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Cancer: do we really understand it? Part 2

-Continued from previous post-

In contradistinction to these patients exposed to tumor cells who did not develop malignancies, other studies have shown that normal cells can become malignant in an environment where a malignancy had developed. One study, for example, followed two leukemia patients whose bone marrows were eradicated with radiotherapy and who subsequently received bone marrow transplants from normal donors. Two to four months following the procedure, the transplanted bone marrow donor cells were found to have become leukemic.(11)

Clearly, cellular environment plays a critical role in cancer development. Malignant cells infused into a normal environment may not produce a tumor while normal cells placed into an environment that had previously harbored a tumor can become malignant. We are no longer even sure from what cell type a particular cancer develops. Stomach cancer in mice has been shown to originate not from the lining cells of the stomach, as we had thought, but from bone marrow cells responding to experimentally-induced stomach inflammation.(12) The problem may be the environment not the “malignant” cell.(13)

Are we at least able to recognize clinically significant cancer? Can we confidently say, as one judge did when defining pornography, “I know it when I see it.?” Apparently not.

Autopsies on people who died of non-malignant causes have caused us to re-examine our definition of cancer. Patients with previously treated Hodgkins disease—showing no clinical evidence of tumor and thought to have been cured, who died of unrelated causes—were found on autopsy to have residual foci of the disease.(14) Although thyroid cancer is diagnosed in only 1 in 1000 adults between the ages of 50 and 70, on autopsy it has been found in 1 of 3 adults.(15) The prevalence of clinically apparent prostate cancer in men 60 to 70 years of age is about 1%; nevertheless, over 40% of men in their 60s with normal rectal examinations have been found to have histologic evidence of the disease,(16) and autopsy studies have found evidence of prostate cancer in 1 out of 3 men by age 50(17), a finding which rises to 7 out of 10 men by age 80.(18) Similarly, clinical breast cancer is diagnosed in 1 out of 100 women between the ages of 40 and 50;(19) on autopsy it was found in a startling 1 out of 2.5 women in this age group. Moreover, over 45% of the autopsied women had more than one focus of breast cancer and 40% had bilateral breast cancer.(20)

What, then, is cancer? What is responsible for the clinical behavior of cancer, sometimes lying dormant and undiagnosed because it causes no symptoms, sometimes progressing inexorably to death?

For the present, we don’t know the answers to these questions. We have developed treatment programs that offer the best current options for cure, but we should, and do, remain unsatisfied with these approaches. First, because they don’t always work and, second, because with rare exception, they are based on trial and error, not on an understanding of the disease process we are treating.

Once we identify the processes responsible for the accumulation of cells into tumors, we can treat these conditions more effectively, reduce or eliminate the side effects associated with many of our current “best practice” treatments, and remove the terror currently shadowing cancer the way terror used to shadow diseases like syphilis, tuberculosis, and pernicious anemia before we learned how they were caused and developed treatments directed at those causes. We are making progress. Stay tuned.


1. Bennington JL. Cancer of the kidney – etiology, epidemiology and pathology. Cancer 1973;32:1017-29

2. Salvador AH, Harrison EG Jr, Kyle RA. Lymphadenopathy due to infectious mononucleosis: its confusion with malignant lymphoma. Cancer 1971;27:1029-40

3. Lukes RJ, Tindle BH, Parker JW. Reed-Sternberg-like cells in infectious mononucleosis. Lancet 1969;2:1003-4

4. Agliozzo CM, Reingold IM. Infectious mononucleosis simulating Hodgkin’s disease: a patient with Reed-Sternberg cells. Am J Clin Pathol 1971;56:730-5

5. Mirra JM, Kendrick RA, Kendrick RE. Pseudomalignant osteoblastoma versus arrested osteosarcoma. A case report. Cancer 1976;37:2005-14

6. Taubert HD, Wissner SE, Haskins AL. Leiomyomatosis peritonealis disseminata. Obstet Gynecol 1965;25:561-74

7. Croslend DB. Leiomyomatosis peritonealis disseminata: a case report. Am J Obstet Gynecol 1973;117:179-81

8. Mintz B, Illmensee K. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci 1975;72(9):3585-9

9. Lanman JT, Bierman HR, Byron RL Jr. Transfusion of leukemic leukocytes in man. Hematologic and physiologic changes. Blood 1950;5:1099-1113

10. Greenwald P, Woodard E, Nasca PC, Hempelmann P, Dayton P, Maksymowicz G, Blando P, Hanrahan R jr, Burnett WS. Morbidity and mortality among recipients of blood from preleukemic and prelymphomatous donors. Cancer 1976;38:324-8

11. Thomas ED, Bryant JI, Bruckner CD, Clift RA, Fefer A, Neiman P, Ramberg RE, Storb R. Leukemic transformation of engrafted human marrow. Transpl Proc 1972;4:567-70

12. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC. Gastric cancer originating from bone marrow-derived cells. Science 2004;306:1568-71

13. Bluming AZ. Cancer: The eighth plague – A suggestion of pathogeneisis. Isr J Med Sci 1978;14:192-200

14. Dorfman RF. Biology of malignant neoplasia of the lymphoreticular tissues. J Reticuloendothelial Soc 1972;12:239-56

15. Harach HR, Franssila KO, Wasenius VM. Occult papillary carcinoma of the thyroid. A “normal” finding in Finland. A systematic autopsy study. Cancer 1985; 56 (3): 531-8

16. Montie JE, Wood DP Jr, Pontes E, Boyett JM, Levin HS. Adenocarcinoma of the prostate in cytoprostatectomy specimens removed for bladder cancer. Cancer 1989;63:381-5

17. Oottamasathien S, Crawford D. Should routine screening for prostate-specific antigen be recommended? Arch Intern Med 2003;163:661-2

18. Pienta KJ, Esper PS. Risk factors for prostate cancer. Ann Intern Med 1993;118:793-803

19. Feldman AR, Kessler L, Myers MH, Naughton MD. The prevalence of cancer, estimates based on the Connecticut Tumor Registry. N Engl J Med 1986; 315:1394-7

20. Nielsen M, Thomsen JL, Primdahl S, Dyreborg U, Andersen JA. Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies. (Br J Cancer 1987; 56:814-9

This post originally appeared on Dr. Val’s blog at

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