Pathology- Neoplasia Flashcards

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1
Q

Hallmarks of cancer:

A

evasion of apoptosis, growth signal self-sufficiency, anti-growth signal insensitivity, Warburg effect (shift of glucose metabolism away from mitochondria toward glycolysis), sustained angiogenesis, limitless replicative potential, tissue invasion, and metastasis.

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2
Q

neoplastic progression

A
  • Normal cells
  • Dysplasia
  • Carcinoma in situ/preinvasive: irreversible dysplasia that involves the entire thickness of epithelium but does not penetrate the intact basement membrane.
  • Invasive carcinoma: Cells have invaded basement membrane using collagenases and hydrolases (metalloproteinases). Cell-cell contacts lost by inactivation of E-cadherin.

Metastasis

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3
Q

Tumor nomenclature

A

Carcinoma implies epithelial origin, whereas sarcoma denotes mesenchymal origin. Both terms generally imply malignancy.

Benign tumors are usually well differentiated, well demarcated, low mitotic activity, no metastasis,
no necrosis.

Malignant tumors may show poor differentiation, erratic growth, local invasion, metastasis, and decrease apoptosis. Upregulation of telomerase prevents chromosome shortening and cell death.

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4
Q

Terms for non-neoplastic malformations include

A

hamartoma (disorganized overgrowth of tissues in
their native location, eg, Peutz-Jeghers polyps).

choristoma (normal tissue in a foreign location,
eg, gastric tissue located in distal ileum in Meckel diverticulum).

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5
Q

Cell type neoplasia

  • Epithelium
  • Mesenchyme
A

Benign: Adenoma, papilloma
Malign: Adenocarcinoma, papillary carcinoma.

Benign: Hemangioma, osteoma, fibroma, lipoma, leiomyoma, rhabdomyoma, nevos/mole
Malign: Angiosarcoma, osteosarcoma, fibrosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, melanoma.

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6
Q

Tumor grade vs stage

A

Grade: Degree of cellular differentiation and mitotic
activity on histology. Range from low grade to high grade.

Degree of localization/spread based on site and size of 1° lesion, spread to regional lymph nodes, presence of metastases. (TNM)

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7
Q

Tumor

  • Diferentiation
  • Anaplasia
A

degree to which a tumor resembles its tissue of origin.

complete lack of differentiation of cells in a malignant neoplasm.

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8
Q

Paraneoplastic syndromes

- Musculoskeletal and cutaneous

A

Dermatomyositis
Acanthosis nigricans
Sign of Leser-Trélat
Hypertrophic osteoarthropathy

*pag. 221

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9
Q

Paraneoplastic syndromes

- Endocrine

A

Hypercalcemia
Cushing syndrome
Hyponatremia (SIADH)

*pag. 221

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10
Q

Paraneoplastic syndromes

- Hematologic

A
Polycythemia
Pure red cell aplasia
Good syndrome
Trousseau syndrome
Nonbacterial thrombotic (marantic) endocarditis

*pag. 221

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11
Q

Paraneoplastic syndromes

- Neuromuscular

A
Anti-NMDA receptor encephalitis
Opsoclonusmyoclonus ataxia syndrome
Paraneoplastic cerebellar degeneration
Paraneoplastic encephalomyelitis
Lambert-Eaton myasthenic syndrome
Myasthenia gravis

*pag. 221

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12
Q

Oncogenes

  • ALK
  • BCR-ABL
  • BCL-2
  • BRAF
  • c-KIT
A

Receptor tyrosine Kinase. Lung Adenocarcinoma (Adenocarcinoma of the Lung Kinase)

Tyrosine kinase. CML, ALL

Antiapoptotic molecule (inhibits apoptosis). Follicular and diffuse large B cell lymphomas

Serine/threonine kinase. Melanoma, non-Hodgkin lymphoma, papillary thyroid carcinoma.

