3. Neoplasia - BP Flashcards
What is the differentiation of a neoplasm?
How histologically similar to the normal tissue is the neoplasm - SUBJECTIVE determination made by the pathologist.
What is carcinoma in situ?
Full thickness dysplasia of the epithelium.
What is an hamartoma?
A disorganized collection of tissue –> tissue composing the mass being tissue that is normally found in the organ in which the mass has occurred –> NOT A NEOPLASM.
What is a choristoma?
A mass composed of ectopic tissue –> NOT A NEOPLASM.
What is a polyp?
Mass projecting from a mucosal surface –> It is a descriptive term, the mass causing the polyp MAY or MAY NOT be a neoplasm.
Mention some important histologic features of malignancy.
- Pleomorphism
- Abnormal mitotic figures
- Hyperchromasia
- Hypercellularity
Benign or malignant neoplasms grow faster?
Malignant –> rate of growth often corresponds to their degree of anaplasia.
When do most neoplasms have their most rapid growth rate?
Prior to detection. By the time of the detection, it is less than 20%.
Mention the 2 malignancies that do not metastasize.
- Gliomas
2. Basal cell carcinomas
What percentage of malignant solid tumors have metastases at the time they are clinically detected?
30%
What is required for eradication of the neoplasm?
Removal of the stem cells.
What must neoplastic stem cells have?
The BMI1 gene –> Inhibits p16INK4a and p14ARF.
What is the mechanism of action of HTLV-1?
TAX gene of HTLV-1 can activate transcription of host cell genes –> c-fos and IL-2 –> Both important in the proliferation and differentiation of T cells.
What neoplasms are associated with EBV?
- Burkitt
- Some HLs
- Nasopharyngeal carcinoma
- B cell lymphomas in AIDS patients
- Post transplantational lymphoproliferative disorder
What is the mechanism of action of EBV?
Enters the B cells through CD21 –> Activate the transcription of LMP1 –> which activates NF-kβ + JAK/STAT signaling pathway –> Promotes B cell survival.
What is the mechanism of action of HBV?
Through chronic inflammation + HBV protein binds p53.
What neoplasms are associated with HHV-8?
- Kaposi sarcoma
2. Primary effusion lymphoma
What is cachexia?
Loss of body fat and muscle + weakness + anorexia associated with a neoplasm.
What is the mechanism of cachexia?
Caused by cytokines produced by the tumor (possibly TNF) + by host response to the tumor.
What is the paraneoplastic syndrome?
Side effects of a neoplasm not attributable to functions normally associated with the cell type of origin or by the location of the tumor.
What neoplasms produce PTHrp?
- SCC of the lung
- Breast carcinoma
- Renal cell carcinoma
What neoplasms produce ACTH?
- Small cell carcinoma of the lung
2. Pancreatic carcinoma
What neoplasms produce ADH, resulting in SIADH?
- Small cell carcinoma of the lung
2. Cerebral neoplasms
What neoplasms produce erythropoietin?
- Renal cell carcinoma
- Hepatocellular carcinoma
- Cerebellar hemangioblastoma
What neoplasms are associated with persistent regeneration and repair?
Hepatocellular carcinomas arising in cirrhosis.
What neoplasms are associated with a hyperplastic process?
Endometrial carcinoma arising in endometrial hyperplasia.
What neoplasms are associated with a dysplastic process?
- SCC of cervix arising in CIN
2. Colonic adenocarcinoma arising in adenomatous polyp
What neoplasms are associated with chronic inflammation?
- Gastric adenocarcinoma arising in atrophic gastritis.
2. Colonic adenocarcinoma arising in ulcerative colitis.
Mention the 4 methods of conversion of proto-oncogene to oncogene.
- Overexpression of the gene
- Amplification of the gene
- Point mutation of the gene
- Translocation of the gene to another region with resultant overexpression of the gene/ production of protein with oncogenic activity.
What are the 5 ways by which oncogenes promote neoplasia?
- Synthesize growth factors.
- Synthesize growth factor receptors.
- Synthesize signal-transducing proteins.
- Synthesize nuclear transcription factors.
- Loss of regulation of cyclins or cyclin-dependent kinases.
What neoplasm is associated with aflatoxin?
Hepatocellular carcinoma
What neoplasm is associated with thorotrast?
Angiosarcoma of the liver
What neoplasm is associated with vinyl chloride?
Angiosarcoma of the liver
What neoplasms is associated with asbestos?
- Mesothelioma
2. Bronchogemic carcinoma
What neoplasm is associated with nitrosamines?
Gastric adenocarcinoma
What neoplasm is associated with polycyclic hydrocarbons?
Bronchogenic carcinoma
What is the mechanism of action of p53?
- Arrests the cell cycle by transcription of CDK1 (p21) which inhibits cyclin/CDK complexes and prevents phopshorylation of RB.
- Promotes production of GADD45 –> repair the cell.
- If cell injury is not repaired –> Bax gene –> apoptosis.
What is the normal function of APC protein?
Down regulation of β-catenin.
What is the effect of APC mutation?
Elevated levels of β-catenin result in interaction with TCF –> incr. c-MYC + cyclin D1.
Where do we see APC mutation?
70-80% of non familial colon carcinomas.
50% of hepatoblastomas and 20% of hepatocellular carcinomas.
Where do we see TGF-β mutation?
70% of colon cancer.
What is the associated mutation with TGF-β mutation?
SMAD4 –> seen in 50% of pancreatic adenocarcinomas.
What is the normal function of NF-1?
Neurofibromin is a GTPase-activating enzyme.
What is the effect of NF-1 mutation?
RAS is trapped in an active form.
What are the associated neoplasms in NF-1 mutation?
Neurofibromas + malignant peripheral sheath tumors.
What is the normal function of VHL?
VHL protein is a ubiquitin ligase whose substrate includes HIF-1 –> regulation of VEGF.
Where do we see PTEN mutations?
Frequently found in endometrial carcinomas and glioblastomas associated with COWDEN syndrome.
What neoplasms are marked by AFP (α-Fetoprotein)?
Hepatocellular carcinomas and yolk sac tumors.
Mention the 6 mechanisms of production of tumor antigens?
- Product of mutated oncogene or tumor suppressor gene.
- Protein produced by oncogenic virus.
- Altered cell surface glycoprotein/glycolipid.
- Overexpressed protein.
- Oncofetal antigens.
- Cell type specific differentiated antigen (such as expression of CD10).
Mention the 4 methods of the tumor to evade the detection by the immune system.
- Growth of antigen negative variant.
- Apoptosis of cytotoxic T cells through production of FAS ligand.
- Immunosuppression.
- Loss of MHC molecule.
What stains HMB-45?
Melanoma
What stains chromogranin A?
Small cell carcinoma
