Module 13 _ Lower GIT_compressed.pdf

MODULE 12. !e module 13. LOWER GASTROINTESTINAL TRACT UPPER GASTROINTESTINAL TRACT LOWER GASTROINTESTINAL TRACT ACCESSORY ORGANS OF THE GASTROINTESTINAL TRACT ESOPHAGUS LARGE INTESTINE LIVER STOMACH APPENDIX GALLBLADDER HEIDELIZ JOY L. TAMIRAY, MD, DPSP SMALL INTESTINE PANCREAS 1 MODULE 12. 2 MODULE...

MODULE 12. !e module 13. LOWER GASTROINTESTINAL TRACT UPPER GASTROINTESTINAL TRACT LOWER GASTROINTESTINAL TRACT ACCESSORY ORGANS OF THE GASTROINTESTINAL TRACT ESOPHAGUS LARGE INTESTINE LIVER STOMACH APPENDIX GALLBLADDER HEIDELIZ JOY L. TAMIRAY, MD, DPSP SMALL INTESTINE PANCREAS 1 MODULE 12. 2 MODULE 13. lower GIT: lar" int#tine ANATOMY & HISTOLOGY Anatomy lower gastrointestinal tract large intestine terminal 1–1.5 m of the gastrointestinal tract regions: cecum, ascending (right) colon, transverse colon, descending (left) colon, sigmoid colon, and rectum rectum forms the distal 8–15 cm of extraperitoneal large bowel that lies within the pelvis and ends at the anal canal hepatic flexure: junction of the ascending and transverse colon splenic flexure: junction of the transverse and descending colon normal anatomy and histology benign disorders malignant disorders 3 4 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: lar" int#tine MODULE 13. ANATOMY & HISTOLOGY lower GIT: lar" int#tine ANATOMY & HISTOLOGY BENIGN DISORDERS Histology mucosa single layer of low columnar to cuboidal epithelium into which the crypts of Lieberkühn open absorptive cells: basally located nuclei, mucin- negative acidophilic cytoplasm, and luminally directed apical striated borders goblet cells: synthesize, store, and secrete mucin granules crypts have a tubular, test tube-like shape and are arranged parallel to each other crypt epithelium contains mature absorptive cells and goblet cells similar to those in the surface epithelium + immature and undifferentiated precursor cells, endocrine cells, and Paneth cell submucosa muscularis externa: ICOL serosa (in rectum, perimuscular tissues) Hirschsprung Diverticulosis Irritable bowel syndrome Inflammatory bowel disease Adenomas FAP 5 MODULE 13. 6 lower GIT: lar" int#tine MODULE 13. BENIGN DISORDERS lower GIT: lar" int#tine BENIGN DISORDERS Hirschsprung disease Hirschsprung disease common congenital disorder (1 in 5000 newborns) that results from lack of coordinated propulsive movement of the distal portion of the large bowel due to the loss of intrinsic inhibitory innervation aganglionic megacolon diagnosed during the first year of life in most patients, but it may present later, occasionally even in adulthood ~80% of the patients are male; 10% have Down syndrome, and another 5% have other serious neurologic absence of parasym- pathetic ganglion cells in the intramural and submucosal plexuses, which in turn may be caused by either failure of migration from the neural crest or by immune-mediated neuronal necrosis abnormalities complications: acute intestinal obstruction and enterocolitis hallmark of the disease is the absence of ganglion cells (aganglionosis) in both plexuses of a segment of bowel Normal submucosal plexus ganglion cells submucosal plexus Gross Specimen of Hirschsprung Disease. The proximally dilated segment of bowel has been resected. 7 ganglion cells 8 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: lar" int#tine MODULE 13. BENIGN DISORDERS lower GIT: lar" int#tine BENIGN DISORDERS Hirschsprung disease Hirschsprung disease Aganglionic Aganglionic submucosal nerves submucosal nerves ganglion cells at interface of muscularis externa & interna absent ganglion cells + hypertrophic submucosal nerves 9 MODULE 13. lower GIT: lar" int#tine 10 MODULE 13. BENIGN DISORDERS absent ganglion cells lower GIT: lar" int#tine BENIGN DISORDERS Diverticulosis Hirschsprung disease biopsy should be taken at a point 2 cm above the anal valve in infants and 3 cm in older children depending on the extent and location of the aganglionic segment, several forms of the disease have been recognized: 1. Classic form: aganglionic segment begins in the distal colorectum and extends for a considerable distance in the adjoining proximal dilated bowel 2. Short-segment form: involves the rectum and rectosigmoid for a distance of only a few centimeters 3. Ultrashort-segment form: aganglionic segment is so short that the diagnosis can be missed if the biopsy is taken too high 4. Long-segment form(total colonic aganglionosis): more extensive abnormality, involving most or all of the large bowel, and occasionally even extending to the small bowel; px present with symptoms of intestinal obstruction without megacolon 5. Zonal colonic aganglionosis: only a short segment of bowel is involved; ganglion cells are present not only above but also below the aganglionic segment most cases are acquired, >40 multiple, preferentially affects left colon main complications of diverticulosis are hemorrhage, perforation, and diverticulitis diverticulitis manifests radiographically with sawtoothed ser- rations and a narrowed lumen. I diverticula