NCM 112: Cellular Aberration

Key Terms
1) Cell Proliferation:
a. Process of cell division and reproduction.
b. Balance: Active dividing cells = Cells dying/shedding.

2) Neoplasm:
a. Means “new growth”.
b. Abnormal cell growth forming a mass (tumor).
3) Cancer:
a. General term for malignant tumors.
4) Hypertrophy:
a. Increase in cell size → Increase in organ size.
b. Causes: Workload, hormones, or compensation for tissue loss.
5) Hyperplasia:
a. Increase in number of cells (reversible).
b. Example: Endometrial hyperplasia, benign prostatic hyperplasia (BPH).
c. Note: If growth control fails, it can lead to cancer.
6) Metaplasia:
a. Cell type conversion to another type not usually found in that tissue.
b. Causes: Inflammation, irritation, vitamin deficiency, chemicals.
c. Example: Columnar cells in the lungs replaced by squamous cells (smoking).
d. Reversible if the stimulus is removed; can progress to dysplasia if it persists.
7) Dysplasia:
a. Abnormal changes in cell size, shape, or organization.
b. Causes: Radiation, inflammation, chemicals, chronic irritation.
c. Examples:
i. Chronic bronchitis in smokers.
ii. Cervical dysplasia (prolonged inflammation).
d. Reversible if the stimulus is removed.
e. Pre-cancerous stage.

8) Benign Neoplasms:
a. Well-differentiated cells.
b. Localized mass; does not spread (metastasize).
c. Not life-threatening unless size/location affects vital functions.
9) Malignant Neoplasms:
a. Poorly differentiated cells.
b. Invasive and can spread (metastasize).
c. If untreated: Can cause death.
 Benign vs. Malignant Tumors
Characteristic Benign Malignant
Well-differentiated; resembles
Differentiation Poorly differentiated; atypical (anaplasia)
tissue of origin
Rate of Slow, may stop/regress; rare,
Erratic, rapid; frequent, abnormal mitosis
Growth normal mitosis
Cohesive, well-defined; no
Local Invasion Invasive; infiltrates surrounding tissue
infiltration
Common; larger & less differentiated tumors
Metastasis Absent
spread more

Quick Recap Mnemonics

 Key Terms:
1. “Hyper = More
2. Meta = Change
3. Dys = Abnormal”
 Benign vs. Malignant:
1. “Benign Stays Put, Malignant Moves Out”

Tumor Classification
Key Terms to Remember
 Benign: Non-cancerous
 Malignant: Cancerous

1. Mesenchymal Tumors
(Connective Tissue & Muscle Origin)
Cell/Tissue of Origin Benign Tumor Malignant Tumor
Fibroblast Fibroma Fibrosarcoma
Fat Cell (Lipo=fat) Lipoma Liposarcoma
Blood Vessels (Angio=vessel) Hemangioma Angiosarcoma
Smooth Muscle (leio=smooth) Leiomyoma Leiomyosarcoma
Striated Muscle (rhabdo=striated) ----- Rhabdomyosarcoma
Cartilage (cartilage= chondro) Chondroma Chondrosarcoma
Bone Cell (bone=osteo) Osteoma Osteosarcoma
2. Epithelial Tumors
(Surface and Glandular Cells)
Cell/Tissue of Origin Benign Tumor Malignant Tumor
Squamous Epithelium Epithelioma (Papilloma) Squamous Cell Carcinoma
Transitional Epithelium Transitional Cell Papilloma Transitional Cell Carcinoma
Glandular/Ductal Epithelium Adenoma Adenocarcinoma
Neuroendocrine Cells Carcinoid Oat Cell Carcinoma

3. Internal Organ-Specific Tumors

Organ Benign Tumor Malignant Tumor
Liver Cell Liver Cell Adenoma Liver Cell Carcinoma
Kidney Cell Renal Cell Adenoma Renal Cell Carcinoma

4. Blood and Lymphocyte Tumors

Cell Type Malignant Tumor
White Blood Stem Cells Leukemia
Lymphoid Cells Lymphoma
Plasma Cells Multiple Myeloma

5. Neural Cell Tumors

Cell Type Benign Tumor Malignant Tumor
Neural Cell Precursors Ganglioneuroma Neuroblastoma
Glial Cells ----- Glioma
Meningeal Cells Meningioma -----
Schwann Cells Schwannoma Malignant Schwannoma

6. Germ Cell Tumors

(Embryonic Cells)
Benign Tumor Malignant Tumor
Teratoma Embryonal Carcinoma
Teratocarcinoma
Seminoma/Dysgerminoma
 Memory Tip

Use Mnemonics for Key Categories:

1. Mesenchymal: Fat Fibers Build Strong Muscles Connecting Bones
(Fibroblast, Fat, Blood, Smooth, Muscle, Cartilage, Bone)
2. Epithelial: Skin Touches Glands
(Squamous, Transitional, Glandular)

Benign suffixes:
1. -ma (Except blood cell and lymphocyte cancers)
2. Papilloma
3. adenoma

