03-06 Tumors of the Bowel + PATH Flashcards
At the end of this lecture, the learner should be able to: • Define and explain the terms: Neoplasia, benign, malignant, tumor, mass, hamartoma, hyperplasia • Outline the nomenclature of Neoplasms found in the intestinal tract • Describe the pathologic features, clinical presentations, prognosis and treatment options of the more common neoplasia, benign and malignant, of the small intestine • Describe the pathologic features, clinical presentations, prognosis and treatment op
<p>
OBJECTIVE: define hamartoma</p>
<ul>
<li>
mass of mature tissues normally found at that site, but present in an abnormal arrangement. </li>
</ul>
<p>Name the benign neoplasm and malignant neoplasm version of normal: <strong>glandular epithelium</strong></p>
<ul>
<li>Adenoma</li>
<li>Adenocarcinoma</li>
</ul>
<p>
Name the benign neoplasm and malignant neoplasm version of normal: Adipose tissue</p>
<p>
lipoma = benign</p>
<p>
liposarcoma = malignant</p>
<p>
Name the benign neoplasm and malignant neoplasm version of normal: vessels</p>
<p>
angioma, angiosarcoma</p>
<p>
Name the benign neoplasm and malignant neoplasm version of normal: neuroendocrine cells</p>
<ul>
<li>
benign = carcinoid*</li>
<li>
malignant = Neuroendocrine carcinoma</li>
</ul>
<p>
1 There is no reliable histopathologic feature to distinguish which of these tumors will behave in a benign vs. malignant fashion. Best "predictors" are size and mural invasion. </p>
<p>
Name the benign and malignant: Smooth muscle neoplasms</p>
<p>
leiomyoma, leiomyosarcoma</p>
<p>
Name the benign and malig Peripheral nerve sheath neoplasms</p>
<ul>
<li>
benign = Schwannoma</li>
<li>
Malignant Peripheral Nerve Sheath Tumor (MPNST) </li>
</ul>
<p>
Interstital cells of Cajal neoplasms</p>
<ul>
<li>
benign = GIST*</li>
<li>
malig = GIST*</li>
</ul>
<p>
Gastrointestinal Stromal Tumor, a unique mesenchymal tumor (formerly lumped in with leiomyoma/leiomyosarcomas or schwannoma/MPNSTs) that demonstrate expression and often mutation of the c-­kit receptor tyrosine kinase proto-­oncogene (Stem cell factor-­receptor; CD117). </p>
<p>
Only \_\_ % of GI tumors are in the small intestine. In fact, most are actually \_\_\_\_\_\_.</p>
<p>
Only <u>1</u> % of GI tumors are in the small intestine. In fact, most are actually <u>mets from other cancers</u>.</p>
<p>
Top 3 most common types of malignant small bowel cancer</p>
<ol>
<li>
adenocarcinoma</li>
</ol>
<p>
followed by carcinoid and lymphoma</p>
<p>
Estimated that the time interval required for progression from adenoma to carcinoma in individuals with sporadic colon cancers ranges from \_\_\_\_ yrs.</p>
<p>
Estimated that the time interval required for progression from adenoma to carcinoma in individuals with sporadic colon cancers ranges from <u><strong>5-12</strong></u> yrs.</p>
<p>
CRC is the \_\_\_\_ most common cancer</p>
<p>
CRC is the 3rd most common cancer</p>
<p>
adenoma of the small intestine</p>
<ul>
<li>
Benign or malignant?</li>
<li>a
Found in \_\_\_\_\_\_\_\_</li>
<li>
Clinical Presentation</li>
<li>
Path Features</li>
<li>
Prognosis</li>
<li>
Treatment options</li>
</ul>
<ul>
<li>
benign (makes up 25% of all benign small bowel tumors), but neoplastic</li>
<li>
found in small intesting (most often by the ampulla of vader)</li>
<li>
Presentation:
<ul>
<li>
♀ = ♂; Age = 50-85</li>
<li>
Sx: often vague & nonspecific, bleeding: active or occult, pain (colicky), n/v, weight loss, (rarely perf)</li>
<li>
Incidence 6200 cases/yr</li>
<li>
25-30% of symptomatic patients have palpable mass.</li>
</ul>
</li>
<li>
Path features
<ul>
<li>
low-grade dysplasia</li>
</ul>
</li>
<li>
Prognosis: may progress to adenocarcinoma</li>
</ul>
<p>
What are other some benign small bowel tumors besides adenoma?</p>
<p>
leiomyoma, lipoma, hamartomatous polyps, hemangioma, neurofibroma and ~carcinoid</p>
<p>SB adenocarcinoma</p>
<ul>
<li>Found in \_\_\_\_\_\_\_\_</li>
<li>Clinical Presentation</li>
<li>Risk Factors</li>
<li>Path Features</li>
<li>Prognosis</li>
<li>Treatment options</li>
</ul>
<p>malignant SB neoplasms</p>
<ul>
<li>Found in: Most occur in the duodenum, near ampulla of Vater. </li>
<li>Clinical Presentation:
<ul>
<li>pain</li>
<li>bleeding/anemia</li>
<li>biliary obstruction (b/c so often near ampulla of Vater)</li>
</ul>
</li>
<li>Risk Factors:
<ul>
<li>h/o IBD --> adenocarcinoma</li>
<li>Celiac dz --> lymphoma</li>
<li>Herid cancer syndromes like Fam. polyposis, HNPCC, Peutz-Jeghers</li>
<li>enviro exposures</li>
</ul>
</li>
<li>Path Features</li>
<li>Prognosis: generally poor
<ul>
<li>50-60% have advanced ds at time of dx</li>
<li>20-50% 5 yr survival for non-lymphoma </li>
</ul>
</li>
<li>Treatment options
<ul>
<li>Segmental resection :
<ul>
<li>small bowel carcinoids</li>
<li>confirmed adenomas/adenocarcinomas</li>
<li>symptomatic lesions & those of uncertain</li>
<li>histology</li>
</ul>
</li>
<li>Whipple resection for duodenal adenocarcinomas</li>
<li>Chemo for SB lymphomas</li>
<li>Endoscopic resection for benign lesions of duodenum or TI</li>
<li>Endoscopic surveillance for benign villous adenomas of duodenum in pts w/ FAP</li>
</ul>
</li>
</ul>
<p>SB carcinoid tumor</p>
<ul>
<li>Found in \_\_\_\_\_\_\_\_</li>
<li>Clinical Presentation</li>
<li>Path Features</li>
<li>Prognosis</li>
</ul>

