Pathology - Neoplasia Flashcards
1
Q
Neoplastic progression
- Hallmarks of cancer
- Progression
A
- Hallmarks of cancer
- Evasion of apoptosis, growth signal self-sufficiency, anti-growth signal insensitivity, sustained angiogenesis, limitless replicative potential, tissue invasion, and metastasis.
- Progression
- Normal cellularity
- Hyperplasia
- Dysplasia
- Carcinoma in situ / preinvasive
- Invasive carcinoma
- Metastasis
2
Q
Neoplastic progression
- Normal cellularity
- Hyperplasia
- Dysplasia
- Carcinoma in situ / preinvasive
- Invasive carcinoma
- Metastasis
A
- Normal cellularity
- Normal cells with basal –> apical differentiation
- Hyperplasia
- Cells increase in number
- Dysplasia
- Abnormal proliferation of cells with loss of size, shape, and orientation
- Carcinoma in situ / preinvasive
- Neoplastic cells have not invaded basement membrane
- High nuclear/cytoplasmic ratio and clumped chromatin
- Neoplastic cells encompass entire thickness
- Invasive carcinoma
- Cells have invaded basement membrane using collagenases and hydrolases (metalloproteinases)
- Can metastasize if they reach a blood or lymphatic vessel
- Metastasis
- Spread to distant organ
- Must survive immune attack
- “Seed and soil” theory of metastasis
- Seed = tumor embolus
- Soil = target organ––liver, lungs, bone, brain, etc.
3
Q
P-glycoprotein
A
- Also known as multidrug resistance protein 1 (MDR1).
- Expressed by some cancer cells (e.g., colon, liver) to pump out toxins, including chemotherapeutic agents (one mechanism of decreased responsiveness or resistance to chemotherapy over time).
4
Q
-plasia definitions
- Hyperplasia
- Metaplasia
- Dysplasia
- Anaplasia
- Neoplasia
- Desmoplasia
A
-
Hyperplasia (reversible)
- Increase in number of cells.
-
Metaplasia (reversible)
- One adult cell type is replaced by another.
- Often 2° to irritation (e.g., Barrett esophagus) and/or environmental exposure (e.g., smoking-induced tracheal/bronchial squamous metaplasia).
-
Dysplasia (reversible)
- Abnormal growth with loss of cellular orientation, shape, and size in comparison to normal tissue maturation
- Commonly preneoplastic.
-
Anaplasia (irreversible)
- Loss of structural differentiation and function of cells, resembling primitive cells of same tissue
- Often equated with undifferentiated malignant neoplasms.
- May see “giant cells” with single large nucleus or several nuclei.
-
Neoplasia (irreversible)
- A clonal proliferation of cells that is uncontrolled and excessive.
- Neoplasia may be benign or malignant.
-
Desmoplasia (irreversible)
- Fibrous tissue formation in response to neoplasm (e.g., linitis plastica in diffuse stomach cancer).
5
Q
Tumor grade vs. stage
- Grade
- Stage
A
- Grade
- Determined by degree of cellular differentiation and mitotic activity on histology.
- Usually graded 1–4
- 1 = low grade, well differentiated
- 4 = high grade, poorly differentiated, anaplastic.
- Stage
- Degree of localization/spread based on site and size of 1° lesion, spread to regional lymph nodes, presence of metastases.
- Based on clinical (c) or pathology (p) findings.
- Example: cT3N1M0
-
TNM staging system (Stage = Spread):
- T = Tumor size
- N = Node involvement
- M = Metastases
- TMN each has independent prognostic value.
- Stage usually has more prognostic value than grade.
6
Q
Tumor nomenclature
- Carcinomas vs. sarcomas
- Exceptions to lymphatic spread
A
- Carcinomas vs. sarcomas
- The term carcinoma implies epithelial origin, whereas sarcoma denotes mesenchymal origin.
- Both terms imply malignancy.
- Most carcinomas spread lymphatically, whereas most sarcomas spread hematogenously.
