Upper GI Flashcards
Biopsy take from oesophagus.
Dx:
Stains to confirm
Key histo features
DDx:
Dx: candida oesophagitis
Stains: PAS, GMS
Key histo features:
ExpertPath
Neutrophilic inflammatory response most common (NB: variable inflammatory response)
Candida stains with GMS and PAS
C. albicans and Candida tropicalis
- Mixture of budding yeast forms, pseudohyphae, occasional true hyphae
Candida (Torulopsis) glabrata
- Tiny budding yeast forms similar to Histoplasma, no pseudohyphae or hyphae
NB: Hyphae usually angled perpendicular to squamous epithelium.
DDx:
- Aspergillosis
- > septate true hyphae branching at acute angles
- Histoplasmosis
- > Histoplasma are smaller than candida, almost exclusively intracellular, halo effect around histoplasma in tissue
Invasion vs superficial colonization? Look for invasive funi in tissue sections. Presence of just a few yeasts without pseudohyphae is not evidence of infection. Appropriate inflammatory response to organiss.
Dx:
IHC:
Histo features
Dx: candida oesophagitis
IHC: PASD/GMS
Histo features: Densely matted pseudohyphae and budding spores in squamous debris, fibrinopurulent exudate or necrotic debris
Adenoid cystic carcinoma (salivary gland tumour)
gastric biopsy N&V in man with anaemia
Dx?
Key features
Dx: Iron pill gastritis
Mucosal injury in the form of erosion, ulceration and granulation tissue, according to the extent of the injury Acute inflammation in surrounding tissue, inflammatory exudate and reactive epithelial changes Crystalline, metallic, brown-black pigmented material deposition in the superficial mucosa and ulcer bed Iron is refractile but does not polarize
antral polyp
dx
Key features demonstrated
ddx
key genetic mutations
Juvenile polyp
hyperplastic non-dysplastic foveolar epithelium and oedematous stroma. (These polyps are characterised by lamina propria oedema, abundant disorted and dilated and mucin filled glands +/- inflammatory cells).
DDx: inflammatory polyp; other syndromic polyps i.e. Peutz-Jeghers polyps or Cronkhite-Canada syndrome polyp
Germline mutations in SMAD4 and the related gene GMPR1A
Below: SMAD4 loss
gastric polyp
dx
IHC
etiology
Gastric pyloric gland adenoma
Key features:
consist of closely packed pyloric-type glands, lined by cuboidal/low columnar epithelia with foamy, ground-glass cytoplasm;
No apical mucin (c.f foveolar type adenoma); nuclei basally orientated.
High-grade PGAs consistently exhibit disturbed architecture, crowded nuclei, and loss of nuclear polarity. High-grade dysplasia is observed in 40–50% of cases,
.
NB: Adenocarcinoma (even focal) is observed in almost half of all cases, however, submucosal invasion does not exceed 10% .
If high-grade dysplasia is present, this is staged as pTis.
IHC: MUC6 (v +), MUC5AC +
Aetiology: sporadic cases normally occur in context of autoimmune gastritis.
stomach lesion
dx?
IHC?
Molecular
GIST with epithelioid morphology
IHC: C-KIT/DOG1, CD34 (nb epithelioid GISTs less consistently (+) for CD34 than spindle cell GISTs.
This image shows cytoplasmic vacuoles.
gastric lesion
dx
IHC
GIST with spindle cells and perinuclear vacuolisation.
IHC: C-kit/DOG1; CD34 (+ more in spindled cell GIST than epithelioid); consider SDHB or SDHA IHC with multinodular/plexiform growth > a/w lymph node involvement
Image: GISTS composed of cytologically bland spindle cells that may feature distinctive perinuclear vacuolization.
GISTs
subtypes
Sclerosing type (a/w calcs)
Pallisaded-vacuolated subtype
GISTs
SDH-deficient GISTs
describe histology
relevance
associated syndrome
Multinodular/plexiform growth, lymphovascular invasion
LVSP/LN mets; more likely to metastasise and are resistant to imatinib therapy
Carey-Stratakis syndrome
gastric biopsy
Atrophic pattern of gastritis:
Key histo features:
Pitfalls:
Common causes:
multifocal loss of th oeriginal gastric glands +/- metaplsia +/- inflammation
NB: Atrophic pattern as an advanced stage of damage is often accompanied by metaplastic pattern. Metaplastic and atrophic pattenrs often coexist as a mixed pattenro f atrophic metaplastic gastritis.