<p>SB carcinoid tumor</p>
<ul>
<li>Found in: appendix #1 place; followed by followed by the small intestine (primarily ileum), rectum, colon, and stomach.
<ul>
<li>also:bronchial tree, GU & GYN tracts</li>
</ul>
</li>
<li>Clinical Presentation: MOST COMMON SB MALIG
<ul>
<li>pain/obstruction most common</li>
<li>rare: carcinoid syndrome
<ul>
<li>Occurs in <10% w/ malig. carcinoids, usu with extensive liver metastases</li>
<li>Release of serotonin into systemic circ. leads to</li>
<li>skin flushing/cyanosis</li>
<li>diarrhea & cramps</li>
<li>bronchospasm</li>
<li>R ventricular subendocardial fibrosis -></li>
<li>Pulmonic & tricuspid valve stenosis/regurge</li>
</ul>
</li>
</ul>
</li>
<li>Path Features
<ul>
<li>yellow submucosa (pic on reverse)</li>
<li>tumor invades muscularis propria, a characteristic muscle fiber stranding</li>
<li>fibrosis often severe enough to kink →obstruction. </li>
<li>organoid (seen here) or gyrating histo</li>
</ul>
</li>
<li>Prognosis:Site, depth of invasion, and size are prognostic indicators:
<ul>
<li><strong>Having symptoms is bad</strong>: 90% of symptomatic pts have mets
<ul>
<li>often found incidentally</li>
</ul>
</li>
<li>appendicial and rectal: likely benign</li>
<li>< 2cm: likely benign</li>
<li>hasn't invaded muscularis mucosa: likely benign</li>
</ul>
</li>
</ul>

