Episode 60: This is Part 2 of the very long Cancer Podcast. Dr. Dan covers Grade versus Stage, paraneoplastic syndromes, and a high-yield list of the most common causes of the various cancers.
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 anemia in malignancy is Anemia of chronic disease (this is the overall most common)
Colon cancer: left side obstructs w/ right side bleeds; if you have RT side bleed in colon cancer, Fe def anemia is very common.
Mets to BM and replace BM. Or, use chemotherapy drugs that are cell cycle specific or cell cycle nonspecific – they wipe out the marrow. Can have autoimmune mechanism with certain malignant dz.
C. Associations with disseminated cancers:
1. Most pts with disseminated cancers are hypercoagulable, meaning that they have a tendency for forming clots. Classic Example: a pt with painless jaundice, left supraclavicular node (this is a distracter), had light color stools, lesions that jump from one part of body to next – trousseau’s sign: a superficial migratory thrombophlebitis due to carcinoma of the head of the pancreas). Pancreatic cancers can ALSO mets to left supraclavicular node (virchow’s node), and often describe trousseau’s sign, which is a vascular problem in the veins that jumps from one place to the next.
2. Another common thing seen is disseminated cancers is thrombocytosis – an elevated platelet count. Other causes of thrombocytosis: Fe def, splenectomy (ie see scar on abdomen), TB, anemias. If you cannot find any obvious cause of thrombocytosis then the cause is cancer. 40% of disseminated cancers are thrombocytosis. Or a do a stool guaic for colon cancer.
D. MCC fever in malignancy = gram neg. infection. An E. coli if you have an indwelling catheter; Pseudomonas if you have a respirator, staph aureus can also be the cause from an indwelling catheter, but this is gram “+”. MCC death in cancer = infection.
XV. Paraneoplastic syndromes
These are signs and sometimes symptoms saying that you may have an underlying cancer present. Its important b/c when you recognize the signs and symptoms, then you can catch the cancer before it metastasize.
MC Paraneoplastic syndrome = hypercalcemia
2 mechanism for hypercalcemia in malignancy:
1) mets to bone, produce a chemical (IL-1, PGE2, both of which activate osteoclasts) that produces lytic lesions in bone, and you get hypercalcemia
2) renal adenocarcinoma or squamous carcinoma of mainstem bronchus that sits there and makes PTH-like peptide and causes hypercalcemia b/c it acts like PTH and breaks down bone. This is Paraneoplastic, but it’s not the most common one.
Example: 2 black lesions – both are markers for gastric adenocarcinoma; usually under the arm – called acanthosis nigricans, and other is called seborrheic keratosis (these are not neoplasms); however, when these suddenly develop overnight, you get multiple outcroppings, and the outcroppings is a phenotypic marker for gastroadenocarcinoma; this is easy to remember b/c 2 black lesions are markers from gastroadenocarcinoma.
Example: clubbing – inflammation beneath on the bone called periostitis; inflamm of underlying bone causes proliferation of the soft tissue around it, which leads to clubbing (called hypertrophic osteoarthropathy). Clubbing is not always assoc with cancer; also assoc with bronchiectasis, IBS. But, if it’s a malignancy, it is due to primary lung dz.
Example: least common collagen vascular dz, but the most often assoc with a certain cancer. They have an elevation of serum CK; this is dermatomyositis; raccoon eyes, so you see inflammation of skin and muscle; high assoc with leukemias, lymphomas and lung cancer. patches of knuckles – Goltrin’s patches (seen in dermatomyositis).
Example: vegetations (sterile) on the mitral valve – assoc with mucous producing cancers such as colon cancer; this is called marantic endocarditis-aka nonbacterial thrombotic endocarditis; they are not infections and these marantic vegetations are assoc with mucous secreting colon cancers. Can they embolize? Yes. You will need history to separate from rheumatic fever, but history will relate more to colon cancer (ie polyarthritis).
Example: hyponatremia or Cushing’s – cancer in the lung = small cell carcinoma, which is secreting either ADH or ACTH; also, for small cell, they are aput tumors, S-100 Ag positive, neural crest origin, neural secretory granules.
Example: Hypercalcemia or secondary polycythemia: renal adenocarcinoma (can make PTH like peptide and/or EPO).
Example: Hypoglycemia or secondary polycythemia: Hepatocellular carcinoma (they can make EPO or insulin-like factor).
Example: Hypocalcemia or Cushing’s: auto dominant, and the rare tumor marker that can be converted to amyloid (calcitonin) – medullary carcinoma of the thyroid.
XVI. Tumor markers
- 2 markers associated with Testicular cancer – alpha feto protein (AFP) (which is really the albumin of a fetus) and HCG.
- AFP is a maker for–yolk sac tumor (endodermal sinus tumor). So the tumors in kids are yolk sac tumors (alpha feto protein). AFP is also assoc with Hepatocellular carcinoma, increased in neural tube defects (must be on folate while pregnant to prevent neural tube defects). In Down’s syndrome AFP is decreased. Marker for malignancy in bone, assoc with monoclonal spike: Bence Jones Proteins (light chain Ig), assoc with Multiple Myeloma.
- Tumor marker for prostate cancer: PSA; not sp for cancer b/c it can be also increased in hyperplasia; it is sensitive but not specific. If you do a rectal exam, it is not increased. PSA is NOT an enzyme; it is an Ag and is within the actual cell. It will not increase with a rectal exam.
- Breast cancer (surface derived) – 15, 3.
- CEA–125: Ovarian cancer
- CEA –Ag for colon cancer; and sometimes used for small cell, and breast ca. CEA can be a part of an immune complex, and will get CEA: anti-CEA immune complexes which deposit in the kidney, and lead to nephrotic syndrome – this is diffuse membranous glomerulonephritis = MC overall cause of nephrotic syndrome. Many of these are related to malignancy b/c CEA can be the Ag that is deposits in the glomeruli.
- Woman with a trophoblastic mole, what would you get? Beta HCG
Most Common Causes (MCC) of Cancer:
- What is MC primary tumor of the brain in kids? Cerebellar cystic astrocytoma (B9). It’s not medulloblastoma. All astrocytomas are B9 (if asked what is the most common malignant primary tumor, and then the answer is medulloblastoma, which derives from cerebellum). MC actual tumor of the brain – cerebellar tumor derived from astrocytes;
- MC childhood cancer = ALL leukemia (other childhood tumors include CNS tumors, neuroblastomas (in the adrenal medulla), Burkitts, Ewing’s (tumor of bone with onion skinning), embryonal rhabdomyosarcoma.)
- Adults: incidence:
- Woman: breast, lung, colon
- Men: prostate, lung, and colon
- Killers: lung is #1 in both (followed by prostate/breast and colon)
- 2nd MC cancer and cancer killer in men and women combined = colon
- Therefore, from age 50 and on, you should get a rectal exam and a stool guaic. After 50, MCC cancer of “+” stool guaic is colon cancer.
- MC gyn cancer: endometrial (#2 is ovarian, and #3 is cervix)
- Cervix is least common b/c Pap smear. When you do a cervical pap, picking up cervical dysplasia, not cervical cancer (therefore the ‘incidence’ isn’t the highest).
- B/c cervical pap smears; the incidence of cervical cancer has gone down significantly b/c the detection of the precursor lesion, cervical dysplasia. So, b/c cervical Pap smear, incidence of cervical cancer has gone down dramatically (picking up the precursor lesion); with mammography, the incidence of breast cancer decreases, same with PSA.
- MC Gyn cancer killer: ovarian (#2 = cervical, #3 = endometrial); therefore to remember, the MC has the best prognosis – endometrial is MC and has the best prognosis. What is the only known existing tumor vaccine? HBV …why? MC infection transmitted by accidental needle stick in the hospital = Hepatitis B. B/c viral burden of Hepatitis B is greater than any infection, even more so than HIV. So, with the Hepatitis B vaccine, you won’t get three things (1) Hepatitis B, (2) Hepatitis D (requires Hep B), and (3) hepatocellular carcinoma (related to Hepatitis B related cirrhosis).
How do you eradicate hepatocellular carcinoma? Vaccination (ie in the Far East).