Benign and malignant lesions of intestines.

BENIGN AND MALIGNANT LESIONS OF INTESTINES.Presenter: Dr Tashi DolmaGuide: Dr Pallavi Agrawal.Dated: 25th Feb 2016

2/23/2016 8:25 AM 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries.The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

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INTRODUCTION.The small intestine and colon account for the majority of GI tract length . The intestines are also the principal site where the immune system interfaces with a diverse array of antigens present in food and gut microbes. Intestinal bacteria outnumber eukaryotic cells in our bodies by tenfold. Thus, it is not surprising that the small intestine and colon are frequently involved by infectious and inflammatory processes.

CANCER BURDEN.Colorectal cancer (CRC) is a formidable health problem worldwide. Small intestinal neoplasm are relatively rare.It is the third most common cancer in men (10.0% of all cancer cases) the second most common in women ( 9.4% of all cancer cases) 60% of cases are encountered in developed countries. account for 8% of all cancer deaths and. In India, Colon cancer ranks 8th and rectal cancer ranks 9th among men. For women, rectal cancer does not figure in the top 10 cancers, whereas colon cancer ranks 9th.

GUT tube development.

Duodenum: 25 cm long, from pyloric sphincter to ligament of Treitz, mostly retroperitoneal, fixed in position Common bile duct (CBD) and pancreatic duct enter second part of duodenum posteromedially at ampulla of vater

LARGE INTESTINE.

Intestinal immune system

Peyers patches in ileum (ovoid lymphoid follicles, partly mucosal and partly submucosal, in antimesenteric side of terminal ileum) Small intestinal goblet cells, deliver low molecular weight soluble antigens from intestinal lumen to CD103+ lamina propria dendritic cells, which regulates development of T cells M (membranous) cells, part of follicle associated epithelia (MALT) in small bowel and colon, which transfer antigen macromolecules from lumen to lymphocytesT cells, usually CD8+ in surface epithelium Lamina propria contains CD4+ T cells and B cells Mucosa associated lymphoid tissue: lymphoid nodules, mucosal lymphocytes, appendiceal lymphoid follicles and mesenteric nodes

Neuromuscular function:

Anterograde and retrograde peristalsis mixes food and promotes maximal contact of nutrients with mucosaColonic peristalsis prolongs contact with mucosaPeristalsis is mediated via myenteric plexus and autonomic innervation (sympathetic-thoracolumbar, parasympathetic-vagal) Also through interstitial cells of Cajal (pacemaker cells) and smooth muscle cells Vagal receptors are abundant in duodenum and scattered throughout wall

Small bowel mucosal biopsy

Important step in evaluating patients with malabsorption.Standard gastroscope for duodenal biopsy.1 or two from doudenal bulp and min 4 from distal duodenum.Proper orientation most critical. H and E stained section , one Alcian blue PAS with hematoxillin counter stain.Alcian blue PAS stain Whipple disease and MAIC infection. Trichrome stain collagen deposition.Iron hematoxillin--- Giardia Lamblia identification.

NORMAL SMALL-INTESTINAL HISTOLOGY

PATTERNS OF ABNORMAL SMALL-BOWEL ARCHITECTUREThe small-bowel mucosal responses to injury are limited, and recognition of a response pattern can be useful in differential diagnosis

SEVERE VILLOUS ABNORMALITY: Flat intestinal mucosa in which no villi are seen. Usually, diffuse, accompanied by epithelial lymphocytosis (at least 30 to 40 intraepithelial lymphocytes per 100 enterocytes) . Crypt hyperplasia, evidenced by numerous mitotic figures.VARIABLE VILLOUS ABNORMALITY The villi either are only focally flat or are less than flat (mild or moderate villous shortening). May show increased intraepithelial lymphocytes. May be associated with features that suggest a specific diagnosis (e.g., numerous eosinophils, granulomas, parasites), or they may be nonspecific.