are located on the mesenteric and lateral aspects of the bowel flask-like shape and may be filled with feces or mucin some extend into the appendices epiploicae and bulge over the serosa IHC: acetylcholinesterase, calretinin, cathepsin D Classic radiographic appearance of diverticulosis 11 12 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: lar" int#tine lower GIT: lar" int#tine MODULE 13. BENIGN DISORDERS BENIGN DISORDERS Diverticulosis Irritable Bowel Syndrome characterized by chronic, relapsing abdominal pain, bloating, and changes in bowel habits peak prevalence is between 20 and 40 years of age, female predominance presently diagnosed using clinical criteria that require the occurrence of abdominal pain or discomfort at least 3 days per month over 3 months with improvement following defecation and a change in stool frequency or form other causes, such as enteric infection or inflammatory bowel disease, must be excluded pathogenesis: remains poorly defined, although there is clearly interplay between psychologic stressors, diet, perturbation of the gut microbiome, increased enteric sensory responses to GI stimuli, and abnormal GI motility Classic radiographic appearance of diverticulosis Diverticula seen traversing the circular muscle layer as outpouchings of mucosa w/ tip of the diverticula in subserosa Whole-Mount Sections of Colonic Diverticulosis 13 MODULE 13. lower GIT: lar" int#tine 14 lower GIT: lar" int#tine MODULE 13. BENIGN DISORDERS BENIGN DISORDERS Inflammatory Bowel Disease Inflammatory Bowel Disease Crohn Disease chronic condition resulting from complex interactions between intestinal microbiota and host immunity in genetically predisposed individuals that leads to inappropriate mucosal immune activation may occur in any area of the GI tract but most commonly involves the terminal ileum, ileocecal valve, and cecum limited to the small intestine in about 40% of cases; the small intestine and colon are both involved in 30% of cases skip lesions: multiple, separate, sharply delineated areas of disease earliest lesion is an aphthous ulcer intestinal wall is thickened and rubbery as a consequence of pathogenesis: results from a combination of abnormalities in immune regulation, hostmicrobe interactions, and epithelial barrier functions in genetically susceptible individuals 15 transmural edema, inflammation, submucosal fibrosis, and hypertrophy of the muscularis propria, all of which contribute to stricture formation ulceration with sparing of interspersed mucosa, a result of the patchy distribution of Crohn disease, results in an irregular, cobblestone appearance of the mucosa if extensive transmural disease, mesenteric adipose tissue frequently extends over the serosal surface (creeping fat) Gross pathology of Crohn disease. (A) Small intestinal stricture. (B) Linear mucosal ulcers, which impart a cobblestone appearance to the mucosa, and thickened intestinal wall. (C) Perforation and associated serositis. (D) Creeping fat. 16 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: lar" int#tine MODULE 13. BENIGN DISORDERS lower GIT: lar" int#tine BENIGN DISORDERS Inflammatory Bowel Disease Inflammatory Bowel Disease Crohn Disease Crohn Disease microscopic findings: abundant neutrophils that infiltrate and damage crypt epithelium clusters of neutrophils within a crypt are referred to as crypt abscesses and are often associated with crypt destruction ulceration (+) abrupt transition between ulcerated and adjacent normal mucosa may be present mucosal atrophy, with loss of crypts, may also occur after years of disease noncaseating granulomas (a hallmark of Crohn disease), are found in approximately 35% of cases and may occur in areas of active disease or uninvolved regions within any layer of the intestinal wall clinical features most patients have intermittent attacks of relatively mild diarrhea, fever, and abdominal pain cigarette smoking is a strong risk factor for development of Crohn disease extraintestinal manifestations of Crohn disease: migratory polyarthritis, ankylosing spondylitis, erythema nodosum, cutaneous granulomas, and clubbing of the fingertips treatment anti-inflammatory agents, e.g., salicylates; immunosuppressive drugs, e.g., corticosteroids; and Microscopic pathology of Crohn disease. (A) Haphazard crypt organization results from repeated injury and regeneration. (B) Noncaseating granuloma. (C) Active Crohn disease, with ulceration and purulent exudate. (D) Transmural Crohn disease with submucosal and serosal granulomas (arrows). biologic therapies, e.g., anti-TNF antibodies 17 MODULE 13. 