GASTROINTESTINAL TRACT PATHOLOGY

by Mary Yvonnette C. Nerves, RMT, MD, FPSP

GIT Pathology
CONGENITAL ABNORMALITIES ESOPHAGUS STOMACH SMALL/LARGE BOWEL APPENDIX

GIT Pathology
CONGENITAL ABNORMALITIES ESOPHAGUS STOMACH SMALL/LARGE BOWEL APPENDIX

CONGENITAL ABNORMALITIES
Atresia/Fistulae Diaphragmatic Hernia/ Omphalocele/Gastroschisis Meckels Diverticulum Pyloric Stenosis Hirschsprung Disease

ATRESIA / FISTULAE
Atresia is a condition in which a body orifice or passage in the body is abnormally closed or absent Fistula is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect.

OMPHALOCELE (Exomphalos)
defect of the anterior abdominal wall at the insertion of the umbilical cord occurs in 1 in 5000 to 1 in 20,000 live births associated with chromosomal defects, (trisomies 13, 18, and 21), and with other disorders such as Beckwith-Wiedemann syndrome

OMPHALOCELE (Exomphalos)

Closure of abdominal musculature is incomplete abdominal viscera herniate into a ventral membranous sac

GASTROSCHISIS (Laparoschisis)
a small (generally < 5 cm) defect of the abdominal wall just to the right of the umbilical cord insertion, allowing evisceration of bowel loops, stomach, and sometimes the gonads Prevalence: 1 in 10,000 livebirths

GASTROSCHISIS (Laparoschisis)

ventral wall defect involving all layers of the abdominal wall

MECKEL DIVERTICULUM
most common type of true diverticulum occurs in the ileum occurs as a result of failed involution of the omphalomesenteric (vitelline) duct RULE of 2s: - 2% of the popn - present within 2 feet of the ICV - approx. 2 inches long - 2x as common in males - symptomatic by age 2

MECKEL DIVERTICULUM

TRUE DIVERTICULUM: blind outpouching lined by mucosa that communicates with the lumen and includes all 3 layers of the bowel wall

MECKEL DIVERTICULUM

PYLORIC STENOSIS
due to progressive thickening of the circular muscle of the pylorus gastric outlet narrowing 3-4x more common in MALES generally presents in the 2nd or 3rd week of life new-onset regurgitation and persistent, projectile, nonbilious vomiting P.E. hyperperistalsis; ovoid abdominal mass Tx: Fredet-Ramstedt pyloromyotomy

HIRCHSPRUNG DISEASE
A.k.a. Congenital aganglionic megacolon when normal migration of neural crest cells from the cecum to rectum is arrested prematurely or when the ganglion cellsundergo premature death distal intestinal segment lacks both Meissner submucosal and the Auerbach myenteric plexus

HIRCHSPRUNG DISEASE
Clinical Features: earliest and most common presentation is delayed (> 48 hrs) passage of meconium in the newborn - Infants and older children: chronic constipation, abdominal distention and vomiting Pathologic Feature: distal narrow aperistaltic hypertonic segment (aganglionic) and a dilated proximal segment caused by obstruction

Aganglionic region may have a grossly normal or contracted appearance while the normally innervated proximal colon may undergo progressive dilation

IMPERFORATE ANUS
most common form of congenital intestinal atresia

due to failure of the cloacal diaphragm to involute

GIT Pathology
CONGENITAL ABNORMALITIES ESOPHAGUS STOMACH SMALL/LARGE BOWEL APPENDIX

ESOPHAGUS
Esophageal Obstruction - Achalasia Esophagitis Barretts Esophagus Esophageal Varices Esophageal Tumors

DIVERTICULUM
an outpouching of the alimentary tract that contains one or more layers of the wall ZENKERS DIVERTICULUM (Cricopharyngeal / Pharyngoesophageal): located above the UES - results from increased intrapharyngeal pressure in areas of weakness along the esophageal wall

