ALK-Positive Lymphoma: A Single Disease With a Broad Spectrum of Morphology

Abstract

The t(2;5)(p23;q35) translocation, associated with anaplastic large-cell lymphoma (ALCL), results in the expression of a chimeric NPM-ALK protein that can be detected by the ALK1 monoclonal antibody. This report describes the morphologic and phenotypic spectrum of 123 cases of lymphoma that all express ALK protein. The results provide strong evidence that the morphologic patterns of ALCL described in previous reports as representing possible subtypes of ALCL, eg, common type, lymphohistiocytic, or small cell patterns, are morphologic variants of the same disease entity. All of these morphologic patterns could be found within this series, and in some patients different subtypes coexisted in a single biopsy or were found in successive biopsies from a single patient. The link between these morphologic subtypes is further reinforced by the presence in all cases of a highly characteristic large cell, with an eccentric nucleus and an eosinophilic paranuclear region. We suggest that this cell can be considered as a major distinguishing feature of ALK-positive lymphomas. Another characteristic of these tumors was the perivascular pattern of neoplastic cell infiltration seen in a significant number of cases. In addition to ALK protein, all tumors expressed epithelial membrane antigen and lacked CD15, features that may be of value in differentiating ALCL from Hodgkin's disease. In the majority of cases (84%), malignant cells showed both a cytoplasmic and nuclear staining for ALK1 and thus presumably carried the 2;5 translocation, but staining was restricted to the cytoplasm in a few cases, suggesting that translocations other than t(2;5) may induce expression of ALK protein. We conclude from this study that ALK-positive neoplasms represent a distinct entity. Because their morphology is often neither anaplastic nor large cell, we suggest that they should henceforward be referred to as ALK lymphomas.

ALK‐negative anaplastic large‐cell lymphoma demonstrates similar poor prognosis to peripheral T‐cell lymphoma, unspecified

“…Included in ALCL were several morphological subtypes such as the small-cell variant, described previously. 9,10 analysis of clinical data For each patient the following characteristics were noted from the medical records: age at diagnosis, sex, Ann Arbor stage at presentation, therapy, achievement of complete remission, occurrence of relapses, and cause of death. Treatment usually consisted of CHOP polychemotherapy regimens.…”

“…8 Another predominantly nodal TCL is the anaplastic large-cell lymphoma (ALCL), first reported in 1985 9 and subsequently shown to possess distinct clinicopathological features, separating it from other mature nodal TCL. Characterized by CD30+ tumour cells with 'anaplastic' morphology, 7,[9][10][11] ALCL has been shown to run a more favourable clinical course than other mature TCL. 3,4,[12][13][14] However, recent studies have shown that the relatively good prognosis of ALCL can be attributed to a subgroup carrying a chromosomal 2p23 abnormality.…”

Peripheral T/NK‐cell lymphoma: a report of the IXth Workshop of the European Assocation for Haematopathology

“…These`hallmark cells' predominate and tend to diffuse through sinuses in ALCL of the common type, are obscured by macrophages in the lympho-histiocytic form, and give rise to perivascular cuffs in the small-cell variant. 62 Seven of eight cases expressed ALK, six cases expressing the protein both within the cytoplasm and nucleus indicative of a t(2;5) (see below). One case presented with prominent subcutaneous lesions and at least one other case had dissemination to the skin.…”

“…In approximately 20±30% of ALCL, ALK is expressed in neoplastic cells with variant translocations other than t(2;5): under these circumstances the staining is limited to the cytoplasm (Figures 2,3). 62,78,81 On the whole, one should bear in mind that: X ALK staining is not observed in lymphomas other than ALCL nor in normal lymphoid elements, thus representing a powerful tool both for the diagnosis at presentation and the detection of minimal residual disease. A single exception is an extremely rare B-cell lymphoma described by Delsol et al, which expresses full length, cytoplasmic ALK without the presence of a translocation at 2p23.…”

“…A single exception is an extremely rare B-cell lymphoma described by Delsol et al, which expresses full length, cytoplasmic ALK without the presence of a translocation at 2p23. 79 X Among ALCLs, ALK staining is limited to the primary systemic and not the primary cutaneous variant, occurring in 60±85% of the forms with common histology, in almost all the lymphohistiocytic and small-cell subtypes, and in a minority of the giant cell-rich and Hodgkin's-like tumours X The positivity is only seen in ALCL carrying T-cell or null phenotype and usually expressing the epithelial membrane antigen (EMA) 62,78,80 These findings support the decisions to limit the term ALCL to T-cell/null neoplasms and to separate the cutaneous from the systemic forms.…”