Pathology -- GI Neoplasia Flashcards
Define adenocarcinoma
Malignant epithelial neoplasm with glandular differentiation
Define squamous cell carcinoma
Malignant epithelial neoplasm with squamous cell differentiation
Define glandular differentiation
- Formation of glands
- Production of mucus (intracellular and/or extracellular)
Architectural malignant features of adenocarcinoma
- Irregularly shaped glands or groups of cells
- Infiltrating growth pattern, either as groups of cells or single cells
Cytologic malignant features of adenocarcinoma (4)
- Neoplastic cells are usually large and irregular in size and shape
- High N/C ratio
- Nuclei irregular in size and shape
- Prominent nucleoli
Miscellaneous malingnant features of adenocarcinoma (3)
- Necrosis
- Frequent mitoses
- Desmoplastic stroma
Describe the histology of invasive (colonic) adenocarcinoma (4)
- 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)
Define dquamous cell differentiaiton
Keratinocyte-like cells with intercellular bridges and/or keratinization
Describe the appearance of keratinocyte-like cells
Polygonal, pavement-like cells with eosinophilic cytoplasm
Architectural malignant features of in situ SCC (2)
- Tumor above the basement membrane
- Architecture approximates that of the normal squamous epithelium (cytology still malignant)
Architectural malignant features of invasive SCC
Irregularly-shaped sheets of cells, sometimes single cells with infiltrating growth pattern
Cytology of SCC (4)
- Neoplastic cells usually large and irregular in size and shape
- High N/C ratio
- Nuclei irregular in size and shape
- Sometimes prominent nucleoli
3 miscellaneous malignant features of SCC
- Necrosis
- Frequent mitoses
- Desmoplastic stroma
Describe the histology of invasive SCC (7)
- 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
What gives invasive SCC a tumor with firm consistency?
The desmoplastic stroma
3 precursor lesions for adenocarcinoma and their specific areas of effect
- Intestinal metaplasia –> dysplasia of glandular mucosa (esophagus and stomach)
- Adenoma (stomach and bowel)
- Dysplasia in the context of chronic inflammatory bowel disease (bowel)
Describe the histology of tubular adenoma
- Nuclear enlargement
- Nuclear stratification
- Lack of maturation
(Versus normal colon on right)
Types of tumors that can be found in the esophagus
- Adenocarcinoma
- Squamous cell carcinoma
Types of tumors that can be found in the stomach
- Adenocarcinoma (intestinal type and diffuse, signet ring cell, type)
- Lymphoma
Types of tumors that can be found in the colorectum
Adenocarcinoma and adenoma
2 other types of GI tumors that are not adenocarcinoma, SCC or lymphoma
- Neuroendocrine tumors/ carcinoid tumors
- Gastrointestinal stromal tumors
Define high grade dysplasia in Barrett esophagus (histology)
Very complex architecture with bridging:
- Absence of maturation of glandular mucosa
- Large, atypical, crowded and stratified nuclei
- Less cytoplasm
Define esophageal adenocarcinoma
Malignant tumor of glandular differentiation usually in the setting of Barrett esophagus
Usual location of esophageal adenocarcinoma and why
Distal esophagus since BE involves distal esophagus
Clinical manifestations of esophageal adenocarcinoma (5)
- Symptoms related to GERD
- Dysphagia
- Pain (epigastric, retrosternal)
- Weight loss
- Anemia
Describe the histological appearance of invasive adenocarcinoma
- Glands of various sizes and shapes infiltrating the stroma
- High N/C ratio
- Large irregular epithelial nuclei
- Clumped chromatin
Groups of people most commonly affected by esophageal squamous cell carcinoma
- >50 YO
- Men
3 risk factors for esophageal SCC
- Smoking
- Alcohol
- Carcinogens in food
3 clinical manifestations of esophageal SCC
Small tumors may be asymptomatic, however symptoms are:
- Dysphagia
- Chest pain
- Weight loss
Diagnostic method of choice for esophageal SCC
Endoscopy with biopsy
Usual location of esophageal SCC
Lower 2/3 of esophagus
Macroscopic features of esophageal SCC
- 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
Demarcate the SCC in situ and the invasive SCC
Top = in situ
Bottom = invasive
3 risk factors for gastric adenocarcinoma
- H pylori infection
- Diet rich in smoked salted food and nitrites and poor in fruits and vegetables
- Smoking
Clinical features of gastric adenocarcinoma
- Early = possibly asymptomatic or may show symptoms related to H pylori infection
- Advanced = possible epigastric pain, anemia
2 types of gastric adenocarcinoma
- Intestinal type
- Diffuse type
Define intestinal type gastric adenocarcinoma
Gross = forms a mass, sometimes ulcerated
Microscopy = Glands infiltrating the stroma
3 macroscopic features of intestinal type gastric adenocarcinoma
- 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
Describe the histology of intetstional type gastric adenocarcinoma
Irregular glands infiltrate in a desmoplastic stroma
2 precursor lesions for intestinal type gastric adenocarcinoma
- Low and high grade dysplasia (many times in the setting of intestinal metaplasia secondary to H pylori infection)
- Gastric adenoma
Gross characteristics of diffuse type gastric adenocarcinoma