- The term carcinoma implies epithelial origin, whereas sarcoma denotes mesenchymal origin.
- Notable exceptions to carcinomas that spread lymphatically include (all of which may spread hematogenously):
- Renal cell carcinoma (often invades renal vein)
- Hepatocellular carcinoma (often invades hepatic vein)
- Follicular carcinoma of the thyroid
- Choriocarcinoma
7
Q
Tumor nomenclature
- For each cell type
- Benign
- Malignant
- Epithelium
- Mesenchyme
- Blood cells
- Blood vessels
- Smooth muscle
- Striated muscle
- Connective tissue
- Bone
- Fat
A
- Epithelium
- Benign: Adenoma, papilloma
- M: Adenocarcinoma, papillary carcinoma
- Mesenchyme
- Blood cells
- Benign:** **N/A
- Malignant: Leukemia, lymphoma
- Blood vessels
- Benign: Hemangioma
- Malignant: Angiosarcoma
- Smooth muscle
- Benign: Leiomyoma
- Malignant: Leiomyosarcoma
- Striated muscle
- Benign: Rhabdomyoma
- Malignant: Rhabdomyosarcoma
- Connective tissue
- Benign: Fibroma
- Malignant: Fibrosarcoma
- Bone
- Benign: Osteoma
- Malignant: Osteosarcoma
- Fat
- Benign: Lipoma
- Malignant: Liposarcoma
- Blood cells
8
Q
Tumor differences
- Benign
- Malignant
A
- Benign
- Usually well differentiated
- Low mitotic activity
- Well demarcated
- No metastasis
- No necrosis.
- Malignant
- May be poorly differentiated
- Erratic growth
- Locally invasive/diffuse
- May metastasize
- Decreased apoptosis (upregulation of telomerase prevents chromosome shortening and cell death).
9
Q
Cachexia
A
- Weight loss, muscle atrophy, and fatigue that occur in chronic disease (e.g., cancer, AIDS, heart failure, TB).
- Mediated by TNF-α (nicknamed cachectin), IFN-γ, and IL-6.
10
Q
Neoplasms associated with these disease conditions
- Acanthosis nigricans (hyperpigmentation and epidermal thickening)
- Actinic keratosis
- AIDS
- Autoimmune diseases (e.g., Hashimoto thyroiditis, SLE)
- Barrett esophagus (chronic GI reflux)
- Chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnants
- Cirrhosis
- Cushing syndrome
- Dermatomyositis
- Down syndrome
- Dysplastic nevus
A
- Acanthosis nigricans (hyperpigmentation and epidermal thickening)
- Visceral malignancy (esp. stomach)
- Actinic keratosis
- Squamous cell carcinoma of skin
- AIDS
- Aggressive malignant lymphomas (non- Hodgkin) and Kaposi sarcoma
- Autoimmune diseases (e.g., Hashimoto thyroiditis, SLE)
- Lymphoma
- Barrett esophagus (chronic GI reflux)
- Esophageal adenocarcinoma
- Chronic atrophic gastritis, pernicious anemia, postsurgical gastric remnants
- Gastric adenocarcinoma
- Cirrhosis
- Hepatocellular carcinoma
- Cushing syndrome
- Small cell lung cancer
- Dermatomyositis
- Lung cancer
- Down syndrome
- ALL (“we ALL fall Down”), AML
- Dysplastic nevus
- Malignant melanoma
11
Q
