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First Aid > Pathology - Neoplasia > Flashcards

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
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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.
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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).
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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).
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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.
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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.
  • 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
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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
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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).
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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.
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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
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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
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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 Ž–> 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
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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 Ž–> 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 Ž–> 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)
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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.
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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.
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16
Q

Cancers associated with these oncogenic microbes

  • EBV
  • HBV, HCV
  • HHV-8
  • HPV
  • H. pylori
  • HTLV-1
  • Liver fluke (Clonorchis sinensis)
  • Schistosoma haematobium
A
  • EBV
    • Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, CNS lymphoma (in immunocompromised patients)
  • HBV, HCV
    • Hepatocellular carcinoma
  • HHV-8 (Kaposi sarcoma–associated herpesvirus)
    • Kaposi sarcoma, body cavity fluid B-cell lymphoma
  • HPV
    • Cervical and penile/anal carcinoma (16, 18), head and neck or throat cancer
  • H. pylori
    • Gastric adenocarcinoma and MALT lymphoma
  • HTLV-1
    • Adult T-cell leukemia/lymphoma
  • Liver fluke (Clonorchis sinensis)
    • Cholangiocarcinoma
  • Schistosoma haematobium
    • Bladder cancer (squamous cell)
17
Q

Carcinogens

  • For each
    • Organ –> Impact
  • Aflatoxins (Aspergillus)
  • Alkylating agents
  • Aromatic amines (e.g., benzidine, 2-naphthylamine)
  • Arsenic
  • Asbestos
  • Carbon tetrachloride
A
  • Aflatoxins (Aspergillus)
    • Liver –> Hepatocellular carcinoma
  • Alkylating agents
    • Blood –> Leukemia/lymphoma
  • Aromatic amines (e.g., benzidine, 2-naphthylamine)
    • Bladder –> Transitional cell carcinoma
  • Arsenic
    • Liver –> Angiosarcoma
    • Lung –> Lung cancer
    • Skin –> Squamous cell carcinoma
  • Asbestos
    • Lung –> Bronchogenic carcinoma > mesothelioma
  • Carbon tetrachloride
    • Liver –> Centrilobular necrosis, fatty change
18
Q

Carcinogens

  • For each
    • Organ –> Impact
  • Cigarette smoke
  • Ethanol
  • Ionizing radiation
  • Nitrosamines (smoked foods)
  • Radon
  • Vinyl chloride
A
  • Cigarette smoke
    • Bladder –> Transitional cell carcinoma
    • Esophagus –> Squamous cell carcinoma/adenocarcinoma
    • Kidney –> Renal cell carcinoma
    • Larynx –> Squamous cell carcinoma
    • Lung –> Squamous cell and small cell carcinoma
    • Pancreas –> Pancreatic adenocarcinoma
  • Ethanol
    • Liver –> Hepatocellular carcinoma
  • Ionizing radiation
    • Thyroid –> Papillary thyroid carcinoma
  • Nitrosamines (smoked foods)
    • Stomach –> Gastric cancer
  • Radon
    • Lung –> Lung cancer (2nd leading cause after cigarette smoke)
  • Vinyl chloride
    • Liver –> Centrilobular necrosis, fatty change
19
Q

Paraneoplastic syndromes

  • For each
    • Effect
    • Neoplasm(s)
  • 1,25-(OH)2 D3 (calcitriol)
  • ACTH
  • ADH
  • Antibodies against presynaptic Ca2+ channels at NMJ
  • Erythropoietin
  • PTHrP
A
  • 1,25-(OH)2 D3 (calcitriol)
    • Effect: Hypercalcemia
    • Neoplasm(s): Hodgkin lymphoma, some non-Hodgkin lymphomas
  • ACTH
    • Effect: Cushing syndrome
    • Neoplasm(s): Small cell lung carcinoma
  • ADH
    • Effect: SIADH
    • Neoplasm(s): Small cell lung carcinoma and intracranial neoplasms
  • Antibodies against presynaptic Ca2+ channels at NMJ
    • Effect: Lambert-Eaton myasthenic syndrome (muscle weakness)
    • Neoplasm(s): Small cell lung carcinoma
  • Erythropoietin
    • Effect: Polycythemia
    • Neoplasm(s): Renal cell carcinoma, thymoma, hemangioblastoma, hepatocellular carcinoma, leiomyoma, pheochromocytoma
  • PTHrP
    • Effect: Hypercalcemia
    • Neoplasm(s): Squamous cell lung carcinoma, renal cell carcinoma, breast cancer
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
    • ƒƒMeningioma
    • ƒƒMalignant mesothelioma
21
Q

Cancer epidemiology

  • Incidence (top 3)
    • Male
    • Female
    • Notes
  • Mortality (top 2)
    • Male
    • Female
    • Notes
A
  • Incidence
    • Male
      • Prostate (32%)
      • Lung (16%)
      • Colon/rectum (12%)
    • Female
      • Breast (32%)
      • Lung (13%)
      • Colon/rectum (13%)
    • Notes
      • Lung cancer incidence has dropped in men, but has not changed significantly in women.
  • Mortality
    • Male
      • Lung (33%)
      • Prostate (13%)
    • Female
      • Lung (23%)
      • Breast (18%)
    • Notes
      • Cancer is the 2nd leading cause of death in the United States (heart disease is 1st).
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.

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