Anus and perianal area - Printer Friendly Version
Copyright © 2004-2007, PathologyOutlines.com, Inc.
Revised 2 July 2007
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Table of Contents
Primary references, normal anatomy, normal histology, congenital defects
Inflammatory diseases: Crohn’s disease, fissure, fistula, granuloma inguinale, HIV, lymphogranuloma venereum, lymphoid polyp, ulcer, ulcerative colitis
Benign/non-neoplastic lesions: granular cell tumor, hemorrhoids, hypertrophic HSV, hypertrophied papillae, Hirschsprung, inflammatory cloacogenic polyp, internal anal sphincter achalasia, leiomyoma, lipoma, radiation proctitis, tailgut cyst
Premalignant lesions: condyloma acuminatum, dysplasia
Carcinoma: general, adenocarcinoma, basal cell, clear cell, highly differentiated squamous lesion, metastases, Paget’s disease, sarcomatoid, small cell, squamous cell, verrucous
Other malignancies: carcinoid, embryonal rhabdomyosarcoma, gastrointestinal stromal tumor, histiocytic sarcoma, leiomyosarcoma, lymphoma, melanoma
Miscellaneous: staging, features to report
American Journal of Surgical Pathology (AJSP), March 1977 to April 2005
Archives of Pathology and Lab Medicine (Archives), October 1975 to March 2005
Human Pathology (Hum Path), March 1970 to February 2005
Modern Pathology (Mod Path), January 1988 to March 2005
AJCC Cancer Staging Manual (6th edition), 2002
Rosai, J: Ackerman’s Surgical Pathology (9th edition), 2004
Sternberg, S: Diagnostic Surgical Pathology (4th edition), 2004
Sternberg: Histology for Pathologists (2nd edition), 1997
Journal search terms: anus, anal, proctitis
Please refer to these primary references for more detailed discussions and photographs
Anal canal is a tubular structure 3-4 cm long
Derives from cloaca (distal hindgut); divided embryologically by urogenital septum (cloacal membrane) into anterior GU and posterior GI compartments; separated from perianal ectoderm by anal membrane, which ruptures at week 7 of gestation
Begins at level of prostatic apex, is directed downward and backward, and ends at anus
Classic anatomic definition of anal canal: between proximal and distal margins of internal sphincter muscle, which includes part of rectum
AJCC definition of anal canal: anal canal begins where rectum enters puborectalis sling at apex of anal sphincter complex (palpable as anorectal ring, but difficult for pathologists to identify), ends at squamous mucocutaneous junction with perianal skin; includes 1-2 cm of rectal-type glandular mucosa and possibly transitional mucosa at the dentate line
Histologic definition of anal canal: anal transitional zone and squamous epithelium down to the perianal skin; cannot be identified by clinicians
Note: “columns”, “valves” and “sinuses” below are macroscopic landmarks, which may not correspond precisely to microscopic structures
Anal columns of Morgagni: longitudinal folds just distal to dentate line, analogous to lower rectum’s rectal columns of Morgagni; less pronounced in adults
Anal crypts of Morgagni: minute pockets with anal valves as boundary; site of discharge of anal glands
Anal cushions: normal structures of anal canal that contribute to anal closure by close apposition to each other; contain blood vessels, connective tissue, smooth muscle; vessels contain abundant smooth muscle; resembles erectile tissue due to numerous arteriovenous communications
Anal papillae: raised toothlike projections on anal columns; extend proximally into rectum
Anal sinuses of Morgagni: depressions between anal columns
Anal valves: also called semilunar valves or transverse plicae; connect distal ends of anal columns; identifiable in children, often obscured in adults
Anal verge: also called Hilton’s line or anal margin; junction between anal canal and anal skin; has cutaneous adnexae
Corpus cavernosum recti: network formed by peculiar vessels with a complex convoluted appearance
Dentate (pectinate) line: midpoint of anal canal, formed by anal valves; circumferential
Musculature of anal canal
