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New WHO Revision for Lymphoma Classification

Carlson, Robert H.

doi: 10.1097/01.COT.0000337616.51377.52

While the 2008 revision of the World Health Organization Classification of Tumors of the Hematopoietic and Lymphoid Tissues does not contain major changes from the 2001 edition, it may answer questions clinicians still have, said Nancy Lee Harris, MD, Professor of Pathology at Massachusetts General Hospital, speaking in a presentation at the International Conference on Malignant Lymphoma.

“The revision might explain some odd things clinicians have been seeing but haven't understood before, like Epstein-Barr virus-positive diffuse large B-cell lymphomas in the elderly.”

These can be difficult for a pathologist, she said, because they may look like infectious mononucleosis and tend to be extra-nodal.

“Patients are very sick but actually respond very well to CHOP-R chemotherapy. As a clinician you still want to know what you are treating—even if the treatment is the same, your expectations for outcome will be different.”

The 2008 classification is a revision of the 2001 edition, which in turn was based on the principles of the Revised European-American Classification of Lymphoid Neoplasms (REAL), published in 1994 by the International Lymphoma Study Group.

“That was a list of ‘real’ disease entities defined by a combination of morphology, immunophenotype, genetic features, and clinical features,” she said. “The relative importance of each of these features varies among diseases, and there is no one ‘gold standard.’”

The process of revising for the fourth edition in 2008 began in 2006, she said, and involved more than 75 international hematopathologists and a similar number of recognized experts in hematology and oncology.

In an interview, Dr. Harris called the 2008 changes incremental, incorporating data from research in the previous seven years. This makes the classification more practical, she said, and some of the entities are better defined—for example, the gray zone between mediastinal large B-cell lymphoma and classical Hodgkin lymphomas is addressed.

And while various subcategories of diffuse large B-cell lymphoma are all treated the same, they actually have slightly different clinical presentations so that clinicians may recognize them when they see patients, she said. “This might change diagnosis and risk stratification and what they tell their patients.”

Dr. Harris was candid when comparing the responses of clinicians to the new classification with less enthusiastic responses from some pathologists.

“Clinicians seem almost more receptive than pathologists because this classification explains the complexity of their patients, and they recognize these diseases. It is not a problem recognizing a lot of diseases if they all mean something to you.

“But pathologists in the community are having a problem with [the revision] because they only see 10 or 20 lymphomas a year, and if each one is different and they have to do this mega-workup with immunostaining and molecular studies, it's daunting.”

This has the unfortunate tendency of making pathologists a bit discouraged about lymphoma, she said.

“They tend to send [lymphoma patients] for consultation, which may be good for standardization of diagnoses, but I have been impressed that clinicians are less resistant to the complexity [of lymphoma] than pathologists are.”

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