<p>
Dx of carcinoid cancers</p>
<ul>
<li>
can use octreotide test: nearly all carcinoid tumors have somatostatin receptors</li>
<li>
CT, biopsy, blah blah</li>
</ul>
<p>SB lymphoma</p>
<ul>
<li>Found in \_\_\_\_\_\_\_\_</li>
<li>Clinical Presentation</li>
<li>Risk Factors</li>
<li>Path Features</li>
<li>Prognosis</li>
<li>Treatment options</li>
</ul>
<p>SB lymphoma</p>
<ul>
<li>Found in: GIT = commonest site for 1° extranodal lymphomas.
<ul>
<li>most often stomach followed by SB, ileocecal region and colon </li>
</ul>
</li>
<li>Clinical Presentation</li>
<li>Risk Factors: 1° GI lymphomas are commonly associated with:</li>
<li>
<ul>
<li>chronic infection (H. pylori gastritis)</li>
<li>celiac disease</li>
<li>immunodeficiency (AIDS, immunosuppression), and</li>
<li>Crohn's disease</li>
<li>Can be sporadic also. </li>
</ul>
</li>
<li>Path Features
<ul>
<li>2 types in both stomach and intestines: DLBCL and Marginal zone types</li>
</ul>
</li>
<li>Prognosis:
<ul>
<li>Lymphomas have a much better prognosis than carcinomas.</li>
<li>5 yr survival rate depends on the stage and histologic type, but, overall, it is >50%.</li>
</ul>
</li>
</ul>
<p>
SB GIST tumor basics</p>
<ul>
<li>
Mesenchymal tumor resembling modified smooth muscle and neural tissue
<ul>
<li>
Hypothesized origin = <u>Interstitial cells of Cajal</u></li>
</ul>
</li>
<li>
Resides in muscularis mucosa (so deep-seated tumor)</li>
<li>
CD117 positive (c-<u>kit tyrosine kinase</u>)</li>
<li>
Spectrum from benign to malignant</li>
</ul>
<p>
Cancers that met to SB</p>
<p>
Melanoma, breast carcinoma, lung carcinoma, renal cell carcinoma. </p>
<p>
#1 gene mutation in colon ca</p>
<p>
APC gene mutations are usually the earliest and, possibly, the initiating event in about 80% of sporadic colon cancers. With clonal progression, additional mutations accumulate, such as in K-­ras and p53 genes. </p>
<p>
When do most CRCs occur?</p>
<p>
90% occur in pts > 50 y/o</p>
<p>
If you see CRC in younger pts you should think</p>
<p>
think FAP, HNPCC, MUTYH, PJS, or IBD</p>
<p>
FAP</p>
<ul>
<li>
caused by?</li>
<li>
present at what age? how?</li>
<li>
natural hx?</li>
<li>
tx?</li>
</ul>
<p>
<strong>Familial Adenomatous Polyposis</strong></p>
<ul>
<li>
-Autosomal dominant disorder
<ul>
<li>
however, <u>25% of pts have no family hx</u></li>
</ul>
</li>
<li>
-mutation in the APC (Adenomatous polyposis coli) gene → > 300 mutation ID's</li>
<li>
-present in the 2nd to 3rd decades w/ 100's or 1000's of adenomatous polyps</li>
<li>
-rate of progression ~variable, but all patients will eventually develop colonic carcinoma(s) in early adult life (age 39)
<ul>
<li>
assoc'd w/ lots of other tumors</li>
</ul>
</li>
<li>
-the treatment is total colectomy.
<ul>
<li>
different options: some with more sparing of fxn than others</li>
</ul>
</li>
</ul>
<p>
MYH Polyps</p>
<ul>
<li>
caused by?</li>
<li>
present at what age? how?</li>
<li>
natural hx?</li>
<li>
tx?</li>
</ul>
<ul>
<li>
caused by: you have to have bi-allelic mutation in MutY Homolog (base excision repair gene)
<ul>
<li>
can lead to mutation of APC which is esp susceptible to these lesions</li>
</ul>
</li>
<li>
presentation can be the same as FAP but usually < 100 polyps
<ul>
<li>
Mean age at cancer dx = 45 yrs</li>
</ul>
</li>
<li>
natural hx?</li>
<li>
tx?</li>
</ul>
<p>
HNPCC</p>
<ul>
<li>
caused by?</li>
<li>
present at what age? how?</li>
<li>
natural hx?</li>
<li>
tx?</li>
</ul>
<p>
Hereditary Non-Polyposis Colon Cancer</p>
<ul>
<li>
Caused by A.D. inherited germline mutation in mismatch repair genes (MSH2, MLH1, MSH6, PMS2)
<ul>
<li>
correct microsatellite repeats that increas r/o mutation</li>
<li>
can do IHC to see qualitatively if these are missing</li>
</ul>
</li>
<li>
Present with two types
<ul>
<li>
Lynch I = CRC ca's only</li>
<li>
Lynch II = CRC ca's + <strong>Endometrial</strong>, ovarian, pancreatic, gastric, SB, transitional cell of kidney/ureter</li>
<li>
Have adenomatous polyps that are slightly more dysplastic
<ul>
<li>
Larger with a villous or dysplastic component</li>
<li>
Flat adenomas/serrated adenomas</li>
</ul>
</li>
<li>
More present in <strong>proximal colon</strong></li>
<li>
present early avg = 45 y/o</li>
<li>
higher incidence of metachronous cancer</li>
<li>
however, no big phenotypic differences → difficult dx</li>
</ul>
</li>
<li>
natural hx:
<ul>
<li>
earlier dx (~45 y/o)</li>
<li>
tumors progress to cancer faster (~3.5 years) so need more screening</li>
<li>
BUT! Better cancer-specific survival!!</li>
</ul>
</li>
<li>
</li>
</ul>
<p>
PJS</p>
<p>
<strong>Peutz-Jeghers Syndrome:</strong><br></br>
-Autosomal dominant<br></br>
-Multiple <strong>hamartomatous polyps</strong> of the entire GIT (esp SB)<br></br>
-Mucocutaneous <strong>melanosis</strong> (lips & buccal mucosa).<br></br>
-PJ polyps themselves have no malignant potential, but these patients have a higher incidence of carcinoma elsewhere in the colon<br></br>
-Increased frequency of extra-GI cancer</p>
<p>
Potential lifestyle, diet, meds that protect against CRC</p>
<ul>
<li>
COX2 inhibition</li>
<li>
fiber</li>
<li>
diet/exercise</li>
<li>
Vit b6</li>
<li>
Calcium and vitamin D
<ul>
<li>
Calcium believed to bind fatty and bile acids</li>
</ul>
</li>
<li>
Folic Acid - deficiency may -> DNA hypermethylation</li>
<li>
Omega 3s</li>
</ul>
<p>
Are most CRCs caused by inheritied syndromes or sporadic occurence?</p>