18 lower GIT: lar" int#tine MODULE 13. BENIGN DISORDERS lower GIT: lar" int#tine BENIGN DISORDERS Inflammatory Bowel Disease Inflammatory Bowel Disease Crohn Disease Ulcerative Colitis intestinal involvement is limited to the colon and rectum ~ 2.5% to 7.5% of individuals with ulcerative colitis also have primary sclerosis cholangitis clinical features: relapsing disorder characterized by attacks of bloody diarrhea with stringy mucoid material, lower abdominal pain, and cramps that are temporarily relieved by defecation gross findings: always involves the rectum, extends proximally in a continuous fashion to involve part or all of the colon entire colon: pancolitis limited distal disease: ulcerative proctitis or ulcerative proctosigmoiditis backwash ileitis: mild mucosal inflammation of the distal ileum colonic mucosa may be slightly red and granular or have extensive, broad-based ulcers ulcers are aligned along the long axis of the colon isolated islands of regenerating mucosa often bulge into the lumen to create pseudopolyps and the tips A. Stricture; B. Cobblestone appearance Patchy active inflammation in mucosa involved by Crohn disease with crypt abscesses. 19 Crohn disease with a mucosal granuloma in the ileum. of these polyps may fuse to create mucosal bridges not transmural: colon wall is not thickened, the serosal surface is normal, and strictures do not occur severe cases: toxic megacolon 20 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: lar" int#tine MODULE 13. BENIGN DISORDERS lower GIT: lar" int#tine BENIGN DISORDERS Inflammatory Bowel Disease Inflammatory Bowel Disease Ulcerative Colitis Ulcerative Colitis Gross pathology of ulcerative colitis. (A) Total colectomy with pancolitis showing active disease, with red, granular mucosa in the cecum (left) and smooth, atrophic mucosa distally (right). (B) Sharp demarcation between active ulcerative colitis (right) and normal mucosa (left). (C) Inflammatory polyps. (D) Mucosal bridges can join inflammatory polyps. Comparison between pseudopolyps in ulcerative colitis (right) and the cobblestone pattern of Crohn disease (left). Toxic megacolon Pseudopolyps 21 MODULE 13. lower GIT: lar" int#tine MODULE 13. BENIGN DISORDERS Inflammatory Bowel Disease Ulcerative Colitis Ulcerative Colitis Carcinoma & Dysplasia incidence of carcinoma is markedly increased overall incidence of this complication is probably in the vicinity of 2% risk factors: extensive colitis, those with disease for greater than 7–10 years, young age of colitis microscopic findings: inflammatory infiltrates, crypt abscesses, lower GIT: lar" int#tine BENIGN DISORDERS Inflammatory Bowel Disease 22 crypt distortion, and pseudopyloric epithelial metaplasia granulomas are NOT present diffuse inflammation is generally limited to the mucosa and superficial submucosa submucosal fibrosis, mucosal atrophy, and distorted mucosal architecture remain as residua of healed disease, but histology may also revert to near normal after prolonged remission. onset, and primary sclerosing cholangitis earliest gross change: thick mucosa with a finely nodular or velvety surface configuration microscopically, most of these tumors are adenocarcinomas of varying degrees of differentiation development of adenocarcinoma is always accompanied—and probably always preceded—by dysplastic changes of the colorectal mucosa diagnosis of dysplasia should not be made in areas of active inflammation Histopathology of ulcerative colitis. (A) Crypt abscess. (B) Pseudopyloric metaplasia (right). (C) Disease is limited to the mucosa (above the arrow). 23 24 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: lar" int#tine MODULE 13. BENIGN DISORDERS lower GIT: lar" int#tine BENIGN DISORDERS Adenomas Adenomas most common neoplastic polyps which are precursors to the majority of colorectal adenocarcinomas epithelial neoplasms that range from small, often pedunculated, polyps to large sessile lesions although most colorectal adenomas are benign lesions, a small proportion harbor invasive cancer at the time of detection size is the most important characteristic that correlates with risk of malignancy while cancer is extremely rare in adenomas less than 1 cm in diameter, nearly 40% of lesions larger than 4 cm in diameter contain foci of invasive cancer high-grade dysplasia is also a risk factor for cancer in an individual polyp, but does not confer an epithelial dysplasia (+) nuclear hyperchromasia, elongation, and stratification prominent nucleoli, eosinophilic cytoplasm, and a reduction in the number of goblet cells range from 0.3 to 10 cm in diameter and can be pedunculated or sessile, with the surface of both types having a texture resembling velvet or a raspberry classification: tubular, tubulovillous, or villous (based on their architecture) tubular adenomas tend to be small, pedunculated polyps composed of rounded, or tubular, glands villous adenomas, which are often larger and sessile, are covered by slender villi & harbor cancers more frequently than tubular adenomas, but this also correlates with their larger size increased risk of cancer in other polyps within the same patient tubulovillous adenomas have a mixed architecture Histologic appearance of colonic adenomas. (A) Tubular adenoma with a smooth surface and rounded glands. Active inflammation is occasionally present in adenomas; in this case, crypt dilation and rupture can be seen at the bottom of the field. (B) Villous adenoma with long, slender projections that are reminiscent of small intestinal villi. (C) Tubulovillous adenoma Colonic adenomas. (A) Pedunculated adenoma (endoscopic view). (B) Adenoma with a velvety surface. (C) Lowmagnification photomicrograph of a pedunculated tubular adenoma. 