Pathology -- GI Neoplasia Flashcards

1
Q

Define adenocarcinoma

A

Malignant epithelial neoplasm with glandular differentiation

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2
Q

Define squamous cell carcinoma

A

Malignant epithelial neoplasm with squamous cell differentiation

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3
Q

Define glandular differentiation

A
  • Formation of glands
  • Production of mucus (intracellular and/or extracellular)
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4
Q

Architectural malignant features of adenocarcinoma

A
  • Irregularly shaped glands or groups of cells
  • Infiltrating growth pattern, either as groups of cells or single cells
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5
Q

Cytologic malignant features of adenocarcinoma (4)

A
  • Neoplastic cells are usually large and irregular in size and shape
  • High N/C ratio
  • Nuclei irregular in size and shape
  • Prominent nucleoli
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6
Q

Miscellaneous malingnant features of adenocarcinoma (3)

A
  • Necrosis
  • Frequent mitoses
  • Desmoplastic stroma
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7
Q

Describe the histology of invasive (colonic) adenocarcinoma (4)

A
  • Irregular complex glands infiltrating the stroma (upper right corner shows some benign crypts)
  • Desmoplastic stroma
  • Necrotic debris within glands
  • Marked cytoplogic atypia in neoplastic cells (increased nuclear size with great variation in size and shape, increased N/C ratio)
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8
Q

Define dquamous cell differentiaiton

A

Keratinocyte-like cells with intercellular bridges and/or keratinization

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9
Q

Describe the appearance of keratinocyte-like cells

A

Polygonal, pavement-like cells with eosinophilic cytoplasm

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10
Q

Architectural malignant features of in situ SCC (2)

A
  • Tumor above the basement membrane
  • Architecture approximates that of the normal squamous epithelium (cytology still malignant)
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11
Q

Architectural malignant features of invasive SCC

A

Irregularly-shaped sheets of cells, sometimes single cells with infiltrating growth pattern

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12
Q

Cytology of SCC (4)

A
  • Neoplastic cells usually large and irregular in size and shape
  • High N/C ratio
  • Nuclei irregular in size and shape
  • Sometimes prominent nucleoli
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13
Q

3 miscellaneous malignant features of SCC

A
  • Necrosis
  • Frequent mitoses
  • Desmoplastic stroma
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14
Q

Describe the histology of invasive SCC (7)

A
  • Tumor extends beyond the basement membrane and infiltrates the stroma
  • Cells are polygonal and focal keratin formation may be seen
  • Infiltrative growth pattern
  • Desmoplastic stroma
  • Cytological atypia
  • Keratinization
  • Intercellular bridges
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15
Q

What gives invasive SCC a tumor with firm consistency?

A

The desmoplastic stroma

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16
Q

3 precursor lesions for adenocarcinoma and their specific areas of effect

A
  • Intestinal metaplasia –> dysplasia of glandular mucosa (esophagus and stomach)
  • Adenoma (stomach and bowel)
  • Dysplasia in the context of chronic inflammatory bowel disease (bowel)
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17
Q

Describe the histology of tubular adenoma

A
  • Nuclear enlargement
  • Nuclear stratification
  • Lack of maturation

(Versus normal colon on right)

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18
Q

Types of tumors that can be found in the esophagus

A
  • Adenocarcinoma
  • Squamous cell carcinoma
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19
Q

Types of tumors that can be found in the stomach

A
  • Adenocarcinoma (intestinal type and diffuse, signet ring cell, type)
  • Lymphoma
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20
Q

Types of tumors that can be found in the colorectum

A

Adenocarcinoma and adenoma

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21
Q

2 other types of GI tumors that are not adenocarcinoma, SCC or lymphoma

A
  • Neuroendocrine tumors/ carcinoid tumors
  • Gastrointestinal stromal tumors
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22
Q

Define high grade dysplasia in Barrett esophagus (histology)

A

Very complex architecture with bridging:

  • Absence of maturation of glandular mucosa
  • Large, atypical, crowded and stratified nuclei
  • Less cytoplasm
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23
Q

Define esophageal adenocarcinoma

A

Malignant tumor of glandular differentiation usually in the setting of Barrett esophagus

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24
Q

Usual location of esophageal adenocarcinoma and why

A

Distal esophagus since BE involves distal esophagus

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25
Q

Clinical manifestations of esophageal adenocarcinoma (5)

A
  • Symptoms related to GERD
  • Dysphagia
  • Pain (epigastric, retrosternal)
  • Weight loss
  • Anemia
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26
Q

Describe the histological appearance of invasive adenocarcinoma

A
  • Glands of various sizes and shapes infiltrating the stroma
  • High N/C ratio
  • Large irregular epithelial nuclei
  • Clumped chromatin
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27
Q

