Wednesday, September 8, 2010

Mystery of the missing prelymphomas

A large problem in pathology is the lack of any consistent nomenclature for the precancers. Consequently, many precancerous lesions are simply not recognized as such, and cannot be included in clinical trials that assess the effectiveness of precancer treatments.

For example, lymphoma experts do not use the terms "precancer" or "prelymphoma" [prelymphomas are lesions that precede the development of lymphomas].

In a recent article, Elaine Jaffe discussed a condition that can be detected by flow cytometry in which monoclonal populations of CD5+ B-cells are found in 3% of healthy adults over the age of 40.

Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Am Soc Hematol Educ Program 523-531, 2009.

Many of these clones have the same marker chromosomes found in chronic lymphocytic leukemia (CLL). A small percentage of patients with these lesions will progress to CLL. This lesion is a precancer for CLL; and is strictly analogous to MGUS (monocloncal gammopathy of undetermined significance) a condition that precedes virtually every case of multiple myeloma (MGUS was discussed in a prior blog entry).

The condition has been given a name: monoclonal B-cell lymphocytosis. This is the only name by which the lesion is addressed in the WHO (World Health Organization) lymphoma classification.

Monoclonal B-cell lymphocytosis has all of the biological properties of a precancer It should be recognized as such (in this specific case, as the prelymphoma for CLL). If it were, it could be included in clinical trials for precancers.

The WHO has grappled with several different proliferative lymphoid lesions that can precede the development of lymphomas. They have used, or currently use, terms such as "proliferations of uncertain malignant potential" or "intrafollicular neoplasia", or "in situ follicular neoplasia." Why bother? There is an accepted term for lesions that precede cancers of every cell type of origin: precancers. The word "precancer" does not appear anywhere in the WHO classification or in Dr. Jaffe's discussion of the WHO classification. It would be very helpful if hematopathologists climbed aboard on this issue.

Though we are currently treating only a few of the different kinds of precancers in man, there is ample evidence that precancer treatment effectively reduces the number of people who die from cancer. In the next blog, I'll expand the topic of precancer treatment.

- © 2010 Jules Berman

key words: lymphoma, lymphoma classification, prelymphoma, pre-lymphoma, precancer, lymphocytosis, precancer treatment

About Precancer: The Beginning and the End of Cancer. Nearly every type of cancer passes through a precancer phase, during which it cannot metastasize or invade other tissues. While medicine is not always successful in treating or curing advanced stages of cancers, recent advances in our understanding of carcinogenesis have helped us to develop strategies to prevent, diagnose, and treat many cancers at the precancer stage. Research in this field is escalating rapidly as the evidence increasingly shows that the number of annual cancer deaths could be drastically reduced through the effective treatment and cure of precancer lesions. This book begins by explaining why it has been so difficult to cure cancers, followed by a review of precancer biology, with descriptions of the most common precancer lesions. The final chapters provide practical socio-political and medical goals for precancer treatment, including discussions of the economics and politics of treating precancers.