Presentation, Treatment, Pathology, Survival (CLINICAL STUFF) Flashcards
What are the four types of cancer I should be pretty knowledgeable about for this unit?
• The ones that kill the most americans
• Lung, pancreas, colon, prostate
○ CARCINOMAS
What are Carcinomas in simple terms?
• Clonal expansions of stem cells in the epithelium that form abnormal growths
What does “invasion” of a carcinoma really mean?
- Small groups of the initial tumor cell have broken off and have broken through the basement membrane that separates the pithelium from the underyling sub mucosal, connective tissue stroma
- It is a group of cells invading a new tissue where it wasn’t from originally
How does the workup of a carcinoma of any of the four tissues we care about here start?
- Get a tissue sample EARLY to see what’s going on
- Examines cells sampled from lesion (core needle biopsy)
- Examine cells from sections of the removed lesion/tissue
- Use special IHC staines to determine certain common cancer variants
What are the two features of a carcinoma that need to be determined?
- Grade and stage
- Stage - extent of tumor spread at time of ddx (strongest predictor of prognosis)
- Grade - state of the differentiation of the cells that are being looked at (also mitotic activity)
What is the TNM classification of a tumor?
- T - size of tumor (Tis for in situ)
- N - lymph node involvement
- M - presence of metastasis (M0= no metastasis, M1=distant metastasis)
What is meant by High grade vs. Low grade in carcinomas?
- High grade is “that cell doesn’t even look like epithelium”
- Low grade is “that cell is trying to be epithelial but it’s still abnormal”
Where can signs and symptoms of neoplasia stem from?
- Both local effects and distant effects
- Cachexia is a result of systemic cytokine secretion (TNF-alpha)
- Can cause severe electrolyte imbalance and arrhythmias
What is the most common immediate cause of death in advanced stage carcinoma?
- Infection (60% of cases)
* Often acute bronchopneumonia
What are the classic signs and symptoms of lung carcinoma?
- Pateints present with coughing (persistant cough)
- DOE
- Chest pain
- Persistent hoarseness because of involvement of the recurrent laryngeal nerve
- Facial swelling
- Weight loss
- B symptoms
How do you diagnose lung carcinoma?
- Imaging (CT, MRI, PET) - looking for masses and infiltrates
- Chest film (imaging)
- Transbronchial biopsy
- Open lung biopsy
- Video-assisted thoroscopic biopsy (VATS)
- Percutaneus biopsy
- Cytology of bronchial alveolar lavage
- Mediastionoscopy to assess mediastinal lymph nodes
What percentage of lung carcinoma patients are long term survivors?
• Only 16%. Lung carcinoma kills pretty easily
Seeing adenocarcinoma in the lungs of non-smoking patients has become “common”. Why is it thought to be there?
• Radon gas exposure is the current idea
What are the four major variants of lung cancer that are seen clinically?
- Squamous cell carcinoma (25-40%)
- Adenocarcinoma (25-40%)
- Large cell carcinoma (10-15%)
- Small cell (oat cell) carcinoma (20-25%)
What is typical of squamous cell carcinomas?
- Strongly linked to cigarrette smoking
- Squamous metaplasia and dysplasia in the major branches of the bronchial tree (centrally)
- Often pretty large (3cm or more)
- Necrosis and hemorrhage at core of lesion is common
- More differentiated than not
- Some have keratin pearls
- P53, loss of Rb, p16 inactivation are common genetic signatures
- Metastasis through lymph nodes and blood
What are commonly mutated genes in squamous cell carcinomas?
• P53, loss of Rb, p16 inactivation are common genetic signatures
What are the common mechanisms of metastasis in squamous cell carcinomas?
Lymphatics and blood spread (hematogenously)
Small Cell Lung Carcinoma (SCLC) is different from other lung cancers in it’s treatment….why?
You don’t treat it with surgery, ONLY CHEMOTHERAPY
Paraneoplasic syndromes can be seen in Lung cancer, but what type in particular?
SCLC (small cell lung carcinoma). Even then, it’s only 1-5% of cases
What hormones or hormone like substances do SCLC’s produce that result in paraneoplasic syndromes?
antidiuretic hormone, ACTH, parathormone (hypercalcemia), gonadotropins (gynecomastia)
What are the classic symptoms of pancreatic cancer?
○ Back pain
○ Unexplained painless jaundice (tumor blocks common bile duct)
○ Cachexia
○ Migratory thrombophlebitis
• What are pancreatic intraepithelial neoplasias?
○ Early stages of pancreatic cancer
○ Focal areas of non-invasive foci of epithelial cell proliferations within pancreatic ducts and ductules
• Why does pancreatic cancer have such a terrible prognosis?
It grows without symptoms, and when it does cause symptoms (also causing the patient to go in) the diagnosis comes too late
- There is metastasis upon diagnosis a great majority of the time
- Liver and lung and lymph nodes
• What is the cause of pancreatic cancer?
○ Still unknown
• What are the risk factors for pancreatic cancer?
