Pathology 30 flashcard
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Here are your 30 Pathology Flashcards - Neoplasia & Oncology (Postgraduate / Residency level), sourced from Robbins & Kumar Basic Pathology:
🃏 Pathology Flashcards: Neoplasia & Oncology
CARD 1
Q: What are the two essential components shared by all tumors, benign and malignant?
A: (1) Parenchyma - the transformed/neoplastic cells, and (2) Stroma - host-derived non-neoplastic connective tissue, inflammatory cells, and blood vessels. Even leukemias circulating in blood depend on stromal interactions.
(Robbins & Kumar Basic Pathology)
CARD 2
Q: Distinguish "benign" from "malignant" in oncological terminology.
A: A benign tumor remains localized and is amenable to surgical removal (generally curable). A malignant tumor (cancer) may be locally invasive AND has capacity to metastasize to distant sites. Not all cancers pursue an aggressive course, but the malignant designation is a red flag.
(Robbins & Kumar Basic Pathology)
CARD 3
Q: What naming convention distinguishes benign from malignant tumors of mesenchymal origin? Give two examples.
A: Benign mesenchymal tumors add the suffix "-oma" to the cell of origin (e.g., lipoma from fat, chondroma from cartilage). Malignant counterparts are called sarcomas (e.g., liposarcoma, chondrosarcoma).
(Robbins & Kumar Basic Pathology)
CARD 4
Q: What is anaplasia and which histological features characterize it?
A: Anaplasia is loss of differentiation and is a hallmark of malignancy. Features include:
- Pleomorphism (variation in cell/nuclear size and shape)
- Hyperchromatic nuclei with coarse chromatin
- Prominent nucleoli
- High nuclear:cytoplasmic ratio
- Atypical mitotic figures (tripolar/multipolar spindles)
- Giant tumor cells
(Robbins & Kumar Basic Pathology)
CARD 5
Q: What is the difference between tumor grade and tumor stage? Which has greater prognostic value in most cancers?
A: Grade = degree of histological differentiation (mitoses, necrosis, architecture loss); ranges typically from low to high (or 1-5). Stage = extent of spread assessed clinically/pathologically using TNM (T=tumor size/invasion, N=nodal involvement, M=metastasis). Staging generally has greater prognostic value than grading.
(Robbins & Kumar Basic Pathology)
CARD 6
Q: In the TNM staging system, what do T0, N0, and M1 each indicate?
A:
- T0 = in situ lesion (confined within basement membrane; no invasion)
- N0 = no regional lymph node involvement
- M1 = distant metastases present
T1-T4 reflects increasing tumor size/invasion; N1-N3 reflects increasing nodal involvement.
(Robbins & Kumar Basic Pathology)
CARD 7
Q: What are the six originally described Hallmarks of Cancer (Hanahan & Weinberg), as reflected in Robbins pathology?
A:
- Self-sufficiency in growth signals
- Insensitivity to growth-inhibitory signals
- Evasion of apoptosis (cell death)
- Limitless replicative potential (immortality)
- Sustained angiogenesis
- Invasion and metastasis
(Additional hallmarks include altered metabolism, immune evasion, and genome instability)
(Robbins & Kumar Basic Pathology)
CARD 8
Q: What is the function of proto-oncogenes, and by what mechanisms are they converted into oncogenes?
A: Proto-oncogenes normally promote cell growth and survival. They become oncogenes (gain-of-function) through:
- Point mutations (e.g., RAS mutations)
- Gene amplification (e.g., MYC, HER2/ERBB2)
- Chromosomal rearrangements/translocations (e.g., BCR-ABL in CML, c-MYC in Burkitt lymphoma)
Only ONE mutant allele is sufficient - oncogenes act dominantly.
(Robbins & Kumar Basic Pathology)
CARD 9
Q: Contrast the mechanism of oncogenes vs. tumor suppressor genes in cancer development.
A:
- Oncogenes: Dominant gain-of-function mutations; one mutant allele is enough to drive proliferation (accelerator stuck "on")
- Tumor suppressor genes: Recessive loss-of-function; both alleles must be inactivated (Knudson's "two-hit hypothesis") to remove the growth brake (brakes removed)
Examples of TSGs: TP53, RB1, APC, BRCA1/2
(Robbins & Kumar Basic Pathology)
CARD 10
Q: Describe the role of RB (retinoblastoma protein) as the "governor of the cell cycle."
