1. Gastric Lymphoma, Carcinoid Tumor and GIST Thomas Rosenzweig, MD

2. MALToma (Extranodal marginal zone B-cell lymphomas)  Two Causes:  H. pylori  NF-κB activation via MLT/BCL-10 pathway in normal MALTomas (without the below translocations)  H. pylori treatment is effective  t(11;18) ↑MALT1  (q21;q21) ↑BCL-10  Normally, activation of NF-κB in B and T cells requires both BCL-10 and MALT1. (Here, only one activates it.)  H. pylori treatment is ineffective constitutive activation of NF-κB, ↑ B-cell growth and survival. *In the stomach these tumors are called lymphomas of mucosa-associated lymphoid tissue (MALT), or MALTomas. *MALT is usually caused by chronic gastritis (H. Pylori)

3.  Symptoms = dyspepsia and epigastric pain  Lymphoepithelial lesions  gastric MALToma takes the form of a dense lymphocytic infiltrate in the lamina propria  MALTomas can develop into diffuse B-cell lymphomas  No longer responsive to H. pylori eradication  Happens with additional genetic changes  (inactivation of p53 and p16)  express the B-cell markers CD19 and CD20 and CD43  do not express CD5 or CD10 MALToma (Extranodal marginal zone B-cell lymphomas)

4. Carcinoid Tumor

5.  60 years old  Location Matters!  Foregut carcinoid tumors (stomach, duodenum proximal to the ligament of Treitz, and esophagus)  rarely metastasize  Midgut carcinoid tumors (jejunum and ileum)  aggressive  Hindgut carcinoids (appendix and colorectum)  typically discovered incidentally and are benign  Hormones determine symptoms  Duodenum Tumors cause Zollinger-Ellison syndrome from gastrin  Ileal tumors cause carcinoid syndrome  (cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhea, and right-sided cardiac valvular fibrosis.)  vasoactive substances secreted by the tumor into the systemic circulation (Causes metastatic disease in the liver)  When tumors are confined to the intestine, the vasoactive substances released are metabolized to inactive forms by the liver, a “first-pass” effect  Exceptions: large tumor or when tumors secrete hormones into a nonportal venous circulation.

6. Carcinoid Tumor – yellow or tan in color and very firm – pink granular cytoplasm and a round / oval nucleus. minimal pleomorphism – Stains are + for synaptophysin and chromogranin A

7. Features of GI Carcinoid Tumors

8. Mesenchymal Neoplasms  Leiomyomas  smooth muscle tumors  Schwannomas  nerve sheath tumors  Glomus tumors  resemble glomus bodies in the nail beds and other sites  GI stromal tumor (GIST)  most common mesenchymal tumor of the abdomen  Usually in the stomach

9. GI stromal tumor (GIST)  GI stromal tumor (GIST)  from interstitial cells of Cajal (pacemaker cells)  most common mesenchymal tumor of abdomen  60 years old (usually in the stomach)  Mutations result in constitutively active KIT or PDGFRA  KIT gain-of-function (stain)  platelet-derived growth factor receptor α (PDGFRA) *Likely on test GIST KIT Stain

10. GI stromal tumor (GIST)  Spindle cell type  composed of thin elongated cells  Epithelioid type  epithelial-appearing cells  Gastric GISTs are less aggressive than small intestine  Smaller than 5cm = safe  Larger than 10cm = metastasis  Treatment: imatinib (for mutations in KIT or PDGFRA)  development of imatinib-resistance is common, due to secondary KIT or PDGFRA mutations

11. Key Concepts