DIVERTICULUM
ZENKERS DIVERTICULUM

Diverticulectomy with myotomy

DIVERTICULUM
TRACTION DIVERTICULUM: located immediately above the UES - located in the lower 3rd of the esophagus and in the region of the hilum of the lung - attributed to fibrosing mediastinal processes or abnormal motility.
EPIPHRENIC DIVERTICULUM: immediately above the LES - located just above the diaphragm - Cause: unclear

ESOPHAGEAL MUCOSAL WEBS

ledge-like protrusions of mucosa Pathogenesis: unknown PATERSON-BROWN-KELLY or PLUMMER-VINSON SYNDROME: webs + IDA + glossitis + cheilosis most common in upper esophagus

ESOPHAGEAL RINGS
A.k.a. Schatzkis / Lower esophageal Esophagogastric rings similar to webs but are circumferential and thicker rings include mucosa, submucosa and, in some cases, hypertrophic muscularis propria A rings: present in distal esophagus, above the GEJ B rings: located at the squamocolumnar junction of the lower esophagus

ESOPHAGEAL RINGS

ACHALASIA
A.k.a. Cardiospasm or megaesophagus failure of the cardiac mechanism to open when peristaltic waves conveying food through the esophagus reach it
nearly complete loss of myenteric ganglion cells is present in the lower 3rd of the esophagus

ACHALASIA
TRIAD:
Aperistalsis Incomplete relaxation of the LES Increased LES tone Barium swallow: dilated, aperistaltic esophagus with a beak-like tapering at distal end Progressive dysphagia starting in teens Pathogenesis: unknown

Technique for pneumatic dilation of achalasia.

Technique for intrasphincteric injection of botulinum toxin for achalasia.

REFLUX ESOPHAGITIS
A.k.a. Gastroesophageal Reflux Disease (GERD) reflux of gastric contents into the lower esophagus (most frequent cause of esophagitis) Most common clinical symptoms: dysphagia, heartburn, regurgitation of sour-tasting gastric contents

REFLUX ESOPHAGITIS
Pathogenesis: reflux of gastric juices is central to the devt of mucosal injury

REFLUX ESOPHAGITIS
Pathogenesis:
- Conditions that decrease LES tone or increase abdominal pressure:

a) alcohol and tobacco use, obesity

b) central nervous system depressants

c) pregnancy
d) hiatal hernia e) delayed gastric emptying f) increased gastric volume

REFLUX ESOPHAGITIS
Gross: marked hyperemia with focal hemorrhage

REFLUX ESOPHAGITIS
Morphology: intraepithelial eosinophils and basal zone hyperplasia

HIATAL HERNIA
Characterized by separation of the diaphragmatic crura and protrusion of the stomach into the thorax through the resulting gap

VARICES
THREE common areas of portal/caval anastomoses

Esophageal Umbilical Hemorrhoidal

100% related to portal hypertension Found in 90% of cirrhotics MASSIVE, SUDDEN, FATAL hemorrhage is the most feared consequence

VARICES

VARICES

VARICES
FACTORS that lead to RUPTURE: - inflammatory erosion of thinned overlying mucosa - increased tension in progressively dilated veins - increased vascular hydrostatic pressure associated w/ vomiting

VARICES

VARICES

BARRETTS ESOPHAGUS
Can be defined as intestinal metaplasia of a normally SQUAMOUS esophageal mucosa.
The presence of GOBLET CELLS in the esophageal mucosa is DIAGNOSTIC. SINGLE most common RISK FACTOR for esophageal adenocarcinoma 10% of GERD patients get it Most common in white males; between 4060 years of age

BARRETTS ESOPHAGUS

GROSS: patches of red, velvety mucosa extending upward from the GEJ

BARRETTS ESOPHAGUS
INTESTINALIZED (GASTRICIZED) mucosa is AT RISK for glandular dysplasia. Searching for dysplasia when BARRETTs is present is of utmost importance MOST/ALL adenocarcinomas arising in the esophagus arise from previously existing BARRETTs

BARRETTS ESOPHAGUS

BARRETTS ESOPHAGUS

TUMORS
BENIGN MALIGNANT
Squamous cell carcinoma Adenocarcinoma

BENIGN TUMORS
LEIOMYOMAS FIBROVASCULAR POLYPS CONDYLOMAS (HPV) LIPOMAS GRANULATION TISSUE (PSEUDOTUMOR)

