GASTROINTESTINAL Flashcards
1
Q
Features of Esophagitis dissecans superficialis
A
MICRO:
- Unaltered basal layer of squamous epithelium.
- Mummification of the superficial squamous epithelium, with ‘ghost’ nuclei.
- Mucosa sloughs with blister-like appearance.
- Numerous neutrophils could indicate superimposed infection.
CLINICAL:
- Etiology unknown but associated with polypharmacy (also associated with the blood thinner Dabigatron), skin conditions, heavy smoking, ingesting hot liquids, IS, impaired mobility.
- Other causes of acute esophagitis need to be excluded: candida, reflux, pill esophagitis, autoimmune bullous disorders (i.e Pemphigus) or Stephens-Johnson syndrome).
ENDOSCOPY:
- Whitish strips or streaks ‘pseudomembranes’.
2
Q
Infection enteritis in small bowel
A
- Giardiasis: (Parasite). Teardrop (pear) shaped organisms (Giemsa +) with paired nuclei in lumen between villi +/- villous blunting, increased inflammation.
- Strongyloides infection: (Parasite) Larvae or eggs on crypts, villous flattening, crypt hyperplasia, increased inflammation including ++Eo
- MAI infection: Small or large bowel. IS patients. Granular mucosa on endoscopy. Micro: Infiltration of lamina propria by foamy histiocytes (filled with PAS/AB+ AFB).
- Whipple disease: Bct infection (Tropheryma Whippleii), white males 4th-5th decades. Blunted and rounded villi, expansion of LP by foamy, pink PASD+ macrophages and dilated lipid-containing lymphatics. There is a Whipple IHC, otherwise PCR.
- Yersiniosis: Bct infection, deep necrotizing granulomas (>likely to be detected in excision rather than bx).
- CMV: Enlarged cells with basophilic intranuclear inclusion bodies (Cowdry bodies) surrounded by a clear halo (owl’s eye). Also increased inflammation, architectural distortion.
- Adenovirus: Lymphoid hyperplasia.
3
Q
Features of Celiac disease and Marsh grading
A
- ‘Tip heavy’ intraepithelial lymphocytosis (6 or more Lymphocytes per 20 enterocytes).
- Expansion of the LP by lymphocytes and plasma cells.
- Attenuated villi to flat mucosa.
- Hyperplastic crypts.
MARSH 0= Pre-infiltrative: normal mucosal and villous architecture.
MARSH 1= Infiltrative: normal mucosal and villous architecture. Prominent IEL.
MARSH 2= Hyperplastic: Same as Marsh 1 + enlarged crypts and increased crypt mitosis.
MARSH 3= Destructive lesion: partial to total villous atrophy, lymphocyte infiltration and enlarged hyperplastic crypts.
A= Partial villous atrophy.
B= Subtotal villous atrophy.
C= Total villous atrophy.
MARSH 4= Hypoplastic: Total villous atrophy, normal IEL count reflecting severe malnutrition (non-specific).
4
Q
Features of eosinophilic esophagitis (5 major and 5 minor)
A
- Children (feeding difficulties, GERD sx) and adults (dysphagia, food impaction). Can have peripheral blood eosinophilia and Hx of allergic diseases. M>F.
- Endoscopy: Rings, pinpoint white mucosal exudates, furrows, strictures.
- Affects long segments of the esophagus, typically proximal or middle and the distal/GEJ equally. Can be patchy.
- Micro: (Some overlap with GERD).
Major features (necessary for Dx, not pathognomonic):
1) Increased intraepithelial Eo (15 or more/HPF) obtained from a peak area.
2) Eosinophilic microabscesses (4 or more).
3) Surface layering of Eo (outer layer of squamous ep).
4) Surface sloughing of squamous cells mixed with Eo.
5) Extracellular eosinophilic granules.
Minor features: - Basal zone hyperplasia (>20% of epithelial thickness).
- Lengthening of the LP papillae (>2/3 of thickness).
