Lymphoma--histopathology in changing clinical perspective. Non-Hodgkin's Lymphoma Classification Project

Lymphoma management has traditionally been dominated by nodal histopathology. Unfortunately, many different classifications coexisted and frequent revisions have often obscured clinical correlations. Some improvement in understanding histogenesis followed the introduction of immunophenotyping, while a number of new entities have been described in the last decade. In addition the whole question of lymphomagenesis is undergoing critical exploration. The use of cellular and molecular biological techniques is therefore shifting focus to the role of oncoproteins and the impact of mutation in the normally modulating suppressor genes. To accommodate these advances the International Lymphoma Study Group has proposed the Revised European-American Lymphoma Classification. While this is an undoubted advance, it has met with persisting concerns regarding applicability to patient management.

In determining the extent to which the latter reservation is valid, and at the same time directly testing the clinicopathological value of the new system, a group of acknowledged experts drawn from nine major academic centres worldwide analysed approximately 1,400 previously unreported cases, focusing on outcome. As part of that study 196 consecutive patients seen in Cape Town were separately examined.

Findings here were similar to those of the overall experience, although distinct geographical differences emerged. Specifically in the follicular centre-cell lymphomas there was no difference in the 5-year failure-free survival rate, but these neoplasms accounted for 33% of lymphomas, which is similar to North America and London but contrasts with the 14% in the remaining six sites. Also, while mean survival for all types of peripheral T-cell lymphoma was 18% at 5 years, these accounted for 8% of lymphomas locally, as seen also in London and Hong Kong, but exceeding the 3-6% reported elsewhere. Local experience, as in the other eight centres, documented good diagnostic concordance between trained haematopathologists when this classification was used by them all. Furthermore, unusual subtypes were generally well accommodated within this revised system. It should be noted that while histopathological features retain predictive value, they should not be considered the predominant factor. It was concluded that for management decisions to be appropriate, renewed and correct weighting must be assigned to other prognostic variables that include clinical features and markers of tumour biology.

This more enlightened prerequisite is the central goal that underlies optimal treatment outcome, since it determines stratification to appropriate and peer-reviewed protocols. It follows that review of histopathology needs to precede management of all newly diagnosed cases, preferably only by accredited multidisciplinary clinics. The previous anachronism of basing therapy on opinions of non-specialist pathologists, without appropriate review, is unwise. Furthermore, treatment by lone practitioners, or even single-specialty groups that lack the discipline to analyse their findings critically and regularly report their updated results, can no longer be considered standard of practice and should be discouraged.