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.

Distribution of NPM1‐ALK and X‐ALK fusion transcripts in paediatric anaplastic large cell lymphoma: a molecular–histological correlation

“…Comparison of the molecular analyses with the immunohistochemical ALK staining pattern revealed complete concordance: all NPM1-ALK positive ALCL expressed ALK in the nucleus while no tumour with a variant ALK fusion transcript showed nuclear ALKstaining. This first molecular-immunohistological correlation in a large cohort of children with ALCL substantiates earlier descriptions from case series (Benharroch et al, 1998;Falini et al, 1999;Perkins et al, 2005).…”

“…This is in line with the results of a smaller study of Perkins et al, (2005), which identified 3/34 (9%) variant fusions by FISH and 4/42 (9AE5%) by ALK cytoplasmic staining. The proportion of the variant ALK-fusion partners seems to be lower in children (£10%) compared to adults (20-25%) according to studies that relied on the ALK staining pattern in adults (Benharroch et al, 1998;Falini et al, 1999). One earlier case series suggested a higher proportion of variant ALK fusion genes among children with ALCL defined by aberrant karyotypes (Liang et al, 2004 ALK-positive ALCL and was hampered by a low concordance between cytogenetics, FISH and ALK-staining pattern.…”

Infant Anaplastic Large Cell Lymphoma with Hemophagocytic Syndrome

“…Morphologically, ALK-positive ALCL has several variants, which may mimic Hodgkin lymphoma, a sarcoma, or an inflammatory process [1,14–18]. Common to all is the presence of cells with eccentric reniform nuclei and an eosinophilic or pale paranuclear hof known as “hallmark cells.” When there is only partial involvement of a lymph node, the cells may grow in a sinusoidal distribution or colonize the paracortex in a cohesive manner and may mimic metastatic carcinoma or other anaplastic epithelioid malignancies [11].…”

Anaplastic Large Cell Lymphomas: A Study of 75 Pediatric Patients

“…A T-cell antigenic phenotype was reported in slightly more than half of the ALCLs; the remaining cases had a null phenotype [22]. However, with a more extensive immunohistochemical study including multiple-surface T-cell antigens (CD2, CD3, CD4, CD5, CD7, CD8, CD43, CD45RO, LAT), we have demonstrated a T-cell phenotype in as many as 88% of the cases.…”