Other GI Tumors Flashcards
What are the 3 categories of “other” (non-epithelial) tumors we’re talking about in the GI?
Mesenchymal -e.g. smooth muscle.
Neuroendocrine
Hematologic (e.g. lymphoma)
Are leiomyosarcomas common in the GI tract?
Very rare.
Where are leiomyomas most commonly found in the GI tract? Where are they uncommon?
Most common: Esophagus, also colon.
Uncommon in the stomach and small intestine.
Immunohistochemical stains for leiomyoma? (2 things)
Smooth muscle actin (SMA)
Desmin
What’s the most common mesenchymal tumor of the GI tract?
GIST - gastrointestinal stromal tumor
From what cell do GISTs probably arise? Where are these cells?
Interstitial cells of Cajal (ICCs) - pacemaker cells.
These cells are associated both this submucous plexus and myenteric plexus.
For what stain are most GISTs positive?
What’s different about the ones that don’t stain for it?
c-kit - about 95%
The rest are more likely to be epithelioid in morphology, and be driven by PDGFRA mutations.
What mutations are thought to drive GISTs?
KIT or PDGRFA
- both are gain of function mutations
Histological buzzwords for GIST?
Spindle cell, “ice cream cones.”
Or epithelioid.
What’s a new stain (other than c-kit) for GISTs?
DOG1
Treatments for GIST?
Surgery.
Tyrosine kinase inhibitors (esp Imatinib - Gleevec)
What is GIST response to imatinib based upon?
Type of mutation in the the tumor.
Best with exon 11/Kit, worst with exon 9.
Where are GISTs most common in the GI tract?
Most common in the stomach, then small intestine.
Rare in colon and esophagus.
(the opposite distribution from leiomyomas)
3 variables in GIST prognosis?
Location
Size
Mitotic count
2 hereditary associations with GIST?
NF1
Carney’s triad
What’s Carney’s triad?
Young females with …
Gastric epithelioid GISTs
Pulmonary chondroma (hamartomas)
Paragangliomas
What does the “neuro” in neuroendocrine (NE) cells refer to?
Production of peptides and amines stored in neurosecretory granules.
How can you distinguish NE cells from Paneth cells?
NE granules point basolaterally.
Paneth granules point toward the lumen.
3 categories of NE tumors (NETs)?
Which is most common in the GI tract?
Well-differentiated NE tumor - most common in GI tract.
Poorly-differentiated NE carcinoma, small cell type.
Poorly-differentiated NE carcinoma, large cell type.
(the latter 2 are very aggressive, but less common)
Why do NE tumors often have intact epithelium over them?
They arise from the epithelial - submucosal junction and push up the epithelium above them.
Buzzword for the histological appearance of NET nuclei?
Salt and pepper (or salt-n-pepa) nuclei.
3 NE markers you should know about?
Synaptophysin
Chromogranin
CD56
What does it mean for an NET to be functional? How does this relate to aggressiveness?
Functional = producing hormones.
In GI tract, functional usually means more aggressive.
Which cells in the GI tract make 5-HT, and what does it do?
Enterochromaffin cells (ECs) 5-HT increases GI motility and blood flow.
What do you call the syndrome where there’s a GI tumor making 5-HT?
Carcinoid syndrome.
Symptoms of carcinoid syndrome?
Flushing, diarrhea, right sided heart disease (due to fibrosis of tricuspid valve).
- can detect excess 5-HIAA (5-HT breakdown product) in urine.
Why does carcinoid syndrome imply metastatic disease? (probably an important concept)
When it’s a primary tumor, the 5-HT is mostly broken down in the liver by first pass metabolism.
When the tumor metastasizes, its hormones can disseminate systemically, causing symptoms.
Why is it important to diagnose gastrinoma? (3 reasons)
They’re aggressive.
Could be associated with MEN1.
ZES -> ulcers.
How can you have gastrinoma symptoms without metastasis?
Gastrin is metabolized renally, so it isn’t affected by first-pass metabolism.
What are some pre-disposing factors for GI lymphoma?
Infection (esp. H. pylori)
Celiac
IBD
several immunodeficiencies
What are 3 common low grade B-cell lymphomas?
Marginal Zone Lymphoma (aka MALT lymphoma).
Follicular lymphoma.
Mantle cell lymphoma. - most aggressive.
2 high grade B-cell lymphomas?
Diffuse large B-cell lymphoma.
Burkitt Lymphoma.
3 parts of a normal B cell follicle, from inside out? What low-grade B cell lymphomas come from each?
Germinal center - Follicular lymphoma. Mantle zone (naive B cells) - Mantle zone lymphoma. Marginal zone (mature B cells) - Marginal zone (aka MALT) lymphoma.
Most common association with Marginal Zone aka. MALT lymphoma? Treatment?
H. pylori
Treatment = H. pylori eradication.
If MALT lymphoma doesn’t respond to H. pylori eradication, what transformation does it likely have? Effect?
t(11:18): API2-MALT1
Causes transformation to Diffuse Large B-cell Lymphoma -> spread.
Where do you see an expanded marginal zone and “lymphoepithelial lesions”?
Marginal zone aka. MALT lymphoma.
Where do most follicular lymphomas occur? How do they appear grossly?
Mass-like lesions in the small intestine.
What are 3 things on the DDx for lymphomatous polyposis?
Reactive lymphoid hyperplasia (usu. in HIV).
Mantle zone lymphoma.
Follicular lymphoma.
How does a follicular lymphoma look different from a reactive follicle?
It’s crowded and “looks clonal” - whatever that means.
Most common gene rearrangement in follicular lymphoma?
t(14:18) BCL-2
Recall: BLC-2 is anti-apoptotic. GC B-cells should be primed to die, and thus shouldn’t express BCL-2.
Mantle cell lymphoma: indolent or aggressive?
aggressive
What translocation drives mantle cell lymphoma? What does this cause?
t(11,14): Form IgH-Cyclin D1 (BCL-1) fusion that drives Cyclin D1 overexpression.
Take home part about Diffuse Large B-Cell Lymphoma (DLBCL)?
Had large lymphocytes… and it’s agressive.
High mitotic rate.
What’s the histological buzzword for Burkitt Lymphoma?
“Starry Sky” pattern due to “tingible body macrophages” amid rapidly dividing lymphocytes.
Translocation that drives Burkitt Lymphoma? (in 80% of cases)
t(8:14) - c-myc to IgH
Of the endemic, sporadic, and immunodeficiency-associated presentations of Burkitt Lymphoma, which usually present in the abdomen?
Sporadic and immunodeficiency-associated Burkitt’s usually present with abdominal lymphoma.
(Endemic usu. presents in Jaw/facial area.)
What is Enteropathy-type T Cell Lymphoma associated with?
Celiac disease that is refractory to gluten-free diet.
Histological buzzword for enteropathy-type T cell lymphoma?
How do you know it’s not celiac?
Mixed inflammatory background - eosinophils, plasma cells, and histiocytes.
(Atypia, immunohistochemistry, loss of CD8s, T cell monoclonality tell you it’s not celiac)
What is t(14:18) - aberrant BCL2 expression associated with?
Follicular Lymphoma
What is t(11:14) - Cyclin D1 overexpression associated with?
Mantle Cell Lymphoma.
What is t(8,14) - c-myc overexpression associated with?
Burkitt Lymphoma
What is t(11,18) associated with?
Marginal Zone aka MALT Lymphoma
Which lymphoma is caused by H. pylori / can be resistant to treatment of H. pylori?
MALT Lymphoma.
