Introduction to Neoplasia Flashcards by Camelita Thrift

Neoplasia

New tissue growth that is unregulated, irreversible, and monoclonal

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What determines the clonality of B lymphocytes?

Immunoglobulin light chain phenotype

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Benign vs malignant tumors of the epithelium

Benign

Adenoma
Papilloma

Malignant

Adenocarcinoma
Papillary carcinoma

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Benign vs malignant tumors of mesenchyme

Benign

Lipoma

Malignant

Liposarcoma

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Benign vs malignant lymphocyte

Benign

Does not exist

Malignant

Lymphoma/Leukemia

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Benign vs malignant tumor of melanocyte

Benign

Nevus (mole)

Malignant

Melanoma

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What is the purpose of the hemoccult test?

Tests for occult blood in stool. It along with a colonoscopy can be used to detect colonic adenoma before it becomes colonic carcinoma or carcinoma before it spreads

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Ras can be considered a possible oncogene. By what mechanism?

Mutated ras inhibits the activity of GTPase activating protein. This prolongs the activated state of ras, resulting in increased growth signals
- ras bound to GDP is inactive, ras bound to GTP is active

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Carcingogenic agent: Aflatoxins

hepatocellular carcinoma

Derived from Aspergillus, which can contaminate stored rice and grains

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Carcingogenic agent: Alkylating agents

Leukemia/Lymphoma

Side effect of chemotherapy

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Carcingogenic agent: Alcohol

Squamous cell carcinoma of oropharynx and upper esophagus, and hepatocellular carcinoma

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Carcingogenic agent: Arsenic

Squamous cell carcinoma of skin, lung cancer, and angiosarcoma of liver

NOTE: Arsenic is present in cigarette smoke

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Carcingogenic agent: Asbestos

Lung carcinoma and mesothelioma

Exposure to asbestos is more likely to lead to lung cancer than mesothelioma

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Carcingogenic agent: Cigarette smoke

Carcinoma of oropharynx, esophagus, lung, kidney, bladder, and pancreas

Most common carcinogen worldwide; polycyclic hydrocarbons are particularyl carcinogenic

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Carcingogenic agent: Nitrosamines

Stomach carcinoma

Found in smoked foods; responsible for high rate of stomach carcinoma in Japan

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Carcingogenic agent: Naphtylamine

Urothelial carcinoma of cladder

Derived from cigarette smoke

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Carcingogenic agent: Vinyl chloride

Angiosarcoma of liver

Occupational exposure; used to make polyvinyl chloride for use in pipes

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Carcingogenic agent: Nickel, chromium, beryllium, or silica

Lung carcinoma

Occupational exposure

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Carcingogenic agent: EBV

Nasopharyngeal carcinoma, Burkitt lymphoma, and CNS lymphoma in AIDS

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Carcingogenic agent: HHV-8

Kaposi sarcoma

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Carcingogenic agent: HBV and HCV

Hepatocellular carcinoma

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Carcingogenic agent: HTLV-1

Adult T- cell leukemia/lymphoma

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Carcingogenic agent:High risk HPV(16,18,31,33)

Squamous cell carcinoma of vulva, vagina, anus, and cervix; adenocarcinoma of cervix

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Overexpression of which growth factor is associated with astrocytoma?

PDGFB

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Amplification of which growth factor receptor is associated with a subset of breast carcinomas?

ERBB2 (HER2/neu)

A point mutation of which growth factor receptor is associated with MEN 2A, MEN2B, and sporadic medullary carcinomas of thyroid?

RET

A point mutation of which growth factor receptor is associated with gastrointestinal stromal tumor?

KIT

Point mutation of which signal trasnducer is associated with carcinomas, melanoma, and lymphoma?

RAS gene family

A translocation of (9,12) with BCR of which signal transducer is associated with CML and some types of ALL?

ABL

A translocation at (8,14) involving IgH and what nuclear regulator is associated with Burkitt lymphoma?

c-MYC

An amplifiction of which nuclear regulator is associated with neuroblastoma?

