Jackson - Gastric Neoplasia Flashcards
1
Q
What are the 3 types of gastric polyps?
A
-
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
Q
What are these?
A
- 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
Q
What do you see here?
A
- 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
Q
What do you see here?
A
- 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
Q
Gastric cancer epi
A
- 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
Q
How have incidence and death by gastric cancer changed in the US? Why (3)?
A
- 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
Q
What are the risk factors for gastric cancer?
A
- 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
Q
What is a common mech by which factors predisposing to gastric cancer INC risk?
A
- May INC production of mutagens, like nitrites
9
Q
What are some of the presenting symptoms of gastric cancer? Warning signs?
A
- 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
Q
What do you see here?
A
- Radiology showing infiltrating gastric carcinoma in region of the incisura
- Irregular narrowing, affecting both the lesser and greater curvatures
11
Q
Which of these is malignant/benign? How do you know?
A
- 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
Q
What do you see here? How would you dx this?
A
- 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
Q
What are the 4 types of gastric cancer?
A
-
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
Q
What are the epi differences b/t the 2 histo types of adenocarcinoma?
A
- 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
Q
How is gastric cancer treated?
A
- 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
Q
What is linitis plastica?
A
- 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
Q
What is the difference b/t these 2 images?
A
- Normal stomach on the left
- Linitis plastica on the right: aggressive, diffuse gastric cancer where wall is infiltrated, leading to rigid, thickened stomach
18
Q
How does gastric cancer metastasize?
A
- May met to liver, peritoneum, or distal lymph nodes
- Virchow’s node: left supraclavicular node (TESTS)
- Sister Mary Joseph node: periumbilical nodule
19
Q
What is this?
A
- Virchow’s node
- Gastric cancer met to L. supraclavicular node
20
Q
What do you see here?
A
- Sister Mary Joseph nodule
- Periumbilical nodule suggestive of metastatic gastric cancer
21
Q
What are the 4 stages of stomach cancer (image)? How does this affect survival?
A
- 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
Q
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?
A
Absolutely
23
Q
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?
A
- NO
- 90% of gastric cancer is adenocarcinoma
24
Q
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?
A
Surgery
25
Q
What are the 4 regions of the stomach? How do they differ in cell type?
A
- 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
Q
What is this?
A
-
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
Q
What do you see here?
A
- Fundic gland gastric polyp: cystically dilated
- Lined by FLATTENED parietal and chief cells
- Typically nice and round
28
Q
What is this?
A
- Fundic gland gastric polyp: cystically dilated
- Lined by FLATTENED parietal and chief cells
- Typically nice and round; some superficial erosion here
29
Q
Briefly describe the multifactorial pathway leading to devo of gastric carcinoma.
A
- 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
Q
What is this?
A
- 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
Q
What do you see here?
A
- 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
Q
What is this? Type?
A
- 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
Q
What are the two types of adecarcinoma in the GI tract?
A
-
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
Q
What is this? Type? Arrows?
A
-
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
Q
What other tumor type also harbors loss-of-function mutations in the tumor suppressor gene CDH1 ?
A
Lobular carcinoma of the breast
36
Q
What is this lesion? Sporadic-type cytology? Histo?
A
-
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
Q
What is Gardner syndrome?
A
- Auto dom form of polyposis: APC mutation
- Multiple colonic adenomas
- Osteomas of the skull
- Epidermoid cysts and desmoid tumors
38
Q
What is Kartagener syndrome?
A
- Auto recessive primary ciliary dyskinesia
- Switched orientation of organs
- Infertility
39
Q
What is Lesch-Nyhan syndrome?
A
- 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
Q
What is Nelson syndrome?
A
- Rapid enlargement of pituitary ACTH adenoma after removal of adrenals
- Hyperpigmentation of skin
41
Q
What is Turcot syndrome?
A
- DNA mismatch repair mutations: mapped to MLH1, MSH2, MSH6 or PMS2 (same as in Lynch syndrome, but bi-allelic)
- Medulloblastoma
- Glioblastoma
42
Q
What do you see here?
A
- Invasive gastric adenocarcinoma: glandular invasion all the way down into submucosa
43
Q
How is HER2 implicated in gastric cancer? How might this impact tx?
A
- 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
Q
What change is seen adjacent to the normal gastric mucosa?
A
- 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