- Increased LP fibrosis and chronic inflammation.
- Increased intercellular oedema.
- Increased IEL and mast cells.
Neutrophils/ulcers/erosions are unusual in EOE.
5
Q
Eosinophils in the esophagus
A
- GERD
- Eosinophilic esophagitis
- Eosinophilic gastroenteritis
- Drug hypersensitivity
- Infection
- Gluten-sensitive enteropathy
- Crohn’s
- GVHD
- Vasculitis
- Connective tissue diseases
6
Q
Features of acute hemorrhagic gastritis
A
- Associated with alcohol abuse, but also some infectious agents and bowel preparations for colonoscopy.
- Micro:
Abundant oedema and haemorrhage
Little inflammation
Reactive epithelial changes
7
Q
Features of chemical gastritis/ reactive gastropathy
A
- Antrum.
- Associated with bile reflux and NSAIDs. Other associations in the pediatric setting: anticonvulsants, psychiatric and chemotherapeutic drugs.
- Micro:
Foveolar hyperplasia
LP edema
Muscular stranding
Vascular ectasia
Minimal inflammation
8
Q
Features of mucosal calcinosis
A
- Incidental finding in patients with renal failure. Reflects disorders of calcium metabolism.
- Deposit is of calcification just beneath the surface epithelium at the tips of the foveola
9
Q
Features of proton pump inhibitor effects
A
PPIs reduce acid secretion by gastric parietal cells.
- Hyperplastic parietal cells (apocrine-like cytoplasmic swelling) with granular cytoplasm and apical snouts.
10
Q
Features of GAVE (Gastric antral vascular ectasia)
A
- Endoscopy: ‘Watermelon stomach’: Longitudinal antral folds with visible, reddened vessels radiating from the pylorus
- Clinical: Iron deficiency anemia 2ry to chronic gastric bleeding. Typically elderly woman with CREST sdme, scleroderma or Lymphoma.
- Micro: (reflects mucosal prolapse)
- Foveolar hyperplasia/tortuosity.
- Fibromuscular hypertrophy: Strands of smooth muscle extend vertically between pits.
- There are dilated, ectatic and congested vessels in the LP.
- Fibrin thrombi in vessels.
DD: Portal hypertension (same without the fibrin thrombi).
11
Q
Features of Lynch Syndrome (HNPCC) including ways to detect it and histologic features of CRC in these patients
A
- Most common form of hereditable colon cancer. Accounts for 2-4% of all colorectal carcinomas.
- Caused by a germline mutation in DNA mismatch repair genes (MSH2, MLH1, MSH6, PMS2). It has an autosomal dominant inheritance.
- Lifetime risk for colorectal cancer is 80%. The precursor lesion is an adenoma. There is also increased risk for endometrial cancer (55%), ovarian cancer (15%), and for other tumours: small bowel, pancreatobiliary, renal pelvis (TCCs), adrenal (ACC) and brain (Gliomas).
Muir-Torre Sdme: Subset of HNPCC patients who also have skin tumours: sebaceous neoplasms and keratoacanthomas - Lynch Syndrome can be detected by:
1) Microsatellite instability (MSI-H) testing: PCR assay done in PEFF tissue. Requires both normal and tumour tissue. Detects instability in short DNA repeats called microsatellites (MS) located in introns: 2 of 5 MS regions must be unstable for positive diagnosis. - Most MSI-H tumours will be sporadic due to methylation of MMR genes.
- Presence of BRAF-V600E mutation excludes Lynch Sdme in MSI-H tumours (This can be tested by IHC). May also test for methylation of MLH1, as presence of methylation excludes Lynch Sdme.
2) IHC for MMR proteins. Lack of staining in tumour cells indicative of deficient protein. Staining patterns: - Mutant MLH1: Loss of MLH1 and PMS2 staining (same if there is methylation of MLH1).
- Mutant PMS2: Loss of PMS2 staining.
- Mutant MSH2: Loss of MSH2 and MSH6 staining.
