Feb23 M1,2-Pathology GI-neoplasia Flashcards
2 cancers in GI tract in general
carcinomas (malignant epithelial neoplasm)
1. adenoCA (CA with glandular differentiation)
2. squamous cell CA (SCC): CA with squamous cell differentiation
(and neuroendocrine CA also possible)
charact of adenoCA glandular diff
- prod of glands
- prod of mucous IC or EC (epith cells surround the space of mucous prod)
charact of adenoCA (malignant features)
- architecture (irregular shape, infiltrating pattern)
- cytology (high NC ratio, prominent nucleoli, large cells w irregular size and shape, irregular nuclei)
- necrosis
- frequent mitoses
- desmoplastic stroma
desmoplasia def (cancer feature)
promoted formation of CT between tumor cells (has fibroblasts producing collagen + vessels feeding)
SCC differentiation charact
- keratinocyte-like cells (polygonal, pavement-like, eosinophilic
- intercellular bridges
- keratinization
SS malignant features
- architecture: 1. in situ: tumor above BM, normal architecture, malignant cytology 2. invasive SCC: irregulary shaped sheets of cells, infiltrating pattern
- cytology (irregular nucleus and cells, prominent nucleoli, high NC)
- necrosis
- mitoses
- desmoplastic stroma
invasive SCC charact + stroma diff with adenoCA
polygonal cells invading desmoplastic stroma (exact same look as adenoCA stroma). focal keratin formation
invasive SCC cells charact
- intercellular borders
- desmosomal junction
- keratinization
- intercell bridges
- cytological atypia
- prominent nucleoli
precursor lesions of adenoCA
- intestinal metaplasia followed by dysplasia of glandular mucosa = stomach or esophagus
- adenoma (stomach or bowel)
- dysplasia in chronic inflam bowel disease (bowel)
precursor lesions of SCC
SCC in situ
intestinal metaplasia def and dysplasia
- metaplasia = in stomach or esophagys: epith replaced by glandular epith with goblet cells
- dysplasia = when cells have features of adenoCA (cyto)
adenoma charact
-nuclear enlargement
-nuclear stratification
-lack of maturation
looks dark bc lot nuclei
gland like
SCC in situ charact
- no maturation, large nuclei, high NC ratio, atypia
- LP is clean
2 tumors of esophagus and most common
- adenoCA (most common bc devs out of intestinal metaplasia. BE with intestinal metaplasia and goblet cells)
- SCC
low-grade dysplasia in Barrett esophagus charact
- normal architecture
- atypica
- lack of maturation
- nuclei enlargement and stratification
high-grade dysplasia in BE
- dysplastic glandular mucosa with bridges under the glands
- absence of maturation of glandular mucosa
- large atypical, crowded, stratified nuclei
- complex architecture
esophageal adenoCA charact and symptoms
- usually out of BE so distal esophagus
- symptoms: GERD symptoms, pain, weight loss, anemia
why anemia in esophageal adenoCA and usual causes of anemia
- usual cause = loss through bleeding (menses, GI = NUMBER ONE CONCERN if see Fe deficiency anemia, ..). diet cause is very unusual
- GI may be ulcer but consider cancer in older people
most likely site of GI bleeding if GI bleeding is happening
colon
esophageal adenoCA macro charact
- stricture of GE junction
- very irregular BE with foci of dysplasia or small CA
- ulceration
- necrotic center of the tumor
micro charac of esophageal adenoCA
-many glands of various sizes infiltrating the stroma
how degree of differentiation is determined in esophageal adenoCA
amount of glands formed
few glands = poor differentiation.
