Jackson - Gastric Neoplasia Flashcards
(44 cards)
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
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