CELIAC SPRUE (Gluten-induced Enteropathy, Gluten-sensitive Enteropathy, and Nontropical sprue)Major cause of malabsorpton. The pathogenesis of CS involves immunologic injury to the enterocyte associated with the ingestion of gluten . human leukocyte antigen (HLA)associated condition that is primarily associated with the MHC class II alleles DQA1*0501 and DQB1*0201. rapid and dramatic clinical, serologic, and histologic improvement with the removal of gluten from the diet, and relapse following its reintroduction .

Pathogenesis of CS.

DEFINITIVE DIAGNOSIS OF CELIAC SPRUEA pathologist does not make the diagnosis of CS. All that can be said is that the specimens contain a severe villous abnormality that is consistent with CS. DEFINITIVE DIAGNOSIS depends on the demonstration of a suitable clinical presentation, compatible serologic tests (e.g., immunoglobulin [Ig] A antiendomysial antibodies, IgA anti-tissue transglutaminase antibodies), appropriate small-bowel histology, and clinical and serologic response to gluten withdrawal

Mucosal lesions of CS Classified into five types (Marsh-Oberhuber scheme).

Type 0: The preinfiltrative lesion, is essentially normal.

Type 1: The infiltrative lesion, with intraepithelial lymphocytosis (at least 40 per 100 enterocytes),

Type 2: hyperplastic lesion, variable villous abnormality with epithelial lymphocytosis.

The type 3: Destructive lesion represents the classic CS lesion. type 3a with partial villous shortening, type 3b with a more severe villous change, and a type 3c that is flat

The hypoplastic type 4: An atrophic end-stage lesion that is seen in a minority of patients unresponsive to gluten withdrawal; it includes the lesion of collagenous sprue

Differential diagnosis of celiac sprueIncludes all entities that may cause at least a focal severe villous abnormality Common variable immunodeficiency, Protein allergies other than gluten, Some cases of infectious gastroenteritis Zollinger-Ellison syndrome Chronic ischemic bowel.Inflammatory bowel disease (IBD) . Clinicopathologic correlation is essential for proper diagnosis. Numerous neutrophils, cryptitis, and crypt abscess formation are usually not part of CS.

Entities Associated with a Variable Villous Abnormality and Crypt Hypoplasia

MARASMUS AND/OR KWASHIORKOR: MEGALOBLASTIC ANEMIA: impaired epithelial cell replacement because of decreased DNA synthesis. Consequently, a variable villous abnormality with or without megaloblastic epithelial changes. the villous abnormality is not severe and associated with decreased mitoses in the crypts; and no increase in inflammatory cellsRADIATION AND CHEMOTHERAPY EFFECT: changes are similar to those in megaloblastic anaemia, are associated with decreased mitotic activity in the crypts. There may also cause focal necrosis of epithelial cells (apoptosis) and increased numbers of chronic inflammatory cells within the mucosa and submucosaMICROVILLOUS INCLUSION DISEASE

TROPICAL SPRUE

Chronic diarrheal process associated with steatorrhea .Prevalent in South and Southeast Asia, West Africa, parts of south America. Patients show dramatic response to folate, vitamin B12, and tetracycline or other broad-spectrum antibiotics, suggesting an infectious etiology.Small-bowel biopsy specimens show a variable villous abnormality. Histologic appearance: mild to moderate villous shortening, increased numbers of chronic inflammatory cells in the lamina propria and epithelium, and crypt hyperplasia On occasion, a severe histologic lesion indistinguishable from CS

STASIS SYNDROMESOccur in surgical blind loops, bowel obstruction, small-intestinal diverticulosis, and intestinal pseudo-obstruction. With stasis, bacteria multiply. Associated with malabsorption of fat and vitamin B12, resulting primarily from the bacterial degradation of bile salts and intestinal mucosal injury Patchy variable villous abnormality associated with increased chronic inflammatory cells in the lamina propria and epithelium Few neutrophils may be seen within the lamina and epithelium. INFECTIOUS GASTROENTERITIS Typically patchy with a variable villous abnormality; rarely, the villous abnormality can be severe, closely mimicking CS. Increased chronic inflammatory cells, acute inflammatory cells are often seen both within epithelial cells and in the lamina.The acute onset of the symptoms, with the acute inflammatory changes in biopsy specimens, usually help in the distinction from CS.

