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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 

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2

What are these?

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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?

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- 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?

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- 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)

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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

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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

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8

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

- May INC production of mutagens, like nitrites

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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 

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10

What do you see here?

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- 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?

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- 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?

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- 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 

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17

What is the difference b/t these 2 images?

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- 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?

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- Virchow's node

- Gastric cancer met to L. supraclavicular node 

20

What do you see here?

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- 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%)

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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

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26

What is this?

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- 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?

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- Fundic gland gastric polyp: cystically dilated 

- Lined by FLATTENED parietal and chief cells 

- Typically nice and round

28

What is this?

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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 

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30

What is this?

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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) 

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31

What do you see here?

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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 

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32

What is this? Type?

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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

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34

What is this? Type? Arrows?

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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?

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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?

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

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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

 

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44

What change is seen adjacent to the normal gastric mucosa?

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- 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