Stomach Flashcards

Question

Describe Gastric Xanthoma

Answer 1

* Collection of bland, foamy histiocytes in the lamina propria * No mitotic activity * No background inflammation Endoscopy: Single/multiple white/yellow nodules IHC: **CD68** positive Cytokeratin negative Associations: * H pylori * bile reflux * hypercholesterolemia

Answer 2

**H Pylori** * Correa's cascade * Chronic infection --> chronic inflammation --> intestinal metaplasia --> dysplasia --> Carcinoma **EBV infection** **Tobacco smoking** **Dietary factors** **Rubber manufacturing industry** **X and gamma radiation**

Answer 3

* CK7+ (50-70%) * CK20+ (30-50%) * CDX2 (60%) * MUC2+ (30%) * MUC5AC+ (70%) * GATA3- All diffuse type gastic carcinomas should be differentiated from metastatic lobular carcinoma of the breast

Answer 4

**EARLY gastric Adeno**: Three types * 0-I -protruding (polypoid) * 0-IIa (superficialk elevated) * 0-IIb (superficial flat) * 0-IIIc (superficial depressed) * 0-III (excavated) **ADVANCED gastric Adeno:** Borrmann Classification * Type I Polypoid tumors that protrude into the gastric cavity and have sharp demarcation from the surrounding tissue * Type II Ulcerative tumors with a clear margin and raised surface * Type III Ulcerative tumors with an unclear margin that infiltrate deeply into the surrounding tissue * Type IV Diffusely infiltrating tumors, also known as linitis plastica

Answer 5

**Lauren Classification** **Intestinal: ** Characterized by cohesive cells that form gland-like structures. It's more common in males and older patients. ** Diffuse: ** Characterized by tumor cells that lack cell-to-cell interactions and infiltrate the stroma. It's more common in women and younger patients. **Mixed: ** Tumors that exhibit features of both the intestinal and diffuse types ** Most important prognostic factor is clinical stage**

Answer 6

**WHO classification** **Tubular:** Most common. Dilated and slit-like branching tubules Solid structures and barely rdcognisable tubles are classed as poorly diff tubular carcinoma. **Papillary:** Relatively rare Exophytic growth pattern Cuboidal/columnar cells, fibrovascular core Frequent invasion by inflammatory cells Associated with higher frequency of liver mets Poor prognosis **Mucinous:** Malignant epithelium in extracellular pools of mucin Mucin >50% of tumour area **Poorly cohesive, which includes signet ring cell carcinoma: ** Second most common Cells in small aggregates without well-formed glands CDH1 mutations (e-cadherin) 1) Signet ring type 2) Non signet ring type Neoplastic cells resembling histiocytes or lymphocytes Deeply eosinophilic cytoplasm and pleomoprhic nuclei **Mixed ** Contains two or more histiological subtypes

Answer 7

**(Adeno)carcinoma with lymphoid stroma** * AKA lymphoepithelioma or medullary * Polygonal cells embedded in prominent lymphocytic infiltrate * Favours proximal stomach or gastric stump * Associated with** EBV ** * Subest of gastric Ca with** microsatellite instability** **Hepatoid adenocarcinoma** * Large polygonal eosinophilic hepatocyte-like cells * **Bile** and **PAS-D **positive - intracytoplasmic globules * **AFP, HepPar-1 **positive **Micropapillary adenocarcinoma ** * Without fibrovascular cores * Small clusters protruding into clear spaces * Worse prognosis **Gastric adenocarcinoma of fundic-gland type** * Very rare * Assumed to develop from oxyntic gland adenoma * Three subcategories Chief-cell predominant (99%) Parietal-cell predominant Mixed phenotype

Answer 8

NB... <2cm into the stomach from GOJ -> treat as oesophagheal ca **HER2 therapy** * unresectable * metastatic/recurrent ERBB2-positive Ca **Immune checkpoint inhibitor therapy** * PD-L1 expression