SYSTEMIC MASTOCYTOSIS

Rare disorder with infiltration of mast cells in the skin (urticaria pigmentosa), bones, lymph nodes, and other parenchymal organs . 90% demonstrate a D816V KIT mutation The gut, almost half of the affected patientspresent as mucosal nodule or nodularity, erosion, friability, thickening ,loss of folds variable villous abnormality associated with increased numbers of mast cells, or increased numbers of eosinophils. The neoplastic mast cells occur in aggregates & sheets, pericryptal below the luminal surface. cells are round, centrally placed nuclei, eosinophilic or clear cytoplasm. Some can be spindled, elongated.Immunohistochemistry: CD117 and mast cell tryptase for mast cells, and these cells coexpress CD2 and/or CD25.

DIAGNOSIS OF MASTOCYTOSIS. MAJOR CRITERIA: Detection of dense infiltrate of mast cells, at least 15 in aggregate, in the bone marrow or at extracutaneous sites. MINOR CRITERIA: Atypical or spindle-shaped morphology in >25% of the mast cells.detection of the D816V KIT mutationcellular expression of CD2 and/or CD25 a serum tryptase > 20 ng/mL. DIAGNOSIS REQUIRES THE MAJOR AND ONE MINOR OR THREE MINOR CRITERIA.

Entities Associated with Variable Villous Abnormalities Illustrating Specific Diagnostic ChangesCOLLAGENOUS SPRUE The excessive subepithelial deposition of collagen associated with severe villous abnormalityin small-bowel with malabsorption unresponsive to a gluten-free diet . Most pts have had a max subepithelial collagen deposit (exceeding 10 m). The collagen distribution is typically patchy and it may not be present early in the disease.. Can coexist with collagenous colitis/ileitis and/or collagenous gastritis. T-cell receptor gene rearrangements in few suggesting lymphoproliferative disorders. Antihypertensive drug olmesartan causing collagenous sprue-like changes as well as lymphocytic and collagenous gastritis and colitis .

Whipple disease, Tropheryma whippeliA chronic systemic illness with gastrointestinal features such as diarrhea and malabsorption.The diagnosis of Whipple disease is usually based on the identification of PAS-positive, diastase-resistant inclusions in small-intestinal biopsy specimens. The diagnosis can be confirmed by PCR for the bacterial 16S ribosomal RNA, EM ad IHC. Infiltration of various organs with macrophages containing the bacilli. (lamina of the small intestine, the mesenteric lymph nodes, the cardiac valves, and the central nervous system).Mucosal biopsy demonstrate infiltration of the lamina propria; muscularis mucosae; and, in some cases, submucosa by macrophages with a foamy gray-blue cytoplasm . fat vacuoles are seen in the lamina propria. The macrophage cytoplasm contains intensely PAS-positive material that is coarsely granular.

NONNEOPLASTIC POLYPS AND NODULES OF THE SMALL BOWELThe most common nonneoplastic polyps of the small bowel are hyperplastic polyps of gastric mucosa arising in gastric foveolar metaplasia or gastric heterotopia.Pancreatic heterotopia presence of pancreatic acinar, islet, or ductular elements outside pancreas. Common sites are stomach, duodenum, and jejunum. May also be seen in meckel diverticula, ampulla of vater, Gall bladder, umblicus FT , mesentry and mediastinum.Present grossly as submucosal nodule, intramural mass or nudular serosal mass.Histologically, acinar element of islet cells with ducts and smooth muscles.Adenomyoma /myoepithelial hamartoma : absence of both acinar and islet-like tissue