25 MODULE 13. 26 lower GIT: lar" int#tine MODULE 13. BENIGN DISORDERS lower GIT: lar" int#tine BENIGN DISORDERS Adenomas Familial Adenomatous Polyposis Sessile serrated lesions (sessile serrated adenomas) overlap histologically with hyperplastic polyps but are more commonly found in the right colon lack typical cytologic features of dysplasia that are present in other adenomas can be differentiated from hyperplastic polyps by the presence of serrated architecture throughout the full length of the glands including the crypt base, crypt dilation, and lateral crypt growth AD disorder in which patients develop numerous colorectal adenomas as teenagers somatic mutations of the adenomatous polyposis coli, or APC gene some polyposis patients without APC loss have bi-allelic mutations of the base-excision repair gene MUTYH (also referred to as MYH) AR disorder = termed MUTYH-associated polyposis, or MAP characterized by fewer than 100 polyps, which appear at later ages colon cancer development is also delayed sessile serrated adenomas and hyperplastic polyps, often with KRAS mutations at least 100 polyps are necessary for a diagnosis of classic FAP, but thousands may be present except for their numbers, FAP-associated polyps are morphologically indistinguishable from sporadic adenomas colorectal adenocarcinoma develops in 100% of untreated FAP patients, often before age 30 and nearly always by age 50 Sessile serrated adenoma distinguished from a hyperplastic polyp by extension of the neoplastic process to the crypts, resulting in lateral growth. 27 Hyperplastic polyp. (A) Polyp surface with irregular tufting of epithelial cells. (B) Tufting results from epithelial overcrowding. (C) Epithelial crowding produces a serrated architecture when crypts are cut in cross section. prophylactic colectomy is the standard of care extraintestinal manifestation: congenital hypertrophy of the retinal pigment epithelium, which can be detected at birth and may be an adjunct to early screening 28 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: lar" int#tine MODULE 13. BENIGN DISORDERS lower GIT: lar" int#tine ANATOMY & HISTOLOGY MALIGNANT DISORDERS Familial Adenomatous Polyposis Adenocarcinoma HNPCC Familial adenomatous polyposis. (A) Hundreds of small polyps are present throughout this colon with a dominant polyp (right). (B) Three tubular adenomas are present in this single microscopic field. 29 MODULE 13. lower GIT: lar" int#tine MODULE 13. MALIGNANT DISORDERS lower GIT: lar" int#tine MALIGNANT DISORDERS Adenocarcinoma Adenocarcinoma most common malignancy of the GI tract incidence peaks at 60 to 70 years of age dietary factors most closely associated with increased risk of colorectal cancer are low intake of 30 unabsorbable vegetable fiber and high intake of refined carbohydrates and fat pathogenesis: at least two genetic pathways have been described APC/β-catenin pathway: activated in the classic adenoma-carcinoma sequence pathogenesis: at least two genetic pathways have been described MSI pathway: defects in DNA mismatch repair and accumulation of mutations in microsatellite repeat regions of the genome Morphologic and molecular changes in the mismatch repair pathway of colon carcinogenesis. Defects in mismatch repair genes result in microsatellite instability and permit accumulation of mutations in numerous genes. If these mutations affect genes involved in cell survival and proliferation, cancer may develop. 31 32 Module 13 | Lower GIT - February 7, 2024 lower GIT: lar" int#tine MODULE 13. MODULE 13. MALIGNANT DISORDERS lower GIT: lar" int#tine MALIGNANT DISORDERS Adenocarcinoma Adenocarcinoma adenocarcinomas are distributed approximately equally over the entire length of the colon proximal colon: grow as polypoid, exophytic masses that extend along one wall of the large-caliber cecum microscopic findings: tall columnar cells that resemble dysplastic epithelium found in adenomas invasive component of these tumors elicits a strong stromal desmoplastic response, which is responsible and ascending colon & rarely cause obstruction distal colon: annular lesions that produce “napkin-ring” constrictions and luminal narrowing, sometimes to for their characteristic firm consistency some poorly differentiated tumors form few glands, or may produce abundant mucin [poor prognosis] the point of obstruction Colorectal carcinoma. (A) Circumferential, ulcerated rectal cancer. Note the anal mucosa at the bottom of the image. (B) Cancer of the sigmoid colon that has invaded through the muscularis propria and is present within subserosal adipose tissue (left).Areas of chalky necrosis are present within the colon wall (arrow). Histologic appearance of colorectal carcinoma. (A) Well-differentiated adenocarcinoma. Note the elongated, hyperchromatic nuclei. Necrotic debris, present in the gland lumen, is typical. (B) Poorly differentiated adenocarcinoma forms a few glands but is largely composed of infiltrating nests of tumor cells. (C) Mucinous adenocarcinoma with signet-ring cells and extracellular mucin pools. 