Block 2 Flashcards
The esophagus has what type of epithelium?
Stratified nonkeratinizing squamous
The stomach has what type of epithelium?
simple columnar epithelium
The ___ junction is defined as the point where rugal folds stop between the stomach and the esophagus
gastroesophageal junction (GEJ)
The ____ junction is defined as the mucosal junction between the stomach and the esophagus.
Also called the ___ line
Squamocolumnar junction (SCJ)
Z line
If the gastroesophageal junction and the squamocolumnar junction (Z line) so not occur at the same level, what disease may be present?
Columnar metaplasia –> Barrett’s esophagus
The respiratory system develops as a diverticulum on the ventral surface of the gut tube at the level of the ___ pharyngeal arch.
This diverticulum is called the ___ ___. Divides in the midline to create the lung buds.
4th
Laryngotracheal groove
Esophageal atresia (which normally occurs as proximal atresia with distal fistula to the trachea) results in ____ in the fetus, because the fetus is unable to swallow amniotic fluid.
The blind esophageal pouch may hypertrophy and compress/thin the trachea, called ____.
polyhydramnios
Tracheomalacia
infant presents immediately after food with choking or vomiting when feeding. Dx and what other abnormalities may be present?
Esophageal atresia
VACTERL: Vertebral anomalies, anal atresia, cardiac defects, tracheoesophageal fistula, renal defects, and limb defects
Alternatively, TACRD: tracheal agenesis/atresia, cardiac abnormalities, radial ray defects, duodenal atresia
Non-circumferential, thin pieces of tissue in the mid or proximal esophagus. Can be congenital or acquired, such as in iron-deficiency anemia (Plummer-Vinson Syndrome)
Mucosal webs
Circumferential, thick rings of tissue in the distal esophagus. Associated with hiatal hernia
Schatzki rings
Dx?
Esophageal, mucosal webs
Iron-deficiency anemia
Glossitis
Cheilosis
Dysphagia
Plummer-Vinson Syndrome
An outpouching of the esophageal wall above the upper esophageal sphincter, which tightens abnormally instead of relaxing when swallowing.
Food may collect, causing halitosis, regurgitation, extrinsic obstruction, and squamous cell carcinoma.
Reflects underlying motor dysfunction.
Esophageal/Zenker diverticulum
List a few causes of extrinsic esophageal obstruction
Mediastinal masses
Vascular compression (aortic aneurysm, etc)
Surgical changes (herniation, fibrosis)
Degeneration of the ganglion cells in the myenteric plexus of the esophagus.
Can be primary (at birth) or acquired (Chagas disease, diabetes, autoimmune).
The inability of the LES to relax after swallowing and lack of peristalsis. Results in periodic obstruction and eventual dilation proximally.
Dysphagia, odynophagia, regurgitation, and increased risk of squamous cell carcinoma.
Achalasia
A 40-yo physician returns from a trip with Doctors Without Borders in South America for 10 years. He suffers from dysphagia and weight loss over the last six months.
Achalasia secondary to Chagas disease
A patient presents with acute profuse bleeding following a night out drinking and vomiting this morning.
Mallory-Weiss tear at GEJ
A patient presents with acute profuse bleeding following a night out drinking and vomiting this morning. He suddenly develops trouble breathing and tachycardia.
Boerhaave’s Syndrome
An immunocompromised patient presents with an esophageal infection that stains as pseudohyphae.
Esophageal candidiasis
An immunosuppressed patient presents with an ulcerated esophagus. Ground glass intranuclear inclusions appear when cells from the periphery of the ulcers are placed on slides.
Herpes simplex esophagitis
An immunosuppressed patient presents with an ulcerated esophagus. Intranuclear and intracytoplasmic inclusions are visible when cells from the base of the ulcer are placed on slides.
Cytomegalovirus esophagitis
Patient presents with dysphagia and a feeling of food in the bottom of his throat. He has a 30 year history of excessive drinking and often eats acidic or fatty foods.
GERD
Dx?
GERD
erosive esophagitis seen as vertical linear streaks in the superficial mucosa
Top picture is normal. Dx the bottom picture.
GERD
Less surface maturation, basal cell hyperplasia, increases lamina propria inflammation, and papillae elongation
Columnar metaplasia with the addition of goblet cells can be defined as ____.
Intestinal metaplasia
Intestinal metaplasia and discontinuity of the GEJ/Z line together are dx for ____.
Barrett’s esophagus
Barrett’s esophagus increases the risk for what type of cancer?