A: RB is the key G1/S checkpoint regulator. In its hypophosphorylated (active) state, RB binds and sequesters E2F transcription factors, blocking S-phase entry. Mitogens activate cyclin D-CDK4/6, which phosphorylates RB, releasing E2F and allowing cell cycle progression. In cancer, RB loss (or CDK4/6 activation) releases this brake, enabling unchecked proliferation.
(Robbins & Kumar Basic Pathology)
CARD 11
Q: Why is p53 called the "guardian of the genome"? What happens when TP53 is mutated?
A: p53 responds to DNA damage by:
- Arresting cell cycle at G1 (via p21/CDKN1A upregulation)
- Inducing DNA repair genes
- Triggering apoptosis or senescence if damage is irreparable
With TP53 loss: damaged DNA goes unrepaired, mutations accumulate, and cells progress to malignant transformation. TP53 is mutated in the majority of human cancers (lung, colon, breast - the three leading causes of cancer death).
(Robbins & Kumar Basic Pathology)
CARD 12
Q: How does MDM2 regulate p53, and how is this exploited in cancer?
A: MDM2 binds p53 and targets it for ubiquitin-mediated proteasomal degradation, keeping p53 levels low in unstressed cells. After DNA damage, kinases phosphorylate p53, preventing MDM2 binding, allowing p53 to accumulate. Some cancers amplify MDM2 as an alternative way to inactivate p53 (without TP53 mutation itself).
(Robbins & Kumar Basic Pathology)
CARD 13
Q: What is the Warburg effect and what advantage does it confer on tumor cells?
A: The Warburg effect is aerobic glycolysis - cancer cells preferentially metabolize glucose via glycolysis even in the presence of oxygen, producing lactate. Although less ATP-efficient than oxidative phosphorylation, this provides:
- Carbon intermediates for biosynthesis (nucleotides, lipids, proteins)
- Rapid energy for proliferating cells
- Acidification of the microenvironment (aiding invasion)
It is exploited in FDG-PET scanning (tumors avidly take up glucose).
(Robbins & Kumar Basic Pathology)
CARD 14
Q: What is telomerase, and why is its reactivation important in cancer?
A: Telomerase is a reverse transcriptase that adds TTAGGG repeats to chromosome ends (telomeres), preventing telomere shortening with each replication. Normal somatic cells have low telomerase activity and undergo replicative senescence after ~60-70 divisions. Cancers reactivate telomerase (in ~90% of cases), conferring limitless replicative potential (immortality) - a critical hallmark of malignancy.
(Robbins & Kumar Basic Pathology)
CARD 15
Q: What are the sequential steps in the metastatic cascade for hematogenous spread?
A:
- Local invasion of ECM and basement membrane
- Intravasation (entry into blood/lymph vessels)
- Survival in transit (resistance to anoikis, immune evasion)
- Arrest at distant capillary beds
- Extravasation from vasculature
- Formation of micrometastases
- Growth into macrometastases (requires angiogenesis and immune evasion)
(Robbins & Kumar Basic Pathology)
CARD 16
Q: What molecular event initiates ECM invasion in the metastatic cascade, and which proteases are responsible?
A: Initiation involves loosening of intercellular connections via downregulation of E-cadherin (releasing β-catenin). Tumor cells then:
- Attach to ECM via integrins
- Secrete matrix metalloproteinases (MMPs) and other proteases to degrade type IV collagen and other ECM components
- Migrate through the degraded matrix using cytoskeletal reorganization
(Robbins & Kumar Basic Pathology)
CARD 17
Q: What is epithelial-mesenchymal transition (EMT) and what role does it play in metastasis?
A: EMT is a process by which epithelial cancer cells acquire mesenchymal properties:
- Loss of E-cadherin expression
- Gain of N-cadherin and vimentin
- Acquisition of motility and invasiveness
- Resistance to apoptosis (anoikis resistance)
Transcription factors driving EMT: SNAIL, TWIST, ZEB1. EMT is a key early step in local invasion and metastatic dissemination.
(Robbins & Kumar Basic Pathology)
CARD 18
Q: What cytokine drives tumor angiogenesis, and how is it therapeutically targeted?
A: VEGF (Vascular Endothelial Growth Factor) is the principal driver of tumor angiogenesis. Hypoxia (via HIF-1α) and oncogene activation upregulate VEGF secretion.
Therapeutic targeting: Bevacizumab - a monoclonal antibody that neutralizes VEGF activity, approved for multiple cancers (colorectal, lung, glioblastoma, etc.). However, benefit is limited (extends life by months) due to escape mechanisms including VEGF-independent angiogenic pathways.