Muscularis mucosa: continues from rectum through upper anal transitional zone; presence of muscle fibers in lamina propria indicates mucosal prolapse syndrome
Musculus submucosae ani: fibers from intersphincteric longitudinal muscle which pass through internal sphincter and from the internal sphincter itself; form a network around the vascular plexus
Internal anal sphincter: continuation of circular muscle of rectum, but thicker (5-8 mm); ends 5-19 mm below dentate line
Intersphincteric longitudinal muscle: between internal and external sphincters; contains fibers from longitudinal muscle layer of rectum and levator ani muscles; distally breaks up into septa that diverge fanwise through subcutaneous layer of external sphincter and ends in corium, which forms characteristic corrugation of perianal skin
External anal sphincter: has superficial, subcutaneous and deep parts; provides voluntary control of defecation
Regional lymph node drainage: above dentate line - anorectal, perirectal, paravertebral nodes; below dentate line - superficial inguinal nodes
Arterial supply: superior, middle and inferior rectal arteries
Venous supply: superior rectal vein
Lacks a peritoneal covering
Three histologic types: glandular (proximal), transitional (also called intermediate, cloacogenic) and keratinized or nonkeratinized squamous (distal)
Proximal colorectal zone: top of puborectalis to dentate line; glandular and transitional mucosa; 1-2 cm long; similar to rectal mucosa but with shorter more irregular crypts, more smooth muscle fibers in lamina propria
Anal transitional zone (ATZ): 0.3 cm to 1.1 cm; zone between uninterrupted columnar mucosa above and uninterrupted squamous epithelium below; wrinkled glistening appearance; transitional epithelium resembles urothelium (small basal cells with nuclei perpendicular to basement membrane, columnar, cuboidal, polygonal or flat) with 4-9 cell layers, minimal mucin production; may have features of squamous epithelium; contains anal glands in submucosa, also endocrine cells, rare melanocytes; expresses CK7 and CK19 but not CK20
Lower distal zone: dentate line to squamous mucocutaneous junction: nonkeratinizing squamous epithelium without skin appendages, without glands; contains melanocytes; anal papillae contain squamous mucosa that joins rectal mucosa; squamous mucosa merges with perianal skin (with keratin, hair follicles and apocrine glands) at anal verge / anal margin
Anal glands and transitional zone epithelium are CK7+/CK20-, different from colorectal carcinoma (CK7-/CK20+, Archives 2001;125:1074)
Notes: ganglion cells are normally absent 1-2 cm above dentate line (important for Hirschsprung’s disease biopsies); multinucleated stromal cells are common (may be fibroblasts)
References: Hum Path 1978;9:579
Occur in one per 5,000 births
High (supralevator) anomalies (40%); also called anorectal agenesis; no anal canal, rectum ends above levator ani muscle; causes severe obstruction; associated with anomalies in vertebrae and urinary tract, defective innervation of pelvic muscles, fistulas from rectum to bladder, urethra or vagina; complicated surgery is needed for reconstruction
Low (translevator) anomalies (40%): includes ectopic (perineal, vestibular or vulvar) anus, anal stenosis and covered (imperforate) anus [failure of cloacal diaphragm to rupture]; simple surgery is curative; no severe obstruction, no/rare associated anomalies, normal pelvic innervation
Intermediate anomalies (15%): includes anal agenesis (may be associated with Larsen’s syndrome, Hum Path 1991;22:1055), anorectal stenoses, anorectal membrane; need complicated surgery
Other (5%): perineal groove, persistent anal membrane
Also persistence of cloaca (bladder, genital tract and bowel empty into single narrow channel that opens onto perineum with small orifice)
Exstrophy of cloacal membrane described at Archives 1987;111:157
Inflammatory diseases
Anal canal involved in 25% or more of patients with small intestinal Crohn’s and 75% with colonic Crohn’s
Symptoms: fissures, fistulas, ulcers, abscesses, skin tags
Anal complaints are usually not the presenting symptom