ADENOCARCINOMA
Arises in a background of Barrett esophagus & long-standing GERD RISK FACTORS: documented dysplasia tobacco use obesity prior radiation therapy

ADENOCARCINOMA
FACTORS that DECREASE RISK: - diet rich in fresh fruits and vegetables - H. pylori serotypes Most frequent in CAUCASIANS; M > F Usually occur in the distal 3rd of the esophagus

ADENOCARCINOMA

ADENOCARCINOMA

ADENOCARCINOMA

ADENOCARCINOMA

SQUAMOUS CELL CARCINOMA

Adults over age 45, affects MALES 4x more than females RISK FACTORS: a) alcohol and tobacco use b) caustic esophageal injury c) achalasia

SQUAMOUS CELL CARCINOMA

RISK FACTORS:
d) Plummer-Vinson syndrome e) frequent consumption of very hot beverages sixfold more common in AfricanAmerican

SQUAMOUS CELL CARCINOMA

Half of SCCs occur in the middle 3rd of the esophagus Begins as an in-situ lesion (SQUAMOUS DYSPLASIA)

SQUAMOUS CELL CARCINOMA

SQUAMOUS CELL CARCINOMA

DYSPLASIAIN-SITUINFILTRATION

Adenocarcinoma
Commonest type in

Squamous cell Carcinoma

Commonest type worldwide Risk factors: esophagitis, smoking, alcohol, genetics Middle 1/3 of esophagus Symptoms: insidious onset; late obstruction

US Risk factor: Barrett esophagus Distal 1/3 of esophagus Symptoms: insidious onset; late obstruction

ESOPHAGEAL CARCINOMA
FACTORS that influence survival:
1. Sex F > M 2. Stage In situ, mucosal CA, superficial CA > deeper tumors 3. LN mets 2 or more involved nodes: worse prognosis 4. Other microscopic findings: vascular/lymphatic invasion & marked tumor necrosis 5. Involvement of circumferential surgical margins high probability of recurrence 6. Overexpression of EGFR/p53 worse prognosis

GIT Pathology
CONGENITAL ABNORMALITIES ESOPHAGUS STOMACH SMALL/LARGE BOWEL APPENDIX

STOMACH
CHRONIC GASTRITIS PEPTIC ULCER GASTRIC POLYPS HYPERTROPHIC GASTROPATHY TUMORS

CHRONIC GASTRITIS
H. pylori gastritis: most common cause of chronic gastritis

Autoimmune gastritis: most common cause of atrophic gastritis and most common cause of chronic gastritis in patients w/o H. pylori infection

CHRONIC GASTRITIS
H. pylori gastritis:
- H. pylori: spiral shaped or curved bacilli - present in almost ALL duodenal ulcers & majority of individuals with gastric ulcers or chronic gastritis - present in 90% of individuals w/ chronic gastritis affecting the ANTRUM

CHRONIC GASTRITIS
H. pylori gastritis:
- increased acid secretion may result in PUD - H. pylori infection confers increased risk of gastric Ca - H. pylori transmission: oral-oral; fecaloral; and environmental spread

CHRONIC GASTRITIS
H. pylori gastritis:
- 4 Features linked to H. pylori virulence:
a) Flagella allow motility in viscous mucus b) Urease generates NH3 from endogenous urea & elevates local gastric pH c) Adhesins enhance bacterial adherence to surface foveolar cells d) Toxins cytotoxin-assoc gene A (cagA) involved in ulcer & cancer devt

CHRONIC GASTRITIS
Autoimmune gastritis: spares the antrum and includes hypergastrinemia - char by: a) Abs to parietal cells & IF b) Reduced serum pepsinogen I conc c) Antral endocrine cell hyperplasia d) Vit. B12 def. e) defective gastric acid secretion (achlorhydria)

CHRONIC GASTRITIS
Autoimmune gastritis: - Pathogenesis: loss of parietal cells (responsible for secretion of gastric acid and IF)

loss of gastric acid stimulates gastrin release hypergastrinemia & hyperplasia of antral gastrinproducing G cells Lack of IF disables ileal vit. B12 abs. B12 def. megaloblastic anemia

