Tombazzi - Carcinoid, GIST, Lymphoma Flashcards
What are the basic features of carcinoid tumors?
- Late middle-aged pts
-
Most in GI tract: 40% in small intestine (also in the lungs and tracheobronchial tree)
1. Often at multiple sites in the GI tract: can be found anywhere b/t stomach and rectum - Make molecules w/effects in other parts of the body, most commonly: histamine or serotonin
- CLINICAL PRESENTATION: often asymptomatic, but may present with abdominal pain if tumor is big enough (via intermittent obstruction, which can also cause bleeding and/or anemia)
What are the 3 types of carcinoid found in the stomach?
- 80% type 1 or type 2: found in body of the stomach (b/c this is where NE/parietal cells are), generally multiple, very small most of the time, and grow in high levels of gastrin -> difference b/t these 2 is that gastrin is coming from different areas
1. T1: assoc w/hyper-gastrinemia in antrum; good prognosis
2. T2: assoc w/gastrinoma outside the stomach; some w/metastasis - T3 (20%): not assoc w/hyper-gastrinemia, and many with mets at diagnosis -> AGGRESSIVE
- NOTE: malignant tumors that often behave in a much more benign way than adenocarcinoma
What are some of the things gastric carcinoid may be associated with?
- Endocrine cell hyperplasia
- Autoimmune chronic atrophic gastritis
- MEN-I
- Zollinger-Ellison syndrome
What is the most frequent cancer in the GI tract?
Adenocarcinoma
71-yo WM presents w/epigastric pain and anemia. Endoscopy shows >10 nodules (7-12mm) in body and fundus of stomach. Biopsy shown. What is going on?
- Type I neuroendocrine/carcinoid tumor: biopsy shows aggregates of neuroendocrine cells
- Multiple, benign, located in body and fundus (more parietal (NE) cells), will show improvement after reducing gastrin by antrectomy
- HISTO: islands of small, round cells with salt and pepper chromatin
- NOTE: all low-grade NE tumors look the same, no matter where they come from
What is the most important prognostic factor for GI carcinoid tumors?
- LOCATION
-
Foregut: stomach, duodenum prox to ligament of Treitz, and esophagus, rarely metastasize and are generally cured by resection
1. Particularly true for gastric carcinoid tumors that arise in association with atrophic gastritis - Midgut: jejunum and ileum are often multiple and tend to be aggressive
- Hindgut: appendix and colorectum are typically discovered incidentally
What are some standard txs for removal of hindgut NE/carcinoid tumors?
- Most comm neoplasm in appendix: can tx with appendectomy, unless large (>1cm)
- Small rectal nodules (<1cm) can be removed endoscopically with the same rubber band used for esophageal banding (see attached image)
What is the pathophysiology of carcinoid tumors?
Chronic gastritis OR gastric acid suppression
leads to
Hyper-gastrinemia compensatory response
leads to
Gastric diffuse neuroendocrine hyperplasia
leads to
Gastric carcinoid tumors
- Any clinical situation w/high gastrin puts pt at risk, i.e., chronic H. pylori infection (can develop atrophic gastropathy)
- PPI’s do NOT INC risk according to current data in humans (in animals, yes)
What do you see here? Describe the disease and the histo.
- Auto-immune gastritis: Ab’s to parietal cells (H/K ATPase or intrinsic factor) in body of the stomach that lead to DEC acid production and INC gastrin
- SEQUELAE: atrophy, pernicious anemia, carcinoid tumor, adenocarcinoma
- ASSOCIATIONS: autoimmune disease -> thyroiditis, diabetes mellitus, Graves disease
- HISTO: lymphos (inflammation) + gland atrophy + intestinal metaplasia + NE hyperplasia
1. Sometimes see little islands in background, but best to stain: synaptophysin/chromogranin show a lot more than you can see on H&E
2. Atrophic gastritis w/NE hyperplasia (in patho)
71-yo WM presents w/epigastric pain and anemia. Endoscopy shows >10 nodules (7-12mm) in body and fundus of stomach. Biopsy shows carcinoid tumors. Tx?
- Antrectomy: can get malabsorption of Vit. B12, iron, and Vit. C in some pts., but they can live w/o significant problems
- So many nodules in this pt, they can’t be removed with scope -> have to remove gastrin, and nodules will go away
What is this? Utility?
- Endoscopic ultrasound: can be used to see how deep tumors go into wall of the stomach
60-yo WM presents w/new onset of iron deficiency anemia and 4-mo hx of diarrhea and abdominal pain. Frequent episodes of cutaneous flushing+ feeling that he is about to pass out. Abdominal CT and upper endoscopy of pancreas attached.
What is going on? What additional studies might you do?