Hyperplasia of Brunner glandsBrunner glands are branched tubuloalveolar glands found only in duodenum mostly in submucosal, Hyperplasias of Brunner glands exist in three forms (a) diffuse glandular proliferation: imparting a coarse nodularity to most of the duodenum; (b) limited discrete nodules in the proximal duodenum; and (c) solitary nodules, often referred to as adenoma of Brunner glands. Mostly incidental findings Histologically, increased numbers of normal-appearing Brunner glands, accompanied by variable proliferations of smooth muscle. Inflammatory cells are often present, and some larger lesions may ulcerate. A gross nodule or polyp composed solely of Brunner-type glands,

Pattern of colonic inflammation.

Chronic colitis Diffuse active colitis, Focal active colitis, Ischemic-type colitis, Trauma change, Apoptotic colopathy, and Intraepithelial lymphocytosis

Active Colitis

Describes an inflammatory condition in which neutrophils are present in the lamina propria, within the epithelial cells (cryptitis), or within the crypt lumens (crypt abscesses). Included under this heading are: (a) UC in an active phase, (b) most examples of Crohn colitis, and (c) infectious colitis and/or acute self-limited colitis Recognition of an inflammatory pattern, coupled with clinical and endoscopic correlation, allows a fairly specific diagnosis to be made in many biopsy specimens.

EVALUATION OF RESECTION SPECIMENS IN INFLAMMATORY BOWEL DISEASEAfter specific causes of enteritis and colitis have been ruled out, a group of diseases referred to as idiopathic IBD is left. IBD describes at least the following three entities: CD, UC, and colitis of indeterminate type. Despite their nonspecific nature, the pathologic features of CD and UC are sufficiently distinctive that they can usually be distinguished from each other and from other kinds of bowel inflammation

INFLAMMATORY BOWEL DISEASE.Chronic condition resulting from inappropriate mucosal response.Ulcerative colitis: severe ulcerating inflammatory disease that is limited to the colon and rectum and extends only into the mucosa and submucosaCrohn disease: referred to as regional enteritis. It may involve any area of the GI tract and is typically transmural.

EPIDEMIOLOGYMore frequently present in teens and early 20s.More in females.Caucasians and eastern jews.IBD worldwide is on the rise. Hygiene hypothesis.

PATHOGENESISBoth UC and CD develops due to defects in host interactions with intestinal microbiota, intestinal epithelial dysfunction and aberrant mucosal immune responses.Genetics

Crohn disease.Small intestinal strictureLinear mucosal ulcers and thickened intestinal wall.Perforation and associated serositisCreeping fat.

Ulcerative colitis

A. Total colectomy with pancolitis showing active disease.B. Sharp demarcation between active UC and normal mucosaC. Inflammatory polypsMucosal bridging.

COLONIC DIVERTICULAColonic diverticula are small, flask-like outpouchings that occur in a regular distribution alongside the taeniae. 0.5 to 1 cm in diameter, most common in the sigmoid colonColonic diverticula have a thin wall composed of a flattened or atrophic mucosa, compressed submucosa, and attenuated or, totally absent muscularis propria Hypertrophy of the circular layer of the muscularis propria Obstruction of diverticulae leads to inflammatory changes, producing diverticulitis and peri-diverticulitis and perforation. Diverticulitis may cause segmental diverticular diseaseassociated colitis, fibrotic thickening in and around the colonic wall, or stricture formation. Perforation can result in pericolonic abscesses, sinus tracts, and, occasionally, peritonitis.

Sigmoid diverticulitis.

Stool filled diverticula arranged regularly.Cross section showing out pouchings of mucosa beneath the muscularis propriaProtrusion of mucosa and sbmucosa through muscularis propria. .