Answer 9

Proposed by The Cancer Genome Atlas (TCGA) **EBV (9%)** * Gastric carcinoma with lymphoid stroma * Better prognosis * CpG island (CIMP) promoter hypermethylation * CDKN2A promoter hypermethylation * PIK3CA mutations * ARID1A mutations * PD-L1 amplified * PD-L2 amplified **Mictosatellite Unstable (22%)** * Better prognosis * CpG island (CIMP) promoter hypermethylation * CDKN2A promoter hypermethylation * MLH1 promoter hypermethylation **Genomically Stable (20%)** * Poorly cohesive (diffuse) moprhology * Poorer prognosis * CDH1 alterations/mutations * RHOA alterations/mutations **Chromosomally Unstable (50%)** * Predominantly intestinal type morphology * TP53 mutations * Receptor Tyrosine kinase (RTK)/ RAF pathway amplifications (EGFR, FGFR2, VEGFA, KRAS, MET, HER2/ERBB) * Extensive DNA copyt number variations

Answer 10

* Gastrointestinal stromal tumor * Most common mesenchymal tumour * Arises from **intersitial cells of Cajal** within myenteric plexus of muscularis propria Can occur anywhere in the GI tract * Stomach (60%) * Jejunum and ileum (30%) * Duodenum (5%) * Rectum (4%) * Colon and appendix (2%) * Oesophagus (1%) Can occur outside of the GI tract * Omentum * Mesentery * Retroperitoneum * Pleura **Four histologic types:** * Spindle * Epithelioid (typically SDH-deficient) * Mixed * (last two more common in stomach) * Dedifferentiated **Five Molecular types:** * KIT mutated (c-KIT/DOG1 +ve) * PDGFR mutated (DOG1 +ve) * SDH deficient (SDHB -ve) * RAS-P mutated (SDHB +ve) * Quadruple wild type (SDHB +ve)

Answer 11

**CD117 (c-KIT)** +ve - membranous, diffusely cytoplasmic, dot-like perinuclear **CD34+ DOG1+** SDHB-, S100- CD117 and DOG1 are **sensitive markers**, not specific Ki67 to assess proliferation rate not superior to mitotic count

Answer 12

* Activating KIT (95%) * Platelet derived growth factor alpha (PDGFRA) * Receptor tyrosine kinase (5%) * SDH deficient (<5%) Do mutational analysis: * All resected moderate or high risk GISTs of any site * All biopsies diagnostic of GIST prior to TKI treatment * All biopsies from unresectable/widely metastatic GIST

Answer 13

**PROGNOSIS** Depends on: * Site * Size * Mitosis Gastric GISTs better than intestinal Oesophageal worst - diagnosed late Small intestine and Rectal - high risk **TREATMENT** Surgical Resection Neoadjuvant small molecule **tyrosine kinase inhibitors** KIT juxta mebrane domain (**exon 11**) mutations -> confers better response to tyrosine kinase inhibitor therapy (imatinib) KIT (**exon 9**) mutant --> benefit from higher dose imatinib' Resistant to imatinib --> benefit from sunitinib

Answer 14

Associated with: 1) SDH deficient GIST: **CARNEY TRIAD** SDH deficient GIST Pulmonary chondroma Paraganglioma * Non hereditary * SDHC promoter hypermethylation * Small percentage have germline SDH mutations **CARNEY-STRATAKIS SYNDROME** GIST Paraganglioma * Hereditary, autosomal dominant * Germline mutations --> SDHB, SDHC or SDHD Lymph nodes --> not core item, but raises suspicion of Carney's triad or Carney-Stratakis syndrome 2) Neurofibromatosis (NF): 7% patients with NF1 develop one or more GIST (usually small bowel)

