Which are more differentiated, benign or malignant neoplasms?
Benign neoplasms (they more closely resemble normal tissue)
Teratoma
Can be benign or malignant, arises from germ cells and contains derivatives from different germ layers
Adenomas
Beign epithelial tumors
Hamartoma
Disorganized tissue components, not a true neoplasm
Carcinoma
Malignant tumor derived from epithelial cells
Sarcoma
Malignant tumor derived from mesenchymal cells
Anaplasia
Dedifferentiation, a hallmark of malignancies
Pleomorphism
Variation between cells in overall size and nuclear morphology
Some frequently utilized tumor markers
PSA, Cytokeratin (epithelial cells), Vimentin (mesenchymal cells), Leukocyte common antigen/CD45 (hematopoietic cells), alpha-fetoprotein (liver cancer and germ cell tumors), carcinoembryonic antigen (GI and breast cancers)
Common sites of hematogenous metastasis
Lungs, liver, brain, bone marrow, adrenal glands
What tumor cell molecules aid in the process of local infiltration?
Proteolytic enzymes (e.g. collagenases) and cytokines
What does neoplasm grading assess?
Degree of anaplasia and proliferative capacity
What does neoplasm staging assess?
Extent of local growth and distant spread of a malignant tumor
TMN cancer staging system
Primary tumor size and extent of local invasion (T), presence or absence of lymph node (N) or distant metastases (M)
Paraneoplastic syndrome
Symptoms not directly attributable to tumor invasion
What symptom is a frequent manifestation of cancer and why?
Fever, because tumor cells release pyrogens as do responding inflammatory cells
Wasting syndrome
Seen in cancers, characterized by anorexia, weight loss, cachexia (due to TNF and other cytokines)
What paraneoplastic syndromes are most commonly seen with small cell carcinoma of the lung?
Cushing syndrome (ACTH) and inappropriate antidiuresis (ADH)
What paraneoplastic syndrome commonly arises in patients with squamous cell carcinoma of the lung?
Hypercalcemia due to synthesis of a PTH-like molecule
What paraneoplastic syndromes are common in germ cell tumors?
Precocious puberty, gynecomastia, oligmenorrhea (excess gonadotropins)
Common neuromuscular paraneoplastic symptoms
Subacute motor neuropathy (LMN weakness), ALS, sensorimotor peripheral neuropathy, dermatomyositis, polymyositis
Eaton-Lambert syndrome
A myasthenia-like disorder, strongly linked to small cell lung carcinoma
What paraneoplastic syndrome is commonly associated with renal cell carcinoma?
Polycythemia (erythtrocytosis) due to excess synethesis of erythropoietin by the tumor
Trousseau syndrome
Thrombosis secondary to pancreatic carcinoma
What paraneoplastic syndrome is commonly seen with metastatic mucin-producing adenocarcinomas and acute promyelocytic leukemia?
Disseminated Intravascular Coagulation (DIC)
What is the most frequent cause of cancer death in the US?
Cancer of the lung
Behind lung cancer, what tumors are frequently seen in men?
Colorectal and prostatic carcinomas
Behind lung, what other tumors are commonly seen in women?
Breast and colorectal carcinomas
List the infectious agent associated with each: cervical cancer, lymphoma, vascular tumor, hepatocellular carcinoma
HPV, EBV, HHV (Human Herpes Virus), Hep B/C
Acromegaly
Excess GH production, can be a paraneoplastic syndrome
Acanthosis nigricans
Brown to black hyperpigmentation of the skin (typically in body folds), can be a paraneoplastic syndrome
Leser-Trelat sign
Multiple seborrheic keratoses (pigmented skin lesions), can be a paraneoplastic syndrome
What phosphorylates Rb and what is the effect of this?
CDKs, the result is release of E2F which increases production of proteins that drive cell through S phase
What family of proteins are p16INK4A and p21WAF1/CIP1?
CKIs (inhibit cell cycling)
What type of proteins are MSH2 and MLH1?
DNA mismatch repair proteins
3 major DNA repair pathways
Mismatch repair, base excision repair, double-strand break repair
DNA damage activates what proteins?
ATM and ATR (which activate p53)
80% of human tumors have high levels of what?
Telomerase
What causes chronic myelogenous leukemia?
Translocation of the ends of the long arms of chromosomes 9 and 22 creating a fusion protein (BRC-ABL)
What is the most common genetic abnormality among human cancers?
Mutant p53
Why is p53 haploinsufficient (ie dominant negative)?
Because it is a tetramer which requires all four subunits to be functional
What does PTEN do?
Converts PIP3 to PIP2
What DNA modification may lead to activation of tumor viruses?
DNA methylation
What histone modification leads to a decrease in gene expression?
Histone deactylation
Cause of malignant lymphoma
Chromosomal rearrangement (t(14:8)) that leads to overexpression of Bcl-2 (anti-apoptotic)
TGF-beta
A short-acting cytokine that tends to suppress tumor development (but can be used by tumor cells to evade host defenses)
Between clonal and heterogenous tumors, which is typically malignant?
Clonal
What allows cancer stem cells to escape chemotherapy
A low mitotic rate
What family of enzymes (among others) do tumor cells use to penetrate basement membranes?
Matrix Metalloproteinases (MMPs)
Invadopodia
Protrusions from tumors which they use to penetrate basement membranes
The only known human tumor virus that is an oncoretrovirus
Human Thymus-Leukemia Virus 1 (HTLV-1)
Most viruses that cause human cancers are what kind of viruses?
DNA viruses
Which HPV serotypes contain major oncoproteins
16, 18, 31, 33, and 35
Which HPV serotypes are common but not cancerous?
6 and 11
What are the major oncoproteins of HPV and what does each do?
E5 activates epidermal growth factor receptor, E6 inactivates p53, E7 inactivates Rb
Besides cancers of the cervix, what cancers do HPV cause?
Squamous carcinomas of the male genital tract, oral cavity, and pharynx
What type of virus is EBV?
A human Herpesvirus
What does EBV do?
Infects and transforms B lymphocytes
What are two main EBV proteins and what does each do?
Nuclear antigen (EBNA) helps maintain viral activity, and Latency-associated Membrane Proteins (LMPs) affect TNF receptor signaling
What cancers is EBV associated with?
Malignant lymphoma (think Africa), Burkitt lymphoma, Hodgkin lymphoma (nasopharyngeal carcinomas), and also lymphoproliferative disorders
What type of virus is hepatitis?
Hep B is a DNA virus, Hep C is a RNA virus
Chronic infection is the rule for one hepatitis virus and the exception for the other, which is which?
Chronic infection is the rule for HCV and the exception for HBV
How might HBV and HCV infections lead to hepatocellular carcinomas?
Repeated cell division leading to mutation, and/or HBV X-protein might inactivate p53 (HCV might also manipulate NFkB)
What cancer does Human Herpesvirus 8 cause?
A vascular tumor called Kaposi sarcoma (KS)
What patient population is HHV8 infection common in?
HIV positive patients
How does HHV8 cause cancer?
It encodes proteins that inactivate p53 and Rb
What type of cells does HTLV-1 infect?
Certain T lymphocytes
How does HTLV-1 cause cancer?
One of its proteins (Tax) promotes cell division and decreases production of p53