May be associated with malignancy late in disease course
Lesions are suspicious for Crohn’s if present in young person with no other cause for fistula or fissure and characteristic small tight granulomas near mucosa; but cannot diagnose only with anal symptoms; internal fistulas are relatively specific for Crohn’s disease
Micro: small, tight granulomas without necrosis near mucosa; may lack multinucleated giant cells
DD: disseminated tuberculosis (usually caseating granulomas, may be acid-fast positive for bacilli, positive cultures), foreign body granulomas
Single linear separation of anal canal tissue extending through mucous membrane
Often post-traumatic, midline
90% at posterior commissure overlying sphincter bifurcation as it divides to circle the rectum
No specific histologic findings
Abnormal tract that opens within anal canal, usually at or above dentate line
Usually leads to skin, may end blindly in perianal soft tissue
Usually caused by abscess in anal duct; may be associated with Crohn’s disease (complex fistulas with irregular edges), ulcerative colitis, actinomycosis, tuberculosis (lung disease usually present)
Micro: tract lined by granulation tissue with acute and chronic inflammation, giant cells, variable granulomas; may epithelialize
Sexually transmitted disease due to Calymmatobacterium granulomatosis, may extend to perianal region
Micro: Donovan bodies (oval) within cytoplasm of macrophages
Positive stains: Warthin-Starry to highlight Donovan bodies
DD: squamous cell carcinoma (resembles grossly)
Associated with abscess, CMV, herpes simplex perianal ulceration, HPV related diseases
Also associated with other sexually transmitted diseases
Sexually transmitted disease caused by Chlamydia trachomatis
Complications: strictures, rectal squamous metaplasia, squamous cell carcinoma
Micro: granulomatous proctitis resembling Crohn’s disease; follicular infiltrates of lymphocytes, histiocytes and plasma cells, neural hyperplasia, extensive fibrosis
Often in young women
Gross: small polypoid lesion with superficial erosions
Micro: lymphoid follicles covered by columnar or transitional epithelium
Chronic process extending into muscularis propria layer
Accompanied by hypertrophic papilla, infected crypt and skin tag (due to edema and fibrosis)
Nonspecific histologic findings
10% of cases have anal lesions, including midline dorsal fissures, skin excoriation, perianal or ischiorectal abscess, rectovaginal fistula
Often involvement of glandular epithelium or hyperplastic changes of transitional mucosa
Benign or non-neoplastic lesions
May be very large and ulcerate
Florid pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma
Gross: may resemble hemorrhoids
Dilated or thrombosed veins in hemorrhoidal plexus, within or external to anus
Causes: dependency or other processes causing deterioration of connective tissue and smooth muscle that anchor anal submucosal venous sinusoids, causing distal displacement of anal canal cushions
Less commonly due to hepatic cirrhosis, pregnancy, rectal carcinoma, uterine leiomyoma
Portal hypertension may cause severe bleeding due to increased portal venous pressure or possibly coagulation abnormalities
Rarely associated with granulomas, condyloma, tuberculosis, herpes, syphilis (plasma cell infiltrate), Crohn’s disease, lymphoma, dysplasia, carcinoma or melanoma, so examine hemorrhoidal specimens carefully
Common finding of pagetoid dyskeratosis is likely due to trauma from prolapse (Archives 2001;125:1058)
Symptoms: bleeding, pain if thrombosed
Treatment: symptomatic, excision
Gross: dilated thick walled vessels
Micro: dilated thick walled submucosal vessels and sinusoidal spaces; also thrombi and reorganized vessels with florid papillary endothelial hyperplasia, adjacent hemorrhage, surface ulceration, inflammatory changes; mucosa may be squamous, colorectal or transitional; pagetoid dyskeratosis (pale cells in epidermis with premature keratinization, resembling Paget’s cells) in 68%, prominent in 22%
Hypertrophic HSV in HIV+ patients
Rare; chronic hyperproliferative plaque or mass that clinically resembles malignancy