with glands prod, also mucous prod (intra and extra cellular, exported in surrounding stroma)
esophageal SCC causes
- smoking
- alcohol
- carcinogens in food
esophageal SCC clinically
- asymptomatic if small
- dysphagia (tumor causes stricture), chest pain, weight loss
- DX BY ENDOSCOPY
esophageal SCC charact
- NO BE (mucosa around it is normal)
- squamous epith
- tumor may protrude in lumen, show ulceration, stricture
- usually in distal esophagus
most common cancers depending on esophagus part
upper = SCC middle = SCC lower = adenoCA
esophagus SCC in situ charact
- above BM
- features of malignancy
- squamous epith pattern
esophagus invasive SCC
- very irregular bottom
- infiltrates stroma underneath (below BM)
- some necrosis, some differentiation
- polygonal cells with focal keratin formation
- desmoplastic stroma
esophageal SCC specific charact
- pavement like cells
- cyto atypia
- keratinization
- intercellular bridges
2 cancers in the stomach
adenoCA (intestinal type or diffuse type (signet ring cell)) and lymphoma
2 types of adenoCA
- intestinal metaplasia
- organ specific type (stomach = signet ring cell type)
risk factors for gastric adenoCA
- H pylori infection
- diet rich in smoked salted food and nitrites and poor in fruits and vegetables
- smoking
clinical features of gastric adenoCA
- asymptomatic
- H pylori infection symptoms
- advanced = epigastric pain, ANEMIA
- stenosis symptoms, only if in pylorus
macro and micro charact of intestinal type gastric adenoCA
- macro: grossly forms a mass, sometimes ulcerated with ELEVATED borders. wall thickening. may have hemorrhage, necrosis
- micro: glands infiltrating stroma
macro and micro charact of diffuse type gastric adenoCA
macro:
- infiltrates stomach, no obvious mass
- thickened wall, gastric folds thickened bc of tumor infiltration
micro: no glands, single cells, sometimes signet ring cells morphology infiltrate stroma
precursor lesions of intestinal type gastric adenoCA
- low and high grade dysplasia (in setting of intestinal metaplasia due to H pylori or to autoimmune gastritis)
- gastric adenoma
gastric mucosa with low-grade dysplasia charact
increased NC ratio, lack of maturation, ..
gastric mucosa with high-grade dysplasia charact
increased complexity
diffuse gastric adenoCA macro charact
- thickening
- thickened folds
- effacement of folds
- possible ulcers
signet ring cell CA of the stomach microscopy
- signet ring cell: round cells with mucus accum in cytoplasm pushing nucleus on the side + nuclei infiltrate
- no glands formation except some glands (a bit)
complication of signet ring cell gastric adenoCA
metastasis to lymph nodes
possible tumor mix in the stomach
mixed intestinal and signet ring cell tyepe adenoCA
why gastric and esophagus cancer can present with anemia
bc the tumors bleed. eventually bone marrow runs out of Fe reserve and intake is insufficient to compensate on the loss
2 cancers in the colon
adenoCA and adenoma (before adenoCA is the polyp that you have to detect early before becomes adenoCA)
colonic adenoma on histo
- nuclear enlargement
- nuclear stratification
- lack of maturation
note: still check anemia
note on sessile villous adenoma of the rectum
have to check on microscopy to make sure there’s no cancer
villous adenoma charact on histo
finger-like projections with fibro-vascular cores lined by adenomatous epithelium
3 types of colorectal adenomas that can dev into colon cancer
- villous
- tubular villous
- tubular
colonic adenoCA macro features
- many polyps
- ulcerated tumor possibly, ulcerated mass
- elevated borders
- regular center
features of a section of colonic adenoCA
- invasion in tunica muscularis: this replaces the submucosa
- possible lymph node metastasis
microscopy of colonic adenoCA
- irregular glands infiltrating the stroma
- desmoplastic stroma
- necrotic debris with glands
possible complication of colonic adenoCA
capillary invasion (vascular invasion)
(IMPORTANT) 2 pathways of colonic adenoCA formation
-chromosomal instability (85%)
-microsatellite instability (15%)
NOTE: both types have hereditary conditions associated
chromosomal instab pathway charact
- structural and numeric chromosomal alterations
- microsat stable
- MUTATIONS: APC, K-ras, p53
microsat instability pathway charact
- diploid
- microsat instab
- dysfct of MMR proteins (MSH2, MLH1, MSH6, PMS2)
- peculiar tumor histology (mucinous differentiation, poorly differentiated tumors)
- BETTER prognosis
hereditary conditions associated with chromosomal instab and microsat instab pathways
- chrom. instab: FAP (familial adenomatous polyposis)
- microsat instab: hereditary nonpolyposis CRC (HNPCC) = Lynch syndrome
FAP charact
- many polyps
- distal colon
- 1 hit in lifetime is sufficient, is a dominant condition. odd for 2nd hit on APC is high.