Adenocarcinoma
A 15 yo male presents with dysphagia, which endoscopy shows as a food bolus obstructing his esophagus. He has a positive history of several childhood allergies, including pollen and nuts. His pH levels are testes and appear normal.
Dx and Tx?
Primary eosinophilic esophagitis (EE)
Elimination diet and corticosteroids
A 60 yo male patient presents with bleeding when coughing. He has a 35 year history of excessive alcoholism. His stomach appears distended with visible striae across the skin. What is the direct cause of the bleeding he is experiencing? Describe the pathogenesis.
Esophageal varices
Alcoholic cirrhosis > portal hypertension > esophageal varices, ascites, hemorrhoids, caput medusa
Abdominal organs shift upward through a defect in the diaphragm. May result in pulmonary hypoplasia.
Congenital diagphramatic hernia
Defect in the abdominal wall muscle that allows herniation of the abdominal contents into a ventral membranous (peritoneal) sac.
Omphalocele
Herniation of the abdominal contents through all layers of the abdominal wall, thus they are completely outside the body.
Gastroschisis
What is the diagnostic difference between an omphalocele and gastroschisis?
Omphalocele: contents within a membranous sac
Gastroschisis: no sac, contents outside of the body
A 4 week old make neonate presents with vomiting after feeding. The milk he expels contains no bile. A mass is palpable in the epigastric region of his abdomen.
Congenital hypertrophic pyloric stenosis
Alcohol, drugs (NSAIDS) or reflux result in foveolar hyperplasia with lack of inflammation.
Reactive (Chemical) Gastropathy
Abrupt onset of abdominal pain and bleeding associated with almost any etiology (alcohol, drugs, iron pills, radiation, etc.) that results in the breakdown of the mucosal barrier of the stomach.
Acute gastritis
NSAIDS contribute to acute gastritis mostly through what primary mechanism?
A. Recruitment of inflammatory cells
B. Inhibition of PG synth
C. Inhibition of bicarb secretion
D. Activation of acid secretion
B. Inhibition of PG synthesis
In turn, decreases bicarb and mucus secretion, which are secondary mechanisms.
Petechiae, erosions, and ulcers limited to the stomach mucosa. Neutrophils can also be seen.
Dx? Tx?
Acute erosive/hemorrhagic gastritis
Tx with acid suppression
1 cause of chronic gastritis, associated with PUD, MALToma and adenocarcinoma. Plasma cells in the lamina propria and neutrophils in the the epithelium/lamina propria.
H. pylori gastritis
Some strains of H. pylori have what toxin, which penetrates gastric cells and causes cell growth, gastritis, and adenocarcinoma.
cytotoxin-associated A (CagA) gene
Some strains of H. pylori promote B cell and T cell proliferation, which can result in ___?
lymphoma
H. pylori infection most commonly occurs in what area of the stomach?
Antrum
Results in gastric as well as duodenal ulcers
Anti-parietal cell and anti-IF factors result in the loss of parietal cells and the inability to absorb B12, limited to the body/fundus. Most commonly occurs in women.
Hypo or achlorhydria, increased gastrin (no negative feedback of HCl)
Degeneration of the spinal cord that cannot be corrected by folate supplementation.
B12 deficiency: Megaloblastic anemia, pancytopenia, peripheral neuropathy, CNS, and cardiovascular disease
Autoimmune gastritis
A patient has a gastric antral biopsy for abdominal pain, the slide of which is pictured. How does this organism survive in the acidic stomach?
A. Ammonia production
B. Hydroxide production
C. Bicarbonate production
D. Sulfate production
A. Ammonia production
H. pylori has a urase, which converts urea and water to CO2 and ammonia, which neutralizes gastric acid.
A 62 yo woman is diagnosed with autoimmune gastritis and pernicious anemia. Which of the following laboratory findings is most likely?
A. High vitamin B12
B. Hypergastrinemia
C. Elevated hematocrit
D. Low serum iron
B. Hypergastrinemia
Loss of parietal cells results in low acid secretion (elevated pH) which signals an increase in gastrin to re-stimulate parietal cell acid secretion.
[Low B12 (elevated methylmalonic acid and homocysteine) and megaloblastic anemia, serum iron should be normal]
Allergy or parasitic infection causes increased ___ in the lamina propria.
Eosinophils
Eosinophil gastritis
Increased intraepithelial lymphocytes in the surface foveolar epithelium. Associated with celiac disease.