N-MYC

An amplification of which nuclear regulator is associated with lung carcinoma (small cell)?

L-MYC

Translocation at (11;14) involvign IgH and which cell cycle regulator is associated with mantle cell lymphoma?

CCND1 (cyclin D1)

Amplification of which cell cycle regulator is associated with melanoma?

CDK4

How does p53 induce apoptosis?

* p53 upregulates BAX which disrupts Bcl2. * Cytochrome c leaks from the mitochondria activating apoptosis **NOTE:** Both copies of the p53 gene must be knocked out for tumor formation

Li-Fraumeni syndrome

* Link to _germline_ mutations in the p53 gene * Characterized by a propensity to develop multiple types of carcinomas and sarcomas

How does Rb regulate the progression from G1 to S phase?

* Rb holds the E2F transcription factor, which necessary for transition to the S phase * E2F is released when Rb is phosphorylated by CDK4 **NOTE:** Rb mutation results in constritutively free E2F, allowing progression through the cell cycle and uncontrolled growth of cells

Germline vs sporaadic mutation of Rb

**Germline** * Familial retinoblastoma * _Bilateral_ retinoblastoma and osteosarcoma **Sporadic** * _Unilateral_ retinoblastoma

Bcl2 is overexpressed in follicular carcinoma. By what mechanism does this take place?

* t(14,18) moves Bcl2 (chromosome 18) to the IgH (chromosome 14), resulting in increased Bcl2 * Because upregulation Bcl2 increases stability of the mitochondrial membrane. B cells that are supposed to apoptosed during **somatic hypermutation** in the lymh node germinal center accumulate, leading to lymphome

What is the mechanism by which tumor cells invade and spread?

* tumor cells are normally attached to each other by E-cadherin * Downregulation of E-cadherin leads to dissociation * Cells attach to **laminin** and destroy the basement membrane (collagen IV) via **collagenase** * Cells attach to **fibronectin** in the extracellular matrix and spread locally * Entrance into vascular or lymphatic spaces allows for metastisis

Lymphatic spread is characteristic of \_\_\_\_\_\_\_\_\_\_.

Carcinomas

Hematogenous spread is characteristic of \_\_\_\_\_\_\_\_. What are the exceptions?

Sarcomas **Exceptions:** * Renal cell carcinoma (often invades renal vein) * Hepatocellular carcinoma (often invades hepatic vein) * Follicular carcinoma of the thyroid * Choriocarcinoma (tumorous trophoblast cells)

Seeding of body cavities is characteristic of \_\_\_\_\_\_\_\_\_\_\_.

Ovarian carcinoma, which often involvs the peritoneum

Benign vs malignant tumors (characteristics)

**Benign** * Slow growing * Well circumscribed * Distinct * Mobile **Malignant** * ****Rapidly growing * Poorly circumscribed * Infiltrative * Fixed **NOTE:** A biopsy or excision is generally required before a tumor can be classified as benign or malignant

What immunohistochemical stain is used to target prostatic epithelium?

PSA

What immunohistochemical stain is used to target breast epithelium?

What immunohistochemical stain is used to target thyroid follicular cells?

Thyroglobulin

What immunohistochemical stain is used to target neuroendocrine cells?

Chromogranin

What immunohistochemical stain is used to target melanoma, Schwannoma and Langerhans cell histiocytosis?

S-100

Grading of cancer

* Well-differentiated (low grade)- resmebles normal parent tissue * Poorly differentied (high grade)- does not resemble parent tissue ## Footnote **Important for determining prognosis**

Staging of cancer

* Assessment of size and spread of a cancer * Key prognostic fact; more important than grade * System: * T- tumor (size and /or depth of invasion) * N- spread to regional lymph nodes * M-metastasis; **single most important prognostic factor**

Mutation of signal transducer JAK2 causes\_\_\_\_\_\_\_\_\_\_.

