cm circumference on the perineum non keratinized squamous epithelium keratinized squamous epithelium hair follicles and apocrine glands present Histology l6-14 Columns of Morgagni 4-10 anal glands at crypts Pathogenesis of fistula/ abcess (Parks 1961) 2/3 glands enter internal sphincter 1/3 cross into intersphincteric plane none penetrate the external sphincter Histology lTransition from columnar epithelium to squamous epithelium (6-12 cm above dentate line) transition zone (cloacogenic anal cancer) lAnal verge hair follicles present apocrine glands Muscles of the Anorectal Region lInternal Sphincter thickening of the circular smooth muscle fibers of the rectum extends 1-1.5 cm below the dentate line inervated by the pelvic autonomic plexus Muscles of the Anorectal Region lConjoined Longitudinal Muscle longitudinal muscle layer of the rectum joins with levator ani muscle complex descends between the internal and external sphincters Muscles of the Anorectal Region lExternal Sphincter somatic inervation lperineal branch of the 4th sacral nerve lInferior rectal nerve Muscles of the Anorectal Region lLevator Ani complex Puborectalis Iliococcygeus Pubococcygeus lInervated by 4th sacral nerve Muscles of the Anorectal Region Muscles of the Anorectal Region lanorectal ring junction of the rectum and anal canal composed of internal sphincter and puborectalis division results in incontinence Anorectal Spaces lischiorectal lperianal lintersphincteric lPostanal lsupralevator lretrorectal Anorectal Spaces lPostanal space connects with ischiorectal fossa bilaterally Vascular anatomy lanorectum has a profuse intramural vascular anastomotic network lthis prevents necrosis of the anus in low rectal resections Vascular anatomy lPortal and systemic venous drainage Lymphatic drainage lImportant in rectal cancer lImportant in anal cancer lImportant in anal margin cancer Innervation lSympathetic innervation L1, L2, L3 preganglionic lpreaortic plexus postganglionic lfollow branches of the IMA lenter via “lateral stalks” of the rectum Innervation lParasympathetic innervation S2, S3, S4 also called nervi erigenti upward path via IMA downward path follows the sympathetic postganglionic nerves Innervation lSexual function erection lparasympathetic and sympathetic ejaculation lparasympathetic emission lsympathetic Innervation lInternal anal sphincter Sympathetic lL5 Parasympathetic lS2, S3, S4 lLevator Ani complex S2, S3, S4 perineal branch of the pudendal nerve inferior rectal nerves (puborectalis) Innervation lExternal Anal Sphincter Inferior rectal branch of the pudendal nerve (S2, S3) and perineal branch of S4 lSensory- Inferior Branch Pudendal Nerve Meissners Corpuscles (touch) Krauses bulbs (cold) Golgi-Mazzoni bodies (pressure) genital corpuscles (friction) Concentrated at anal valve area ANAL CANCER OVERVIEW lCarcinomas in the anal canal account for about 1.5% of gastrointestinal cancers in the United States, and approximately 80% of these are squamous cell carcinomas (SCCs). lSCCs of the anus are frequently related to chronic infection with human papilloma virus (HPV) ANAL CANCER OVERVIEW lUsually occur in the sixth to seventh decade of life, occur in younger patients when they are immunocompromised lMale:Female=2:1 lHIV/AIDS, and the increasing use of immunosuppressive therapy for solid organ transplantation, inflammatory bowel disease and collagen vascular diseases has meant an increasing incidence of HPV infection and anal SCC. ANAL CANCER OVERVIEW Rare in general population, but high and growing in at-risk populations1 Men who have sex with men (HIV+/-) Women (HIV) Incidence Rates2, 3 Men who have sex with men (MSM) HIV- 35/100,000 HIV+ est 70/100,000 General Population 5 cm Distal visceral mets at presentation is rare but should be evaluated with CT of the abdomen and pelvis to assess for liver metastases, as well as the presence of nodal disease Chest X-ray can be performed for lung mets These tumors are generally slow growing and histologically are well differentiated with well-developed patterns of keratinization Treatment Options 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 (18% 63%) 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 Since it was introduced in the early 1970s, radiation therapy has become the mainstay of therapy for SCC of the anal canal and its application to tumors of the anal margin is increasing Local control rates for radiation therapy reported by T stage: T1, 50% 100%; T2, 60%100%; T3, 37%100% In patients with T1 or early T2 lesions, local excision or radiation therapy provides similar local control rates (60%100%) For less favorable lesions, chemoradiation is now used as the first-line therapy using a perineal field and inguinal fields, even without clinically detectable disease in the groin Pelvic lymph nodes are also treated for those patients with T3 and T4 tumors SCC of the Anal Canal All large-cell keratinizing, large-cell nonkeratinizing (transitional), and basaloid histologies Terms epidermoid, cloacogenic, and mucoepidermoid carcinoma are all encompassed in the SCC group SCC of the anal canal is 5 times more common than SCC of