33 lower GIT: lar" int#tine MODULE 13. 34 MODULE 13. MALIGNANT DISORDERS lower GIT: lar" int#tine MALIGNANT DISORDERS Adenocarcinoma Adenocarcinoma cecal and other right- sided colon cancers are most often called to clinical attention by the appearance of fatigue and weakness due to iron deficiency anemia underlying cause of iron deficiency anemia in an older man or postmenopausal woman is GI cancer until proven otherwise left-sided colorectal adenocarcinomas may produce occult bleeding, changes in bowel habits, or cramping and left lower quadrant discomfort 2 most important prognostic factors: depth of invasion and the presence of lymph node metastases mets may involve regional lymph nodes, liver (mc), lungs, and bones overall 5-year survival rate in the United States is 65% VS. overall survival rates in other countries, such as China, India, the Philippines, and Thailand (30% to 42%) other microscopic types: mucinous signet ring micropapillary hepatoid sarcomatoid neuroendocrine differentiation squamous differentiation 35 36 Module 13 | Lower GIT - February 7, 2024 lower GIT: lar" int#tine MODULE 13. MODULE 12. MALIGNANT DISORDERS Hereditary Non-polyposis Colorectal Cancer (HNPCC) Lynch syndrome inherited mutations in mismatch repair genes that encode proteins responsible for the detection, excision, and repair of errors that occur during DNA replication 2% to 4% of all colorectal cancers, making it the most common syndromic form of colon cancer at least five mismatch repair genes majority of patients with HNPCC have mutations in MSH2 or MLH1 increased risk for the development of malignant tumors at other sites, such as liver (cholangiocarcinoma), uterine corpus, urinary bladder, renal pelvis, ureter, pancreas, and several other organs common features: young patient age right-sided location mucinous features poor differentiation (solid or medullary appearance) tumor-infiltrating lymphocytes lack of “dirty” necrosis presence of a Crohn-like inflammatory reaction lower gastrointestinal tract anus normal anatomy and histology benign disorders malignant disorders 37 38 MODULE 13. lower GIT: anus MODULE 13. lower GIT: anus ANATOMY & HISTOLOGY ANATOMY & HISTOLOGY Anatomy Anatomy tubular structure measuring 3–4 cm in length and includes the squamous zone (distal), the transition zone, and the colorectal zone (proximal) squamous zone is the most distal aspect of the anal canal, and it extends from the perianal skin to the lower end of the rectum and is demarcated by the proximal and distal margins of the internal sphincter muscle transition zone: circular zone, 0.3–1.1 cm in width, has a glistening, wrinkled appearance made discontinuous by the presence of the anal papillae some people lack transitional epithelium altogether and have an abrupt transition from glandular to squamous mucosa anal papillae: ridges of squamous mucosa directly joining the rectal mucosa longitudinal folds with depressions b/n them anal sinuses (of Morgagni) glandular epithelium anal/semilunar valves (transverse plicae) “transitional” epithelium Intermediate/cloacogenic zone pectinate line; line formed by the anal valves, anal sinuses, and the bases of the anal columns non-keratinized squamous epithelium pecten Hilton’s white line; junction between the anal canal and the perianal skin cutaneous adnexa and the presence of squamous epithelium 39 40 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: anus MODULE 13. lower GIT: anus ANATOMY & HISTOLOGY BENIGN DISORDERS Histology Anal fissures Brief central zone that is transitional (b/n colorectal mucosa on left & squamous mucosa on right) linear tears in the anal mucosa overlying the internal sphincter muscle 90% are found at the posterior midline overlying the bifurcation of the sphincter constipation, chronic diarrhea, childbirth or other trauma, and stress-related clenching of the sphincters microscopic appearance: nonspecific, featuring acute and chronic inflammation with associated ulceration, granulation tissue, fibrosis, and reactive epithelial changes The stratified epithelium resembles bladder epithelium/ immature squamous epithelium histologically. 