Polycythemia Vera (a slow-growing blood cancer in which your bone marrow makes too many red blood cells)

Mutation of DNA mismatch repaire genes MLH and MSH cause \_\_\_\_\_\_\_\_\_\_\_\_\_\_.

Sporadic colon cancer Hereditary- HNPCC (Lynch syndrome)

A DNA breaks in BRCA1 and BRCA2 can cause\_\_\_\_\_\_\_\_\_\_.

Hereditary breat/ovarian cancer

Tumors from what sites are likely to metastisis in the liiver and lungs

**All** portal and vena cava blood pass through

Steps to Invasion and metastasis

1. Detachement (E-cadherin) 2. Degradation of basement membrane * Matrix metaloproteinase, collagenase 3. Attach to ECM, migrate 4. Vascular dissemination and homing * Enter and leave blood vessels- break basement membrene-adhere to endothelium * Homing vascular bed/lymphatic drainage

What are the frequent sites of hematogenous spread?

Liver, lungs, bone

Tumors from what sites are likely to metastisis in the bone?

From prosate, breast, kidney, thyroid, and lung

Where do metastisis in the brain come from?

Lung, breast, melanoma

Where do metastisis in the adrenal gland come from?

Lung and breast

Virchow node

Supraclavicular lymph node- from **gastric carcinoma**

Krukenberg tumor

Metastasis to ovary from gastric

Analine dyes (naphytlamine) are associated with what type of cancer?

Urothelial carcinoma (bladder) \*Found in dye and rubber

What neoplasias are associated with hypercarcemia?

Lung squamous cell carcinoma, breast carcinoma

What neoplasias are associated with Cushing's syndrome?

Lung small cell carcinoma

What neoplasias are associated with syndrome of inappropriate ADH secretion?

Lung small cell carcinoma **Symptoms:** Headache, confusion, gait disturbance, nausea, cramps, hyponatremia, increased urine osmolality

What neoplasias are associated with polycythemia?

Renal cell carcinoma, pheochromcytoma, hepatocellular carcinoma, hemagioblastoma **Symptoms:** Increased erythropoietin, elevated hemoglobin and hematocrit, facial redness, headache

What neoplasias are associated with acanthosis nigrans?

Gastric carcinoma

What neoplasias are associated with dermatomyositis?

Breast, ovary, lung

What neoplasias are associated with Leser-Trelat syndrome?

GI malignancy

What neoplasias are associated with hypertrophic osteoarthropathy?

Lung cell carcinoma **Symptom:** Finger clubbing

What neoplasias are associated with myasthenia gravis?

Thymoma

What neoplasias are associated with Lambert-Eaton?

Small cell lung cancer

What neoplasias are associated with migratory thromboplebitis?

Pancreatic carcinoma

What neoplasias are associated with DIC?

Acute promyeloctyic leukemia

What neoplasias are associated with pure red cell aplasia?

Thymoma

What neoplasias are associated with nonbacterial thrombotic endocarditis?

Pacreatic adenocarcinoma

a- fetoprotein (serum marker)

* High levels associared with neural tube and abdominal wall defects * Low levels associated with Down syndrome * Hepatocellular carcinoma * Endodermal sinus tumor

hCG

* Hydatidiform moles * Choriocarcinomas

CA 19-9

Pancreatic adenocarcinoma

CA 125

Ovarian cancer

CEA

Major associations * Colorectal and pancreatic cancers Minor associations * Gastric, breast, and medullary thyroid carcinomas

Target therapy for breast carcinoma

* Anti-estrogen- Tamoxifen * Anti-HER2NEU receptor- Herceptin

Targeted therapy for chronic myeloid leukemia

Tyrosine kinase inhibitor- Imatinib

Targeted therapy for lung carcinoma

Anti-EGFR Checkpoint inhibitors (PD1)

Targeted therapy for melanoma

Anti-BRAF

Targeted therapy for lymphoma

Anti CD20 (Rituximab)