- 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
Microscopic characteristics of diffuse type gastric adenocarcinoma
- No gland formation
- Single cells, sometimes with a signet ring morphology, infiltrate the stroma
Define signet ring cell carcinoma
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)
Describe villous adenoma
Numerous finger-like projections with fibro-vascular cores lined by adenomatous epithelium
Lining epithelium shows adenomatmous changes:
- Nuclear enlargement
- Nuclear stratification
- Lack of maturation
2 pathways in colorectal cancer
- Chromosomal instability (85%)
- Microsatelite instability (15%)
3 characteristics of the chromosomal instability pathway of CRC
- Structural and numeric chromosomalalterations
- Microsatellite stable
- Frequent mutations of APC, K-ras, p53
5 characteristics of the microsatellite instability pathway of CRC
- Diploid
- Microsatellite instability
- Dysfunctions of mismatch repair proteins
- Peculiar tumor histology
- Better prognosis than chromosomal instability CRC
4 mismatch repair proteins involvedi n microsatellite instability CRC
- MSH2
- MLH1
- MSH6
- PMS2
Describe the peculiar tumor histology of microsatellite instability type CRC
- Mucinous differentiation
- Poorly differentiated tumors
2 inherited CRC syndromes
- Familial adenomatous polyposis (FAP)
- Hereditary nonpolyposis colorectal cancer (HNPCC) – Lynch syndrome
4 characteristics of familial adenomatous polyposis
- Autosomal dominant
- Mutation of APC gene
- Hundreds of polyps covering the colonic mucosa
- More frequent in distal colon (CRC also more frequent here)
4 characteristics of HNPCC (Lynch syndrome)
- Autosomal dominant
- Mutations of mismatch repair proteins
- Rare polyps, frequent CRCs
- Mainly proximal colon
Describe the gross characteristics of FAP
Numerous adenomatous polyps covering the colonic mucosa
Describe the gross characteristics of HNPCC
- May find synchronous tumors (i.e. in cecum in this example)
- No polyps remaining in colon
Type of adenoma that HNPCC patients are more susceptible to compared to the general population
Tubular adenoma
Define carcinoid tumor
Well-differentiated neoplasm arising in the mucosal neuroendocrine cells
2 clinical manifestations of carcinoid tumor
- Incidental finding at endoscopy
- Carcinoid syndrome
7 features of carcinoid syndrome
- Flushing
- Teleangiectasias
- Cyanosis
- Bronchoconstriction
- Edema
- Hyperperistalsis
- Pulmonary and tricuspid valvular disease
Gross characteristics of carcinoic tumors
Can vary from tiny polyp-like lesions to large tumors, sometimes multiple
Very firm, with a beige or tan homogenous cut surface
3 types of carcinoid tumors of the stomach
- Type 1 = inthe background of atrophic gastritis
- Type 2 = Zollinger-Ellison syndrome
- Type 3 = sporadic
3 possible microscopic findings for carcinoid tumors
- 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
Positive endocrine markers for carcinoid tumors
- Synaptophysin
- Chromogranin (image)
Define gastrointestinal stromal tumor
Tumors arising from the interstitial cells of Cajal
Define interstitial cells of Cajal
Pacemaker cells involved in controlling the gastric peristalsis
Clinical manifestations of gastrointestinal stromal tumors
Asymptomatic or with symptoms related to bleeding or compression of adjacent structures
Characteristics of most cases of GIST
- Gain in function mutations of either c-KIT or platelet-derived growth factor receptor alpha (PDGFRA)
What are c-KIT and PDGFRA
Transmembrane receptors with tyrosine kinase activity, involved in cell proliferation and apoptosis
6 gross characteristics of GIST
- 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
Microscopic characteristics of GIST
- Intersecting bundles of spingle shaped cells
- Sometimes cells are polygonal instead (epihtelioid GIST)
Positive endocrine marker for GIST
Immunostaining for c-kit (CD117)
How may a stomach have lymphoma?
As primary site or involvement by a lymphoma arising elsewhere
Most frequent types of lymphoma found in stomach
- Marginal zone lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma)
- Diffuse large B-cell lymphoma
4 characteristics of MALT lymphoma
- 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
Microscopic findings of MALT lymphoma in stomach
Mucosa infiltrated by small lymphoid cells showing partial replacement of the glands. H Pylori may be present.
Immunostaining for MALT lymphoma in stomach
CD20+ (due to B-cell origin)
Define lymphoepithelial lesions involving MALT lymphoma in GIT
Neoplastic lymphoid cells infiltrating and replacing the glands
Most frequent setting of lymphoepithelial lesions of GIT-involved lymphoma
MALT lymphomas
NOTE: may be seen in other segments of the GI tract and with other types of lymphomas
Immunostaining for MALT lymphoma lymphoepithelial lesions
Cytokeratin stain
3 characteristics of diffuse large B-cell lymphoma (DLBCL)
- 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
Microscopic features of DLBCL
- Diffuse proliferation or large cells
- CH20 positive
- Neoplastic
NOTE: No stromal reaction to tumor
Why are DLBCL tumors soft?
No desmoplasia
