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
- Zollinger-Ellison syndrome
What is the most frequent cancer in the GI tract?
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?
- 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
Hyper-gastrinemia compensatory response
Gastric diffuse neuroendocrine hyperplasia
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?
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
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?
- 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