(Robbins & Kumar Basic Pathology)
CARD 19
Q: What are tumor antigens? List the three main categories.
A: Tumor antigens are molecules expressed by tumor cells that can be recognized by the host immune system:
- Neoantigens - novel peptides from cancer-specific mutations (driver and passenger mutations); recognized by T cells as non-self
- Unmutated self-antigens aberrantly expressed (e.g., tyrosinase in melanoma; cancer-testis antigens like MAGE that are normally expressed only in germ cells)
- Viral antigens - proteins from oncogenic viruses (HPV E6/E7, EBV LMP) in virus-transformed cells
(Robbins & Kumar Basic Pathology)
CARD 20
Q: Describe the mechanism by which cancers evade immune destruction via the PD-1/PD-L1 axis.
A: Tumor cells upregulate PD-L1 (CD274) on their surface. When PD-L1 binds PD-1 (expressed on activated T cells), it delivers an inhibitory signal that:
- Suppresses T-cell proliferation and cytokine production
- Induces T-cell exhaustion/anergy
- Prevents CTL-mediated killing
Therapeutic reversal: Anti-PD-1 (nivolumab, pembrolizumab) and anti-PD-L1 (atezolizumab) antibodies (immune checkpoint inhibitors) block this interaction, restoring antitumor immunity.
(Robbins & Kumar Basic Pathology)
CARD 21
Q: What is clonal evolution in cancer, and what is its implication for therapy?
A: Cancers are initiated from a single cell (clonal origin), but Darwinian selection drives the outgrowth of genetically distinct subclones with increasingly aggressive characteristics (tumor progression). Subclones with mutations conferring growth/survival advantages dominate over time.
Implication: Intratumoral heterogeneity means therapy directed at a single molecular target may select for resistant subclones, explaining why cancers recur and become refractory to treatment.
(Robbins & Kumar Basic Pathology)
CARD 22
Q: Distinguish driver mutations from passenger mutations in cancer genomics.
A:
- Driver mutations: Confer selective growth or survival advantage; are subject to positive selection during clonal evolution; are targets for therapy (e.g., KRAS, EGFR, BRAF V600E)
- Passenger mutations: Randomly accumulated mutations with no selective advantage; do not contribute to cancer biology but are numerous (especially in cancers caused by mutagenic exposures); some may generate neoantigens recognizable by the immune system
(Robbins & Kumar Basic Pathology)
CARD 23
Q: What is microsatellite instability (MSI) and which cancers commonly display it?
A: MSI results from defective DNA mismatch repair (MMR), causing accumulation of mutations in repetitive sequences (microsatellites). High-MSI (MSI-H) tumors have a high mutational burden and abundant neoantigens.
Common cancers: Lynch syndrome-related CRC (germline MMR mutations - MLH1, MSH2, MSH6, PMS2), sporadic CRC (MLH1 promoter hypermethylation), endometrial cancer, gastric cancer.
Clinical relevance: MSI-H tumors respond exceptionally well to PD-1 checkpoint inhibitors (pembrolizumab is FDA-approved pan-tumor for MSI-H/dMMR).
(Robbins & Kumar Basic Pathology)
CARD 24
Q: What are cancer-testis antigens and why are they immunogenic?
A: Cancer-testis antigens (e.g., MAGE family) are encoded by genes silent in all adult somatic tissues but expressed in germ cells (testis) and in many cancers. They are immunogenic because:
- Adult somatic cells never express them - no central tolerance is established
- The testis lacks MHC class I expression, so no peripheral tolerance develops
- When expressed in cancer cells (which do have MHC I), they can be presented to CD8+ T cells as foreign antigens
(Robbins & Kumar Basic Pathology)
CARD 25
Q: What are the main chemical carcinogens and their associated cancers? Give three examples.
A:
| Carcinogen | Cancer |
|---|---|
| Tobacco (polycyclic aromatic hydrocarbons, nitrosamines) | Lung, oropharynx, bladder, pancreas |
| Asbestos | Mesothelioma, lung carcinoma (synergistic with smoking) |
| Aflatoxin B1 (Aspergillus in stored grains) | Hepatocellular carcinoma (with HBV) |
| Aromatic amines (e.g., β-naphthylamine, aniline dyes) | Bladder carcinoma |
| Vinyl chloride | Hepatic angiosarcoma |
| Benzene | Acute myeloid leukemia (AML) |
(Robbins & Kumar Basic Pathology)
CARD 26
Q: Which oncogenic viruses are associated with which human cancers?
