Module 4 Path -Continued Flashcards
One of the malignant tumors of mesenchymal origin is called a sarcoma. What metastatic pathway is favored by sarcomas?
Hematogenous spread: liver (via portal vein) and lung (via vena cava) have largest capillary bed, which pre-disposes to sarcomas
For osteosarcoma goes to the lung first
An osteosarcoma is a malignant tumor of osteoblasts (derived from mesenchyme). What is the pathogenesis of an osteosarcoma?
Mutation in Rb gene (child would present with both eyes removed at a young age due to retinoblastoma)
presents around 12-20 y.o
How would an osteosarcoma present?
Painful enlarged mass (swelling) around the knee (metaphyseal plate of long bones because this site of continous cell replication)
Pathological fractures
more common in distal femur or proximal tibia
What is a good investigation for an osteosarcoma?
Histology: malignant osteoblasts, hemorrhage, necrosis, invasiveness and lack of demarcation
What are some complications to an osteosarcoma?
Invades venous channels: cough with blood and sputum (hemoptysis) b/c metastasize to lung via blood
Most sarcomas end up in the liver and lung (because organs with most blood flow)
What is metastasis?
is a defined as a tumor implant discontinuous from the primary tumor
it is an unequivocal sign of malignancy
what are the three metastasis pathways?
- Seeding via body cavities: peritoneal cavity is most common site, ovarian and gastric carcinoma through the omentum, and pericardial/pleural/subarachnoid cavities
- Lymphatic spread: most common initial dissemination for carcinomas, follow natural drainage
- Hematogenous spread: favored by sarcoma, liver and lung are frequent sites
What the phases of metastasis?
- Invasion of extracellular matrix
- movement through the interstitial tissue
- Vascular dissemination and homing of tumor cells
The first phase of metastasis is invasion of the extracellular matrix. There are 4 steps involved in actually invading the matrix. What are these steps?
- Detachment of tumor cells (reduced cadherins: normally causes cell adhesion)
- Extracellular matrix protein degradation by enzymes (collagense, cathepsin B, benign tumors secrete little or no such enzyme)
- Attachments to the extracellular matrix protein component. (laminin receptors, integrins) (new sites generated by MMP2 and MMP9- secreted by tumors
- Movement through extracellular matrix proteins (autocrine motility factors)
The last phase of metastasis is vascular dissemination and homing. Tumor cells erode through the wall of the lymphatics or blood vessels and spread as what?
single cell or multiple cell emboli with platelets and WBC
The homing (metastatic site) of tumor related to: what three things?
presence or absence of specific molecules
chemo-attractant (Chemokines)
unfavorable environment (muscle)
Once in the new metastatic site, what do tumors do?
grow
stimulate angiogenesis
All carcinomas eventually end up where?
in the blood due to the emptying of lymph in thoracic duct
remember metastasis of carcinoma is via lymphatics
What is paraneoplastic syndrome?
- Squamous cell carcinoma of the lungs giving you hypercalcemia: tumor releases PTH related peptide this mimics PTH this causes bone resorption and reabsorption from kidneys and hydroxylation of vit D
- Small Cell carcinoma of lung secreting ACTH: causes adrenal cortex to release cortisol this give you cushings syndrome
What is an endometrial carcinoma?
Hormone producing cancer
What is the etiology of an endometrial carcinoma?
Etiology: Unopposed Estrogen (estrogen without progesterone)
Pre dispoing factors: Post-menopausal women taken estrogen replacement therapy, patients taking tamoxifen for breast cancer (antagonist in breast and antagonistic in endometrium), obesity, diabetes mellitus, nulliparous and POD
In patients that have Cowden’s syndrome, they can have an endometrial adenocarcinoma as well. What is the etiology of Cowdens Syndrome?
Mutation in mismatch repair gene PTEN
What is the pathogenesis for endometrial adenocarcinoma?
Endometrial hyperplasia (pathological) ---- atypical endometrial hyperplasia ---- endometrial carcinoma Spreads to regional lymph nodes first
What is the presentation for endometrial adenocarcinoma?
Vaginal bleeding post menopausal women and leukorrhea (White vaginal discharge)
What are investigations for an adenocarcinoma?
Histology: malignant endometrial glands invading the myometrium
Immunohistochemical stain: cytokeratin
What is the spread for endometrial adenocarcinoma?
Spread via lymph nodes, seeding via peritoneal cavity to peritoneal tubes, invasion of myometrium and hematogenous spread
What are some features of a gastric adenocarcinoma?
Irregular
Headed up by margins
Necrotic
Hemorrhagic
What is the etiology of a gastric adenocarcinoma?
H. pylori (gram negative) --- directly to stomach cancer ---found in atrum and pylorus ----how does it survive acid in stomach? Makes urase which breaks down urea and this releases ammonia (neutralizes acid). Most damage is due to host immune response. Causes chronic gastritis --- leads to intestinal metaplasia --- intestinal dysplasia --- intestinal gastric adenocarcinoma Japanese Smoked foods (have nitrosamines)
What benign tumor is associated with H. pylori?
B cell lymphoma