Neoplasms associated with these disease conditions
- Hypercalcemia
- Immunodeficiency states
- Lambert-Eaton myasthenic syndrome
- Myasthenia gravis, pure RBC aplasia
- Paget disease of bone
- Plummer-Vinson syndrome (decreased iron)
- Polycythemia
- Radiation exposure
- SIADH
- Tuberous sclerosis (facial angiofibroma, seizures, intellectual disability)
- Ulcerative colitis
- Xeroderma pigmentosum, albinism
A
- Hypercalcemia
- Squamous cell lung cancer
- Immunodeficiency states
- Malignant lymphomas
- Lambert-Eaton myasthenic syndrome
- Small cell lung cancer
- Myasthenia gravis, pure RBC aplasia
- Thymoma
- Paget disease of bone
- 2° osteosarcoma and fibrosarcoma
- Plummer-Vinson syndrome (decreased iron)
- Squamous cell carcinoma of esophagus
- Polycythemia
- Renal cell carcinoma, hepatocellular carcinoma
- Radiation exposure
- Leukemia, sarcoma, papillary thyroid cancer, and breast cancer
- SIADH
- Small cell lung cancer
- Tuberous sclerosis (facial angiofibroma, seizures, intellectual disability)
- Giant cell astrocytoma, renal angiomyolipoma, and cardiac rhabdomyoma
- Ulcerative colitis
- Colonic adenocarcinoma
- Xeroderma pigmentosum, albinism
- Melanoma, basal cell carcinoma, and especially squamous cell carcinomas of skin
12
Q
Oncogenes
- Definition
- For each gene
- Associated tumor
- Gene product
- BCR-ABL
- bcl-2
- BRAF
- c-kit
- c-myc
- HER2/neu (c-erbB2)
- L-myc
- N-myc
- ras
- ret
A
- Definition
- Gain of function –> increased cancer risk.
- Need damage to only 1 allele.
- BCR-ABL
- Associated tumor: CML, ALL
- Gene product: Tyrosine kinase
- bcl-2
- Associated tumor: Follicular and undifferentiated lymphomas
- Gene product: Anti-apoptotic molecule (inhibits apoptosis)
- BRAF
- Associated tumor: Melanoma
- Gene product: Serine/threonine kinase
- c-kit
- Associated tumor: Gastrointestinal stromal tumor (GIST)
- Gene product: Cytokine receptor (for stem cell factor)
- c-myc
- Associated tumor: Burkitt lymphoma
- Gene product: Transcription factor
- HER2/neu (c-erbB2)
- Associated tumor: Breast, ovarian, and gastric carcinomas
- Gene product: Tyrosine kinase
-
L-myc
- Associated tumor: Lung tumor
- Gene product: Transcription factor
-
N-myc
- Associated tumor: Neuroblastoma
- Gene product: Transcription factor
- ras
- Associated tumor: Colon cancer, lung cancer, pancreatic cancer
- Gene product: GTPase
- ret
- Associated tumor: MEN 2A and 2B
- Gene product: Tyrosine kinase
13
Q
Tumor suppressor genes
- Definition
- For each gene
- Associated tumor
- Gene product
- APC
- BRCA1/BRCA2
- CPD4/SMAD4
- DCC
- MEN1
- NF1
- NF2
- p16
- p53
- PTEN
- Rb
- TSC1
- TSC2
- VHL
- WT1/WT2
A
- Definition
- Loss of function –> increased cancer risk
- Both alleles must be lost for expression of disease.