-
Type 2 neuroendocrine/carcinoid tumor: primary tumor outside of the stomach + high gastrin level due to associated gastrinoma
1. See attached image of small nodules in stomach detected via upper endoscopy - CT: white spots = hyper-dense lesions -> NE tumors are 1 of the few cancers that are hyper-dense
- EUS: hyper-echoic, rounded lesion sitting at head of the pancreas
- ADDITIONAL STUDIES: 5-HIAA, chromogranin, serum gastrin, Octreotide scan, biopsy of liver lesion
What is this?
- Octreotide scan with SPECT (single-photon emission computed tomography): shows where tumors are
- Located in 2 different areas here: mass near pancreatic head and multiple lesions within the liver c/w neuroendocrine tumor
What do you see here? What hormone might you stain this for?
- Neuroendocrine tumor from liver biopsy: nests, trabeculae and gland-like arrangements of mid-size cells
- Small round nuclei and moderate basophilic cytoplasm
- No normal liver here
- (+) immunostain for gastrin attached: hormone expression NOT sufficienctly specific to assign origin of metastasis
What immunostains would be positive in a NE tumor?
- Chromogranin
- Synaptophysin
- CD56
What are the clinical features of carcinoid syndrome? Dx? Tx?
- 10% of pts w/carcinoid tumors: typically ileal tumors w/liver mets -> bioactive products can be released directly into systemic circulation
- Episodes of cutaneous flushing, sweating, diarrhea, bronchospasm, and colicky abdominal pain
1. Due to vasoactive polypeptides, SEROTONIN - R heart endocardial/valvular fibrosis (50%): these substances disappear in lung, so no problems L heart
- Also can be overcome with large tumor burden and hormones secreted into non-portal circulation
- DX: high urine 5-hydroxyindole acetic acid (5-HIAA), a metabolic product of serotonin; limited sensitivity and specificity
- TX: Octreotide injections once per week
- NOTE: may be an exam question on this…
What is the clinical presentation of Z-E? Diagnosis?
- CLINICAL PRESENTATION: complicated peptic ulcer disease, diarrhea, abdominal pain, weight loss, other
1. Diarrhea b/c extra acid in small intestine from stomach, inactivating pancreatic enzymes
2. Risk for devo of T2 gastric carcinoma - DIAGNOSIS:
1. Fasting gastrin >1000 pg/ml + gastric pH <5
2. Secretin stimulation test: gastrin levels 0, 2, 5, 10, 15 & 20 min after IV Secretin -> INC in gastrin of >200 pg/ml (“normally” a DEC in gastrin)
a. Sensitivity 83%, specificity 100%
What are the treatments for Z-E syndrome?
- SURGICAL RESECTION: if solitary, non-metastatic
- MEDICAL MGMT: all should receive high-dose PPI
1. Long-acting somatostatin analog (Sandostatin)
2. Metastatic disease: streptozocin/doxorubicin or temozolomide
a. Resection, orthotopic liver transplant (OLT) trans-arterial chemo-embolization (TACE), radiofrequency ablation (RFA)
What do you see here?
- Ménétrier disease: hypertrophic gastropathy
- Characterized by irregular enlargement of gastric rugae in body and fundus
1. MICRO: sheet of polypoid structures - Antrum generally spared
- Unknown cause: may be precipitated by infection
What is going on here?
- Z-E syndrome: doubling of oxyntic mucosal thickness due to a five-fold INC in # of parietal cells
Based on this endoscopic presentation (submucosal lesion) what is the least likely diagnosis?
- Adenocarcinoma
- Comes from the mucosa -> you would expect changes in the mucosa
What is a GIST? Clinical presentation? Prognosis?
- Most frequent sub-mucosal tumor in stomach
- Neoplasms of spindle, epithelioid, or pleomorphic mesenchymal cells, and often express KIT (CD117)
1. Neoplastic transformation of pluripotent mesenchymal cells in G.I. tract. formerly labeled leiomyomas and neurofibromas, among others - CLINICAL PRESENTATION: from asymptomatic (benign) to very aggressive
1. More common manifestations: incidental finding, GI bleeding, abdominal mass or pain - PROGNOSIS: behaves depending on size and histo (biopsy)
What are 2 causes of hypertrophic gastropathy?
- Ménétrier disease
- Zollinger-Ellison Syndrome
55-yo M w/heartburn for 8 yrs. Normal appetite, no weight loss. PE = normal. Upper endoscopy attached.
What is going on? Why? What next?
- GIST: smooth nodules covered in normal-appearing mucosa
- EUS/FNA (biopsy): tumor coming from muscularis propria (interstitial cells of Cajal)
65-yo M presents w/hx of black stools for 5d. Weak. Normal appetite, and no weight loss. PE = melena. Hb: 7g/dl, Hct: 21%. Upper endoscopy attached.
What is going on? Tx?