Pitfalls: mistaking of transitional zones of the gastric mucosa (antrum and body, fundus and cardia) that may show a reduciton of expectednormal components as atrophy).
Common causes (2): AIG and HPG
1. autoimmune gastritis: oxyntic gland atrophy + antral sparing
2. HPG shows antrophyloric gland atrophy (oftne a/w IM)
Therefore, antral predominant gastritis is consistent with Hpylori associated chronic atrophic gastritis whiel antral sparing gastritis is typical fo AIG.
stomach, intestinal metaplasia
Endoscopic findings:
Types:
Endo: multiple white plaques
Type 1: metaplastic glands phenotypically resemble those of the small intestine, with eosinophilic absorptive neterocytes with a brush border, alternating with mucus-producing goblet cells and Paneth cells. “Complete IM” or “small intestinal type metaplasia”. When advanced may show villiform architecture.
Type 2: Incomplete IM shows irregular goblet cells interspersed within the gastric epithelium and lacks the brush border, absorptive cells, and paneth cells and resembles colonic mucosa, called “colonic metaplasia”. in type 2 IM, the presence of sulfomucins within the non-goblet cells is beieved to be a/w an icnreased risk of progressio to gastric cancer.
Immunohistochemical markers for subtyping intestinal metaplasia
Complete (type 1) IM vs Incompete (type 2)
Complete (type 1) IM: shows expression of MUC2 in goblet cells, (intestinal mucin) as well as luminal CD10 expression highlighing the presence of enterocytes and decreased expression of “gastric” mucins (MUC5AC and MUC6)
Incomplete IM shows “gastric” mucins (MUC5AC and MU6) coexpressed with “intestinal” mucins MUC2 and lacks CD10 representing an aberrant differentiation.
IM occurs frequently in a/w Paneth cells. The presence of paneth cells should prompt vigilant search for goblet cells.
Mucins by IHC
positive cells:
MUC2
MUC5AC
MUC6
MU1
MUC2: Goblet cells (“intestinal”)
MUC5AC: Foveolar epithelium (cytoplasmic)
MUC6: Pyloric glands (cytoplasmic)
MUC1: not expressed in non-neoplastic stomach.
IHC used to confirm pseudopyloric metaplasia from trual antral mucosa
Gastrin. confirms presence of G cells which are not seen in PPM.
reactive (mucosal) gastropathy
key histo featurs:
aetiological considerations:
Common sites in stomach
reduction in foveolar mucin cap resulting in darker foveolar surface, corkscrew-like changes in the gastric pits, superficial mucosal oedema with dilated capillaries, and “tongues” of smoothmuscle fibres extending from tehmuscularis mucosae upward into the lamina propria (muscularisation); inflammation is uncommon
Aetiologies: bile reflux, medications and alcohol, gastric pH and bacterial contamination by faecal-type microflora.
Reactive gastropathy is common in th antrum
biopsy fundic polypoid lesion
dx
Locations where found
Key features (macro +micro)
Aetiology:
Px:
Fundic gland polyp
Found exclusively in fundic glands (body and fundus)
Macro: typically small and sessile (< 2mm, rarely > 1cm)
Micro: consist of dilated cystic oxyntic glands with disotrted glandular architecture admixed with normal-appearing glands. Parietal cells balloon into the lumen with snoutlike protuberances, sometimes resulting in exfoliated anucleate blebs with eosinophilic granules that clog the gland outlets (findings are identical to that of PPI effect).
Aetiology: sporadic or a/w syndrome (FAP - higher incidence of dysplasia; gastric adneocarcinoma and prox polyposisi sydnrome GAPPS). C.F. hyperplastic polyps, FGPs are NOT a/w inflammatory or atrophic mucosal backdrop. Their presence is inversely correlated w/ Helicobacter infection/active gastritis. In the sporadic setting, it is widely accepted that PPI use is a/w FGPs, these lesions regress w/ medication cessation.
Px: risk of maligannt transformation is exceptionally low
features of gastric hyperplastic polyps
A/w b/g mucosal injury (85%) (inclus. h/pylori, reactive/chemical gastropathy etc)
Occur more frequently with increasing age (mean age 65 to 75 yrs) (c.f. syndromic FGP)
More frquently solitary in 75%
Owing to their foveolar origin, found in all regions fo the stomach (c.f. FGP)
High recurrence rate following polypectomy
Histo: has broad pedicle; shows elongated and distorted pits lined by a single layer of foveolar epithelial cells. Wide histo variability: gastric pits/glands may show cystic dilation separated by oedematous lamina propria with mixed inflammatory cells, there may be glandular crowding with gastric foveolar hyperplasia. Surface erosions are common. Always ensure a quick search fo r IM and dysplasia.