Groups of people most commonly affected by esophageal squamous cell carcinoma

A
  • >50 YO
  • Men
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28
Q

3 risk factors for esophageal SCC

A
  • Smoking
  • Alcohol
  • Carcinogens in food
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29
Q

3 clinical manifestations of esophageal SCC

A

Small tumors may be asymptomatic, however symptoms are:

  • Dysphagia
  • Chest pain
  • Weight loss
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30
Q

Diagnostic method of choice for esophageal SCC

A

Endoscopy with biopsy

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31
Q

Usual location of esophageal SCC

A

Lower 2/3 of esophagus

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32
Q

Macroscopic features of esophageal SCC

A
  • Tumor may be protruding into the lumen, show ulceration and cause stricture
  • Beige and firm
  • Uninvolved esophageal mucosa is normal (NOT associated with BE)
  • Thickening of esophageal wall
  • Narrowing of lumen
  • Irregular surface
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33
Q

Demarcate the SCC in situ and the invasive SCC

A

Top = in situ

Bottom = invasive

34
Q

3 risk factors for gastric adenocarcinoma

A
  • H pylori infection
  • Diet rich in smoked salted food and nitrites and poor in fruits and vegetables
  • Smoking
35
Q

Clinical features of gastric adenocarcinoma

A
  • Early = possibly asymptomatic or may show symptoms related to H pylori infection
  • Advanced = possible epigastric pain, anemia
36
Q

2 types of gastric adenocarcinoma

A
  • Intestinal type
  • Diffuse type
37
Q

Define intestinal type gastric adenocarcinoma

A

Gross = forms a mass, sometimes ulcerated

Microscopy = Glands infiltrating the stroma

38
Q

3 macroscopic features of intestinal type gastric adenocarcinoma

A
  • Walls are irrgeular and margins of the ulcer are higher than the surrounding mucosa
  • Irreuglar, sometimes necrotic base
  • Gastric folds do not reach the edge of the ulcer
39
Q

Describe the histology of intetstional type gastric adenocarcinoma

A

Irregular glands infiltrate in a desmoplastic stroma

40
Q

2 precursor lesions for intestinal type gastric adenocarcinoma

A
  • Low and high grade dysplasia (many times in the setting of intestinal metaplasia secondary to H pylori infection)
  • Gastric adenoma
41
Q

Gross characteristics of diffuse type gastric adenocarcinoma

A
  • Infiltrates the stomach without formation of an obvious mass
  • Wall thickened and rigid
  • gastric folds may be thickened or effaced due to tumor infiltatrion

NOTE: Compare first five sections to normal bottom right section

42
Q

Microscopic characteristics of diffuse type gastric adenocarcinoma

A
  • No gland formation
  • Single cells, sometimes with a signet ring morphology, infiltrate the stroma
43
Q

Define signet ring cell carcinoma

A

Round cells with cytoplasmic mucus accumulation and eccentric nuclei infiltrate the gastric mucosa. No gland formation –> diffuse gastric cancer

NOTE: Some remaining benign mucosal glands may be scattered (arrows)

44
Q

Describe villous adenoma

A

Numerous finger-like projections with fibro-vascular cores lined by adenomatous epithelium

Lining epithelium shows adenomatmous changes:

  • Nuclear enlargement
  • Nuclear stratification
  • Lack of maturation
45
Q

2 pathways in colorectal cancer

A
  • Chromosomal instability (85%)
  • Microsatelite instability (15%)
46
Q

3 characteristics of the chromosomal instability pathway of CRC

A
  • Structural and numeric chromosomalalterations
  • Microsatellite stable
  • Frequent mutations of APC, K-ras, p53
47
Q

5 characteristics of the microsatellite instability pathway of CRC

A
  • Diploid
  • Microsatellite instability
  • Dysfunctions of mismatch repair proteins
  • Peculiar tumor histology
  • Better prognosis than chromosomal instability CRC
48
Q

4 mismatch repair proteins involvedi n microsatellite instability CRC

A
  • MSH2
  • MLH1
  • MSH6
  • PMS2
49
Q

Describe the peculiar tumor histology of microsatellite instability type CRC

A
  • Mucinous differentiation
  • Poorly differentiated tumors
50
Q

2 inherited CRC syndromes

A
  • Familial adenomatous polyposis (FAP)
  • Hereditary nonpolyposis colorectal cancer (HNPCC) – Lynch syndrome
51
Q

4 characteristics of familial adenomatous polyposis

A
  • Autosomal dominant
  • Mutation of APC gene
  • Hundreds of polyps covering the colonic mucosa
  • More frequent in distal colon (CRC also more frequent here)
52
Q

4 characteristics of HNPCC (Lynch syndrome)

A
  • Autosomal dominant
  • Mutations of mismatch repair proteins
  • Rare polyps, frequent CRCs
  • Mainly proximal colon
53
Q