CHRONIC GASTRITIS
Autoimmune gastritis: - Morphology:

Diffuse atrophy Intestinal metaplasia Antral endocrine hyperplasia

GASTRITIS
H. PYLORI-ASSOCIATED LOCATION INFLAM INFILTRATE ACID PRODUCTION GASTRIN OTHER LESIONS SEROLOGY SEQUELAE antrum PMNs, subepith plasma cells Increased to sl. decreased Normal to decreased Hyperplastic/inflam polyps Abs to H. pylori Peptic ulcer, adenoCA AUTOIMMUNE body Lymphocytes, macrophages Decreased Increased Neuroendocrine hyperplasia Abs to parietal cells Atrophy, PA, AdenoCA, carcinoid tumor

ASSOCIATIONS

Low socioeconomic status, poverty, residence in rural areas

Autoimmune disease; thyroiditis, DM, Graves dse

COMPLICATIONS of CHRONIC GASTRITIS

Peptic Ulcer Disease Mucosal atrophy and intestinal metaplasia Dysplasia

PEPTIC ULCER DISEASE

Most often associated with H. pylorihyperchlorhydric chronic gastritis Present in 85-100% persons with duodenal ulcers and 65% with gastric ulcers

PEPTIC ULCER DISEASE

Pathogenesis: imbalances of mucosal defenses and damaging forces that cause chronic gastritis H. pylori & NSAID use: primary underlying cause of PUD
Gastric hyperacidity: - H. pylori infection, parietal cell hyperplasia, excessive secretory responses or impaired inhibition of stimulatory mechanisms such as gastrin release

PEPTIC ULCER DISEASE

Common co-factors in peptic ulcerogenesis:
- chronic NSAID use: direct chemical irritation & suppress PG release necessary for mucosal protection - Cigarette smoking: impairs mucosal blood flow & healing - high-dose corticosteroids: suppress PG synthesis & impair healing

PEPTIC ULCER DISEASE

Solitary in > 80% of patients < 0.3 cm. shallow ulcers > 0.6 cm. - deeper ulcers Round or oval, sharply punched-out defect mucosal surface overhang the base (heaped up margins cancer)

PEPTIC ULCER DISEASE

Gnawing, burning, aching pain, epigastric Fe deficiency anemia Acute hemorrhage Penetration, perforation:

Pain in BACK Pain in CHEST Pain in LUQ

MALIGNANT TRANSFORMATION very rare

PEPTIC ULCER DISEASE

COMPLICATIONS of Gastric Ulcers

Bleeding
Occurs in 15% to 20% of patients Most frequent complication May be life-threatening Accounts for 25% of ulcer deaths May be the first indication of an ulcer

COMPLICATIONS of Gastric Ulcers

Perforation
Occurs in about 5% of patients Accounts for two thirds of ulcer deaths Rarely, is the first indication of an ulcer

COMPLICATIONS of Gastric Ulcers

Obstruction from edema or scarring
Occurs in about 2% of patients Most often due to pyloric channel ulcers May also occur with duodenal ulcers Causes incapacitating, crampy abdominal pain Rarely, may lead to total obstruction with intractable vomiting

MUCOSAL ATROPHY and INTESTINAL METAPLASIA

Strongly associated with increased risk of gastric adenoCA The risk of adenoCA is greatest in autoimmune gastritis

DYSPLASIA
Chronic gastritis exposes epith to inflam-related free radical damage & proliferative stimuli genetic alterations Morphologic HALLMARKS:
a) Variations in epithelial size, shape and orientation b) coarse chromatin texture c) hyperchromasia and nuclear enlargement

HYPERTROPHIC GASTROPATHY
Rugal prominence (cerebriform) No inflammation Hyperplasia of mucosa

HYPERTROPHIC GASTROPATHY
Mntrier disease: resulting from profound hyperplasia of the surface mucous cells with accompanying glandular atrophy, ass. w/ CMV, H. Pylori, TGF- Hypertrophic-hypersecretory gastropathy: associated with hyperplasia of the parietal and chief cells within gastric glands
(normal gastrin)