A:
| Virus | Cancer |
|---|---|
| HPV 16/18 (high-risk) | Cervical, oropharyngeal, anal, vulvar carcinoma |
| EBV | Burkitt lymphoma, nasopharyngeal carcinoma, EBV+ DLBCL, Hodgkin lymphoma |
| HBV/HCV | Hepatocellular carcinoma |
| HTLV-1 | Adult T-cell leukemia/lymphoma |
| HHV-8 (KSHV) | Kaposi sarcoma, primary effusion lymphoma |
| Merkel cell polyomavirus | Merkel cell carcinoma |
(Robbins & Kumar Basic Pathology)
CARD 27
Q: What are tumor markers and what is their clinical utility? Give five examples.
A: Tumor markers are molecules produced by tumor cells (or by host cells in response to tumors), detectable in blood or tissue. Uses: screening, diagnosis, monitoring response to treatment, and detecting recurrence. Not diagnostic alone due to limited specificity.
| Marker | Cancer |
|---|---|
| PSA | Prostate |
| AFP (α-fetoprotein) | HCC, non-seminomatous germ cell tumors |
| β-hCG | Gestational trophoblastic disease, germ cell tumors |
| CA-125 | Ovarian cancer (monitoring) |
| CEA | Colorectal, gastric, pancreatic (monitoring) |
| CA 19-9 | Pancreatic cancer |
(Robbins & Kumar Basic Pathology)
CARD 28
Q: What is carcinoma in situ (CIS), and how does it differ from invasive carcinoma?
A: Carcinoma in situ is a pre-invasive lesion in which malignant epithelial cells show full-thickness cytological features of malignancy (nuclear atypia, pleomorphism, mitoses) but have NOT breached the basement membrane. Coded as T0 in TNM.
Invasive carcinoma has broken through the basement membrane, allowing access to lymphatics and blood vessels - and thus metastatic potential. CIS is potentially curable by local excision; invasive carcinoma carries metastatic risk.
(Robbins & Kumar Basic Pathology)
CARD 29
Q: What is paraneoplastic syndrome and list three classic examples with their associated tumors?
A: Paraneoplastic syndromes are clinical findings caused by hormones, cytokines, or immune cross-reactivity produced by the tumor - NOT by direct local or metastatic effects.
| Syndrome | Mediator | Tumor |
|---|---|---|
| Hypercalcemia of malignancy | PTHrP | Squamous cell carcinoma of lung, renal cell carcinoma |
| SIADH (hyponatremia) | Ectopic ADH | Small cell lung carcinoma |
| Cushing syndrome | Ectopic ACTH | Small cell lung carcinoma, carcinoid |
| Lambert-Eaton syndrome | Anti-VGCC antibodies | Small cell lung carcinoma |
| Polycythemia | Ectopic EPO | Renal cell carcinoma, HCC |
(Robbins & Kumar Basic Pathology)
CARD 30
Q: Describe the principles and clinical relevance of liquid biopsy in oncology.
A: Liquid biopsy involves detection and analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), or cell-free DNA in blood (or other body fluids) released by tumor cells.
Clinical applications:
- Early cancer detection (detecting mutations before radiological evidence)
- Monitoring treatment response (ctDNA levels fall with effective therapy)
- Detecting minimal residual disease (MRD) and predicting relapse
- Identifying resistance mutations (e.g., EGFR T790M in NSCLC post-erlotinib) without repeat tissue biopsy
- Tumor heterogeneity profiling (captures subclonal variation missed by single-site biopsy)
(Robbins & Kumar Basic Pathology; current oncology practice)
Quick Reference Summary
| Theme | Cards |
|---|---|
| Nomenclature & Classification | 1, 2, 3, 4 |
| Grading & Staging | 5, 6 |
| Hallmarks of Cancer | 7, 13, 14 |
| Oncogenes & TSGs | 8, 9 |
| Cell Cycle Checkpoints (RB, p53) | 10, 11, 12 |
| Metastasis | 15, 16, 17 |
| Angiogenesis | 18 |
| Tumor Immunology | 19, 20, 24 |
| Cancer Genomics | 21, 22, 23 |
| Carcinogens & Viruses | 25, 26 |
| Diagnosis & Markers | 27, 28 |
| Paraneoplastic & Liquid Biopsy | 29, 30 |
All cards sourced from Robbins & Kumar Basic Pathology (9780323790185), the gold standard postgraduate pathology reference.
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