Lymphocytic gastritis
Chronic infection
Granulomatous gastritis
Body and fundus-restricted hyperplasia of foveolar epithelium with hypoproteinemia. Loss of plasma proteins (albumin) through the gastric mucosa leads to peripheral edema. TGF-a overexpression. May occur after infection.
Menetrier’s Disease (hyperplastic gastropathy)
Diffuse hyperplasia of the fundic and body parietal cells in response to hypergastrinemia, usually a gastrinoma in the pancreas, duodenum, or antrum.
25% associated with MEN-1, 60-90% malignant.
Increased oxyntic mucosal thickness, so increased gastric acid.
Fundus > body affected
Duodenal ulcers and chronic diarrhea present clinically
Zollinger-Ellison Syndrome
Hereditary gastric cancer is associated with what mutation?
E-cadherin/CDH1 tumor-suppressor-gene
Loss of E-cadherin
What type of gastric cancer?
Wnt pathway mutation
Intestinal type
What type of gastric cancer?
Loss of E-cadherin
Diagnostic cells?
Diffuse gastric cancer
Signet ring cells
Enlarged supraclavicular node with gastric cancer
Virchow’s node
Enlarged periumbilical node with gastric cancer
Sister Mary Joseph’s node
Bilateral ovarian tumors metastasized from gastric cancer
Krukenberg tumors
___ Shelf due to metastasis of gastric tumors into Douglas’ pouch.
Blumer shelf
Mesenchymal tumor derived from interstitial cells of Cajal (pacemakers of the GI tract)
Gastrointestinal stromal tumors (GIST)
marker for gastrointestinal stromal tumors (GIST)
C-KIT, a tyrosine kinase
Most common primary gastric B cell lymphoma. Most commonly arises from chronic H. pylori gastritis. Treatment of infection can lead to tumor remission unless it has undergone genetic translocation.
Glands with intraepithelial lymphocytes and destruction of glands.
Gastric MALT lymphoma
Genetic mutation of gastric MALT lymphoma
t(11;18)
true (includes muscle) diverticulum of the ileum
failure of vitelline duct to involute (vitelline duct connects the developing gut to yolk sac)
Rule of 2’s
technetium-99m pertechnetate scintiscan scan
Image shows retained gastric mucosa, including chief and parietal cells
Meckel’s diverticulum
Causes of ____
herniation
adhesions
volvulus
intussusception
Small bowel obstruction
Most common cause of small bowel obstruction in children <2 yo
Intussusception
Acute vascular compromise that results in transmural necrosis in neonates when they begin oral feeding.
Form of ischemia
Distention, bloody stools, perforation and possible death
Especially in premie or low birth weight neonates (likely bowel immaturity)
Neonatal necrotizing enterocolitis (NEC)
AR disease of ion transport protein for chloride and bicarbonate across epithelial linings in the respiratory, GI and reproductive tracts
CFTR gene encodes the channel protein as well as inhibits ENaC (loss results in uncontrolled salt loss from the sweat ducts = salty skin and uncontrolled salt reabsorption from the other tracts, so mucous becomes dehydrated and thick)
Cystic fibrosis
Immune-mediated enteropathy triggered by foods containing gluten in genetically susceptible individuals
Association with other autoimmune diseases: HLA DQ-2, DQ-8
Gliadin digestion induces inflammation
Most sensitive test: anti-tissue transglutaminase IgA
Blunted villi = malabsorption
Celiac disease
Celiac disease is caused by a sensitivity to the products of gluten metabolism, particularly ____
Gliadin
All of the following are used to make a diagnosis of celiac disease EXCEPT:
a. anti-tissue transglutaminase Ab
b. anti-endomysial Ab
c. Anti-nuclear Ab
d. HLA DQ2 or DQ8
e. duodenal biopsy
C
Molecules in wheat, rye, and barley can cause symptoms but patients tests negative for celiac disease.
Amylase-trypsin inhibitors
FODMAPs (fermentable oligosaccharides, di-saccharides, mono-saccharides, and polyols)
Non-celiac gluten sensitivity (NCGS)
What is the main importance of differentiating celiac disease from NCGS?
Celiac disease increases the risk for adenocarcinoma. NCGS does not.
A 40yo man has a 5-year history of diarrhea, bloating, and crampy abdominal pain. He complains that his stools are “very greasy and very smelly.” He has similar symptoms as a child, but this resolved spontaneously after his mother starting banning processed foods in the house. In addition to his GI complaints, the patient complains of the following pruritic rash that is seen on his elbows below. What is the likely diagnosis?