MENETRIER DISEASE

HYPERTROPHIC GASTROPATHY
Gastric gland hyperplasia secondary to

excessive gastrin secretion, in the setting

of a gastrinoma (Zollinger-Ellison syndrome)

ZOLLINGER-ELLISON SYNDROME

GASTRIC POLYPS
Polyps: nodules or masses that project above the level of the surrounding mucosa Inflammatory and Hyperplastic Polyps:
approx. 75% of all gastric polyps usually develop in assoc with chronic gastritis Gross: majority are smaller than 1 cm. & frequently multiple; ovoid w/ smooth surface

HYPERPLASTIC POLYP

Micro: irregular, cysticaly dilated and elongated foveolar glands

GASTRIC POLYPS
Fundic Gland Polyps:
occur sporadically and in individuals w/ familial adenomatous polyposis 5x more common in females (ave. 50 y/o) occur in the gastric fundus Gross: well-circumscribed & smooth Micro: cystically dilated, irregular glands lined by flattened parietal or chief cells

GASTRIC POLYPS
Gastric adenoma:
almost always occur on a background of chronic gastritis with atrophy and intestinal metaplasia 3x more common in males (50-60 y/o) increased incidense in pts w/ FAP Risk of adenoCA is related to the size of the lesion (> 2 cm.) CA may be present in up to 30% of gastric adenomas

GASTRIC POLYPS
Gastric adenoma:
most commonly located in antrum Gross: solitary, < 2 cm. Micro: ALL GI adenomas have epithelial dysplasia

GASTRIC ADENOMA

CARCINOMA
Pathogenesis: closely related to environmental factors Arise from the generative or basal cells of the foveolae, on a background of chronic atrophic gastritis w/ intestinal metaplasia and preceded by various stages of dysplasia, CIS, and superficial CA Accompanied by hypochlorhydria in 8590% of cases

CARCINOMA
(2) Major categories of gastric adenocarcinoma: a. INTESTINAL-TYPE - arise from metaplastic epithelium B. DIFFUSE-TYPE - best represented by linnitis plastica or signet ring (adeno)carcinoma

ADENOCARCINOMA GROWTH PATTERNS

LINITIS PLASTICA

LINITIS PLASTICA

ADENOCARCINOMA
Depth of invasion & extent of nodal and distant metastasis at time of diagnosis: MOST powerful prognostic indicators for gastric cancers Advanced CA: first detected as mets to the supraclavicular sentinel LN (Virchows node) Sister Mary Joseph nodule: marker of metastatic CA - subcutaneous nodule in periumbilical region

GASTRIC CARCINOMA
FACTORS related to prognosis:
1. Patients age CA in the young: worse 2. Tumor stage the deeper the penetration, the greater the chance of mets; polypoid, large intraluminal tumors have lower mets < tumors growing within the wall 3. Location within the stomach: 80% of 5-yr survivors, the lesion is in the distal half of the stomach 4. Tumor margins: pushing/expanding border vs. Diffuse infiltration

GASTRIC CARCINOMA
FACTORS related to prognosis:
5. Microscopic type and grading intestinal type > diffuse type 6. Inflammatory reaction: cellular infiltrate at the interface bet tumor & normal tissue: GOOD px sign 7. Perineural invasion: poor px 8. Regional LN involvement: if NEG, >50% may survive for 5 years

GASTRIC CARCINOMA
FACTORS related to prognosis: 9. Type of surgery radical subtotal
gastrectomy: best survival 10. Overexpression of c-erbB2 protein, p53 poor prognosis 11. Detection of cathepsins and cyclindependent kinase inhibitor (p27Kip1) expression by IHC: reduced survival

LYMPHOMA
5% of gastric malignancies Most common are extra-nodal marginal zone B-cell lymphomas (lymphoma of mucosaassociated lymphoid tissue or MALToma) Pathogenesis: Usually arise at sites of chronic inflammation - pro-lymphomatous inflam: H. Pylori infection - translocations: t(11;18)(q21;q21) most common activation of NF-kB, a transcription factor that promotes B cell growth & survival

