GI TRACT SURGICAL PATHOLOGY

Dr Rasti

•Case 1:lower esopahgus mucosal biopsy

•(tubular esophagus)

•What is diagosis:

1)Fundal glands intestinal aplasia

2)Barrets esophagus without dysplasia

3)Barrets esophus with low gade dysplasia

Hematoxylin & eosinshows the deeper portionsof glands found in Barrettmucosa. These displaysome nuclear changes thatcan be overinterpreted asdysplasia on tangentiallyembedded samples. Notethe prominent goblet cells.

•Case 2 lower :esopahgus mucosa

Hematoxylin & eosinof mucosa displays featuresof both squamous andcolumnar mucosa, which hasbeen termed "multilayeredepithelium." It demonstratesmucin profiles like to those

of Barrett mucosa .(

Lower esophagus mucosa

Endoscopic findings are consist with Barret’s esophagus

•Diagnosis:

•1)Barrets with low grade dysplasia

•2)barrets IFD

3)Barrets mucosa without dysplasia

4)Regnerative changes

These maybe reactive (neutrophilsin the adjacent squamousmucosa), but the nucleiare hyperchromatic. Thismight be regarded as IFDby some observers butreactive by others.

Lower esophagus

1)low garde dysplasia

2)High garde dysplasia

3)IFD

Hematoxylin & eosin shows

the architectural appearance

of LGD. There is poor surface

maturation, but nuclei remain

aligned with their long axes

perpendicular to the basement

membrane (maintained

nuclear polarity.(

Lower esophagus

1)low garde dysplasia

2)High garde dysplasia

3)IFD

Hematoxylin & eosin

shows LGD at the surface in

,Notice the size and

chromatin density of the

nuclei. These are larger and

darker. The inverted goblet cell

Lower esophagus

1)low garde dysplasia

2)High garde dysplasia

3)IFD

Hematoxylin & eosin

high-grade dysplasia showshyperchromatic glands thatare crowded, and there areseveral markedly enlargednuclei~. There is no surfacematuration, and nuclearpolarity is lost at the surface.

Lower esophagus

1)low garde dysplasia

2)High garde dysplasia

3)IFD

The glands are dysplastic and composed oftiny hyperchromatic cells.

This "small cell" patternis unrelated to endocrinedifferentiation. There is alsoprominent inflammation; asubset of HCD cases displayprominent inflammation. Insuch cases, labeling with p53can be helpful.

•COLORECTALCARCINOMA

CRC

Hematoxylin & eosin

shows a low-power view of

moderately differentiated

microsatellite stable colorectal

adenocarcinoma with dirty or

garland necrosis ~

Hematoxylin & eosin highpower

view shows infiltrative

growth pattern and lack of

host response, 2 findings

more typical of microsate/lite

stable tumors than of unstable

tumors.

poorly differentiated MSI-Hcolorectal carcinoma withlarge numbers of tumor

infiltrating lymphocytes .~MSI-H colorectalcarcinoma with histologic

heterogeneity .mucinous differentiation,

poorlydifferentiated tumor withincreased numbers of tumorinfiltrating lymphocytes.

Molecular Genetics ·85-88% of CRCs are microsatellite stable )MSS(tumors,

many arise via mutations in Wnt signaling pathwayo Adenoma-carcinoma sequence·

·12-15% of CRCs are microsatellite unstable )MSIH(tumors that arise due to errors in DNA mismatchrepairo Serrated pathway: Sessile serrated adenomas give riseto sporadic MSI-H cancers · Methylation of hMLHl key molecular event · Often have BRAF mutationo 10% of MSI-H tumors arise via germline mutations

in mismatch repair genes )Lynch syndrome/HNPCC(· serrated lesions( · Lynch tumors are thought to grow much fastero MSI-H tumors have better prognosis than MSStumors )stage for stage(

•Microsatellite instability )MSI( is the condition of genetic hypermutability that results from

impaired DNA Mismatch Repair )MMR(. In other words, MSI is the phenotypic evidence that MMR isn't functioning normally. DNA MMR

corrects errors that spontaneously occur during DNA replication like single base mismatches or

short insertions and deletions. The proteins involved in MMR form a complex that binds to

the mismatch, identifies the correct strand of DNA, then subsequently excises the error and

repairs the mismatch.[

•Cells with abnormally functioning MMR tend to accumulate errors rather than

correcting those errors. As a result, gene sequences are not preserved faithfully

through DNA replication, and novel Microsatellites fragments are created. Microsatellite instability is detected by

PCR based assays that reveal these novel microsatellites.