Celiac disease
chronic diarrhea + processed food (gluten) + dematitis herpetiformis
Malabsorptive chronic diarrheal disease in regions with poor sanitation, likely bacterial, but compounded by poor nutrition which creates an impaired mucosal barrier in the gut. Malabsorption results in folate/B12 deficiency, megaloblastic anemia, failure to respond to oral vaccines, and early death.
Villous atrophy believed to affect the entire length of the bowel
Tropical sprue
A congenital or acquired deficiency that presents as the inability to digest lactose. Presents as bloating and flatulence after consumption of dairy.
Congenital: mt in lactase gene
Acquired: down-regulated lactase expression
Lactase deficiency or Lactose intolerance
AR disease that results in the inability to assemble TAG-rich lipoproteins due to a mt in a transporter. Thus, FFA accumulate within enterocyte cytoplasm. No apoprotein B in plasma.
Presents in infancy as diarrhea, steatorrhea, fat-soluble vitamin deficiencies, and lipid membrane defects (spikey RBCs, aka acanthocytes)
abetalipoproteinemia
Abetalipoproteinemia is associated with which hematologic abnormality?
a. schistocytes
b. sickle cells
c. acanthocytes
d. spherocytes
e. ringed sideroblasts
C
Infection with Tropheryma whipplei
Macrophages filled with organisms accumulate in small intestine lamina propria, mesenteric lymph nodes, joints, heart and brain.
Triad: diarrhea, weight loss, arthralgia
Villi are not blunted but are distended bt foamy macrophages
Tx: antibiotics
Whipple disease
Most common parasite in humans. Fecal-oral, usually rural streams or campers. Non-invasive but causes microvillus damage and apoptosis of intestinal epithelial cells. Asymptomatic to diarrhea. Most commonly seen in the duodenum.
Giardia
Parasite, fecal-oral, with increased prevalence in immunocompromised patients. The parasite resides in an endocytic vacuole within apical enterocyte cytoplasm (microvillus), although it appears to sit on top of the cell. Causes sodium malabsorption and chloride secretion –> watery diarrhea.
Cryptosporidium
Dx?
Hamartomatous polyps
(Peutz-Jeghers syndrome)
Dx?
Hamartomatous polyps
(Peutz-Jeghers syndrome)
Shows arborizing smooth muscle of the jejunum
Dx?
Hamartomatous polyps
(Peutz-Jeghers syndrome)
Shows arborizing smooth muscle + lobulated glands without dysplasia
Mucocutaneous pigmentation as typically seen in __?
Hamartomatous polyps
(Peutz-Jeghers syndrome)
Dx?
Intestinal obstruction (usually due to intussusception), abdominal pain, blood in the stool, prolapse of polyps through the anus, and mucocutaneous pigmentation.
Increased risk of cancers
AD germline mutation of STK11 (aka LKB1), a tumor suppressor gene.
Hamartomatous polyps
(Peutz-Jeghers syndrome)
Which embryological section of the GIT is most likely to present with aggressive tumors, rather than benign?
Midgut
Neuroendocrine tumor that presents as flushing, diarrhea, wheezing, pellagra, and cardiac disease
Carcinoid syndrome - Serotonin
A neuroendocrine tumor that presents as gastric acid hypersecretion (pain, ulcers, diarrhea)
Zollinger-Ellison Syndrome - gastrinoma
Neuroendocrine tumor that presents as neuroglycopenia, sympathetic overdrive, and obesity
Insulinoma
neuroendocrine tumor that presents as hyperglycemia, rash, anemia, hypoaminoacidemia, weight loss, thromboembolism, and glossitis
Glucagonoma
neuroendocrine tumor that presents as watery diarrhea, hypokalemia, achlorhydria, and other (hyperglycemia, hypercalcemia, and flushing)
VIPoma
Failure of neural crest cells to fully migrate from cecum –> rectum –> distal colon. Begins at anal sphincter and extends a variable distance proximally. Failure of peristalasis to travel full length of bowel; functional obstruction. Patient presents with failure to pass meconium in the first few days of life, followed by abdominal distention.
Hirschprung disease
aka congenital aganglionic megacolon
Barium enema. Dx?
Hirschprung disease
Most common form of congenital intestinal atresia. Failure of cloacal diaphragm to involute. Patient presents with failure to pass meconium and abdominal distention.