Always review b/g mucsoa for mucosal inflammation/damage/H.pylori.
oesophagus
ddx of polypoid oesophageal tumors (bening and malignant)
Benign:
Squamous papilloma
Fibrovascular polyp
Submucosal tumors
Inflammatory oesophagogastric polyp
Malignant
SCC
adneocarcionma
sarcomatoid camalignant melanoma
sarcomas
metastatic tumors
Define adenocarcinoma of the GOJ
(AJCC)
Any tumor that invovles the GOJ with an epicenter within the proximal 2 cm ofhte stomach.
Many junctional tumors are accompanied by BO, often of the short-segment type, providing evdience of an oesophageal derivation.
stomach lesion
dx
ddx
Xanthoma
DDx:
Adenocarcinoma (PAS(+) mucin + more pleomorphism/atypical cytology)
Whipple disease
Mycobacterium avium-intracellulare infection
granulomatous inflammation of the stomach
list non-infectious causes
Crohn disease
foreign-body rxn
tumor-associated granulomas
sarcoidosis
isolated granulomatous gastritis
fundic gland polyposis
definition
occurs in which settings
10 or more fundic gland polyps
1. following drug therapy for acid suppression
2. FAP
3. Gastric adenocarcinoma and proximal polyposis syndrome
60M gastric polyp
dx
key features
fundic gland polyp
Key features:
Hyperplastic expansion of hte glandular compartment of oxyntic mucosa
Cystically dilated glands lined by attenated but otherwise normal layer of chief/parietal and mucous neck cells. Overlying foveolar epithelium is normal.
Hyperplastic parietal cells with apocrine snouting is seen in patients on proton pump inhibitors
May harbor dysplasia (esp in FAP-associated or GAPPS)
gastric polyp
dx
Key features
Hyperplastic polyp
Key features: showing elongated, tortuous and dilated gastric pits (foveolar epithelium). Can also show abundant LP that is inflamed and oedematous. Can show smooth muscle strands extending from the muscularis propria and thick walled blood vessels at the base
52M white spot duodenum
Dx?
Key features demonstrated?
Lymphangioma
Proliferation of lymphatic vessels within the lamina propria
70M antral polyp
dx
Key features demonstrated
Hyperplastic polyp
Infolding/hyperplasia and branching of foveolar epithelium and cystic dilatation
stomach polyp
dx
Key features
demographic
IHC
tx:
Pyloric gland adenoma (low-grade dysplasi)
Lacks apical mucin cap and goblet cells. LIned by cuboidal/low columnar epithelium with eosinophilic cytoplasma with plae ground glass appearance.
Elderly women, a/w autoimmune metaplastic atrophci gastritis
IHC: MUC6(+), MUC5AC v
10% of PGAs exhibit focal expression of MUC2 and/or CDX2
Because of the relatively high risk of high-grade dysplasia / gastric cancer, complete resection is mandatory. Progression to high-grade dysplasia / gastric cancer is more frequent in patients with autoimmune gastritis.
60M stomach polyp
dx
gastric oxyntic gland adenoma
gastric cancer
Increased in which inherited conditions (6)
hereditary diffuse gastric cancer
FAP syndrome
Lynch syndrome
GAPPS
Li-Fraumeni syndrome
Juvenile polyposis syndrome
gastric lesion bx
dx
Key features
IHC:
Molecular
gastroblastoma
biphasic tumor arising in the muscularis propria. consists of varying proportions of uniform epithelial cell and uniform spindle cells arranged in nests. IHC epithelioid cells are (+) for CK, spindel cells express CD10, and CD56. (-) CD117, DOG1, CD34, desmin, SMA, syn, chromo, and S100.
Molecular: identification of a MALAT1-GLI1 fusion in the tumor cells
4F with diarrhoea and delayed growth development
dx?
IHC?
Cause?
Whippple’s disease
Key features:
Lamina propria expanded by foamy macrophage infiltrate
Fat vacuoles within lamina propria
Overlying enterocyte vacuolization due to intracytoplasmic lipid accumulation
Acute inflammation (variable)
IHC: PAS shows positive granular staining of macrophages
Cause:
Above image: LP infiltrated by foamy macrophages
Below: Foamy macros crowd the villous LP
60M PR bleeding; ampullary mass bx
Dx?