•COLOSCOPIC BIOPSY

Microscopic Pathology

.Basal lymphoplasmacytosis ,

crypt branching/dropout

·Crypt abscesses, polypoid granulation tissue ·Paneth cell and pseudopyloric gland metaplasia ·Fissuring ulcers to muscularis propria ·.Transmural lymphoid aggregates

Submucosal fibrosis ,

muscle and nerve hypertrophy

·Large, well-formed epithelioid cell granulomas

o Mostly in submucosa, subserosa ;

•DIFFERENTIAL DIAGNOSIS•Ulcerative Colitis

• ·Diffuse, primarily mucosal involvement of colorectum ·Absence of skip lesions )unless treated(, transmural

•inflammation )except near ulcer(, granulomas )except•due to foreign body or crypt-rupture(, upper GI/ileal

•disease )except nonspecific duodenitis, pediatric UC(• ·"Backwash" ileitis

• :Only seen in severe right-sided UC•o No severe activity or chronic inflammatory changes

•Indeterminate Colitis (lC)• ·Not a specific disease entity: No diagnostic criteria

•o Impossible to distinguish CD vs. UC )5-15% of IBD(•o Overlapping features of both CD, UC )resections(

·Used by some if insufficient clinical, histologic data•o Instead: "Active chronic )ileo(colitis, type unknown"•o 80% of IC: Underlying IBD type eventually apparent

•5

•WHAT IS YOUR DIAGNOSIS?

•Hematoxylin & eosin showsarchitectural distortion of themucosa, indicative of chronicinjury. Several abnormally

shaped ~ and branched ~crypts are visible.

Hematoxylin & eosin

shows clustered epithelioidhistiocytes ~ resemblinga granuloma in the laminapropria. Such "crypt rupturegranulomas" are common inareas of ongoing or recentcrypt injury and are notspecific to Crohn disease.

•Hematoxylin&

•eosin shows quiescent chronic

•colitis. Note the lack of acute

•inflammation and sparse

•chronic inflammation. Crypt

•distortion = and areas devoid

•of crypts.

Collagenous colitis

–Microscopic Pathology ·–Patchy subepithelial increased collagen–o Most reliable biopsies from transverse colon–Irregular collagen band extends entraps capillaries,–inflammatory cells, and fibroblast nuclei– ·Increased intra epithelial lymphocytes )IELs(–o > 10-20 IELs/lOO surface epithelial cells ·Chronic or

mixed inflammation in lamina propria–Increased eosinophils )may be marked( ·Detachment

of surface epithelial cells from collagen–band ·Normal crypt size and shape; rare distortion

Diff diagnosis CC

·Lymphocytic colitiso No increased subepithelial collagen

·Inflammatory bowel diseaseo Erosion/ulceration, crypt architectural distortion,basal plasmacytosis

·Amyloidosiso Stains with Congo red, not trichromeo Tangential sectioning

·Ischemic/radiation colitiso No t intraepithelial or lamina propria lymphocytes

·Entities mimicking thickened collageno Tangential sectioning of tissue, hyperplastic polyp

•Hematoxylin• &eosin shows increased•Intraepithelial lymphocytes• =and subepithelial•collagen and infiltration•of surface epithelium•and lamina propria by•eosinophils ~, not typically•seen to this extent in•lymphocytic colitis.

COLLAGENOUS COLITIS

•Hematoxylin• &eosin shows sloughing•of surface epithelium from•the subepithelial collagen•band~, increased chronic•inflammation in the lamina•propria, and normal crypt•architecture.

•Hematoxylin & eosin•shows ulcerative colitis•with markedly increased•chronic inflammation in the•lamina propria, including•plasmacytosis at the bases of•the crypts ~, architectural•distortion (branching•crypts), and no increased•subepithelial collagen

Evidence based pathology

How we can increase or evidence?

•http://surgpathcriteria.stanford.edu/

•http://pathology2.jhu.edu/gicases/