<p>
Polyps</p>
<ul>
<li>
Two types</li>
<li>
Causes of and percent that are neoplastic</li>
<li>
Cause of and percent that are non-neoplastic</li>
</ul>
<ul>
<li>
sessile and pedunculated</li>
<li>
90% are <u>non</u>-neoplastic caused by:
<ul>
<li>
Hyperplastic</li>
<li>
Hamartomatous polyps (Juvenile, PJS)</li>
<li>
Inflam. pseudopolyps</li>
</ul>
</li>
<li>
neoplastic (adenomas) are only 10%</li>
</ul>
<p>
Tubular adenomatous polyp</p>
<ul>
<li>
appearance</li>
<li>
malig risk</li>
</ul>

<p>
Tubular</p>
<ul>
<li>
LOWEST MALIG RISK</li>
<li>
small and pedunculated
<ul>
<li>
polyp only in head</li>
</ul>
</li>
<li>
most pedunculated polyps are TAs</li>
</ul>

<p>
Tubulovilous adenoma polyp</p>
<ul>
<li>
apperance</li>
<li>
malig risk</li>
</ul>
<p>
mix of other two (Combined tubular and villous architecture)</p>
<p>
Risk of harboring in situ or invasive carcinoma generally correlates with the proportion of the lesion that is villous (i.e. more villous = worse)</p>

<p>
vilous adenoma polyp</p>


<p>
Hyperplastic polyp</p>
<ul>
<li>
malig risk</li>
<li>
appearance</li>
<li>
other</li>
</ul>