Imperforate anus
Commonly presents with other malformations - VACTERL
This a radiograph of a newborn taken after he failed to pass meconium and developed abdominal distention. A biopsy of his rectum is taken. What is the leading differential diagnosis?
a. imperforate anus
b. esophageal atresia with tracheoesophageal fistula
c. Hirschsprung disease
d. hypertrophic pyloric stenosis
a. imperforate anus
can also present with esophageal atresia and tracheoesophageal fistula, but that is secondary
Hirschprung presents as MEGAcolon
Chronic inflammatory condition resulting from dysfunctional mucosal immune activation. Usually presents in teens-20s in Caucasians and Ashkenazi Jews. Idiopathic but genetic elements? Also, research suggests epithelial defects in tight junctions, “leaky gut,” allowing microbial components to invade the lamina propria and trigger an immune response. An altered microbiome may also play a role.
Inflammatory bowel disease
Inflammatory (non-necrotizing granulomas) and ulcerative lesions that may present from mouth to anus, but tend to appear in the terminal ileum. Discontinuous lesions. Patient presents with diarrhea, fever, abdominal pain, and malabsorptive nutritional defects. Fistulae may also develop, signifying transmural involvement. Extraintestinal manifestations include uveitis and arthritis (other inflammatory processes), along with other autoimmune disorders. Increased risk of adenocarcinoma.
Crohn Disease
Inflammatory and ulcerative lesions limited to the colon and rectum in a continuous fashion, distal to proximal. Mucosal and submucosal inflammation only, so no fistulas occur. Active cryptitis, no granulomas. Patient presents with relapsing attacks of bloody diarrhea and abdominal pain relieved by defecation. Sometimes associated with primary sclerosing cholangitis (seen in women), and an increased risk of adenocarcinoma.
Ulcerative colitis
A 17yo male has abdominal pain with long-standing intermittent bloody diarrhea. All of the following findings from the physical and endoscopic examination would favor UC over Crohn’s EXCEPT:
a. perianal fistula
b. inflammation limited to the mucosa
c. inflammatory pseudopolyps
d. continuous disease from rectum to sigmoid colon
A. perianal fistula
Fistulas only occur with transmural necrosis, which is characteristic of Crohn’s not UC, which involved inflammation in only the mucosa and submucosa.
A 30yo female presents with abdominal pain for a few days at a time over the course of the last few months. The pain improves after defecation, and she has noted some changes in her stool. Biopsy shows no changes in her GIT.
Inflammatory bowel SYNDROME
Colitis in a portion of the colon excluded from the normal fecal stream (blind pouch). Diversion of the fecal flow deprived the diverted segment from the nutritional short fatty acid chains available in fecal material.
Diversion colitis
Tx: short FA enema
Idiopathic disease that is associated with celiac disease, autoimmune disease, drugs (NSAIDs)
Patient presents with watery diarrhea and normal findings on colonoscopy.
Biopsy shows two forms: lymphocytic or collagenous.
Microscopic colitis
Idiopathic disease that is associated with celiac disease, autoimmune disease, drugs (NSAIDs)
Patient presents with watery diarrhea and normal findings on colonoscopy.
Biopsy reveals intraepithelial lymphocytes, which prevent absorption water, leading to the watery diarrhea.
Lymphocytic (microscopic) colitis
Idiopathic disease that is associated with celiac disease, autoimmune disease, drugs (NSAIDs)
Patient presents with watery diarrhea and normal findings on colonoscopy.
Biopsy shows thickened subendothelial collagen layer.
Outpouchings of the colonic mucosa/submucosa, typically in the sigmoid colon (highest intraluminal pressure), which may become infected or inflamed. Incidence may increase in connective tissue disorders and is also higher in western countries with low fiber diets and the habit of sitting while defecating. Patient presents with lower left quadrant cramping, constipation or diarrhea, the sensation of never emptying the rectum.
Diverticulosis/diverticulitis
Acute inflammation of the appendix with neutrophilic infiltration and ulceration of the appendiceal wall, typically in children or young adults. Patient presents with periumbilical pain that later localizes to the RLQ.
Acute appendicits
Patient presents with acute abdominal pain, bloody diarrhea, vomiting, distention, and possibly death.
In adults, this is occlusion of a major blood vessel due to atherosclerosis, tumor, masses, volvulus, or shock.
In children, volvulus from malrotation.
The mucosa is most susceptible as it is furthest from the blood supply and presents as ulceration/atrophy through to normal submucosa or muscular layer.