In vulva or perianal region
Case reports: Case of Week #53, 44 year-old African American man with a hypertrophic gluteal cleft plaque (J Drugs Dermatol 2003;2:198, free full text)
Treatment: often ineffective, often recurs
Micro: epithelial hyperplasia, brisk infiltrate of lymphocytes and plasma cells
Positive stains: HSV
References: Dis Colon Rectum 2005;48:2289, BHIVA Conf 2005 Apr 20-23;11:PA8
Also called anal skin tags, fibroepithelial polyps
Common; due to edema, inflammation, fibrosis
Protrude into anal canal, adjacent to anal ulcers
Benign; may be reactive hyperplasia of connective tissue
Gross: polypoid, may resemble hemorrhoids
Micro: projections
of submucosa and overlying mucosa; squamous epithelium with central core of
inflamed, edematous, myxoid or fibrovascular stroma with thin walled vessels;
80% have large, multinucleated, CD34+ stellate cells, often with atypical
nuclear features; frequent mast cells; no thick walled vessels, no organizing
thrombi, no hemorrhage
EM: fibroblastic and
myofibroblastic stromal cells
References: AJSP 1998;22:70
Absence of ganglion cells in distal bowel extending proximally for varying distances (note: ganglion cells are usually absent or sparse in anorectal wall for 1-2 cm above dentate line)
Marked reduction or absence of interstitial cells of Cajal in internal anal sphincter in these patients (Archives 2003;127:1192)
Inflammatory cloacogenic polyp
Middle aged patients with rectal bleeding
Single or multiple polyps in anal canal, resemble hemorrhoids
Associated with solitary rectal ulcer syndrome or mucosal prolapse; may be due to prolapse with ischemic damage and subsequent repair
Patients may also have HPV related disorders
Treatment: excision
Gross: sessile, 1-2 cm
Micro: tubulovillous with elongated, irregular crypts extending into submucosa (resembles colitis cystica profunda); squamous, colorectal or transitional epithelium, eroded at surface or covered with exudates; may be hyperplastic or regenerative; thickened muscularis mucosa with irregular strands penetrating lamina propria; no dysplastic changes, no desmoplasia, no invasion
DD: villous adenoma
References: AJSP 1981;5:761
Internal anal sphincter achalasia
Similar presentation to Hirschsprung’s disease, but ganglion cells are present on rectal biopsy
Anorectal manometry shows absence of rectosphincteric reflex on balloon inflation
Marked reduction or absence of interstitial cells of Cajal in internal anal sphincter in these patients (Archives 2003;127:1192)
Intramural tumors are rare; when found are often in young women
Leiomyomas of muscularis mucosa more common; small and present as intraluminal polyps
Leiomyomas externally attached to rectum occur almost always in women, positive for ER, PR, negative for CD117, analogous to uterine leiomyomas
Gross: in small study, rectal tumors were 1.5-4 cm
Micro: limited cellularity resembling esophageal leiomyoma or higher cellularity without mitotic activity
Positive stains: desmin, alpha smooth muscle actin
Negative stains: CD117, CD34
Case report of spindle cell lipoma (Hum Path 1982;13:1052)
Also called retrorectal cyst hamartoma
Rare congenital presacral lesion
May arise from remnants of postanal gut (tailgut)
Usually occurs in retrorectal (presacral) space of all ages, more common in females, associated with pain/discomfort
May become infected, be associated with recurrent perianal fistulas
Rarely associated with malignancy
Treatment: complete excision with free margin of normal tissue, generous sampling
Case reports: carcinoid tumor arising in tailgut cyst in 41 year old woman (Archives 2004;128:578)
DD: teratoma, dermoid cyst, duplication (enterogenous) cyst, anal gland cyst, anterior sacral meningocele
Premalignant lesions
Associated with HPV 6, 11, 16, 18; also 31, 35, 39
Associated with other HPV lesions (anal dysplasia / CIS, verrucous carcinoma, squamous cell carcinoma / basaloid carcinoma)
Gross: papillary excrescences
Micro: papillary squamous epithelium with hyperkeratosis, variable koilocytotic atypia; variable dysplastic changes
