Summary: Episode 24: Doctor Dan gives part 2 of his Cancer lecture series available in full at www.Medical-Mastermind-Community.com. Cancers and Associated Diseases - Part II Xeroderma pigmentosa – sun exposed areas, auto recessive, can cause all skin cancers (BCC, SCC, and melanomas), and the defect is in DNA repair enzymes. Other DNA repair defects are associated with BRCA1 and BRCA2, p53, they splice out the defects, this group is called the chromosomal instability syndromes – Wiskott Aldrich, Blooms, Ataxia Telangiectasias, and Fanconi’s, all have probs with DNA repair. Basic rule of thumb for BCC and SCC: Upper lip and up is basal cell carcinoma; lower lip and down is squamous cell (therefore, lesion on lower lip = sq cell; lesion on upper lip = basal cell) Example: inside nose is BCC, b/c above the upper lip Example: keloid – sq cell carcinomas and 3rd degree burns and sq cell carcinoma developing in areas of drainage from the sinus and ulcer that doesn’t heal from antibiotics. So, wherever there is constant irritation, and division of cells related to irritation, there is an increase susceptibility to cancer. This does not hold true for scar cancer tissue related cancers of the lungs or adenocarcinoma (just applies to things on the skin – ie burns and draining of sinus tracts). Only bacteria assoc with cancer? H. pylori – adenocarcinoma and low grade malignant lymphomas. XII. Grade vs Stage A. Grade = what does it look like? The term well differentiated means that the tumor is making something like keratin or glands, and if it’s identifiable it’s called low grade. When the cells are anaplastic, poorly differentiated under the microscope, and if you cannot tell what it is, then it’s called high grade. Example: sq cell carcinoma can see keratin pearls; can ID it, so it’s a low grade cancer. Example: see gland like spaces, can ID so its low grade B. Stage = (TNM) MC staging system; goes from least imp to most imp (TNM) Example: breast cancer with axillary node involvement; therefore, the N=1, but the “M” is worse, b/c it indicates that cancer has spread to other organs like bone, etc. Just b/c it goes to lymph nodes doesn’t mean it is the most imp prognostic factor. T=size of tumor; if tumor is over 2 sonometers, it has a chance of mets N=nodes (next most imp for prognosis) M=mets outside of nodes (most imp prognostic factor) Stage is more important than grade for prognosis; and within staging, M is the most imp factor for prognosis. Example: pt with prostate cancer, which of following has it the worst? The answer choices were cancer limited to prostate, it went into seminal vesicles, it involved the wall of bladder, went to lymph nodes, or bone? Answer = bone (bone represents the “M” of the TNM system – this is stage 4 by definition=mets) Example: a slide of a colon cancer and a lymph node: what is most important – size of tumor or lymph node involvement? Lymph node. If it was also in the liver, what is most imp? Liver specimen is the most imp prognostic factor. XIII. Host defenses – most important is Cytotoxic CD8 T cell Others – NK cells, Ab’s, macrophages, type 2 HPY. In hospital, they look for altered MHC class I Ag’s in the cancer pt, b/c cancer wants to kill T cells; they do this by putting in perforins, which activate caspasases, and this leads to apoptosis (the signal, from the perforins, activate the caspasases, which have proteases, which break down the nucleus and mitochondria, and cell dies, without any inflammatory infiltrate). XIV. Other diseases seen in malignancy: A. Cachexia – cause is TNF alpha; it is irreversible. Once you see a pt with disseminated cancer about to go into catabolic state, can give then total nutrition, but still won’t help. (Will not get muscle mass back, and this is due to TNF-alpha) B. Many hematologic causes of anemia seen in malignancy MC