LYMPHOMA
Micro: dense lymphocytic infiltrate in the lamina propria lymphoepithelial lesions - express B cell markers CD19 and CD20 Clinical Features: most common presenting symptoms dyspepsia & epigastric pain

CARCINOID TUMOR
Arise from the diffuse components of the endocrine system Gross: intramural or submucosal masses that create small polypoid lesions

CARCINOID TUMOR
Micro: islands, trabeculae, strands, glands, or sheets of uniform cells with scant, pink granular cytoplasm and a round to oval, stipples nucleus

CARCINOID TUMOR
Immuno: (+) for endocrine granule markers (synaptophysin and chromogranin A) The MOST important prognostic factor for GI carcinoid tumors is LOCATION Foregut carcinoid tumors RARELY METASTASIZE

G.I.S.T.
Can behave and/or look benign or malignant Usually look like smooth muscle, i.e., stroma, spindly tumor cells are derived from the interstitial cells of Cajal, a neural type of cell, similar to the neural plexi found in the intestines (pacemaker cells for gut peristalsis)

G.I.S.T.
Pathogenesis: 75-80% of all GISTS have oncogenic, gain-of-function mutations of the gene encoding the tyrosine kinase c-KIT (receptor for stem cell factor) Gross: solitary, well-circumscribed, fleshy mass

G.I.S.T.

G.I.S.T.

Spindle cell type Epithelioid type

G.I.S.T.

CD 117

G.I.S.T.
Can behave and/or look benign or malignant Usually look like smooth muscle, i.e., stroma, spindly Are usually POSITIVE for c-KIT (CD117) tumor cells are derived from the interstitial cells of Cajal, a neural type of cell, similar to the neural plexi found in the intestines.

G.I.S.T.

G.I.S.T.

G.I.S.T.

CD 117

GIT Pathology
CONGENITAL ABNORMALITIES ESOPHAGUS STOMACH SMALL/LARGE BOWEL APPENDIX

SMALL/LARGE INTESTINE
INFLAMMATORY BOWEL DISEASE Crohns Disease Ulcerative Colitis OBSTRUCTION TUMORS

IBD
CROHNS DISEASE (granulomatous
colitis)

ULCERATIVE COLITIS

IBD DIFFERENCES

Crohns disease

Ulcerative colitis

CHROHNS DISEASE

CHROHNS DISEASE

CHROHNS DISEASE

ULCERATIVE COLITIS

ULCERATIVE COLITIS

ULCERATIVE COLITIS

OBSTRUCTION
Small Intestine most often involved Clinical manifestations: - abdominal pain & distention, vomiting and constipation

OBSTRUCTION
ANATOMY
ADHESIONS (post-surgical) IMPACTION HERNIAS VOLVULUS INTUSSUSCEPTION TUMORS INFLAMMATION, such as IBD (Crohn) or diverticulitis STRICTURES/ATRESIAS STONES, FECALITHS, FOREIGN BODIES CONGENITAL BANDS, MECOMIUM, INPERF. ANUS

OBSTRUCTION

HERNIAS
Any weakness in the wall of the peritoneal cavity that permits protrusion of a serosa-lined pouch of peritoneum (hernial sac) Acquired hernias: most commonly occur anteriorly via the femoral and inguinal canal or umbilicus or sites of surgical scars visceral protrusion (external herniation)

HERNIAS

ADHESIONS
Surgical procedures, infection or other causes of peritoneal inflam (eg. Endometriosis) adhesions between bowel segments, abdominal wall & operative sites fibrous bridges create closed loops internal herniation

INTUSSUSCEPTION
A length of intestine (intussuscipiens) literally swallows part of the bowel just proximal to it (intussusceptum) most cases are seen during the first 5 yrs of life Infants & children: rotavirus infection Older children and adults: intraluminal mass or tumor serves as point of traction

OBSTRUCTION
PHYSIOLOGY
ILEUS, esp. postsurgical INFARCTION MOTILITY DISEASES, esp., HIRSCHSPRUNG DISEASE

TUMORS
NON-NEOPLASTIC (POLYPS) BENIGN MALIGNANT

POLYPS
Inflammatory Polyps - forms as a result of chronic cycles of injury and healing

POLYPS
Hamartomatous Polyps - occur sporadically - hamartoma: tumor-like growths of mature tissues that are normally present at the site in which they develop - assoc w/ genetically determined or acquired syndromes

POLYPS
Hamartomatous Polyps

POLYPS
Juvenile Polyp - focal malformations of the mucosal epith & lamina propria - majority occur in children <5 y/o - majority are located in rectum rectal bleeding

Juvenile (retention) polyp. Note the ulcerated, highly hyperemic surface.