DD (other HPV associated lesions): anal dysplasia / CIS, verrucous carcinoma, squamous cell / basaloid carcinoma
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Also called anal intraepithelial neoplasia (AIN), anal canal
intraepithelial neoplasia (ACIN), carcinoma in situ (if high grade)
AIN/ACIN I-III (1-3) represents low grade/condyloma, intermediate grade and high grade/CIS lesions, respectively
Occurs in perianal skin or anal canal in flat mucosa or with condyloma acuminatum
May be incidental finding in hemorrhoid specimen; in these cases, excision is usually curative even for high grade AIN/ACIN (Hum Path 1991;22:528)
Often multicentric
HPV is commonly detected in these lesions (usually HPV 16, 18); presence does not appear to be associated with histologic features
Cytology helpful for detection, Thin-Prep is better than smears (Mod Path 1995;8:270)
HIV patients often have high risk HPV types within low grade lesions (Archives 1997;121:820)
Carcinoma
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Incidence increasing in males and females; more common in
women (2-4:1)
4000 new cases and 620 deaths annually from anal cancer in US
Associated with HPV in 85% of cases, usually HPV 16
HPV negative tumors occur in older patients, often no dysplasia; most rectal adenocarcinomas are HPV negative
Symptoms: bleeding, pain, mass, itching, none (25%)
Risk factors: Crohn’s disease, lymphogranuloma venereum, condyloma acuminatum or other sexually transmitted diseases, cervical cancer, receptive anal intercourse in homosexuals, heavy smoking, immunosuppression
Poor prognostic factors: high stage (based on large size, increased depth of invasion, nodal involvement, metastases), recurrence, possibly poorly differentiated (basaloid) tumors, possibly aneuploidy
Treatment: local excision for small tumors; larger tumors get radiation therapy or chemotherapy, rarely abdominoperineal resection
5 year survival: 50-70%; 100% if less than 2 cm, confined to mucosa or submucosa and well differentiated
Metastases: rectal and inguinal lymph nodes, liver, lungs
WHO classification of anal carcinomas: squamous cell, adenocarcinoma (rectal type, of anal glands, or within anorectal fistulae), mucinous adenocarcinoma, small cell, undifferentiated
Gross: usually near dentate (pectinate) line growing upward into rectum or outward towards perianal tissues; if proximal to pectinate line, often cannot distinguish grossly from rectal adenocarcinoma; perianal skin involvement varies from none, surface ulceration or ulcerated tumor with rolled edges
Positive stains: cytokeratin, EMA, CEA, p53
Negative stains: ER, PR
References: Mod Pathol 1996;9:614, Mod Path 1989;2:439
Tumors that arise from downward extension of rectal tumors or from columnar epithelium of proximal zone are considered rectal tumors, are usually CK7-/CK20+ (Archives 2001;125:1074)
Rare from anal canal; may arise from anal glands or from congenital anorectal duplications, usually in older patients
May present with fistulous tracts or as vaginal cysts
Often long history of perianal fistulas, abscesses, surgery
Indolent course with gradual progression
HPV 18 is present in 2/ 6; 0/6 were HPV 16+ (Mod Path 1991;4:58)
May contain melanin pigment, perhaps due to tumor cell phagocytosis of melanin from melanocytes (AJSP 1981;5:711)
Gross: may be large, ulcerated buttock masses with gelatinous consistency
Micro: mucin producing epithelium; often well differentiated resembling trapped glands; may have dilated, mucin-filled cysts containing free floating tumor cells (colloid adenocarcinoma), granulomatous reaction to mucin; rectal mucosa not involved
Very rare tumor of perianal skin
Treatment: wide local excision with negative margins or irradiation
Micro: resembles basal cell carcinoma of skin
DD: basaloid type of squamous cell carcinoma of anal canal (much more common)
Case report at Hum Path 1990;21:350
Highly differentiated squamous lesion
Highly differentiated squamous lesion that appears to be invasive
