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Flashcards in Jackson - Gastric Neoplasia Deck (44):
1

What are the 3 types of gastric polyps?

Non-neoplastic

1. Inflammatory/hyperplastic 

2. Fundic gland 

a. Sporadic (more common) - beta catenin 

b. Syndromic - APC 

Neoplastic

1. Adenomas -> precursor lesions to cancer 

2

What are these?

Hyperplastic gastric polyps: devo driven by chronic inflammation -> H. pylori 

- Most in the antrum: 60%

- Most BENIGN, small risk of dysplasia

- Some will regress when pts are treated for H. pylori 

3

What do you see here?

- Fundic gastric polyps: body or fundus

- Usually <1cm, cystic appearing, and clustered

- Surrounding stomach normal

- May be sporadic, associated with PPI use, or associated with familial adenomatous polyposis (FAP)

- Rare malignant potential, unless assoc with FAP

4

What do you see here?

- Gastric adenoma (up to 10% of all gastric polyps): INC incidence in pts w/FAP (like fundic gland polyps)

- Almost always on a background of chronic gastritis, with atrophy and intestinal metaplasia

1. Intestinal-type columnar epi w/varying degrees of dysplasia 

- Most are ANTRAL

- Pre-malignant neoplastic lesions with a high risk of transformation to invasive cancer -> usually removed

1. Risk of malignancy INC with size, villous lesions, or high-grade dysplasia

5

Gastric cancer epi

- More common in lower SES, developing countries

- Male:female = 2:1

- Peaks in 7th decade

- Declining incidence in US of distal gastric cancers, except in Caucasians age 29-39 (reason for this not really clear)

6

How have incidence and death by gastric cancer changed in the US? Why (3)?

- Incidence of cases and deaths have DEC

- Decreased incidence:

1. Tx H. pylori (carcinogen)

2. Refrigeration and DEC meat curing: addition to meats of some combo of salt, sugar, nitrite and/or nitrate for preservation, flavor and color

3. INC consumption of vegetables

7

What are the risk factors for gastric cancer?

- Chronic atrophic gastritis: DEC acid production

- Pernicious anemia: change in pH of stomach (loss of gastric parietal cells)

- Prior gastric surgery: INC risk after 10 years 

- High dietary nitrates: cured meats 

- Adenomatous gastric polyps: FAP

- Helicobacter pylori infection: INC risk 3-6x

8

What is a common mech by which factors predisposing to gastric cancer INC risk?

- May INC production of mutagens, like nitrites

9

What are some of the presenting symptoms of gastric cancer? Warning signs?

- Epigastric pain: can be relieved or exaggerated by food (can present like PUD)

- Ulceration/bleeding: can cause anemia, melena (black, tarry feces assoc w/upper abdominal bleeding)

- Distal lesions may obstruct stomach outlet 

Weight loss + epigastric pain + anemia -> think of gastric cancer 

- Nausea and dysphagia also reported 

10

What do you see here?

- Radiology showing infiltrating gastric carcinoma in region of the incisura 

- Irregular narrowing, affecting both the lesser and greater curvatures 

11

Which of these is malignant/benign? How do you know?

- TOP: malignant gastric ulcer of the cardia -> note the absence of folds radiating to the base, and the exophytic appearance 

- BOTTOM: benign gastric ulcer in prepyloric region; well-circumscribed, with folds radiating to ulcer base 

- NOTE: carcinoma may look like gastric ulcer endoscopically, so ALWAYS biopsy these 

12

What do you see here? How would you dx this?

- Gastric cancer ID'd by endoscopy: may show mass or malignant gastric ulcer 

- BIOPSY for diagnosis 

- NOTE: this patient would probably have anemia and abdominal pain due to evidence of bleeding 

13

What are the 4 types of gastric cancer?

- Adenocarcinoma: >90% in US 

1. Intestinal: DEC rates due to tx of H. pylori 

2. Diffuse 

- Lymphoma: 3% in US, and better prognosis than adenocarcinoma 

- Carcinoid: 0.2% in US 

- Gastrointestinal stromal tumor (GIST)

14

What are the epi differences b/t the 2 histo types of adenocarcinoma?

