Clinical Models of Altered Cellular Proliferation and Differentiation
Leading cause of cancer deaths worldwide
Smoking and industrial exposures often implicated
Tumors originate most frequently in the epithelial lining of the bronchi, bronchioles, and alveoli
Tropic to the bone, liver, brain (affinity to spread to distant site)
1. Adenocarcinoma: **women/nonsmokers, leads to plural fibrosis/adhesions
2. Squamous cell carcinomas: linked to smoking. Bronchial columnar leads to squamous
metaplasia, dysplasia, carcinoma in situ and tumor. Can be detected in sputum
3. Small cell carcinomas: highly malignant (rapid). Smoking related (men). Linked to poor
4. Large cell carcinomas: large cells, high anaplasia, diagnosis based on exclusion, poor
Hemoptysis- bloody sputum
Shortness of breath
Explained as smokers cough or bronchitis
Staging of Lung Cancer
Carcinoembryonic antigen (CEA)- prognosis often related to the levels of this antigen
Adverse prognosis: presence of pulmonary symptoms, large tumor size, nonsquamous history,
lymph node metastisis or vascular invasion.
Based on tumor type Small cell carcinoma (most likely to be spread at diagnosis)
Surgery, radiation rarely work
Non-small cell carcinoma (often based on ability to operate)
Chemotherapy (may be used when cant get ALL cancer cells)
Radiation, if surgery not feasible (Radiation can help control tumor when it cant be removed, but
will not cure the cancer). Colorectal Cancer
(24-40% if resectable)
Multiple lifestyle risk factors (75% unknown etiology, 25% familial) ** Age is greatest risk factor
(others= smoking, alcohol, diet high in fat, low in fiber, IBD, obesity and inactivity)
Disruption of p53 gene implicated in 3 of 4 cases of colorectal cancer
Cellular transformation in mucosal epithelium of the bowel begins at the base of the crypts (where
mitosis occurs, mature cells move up the crypt and dies and gets sloughed off).
High fiber diets- bind to mutagens and move it quickly through colon, helps prevent cancer.
High fat diet- increases secretion of bile because that is needed to break down fats. Linked to cancer.
Protective factors- selenium, vitamin E,C, A and veggies (Brussels, cabbage, cauliflower, broccoli.
Groups: from benign polyps to invasive tumors (adenoma- adenocarcinoma)
1. Nonneoplastic polyps: non a cancer precursor
2. Neoplastic polyps: adenoma, at risk for cancer
3. Cancer: adenocarcinoma
Usually start from a series of events triggering chromosomal instability or replication errors.
Aneuploidy- alterations in chromosomal number.
Change in bowel habits (First clue!!)
Occult – hidden blood, in the ascending colon
Frank- visible blood, in the descending colon
Anemia- caused by loss of blood
Systematic/ paraneoplastic manifestations
Digital rectal exam
NOT CEA values!!
Radiation Brain Cancer
Dont use TNM classification
Metastasis much more common to brain than primary tumors (10:1 ratio) (∆ not primary tumors, usually
from lung, breast, skin or colon origin)
Primary tumors originate from:
Glial cells- non neurons
Meninges – emerge in middle- late adulthood, slow growing, erodes cranium
Schwann cells-Schwannomas arise in the brain, spinal nerves, peripheral nerves **rarely malignant
Ectopic tissues – originate in embryonic cells that have migrated to brain/spinal cord. Can grow
slowly over a life time.
Gliomas- most common tumor type. Vary in differentiation (20% well differentiated, 40% are highly
undifferentiated) Benign or malignant. Rarely metastasize outside CNS.
Headache (due to increased pressure in the brain, with inflammation + fluid)
Vomiting (due to increased pressure in the brain, with inflammation + fluid)
Seizures (from irritation + discharge of neurons)
Loss of motor or sensory function (vision changes, numbness, weakness, paralysis)
Cognitive or behavioral changes (personality, irritability, forgetfulness, depression)
Surgery- usually for primary tumors
Radiation- almost always indicated
Chemotherapy- into spinal canal for some of the ‘omas’
Palliative care Leukemia
Malignant neoplasms of blood and blood-forming organs
Most often associated with overproliferation and lack of differentiation in WBC’s
Replaces cells in the bone marrow with immature, proliferating neoplasms (blast cells)
May happen to ppl treated with chemotherapy for other types of cancer.
Lymphocytic (ALL)- involve immature lymphocytes that originate in bone marrow
Myelogenous (AML)- myeloid stem cells in the marrow, interfere with maturation of all blood cells
Acute- sudden rapid loss of function
Lymphocytic (ALL)- most common cancer in children, 85% prognos