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
What is a precursor lesion for gastric adenocarcinoma?
Chronic atrophy gastritis
What is the presentation for gastric adenocarcinoma?
epigastric pain, hematemesis, iron deficiency anemia, melena (dark tarry stools, digest blood – upper GI), enlarged Virchows node (left supraclavicular lymph nodes)
Satiation
Projectile vomiting without bile because no bile is stomach with with blood
What is the investigation for a gastric adenocarcinoma?
Tumor marker: CEA
nonspecific used for (colon, lung, breast and stomach cancers)
Biopsy: malignant glands invading basement membrane
What is the distinguishing factors between gastric adenocarcinoma and peptic ulcer?
Heaped up margins and irregular boarders
What is an ulcer?
Defect of excavation on surface of organ covered or lined by epithelium
Bilateral ovarian tumors have metastases to both ovaries from a primary site what is this process called?
Krukenberg (there usually referred to as Krunkenberg tumor)
always bilateral
On histological stain what is the defining features of bilateral ovarian tumor?
Signet ring cells (malignant cells coming from periphery tumors)
- -filled with mucins that push nuclei to the periphery
- -mucin has glycogen so stain with PAS
Bilateral ovarian tumors are usually a result of a metastasis event from a primary site. what are the three primary sites?
Stomach (Stomach adenocarcinoma)
Colon
Breast
(all primary tumors have E-cadherin mutations)
Patient will present with symptoms of a primary tumor. So what is the prognosis of patients?
patients die within a year
What tumor marker can be used for test?
CEA
What is a teratoma?
Derived from 2 or more germ layers
What is a mature teratoma?
Benign dermoid cyst -well differentiated
What is an immature teratoma?
malignant
What is a cystic ovarian teratoma or dermoid cyst?
Cyst inside the tumor of the ovary
consists of 2+ germ layers arising from the totipotent germ cells
in testes or ovaries and able to produce all cell types
99% of all ovarian teratomas are benign or malignant?
Benign
What is the appearance of the dermoid cyst or cystic ovarian teratoma?
consists of ectodermal elements: hair follicles and teeth
Mesoderm elements: sebaceous/sebum glands = greasy appearance
What is the presentation of a patient with dermoid or cystic ovarian teratoma?
Usually no symptoms - found incidentally on findings of calcified tooth on x-ray, ultrasound, CT
What are some complications of a mature cystic teratoma?
infertility, rupture, torsion, malignant transformation to invasive squamous cell carcinoma (from ectodermal component)
upon removal of tumor women are not infertile any longer
What is a Wilms Tumor?
(mother notices palpable mass while bathing child)
Nephroblastoma (malignant mixed tumor) in children 2-5 years old
mixed = 1 germ layer with different types of cells
What is the pathogenesis of a Wilms Tumor?
Divergent Differentiation:
- Mutation in WT-1 and WT-2 tumor suppressor genes (need two hits)
- Sporadic (unilateral) and Familial (bilateral)
- Tendency to metastasize early, esp to the lungs
- Precursor lesion=nephrogenic rests (abnormally persistent clusters of embryonal cells)
What is the presentation for a Wilm’s Tumor/
Palpable abdominal mass, abdominal pain , tumor compresses renal vessels and JG cells secrete renin and leads to hypertension
pain because it stretches renal capsule
What are the three classic signs on histology?
Triphasic- all three are malignant
- Blastemal: small, immature blue cells with high nuclear; cytoplasmic ratio
- Stromal/Mesenchymal: spindle-shaped cells
- Epithelial: defective tubules/glomeruli
For a Wilms tumor you need to do a partial nephrectomy or what happens to the patient?
metastasize to lungs
remember this partial nephrectomy is an excisional biopsy
What causes wasting or weight loss in cancer (cachexia)?
TNF
Hard Fixed and non tender are what kind of lymph nodes?
Cancerous
What are the exceptions to the lymph and carcinoma rule?
Follicular Caricoma of the thyroid
Renal Cell
Choriocarcinoma
Hepatocellular
What are the two types of gastric cancer?
Intestinal
and
Diffuse ( this causes Kruckenburg and has nothing to do with H. pylori. Singnet rings this is due to a mutation )
Tertaomas can be found in men and women, what is the major difference between the teratomas?
Women: ovaries usually benign, mature
Men: testes usually malignant, immature
What is the difference between an incisional biopsy and an excisional biopsy?
Incisional: put the needle through the specimen
Excisional: Take everything out (in regards to the tumor)
How does Wilm’s tumor spread?
Blood to lungs