- GIST with active bleeding: very low hemoglobin + active bleeding from tumor on endoscopy
- Normal-appearing mucosa covering the tumor
- This is an emergency
- TX: coat tumor in epinephrine to stop bleeding, and remove (surgery)
69-yo presents w/DOE. PE = epigastric mass. Hct: 30.7%. Large, ulcerated gastric mass measuring 23 x 13 x 20 cm. No LAD.
What is going on? Why does he have DOE?
- Big, aggressive GIST: unresectable (attached), and he had tumor embolism and died
- DOE: anyone with baseline CV disease and anemia will not have enough red cells to supply body with O2
This is a GIST. What stain is this? Characteristic histo?
-
C-kit stain: 75-80% of GIST’s have oncogenic, GOF mutations in the receptor tyrosine kinase KIT (=CD117)
1. Newer/better stain = DOG-1 (more specific) - Spindle-cell (or epithelioid) lesion of the GI tract (see image)
- Most common mesenchymal tumor of the abdomen, and >50% occur in the stomach
- From interstitial cells of Cajal, or pacemaker cells, of the GI muscularis propria
How might you distinguish a GIST from a leiomyosarcoma?
- Leiomyosarcoma much more pleomorphic, and will NOT stain (+) for C-kit (CD117) -> see attached images
What is the Carney triad?
- Non-hereditary syndrome of unknown etiology seen primarily in young females that includes:
1. Gastric GIST,
2. Paraganglioma (pheos not in the adrenal; Zellballen appearance*), and
3. Pulmonary chondroma - INC incidence of GIST in pts w/neurofibromatosis T1
- *Nest-like clusters of uniform, round-to-polygonal chief cells surrounded by delicate, richly vascular tissue and sustentacular cells
How are GIST’s diagnosed and treated?
- DX: endoscopy shows a submucosal lesion
1. Endoscopic US-guided FNA has 82% sensitivity and 100% specificity - TX: surgery
1. If metastatic, can usually be given tyrosine kinase inhibitor, Imatinib mesylate
How do GI lymphomas present? Most common?
- More frequent in stomach and small bowel, but infrequent overall
- Almost all are Non-Hodgkin lymphoma, and most are B-cell (MALT and diffuse large B-cell most comm in the US)
1. 2o involvement common: 10% in limited and 60% in advanced NHL - Most PRESENT similar to adenocarcinoma: epigastric pain > anorexia > weight loss > N/V > GI bleeding > early satiety
2. 12% have Systemic B symptoms: weight loss, fever, and night sweats
What are the 5 GI lymphomas we need to know (and their associations)?
- Extra-nodal marginal zone lymphoma of mucosa-associated lymphoproliferative tissue (MALT): assoc w/H. pylori (can cure with AB’s)
- Diffuse large B-cell lymphoma, NOS (not otherwise specified): aggressive
- Immunoproliferative small intestinal disease (IPSID): malabsorption & Ig (esp. IgA); weight loss + diarrhea (more common in Middle East)
- Enteropathy-associated T-cell lymphoma (EATCL) : associated to sprue (celiac pt. not responding to gluten-free diet)
- Post-transplant lymphoproliferative disorder: assoc w/Epstein-Barr -> DEC immunosuppression, and they do much better
45-yo AAM w/dyspepsia. No weight loss, fever, or night sweats. Normal PE. Endoscopy and EUS attached.
What should you do next?
- BIOPSY -> this guy had MALT, and was treated for H. pylori
- Doing well now, and asymptomatic off treatment
- NOTE: no significant changes on endoscopy, but thickened gastric wall on EUS
65-yo w/hx of Hep C. Screening CT attached: gastric tumor w/diffuse perigastric adenopathy and extragastric extension.
What might be going on? Histo?
-
MALToma: this is a “bad” one, however, and pt. did not respond to typical tx
1. Chemo (Rituximab), but pt. ended up with sepsis and multi-organ failure
2. Dr. T said he gave this example to show that not all MALTomas have a good course - HISTO: atypical lymphoid infiltrate (attached)
73-yo WM presenting for failure to thrive and abdominal pain. CT of abdomen: wall thickening, multiple periaortic lymph-nodes, multiple liver masses and splenomegaly.
What might this be? Tx?
- Gastric ulcer consistent with diffuse large B-cell lymphoma (DLBCL): started on chemo (R-CHOP)
- This guy had low Plt, Hct, and WBC, so probably had BM involvement -> died 3 mos after dx
- VERY aggressive type of tumor
What do you see here?
- Diffuse large B-cell lymphoma: worse prognosis (5yr survival 46%)
- Common histo in gastric lymphoma: 68-75% of GI lymphomas
- 3% of gastric neoplasms and 10% of lymphomas
- Age 50-60 years, and male predominance