41 MODULE 13. lower GIT: anus 42 MODULE 13. lower GIT: anus BENIGN DISORDERS BENIGN DISORDERS Anal fistulas Fibroepithelial polyps & skin tags abnormal inflammatory tracts having two or more internal openings within the anal canal fistulous tract may lead to the skin, or it may end blindly in the perianal soft tissues and/or musculature lining of the fistula is made of acute and chronic inflammation and granulation tissue, although epithelium covered by squamous epithelium and contain a central core of edematous and inflamed, sometimes hyalinized fibrovascular stroma (sometimes hyperplastic and with reactive epithelial changes) may eventually grow at either end of the tract intersphincteric infection/ abscess originating in a traumatized or infected anal crypt; radiation, tumors, and Crohn disease A, Fibroepithelial polyps, anal skin tags, and hypertrophic papillae are essentially identical and consist of a central core of edematous and inflamed fibrovascular stroma covered by squamous epithelium. (Courtesy of Dr. Sara Shalin.) B, These lesions can grow to an impressive size. 43 44 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: anus MODULE 13. lower GIT: anus BENIGN DISORDERS BENIGN DISORDERS Hemorrhoids Hemorrhoids ectasia of the hemorrhoidal vascular plexus px typically present with hematochezia, itching, and anorectal pain most frequent predisposing influences are straining at defecation, e.g., in constipation, and venous stasis of pregnancy; may also develop secondary to portal hypertension divided into external (derived from the external/inferior hemorrhoidal plexus below the dentate line, and covered by skin or squamous mucosa) and internal (derived from the superior hemorrhoidal plexus above the dentate line, and covered by rectal or transitional mucosa) Large external hemorrhoid protruding through the anal orifice. Engorged vessels are clearly visible. 45 46 MODULE 13. lower GIT: anus MODULE 13. lower GIT: anus BENIGN DISORDERS BENIGN DISORDERS Hemorrhoids Infections dilated submucosal vessels with thick or thin walls and variably present thrombosis with hemorrhage and recanalization Lymphogranuloma venereum [Chlamydia trachomatis] Granuloma inguinale [Calymmatobacterium granulomatis] ulcers, often accompanied by lymphadenopathy, fever, anus is involved in approximately 7% of cases - bleeding, and anal pain SCC develops in association with these lesion numerous large dilated submucosal veins w/ underlying glandular & squamous mucosa hemorrhoid w/ overlying squamous & transitional cell mucosa 47 necrotizing ulcers that progressively enlarge and that may be confused clinically with SCC Donovan bodies are pathognomonic if found in biopsies (Warthin-Starry/Giemsa stains) thrombosed hemorrhoid venous plexus w/ overlying ulceration 48 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: anus MODULE 13. lower GIT: anus MALIGNANT DISORDERS MALIGNANT DISORDERS Squamous Intraepithelial Neoplasia Squamous Intraepithelial Neoplasia rising incidence in homosexual men who practice anal receptive intercourse and/or are HIV positive but still w/ slight female predominance (HPV-related) Anal Intraepithelial Neoplasia (AIN): used for lesions in squamous mucosa of the anal canal itself Perianal Intraepithelial Neoplasia (PAIN): lesions affecting the perianal skin within 5 cm of the anal verge Condyloma acuminatum grossly visible lesions featuring koilocytes and squamous hyperplasia or acanthosis most common and best known HPV- associated anorectal lesion harbor low-grade dysplasia *included in the category of LGSIL (AIN 1) anal bleeding, pain, and itching gross findings: fleshy, pink/white papillary or “cauliflower-like” masses 49 50 MODULE 13. lower GIT: anus MODULE 13. lower GIT: anus MALIGNANT DISORDERS MALIGNANT DISORDERS Squamous Intraepithelial Neoplasia Squamous Intraepithelial Neoplasia Condyloma acuminatum HGSIL microscopic findings: koilocytes with wrinkled nuclear contours or “raisinoid” appearance sharply demarcated perinuclear clearing or halo; and variably present binucleation Characteristic features of koilocytes include wrinkled nuclear contours, sharply demarcated perinuclear clearing, and binucleation. 51 Dyskeratotic (abnormal keratinization occurring prematurely) keratinocytes microscopic findings: nuclear membrane irregularity, hyperchromasia, enlargement, and pleomorphism overlying atypical parakeratosis and mitoses in the upper third of the mucosa are often present High-Grade SIL (AIN2/3) Features Full Thickness Nuclear Atypia. A, Increased nuclear density and loss of maturation are apparent, as seen here at the transition zone. B, Dysplastic cells are characterized by nuclear membrane irregularity, hyperchromasia, enlargement, and pleomorphism; increased mitoses are obvious as well, including atypical mitoses mitotic figures present well above the basal zone. C, Overlying atypical parakeratosis is common 52 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: anus MODULE 13. lower GIT: anus MALIGNANT DISORDERS MALIGNANT DISORDERS Squamous Intraepithelial Neoplasia Squamous cell carcinoma infection with high-risk HPV genotypes upregulates p16 (a tumor suppressor gene product that is a surrogate marker of HPV infection) and is associated with increased cellular proliferation HGSIL typically shows diffuse, block-like overexpression of p16 most common primary neoplasm of the anus, although it accounts for less than 5% of large bowel malignancies bleeding, anal pain (much more commonly than in colorectal cancer), mass, and pruritus strong evidence that sexually transmitted HPV infection is an important cause of anal cancer ~80%–90% of anal SCC are associated with HPV infection (HPV 16 > HPV 18) HPV-negative SCC appear to have a worse prognosis (shorter disease-free survival) than patients with HPV-positive tumors A, This squamous cell carcinoma (SCC) of the anal canal has a verrucoid appearance and protrudes out through the anal orifice. Note the small adjacent condylomata (arrows). B, This ulcerated SCC with rolled edges extends out to involve the perianal skin. A, Diffuse, ‘block-like’ staining with p16 in a case of anal HGSIL. B, In contrast, LGSIL and reactive processes usually show absent or weak, patchy staining. 