the anal margin Incidence is 1/10 that of rectal cancer The most common presenting symptom is bleeding occurs in 50% of patients with many complaining of anal pain Other symptoms include palpable lump, pruritus, discharge, tenesmus, change in bowel habits, fecal incontinence, and rarely, inguinal lymphadenopathy A small number of patients will be asymptomatic Unfortunately, most patients are diagnosed late, with up to 55% of patients being misdiagnosed at the time of presentation Evaluation PE should include a complete anorectal examination with external inspection of the anoderm, digital examination, anoscopy and proctoscopy and exam of inguinal areas Notation should be made of size, location, and mobility of the mass, associated perirectal lymphadenopathy 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, and invasion of adjacent organs as an adjunct to the physical examination 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. 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 5 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 40 Gy is administered) Serious late complications: anal necrosis, stenosis, and ulcerations, diarrhea, urgency, and fecal incontinence, cystitis, urethral stenosis, and sbo Dose-dependent effect on morbidity Requirement of a colostomy in 6%12% of patients-tumor size was the only risk factor Brachytherapy used alone with external beam is also effective Local control rates of 75%79% and 5-year survival of 61%65% 3%6% of patients had serious complications that required surgery Chemoradiation Therapy Introduction of by Nigro et al. in 1974 revolutionized the treatment of anal canal SCC demonstrated equivalent local control and survival rates with preservation of sphincter function and thus avoidance of a colostomy Described using 30-Gy external beam radiation with 5-FU and mitomycin C Complete pathologic response in 21 of 26 patients (81%) Since that time, has become the standard therapy for SCC of the anal canal Operative treatment for anal canal SCC was largely abandoned and reserved for those patients with persistent or recurrent disease after chemoradiation Cisplatin has replaced mitomycin C because it is a radiation sensitizer, is less myelosuppressive, and has been used for those patients who failed to respond to mitomycin C Follow-up No consensus has been reached on appropriate follow-up after treatment of SCC Generally agreed that early intervention for persistent disease and recurrent locoregional disease can lead to successful salvage therapy Routine examination with digital rectal examination and proctoscopy every 2 months in the first year, every 3 months in the second year, and every 6 months thereafter has been recommended Ultrasound examination has also become popular in detecting recurrence although the literature is mixed on its benefit CT scan or MRI performed after completion of chemoradiation may also be useful as a baseline for future comparison MRI is useful for distinguishing surrounding tissues and detecting persistent or recurrent disease 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 24%47% Positive margins, nodal disease at salvage, and persistent disease after chemoradiation have poorer outcomes Morbidity for APR in this setting is significant with an increased risk of perineal wound complications This has prompted the use of plastic surgery reconstruction using rotational or advancement flaps to promote healing The benefit of adjuvant chemotherapy after APR is currently unknown Clinically evident inguinal disease after chemoradiation of the primary tumor can be treated with radical groin dissection if radiation has already been administered Additional radiotherapy can be considered if maximal doses of radiation were not delivered Radical groin dissection in selected patients can result in a 5-year survival of 55% Distant metastases have been found in 10%17% of patients treated with chemoradiation, and are usually treated with systemic chemotherapy such as cisplatin or 5-FU for palliation If the metastases are isolated in the liver or lung and the primary disease is controlled, resection can be considered AJCC staging of SCC Primary tumor (T)Anal margin Anal canal TxTumor cannot be assessed Tumor cannot be assessed T0No evidence of primary tumorNo evidence of primary tumor TisCarcinoma in situ Carcinoma in situ T1Tumor 2 cm in greatest dimension Tumor 2 cm in greatest dimension T2Tumor 25 cm in greatest dimension Tumor 25 cm in greatest dimension T3Tumor 5 cm in greatest dimension Tumor 5 cm in greatest dimension T4Tumor invades deep structures (muscle, bone, cartilage) Tumor invades deep structures (vagina, urethra, bladder, but not sphincter) AJCC staging of SCC Nodal status (N)Anal marginAnal canal NxRegional lymph nodes cannot be assessed Regional lymph nodes cannot be assessed N0No regional lymph node metastasis No regional lymph node metastasis N1Regional lymph node metastasis present Perirectal lymph node metastasis present N2Unilateral internal iliac/inguinal lymph node metastasis present N3N1 and N2 and/or bilateral internal iliac and/or inguinal lymph node metastasis AJCC staging of