B-Cell Anaplastic Large Cell Lymphoma—The Forgotten Entity

The authors thank Dr. Naresh for his interest in our article 8 and for giving us the opportunity to discuss some further aspects related to our study. Concerning his first comment, large B-cell lymphomas expressing CD30 have been recognized for a long time and they were included as an entity in the updated Kiel classification. 5 Since then, evidence has been collected about the fundamental differences between CD30-expressing lymphomas of B-type versus those of T/null-type. Lymphomas that are composed of sheets of blast cells expressing strongly CD20 are a variant of large B-cell lymphoma. The expression of CD30 is usually only seen on a minority of tumor cells and there is no proven prognostic significance with regard to therapy or survival. 1,6 Furthermore, CD30 is also expressed on plasma cells and their precursors and may in some cases of diffuse large B-cell lymphoma be related to plasmoblastic differentiation rather than “anaplasia.” The term diffuse large B-cell lymphoma with CD30 expression may be optionally used in order to avoid confusion with typical anaplastic large cell lymphoma. In contrast, anaplastic large cell lymphoma is an entity of T-cell origin and T-cell lineage can be proven by molecular studies in most cases, even if there is no T-cell antigen expression. 2 These CD30+ anaplastic large cell lymphomas of T-type show a unique clinical presentation and their prognosis is more favorable than other peripheral T-cell lymphomas. As recently discussed by Gascoyne et al. 3, nodular lymphocyte predominance Hodgkin's lymphoma and T-cell rich B-cell lymphoma share conceptually and cytologically (but not with respect to their clinical and prognostic features) many similarities and could be extremes of the malignant transformation of identical tumor stem cells. The immunophenotype and immunoglobulin mutation pattern of the tumor cells is very similar. Some patients presenting with lymphomas showing areas of nodular lymphocyte predominant Hodgkin's lymphoma or T-cell rich B-cell lymphoma in the same lymph node are observed. However, significant differences with regard to phenotype (J-chain expression, IgM expression) are seen. On the other hand, both clinical presentation and, more importantly, the prognosis of these entities are completely different, requiring different treatment modalities. 4,9 Therefore, criteria of distinction may be more relevant than morphologic similarities. Even by applying the most sophicated methods it will not be possible to resolve the biological and diagnostic continuum or “grey zone”7 of the discussed entities in every case. However, in our experience of 2000 cases submitted to a German HD trial over the last two and a half years it should not be more than 0.5%. Thomas Rüdiger M.D. German Ott M.D. Maria Michaela Ott M.D. Sigrid Maria Müller-Deubert Ph.D. Hans Konrad Müller-Hermelink M.D.