- 100% penetrance
HNPCC (Lynch) charact
- autosomal dominant
- MMR genes mutations
- rare polyps (BUT have more polyps than general population)
- proximal colon
- high penetrance but not 100%
carcinoid (neuroendocrine) tumor def
well differentiated neoplasm arising in mucosal neuroendocrine cells
carcinoid tumor clinical charact
- incidental finding on endoscopy
- carcinoid syndrome (flushing, teleangiectasias, cyanosis, bronchoconstriction, edema, hyperperistalsis, pulmonary and tricuspid valvular disease)
carcinoid tumor charact and location
- esophagus to rectum
- tiny polyp-like to large tumors
- firm and beige, tan homogenous surface
- grow very slowly
- produce endocrine mediators
- can still metastasize
significant of carcinoid syndrome in carcinoid tumor
sign of BAD prognosis:
- if not metastasis, liver inactivates the mediators
- so syndrome = metastasized
carcinoid tumor types IN THE STOMACH
- in background of atrophic gastritis
- Zollinger-Ellison syndrome
- sporadic
atrophic gastritis pathophgy
lot of gastrin prod to increase acid release and no response so even more gastrin produced
ZE syndrome pathophgy
tumor producing gastrin. covered in pancreatic and biliary tree material
atrophic gastritis carcinoid tumor of the stomach and ZE syndrome carcinoid tumor of the stomach: thing in common
hypergastrinemic state
carcinoid tumors of the stomach: prognosis
- type 1 (in atrophic gastritis): good prognosis
- type 2 (in ZE): stomach is good prognosis but bc pancreatic tumor causing carcinoid is also there, bad prognosis
carcinoid tumors on microscopy (same for 3 gastric types, lung carcinoid, etc.)
- solid sheets separated by thick collagen
- sometimes gland like or tubular structures form or may grow in ribbons or pseudoglandular or cords
carcinoid tumor cytology
- rounded or oval nuclei
- speckled chromatin
- small cytoplasm
- can’t see nucleoli (inconspicuous)
possible complication of carcinoid tumor
lymph node metastasis
carcinoid tumor special stain
chromogranin or synaptophysin immunostain (neuroendocrine markers: synaptophysin and chromogranin)
gastrointestinal stromal tumors (GIST) def
tumors arising from ICC (pacemaker cells of peristalsis)
GIST clinically
- no symptoms
- symptoms related to bleeding or compression of adjacent structures
GIST usual cause
gain of fct mutations of either c-KIT or PDGFRA (platelet-derived growth factor receptor A) which is a TM R for tyrosine kinase activity involved in cell prolif and apoptosis
GIST macro features
- nodular masses protruding in lumen, covered by stretched mucosa
- erosion, ulceration of mucosa possible
- beige and rubbery type
GIST vs adenoCA of stomach difference
adenoCA of stomach: mucosa not stretched bc cancer starts in mucosa
GIST: stretches mucosa: possibly diminishing blood supply
GIST on microscopy
- intersecting bundles of SPINDLE cells
- if epithelioid GIST = polygonal cells
staining of GIST
immunostain for c-KIT (CD117)
lymphomas in the stomach def
stomach is primary site or lymphoma arising there from somewhere else
most frequent lymphomas in the stomach
- marginal zone lymphoma of the MALT
- diffuse large B-cell lymphoma
how is it possible to have marginal zone lymphoma of MALT in stomach if there is NO MALT in the stomach
MALT arises in the stomach in the setting of H pylori infection and active gastritis
MALT lymphoma of stomach charact
- low grade B cell lymphoma
- assoc with H pylori infection (may regress if removed)
- macro = small mucosal lesions, thickening of folds. DOESN’T form masses
stomach MALT lymphoma microscopy
- infiltration of small lymphoid cells in mucosa
- partial replacement of glands (lymphoepithelial lesions)
MALT lymphoma of stomach: how to check for B cells
stain for CD20 (a B cell is CD20+)
(IMPORTANT) main feature of stomach MALT lymphoma
on cytokeratin stain, lymphoepithelial lesions (infiltrating lymphocytes in mucosa replace glands)
MALT lymphoma prognosis
is a mild cancer. good prognosis
diffuse large B cell lymphoma o the stomach (DLBCL) def
- high grade B cell lymphoma
- de novo or in setting of MALT lymphoma
- endoscopy (macro): large soft mass, sometimes ulcerated
DLBCL stomach microscopy (all in the name)
- diffuse proliferation
- LARGE cells (MALT lymphoma, cells are smaller)
- CD20+ (B cells)
- neoplastic (lymphoma)
DLBCL stomach: why the tumor is soft
no stromal reaction to the tumor, no desmoplasia
management of gastric CA vs lymphoma
gastric CA = gastrectomy
lymphoma = chemotherapy (no gastrectomy)