- INTESTINAL: more frequent in M, and at older ages 

1. Environmental? Dietary association 

- DIFFUSE: little difference b/t sexes, and more freq at younger ages 

15

How is gastric cancer treated?

- CT for staging prior to surgery, looking for metastatic disease (about 50% present with mets)

- Endoscopic ultrasound (EUS) used for staging for potential surgical candidates to assess depth of invasion into gastric wall (deeper lesion may benefit from neoadjuvant therapy)

- Surgery is only chance for cure, but rarely curative

1. May also be used for palliation -> obstruction or bleeding

- Chemo may improve survival in pts who have sx

16

What is linitis plastica?

- Aggressive diffuse gastric cancer where gastric wall and submucosa infiltrated by malignancy -> rigid, thickened stomach

- 5% of gastric cancers; may not be resectable, so poor prognosis 

- Endoscopic biopsies may not pick up the diagnosis because may be submucosal -> also hard to identify because diffuse change 

17

What is the difference b/t these 2 images?

- Normal stomach on the left 

- Linitis plastica on the right: aggressive, diffuse gastric cancer where wall is infiltrated, leading to rigid, thickened stomach 

18

How does gastric cancer metastasize?

- May met to liver, peritoneum, or distal lymph nodes

- Virchow’s node: left supraclavicular node (TESTS)

- Sister Mary Joseph node: periumbilical nodule

19

What is this?

- Virchow's node

- Gastric cancer met to L. supraclavicular node 

20

What do you see here?

- Sister Mary Joseph nodule 

- Periumbilical nodule suggestive of metastatic gastric cancer 

21

What are the 4 stages of stomach cancer (image)? How does this affect survival?

- Based on penetration into stomach wall: 

Stage 0: mucosa only 

Stage 1: submucosal 

Stage 2: muscle 

Stage 3: impinging on serosa 

Stage 4: extra-serosal (outer-most layer) 

- 5-year survival: localized (61%), regional nodes (28%), distant metastases (4%)

22

66-y/o F with 6-mo history of vague epigastric pain, early satiety, 25 # weight loss, intermittent melenic stools. Her lab shows anemia. Does H. pylori predispose her to this lesion?
 

Absolutely

23

66-y/o F with 6-mo history of vague epigastric pain, early satiety, 25 # weight loss, intermittent melenic stools. Her lab shows anemia. Is this tumor most likely a lymphoma?

- NO 

- 90% of gastric cancer is adenocarcinoma 

24

66-y/o F with 6-mo history of vague epigastric pain, early satiety, 25 # weight loss, intermittent melenic stools. Her lab shows anemia. What is the best tx for her disease?

Surgery

25

What are the 4 regions of the stomach? How do they differ in cell type?

- Cardia: mucin-secreting foveolar cells that form small glands

- Body and fundus: also contain chief cells that produce and secrete digestive enzymes, i.e., pepsin

- Antrum/pylorus: similar, but also endocrine cells, like G cells, that release gastrin to stimulate luminal acid secretion by parietal cells in gastric fundus and body

26

What is this?

- Hyperplastic gastric polyp: dilated, elongated and torturous gastric foveolar epithelium

1. Torturous, deeper, and architecture different

- Edematous lamina propria containing inflam cells

- Note the erosion with granulation tissue -> getting beat up (erosion: superficial; ulcers: deep)

27

What do you see here?

- Fundic gland gastric polyp: cystically dilated 

- Lined by FLATTENED parietal and chief cells 

- Typically nice and round

28

What is this?

Fundic gland gastric polyp: cystically dilated 

- Lined by FLATTENED parietal and chief cells 

- Typically nice and round; some superficial erosion here

29

Briefly describe the multifactorial pathway leading to devo of gastric carcinoma.

- Many host, bacterial, and envo factors act in combo to contribute to precancerous cascade 

Superficial gastritis: reactive/chronic gastritis, i.e., via H. pylori infection

- Atrophic gastritis: process of chronic inflammation of the stomach mucosa, leading to loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues

- Things to note: H. pylori, cigarette smoking, bac overgrowth/low acidity 

30

What is this?

