Abstract
The tumor cells in ALK-positive lymphoma ('ALKoma') usually express the product of the NPM-ALK chimeric gene, generated by the t(2;5) chromosomal translocation. However, 10% to 20% of ALK-positive lymphomas express ALK fusion protein(s) other than NPM-ALK, and in this report, we describe the immunohistologic and clinicopathologic features of 15 such cases. The absence of the NPM-ALK fusion gene was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 8 cases and by fluorescence in situ hybridization (FISH) analysis in a further 2 cases. In each case, ALK staining was restricted to the cytoplasm and the N-terminus of NPM to the nucleus (contrasting with lymphomas expressing NPM-ALK in which cytoplasmic as well as nuclear labeling is seen). However, in the course of screening 53 ALK- positive lymphomas, 2 biopsies were found that had a 'cytoplasm-only' ALK staining pattern but that nevertheless were shown to carry the (2;5) (by NPM staining and RT-PCR). The 15 cases resembled typical NPM-ALK-positive lymphomas in that all were of T or null phenotype, usually occurred in young male patients, and frequently presented with advanced disease associated with systemic symptoms and extranodal involvement. Moreover their prognosis was excellent and indistinguishable from that of classical t(2;5)positive tumors, but was clearly different from that of ALK-negative anaplastic large-cell lymphomas. These results suggest that lymphomas carrying variants of the NPM- ALK fusion protein can be detected by immunostaining for ALK and NPM and also that they can be grouped with classical t(2;5)-positive tumors as a single entity (ALK-positive lymphoma or 'ALKoma') that shows a better prognosis than ALK-negative anaplastic large-cell lymphoma.
| Original language | English |
|---|---|
| Pages (from-to) | 3509-3515 |
| Number of pages | 7 |
| Journal | Blood |
| Volume | 94 |
| Issue number | 10 |
| Publication status | Published - Nov 15 1999 |
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ASJC Scopus subject areas
- Hematology
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Lymphomas expressing ALK fusion protein(s) other than NPM-ALK. / Falini, Brunangelo; Pulford, Karen; Pucciarini, Alessandra; Carbone, Antonino; De Wolf-Peeters, Chris; Cordell, Jacqueline; Fizzotti, Marco; Santucci, Antonella; Pelicci, Pier Giuseppe; Pileri, Stefano; Campo, Elias; Ott, German; Delsol, Georges; Mason, David Y.
In: Blood, Vol. 94, No. 10, 15.11.1999, p. 3509-3515.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Lymphomas expressing ALK fusion protein(s) other than NPM-ALK
AU - Falini, Brunangelo
AU - Pulford, Karen
AU - Pucciarini, Alessandra
AU - Carbone, Antonino
AU - De Wolf-Peeters, Chris
AU - Cordell, Jacqueline
AU - Fizzotti, Marco
AU - Santucci, Antonella
AU - Pelicci, Pier Giuseppe
AU - Pileri, Stefano
AU - Campo, Elias
AU - Ott, German
AU - Delsol, Georges
AU - Mason, David Y.
PY - 1999/11/15
Y1 - 1999/11/15
N2 - The tumor cells in ALK-positive lymphoma ('ALKoma') usually express the product of the NPM-ALK chimeric gene, generated by the t(2;5) chromosomal translocation. However, 10% to 20% of ALK-positive lymphomas express ALK fusion protein(s) other than NPM-ALK, and in this report, we describe the immunohistologic and clinicopathologic features of 15 such cases. The absence of the NPM-ALK fusion gene was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 8 cases and by fluorescence in situ hybridization (FISH) analysis in a further 2 cases. In each case, ALK staining was restricted to the cytoplasm and the N-terminus of NPM to the nucleus (contrasting with lymphomas expressing NPM-ALK in which cytoplasmic as well as nuclear labeling is seen). However, in the course of screening 53 ALK- positive lymphomas, 2 biopsies were found that had a 'cytoplasm-only' ALK staining pattern but that nevertheless were shown to carry the (2;5) (by NPM staining and RT-PCR). The 15 cases resembled typical NPM-ALK-positive lymphomas in that all were of T or null phenotype, usually occurred in young male patients, and frequently presented with advanced disease associated with systemic symptoms and extranodal involvement. Moreover their prognosis was excellent and indistinguishable from that of classical t(2;5)positive tumors, but was clearly different from that of ALK-negative anaplastic large-cell lymphomas. These results suggest that lymphomas carrying variants of the NPM- ALK fusion protein can be detected by immunostaining for ALK and NPM and also that they can be grouped with classical t(2;5)-positive tumors as a single entity (ALK-positive lymphoma or 'ALKoma') that shows a better prognosis than ALK-negative anaplastic large-cell lymphoma.
AB - The tumor cells in ALK-positive lymphoma ('ALKoma') usually express the product of the NPM-ALK chimeric gene, generated by the t(2;5) chromosomal translocation. However, 10% to 20% of ALK-positive lymphomas express ALK fusion protein(s) other than NPM-ALK, and in this report, we describe the immunohistologic and clinicopathologic features of 15 such cases. The absence of the NPM-ALK fusion gene was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in 8 cases and by fluorescence in situ hybridization (FISH) analysis in a further 2 cases. In each case, ALK staining was restricted to the cytoplasm and the N-terminus of NPM to the nucleus (contrasting with lymphomas expressing NPM-ALK in which cytoplasmic as well as nuclear labeling is seen). However, in the course of screening 53 ALK- positive lymphomas, 2 biopsies were found that had a 'cytoplasm-only' ALK staining pattern but that nevertheless were shown to carry the (2;5) (by NPM staining and RT-PCR). The 15 cases resembled typical NPM-ALK-positive lymphomas in that all were of T or null phenotype, usually occurred in young male patients, and frequently presented with advanced disease associated with systemic symptoms and extranodal involvement. Moreover their prognosis was excellent and indistinguishable from that of classical t(2;5)positive tumors, but was clearly different from that of ALK-negative anaplastic large-cell lymphomas. These results suggest that lymphomas carrying variants of the NPM- ALK fusion protein can be detected by immunostaining for ALK and NPM and also that they can be grouped with classical t(2;5)-positive tumors as a single entity (ALK-positive lymphoma or 'ALKoma') that shows a better prognosis than ALK-negative anaplastic large-cell lymphoma.
UR - http://www.scopus.com/inward/record.url?scp=0033570945&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033570945&partnerID=8YFLogxK
M3 - Article
C2 - 10552961
AN - SCOPUS:0033570945
VL - 94
SP - 3509
EP - 3515
JO - Blood
JF - Blood
SN - 0006-4971
IS - 10
ER -