Clinical Aggressiveness

The REAL and WHO classifications clearly distinguish between histological grade and clinical aggressiveness. Histological grade is based on cell and especially nuclear size, density of nuclear chromatin, and the proliferation fraction determined by immunos-taining with Ki-67. Low-grade lymphomas are composed of small cells with dense nuclear chromatin and a low proliferation fraction; the converse is true for high-grade tumors. The REAL and WHO classifications, unlike the Kiel classification, do not separate lymphomas according to grade in recognition of the fact that low-grade lymphomas may transform to high-grade tumors without changing the disease "entity." Histological grade mostly correlates with clinical aggressiveness, but this is not always the case. Mantle cell lymphoma is histologically low grade but clinically aggressive15 as are some T-cell lymphomas such as angioimmunoblastic T-cell lymphoma.16 The Working Formulation and the Kiel classification both stressed the fundamental importance of "grade" in determining treatment, although using the term to mean different things. The REAL and WHO classifications instead stress the disease entity. Thus, not all "low-grade" B-cell lymphomas are necessarily treated alike as exemplified by hairy cell leukemia, for which highly specific therapy has evolved.17 It is likely that as the different entities become more sharply defined and are recognized clinically, more disease-specific therapies will emerge.

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