Cytokine receptor. Gastrointestinal stromal tumor (GIST)

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13
Q

Oncogenes

  • c-MYC
  • HER2/neu (c-erbB2)
  • JAK2
  • KRAS
  • MYCL1
  • N-myc (MYCN)
  • RET
A

Transcription factor. Burkitt lymphoma

Receptor tyrosine kinase. Breast and gastric carcinomas

Tyrosine kinase. Chronic myeloproliferative disorders

GTPase. Colon cancer, lung cancer, pancreatic cancer

Transcription factor. Lung tumor

Transcription factor. Neuroblastoma

Receptor tyrosine kinase MEN 2A and 2B, papillary thyroid carcinoma

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14
Q

Tumor suppressor genes

  • APC
  • BRCA1/BRCA2
  • CDKN2A
  • DCC
  • SMAD4 (DPC4)
A

Negative regulator of β-catenin/WNT pathway. Colorectal cancer (associated with FAP).

DNA repair protein. Breast, ovarian, and pancreatic cancer

p16, blocks G1, S phase. Melanoma, pancreatic cancer

DCC—Deleted in Colon Cancer

DPC—Deleted in Pancreatic Cancer

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15
Q

Tumor suppressor genes

  • MEN1
  • NF1
  • NF2
  • PTEN
  • Rb
A

Menin. Multiple Endocrine Neoplasia 1

Neurofibromin (Ras GTPase activating protein). Neurofibromatosis type 1.

Merlin (schwannomin) protein. Neurofibromatosis type 2

Negatively regulates PI3k/AKT pathway. Breast, prostate, and endometrial cancer

Inhibits E2F; blocks G1 Ž S phase. Retinoblastoma, osteosarcoma

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16
Q

Tumor suppressor genes

  • TP53
  • TSC1
  • TSC2
  • VHL
  • WT1
A

p53, activates p21, blocks G1 Ž S phase. Most human cancer, SBLA cancer syndrome: Sarcoma, Breast, Leukemia, Adrenal gland.

Hamartin protein. Tuberous sclerosis

Tuberin protein. Tuberous sclerosis

Inhibits hypoxia inducible factor 1a. von Hippel-Lindau disease.

Transcription factor that regulates urogenital development. Wilms tumor (nephroblastoma)

17
Q

Oncogenic microbes

  • EBV
  • HBV, HCV
  • HHV-8
  • Schistosoma haematobium
A

Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, 1° CNS lymphoma.

Hepatocellular carcinoma

Kaposi sarcoma

Bladder cancer (squamous cell)

18
Q

Oncogenic microbes

  • HPV
  • H pylori
  • HTLV-1
  • Liver fluke (Clonorchis sinensis)
A

Cervical and penile/anal carcinoma (types 16, 18), head and neck cancer.

Gastric adenocarcinoma and MALT lymphoma

Adult T-cell leukemia/lymphoma

Cholangiocarcinoma

19
Q

Carcinogens (Exposure and neoplasia)

  • Aflatoxins (Aspergillus)
  • Alkylating agents
  • Aromatic amines (eg, benzidine, 2-naphthylamine)
  • Arsenic
  • Asbestos
A

Stored grains and nuts. Hepatocellular carcinoma

Oncologic chemotherapy. Leukemia/lymphoma

Textile industry (dyes), cigarette smoke (2-naphthylamine). Bladder Transitional cell carcinoma.

Herbicides (vineyard workers), metal smelting. Angiosarcoma, Lung cancer, Squamous cell carcinoma (skin)

Old roofing material, shipyard workers. Bronchogenic carcinoma > mesothelioma

20
Q

Carcinogens (neoplasia)

- cigarrete

A

Transitional cell carcinoma (bladder)
Squamous cell carcinoma (cervix)
Squamous cell carcinoma/ adenocarcinoma(esophagus)
Renal cell carcinoma
Squamous cell carcinoma (larynx)
Squamous cell and small cell carcinoma (lung)
Pancreatic adenocarcinoma

21
Q

Carcinogens (Exposure and neoplasia)

  • Ethanol
  • Ionizing radiation
  • Nitrosamines
  • Radon
  • Vinyl chloride
A

Squamous cell carcinoma (esophagus), Hepatocellular carcinoma.

Papillary thyroid carcinoma

Smoked foods. Gastric cancer

By-product of uranium decay, accumulates in basements. Lung cancer (2nd leading cause after cigarette smoke).