Malignant suffixes:
1. Sarcoma
2. Carcinoma

Cancer Cell Characteristics

5 Key Characteristics of Cancer Cells Quick Recap Mnemonics
1. Altered Cell Differentiation
2. Appearance Changes 1. Differentiation: D-FLAM
3. Altered Metabolism 2. Appearance: PANIC
4. Tumor-Specific Antigens 3. Metabolism: G-MAH
5. Altered Cellular Function 4. Antigens: TAG

1. Altered Cell Differentiation

Normal Cells:
o Mature and specialize (differentiation).
o Acquire specific functions and structures.
Cancer Cells:
o Loss of specialization and normal function.
o Undifferentiated (Anaplastic) cells are aggressive.
o Altered differentiation linked to:
 Appearance changes
 Metabolic changes
 Tumor-specific antigens
 Mnemonic: D-FLAM — Differentiation, Function loss, Looks different, Antigens, Metabolism.
2. Appearance Changes
 Pleomorphism: Cancer cells vary in size and shape.
 Nuclear Changes:
o Large or multiple nuclei.
 Chromosomal Abnormalities:
o Aneuploidy: Abnormal chromosome number.
o Disorganized chromosomes.
Well-Differentiated = Cells resemble original tissue.
Undifferentiated (Anaplastic) = No resemblance; more aggressive.
 Mnemonic: PANIC — Pleomorphism, Aneuploidy, Nuclei, Irregular size, Chromosome issues.

3. Altered Metabolism
Key Changes:
o Loss of glycoproteins (cell adhesion).
o Increased mobility and invasion.
o Higher rates of anaerobic glycolysis (less oxygen-dependent).
o Abnormal growth factor receptors (signal independent growth).
Paraneoplastic Syndromes:
o Inappropriate hormone production (e.g., ADH in small cell lung cancer → Hyponatremia).
 Mnemonic: G-MAH — Glycoproteins loss, Mobility, Anaerobic glycolysis, Hormones
(paraneoplastic).

4. Tumor-Specific Antigens
 Markers on Cancer Cells:
o Identify cells as “non-self.”
 Example:
o PSA (Prostate-Specific Antigen) → Prostate Cancer.
 Use:
o Diagnosis
o Monitor Treatment Effectiveness
 Mnemonic: TAG — Tumor-specific, Antigens, Guides for diagnosis.

Memory Tips
1. Hormones: Remember hCG for pregnancy-related tumors (trophoblastic), Calcitonin for the thyroid.
2. Oncofetal: AFP for Liver, CEA for Colon (L-C).
3. Isoenzymes: PAP = Prostate, NSE = Neuro (Lung, Brain).
4. Specific Proteins: PSA = Prostate.
5. Glycoproteins: CA markers by type:
1. CA-125 → Ovarian
2. CA 19-9 → Colon/Pancreas
3. CA 15-3 → Breast
6. Molecular Markers: P53/RAS mutations affect multiple organs.

Hormones
Hormone Cancer(s)
Human Chorionic Gonadotropin Trophoblastic tumors, Non-seminomatous testicular
(hCG) tumor
Calcitonin Medullary carcinoma of the thyroid
 Hormone Cancer(s)
Catecholamines & Metabolites Pheochromocytoma and related tumors
Ectopic Hormones Various cancers with hormone production

Oncofetal Antigens
Antigen Cancer(s)
Alpha-fetoprotein (AFP) Liver cell cancer, Non-seminomatous germ tumors of testis
Carcinomas of the colon, pancreas, lung, stomach, and
Carcinoembryonic Antigen (CEA)
heart

Isoenzymes
Isoenzyme Cancer(s)
Prostatic Acid Phosphatase (PAP) Prostate cancer
Neuron-Specific Enolase (NSE) Small cell lung cancer, Neuroblastoma

Specific Proteins
Protein Cancer(s)
Immunoglobulins Multiple myeloma, Other gammopathies
Prostate-Specific Antigen (PSA) &
Prostate-Specific Membrane Prostate cancer
Antigen

Mucins and Glycoproteins

Marker Cancer(s)
CA-125 Ovarian cancer
CA 19-9 Colon cancer, Pancreatic cancer
CA 15-3 Breast cancer

New Molecular Markers

Mutation Sample Type Cancer(s)
P53, APC, RAS Stool & Serum Colon cancer
P53, RAS Stool & Serum Pancreatic cancer
P53, RAS Sputum & Serum Lung cancer
P53 Urine Bladder cancer

5. Altered Cellular Function

 Cancer cells may lose normal function and:
o Invade nearby tissues.
o Metastasize (spread to distant sites).
 Tumor Growth
Factors Affecting Tumor Growth

1. Cell Cycle Duration

2. Number of Dividing Cells
3. Cell Loss

1. The Cell Cycle

Definition: The process by which cells duplicate their DNA and divide into two daughter cells.
Phases of the Cell Cycle:

Phase Description Duration

G1 (Gap 1) RNA & protein synthesis for DNA replication prep. Hours to days
S (Synthesis) DNA replication occurs 10-20 hours
G2 (Gap 2) Prepares for mitosis (final checks) Hours
Cell division: Prophase, Prometaphase, Metaphase,
M (Mitosis) 30-60 minutes
Anaphase, Telophase
Variable (can be
G0 (Resting) Cells perform normal functions (not dividing)
permanent)

 Mnemonic for Phases: Go, Synthesize, Grow, Multiply!