Intestinal ischemia
Most common location of intestinal ischemia? Explain
Small/large intestine near the splenic flexure. The anastomosis of the super mesenteric artery and arcuate arteries/inferior mesenteric creates a watershed area.
Tortuous focus of mucosal and submucosal vessels, usually within the cecum/right colon. increased incidence with age.
Angiodysplasia
Swelling of internal or external perianal tissue due to persistently elevated venous pressure. Causes include straining at defecation, pregnancy, portal hypertension, and a sedentary lifestyle.
Hemorrhoids
Difference between internal and external hemorrhoids?
internal = transitional epithelium
external = squamous epithelium, frank blood, and itching or pain
Bacterial overgrowth due to longterm antibiotic use and the elimination of beneficial colonic flora. Toxin is released and causes loss of epithelial tight junctions, sloughing of epithelium, and watery diarrhea.
Pseudomembranous colitis (C. difficile)
Amebic cysts resistant to gastric acid are passed to the colon where they release trophozoites. If they invade the colon, they produce flask-shaped ulcers and bloody diarrhea. Fecal-oral transmission in countries with poor sanitation.
Entamoeba histolytics colitis
What is the major histologic clue to distinguish an acute from a chronic clolitis?
a. presence of neutrophils
b. presence of crypt architectural distortion
c. presence of lymphocytes
d. presence of mucosal granulomas
b. presence of crypt architectural distortion
see chronic crypt distortion below
Benign epithelial proliferation with no malignant potential. Commonly occurs in the LEFT colon. Crowding of epithelial cells, serrations and star shapes, but NO cytological atypia
Hyperplastic polyp
An inflammatory polyp typically seen in the rectum, resulting from impaired relaxation of the anorectal sphincter with recurrent abrasion. Thickened muscularis mucosa herniates upward into the mucosa, enveloping crypts.
Clinical triad: rectal bleeding, mucus discharge, inflammatory lesion of the anterior rectal wall
Mucosal prolapse polyps
An island od regenerating mucosa in a sea of ulceration, as commonly seen in ulcerative colitis.
Inflammatory pseudopolyp
AD inheritance of up to 100 hamartomatous colonic polyps. SMAD4 or BMPR1a mutation, upregulated cellular growth, mucosal hyperplasia. Most polyps within the rectosigmoid. Increased risk of cancer throughout the GIT, requiring endoscopic surveillance throughout their lifetime.
Globoid shaped polyp with many dilated, branching, mucin-filled cysts. May see stromal infiltration.
Juvenile polyposis syndrome
Cytologic dysplasia in the colon that is a premalignancy (precursor), and risk of progression directly correlates to size.
Dysplasia = enlarged, cigar-shaped hyperchromatic nuclei, pseudostratified
Can be sessile, pedunculated, and villous
Colonic adenoma
A type of polyp that most commonly occurs in the RIGHT colon and resembles a hyperplastic polyp but possesses malignant potential. Often MLH1 mutated, DNA mismatch repair gene. Architectural dysplasia but no cytologic dysplasia.
Seen below: crypt basal dilation (inverted T) and crypts growing horizontally.
Sessile serrated adenoma
Chromosomal instability pathway to colon cancer as seen in familial adenomatous polyposis (FAP), which accounts for approximately 75% of sporadic colorectal neoplasias. CIN+
APC/WNT
The pathway that leads to colon cancer as seen in Lynch Syndrome.
Microsatellite instability
A minor pathway to colon cancer that is CIMP+
Acquired CpG island hypermethylation
AD inheritance that all but guarantees colon cancer by 30yo. An inherited mutation in APC, a tumor suppressor gene that is a negative regulator of the Wnt signaling pathway. Additional mutations, such as KRAS or TP53, result in cancer. Also has extracolonic manifestations.
Familial adenomatous polyposis (FAP)
Most common cause of hereditary colon cancer. AD defect in one of several DNA mismatch repair enzymes: MLH1, MSH1, MSH6, PMS2. Leads to microsatellite instability –> rapid somatic mutations in genes that control tumor progression. Cancers occurring at younger ages than sporadic cancers. RIGHT sided. Extracolonic manifestations too.
Hereditary non-polyposis colon cancer (Lynch syndrome)
Malignant neoplasm of the colon with varying degrees of atypia. Atypical cells form glands with necrotic debris visible in the lumen.
Adenocarcinoma
Malignant neoplasm of the colon with >50% extracellular mucin
Occurring R side = L side
Can see debris floating within the mucin and lumen of atypical glands.
Mucinous adenocarcinoma