POLYPS
Hyperplastic Polyp - epithelial proliferations discovered in the 6th and 7th decades of life - Pathogenesis: decreased epith turnover & delayed shedding of surface epith cells piling up of goblet & absorptive cells - NO malignant potential

Gross appearance of multiple hyperplastic polyps. The lesions are characteristically small, sessile, and pale.

Microscopic appearance of hyperplastic polyp. The individual glands show a typical serration of their mid portion.

POLYPS
Neoplastic Polyp (Adenomas) - precursors to the majority of colorectal adenocarcinomas - char by the presence of epithelial dysplasias

POLYPS

Sessile polyp

Pedunculated polyp

POLYPS
Neoplastic Polyp (Adenomas) - Micro: HALLMARK of epithelial dysplasia nuclear hyperchromasia, elongation and stratification - classified as TUBULAR, TUBULOVILLOUS OR VILLOUS

Adenomatous polyp showing marked contrast between the dysplastic glands of the polyp and adjacent normal glands.

Microscopic appearance of villoglandular polyp. There is an admixture of villous and glandular structures.

ADENOCARCINOMA
Most common malignancy of the GIT Dietary factors assoc w/ increased risk: low intake of unabsorbable vegetable fiber & high intake of refined CHOs & fat Pathogenesis: APC/Beta-catenin pathway and microsatellite instability pathway

GROWTH PATTERNS
POLYPOID: proximal colon ANNULAR, CONSTRICTING: distal colon DIFFUSE

Polypoid pattern of growth in a rectal lesion.

Cake-like configuration with central ulceration.

Deeply penetrating and ulcerated tumor.

Moderately differentiated colonic adenocarcinoma.

Polypoid pattern of growth in a rectal lesion.

Cake-like configuration with central ulceration.

Gross appearance of signet ring carcinoma. This tumor type is highly malignant, narrows the lumen, and has a pebbly mucosal surface and thickened muscular wall.

Dukes Classification (Astler-Coller modification)

Stage A Stage B1 tumors invade through the muscularis mucosae into the submucosa but do not reach the muscularis propria tumors invade into the muscularis propria tumors completely penetrate the smooth muscle layer into the serosa tumors encompass any degree of invasion but are defined by regional lymph node involvement tumors invade the muscularis propria with fewer than four positive nodes tumors completely penetrate the smooth muscle layer into the serosa with four or more involved nodes

Stage B2
Stage C

Stage C1
Stage C2

Stage D
Carcinoma in situ

lesions with distant metastases

(may be referred to as high grade dysplasia) intramucosal carcinoma that does not penetrate the muscularis mucosae

TNM Staging
Tumor Stage Tis T1 T2 Histologic Features of the Neoplasm Carcinoma in situ (high-grade dysplasia) or intramucosal carcinoma (lamina propria invasion) Tumor breaches the musc. Muc. invades into submucosa Extending into the muscularis propria but not penetrating through it

T3
T4

Penetrating through the muscularis propria into subserosa

Tumor directly invades other organs or structures

Nx
N0 N1 N2 Mx M0 M1

Regional lymph nodes cannot be assessed

No regional lymph node metastasis Metastasis in 1 to 3 lymph nodes Metastasis in 4 or more lymph nodes Distant metastasis cannot be assessed No distant metastasis Distant metastasis

COLORECTAL CARCINOMA
Clinical: - Right-sided: fatigue & weakness due to IDA - Left-sided: occult bleeding, changes in bowel habits or cramping LLQ discomfort - Most important prognostic factors: depth of invasion & +/- LN mets