Composed of large, mature squamous cells except at base and edges, which have more undifferentiated cells with mitotic activity
Epithelium is acanthotic and hyperkeratotic; lamina propria has lymphoplasmacytic infiltrate
May be invasive, but local excision appears to be curative
Metastases to anus or perianal area
Rectal carcinomas most common, rare case reports from other sites (lung, breast, kidney)
Case report of renal cell carcinoma metastasis (Archives 2002;126:856)
Intraepithelial tumor of apocrine glands
Variable percentage (15-50%) of perianal Paget’s disease is associated with an underlying local malignancy
May extend into anal canal to dentate line
Tumors that are GCDFP+, CK20- are associated with primary cutaneous intraepithelial malignancy with sweat gland differentiation
Tumors that are MUC2+, CK20+ or GCDFP-15 negative may have an underlying rectal adenocarcinoma (AJSP 2001;25:1469, Archives 2001;125:1074, Archives 1998;122:1077)
Associated with squamous hyperplasia, fibroepithelioma-like hyperplasia and papillomatous hyperplasia (AJSP 2000;24:543)
Gross: erythematous, ulcerated or eczematous
Micro: usually single, occasionally nests or gland like formations of large, pale-staining to clear intraepidermal carcinoma cells with abundant mucin
Positive stains: mucin (mucicarmine, PAS), CK7, CEA, EMA; variable CK20
Also called spindle cell carcinoma
Small cell (neuroendocrine) carcinoma
Rare, very aggressive, 5 year survival only 10%
Associated with HPV
Usually present with disseminated disease
Micro: undifferentiated tumor composed of solid nests of small cells with minimal cytoplasm, hyperchromatic nuclei with molding, central necrosis; resembles pulmonary tumor
Positive stains: chromogranin (usually), synaptophysin, neuron specific enolase, Leu7
DD: basaloid carcinoma
Includes variants formerly called cloacogenic (obsolete term for basaloid features), basaloid, mucoepidermoid carcinoma
Usually middle-aged patients, predominantly women (60-80%), present with rectal bleeding, pain or mass
WHO recommends generic term “squamous cell carcinoma” be used for all squamous tumors, since no significant prognostic differences between subtypes, most tumors are mixtures of various subtypes, and reproducibility is low; however, additional comments on histologic features may be helpful
Prominent basaloid features and small tumor cell size associated with high risk HPV
Gross: 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
Micro: variable features; resembles counterpart in skin or upper aerodigestive tract (keratinizing / well differentiated); may have glandular differentiation; may be basaloid with plexiform pattern and palisading of small undifferentiated cells around the border and central necrosis of tumor nodules (also mitotic figures, invasion, desmoplastic stroma); may have massive eosinophilic infiltration, mucoepidermoid features, poorly differentiated morphology; often replaces crypts of adjacent rectal mucosa; often adjacent dysplastic changes
DD: basal cell carcinoma (fewer mitotic figures, smaller cells, less “flagrant” invasion)
Mucinous microcysts
Well formed cystic spaces containing PAS+ or Alcian blue+ mucin
Poorer prognosis than standard squamous cell carcinoma
Related or identical to giant condyloma acuminatum of Buschke-Loewenstein
Considered intermediate between condyloma and squamous cell carcinoma
Gross: polypoid, resembles a condyloma but is larger
Micro: very well differentiated squamous epithelium with minimal atypia and pushing borders that invade stroma; similar to tumor of lower female genital tract and other sites
Other malignancies
Usually small, classified as a rectal tumor
30% of anorectal carcinoids have a second tumor, often colonic adenocarcinoma
Good prognosis: less than 2 cm, confined to mucosa or submucosa; treat with local excision
In perianal region of children and infants
Micro: undifferentiated small round blue cell tumor; may have multinucleated tumor cells
EM: evidence of muscle differentiation
Gastrointestinal stromal tumor
Anorectal GISTS usually occur in men (70%), age 40+
