title: A novel immunohistochemical classifier to distinguish Hodgkin lymphoma from ALK anaplastic large cell lymphoma.
abstract: Classical Hodgkin lymphoma and ALK(-) anaplastic large cell lymphoma share many features like strong CD30 expression and usually loss of B- and T-cell markers. However, their clinical course is dramatically different with curability rates of >90% for classical Hodgkin lymphoma and an unfavorable prognosis for anaplastic large cell lymphoma. Classical Hodgkin lymphoma and ALK(-) anaplastic large cell lymphoma can usually be distinguished by PAX5 expression in the Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma and expression of cytotoxic molecules in tumor cells of anaplastic large cell lymphoma. However, in some cases the differential diagnosis is difficult owing to absence of established markers. To be able to better classify these cases, we reevaluated gene expression data of microdissected tumor cells of both lymphomas for differentially expressed genes. A classifier was established, comprising four genes strongly expressed in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma (MDC/CCL22, CD83, STAT3, and TUBB2B). Applying this classifier to a test cohort, Hodgkin lymphoma was successfully distinguished from ALK(-) anaplastic large cell lymphoma with an accuracy of 97% (43/44). MDC/CCL22, CD83, and STAT3 have also been found to be expressed in antigen-presenting cells. Therefore, based on our established classifier, Hodgkin and Reed-Sternberg cells differ from tumor cells of anaplastic large cell lymphoma, which can successfully be applied for practical purposes in histopathologic diagnostics.
authors.affiliation: Dr Senckenberg Institute of Pathology, Goethe University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Döring
authors.affiliation: Dr Senckenberg Institute of Pathology, Goethe University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Haematopathology Section, S Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Agostinelli
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Haematopathology Section, S Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Pier P
authors.initials: PP
authors.lastname: Piccaluga
authors.affiliation: Department of Pathology, University of Brescia, Brescia, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, Haematopathology Section, S Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pileri
authors.affiliation: Institute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.affiliation: Dr Senckenberg Institute of Pathology, Goethe University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Newrzela
authors.affiliation: Dr Senckenberg Institute of Pathology, Goethe University Hospital Frankfurt, Frankfurt, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hartmann
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000032:analysis*; D054422:Chemokine CCL22; D016000:Cluster Analysis; D003937:Diagnosis, Differential; D005260:Female; D006689:Hodgkin Disease / Q000145:classification* / Q000175:diagnosis*; D006801:Humans; D007136:Immunoglobulins; D007150:Immunohistochemistry; D017728:Lymphoma, Large-Cell, Anaplastic / Q000145:classification* / Q000175:diagnosis*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D016539:Reed-Sternberg Cells / Q000473:pathology; D050796:STAT3 Transcription Factor; D046888:Tissue Array Analysis; D059467:Transcriptome; D014404:Tubulin; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D054422:Chemokine CCL22; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D050796:STAT3 Transcription Factor; D014404:Tubulin; D000097802:CD83 Antigen; C515482:CCL22 protein, human; C494086:STAT3 protein, human; C576987:TUBB2B protein, human