○ Age, smoking, chronic pancreatitits from alcoholism, diabetes mellitus, family history
• Where in the pancreas can the cancer originate/be?
○ Anywhere in the body, head or tail
• What is the diagnostic workup of pancreatic cancer?
○ Imaging (CT, MRI)
○ Percutaneous and ultrasound guided biopsy (via endoscopy)
• What can you do with small lesions that are discovered early
○ You can go all crazy and do a whipple, or you can get out the focal lesions and cure it surgically
- The cure rate the focal lesion resection is RARE
- The whipple takes out most of the pancreas, common bile duct, gall bladder, duodenum so that’s not the first case scenario of what you want
• What does “desmoplasia” mean in the context of pancreatic cancer?
○ This cancer has a specific flavor of stimulating stromal cells
○ There is a distinctive connective tissue support network around pancreatic cancer cells
Where is pancreatic cancer wont to metastasize?
○ Liver, lung, lymph nodes
○ Peri-gastric, peri-aortic, omental lymph nodes are common sites
Why would you need to place a stent in the common bile duct in pancreatic cancer patients?
○ Obstruction can lead to chronic pancreatitis
○ Acute ascending cholangitis can lead to life threatening infection and septtic shock
What is the second leading cause of cancer death in men AND women?
Colorectal cancer
Are colorectal cancers differentiated or not?
They are often fairly well differentiated
What is the first stage of colon cancer development?
It forms a polyp in the innermost, mucosal layer of the bowel wall. It eventually can invade the muscle layers and lumen
What subset of carcinoma does colon cancer normally form?
Adenocarcinoma
How is colon cancer metastasis often mediated?
through the lymphatics and blood both
What are the two types of neoplastic colonic polyps?
tubular adenoma and villous adenoma
What correlates with the size of the polyp?
the risk for progression into adenocarcinoma (over 3cm). The other prognostic marker is dysplastic changes in the epithelium
What are the common symptoms of cancer in the ascending colon vs. descending colon?
In descending colon, not as much pain because stool there is looser. In ascending colon, can result in blockage, pain and inflammation, and change in stool caliber
Which side of the colon is a lesion more likely to get larger before onset of any symptoms?
the right, where stool is more liquid so an obstruction isn’t so severely felt
How is advanced stage colon cancer treated?
chemotherapy
- 5-flurouracil
- eribitux (monoclonal Ab anti-EGFR)
How is early stage colon cancer treated?
Usually with removal of the polyps (surgery)
What are the inherited genetic predispositions for colon cancer?
APC (inherited) HNPCC (inherited condition where mismatch repair is gone), loss of mutY base excision repair enzyme
What are the common sporadic mutations seen in colon cancer?
APC, Ki-ras, p53, DCC, MCC (and lots of others…this guy is heavily studied)
Why might IBS be a scare for colon cancer?
Chronic inflammation means chronic cellular injury and repair, which is a nursery of cancer-causing genetic mutations
What is the leading cause of cancer in men and the second leading cause of cancer death in men?
Prostatic adenocarcinoma (notes had both carcinoma and adenocarcinoma all over the place, so be ready for both)
Where does prostate cancer tend to arise?
Outer zone, so you can feel it on digital rectal exam
Does BPH or prostate cancer tend to mess with urinary voiding?
BPH much more than prostate cancer
What is the cause of prostate cancer?
unknown, though androgens are thought to play a role. Whatever it is…every man eventually gets it
How is the definitive diagnosis made?
Guided biopsy (ultrasound), often confirmed with increasing, elevated PSA (above 4 ng/mL)
What is “PIN” in prostate cancer?
prostatic intraepithelial neoplasm - the first stage of this cancer’s growth
What are the common genes messed up in prostate cancer?
PTEN and GSH
Normally there are two layers of cells in a prostate gland. What are they and which one is missing in malignant glands?
The inner columnar secretory cells and the outer flattened basal cell layer. The outer basal cell layer is missing in the malignant glands. THUS PROSTATE CANCER GLANDS ARE SINGLE CELL LAYER
Can you accurately predict how Prostate cancer is going to behave?
NOPE. it can kill you, or it can be there and do nothing. It can be agressive, or it can be dormant. it’s best to treat it with respect if its there
what’s the treatment for prostate cancer?
Often radical prostectomy. You can combine that with chemo and radiation, but not always. Late stage…palliative care with anti-androgen will relieve pain from bone metastasis (androgens will cause those metastatic lesions to grow or swell, so shut off those signals)
What tissues/organs does prostate cancer tend to classically spread?
Bone (pelvis), regional lymph nodes, seminal vesicles, adjacent abdominal wall, rectum. (spread through blood and lymph)
What’s the most widespread grading system for prostate cancer?
Gleason system
* grade 1 - well differentiated, neoplastic glads appear uniform
* Grade 5 - no gland formation…those cells are so messed up they don’t even try to be adenocarcinoma anymore
YOU ADD THE MAIN GRADE TO THE NEXT MOST COMMON GRADE - 8-10 INDICATES AGGRESSIVE BEHAVOIR