Small asymptomatic intramural nodules to large masses that bulge into pelvis causing pain, rectal bleeding or obstruction
May have late recurrence and distant metastases to liver, bone, lungs
Poor prognostic factors: size > 5 cm with 5+ mitotic figures/50 HPF
Micro: usually highly cellular spindle cell tumors; occasionally epithelioid morphology
Positive stains: CD117, CD34
Negative stains: smooth muscle actin (usually), desmin (usually), S100
References: AJSP 2001;25:1121, AJSP 1999;23:946, Hum Path 1992;23:762
Discussion of extranodal histiocytic sarcoma with one case in anus (AJSP 2004;28:1133)
Most common stromal tumor of anus
Usually forms polypoid intraluminal mass; may be confused with a hemorrhoid
Often women, median age 58 years (range 24-79 years)
Presents with rectal obstruction or bleeding
Most do not die of disease (AJSP 2001;25:1121)
Gross: median 3 cm (range 2 to 5.5 cm); usually polypoid, ulcerated, intraluminal masses
Micro: spindle cell tumors, usually resembling well differentiated smooth muscle cells; oval to moderated elongated, often blunt-ended, with distinctly eosinophilic cytoplasm, atypical nuclei, focal nuclear pleomorphism; usually mucosal ulceration; high mitotic activity in all cases (26+ mitotic figures/10 HPF)
Positive stains: actin
Negative stains: CD117
3% of GI lymphomas arise in rectum or anus in general population vs. 26% in AIDS patients
AIDS lymphomas: usually high grade, EBV+
Non-AIDS lymphomas: EBV-, less often high grade
High incidence of AIDS lymphomas may be due to prior local trauma or chronic infections
References: AJSP 1997;21:997
Relatively rare; 10% as common as squamous cell carcinoma
Often mistaken for hemorrhoids, causing late diagnosis
5 year survival 15%
Prognosis related to tumor size and depth of invasion (2 mm or less have excellent prognosis)
Case report associated with neurofibromatosis (Archives 1995;119:285)
Must have high index of suspicion to diagnose
Gross: single or multiple, large polypoid mass, 80% pigmented, grow near dentate line
Micro: resemble mucosal melanomas; pigmented epithelioid or spindle cells in nesting pattern, usually with junctional component with lentiginous appearance (may be absent in ulcerated tumors); invade crypts in pattern similar to lymphoma; rarely desmoplastic (Hum Path 1985;16:1277)
Positive stains: HMB45, S100, MelanA/Mart1
Negative stains: keratin
DD: poorly differentiated squamous cell carcinoma, lymphoma, adenocarcinoma with melanin containing tumor cells (rare)
Miscellaneous
Usually staged based on clinical observations, since surgical excision is infrequent for anal carcinomas
This staging system applies to anal canal tumors but excludes anal margin tumors, melanoma, carcinoid tumors, sarcomas
Use skin staging system for anal margin tumors (arise from skin or distal to squamous mucocutaneous junction)
Stage tumors overlapping the anorectal junction as anal tumors if epicenter is distal to or 2 cm or less proximal from dentate line, and as rectal tumors if epicenter is more than 2 cm proximal to dentate line
Primary tumor (pT) - pathologic staging
pTX: Primary tumor cannot be assessed
pT0: No evidence of primary tumor
pTis: Carcinoma in situ
pT1: Tumor 2 cm or less in greatest dimension
pT2: Tumor more than 2 cm but not more than 5 cm in greatest dimension
pT3: Tumor more than 5 cm in greatest dimension
pT4: Tumor of any size that invades adjacent organ(s): vagina, urethra, bladder
Note: direct invasion of the rectal wall, perirectal skin, subcutaneous tissue or sphincter muscle is not classified as pT4
Regional lymph nodes (pN) - pathologic staging
pNX - Regional lymph nodes cannot be assessed
pN0 - No regional lymph node metastasis
pN1 - Metastasis in perirectal lymph node(s)
pN2 - Metastasis in unilateral internal iliac or inguinal lymph node(s)
pN3 - Metastasis in perirectal and inguinal lymph nodes or bilateral internal iliac or inguinal lymph nodes
Isolated tumor cells (ITC)
ITC are single cells or small clusters of cells 0.2 mm or less, found by routine H&E, immunohistochemistry, PCR or other. Lymph nodes or distant sites with ITC are classified as pN0 or pM0.