53 54 MODULE 13. lower GIT: anus MODULE 13. lower GIT: anus MALIGNANT DISORDERS MALIGNANT DISORDERS Squamous cell carcinoma Squamous cell carcinoma conventional SCC of the anal canal most often arise distal to the dentate line gross findings: early lesions are often small and mobile, sometimes with a verrucoid appearance Conventional keratinizing SCC invasive nests of malignant squamous cells keratin whorls or “pearls” may be present, along with intercellular bridges and variably present necrosis often found in a background of squamous dysplasia A and B, Invasive conventional-type (keratinizing) anal squamous cell carcinoma undermining perianal skin. C, Keratinization, including keratin whorls or “pearls,” may be prominent. 55 Basaloid (non-keratinizing) SCC irregular, angulated, or trabecular nests of basophilic cells with relatively scant cytoplasm and peripheral palisading squamous nests may be present but lack keratinization can mimic basal cell carcinoma arising in the perianal skin, as well as neuroendocrine carcinomas that rarely occur in this area A and B, Basaloid (nonkeratinizing) SCC features irregular nests of basophilic cells that may have peripheral palisading of nuclei. 56 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: anus MODULE 13. lower GIT: anus MALIGNANT DISORDERS MALIGNANT DISORDERS Squamous cell carcinoma Squamous cell carcinoma Verrucous SCC polypoid tumors that grossly resemble condylomas well differentiated and often have extensive and well-developed surface maturation aggressive, invades local structures and sometimes involving the deep soft tissues of pelvis carcinomas arising above the dentate line typically metastasize to pelvic, perirectal, and para-aortic/ paravertebral nodes tumors distal to the dentate line typically metastasize to inguinal nodes 5-year disease-free survival rate using a combination chemoradiation protocol is 68%, while the overall survival rate is 58%–67% and the colostomy free survival rate is 85% local excision is sometimes used for small (< 2.0 cm) tumors of the anal margin and can be adequate if margins are clear by more than 0.5 cm Prognosis: Patient age, gender, and race. It is worse in older (≥65 years) individuals, men, and African-American patients Tumor location. Current studies indicate that tumors above the dentate line have a better overall prognosis than those below the dentate line Tumor size and stage. depth of invasion, nodal involvement, and presence of distant metastases Microscopic grade. poorly differentiated tumors are associ- ated with shorter survival Presence of HPV. Patients with HPV-negative SCC appear to have a worse prognosis (shorter diseasefree survival) in some studies than patients with HPV-positive tumors Verrucous carcinoma of the anus has a pushing, rather than an infiltrative, border. Note the juxtaposition of the tumor with the muscle of the anal canal wall. Squamous cell carcinoma (SCC) with mucinous microcysts has also been referred to as microcystic SCC or mucoepidermoid car- cinoma of the anus. 57 58 MODULE 13. lower GIT: a$en%x MODULE 12. ANATOMY & HISTOLOGY Anatomy & Histology lower gastrointestinal tract appendix tubular structure arising from the medial wall of the cecum averages 9 cm in length and 0.7 cm in greatest diameter reaches its maximum diameter by 4 years of age and becomes narrower (particularly after age 40) as lymphoid tissue decreases and fibrosis increases often lies posterior to the cecum or ascending colon, below the ileocecal valve normal anatomy and histology benign & malignant other tumors 59 60 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: a$en%x MODULE 13. lower GIT: a$en%x ANATOMY & HISTOLOGY BENIGN DISORDERS Anatomy & Histology Acute Appendicitis most common abdominal surgical emergency obstruction (by fecalith, adhesions, tumor, lymphoid hyperplasia, etc.) leads to increased intraluminal pressure and that the resulting secretions under pressure impair the resistance of the mucosa to invasion by microorganism other theories include compromise of the extramural vascular supply, mucosal ulceration (possibly secondary to viral infection) with superimposed bacterial infection, and low-fiber diets resulting in retention of stool and resultant susceptibility to infection colicky periumbilical pain that eventually migrates to the right lower quadrant, accompanied by tenderness to palpation, nausea and vomiting, fever, leukocytosis, and elevated erythrocyte sedimentation rate and C-reactive