 G0
 S: Synthesis
 G2
 M: Mitosis

Cell-Cycle Time

 Time for a cell to complete one full cycle (M → M).

 Misconception: Cancer cells don’t always proliferate faster; they proliferate continuously.
 G0 Length: Determines overall cell-cycle time.

Doubling Time

 Definition: Time it takes for a tumor to double in size.

 Growth is Exponential (2 → 4 → 8 → 16...).
 Average Doubling Time:

o Fast-Growing Tumors (e.g., Testicular Cancer): 1 month

o Slow-Growing Tumors (e.g., Prostate Cancer): 1 year
 Molecular Pathogenesis of Cancer

7 Key Changes in Cancer Cells:

1. Self-Sufficiency in Growth Signals (Cells grow without external signals).

2. Insensitivity to Growth-Inhibitory Signals (Ignore “stop” signals).
3. Evasion of Apoptosis (Avoid programmed cell death).
4. Defects in RNA Repair (Increased mutations).
5. Limitless Replication Potential (Immortal cells).
6. Sustained Angiogenesis (Form new blood vessels for nutrients).
7. Ability to Invade and Metastasize (Spread to other tissues).

Mnemonic: SAD LIES

 Self-sufficiency
 Ability to spread (Metastasize)
 Defects in RNA repair
 Limitless replication
 Insensitivity
 Evasion of apoptosis
 Sustained Angiogenesis

Quick Review Summary

1. Tumor Growth Factors: Cell cycle duration, dividing cells, cell loss.
2. Cell Cycle Phases: G1 → S → G2 → M (G0 = Resting).
3. Doubling Time: Exponential growth; varies by tumor type.
4. Cancer Pathogenesis: 7 fundamental changes (Mnemonic: SAD LIES ).

Cancer Assessment & Screening Guidelines

Breast Cancer Screening
Mammogram:
o Starting Age: 40
o Frequency: Every year
o Stopping Age: Individualized based on health and longevity.
Clinical Breast Exam (CBE):
o Ages 20-39: Every 3 years
o Age 40+: Every year
High-Risk Individuals:
o Examples: Family history, genetic factors, past breast cancer
o Consider: Earlier mammography, breast ultrasound, MRI, or more frequent exams.
Mnemonic: “40 for Mammos, 20-30s Every 3, 40+ Every Year”

Colon & Rectal Cancer Screening

 Starting Age: 50 (men and women)
  Screening Options:

Test Frequency
FOBT/FIT Every year
Flexible Sigmoidoscopy (FSIG) Every 5 years
FOBT/FIT + FSIG Every year + every 5 years
Double-Contrast Barium Enema Every 5 years
Colonoscopy Every 10 years
 High-Risk Individuals: Consult a doctor for a personalized schedule.
Mnemonic: “50 Starts Screening; 5 or 10-Year Options”

Prostate Cancer Screening

Starting Age:
o Average Risk: 50
o High Risk (African American men, strong family history): 45

Tests:
o PSA Test or Digital Rectal Exam (DRE)
o Frequency: Annually

Informed Decision: Understand benefits and limitations before screening.

Mnemonic: “50 or 45 for Prostate Check”

Uterine Cancer Screening

Cervical Cancer
Starting Age: 3 years after first intercourse or by age 21
Frequency:
o Pap Test: Every year
o Liquid-Based Test: Every 2 years
After Age 30:
o If 3 Normal Tests: Screen every 2-3 years
o HPV + Cytology: Every 3 years
Stopping Age:
o 70+ Years: Stop if 3 normal Pap tests in the past 10 years
o After Hysterectomy: No screening unless due to cervical cancer.
Mnemonic: “21 to Start, 30 for 3-Year Rule, 70 to Stop”
Endometrial Cancer
Menopause:
o Discuss risks and symptoms.
o Report unexpected bleeding/spotting.
High Risk (HNPCC):
o Annual Biopsy starting at age 35.
Mnemonic: “Menopause Means Monitor; 35 Biopsy for High Risk”

Cancer-Related Check-Up
 Include:
o Thyroid
o Oral Cavity
o Skin
o Lymph Nodes
o Testes & Ovaries
Frequency: During regular health exams (based on age/gender).

Quick Recap Mnemonics

1. Breast: “40 for Mammos”
2. Colon: “50 Starts Screening”
3. Prostate: “50 or 45 for Prostate Check”
4. Cervical: “21 to Start, 30 for 3-Year Rule”
5. Endometrial: “Menopause Means Monitor”