COLORECTAL CARCINOMA
FACTORS related to prognosis:
1. Patients age very young and very old: poor px 2. Sex better px: F > M 3. CEA serum levels > 5.0 ng/ml 4. Tumor location: favorable px - lesions located in the left colon > lesions in sigmoid colon and rectum 5. Local extent focal microscopic CA in a polyp/tumor restricted to mucosa & submucosa: good px

COLORECTAL CARCINOMA
FACTORS related to prognosis:
6. Obstruction poor px 7. Perforation poor px 8. Tumor margins & inflammatory reaction better px 9. Vascular/perineural invasion: poor px 10. Microscopic tumor type Mucinous CA, signet ring CA and anaplastic CA: worse px 11. LN involvement - > 6 LNs: <10% survive >5 yrs.

HEMORRHOIDS
Develop secondary to persistently elevated venous pressure w/in the hemorrhoidal plexus Most common predisposing influences: straining at stool fr constipation & venous stasis of pregnancy Pathogenesis: variceal dilatations of anal & perianal venous plexus that forms collaterals that connect portal & caval venous systems to relieve venous HPN

HEMORRHOIDS
External hemorrhoids: collateral vessels w/in the inferior hemorrhoidal plexus located below the anorectal line Internal hemorrhoids: dilatation of the superior hemorrhoidal plexus within the distal rectum

HEMORRHOIDS

Micro: thin-walled, dilated, submucosal vessels that protrude beneath the anal or rectal mucosa

HEMORRHOIDS

ANAL CARCINOMAS
MORE LIKELY TO BE SQUAMOUS, or basaloid F > M (3:1) Worse in prognosis HPV related (HPV16)

ANAL CARCINOMAS

NORMAL

ANAL CARCINOMA
FACTORS related to prognosis:
1. Tumor stage depth of invasion & regional LN involvement; inguinal LN involvement (grave px sign) 2. Tumor size inversely related to px 3. Tumor recurrence - tumor recurrence in the pelvic or perineal regions following APR: ominous px

GIT Pathology
CONGENITAL ABNORMALITIES ESOPHAGUS STOMACH SMALL/LARGE BOWEL APPENDIX

ACUTE APPENDICITIS
A normal TRUE DIVERTICULUM of the cecum GENERALLY, a disease of YOUNGER people Pathogenesis: OBSTRUCTION by FECALITH the classic cause but fecaliths present only about half the time - Other causes: gallstones, tumor, mass of worms eg. O. vermicularis - Ischemic injury & stasis of luminal contents bacterial proliferation trigger inflam response eg. tissue edema, PMN infiltration

ACUTE APPENDICITIS
DDx: - mesenteric lymphadenitis (sec. to unrecognized Yersinia infection or viral enterocolitis) - acute salpingitis - ectopic pregnancy - mittelschmerz (pain fr minor pelvic bleeding during ovulation) - Meckel diverticulitis

ACUTE APPENDICITIS

ACUTE APPENDICITIS
EARLY APPENDICITIS: NEUTROPHILSMucosa, submucosa NEED NEUTROPHILS in the MUSCULARIS to confirm the DIAGNOSIS Classic clinical finding: MCBURNEYS SIGN Perforationperitonitis the rule, if no surgery Perforationperitonitis the rule, if no surgery Complications: perforation, pyelophlebitis, portal venous thrombosis, liver abscess and bacteremia

ACUTE APPENDICITIS

TUMOR
Carcinoid: most common - incidental finding - most frequent location: DISTAL TIP - distant spread: rare Mucocele (common): obstructed appendix w/ inspissated mucin Mucinous Cystadenoma (rather rare) Mucinous Cystadenocarcinoma (rare) - invasion of wall peritoneal implants

MUCOCELE
COMMON CYST on APPENDIX filled with MUCIN Can RUPTURE to become:

PSEUDOMYXOMA PERITONEI
(mucinous ascites and mucinous tumor disseminated on peritoneal surfaces)

MUCOCELE

MUCOCELE

MUCINOUS CYSTADENO(CARCINO)MA

MUCINOUS CYSTADENO(CARCINO)MA

Have a nice day!