<ul>
<li>
benign</li>
<li>
Small (usually <5 mm) sessile polyps
<ul>
<li>
Elongated and serrated, stellate crypts lined by “hypermature” goblet cells</li>
</ul>
</li>
<li>
Most common in the rectum/sigmoid</li>
</ul>

<p>
Juvenile or Retention Polyp</p>
<ul>
<li>
<strong>Rare</strong> A.D. hamartomatous malformations</li>
<li>
Most frequent in the rectum</li>
<li>
Most often in children (<5yoa)</li>
<li>
Usually large (1 to 3 cm), round, smooth lesions with stalks</li>
<li>
Inflamed lamina propria with cystically dilated glands</li>
<li>
No malignant potential but <strong>slight incr risk of adenomas and adenocarcinoma</strong></li>
</ul>
<p>
PJS</p>

<p>
<strong>Peutz-Jeghers Polyp</strong></p>
<ul>
<li>
Hamartomatous</li>
<li>
Branching smooth muscle and glands lined by goblet cells</li>
<li>
Slight malignant potential</li>
<li>
(LOH at LKB1 locus)</li>
<li>
PJS pts at increased risk of developing CA of pancreas, breast, lung, ovary, and uterus.</li>
</ul>

<p>OBJECTIVE: Outline the different screening options and recommendations for CRC.</p>
<p><span>Starting at age 50 USPSTF gives A-level evidence for: </span></p>
<ul>
<li><u>FOBT</u> - every year, if normal; (if abnormal order colo)</li>
<li><u>Sigmoidoscopy</u> - Every five years if normal (more often and/or order full colo if polyp removed)</li>
<li><u>Colonoscopy</u> - Every ten years if normal (more often if polyps removed)</li>
</ul>
<p>Classic presentation and pathological apperance of left- vs. right-sided colon tumors?</p>
<p><strong>Left - obstructs <u>apple core</u></strong></p>
<ul>
<li><em>grow as annular, circumferential ("napkin ring"), ulcerated masses</em></li>
</ul>
<p><strong>Right - bleeds <u>cauliflower</u></strong></p>
<ul>
<li>grow as polypoid, exophytic masse
<ul>
<li>May still be deeply infiltrating</li>
</ul>
</li>
<li>Obstruction is uncommon</li>
<li>bleeding either occult or melena</li>
</ul>
<p>Staging of tumors</p>
<p>Uses TNM (tumors, nodes, mets) rubric</p>
<p><strong>pT</strong> is based on how far it invades, you just add one number for each layer of the colon it busts through (p stands for <u>p</u>rimary tumor)</p>
<p><strong>N</strong> is number of nodes involved</p>
<p><strong>M</strong> is number of distant mets</p>
<ul>
<li>pTis =
<ul>
<li>Intraepithelial carcinoma<span>(Severe dysplasia)</span>
<ul>
<li>No met risk</li>
</ul>
</li>
<li>Intramucosal carcinoma: Ltd to lamina propria.
<ul>
<li>Very low met risk</li>
</ul>
</li>
</ul>
</li>
<li>pT1 = Invasion into submucosa
<ul>
<li>95% survival</li>
</ul>
</li>
<li>pT2 = Into muscularis propria</li>
<li>pT3 = Through muscularis propria</li>
<li>pT4 = Penetration of serosa or invasion<span>of adjacent viscera</span>
<ul>
<li><span>30% survival</span></li>
</ul>
</li>
</ul>

<p>Barium enema in pt w/ ∆ in bowel habits shows the following. Thoughts? n/ame for sign?</p>

<p>This is the apple core sign in the sigmoid colon which is suggestive of the annular, napkin ring-type lesions typical of the L colon.</p>
<p>What are the main goals of surgery to resect CRC?</p>
<ol>
<li>to stage dz</li>
<li>Resection of 1° lesion, w/ en-bloc excision of adjacent organ extension PRN</li>
<li>Remove regional LNs
<ul>
<li>They follow the regional blood supply</li>
</ul>
</li>
<li>Remove isolated mets</li>
</ol>
<p>Lynch Syndrome</p>
<p>Hereditary nonpolyposis colorectal cancer (HNPCC)</p>
<p>—CRCs due to Lynch Syndrome are at higher risk for malignancy/seriousness</p>