- APC (no gene product)
- Associated tumor: Colorectal cancer (associated with FAP)
-
BRCA1/BRCA2
- Associated tumor: Breast and ovarian cancer
- Gene product: DNA repair protein
- CPD4/SMAD4
- Associated tumor: Pancreatic cancer
- Gene product: DPC—Deleted in Pancreatic Cancer
- DCC
- Associated tumor: Colon cancer
- Gene product: DCC—Deleted in Colon Cancer
- MEN1 (no gene product)
- Associated tumor: MEN type I
-
NF1
- Associated tumor: NeuroFibromatosis type 1
- Gene product: RAS GTPase activating protein (neurofibromin)
-
NF2
- Associated tumor: NeuroFibromatosis type 2
- Gene product: Merlin (schwannomin) protein
- p16
- Associated tumor: Melanoma
- Gene product: Cyclin-dependent kinase inhibitor 2A
- p53
- Associated tumor: Most human cancers, Li-Fraumeni syndrome
- Gene product: Transcription factor for p21, blocks G1 –> S phase
- PTEN (no gene product)
- Associated tumor: Breast cancer, prostate cancer, endometrial cancer
-
Rb
- Associated tumor: Retinoblastoma, osteosarcoma
- Gene product: Inhibits E2F; blocks G1 –> S phase
- TSC1
- Associated tumor: Tuberous sclerosis
- Gene product: Hamartin protein
- TSC2
- Associated tumor: Tuberous sclerosis
- Gene product: Tuberin protein
-
VHL
- Associated tumor: von Hippel-Lindau disease
- Gene product: Inhibits hypoxia inducible factor 1a
-
WT1/WT2 (no gene product)
- Associated tumor: Wilms Tumor (nephroblastoma)
14
Q
Tumor markers
- Definition
- Alkaline phosphatase
- α-fetoprotein
- β-hCG
- CA-15-3/CA-27-29
- CA-19-9
A
- Definition
- Tumor markers should not be used as the 1° tool for cancer diagnosis.
- They may be used to monitor tumor recurrence and response to therapy, but definitive diagnosis can be made only via biopsy.
- Alkaline phosphatase
- Metastases to bone, liver, Paget disease of bone, seminoma (placental ALP).
- α-fetoprotein
- Normally made by fetus.
- Hepatocellular carcinoma, hepatoblastoma, yolk sac (endodermal sinus) tumor, testicular cancer, mixed germ cell tumor (co-secreted with β-hCG).
- β-hCG
- Hydatidiform moles and Choriocarcinomas (Gestational trophoblastic disease), testicular cancer.
- Commonly associated with pregnancy.
- CA-15-3/CA-27-29
- Breast cancer.
- CA-19-9
- Pancreatic adenocarcinoma.
15
Q
Tumor markers
- CA-125
- Calcitonin
- CEA
- PSA
- S-100
- TRAP
A
- CA-125
- Ovarian cancer.
- Calcitonin
- Medullary thyroid carcinoma.
-
CEA
- CarcinoEmbryonic Antigen.
- Very nonspecific but produced by ∼ 70% of colorectal and pancreatic cancers
- Also produced by gastric, breast, and medullary thyroid carcinomas.
- PSA
- Prostate-specific antigen.
- Used to follow prostate adenocarcinoma.
- Can also be elevated in BPH and prostatitis.
- Questionable risk/benefit for screening.
- S-100
- Neural crest origin (e.g., melanomas, neural tumors, schwannomas, Langerhans cell histiocytosis).
- TRAP
- Tartrate-Resistant Acid Phosphatase (TRAP).
- Hairy cell leukemia—a B-cell neoplasm.
- TRAP the hairy animal.
- Largely replaced by flow cytometry.
20
Q
Psammoma bodies
A
- Laminated, concentric, calcific spherules [A]
-
PSa_MM_oma bodies seen in:
- Papillary carcinoma of thyroid
- Serous papillary cystadenocarcinoma of ovary
- Meningioma
- Malignant mesothelioma
22
Q
Common metastases
- For each
- 1º tumor
- Notes
- Brain
- Liver
- Bone
A
- Brain
- 1º tumor: Lung > breast > genitourinary > osteosarcoma > melanoma > GI.
-
Notes:
- 50% of brain tumors are from metastases [A].
- Commonly seen as multiple well-circumscribed tumors at gray/white matter junction.
- Liver
- 1º tumor: Colon >> stomach > pancreas.
- Notes: Liver [B, C] and lung are the most common sites of metastasis after the regional lymph nodes.
- Bone
- 1º tumor: Prostate, breast > lung > thyroid.
-
Notes:
- Bone metastasis [D] >> 1° bone tumors (e.g., multiple myeloma, lytic).
- Whole-body bone scan [E] shows tumor predilection for axial skeleton.
- Prostate = blastic.
- Breast = lytic and blastic.
