GI pathology Flashcards
Learn about all pathological conditions related to GI System
Describe Pleomorphic Adenoma under — Intro, Incidence, Site, Eitio/Pathogenesis/ Morphology.
Pleomorphic Adenoma is the most common tumor of the salivary gland.
> Incidence:
3rd-5th decade of life
Males>Females
> Site : 60% of them in Parotid. Sometimes in Submandibular but rare in minor salivary glands.
> Nature: Benign, mixed tumor as it contains epithelial, myoepithelial and mesenchymal elements
> Pathogenesis: 1) PLAG1 TF overexpression
2) HMG2A gene mutation
> Morphology:
GROSS: Round,well demarcated. Capsule is not well defined, so infiltrates surrounding gland. Less than 6 cm in size.
MICROSCOPY:
1. 3 components- epi, myoepi, mesenchymal
2. Epithelial elements— form ducts, acini, tubules, sheets etc
-Some epi cells form well defined glands lined by inner layer of epi cells and underlying layer of myoepi cells
-Islands of well-diff squamous cells may be found
- Mesenchymal elements-
The epithelial elements are dispersed in a BG of myxoid or hyaline stroma
Contain islands of cartilage, rarely foci of bone
What is Paraganglioma?
Describe morphology of Carotid body Tumor.
Arise from neuroendocrine cells, related to symp and parasymp nervous systems and occur at many sites of the body.
Pathogenesis: LOF mutations in SDH genes or genes coding for cofactors of mitochondrial oxidative phosphorylation pathway.
M/c Paraganglioma is adrenal pheochromocytoma.
Locations of PG:
1) Paravertebral paraganglia
2) Related to great vessels of head&neck (aorticopulomary chain) Eg. carotid body, aortic body
Carotid body Tumor Morphology:
GROSS- Parasymp PG not more than 6cm size.
Located at bifurcation of CCA.
HPE:
1) Nests of chief cells surrounded by vascular septae
Chief cells are +ve for neuroendocrine IHC markers:
-Chromogranin
-Synaptophysin
-NSE, CD57, CD56
2) Very little pleomorphism or mitoses
3) Supporting stromal cells (Sustantecular cells) are positive for S-100 IHC marker
EM: Dense core Neurosecretory granules
Describe Barrett Esophagus: Intro, Incidence, Pathogenesis, Morphology, Diagnosis.
Barrett Esophagus is a complication of GERD, characterized by intestinal metaplasia of the squamous mucosa of Esophagus. It is associated with increased risk of esophageal cancer.
Incidence: More than 45 years of age. M>F
Pathogenesis: It is a type of metaplasia, occurring in response to chronic GERD. Transient relaxation of LES is the underlying cause. Conditions which can lead to GERD are obesity, tobacco use, pregnancy, CNS depressants etc
Morphology:
-GROSS- Tongues of red, velvety mucosa extending from GE junction upwards toward Esophagus.
Based on length of Esophagus involved it may be:
(1) Short Segment - <3cm
(2) Long segment - >3 cm- increased risk of malignancy
- MICRO-
1) Intestinal metaplasia- Normal stratification sq epi replaced by columnar epithelium, identified by presence of goblet cells
Goblet cells stain positive with Alcian blue
2)Dysplasia of variable degree
Diagnosis: Requires endoscopy or biopsy, prompted by symptoms of GERD
Peptic ulcer disease - Definition and Pathogenesis.
PUD is a chronic mucosal ulceration/damage which penetrates into the muscularis mucosae and usually affects the stomach (gastric ulcer) or duodenum (duodenal ulcer).
RISK FACTORS: Most commonly occurs as a complication of H.pylori induced Chronic gastritis, NSAIDs or cigarette smoking. Other risk factors are alcohol, psychological stress and ZES.
PATHOGENESIS:
- Imbalance between defensive forces and damaging factors in the gastric mucosa
- Damaging forces - Gastric acid, Peptic enzymes (Pepsin)
- Protective forces-
(1) Preepithelial- Mucus, Phospholipid, Unstirred fluid layer, Bicarbonate
(2) Epithelial barrier- Restitution, Regeneration, Barrier against leakage, PG synthesis
(3) Subepithelial - Mucosal blood flow delivering O2, nutrients, removing toxic metabolites and removing any acid leaking into lamina propria
Direct Damage-
1. H.pylori (Increases secretion of gastric acid, produces ammonia due to urease and decreases secretion of bicarbonate) - Most imp cause of PUD
- Others
NSAIDs, Cigarette, Alchohol-radiation-chemo, Ingested chemicals, Hyperacidity
Host factors- Decreased mucin production in old age, decreased O2 delivery (high alt), shock, delayed gastric emptying
How does H.pylori increase the risk of Gastric Adenocarcinoma?
H. pylori increases the risk of Gastric Adenocarcinoma by 5-6 fold.
H.pylori induced Chronic gastritis — Mucosal inflammation— atrophic gastritis involving body and fundus of stomach— decreases parietal cell mass— decreased acid and pepsin secretion— progresses to intestinal metaplasia— dysplasia— carcinoma
What is the pathogenesis and morphology of Celiac disease? Clinical features?
It is aka Gluten sensitive enteropathy.
