ALK-positive lymphoma

A single disease with a broad spectrum of morphology

Daniel Benharroch, Zarouhie Meguerian-Bedoyan, Laurence Lamant, Chauki Amin, Laurence Brugières, Marie Jose Terrier-Lacombe, Eugenia Haralambieva, Karen Pulford, Stefano Pileri, Stephan W. Morris, David Y. Mason, Georges Delsol

Research output: Contribution to journalArticle

405 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2076-2084
Number of pages9
JournalBlood
Volume91
Issue number6
Publication statusPublished - Mar 15 1998

Fingerprint

Anaplastic Large-Cell Lymphoma
Lymphoma
Biopsy
Tumors
Proteins
Mucin-1
Infiltration
Staining and Labeling
Neoplasms
Monoclonal Antibodies
Hodgkin Disease
Cytoplasm

ASJC Scopus subject areas

  • Hematology

Cite this

Benharroch, D., Meguerian-Bedoyan, Z., Lamant, L., Amin, C., Brugières, L., Terrier-Lacombe, M. J., ... Delsol, G. (1998). ALK-positive lymphoma: A single disease with a broad spectrum of morphology. Blood, 91(6), 2076-2084.

ALK-positive lymphoma : A single disease with a broad spectrum of morphology. / Benharroch, Daniel; Meguerian-Bedoyan, Zarouhie; Lamant, Laurence; Amin, Chauki; Brugières, Laurence; Terrier-Lacombe, Marie Jose; Haralambieva, Eugenia; Pulford, Karen; Pileri, Stefano; Morris, Stephan W.; Mason, David Y.; Delsol, Georges.

In: Blood, Vol. 91, No. 6, 15.03.1998, p. 2076-2084.

Research output: Contribution to journalArticle

Benharroch, D, Meguerian-Bedoyan, Z, Lamant, L, Amin, C, Brugières, L, Terrier-Lacombe, MJ, Haralambieva, E, Pulford, K, Pileri, S, Morris, SW, Mason, DY & Delsol, G 1998, 'ALK-positive lymphoma: A single disease with a broad spectrum of morphology', Blood, vol. 91, no. 6, pp. 2076-2084.
Benharroch D, Meguerian-Bedoyan Z, Lamant L, Amin C, Brugières L, Terrier-Lacombe MJ et al. ALK-positive lymphoma: A single disease with a broad spectrum of morphology. Blood. 1998 Mar 15;91(6):2076-2084.
Benharroch, Daniel ; Meguerian-Bedoyan, Zarouhie ; Lamant, Laurence ; Amin, Chauki ; Brugières, Laurence ; Terrier-Lacombe, Marie Jose ; Haralambieva, Eugenia ; Pulford, Karen ; Pileri, Stefano ; Morris, Stephan W. ; Mason, David Y. ; Delsol, Georges. / ALK-positive lymphoma : A single disease with a broad spectrum of morphology. In: Blood. 1998 ; Vol. 91, No. 6. pp. 2076-2084.
@article{0503dd29847e4517bcc3a415450c0701,
title = "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.",
author = "Daniel Benharroch and Zarouhie Meguerian-Bedoyan and Laurence Lamant and Chauki Amin and Laurence Brugi{\`e}res and Terrier-Lacombe, {Marie Jose} and Eugenia Haralambieva and Karen Pulford and Stefano Pileri and Morris, {Stephan W.} and Mason, {David Y.} and Georges Delsol",
year = "1998",
month = "3",
day = "15",
language = "English",
volume = "91",
pages = "2076--2084",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "6",

}

TY - JOUR

T1 - ALK-positive lymphoma

T2 - A single disease with a broad spectrum of morphology

AU - Benharroch, Daniel

AU - Meguerian-Bedoyan, Zarouhie

AU - Lamant, Laurence

AU - Amin, Chauki

AU - Brugières, Laurence

AU - Terrier-Lacombe, Marie Jose

AU - Haralambieva, Eugenia

AU - Pulford, Karen

AU - Pileri, Stefano

AU - Morris, Stephan W.

AU - Mason, David Y.

AU - Delsol, Georges

PY - 1998/3/15

Y1 - 1998/3/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0032521239&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032521239&partnerID=8YFLogxK

M3 - Article

VL - 91

SP - 2076

EP - 2084

JO - Blood

JF - Blood

SN - 0006-4971

IS - 6

ER -