Anaplastic large cell lymphoma: changes in the World Health Organization classification and perspectives for targeted therapy

Abstract

The accompanying perspective by Drs. Falini and Martelli provides a clear description of the current WHO classification with a focus on the distinction between ALK-positive anaplastic large cell lymphoma ALCL and ALK-negative disease. Additionally, they provide a rationale for potential new targets for therapy including flavopiridol. See related paper on page 944.

Figure 1.

(A) Morphological appearance of ALK⁺ anaplastic large cell lymphoma (ALCL) of common type (hematoxylin-eosin; x 800). The arrow indicates a typical hallmark tumor cell. Cases with the same morphological features but lacking the ALK protein are classified as ALK-negative ALCL. (B) Minimal lymph node involvement with an intrasinusoidal pattern in ALK⁺ ALCL. The arrows points to an ALK⁺ lymphoma cell within the subcapsular sinus (x 200). (C) In ALCL carrying the NPM-ALK fusion protein, positivity for ALK (in red) is found both in the cytoplasm and nucleus of neoplastic cells (x 800, arrow). (D) In ALCL carrying a ALK variant fusion protein, positivity for ALK (in red) is restricted to the cytoplasm of neoplastic cells (x 800, arrow). B-D: immunostaining of lymph node paraffin sections with anti-ALK monoclonal antibody (clone ALKc); APAAP technique and hematoxylin counter-staining.

Figure 2.

Alterations of the ALK gene (translocations or mutations) are found in a large variety of human neoplasms including hematopoietic tumors such as ALK⁺ ALCL and ALK⁺ diffuse large B-cell lymphoma (both included as distinct entities in the 2008 WHO classification), a small subset of non-small cell lung cancer carrying the EML4-ALK rearrangement and neuroblastoma, which may harbor ALK gene mutations. IMT indicates inflammatory myofibroblastic tumor. ALK expression in IMT usually occurs in young patients. * Three cases of ALK⁺ histiocytosis have been reported. This entity occurs in early infancy and is characterized by a good outcome (Chan JK, Blood, 112:2965, 2008).