Gastric adenoma: equivalent of low-grade dysplasia

- Nuclei more elongated; hyperchromatic

- More cigar-like

- May be a goblet cell in upper left corner

- Compare to normal (attached here) 

31

What do you see here?

Adenomatous gastric polyp: irregulary-shaped glands lined by intestinal-type epithelium 

- Dysplasia: crowded, enlarged, hyper-chromatic, elongated nuclei in pseudostratified configuration 

1. High-grade: budding glands, glands within glands, cribriform pattern, ARCHITECTURAL DISTORTION, atypical mitoses 

- Architecture changes or weird cytology moves into high-grade status 

32

What is this? Type?

Gastric adenocarcinoma: intestinal type -> looks like any adenocarcinoma of the GI tract

- Cytological evidence of malignancy: variation in nuclear size and shape, hyperchromasia, INC and abnormal mitoses 

1. Chromatin pattern really clumped: prominent nuclei

2. Cells not organized 

33

What are the two types of adecarcinoma in the GI tract?

- Intestinal type: tends to form bulky antral (along lesser curvature) masses

1. Top image intestinal type adenocarcinoma with well-formed glandular and tubular architecture

- Diffuse type: infiltrates the wall diffusely, thickens it, and is typically composed of signet ring cells

1. Bottom image diffuse type adenocarcinoma with intracellular mucin and signet ring cell features

34

What is this? Type? Arrows?

Diffuse-type gastric adenocarcinoma: if large areas infiltrated, diffuse rugal flattening + rigid, thickened wall = leather bottle appearance, aka linitis plastica

1. ARROWS: top pointing to thickened wall, and bottom showing rugal flattening 

- Familial gastric cancer (10% of cases) strongly assoc with germline loss-of-function mutations in the tumor suppressor gene CDH1, which encodes cell adhesion protein E-cadherin

- BRCA2 mutations = INC risk of diffuse-type

- Can be hard to pick these up endoscopically and on histology: don’t have same atypia as intestinal type 

35

What other tumor type also harbors loss-of-function mutations in the tumor suppressor gene CDH1 ?

Lobular carcinoma of the breast

36

What is this lesion? Sporadic-type cytology? Histo?

Intestinal-type gastric adenocarcinoma: sporadic-type may have:

1. LOF muts in adenomatous polyposis coli (APC) tumor suppressor gene 

a. FAP pts, who carry germline APC mus, have an INC risk of intestinal-type

2. GOF muts in β-catenin gene (INC signaling via Wnt pathway)

- Sporadic types are associated with APC, K-RAS and Tp53 alterations

- HISTO: glands show marked architectural distortion with crowding, back-to-back pattern

37

What is Gardner syndrome?

- Auto dom form of polyposis: APC mutation

- Multiple colonic adenomas

- Osteomas of the skull

- Epidermoid cysts and desmoid tumors

38

What is Kartagener syndrome?

- Auto recessive primary ciliary dyskinesia

- Switched orientation of organs

- Infertility 

39

What is Lesch-Nyhan syndrome?

- Deficiency of the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGPRT), produced by mutations in the HPRT gene located on the X chromosome -> HYPERURICEMIA

- Kidney stones

- Can’t control muscles

- Bite themselves 

40

What is Nelson syndrome?

- Rapid enlargement of pituitary ACTH adenoma after removal of adrenals 

- Hyperpigmentation of skin 

41

What is Turcot syndrome?

- DNA mismatch repair mutations: mapped to MLH1, MSH2, MSH6 or PMS2 (same as in Lynch syndrome, but bi-allelic)

- Medulloblastoma

- Glioblastoma

42

What do you see here?

- Invasive gastric adenocarcinoma: glandular invasion all the way down into submucosa

43

How is HER2 implicated in gastric cancer? How might this impact tx?

- Key driver of tumorigenesis, and over-expression as a result of HER2 gene amplification in a number of solid tumors 

- Trastuzumab approved for metastatic gastric cancer

 

44

What change is seen adjacent to the normal gastric mucosa?

- Intestinal metaplasia 

- NOTE: Dr. Gupta said even this "normal" mucosa might be called "reactive chemical gastropathy" by some pathologists due to the elongated, semi-torturous appearance of the glands