IHC?
Gangliocytic paraganglioma
Key features:
Unencapsulated submucosal lesion
Triphasic, with epithelioid, spindle cell (Schwann cell-like) and ganglion type cells of varying proportions
May therefore resemble well differentiated neuroendocrine tumor, paraganglioma or ganglioneuroma
Variable stromal amyloid
Epithelioid cells: pancreatic polypeptide, progesterone receptor, somatostatin, synaptophysin, chromogranin, CD56 (BMC Cancer 2015;15:269)
Ganglion cells: S100, pancreatic polypeptide, somatostatin, synaptophysin, chromogranin, CD56
Spindle cells: S100, BCL2 (67%)
How is Barrett oeosophagous defined by the American college of gastroenterology?
The american college of Gastroenterology define Barrett esophagus as an “extension of salmon-colored mucosa into the tubular oesophagus extending greater than or equal to 1 cm proximal to the GEJ with bx confirmation of intestinal metaplasia”. Thus, both the endoscopic appearance and the presence of goblet cells are required for a dx of BO.
ddx of oesophageal glandular epithelium on bx
DDx of oesophageal glandular epithelium:
Inadvertently sampled gastric mucosa
Eosphageal junctional mucosa (cardiac-type mucosa located in distal 1-2cm)
Oesophageal cardia-type glands (often located in the LP of tdistal and proxijmal oesophagous)
Heterotopic gastric fundic mucosa (gastric inlet patch) (noted in mid-oesophagous of 4-10% of normal subjects.
Cilitated columnar epithelium (embryological remant found in infants or metaplastic )
SEbaceous glands (present endoscopically as msall, yellow papules).
What two genes are commonly mutation in GISTs?
KIT
PDGFRA
gastric cancer
Gastric carcinoma:
what are the 5 main histological subtypes (as per WHO)?
tubular
papillary
poorly cohesive (including signet-ring cell nad other subytpes)
mucinous
mixed adenocarcinomas.
key features of celiac sprue:
crypt hyperplasia
loss of villous height
chronic inflammatory cell infiltration
surface IEL (greater than 40 per 100 enterocytes).
According to the american college of gastroenterology what is the definition of Barrett’s oesophagus?
“extension of salmon-colored mucosa into the tubular oesophagus extending greater than or equal to 1 cm proximal to the GEJ with bx confirmation of intestinal metaplsia”.
DDx of glandular epithelium (from oesophagous)
Inadvertently sampled gastric mucosa
Eosphageal junctional mucosa (cardiac-type mucosa located in distal 1-2cm)
Oesophageal cardia-type glands (often located in the LP of distal and proximal oesophagous)
Heterotopic gastric fundic mucosa (gastric inlet patch) (noted in mid-oesophagous of 4-10% of normal subjects.
Cilitated columnar epithelium (embryological remnant found in infants or metaplastic )
Sebaceous glands (present endoscopically as msall, yellow papules).
AJCC staging of oesophageal carcinoma (T stage)
what molecular testing is done on oesophageal adenocarcinomas?
What treatment can be offered if mutated?
HER2 testing is done routinely and if amplified is approved for treatment with Trastuzumab.
three types of adenoma that occur in the small bowel?
intestinal
foveolar
pyloric
Multiple gastric GISTS can be found in which following 4 scenarios:
Carney syndrome (GIST, pulmonary chondroma and functioning extraadrenal paraganglioma). Young females. GISTS indolent.
Carney-stratakis syndrome: AD. Characterised by GIST and (familial) paraganglioma. Pts have germline mutations in one of the SDH genes (SDHB, SDHC, SDHD),
Sporadic SDH B deficient GIST tumors: pediatric population. NB: both sporadic and syndrome succinate dehydrogenas-deficient GISTS show a high propensity for LN metastasis but overall have a very protracted clinical course.
Familial GIST – germline mutations in KIT and PDGFRA.
Which immunomodulatory drug revolutionised the tx and px of metastatic GISTs?
Imatinib revolutionized the treatment and px of metastatic GISTS.
GIST mutations
75% of GISTs harbour gain-of-function mutations of the KIT and 10% harbor PDGFRA activating mutations.
Both oncogenes are located on chromosome 4. Mutations are mutally exclusive and result in ht econstitutive actiation of eithe rKIT or PDGFRA
