Absence of anaplastic lymphoma kinase (ALK) and Epstein-Barr virus gene products in primary cutaneous anaplastic large cell lymphoma and lymphomatoid papulosis.
The prevalence of the t(2;5)(p23;q35) and/or anaplastic lymphoma kinase (ALK) gene products in cutaneous anaplastic large cell (ALC) lymphomas and a potential precursor lesion, lymphomatoid papulosis (LyP), is controversial. ALK gene products, which are absent from normal lymphohaematopoietic cells, are a phenotypic marker of lymphomas carrying the t(2;5). We used in situ hybridization and immunohistology to screen 14 cutaneous ALC lymphomas, 21 cases of LyP, and one nodal ALC lymphoma associated with LyP for ALK gene products. ALK gene products were not detectable in these cases. In contrast, ALK gene products were found in a lymphonodal ALC lymphoma with subsequent extension to the skin and in t(2;5)-positive cell lines. Detection of the Epstein-Barr virus (EBV)-encoded small nuclear transcripts (EBER), and of immunoglobulin light chain transcripts served to check for the presence of cellular RNA in the tissue sections. EBER transcripts were found in scattered reactive lymphoid cells, but not in atypical or tumour cells. ALK gene expression and EBV infection seem to be a rare finding in cutaneous ALC lymphomas and LyP. This points to a molecular aetiology of primary cutaneous ALC lymphomas and LyP distinct from that of extracutaneous CD30+ lymphoproliferative disease. Detection of the t(2;5) or ALK gene products in cutaneous lymphoproliferative lesions therefore requires exclusion of extracutaneous ALC lymphoma in such patients.
Herbst
H
H
Institut für Pathologie, Universitätsklinikum Benjamin Franklin, Freie Universität, Berlin, Germany.
Sander
C
C
Tronnier
M
M
Kutzner
H
H
Hügel
H
H
Kaudewitz
P
P
D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000032:analysis; D017403:In Situ Hybridization; D017728:Lymphoma, Large-Cell, Anaplastic / Q000201:enzymology* / Q000821:virology; D017731:Lymphomatoid Papulosis / Q000201:enzymology* / Q000821:virology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015347:RNA Probes; D012334:RNA, Neoplasm / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases; D012269:Ribosomal Proteins; D012878:Skin Neoplasms / Q000201:enzymology* / Q000821:virology; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D007145:Immunoglobulin kappa-Chains; D015347:RNA Probes; D012334:RNA, Neoplasm; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; C067169:RPL22 protein, human; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases