CAUSES OF CANCER
EFFECTS OF CANCER
Ed Friedlander, M.D., Pathologist
scalpel_blade@yahoo.com

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Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected. No texting or chat messages, please. Ordinary e-mails are welcome.

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Freely have you received, give freely With one of four large boxes of "Pathguy" replies.

I'm still doing my best to answer everybody. Sometimes I get backlogged, sometimes my E-mail crashes, and sometimes my literature search software crashes. If you've not heard from me in a week, post me again. I send my most challenging questions to the medical student pathology interest group, minus the name, but with your E-mail where you can receive a reply.

Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource.

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Freely have you received, freely give. -- Matthew 10:8. My site receives an enormous amount of traffic, and I'm still handling dozens of requests for information weekly, all as a public service.

Pathology's modern founder, Rudolf Virchow M.D., left a legacy of realism and social conscience for the discipline. I am a mainstream Christian, a man of science, and a proponent of common sense and common kindness. I am an outspoken enemy of all the make-believe and bunk that interfere with peoples' health, reasonable freedom, and happiness. I talk and write straight, and without apology.

Throughout these notes, I am speaking only for myself, and not for any employer, organization, or associate.

Special thanks to my friend and colleague, Charles Wheeler M.D., pathologist and former Kansas City mayor. Thanks also to the real Patch Adams M.D., who wrote me encouragement when we were both beginning our unusual medical careers.

If you're a private individual who's enjoyed this site, and want to say, "Thank you, Ed!", then what I'd like best is a contribution to the Episcopalian home for abandoned, neglected, and abused kids in Nevada:

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Especially if you're looking for information on a disease with a name that you know, here are a couple of great places for you to go right now and use Medline, which will allow you to find every relevant current scientific publication. You owe it to yourself to learn to use this invaluable internet resource. Not only will you find some information immediately, but you'll have references to journal articles that you can obtain by interlibrary loan, plus the names of the world's foremost experts and their institutions.

Alternative (complementary) medicine has made real progress since my generally-unfavorable 1983 review. If you are interested in complementary medicine, then I would urge you to visit my new Alternative Medicine page. If you are looking for something on complementary medicine, please go first to the American Association of Naturopathic Physicians. And for your enjoyment... here are some of my old pathology exams for medical school undergraduates.

I cannot examine every claim that my correspondents share with me. Sometimes the independent thinkers prove to be correct, and paradigms shift as a result. You also know that extraordinary claims require extraordinary evidence. When a discovery proves to square with the observable world, scientists make reputations by confirming it, and corporations are soon making profits from it. When a decades-old claim by a "persecuted genius" finds no acceptance from mainstream science, it probably failed some basic experimental tests designed to eliminate self-deception. If you ask me about something like this, I will simply invite you to do some tests yourself, perhaps as a high-school science project. Who knows? Perhaps it'll be you who makes the next great discovery!

Our world is full of people who have found peace, fulfillment, and friendship by suspending their own reasoning and simply accepting a single authority that seems wise and good. I've learned that they leave the movements when, and only when, they discover they have been maliciously deceived. In the meantime, nothing that I can say or do will convince such people that I am a decent human being. I no longer answer my crank mail.

This site is my hobby, and I do not accept donations, though I appreciate those who have offered to help.

During the eighteen years my site has been online, it's proved to be one of the most popular of all internet sites for undergraduate physician and allied-health education. It is so well-known that I'm not worried about borrowers. I never refuse requests from colleagues for permission to adapt or duplicate it for their own courses... and many do. So, fellow-teachers, help yourselves. Don't sell it for a profit, don't use it for a bad purpose, and at some time in your course, mention me as author and KCUMB as my institution. Drop me a note about your successes. And special thanks to everyone who's helped and encouraged me, and especially the people at KCUMB for making it possible, and my teaching assistants over the years.

Whatever you're looking for on the web, I hope you find it, here or elsewhere. Health and friendship!

BIBLIOGRAPHY / FURTHER READING

PicoSearch
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More of Ed's Notes: Ed's Medical Terminology Page

Perspectives on Disease
Cell Injury and Death
Accumulations and Deposits
Inflammation
Fluids
Genes
What is Cancer?
Cancer: Causes and Effects
Immune Injury
Autoimmunity
Other Immune
HIV infections
The Anti-Immunization Activists
Infancy and Childhood
Aging
Infections
Nutrition
Environmental Lung Disease
Violence, Accidents, Poisoning
Heart
Vessels
Respiratory
Red Cells
White Cells
Coagulation
Oral Cavity
GI Tract
Liver
Pancreas (including Diabetes)
Kidney
Bladder
Men
Women
Breast
Pituitary
Thyroid
Adrenal and Thymus
Bones
Joints
Muscles
Skin
Nervous System
Eye
Ear
Autopsy
Lab Profiling
Blood Component Therapy
Serum Proteins
Renal Function Tests
Adrenal Testing
Arthritis Labs
Glucose Testing
Liver Testing
Porphyria
Urinalysis
Spinal Fluid
Lab Problem
Quackery
Alternative Medicine (current)
Preventing "F"'s: For Teachers!
Medical Dictionary

Courtesy of CancerWEB

LEARNING OBJECTIVES

Define the following terms and use them appropriately:

Recognize the ways in which the growth properties of cancer cells differ from normal. Explain the Nowell multi-step clonal evolution model for tumorigenesis, and cite evidence that it is true.

Briefly describe how the classic transforming viruses caused cancer in experimental animals. Explain why cancers produced by a particular transforming virus in a particular experiment will, as a rule, be antigenically identical.

Tell the features common to most or all genuine chemical carcinogens. Explain why cancers produced by a particular chemical carcinogen in a particular experiment will, as a rule, be antigenically dissimilar.

Give the evidence for radiation carcinogenesis in humans, and the resulting tumors.

Discuss oncogenes in some detail. Explain how we believe certain mutations make ras oncogenic. Explain the importance of myc oncogenes in certain cancers, and the two ways myc is activated.

Describe tumor-suppressor genes (anti-oncogenes) in considerable detail, and explain why tumors tend to show loss of heterozygosity at their loci. Explain the Knudson two-hit model.

Recognize the important tumor viruses for humans. Tell how they differ from the transforming viruses of the classic animal experiments. Tell how they effect their damage.

Recognize the major known and suspected human chemical carcinogens and the tumors they produce. Describe the Delaney Clause and its repeal.

Evaluate media and government claims about "things that cause cancer" intelligently and honestly.

Critique the following statement, overheard in a supermarket check-out line: "Cancers are continually forming in our bodies, but our immune system destroys them. The natural way to cure cancer is by strengthening the immune system."

Give the overall cure rate for newly-diagnosed cancers in the US today. Identify cancers that are increasing and decreasing in the U.S., and suggest reasons why. Identify cancers that are common in some countries and rare in others. Suggest reasons why.

Distinguish "benign" and "malignant" tumors. Explain how certain benign tumors cause serious disease.

Explain the various mechanisms by which cancer causes pain, disability, and death.

Explain how paraneoplastic syndromes happen (tumor products, tumor immunity). Given the name of a paraneoplastic syndrome, tell its effect on the patient.

Explain the concept of "tumor markers", substances produced by the tumor that appear in the bloodstream and assist diagnosis. Explain what is meant by an "oncofetal antigen".

Describe the common tumor-suppressor gene deletion syndromes ("autosomal dominant tumor susceptibility syndromes") in principle.

Recognize each of the following tumor-family syndromes by physical signs:

Recognize cancer quackery and its methods. Recognize why a scientific physician must not "keep an open mind" toward obvious untruths, or "debate / dialogue" with these people.

Appreciate the devastating impact of a cancer diagnosis to a patient, and the need for intelligent, humane care of the whole person.

RECOMMENDED READING: The "Neoplasia" chapters in Big or Pocket Robbins. or R&F. All are pretty good. I've followed the sequence in Big Robbins.

KCUMB Students
"Big Robbins" -- Neoplasia
Lectures follow Textbook

QUIZBANK

Neoplasia
Photo Library of Pathology
U. of Tokushima

Growth Disturbances / Neoplasia
Iowa Virtual Microscopy
Have fun

Disseminated breast cancer
Pittsburgh Pathology Cases

LEARN FIRST

INTRODUCTION

ATTRIBUTES OF CANCER CELLS

CHEMICAL CARCINOGENESIS (JAMA 266: 681, 1991; Science 250: 1644, 1990; Science 251: 10 & 387, 1991; little has changed since and this is no longer "cutting edge"; update for the truly-hardcore Mut. Res. 489: 17, 2001)

      Silica / Sand: Lung cancer. Yes, sand is now an "official" EPA carcinogen (Am. J. Epidemiol. 153: 695, 2001 shares my skepticism). The numbers are very soft and there is no easy-to-believe mechanism.
* Agent Orange (which was sprayed on the Vietnam jungles to make the enemy more visible) was contaminated by the experimental carcinogen 2,3,7,8-tetrachlorodibenzoparadioxin (TCDD), which remains present in measurable quantities in some veterans even now (Am. J. Ind. Med. 30: 647, 1996). This is the stuff that greens call "dioxin" for short, which generates great confusion since real "dioxin" is a common, simple diether solvent. There is apparently total agreement by now that the Agent Orange contaminant is not a mutagen / initiator. Even the folks who use it as an experimental carcinogen say it's just a mitogen (Exp. Tox. Path. 51: 555, 1999). Despite the decision by politicians to compensate Vietnam veterans with lymphoma (the son of Admiral Zumwaldt, who ordered the spraying of agent orange, got lymphoma...) and (1993) tobacco-induced lung cancer (I'm not making this up), any link between agent orange (tetrachlorodibenzodioxin) and a plethora of alleged health problems (cancers, birth defects) remains very soft. So is evidence that most of our soldiers were even exposed. See JAMA 265: 898, 1991; Am. J. Pub. Health 81: 289 & 344, 1991; Arch. Env. Health 53: 199, 1998 (Air Force; no chloracne or noted increase in common acne in veterans who sprayed it during Operation Ranch Hand); Am. J. Epidem. 148: 786, 1998 (no increased mortality; no increase in total cancer); J. Occ. Env. Med. 39: 740, 1997 (VA study finds lung cancer claim fails totally); Arch. Env. Health 51: 368, 1996 (gestational trophoblastic disease claim fails); Epidemiology 7: 454, 1996; Ann. Epidem. 5: 414, 1995 (VA; Hodgkin's claim fails completely); Epidemiology 6: 17, 1995 (claims of more stillbirths and birth defects fails completely). No link to prostate cancer: J. Urol. 166: 100, 2001). No link to trophoblastic disease in the Vietnamese people: Arch. Env. Health 41: 368, 1996. People heavily exposed in industry have only a slight increase in overall cancer risk, even assuming that the effect isn't due to confounding variables (Occ. Env. Med. 53: 606, 1996; Env. Health Perspect. 106 S2: 663, 1998); one epidemiologist actually showed how to juggle the statistics, including studies the EPA chose to ignore, to claim tetrachlorodibenzodioxin protects against cancer (sort of like broccoli sprouts, I guess; Reg. Tox. Pharm. 26: 134, 1997.) Nevertheless, in 1994, the Environmental Protection Agency issued a report concluding that tetrachlorodibenzodioxin as among the "greatest threat[s] to public health", i.e., was a grave danger that could be the cause of 1.3 out of every 100 American cancer deaths. Of course, its own Science Advisory Board refused to accept this groundless claim, both in 1995 and after the EPA's 2000 revision (Tox. Sci. 64: 7, 2001 points out even the EPA is not allowed to divide by zero; also Reg. Tox. 36: 211, 2002, which considers among other strange things the EPA's willingness to believe in "U-shaped dose-response curves"). In 1997 the government decided to compensate Vietnam vets whose children have neural tube defects; again this is politics rather than science. Of course, the Hanoi government claims a tremendous increase in birth defects "caused by Agent Orange"; there was a conference in 2001 (Nature 413: 442, 2001) that produced the expected agreement for joint study (Nature 416: 252, 2002). The fiasco continues: One group estimates "'dioxin' body burden" in survivors of "Operation Ranch Hand", and discovers that the "most heavily exposed" people have 50% LESS cancer than controls (Exotoxicity and Env. Saf. 50: 167, 2001); they come up with a weird explanation ("both a promoter blocker and a cancer causation agent...") for this. As the population ages, one study found no effect on prostate cancer (J. Urol. 166: 100, 2001; another found that these veterans seem to come in with more and higher-grade prostate cancers (Cancer 113: 2464, 2008); whether this is real or an artifact remains to be seen.

      * John Travolta's "A Civil Action" popularized the idea that the Woburn cluster of childhood leukemia cases resulted from trichloroethylene from a tannery entering the drinking water. You'll have trouble finding details of the case, but the jury was totally unimpressed, especially since the main company that got sued didn't even use the chemical; another settled. Trichloroethylene-exposed workers are not coming down with more leukemia themselves (Epidemiology 9: 424, 1998; Int. J. Occup. Med. 11: 81, 1998; Cancer Causes & Control 8: 406, 1997). Whatever really happened; I have thought that perhaps trichlorophenol (which has been used in tanning and which is an animal carcinogen) is more suspect.
A Civil Action

RADIATION CARCINOGENESIS

ONCOGENIC VIRUSES

OTHER REPUTED CARCINOGENS

ONCOGENES (review NEJM 358: 502, 2008; older cancer genetics update: Nat. Genet. 33S: 238, 2003.)

DNA IN-SITU HYBRIDIZATION was developed in the late 1980's and has come into its own as an adjunct for cancer diagnosis (Am. J. Clin. Path. 112(S1): S11, 1999). For several tumors, it is now used routinely for every newly-diagnosed case.

TUMOR SUPPRESSOR GENES (anti-oncogenes): Many reviews; Knudson himself in Proc. Nat. Acad. Sci. 90: 10914, 1993; at the bedside Lancet 349-S2: 16, 1997; kids Ped. Clin. N.A. 49: 1393, 2002; adults Arch. Path. Lab. Med. 125: 85, 2001.

LATE PROGRESSION

TUMOR IMMUNOLOGY (mega-review NEJM 358: 2704, 2008)

      Nude mice have no cell-mediated immunity but are no more susceptible to spontaneous cancers than any other mice.

      Today, there are about a dozen strains of genetically modified immunodeficient mice that get increased numbers of particular cancers. However, in every case, we don't see the increased susceptibility to overall cancers that the classic "immune surveillance theory" predicts.

        In most strains, the tumors are malignant lymphomas, just as one would expect -- when part of the immune system is deficent, other portions

        Malignant melanoma, the one common cancer in which the patient's immune response does seem to be an important factor, is somewhat more common in people who are immunocompromised; the business is being sorted out: Mayo Clin. Proc. 87: 991, 2012.

        The Rag2-negative strains develop adenocarciomas of the bowel ... but only if they are inoculated with the bacterium that causes it in mice (Am. J. Path. 162: 691, 2003).

        Read the stuff from the remaining true-believers and decide for yourself: J. Clin. Invest. 117: 1137, 2007;

CANCER IN THE UNITED STATES

CANCER AROUND THE WORLD: Science 254: 1114, 1991 is still good

EFFECTS OF BENIGN TUMORS ON THE PATIENT

EFFECTS OF MALIGNANT TUMORS ON THE PATIENT

{07562} neglected breast cancer

{21118} bone fracture secondary to osteosarcoma

{07138} exsanguination, larynx cancer (probably a jugular-esophageal fistula in neck)

{25669} Cushing's, before and after
{25670} Cushing's
{49426} Cushing's

{16598} clubbing
{46265} clubbing
{12337} clubbing

        Wrong-headed as it seems to most of us today, in the early part of the 20th century (up through the 1960's or thereabouts), it was not just routine to lie to cancer patients about their diagnosis -- it was considered the ethical thing to do. Today, you cannot conceal the diagnosis of cancer from the patient (JAMA 266: 2550, 1991, and probably we never really could).

        You said it yourself, Big Daddy, mendacity is a system we live in.

            -- Brick Pollitt, in "Cat on a Hot Tin Roof"
Mendacity

TUMOR MARKERS (nice review: Am. Fam. Phys. 68: 1075, 2003)


AUTOSOMAL DOMINANT
(i.e., you inherited the first mutation in your germline)


AUTOSOMAL RECESSIVE
(i.e., your genes tend to mutate more)


LEARN THESE TUMOR FAMILY SYNDROMES NOW:

{27883} neurofibromatosis, many neurofibromas
{27886} neurofibromatosis
{37725} neurofibromatosis
{53742} neurofibromatosis, note café au lait spots, elephant skin on right elbow
{53743} neurofibromatosis, elephant skin over large neurofibroma
{13474} neurofibromatosis, armpit freckles
{37735} neurofibromatosis, cauda equina; all nerves seem thickened by neurofibromatous change

Neurofibromatosis
Patient skin
KU Collection

Joseph Merrick * Joseph Merrick, "the elephant man" (the name "John" is propagated error), had Proteus syndrome, not von Recklinghausen's neurofibromatosis (Br. Med. J. 293: 683, 1986). Proteus syndrome is now clearly the result of post-zygotic mutation, as pathologists have thought for decades. It features hemihypertrophy (especially of half the face and the corresponding hand; look at this photo of Mr. Merrick), rib thickening (observed in his skeleton), and various hamartomas. Review JAMA 285: 2240, 2001. More on its being a post-zygotic mutation: Nature 417: 10, 2002, Arch. Derm. 140: 947, 2004; occasionally it's PTEN, the Cowden's locus (Lancet 358: 210, 2001); the most common locus may be AKT1 (NEJM 365: 611, 2011).

{11975} "adenoma sebaceum", mild
{37746} "adenoma sebaceum"
{11976} ash-leaf spot
{11977} ash-leaf spot, as seen under ultraviolet "Woods lamp"
{12190} ash-leaf spot
{27946} tuberous sclerosis, brain, showing tubers (like little white potatoes)
{01828} candle gutterings, walls of ventricles
{01830} candle gutterings, walls of ventricles
{01872} candle guttering, histopathology (don't worry about it)

CANCER QUACKERY (updates CA: 54: 110, 2004; helping victims of expensive fakes NEJM 366: 783, 2012)

SLICE OF LIFE REVIEW: In response to student requests, I have chosen a grab-bag of "normal" pictures of material from the Year I curriculum content for some of the upcoming units. This will appear at the end. For each unit, the order is by picture number. As per my "make 'em think, 'cause they have too much to read already" policy, no long explanations will be provided. Viewing this is STRICTLY OPTIONAL.

{03680} mediastinum, normal
{06227} pulmonary arteries, normal
{09130} cilia, normal
{09131} cilia, abnormal
{13424} karyotype, normal
{13425} karyotype, normal
{13426} karyotype, normal
{14270} immunoelectrophoresis, normal
{14536} umbilical cord, normal, trichrome stain
{14541} loose connective tissue, normal
{14545} loose connective tissue, normal
{14546} loose connective tissue, normal
{14565} tendon, normal
{14687} capillary, normal
{14688} arteriole-venule, normal
{14689} arteriole-venule, normal
{14690} capillary (or venule), normal
{14691} capillary (or venule), normal
{14902} olfactory epithelium, normal
{14941} transitional epithelium, normal
{14952} microtubles, cell biology
{14954} microtubles microfilaments, cell biology
{14960} cytoskeleton membrane interactions, cell biology
{15115} adipose tissue, normal
{15116} connective tissue, loose
{15117} mast cell in loose connective tissue, #3
{15118} fibroblast, in loose connective tissue
{15402} desmosome
{15926} nerve, normal
{16497} mesothelial cells, normal
{16499} mesothelial cells, normal
{17336} neutrophilic wbc, normal em
{20234} ecg, normal
{20255} chest, normal x-ray
{20621} CT, normal CT
{20622} CT, normal CT
{20623} CT, normal CT
{20624} CT, normal CT
{20625} CT, normal CT
{20626} CT, normal CT
{20627} CT, normal CT
{20628} CT, normal CT
{20629} CT, normal CT
{20630} CT, normal CT
{20631} CT, normal CT
{20632} CT, normal CT
{20633} CT, normal CT
{20634} CT, normal CT
{20635} CT, normal CT
{20636} CT, normal CT
{20637} CT, normal CT
{20638} CT, normal CT
{20639} CT, normal CT
{20640} CT, normal CT
{20641} CT, normal CT
{20642} CT, normal CT
{20643} CT, normal CT
{20644} CT, normal CT
{20645} CT, normal CT
{20646} CT, normal CT
{20647} CT, normal CT
{20648} CT, normal CT
{20649} CT, normal CT
{20650} CT, normal CT for orientation
{20717} epithelium, stratified squamous
{20718} epithelium, stratified squamous
{20719} epithelium, transitional
{20720} epithelium, pseudostratified
{20721} epithelium, simple columnar
{20730} adipose tissue, normal
{20730} adipose tissue, normal
{20731} adipose tissue, arrow on nucleus
{20732} connective tissue, loose
{20733} mast cell, connective tissue
{20734} fibroblast, connective tissue
{20735} connective tissue, dense
{20736} connective tissue, dense
{20772} nerve, peripheral
{20773} nerve, peripheral
{20776} nerve, perineurium
{20777} nerve, longitudinal section
{20778} basophil
{20779} lymphocyte, small
{20780} red blood cell, erythrocyte
{20781} lymphocyte, large
{20782} polymorphonuclear leukocyte, normal
{20783} monocyte
{20784} platelets
{20792} epithelium, stratified squamous
{22910} capillary, normal
{24630} joint, normal
{25798} urothelium, normal
{25800} basophilic cytoplasm, urothelium - normal
{26078} urothelial cells, normal
{29914} spine, normal - cryosection
{29915} spine, normal
{29916} spine, normal - cryosection
{29917} spine, normal
{29918} spine, normal - cryosection
{29919} spine, normal
{29920} spine, normal - cryosection
{29921} spine, normal
{29922} spine, normal - cryosection
{29923} spine, normal
{29924} spine, normal - cryosection
{29925} spine, normal
{29926} spine, normal
{29927} spine, normal
{29928} spine, normal
{29929} spine, normal
{29930} spine, normal
{29931} spine, normal
{29932} spine, normal cryosection
{29933} spine, normal
{29934} spine, normal
{29935} spine, normal
{29936} spine, normal cryosection
{29937} spine, normal
{29938} spine, normal
{29939} spine, normal
{29940} spine, normal
{29941} spine, normal
{29942} spine, normal
{29943} spine, normal
{41522} glycogen stores, normal and depleted
{46429} plasma cell, normal
{46431} secretory granules, normal
{46432} nucleolus, normal
{46433} mitosis, normal
{46436} mitochondria, normal
{46437} mitochondria and rough ER, normal
{46550} karyotype, normal

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Teaching Pathology

Pathological Chess


Taser Video
83.4 MB
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