Answer 15

Neuroendocrine tumour * Well-differentiated neuroendocrine tumour (NET) * Poorly differentiated neuroendocrine carcinoma (NEC) - small and large cell * Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) Micro: Well-differentiated cells Nests, acini, trabeculae, ribbons Abundant eosinophilic cytoplasm monoimorphic round nuclei (salt and pepper chromatin) **Type I:** Derived from enterochromaffin-like (ECL) cells Occurs in a setting of **chronic atrophic gastritis** (type A) and **hypergastrinemia** More frequent in women **Type II:** Derived from ECL cells Occurs in a setting of **hypergastrinemia **due to **Zollinger-Ellison syndrome** Can be seen in patients with multiple endocrine neoplasia type 1 (MEN1) syndrome Affects men and women equally **Type III:** Sporadic More frequent in men **Type IV:** Discussed in the literature but not currently recognized by the WHO **Serotonin producing EC cell NET:** Rare and usually nonfunctional **Gastrin producing G cell NET:** Usually nonfunctional but can cause Zollinger-Ellison syndrome and is then referred to as a gastric gastrinoma All types tend to occur in the age range of 50 - 60 years **PROGNOSIS** Type I: excellent prognosis with a 5 year survival of 90 - 95% Type II: good prognosis with a 5 year survival of 60 - 90% Type III: worse prognosis with a 5 year survival rate of < 35%

Answer 16

**G1 ** Mitotic count <2 per 20 HPF Ki-67 <2% **G2** Mitotic count 2-20 per HPF Ki-67 3-20% **G3** Mitotic count >20 per HPF >30% TP53 and RB1 mutations can distinguish from from NEC

Answer 17

**Positive:** Chromogranin synaptophysin CD56 **Negative: ** CD7 CD20

Answer 18

* Extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma). Strong association of H. Pylori Treatment of H pylori induces regression indolent behaviour and generallly excellent prognosis **Lugano staging system**: most widely accepted staging system **Endoscopy:** Most arise in antrum Early lesions form a plaque or small erosions Advanced lesions cause ulcers, diffuse thickening, masses **Micro:** Heterogenous inflitrate - neoplastic lymphocytes **Centrocyte-like cells**: Small lymphocytes with irregular nuclear contours and pale cytoplasm. **Monocytoid B-cells** **Centroblasts/Immunoblasts**: Large cells **Lymphoepithelial lesion**: classic finding **Neoplastic Plasma cells** **Lymphoid follicles:** Germinal centres MALToma can infiltrate germinal centers --> Follicular colonisation Can get Amyloid deposition

Answer 19

**POSITIVE**: CD20 CD43 (variable) BCL-2 CD79a **NEGATIVE:** CD3 CD5 CD10 CD23 Cyclin D1 CD43 and CD5 support the diagnosis **Kappa / lambda**: can be useful to demonstrate light chain restriction (especially if there are abundant neoplastic plasma cells) **Congo red:** can highlight amyloid deposition present in a subset of cases

Answer 20

**t(11;18): BIRC3 (API2)-MALT1 (6 - 26%) ** Associated with resistance to H. pylori eradication therapy **t(14;18)(q32;q21): IGH-MALT1 (1 - 5%)** **Trisomy 3** (11%) **Trisomy 18** (6%) **TNFAIP3 deletion / hypermethylation**

Answer 21

Very rare Presents late, poor outcome

Answer 22

**Micro:** Anaplasic cells, diffuse sheets Variable cytology - Polygonal, rhabdoid, spindled, osteoclast-like giant celkls Driven by **SWI/SNF chromatin-remodeling complex** Aggressive **IHC:** Variable pan-cytokeratin Vimentin +ve EMA may be helpful in keratin-poor tumour

Answer 23

Very rare Males more affected Glandular and Squamous - squamous must be >25% Aggressive - mets to LN, liver and peritoneum are common Mucin stain p63/p40

Answer 24

**Micro:** Biphasic tumour * Uniform spindle cells * Epithelial cells arranged in nests **Molecular:** MALAT1-GL1 **IHC:** EPITHELIAL COMPONENT * Pan cytokeratins * Focal CD56+ * Focal CD10+ SPINDLE CELL COMPONENT * negative for keratins * CD56+ * CD10+ Negative for C-KIT, DOG1, CD34, SMA, Desmin, Synaptophysin, Chromogranin, S100

Stomach Flashcards

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