Patient is sensitive to B,R,O,W which contain gluten.
M/c site affected: Duodenum
Gluten digested by luminal & brush bordered enzymes into amino acids and peptides. One such peptide is alpha-Gliadin which is resistant to digestion by proteases.
It induces IL-15 secretion by epithelial cells.
Activation & proliferation of intraepithelial C8+ T lymphocytes which now express NKG2D (receptor of MIC-A)
Under stress, epithelial cells express MIC-A.
Lymphocytes with NKG2D attack the cells —> epithelial damage —> allows gliadin to enter lamina propria
—> Gliadin interacts with HLA-DQ2 and HLA-DQ8 on APCs—> activation of CD4+ T cells to secrete cytokines —> more tissue damage
Morphology:
- Intraepithelial lymphocytosis with CD8+ T cells (most sensitive marker of celiac disease)
- Villous Atrophy
- Crypt Hyperplasia
Clinical Features: Steatorrhea, diarrhea, bloating, chronic fatigue, malabsorption leading to nutrient deficiency symptoms
- Dermatitis Herpetiformis
- Increased risk of cancer, most commonly Enteropathy associated T-Cell Lymphoma
Whipple’s Disease- Cause, Morphology, Clinical features.
Cause: A gram positive Actinomycetes — Tropheryma whipplei
Morphology:
1) Dense accumulation of foamy macrophages within the Lamina propria of small intestine, filled with PAS +ve granules which are the digested bacilli in the lysosomes
2) Villous Expansion caused by dense macrophage infiltrate
Gross:
1) Shaggy appearance of mucosa, yellow-white mucosal plaques seen on endoscopy
2) Foamy macrophages accumulate within mesenteric lymph nodes— lymphatic obstruction— malabsorption
3) Macrophages also accumulate in heart valves, brain etc.
Clinical: Multiorgan disease. Classical triad: Diarrhoea, weight loss and arthralgia. Other organs involved are CNS, heart, lungs.
Gastrointestinal Stromal Tumor— Cell of origin, Pathogenesis, Morphology, Prognosis.
GIST is the m/c mesenchymal tumor of the abdomen.
Cell of origin: Interstitial cells of Cajal (ICC)
Pathogenesis: mutations in— C-Kit, PDGFRA, SDH gene
Frequently associated with Carney’s triad: Stomach GIST, Pulmonary chondroma and Paraganglioma
Morphology
Gross-
1) Large (may be as large as 30 cm)l bulky, well circumscribed
2) Ulcerated
Microscopy: 2 types of patters seen
1) Spindle cell Type: Elongated cells with tapering ends seen
2) Epithelioid Type: Elongated cells with rounded ends
Prognosis: Depends on:
1) Size (More than 10 cm size has greater chance of metastasis- bad prognosis)
2) Location (Intestinal has bad prognosis compared to stomach GIST)
3) Mitoses (More than 10/HPF = poor prognosis)
Colorectal adenicarcinoma: morphology.
Location: Colonic adenocarcinomas can be found in any location of the colon.
Types: Grossly colonic carcinomas can be 4 types:
1. Exophytic polypoid mass in the right-side of colon : - proximal colon - cauliflower-like masses - extend along wall of the cecum and ascending colon.
2. Annular and constricting tumors in the left-side of colon: “napkin-ring” or “apple core” constrictions & luminal narrowing. Causes intestinal obstruction, desmoplasia.
3. Diffuse/tubular tumor : diffuse flattening and thickening of the colon, initially involving mucosa, but later involve the entire wall of intestine.
4. Ulcerating tumors
Microscopy
- May be well-differentiated, moderately or poorly differentiated.
- Most show glands of variable size and shape separated by moderate amount of stroma.
- Mitotic figures are usually abundant.
- The lumen of the glands is usually filled with inspissated eosinophilic mucus and nuclear and cellular debris (“dirty” necrosis).
- Stromal desmoplasia causes firm consistency.
- Poorly differentiated carcinoma shows only few glands.
- Mucinous adenocarcinomas: They secrete lots of mucin and & have poor prognosis.
Define Leukoplakia and erythroplakia.
Leukoplakia- A white patch or plaque which cannot be scrapped off and cannot be classified as any diagnosable disease.
Erythroplakia- A red velvety area in the oral cavity.
Microscopy of leukoplakia and erythroplakia.
Leukoplakia:
1) Surface stratified sq epithelium shows varying degrees of changes ranging from hyperkeratosis and acanthosis to dysplasia.
2) Subepithelial region shows inflammatory infiltrate proportional to the dysplasia
Erythroplakia:
1) Epithelium shows dysplasia, carcinoma in situ and even Frank carcinoma
2) Subepithelial region shows intense inflammatory infiltrate, vascular dilation leading to red color
Hairy leukoplakia.
It is an oral lesion occuring in immunocompromised patients.
80% associated with HIV, while the rest are seen in other immunocompromised states.
Etiology: Caused by EBV infection
Site: Lateral borders of the tongue
Gross: White fluffy patches which cannot be scraped off.
Microscopy: -Hyperkeratosis,acanthosis
-Balloon cells in the uper spinous layer of stratified sq epithelium