FOLICULAR PROCTITIS demonstrating prominent lymphoid follicle formation with cryptitis and superficial erosions

Acute Ischemic-Type ChangeHemorrhage into the lamina propria with superficial epithelial coagulative necrosis with sparing of deep portions of the crypts. Extensive necrosis of the superficial epithelium with inflammatory pseudomembrane formation. acute and chronic inflammatory cells (e.g., plasma cells) are typically few. The differential diagnosis: inadequate perfusion, narrowing of blood vessels for any reason, trauma/prolapse and obstructing lesions of the bowel, and bowel distention. Associated with a wide variety of drugs, including vasopressors, oral contraceptives, NSAIDs, cocaine, and glutaraldehyde Some infectious agents, such as cytomegalovirus (CMV), Clostridium difficile, Clostridium septicum, and the enterohemorrhagic Escherichia coli,

Pseudomembranous colitis. An inflammatory pseudomembrane exudes from the dilated degenerating crypt in an eruptive fashion. The karyorrhectic debris and neutrophils within the pseudomembrane tend to align in a linear configuration within the mucin.

Collagenous colitis. Thickened subepithelial collagen layer accompanied by chronic inflammatory cells in the lamina propria and the surface epithelium. The surface epithelial degenerative changes are accompanied by epithelial lymphocytosis.

Lymphocytic colitis. (A) Chronic inflammatory cells are increased within the lamina propria, and they are not associated with architectural distortion. (B) Higher magnification reveals a striking epithelial lymphocytosis.

Acute graft-versus-host disease..

Numerous apoptotic bodies (eosinophilic globules and nuclear debris) are present

Biopsy specimen of the mucosa adjacent to an ulcer from a patient with solitary rectal ulcer syndrome. The normal lamina propria has been replaced by fibrosis and smooth muscle. The mucosal capillaries are ectatic.

Follicular proctitisprominent lymphoid follicle formation associated with cryptitis and superficial erosion

defunctionalized rectum Lymphoid follicle formation accompanied by cryptitis and crypt abscess formation, and it appears similar to follicular proctitis.

Tumours of intestinesPolypsCarcinomaCarcinoid Lymphoma.

polypClinical term or gross description of any circumscribed tumour or growth that projects above the surrounding mucosa.A polyp can be neoplastic, inflammatory, or hamartomatous.Only by histologic examination one can be certain of the nature and clinical significance.

Types of polyps Non neoplastic polyps: 90%Hyperplastic polypHamartomatous (juvenile and Peutz Jhegers polyps)Inflammatory polyplymphoid Polyp.

Neoplastic polyps: 10%Adenoma

Serrated polyps:

Hyperplastic polyp: distal colon/rectum. 10 mm size. premalignantSerrated polyposis syndrome. Previously called hyperplastic polyposis

WHO definition of SPS.At least 5 histologically diagnosed serrated polyp prox. to sigmoid colon, two>10cm size.Any no of polyps occurring prox. To sigmoid colon wih F/o SPS.> 30 serrated polyps of any size throughout colorectum.

Polyps Hyperplastic Polyp

Asymtomatic > 50% are located in the rectosigmoid Sawtooth surface Star shaped crypts Composed of well-formed glands and crypts lined by differentiated goblet or absorptive cells.

Types of hyperplastic polyp. Microscopically, three types.

Microvesicular hyperplastic polyp (MVHP)goblet cell hyperplastic polyp ( GCHP)Mucin poor hyperplastic polyp (MPHP)

They are molecular difference between diff subtypes.

mutationGCHPMVHPK-ras mutation43%13%BRAF(V600E) mutation 21%76%CIMP-H mutation14%47%

Serrated sessile adenoma/polyp.Flat and sessile lesion.Diagnosis is based on architectural features .Branching and dilatation of the base of cryptsInverted T or L shaped

Traditional serrated adenoma pedunculated/ polypoid in nature Complex serrated architecture misdiagnosed as villous adenoma.Cells are uniform, pencilate cells with bright eosinophilic cytoplasm.Pseudostratified nuclei, increased NC ratio, hyperchromatism and mitosis mild.