Describe the gross characteristics of FAP

A

Numerous adenomatous polyps covering the colonic mucosa

54
Q

Describe the gross characteristics of HNPCC

A
  • May find synchronous tumors (i.e. in cecum in this example)
  • No polyps remaining in colon
55
Q

Type of adenoma that HNPCC patients are more susceptible to compared to the general population

A

Tubular adenoma

56
Q

Define carcinoid tumor

A

Well-differentiated neoplasm arising in the mucosal neuroendocrine cells

57
Q

2 clinical manifestations of carcinoid tumor

A
  • Incidental finding at endoscopy
  • Carcinoid syndrome
58
Q

7 features of carcinoid syndrome

A
  • Flushing
  • Teleangiectasias
  • Cyanosis
  • Bronchoconstriction
  • Edema
  • Hyperperistalsis
  • Pulmonary and tricuspid valvular disease
59
Q

Gross characteristics of carcinoic tumors

A

Can vary from tiny polyp-like lesions to large tumors, sometimes multiple

Very firm, with a beige or tan homogenous cut surface

60
Q

3 types of carcinoid tumors of the stomach

A
  • Type 1 = inthe background of atrophic gastritis
  • Type 2 = Zollinger-Ellison syndrome
  • Type 3 = sporadic
61
Q

3 possible microscopic findings for carcinoid tumors

A
  • Solid sheets or…
  • … pseudoglandular structures or cords or cells or…
  • … cell that have round to oval nuclei with speckled “salt and pepper” chromatin, inconspicuous nucleoli and moderate cytoplasm
62
Q

Positive endocrine markers for carcinoid tumors

A
  • Synaptophysin
  • Chromogranin (image)
63
Q

Define gastrointestinal stromal tumor

A

Tumors arising from the interstitial cells of Cajal

64
Q

Define interstitial cells of Cajal

A

Pacemaker cells involved in controlling the gastric peristalsis

65
Q

Clinical manifestations of gastrointestinal stromal tumors

A

Asymptomatic or with symptoms related to bleeding or compression of adjacent structures

66
Q

Characteristics of most cases of GIST

A
  • Gain in function mutations of either c-KIT or platelet-derived growth factor receptor alpha (PDGFRA)
67
Q

What are c-KIT and PDGFRA

A

Transmembrane receptors with tyrosine kinase activity, involved in cell proliferation and apoptosis

68
Q

6 gross characteristics of GIST

A
  • Often show as nodular masses protruding into the lumen, covered by mucosa
  • Erosion/ulceration of the mucosa may be present
  • Sometimes may be protruding under the serosal surface of the stomach
  • Consistency ranges from soft to rubbery
  • Cut surface usually beige to gray and homogenous
  • Hemorrhage and/or necrosis may occur
69
Q

Microscopic characteristics of GIST

A
  • Intersecting bundles of spingle shaped cells
  • Sometimes cells are polygonal instead (epihtelioid GIST)
70
Q

Positive endocrine marker for GIST

A

Immunostaining for c-kit (CD117)

71
Q

How may a stomach have lymphoma?

A

As primary site or involvement by a lymphoma arising elsewhere

72
Q

Most frequent types of lymphoma found in stomach

A
  • Marginal zone lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma)
  • Diffuse large B-cell lymphoma
73
Q

4 characteristics of MALT lymphoma

A
  • Low-grade B-cell lymphoma
  • Strongly associated with H pylori infectionàMay regress after H pylori eradication
  • On endoscopy, presents like small mucosal lesions, thickening of the folds
74
Q

Microscopic findings of MALT lymphoma in stomach

A

Mucosa infiltrated by small lymphoid cells showing partial replacement of the glands. H Pylori may be present.

75
Q

Immunostaining for MALT lymphoma in stomach

A

CD20+ (due to B-cell origin)

76
Q

Define lymphoepithelial lesions involving MALT lymphoma in GIT

A

Neoplastic lymphoid cells infiltrating and replacing the glands

77
Q

Most frequent setting of lymphoepithelial lesions of GIT-involved lymphoma

A

MALT lymphomas

NOTE: may be seen in other segments of the GI tract and with other types of lymphomas

78
Q

Immunostaining for MALT lymphoma lymphoepithelial lesions

A

Cytokeratin stain

79
Q

3 characteristics of diffuse large B-cell lymphoma (DLBCL)

A
  • High-grade B-cell lymphoma
  • May arise de novo or in the setting of MALT lymphoma
  • On endoscopy, a large soft mass, sometimes ulcerated, is seen
80
Q

Microscopic features of DLBCL

A
  • Diffuse proliferation or large cells
  • CH20 positive
  • Neoplastic

NOTE: No stromal reaction to tumor

81
Q

Why are DLBCL tumors soft?

A

No desmoplasia