Used to make PVC pipes (plumbers). Angiosarcoma

22
Q

Psammoma bodies

A

Laminated, concentric spherules with dystrophic calcification

PSaMMoma bodies are seen in:
ƒƒ Papillary carcinoma of thyroid
ƒƒ Serous papillary cystadenocarcinoma of ovary
ƒƒMeningioma
ƒƒMalignant Mesothelioma
23
Q

Serum tumor markers

  • Alkaline phosphatase
  • α-fetoprotein
  • β-hCG
A

Metastases to bone or liver, Paget disease of bone, seminoma (placental ALP).

HE-MAN: Hepatocellular carcinoma, Endodermal sinus
(yolk sac) tumor, Mixed germ cell tumor, Ataxia-telangiectasia, Neural tube defects. *low levels
associated with Down syndrome.

“hCG”: Hydatidiform moles and Choriocarcinomas
(Gestational trophoblastic disease), testicular cancer, mixed germ cell tumor.

24
Q

Serum tumor markers

  • CA 15-3/CA 27-29
  • CA 19-9
  • CA 125
  • Calcitonin
A

Breast cancer.

Pancreatic adenocarcinoma.

Ovarian cancer

Medullary thyroid carcinoma (alone and in MEN2A, MEN2B).

25
Q

Serum tumor markers

  • CEA
  • Chromogranin
  • LDH
  • PSA
A

Major associations: colorectal and pancreatic cancers.
Minor associations: gastric, breast, and medullary thyroid carcinomas.

Neuroendocrine tumors.

Testicular germ cell tumors, ovarian dysgerminoma, other cancers. *Can be used as an indicator of tumor burden.

Prostate cancer. *Can also be elevated in BPH and prostatitis.

26
Q

P-glycoprotein

A

Also known as multidrug resistance protein 1 (MDR1). Classically seen in adrenocortical carcinoma but also expressed by other cancer cells (eg, colon, liver).

27
Q

Important immunohistochemical stains

  • Vimentin
  • S-100
  • DesMin
  • Cytokeratin
A

Mesenchymal tumors but also other tumors (endometrial carcinoma, renal cell carcinoma, meningioma).

Melanoma, schwannoma, Langerhans cell histiocytosis.

Muscle tumors

Epithelial tumors (eg, squamous cell carcinoma)

28
Q

Important immunohistochemical stains

  • GFAP
  • Neurofilament
  • PSA
  • TRAP (Tartrate-resistant acid phosphatase)
  • Chromogranin and synaptophysin
A

Astrocytoma, Glioblastoma

Neuronal tumors (eg, neuroblastoma)

Prostate cancer

Hairy cell leukemia

Small cell carcinoma of the lung, carcinoid tumor

29
Q

Cancer incidence

Men

A
  1. Prostate
  2. Lung
  3. Colon/rectum
30
Q

Cancer incidence

Women

A
  1. Breast
  2. Lung
  3. Colon/rectum
31
Q

Cancer incidence

Children (age 0-14)

A
  1. Leukemia
  2. CNS
  3. Neuroblastoma
32
Q

Cancer mortality

Men

A
  1. Lung
  2. Prostate
  3. Colon/rectum
33
Q

Cancer mortality

Women

A
  1. Lung
  2. Breast
  3. Colon/rectum
34
Q

Cancer mortality

Children (0-14)

A
  1. Leukemia
  2. CNS
  3. Neuroblastoma
35
Q

2nd leading cause of death in USA

A

Cancer is the 2nd leading cause
of death in the United States
(heart disease is 1st).

36
Q

Common metastases

A

sarcomas spread hematogenously; most carcinomas spread via lymphatics.

"Four Carcinomas Route Hematogenously"
Follicular thyroid carcinoma, 
Choriocarcinoma, 
Renal cell carcinoma, 
Hepatocellular carcinoma.
37
Q

Brain metastasis

A

Lung > breast > melanoma, colon, kidney.

*50% of brain tumors are from metastases

38
Q

Liver metastasis

A

Colon&raquo_space; stomach > pancreas.

+Liver and lung are the most common sites of metastasis after the regional lymph nodes.

39
Q

Bone metastais

A

Prostate, Breast > Kidney, Thyroid, Lung.
“lead (PB) KeTtLe.”

Common mets to bone: breast (mixed), lung (lytic), thyroid (lytic), kidney (lytic), prostate (blastic).