- Mutant MSH6: Loss of MSH6 staining.
3) Specific gene testing may be indicated if any of these tests is positive (sequencing of MMR genes). Once missing protein is determined using IHC, the gene is sequenced to identify specific mutation for family screening. - Histologic features of CRC in Lynch Sdme patients:
- Right sided.
- Increased tumour infiltrating lymphocytes (>2/HPF) and Crohn-like reaction.
- Poorly differentiated, well differentiated or mucinous.
12
Q
Features of GIST
A
- KIT or PDGFRA mutation-driven mesenchymal tumours of the GI tract.
- Median age 60 yo. Locations: Stomach 60%, SB 30%, Duodenum 5%, colorectum <5%.
- Micro:
- Uniform spindle or epithelioid cells arranged in lobules.
- Eosinophilic cytoplasm, cytoplasmic vacuoles common.
- Minimal inflammation, inconspicuous vessels.
- Occasional extension into mucosa and uncommon tumour necrosis (both poor prognostic fxs).
- Prognostic algorithms based on tumour size and mitotic count, with site being an important risk fx. 25% of gastric GISTs and 45% of SB GISTs are malignant.
Size cut off values: =2cm, 2-5cm, >5cm. Mitosis/50 HPF: =5, >5. - IHC: CD117 +, DOG1+
- DD: Schwannoma, Melanoma, Fibromatosis, Leiomyoma/sarcoma, Inflammatory fibroid polyp.
13
Q
Features of SSA/P
A
- Large (>1cm), sessile, right sided serrated colorectal polyp.
- Molecular:
- CpG island methylation phenotype (CIMP).
- BRAF oncogene activating mutations (usually occurs together with CIMP).
- MSI, loss of expression of MMR protein MLH1 . Due to epigenetic promoter silencing (via CIMP).
15-35% of CRC arise via serrated pathway. SSA/P is the precursor lesion, probably through SSA/P with dysplasia. Faster progression than conventional adenoma to CRC. - Micro (abnormal architecture and proliferation):
- Serration/ infolding of crypt epithelium and dilation down to crypt base.
- Branching, lateral growth along muscularis mucosae (L-shaped or boot-shaped crypt bases).
- Basal crypt proliferation or extension to middle of crypt, mitosis asymmetrically extend to upper crypts.
- Inverted maturation with Goblet cells down to crypt base, also > paneth cells than normal.
- Can have submucosal mature adipose tissue (lipoma).
- IHC: Loss of MLH1 is seen in areas of dysplasia within a SSA/P.
14
Q
Features of Serrated (Adenomatous) Polyposis Syndrome (SPS)
A
- Patients with multiple, large HP and SSA/P.
- Malignancy risk (x5 higher). Up to 50% patients develop CRC.
- Diagnostic criteria (any of):
- > /= 5 SPs proximal to sigmoid colon. At least 2 of which are >10mm.
- Any proximal SP in 1st degree relative of SPS patient.
- > 20 SPs of any size, anywhere in the colorectum.
- All SPs need to be confirmed histologically.
15
Q
Features of Peutz-Jeghers polyp (PJP)
A
- May arise sporadically or as part of a PSPS.
- Jejunum and ileum most common sites. Small polyps are sessile, large ones are pedunculated. They can present with SBO 2ry to intussusception. Can also happen in colon, duodenum and stomach.
- Micro:
- Tree-like arborizing strands of smooth muscle that separate epithelial component into lobules.
- Secondary erosion/ulceration may be present.
- Submucosal misplacement common (DD: Ca).
- Dysplastic change or cancer can occur in polyp.
- In stomach, small PJPs are less characteristic and resemble hyperplastic, juvenile or mucosal prolapse.
- DD:
_Mucosal Prolapse Polyp (rectosigmoid, smooth muscle shows disarray, not compact, wrapping around individual crypts).
_Juvenile Polyp (loose, oedematous, inflamed lamina propria, marked dilatation of the epithelial component, smooth muscle not prominent).