protein macroscopic pathology of acute appendicitis is very variable, and the external appearance may not correlate with the extent of inflammation microscopically Lymphoid hyperplasia in children may be striking and is associated with viral infections as well as intussusception. Paneth cells may be seen in the appendiceal mucosa (arrow), along with neuroendocrine cells. **inflammation limited to the mucosa and submucosa of the appendix alone are not adequate to explain the patient’s symptoms and that the diagnosis of acute appendicitis requires the finding of neutrophils within the wall VS. early acute appendicitis consists of mucosal neutrophilic inflammation and mucosal ulceration 61 MODULE 13. lower GIT: a$en%x 62 MODULE 13. lower GIT: a$en%x BENIGN DISORDERS BENIGN DISORDERS Acute Appendicitis Acute Appendicitis A, The earliest gross findings in acute appendicitis consist of dullness of the serosal surface, with injection of the serosal vessels. B, As the inflammatory process progresses, there is variably present fibrinous or purulent exudates along with hyperemia or hemorrhage. C, Green, black, or purple discoloration of the appendiceal wall indicates gangrene. 63 A, Early acute appendicitis with acute inflammation arising from a small mucosal defect. B and C, A more advanced case with massive acute inflammation extending into the muscular wall of the appendix, with extensive ulceration; residual mucosa is seen at the edges in B. D, Transmural inflammation and necrosis in gangrenous appendicitis. 64 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: a$en%x MODULE 13. lower GIT: a$en%x BENIGN DISORDERS BENIGN DISORDERS Acute Appendicitis Acute Appendicitis Periappendicitis: acute or chronic inflammation of the appendiceal serosa Negative appendectomy: appendices removed for signs and symptoms of acute appendicitis but are histologically normal Stump appendicitis: residual or progressive acute inflammation in the postresection appendiceal stump 65 66 MODULE 13. lower GIT: a$en%x MODULE 13. lower GIT: a$en%x MALIGNANT DISORDERS MALIGNANT DISORDERS Low grade Appendiceal Mucinous Neoplasm (LAMN) Low grade Appendiceal Mucinous Neoplasm (LAMN) low grade noninvasive epithelial proliferation that can cause pseudomyxoma peritoneal (if appendix ruptures) the term LAMN is used to indicate those appendiceal mucinous tumors that have features portending at least some increased risk of peritoneal dissemination clinical features: typically occurs in px in their 6th decade of life but age range is broad F>M px w/ dse restricted to appendix present w/ acute appendicitis-like sx while those w/ disseminated dse may present w/ abdominal or ovarian masses or pseudomyxoma peritonei gross findings: dilated lumen containing mucin serosa appears smooth when appendiceal wall is intact adhesions/extra-appendiceal mucin if ruptured 67 Flat proliferation of mucinous epithelial cells originating from appendiceal lumen Dilated appendix w/ perforation, hemorrhages, luminal & extraappendicial mucin abundant apical mucin w/ elongated nuclei & low grade nuclear atypia 68 Module 13 | Lower GIT - February 7, 2024 MODULE 13. lower GIT: a$en%x MODULE 13. lower GIT: a$en%x MALIGNANT DISORDERS MALIGNANT DISORDERS High grade Appendiceal Mucinous Neoplasm (HAMN) Neuroendocrine Tumor (NET/Carcinoid tumor) lesion arising in appendix w/ high grade epithelial features in the absence of infiltrative growth rare lesions mc appendiceal tumor identified in less than 1% of appendectomy high grade dysplasia & convoluted architectural patterns (focal micropapillarity & cribriforming) specimens, more common among adults than children tip/distal third measure less than 1.0 cm in diameter and only rarely measure 2.0 cm or more gross findings: firm, grayish white, and fairly well circumscribed but not encapsulated acquire a characteristic yellow color after formalin fixation microscopic findings: abundant amphophilic, often granular, cytoplasm and are both argentaffin and argyrophil positive nuclei are typically round with coarse “salt and pepper” chromatin and small nucleoli mitotic figures are rare 69 70 MODULE 13. lower GIT: a$en%x MODULE 13. lower GIT: a$en%x MALIGNANT DISORDERS OTHER TUMORS/TUMOR-LIKE CONDITIONS Neuroendocrine Tumor (NET/Carcinoid tumor) Tubular carcinoids: 10%–20% of appendiceal NETs that are composed of enteroglucagon (L) cells characterized by glandular structures rather than solid nests typically small (2–3 mm) and composed of trabeculae and cords of cytologically bland tumor cells tumor cells are argyrophilic but argentaffin negative endometriosis: endometrial gland/s & stroma in the appendiceal wall A, L-cell NETs, formerly known as tubular carcinoids, are composed of trabeculae and cords of neoplastic cells that may be mistaken for a carcinoma. B, Small red acidophilic neuroendocrine granules may be present. 71 A, Metastatic SCCa (cervix); B, Metastatic high-grade serous carcinoma from the ovary. primary GIST: positive CD117, appendiceal wall 72 Module 13 | Lower GIT - February 7, 2024