pN0 (i+): ITC detectable by any morphologic method but not histologically
pN0 (i-): ITC not detectable by any morphologic method or histologically
pN0 (mol+): ITC detectable by any molecular method but not histologically
pN0 (mol-): ITC detectable by any molecular method or histologically
Distant metastases (pM)
pMX - Distant metastasis cannot be assessed
pM0 - No distant metastasis
pM1 - Distant metastasis
Stage grouping
Stage 0: Tis N0 M0
Stage I: T1 N0 M0
Stage II: T2-T3 N0 M0
Stage IIIA: T1-T3 N1 M0 or T4 N0 M0
Stage IIIB: T4 N1 M0 or Any T N2-N3 M0
Stage IV: Any T, Any N, M1
Alternative staging
A: intraepithelial or superficially invasive
B: penetrate into muscularis propria or adjacent pelvic tissue
C: regional nodal metastases
D: massive local spread or distant metastases; unresectable
Mandatory / optional are for accreditation purposes by the American College of Surgeons Committee on Cancer
Polypectomy (excisional biopsy) - applies to all invasive carcinomas
Mandatory
Polyp size: at least one dimension
Histologic type: squamous cell carcinoma, adenocarcinoma, mucinous adenocarcinoma, small cell carcinoma, undifferentiated carcinoma, other, carcinoma-cannot determine
Histologic grade: well, moderate or poorly differentiated, undifferentiated, cannot determine or not applicable; for adenocarcinoma, is based on % of tumor that forms glands: well - >95%, moderate - 50-95%, poor - 5-49%, undifferentiated - < 5%
Depth/extent of invasion: no invasion, cannot determine, into lamina propria, into muscularis mucosa, into submucosa
Resection margin: cannot assess, positive / negative for invasive carcinoma; if negative, closest tumor to mucosal margin is __ mm, carcinoma in situ absent / present at mucosal margin
Angiolymphatic invasion: absent, present for large / small vessels, indeterminate
Recommended if known but not required for accreditation purposes
Tumor site
Polyp configuration: pedunculated, sessile, unknown
Additional findings: none, colitis, other
Local excision (transanal disk excision) - applies to all invasive carcinomas
Mandatory
Specimen type: intact, fragmented, other
Tumor size: at least one dimension
Histologic type: squamous cell carcinoma, adenocarcinoma, mucinous adenocarcinoma, small cell carcinoma, undifferentiated carcinoma, Paget’s disease, other, carcinoma-cannot determine
Histologic grade: well, moderate or poorly differentiated, undifferentiated, cannot determine or not applicable; for adenocarcinoma, is based on % of tumor that forms glands: well - >95%, moderate - 50-95%, poor - 5-49%, undifferentiated - < 5%
Depth/extent of invasion: no invasion, cannot determine, into lamina propria, into muscularis mucosa, into submucosa
For each resection margin: cannot assess, positive / negative for invasive carcinoma; if negative, closest tumor is __ mm from margin, carcinoma in situ absent / present at margin
Angiolymphatic invasion: absent, present for large / small vessels, indeterminate
pTNM and stage
Recommended if known but not required for accreditation purposes
Tumor site
Tumor configuration: polypoid, infiltrative, ulcerating, other
Perineural invasion: absent, present
Additional findings: none, Crohn’s disease, condyloma, dysplasia, Paget’s disease, other
Anus resection - applies to all invasive carcinomas
Mandatory
Specimen type: abdominoperineal resection, other, not specified
Tumor site: anterior wall, anal margin, not specified
Tumor size: at least one dimension
Histologic type: squamous cell carcinoma, adenocarcinoma, mucinous adenocarcinoma, small cell carcinoma, undifferentiated carcinoma, Paget’s disease, other, carcinoma-cannot determine
Histologic grade: well, moderate or poorly differentiated, undifferentiated, cannot determine or not applicable; for adenocarcinoma, is based on % of tumor that forms glands: well - >95%, moderate - 50-95%, poor - 5-49%, undifferentiated - < 5%
Depth/extent of invasion: no invasion, cannot determine, into lamina propria, into muscularis mucosa, into submucosa, into muscularis propria, into subserosa
For each resection margin (proximal, distal, radial [soft tissue closest to deepest tumor penetration]: cannot assess, positive / negative for invasive carcinoma; if negative, closest tumor is __ mm from margin, carcinoma in situ absent / present at margin
Angiolymphatic invasion: absent, present for large / small vessels, indeterminate
Invasion of other structures
Nodal involvement (# identified, # involved)
pTNM and stage
Optional
Tumor configuration: polypoid, infiltrative, ulcerating, other
Perineural invasion: absent, present
Additional findings: none, Crohn’s disease, condyloma, dysplasia, Paget’s disease, fistula, active colitis, polyps, other
References: Archives 2000;124:21
Link to College of American Pathologist protocols
End of Anus and perianal area Chapter/Outline