SESSILE SERRATED ADENOMA/POLYP WITH DYSPLASIA.

Hamartomatous polyp Juvenile Polyps (retention polyp

Developmental malformations affecting the glands and lamina propria. Commonly occur in children under 5 years old in the rectum. In adult called retention polyp.

Junenile polyp.Mainly occurs in first two decades of life.Localised chiefly in rectum, usually solitary.Bleeding is most common symptom.Criteria of juvenile polyposis >5 polyps of the colon and rectum.Juvenile polyps in pt with a F/O.Juvenile polyp through entire length of GI tract.Any no. polyp in pts with F/o.

JUVENILE POLYP

Familial adenomatous polyposisAutosomal dominant disorder with development numerous colorectal adenomas as teenagers. Mutations of the adenomatous polyposis coli (APC) gene>100 polyps are necessary for a diagnosis of classic FAP. Microscopic adenomas, consist of only one or two dysplastic glands observed in otherwise normal mucosa. Colorectal adenocarcinoma develops in 100% of untreated FAP cases, often before age of 30. Extra-intestinal manifestations: congenital hypertrophy of the retinal pigment epithelium. Screening. Gardner syndrome families have osteomas of mandible, skull, and long bones, epidermal cysts, desmoid tumors, thyroid tumors, and dental abnormalities, including unerupted and supernumerary teeth. Turcot syndrome is rarer and characterized by intestinal adenomas and tumors of the central nervous system.

Peutz-Jehgers syndrome

Non-Neoplastic Hamartomatous Polyps.Rare, autosomal dominant hamartomatous polyps accompanied by mucosal and cutaneous pigmentation around the lips, oral mucosa, face and genitalia. Polyps tend to be large and pedunculated. Increased risk of developing carcinoma of the pancreas, breast, lung, ovary and uterus.

Non-Neoplastic Polyps Inflammatory Polyps longstanding IBD, especially in chronic ulcerative colitis. Represent an exuberant reparative response to longstanding mucosal injury called pseudopolyps

GANGLIONEUROMA

Inflammatory polyp.

Bizarre stromal changes.High power view shows cells with enlarged bizarre nuclei.

Lymphoid polyp

Low power view showing polyp secondary to lymphoid tissue with germinal centre.High power view showing a lymphoid nodule with a reactive germinal centre.

Neoplastic polyp (adenoma) Tubular TubulovillousVillous.Polypoid or non polypoid.Clinically important: premalignant lesionsCommon in large intestine, and rare in small intestine.Small intestine: tubular or villous and sessile.90% pt with FAP coli hav small intestinal adenoma.

Small intestinal adenoma

Familial adenomatous polyposis. High power view showing a villus half of which has adenomatous change.

Large intestine adenoma Prevelance Invasive cancertubular95%2-3%tubulovilous2-4%6-8%villous1-3%10-18%

Villous adenoma

Whole mount view showing adenomatous epithelium in villous arrangement.High power view showing elongated nuclei with palisading. Nuclei do not reach cell surface with mucin production at the apical portion.

Examples of reporting malignant polypsExample 1: sigmoid colon, polypectomy: grade III adenocarcinoma arising within an adenoma. The cancer extends to the transected margin of resection. No evidence of lymphatic or venous invasion.

Example 2: Rectum, polypectomy: grade II adenocarcinoma arising within adenoma. Cancer is 2.5cm from transected margin (the margin is negative for cancer). No evidence of lymphatic or venous invasion.

Adenoma with pseudoinvasion.

Familial adenomatous polyposisAutosomal dominant disorder.Colon is carpeted with adenomas (100-1000) Diagnostic criteria:100 or more colorectal polyps.Germline mutation in APC gene.F/o APC.At least one of the following: epidermal cyst, osteoma, desmoid tumour.ALL patient of FAP develop colonic adenocarcinoma if disorder is left untreated.

Familial adenomatous poyposis.

Attenuated FAPLess severe form of polyposis with lower number of polyps (