Compared with nodal-only disease, skeletal classic Hodgkin lymphoma more often showed high expression of macrophage markers (CD68, CD163, CD206) and less often showed high CD20 expression, according to a recent study.
Classic Hodgkin lymphoma with skeletal involvement was characterized by a macrophage-rich, B-cell-poor tumor microenvironment and worse overall survival among patients receiving adriamycin, bleomycin, vinblastine, and dacarbazine. Researchers compared pretreatment nodal biopsies from patients with skeletal disease versus nodal-only disease and found consistent enrichment of tumor-associated macrophage markers alongside depletion of B-cell signatures.
In a retrospective analysis, the team assembled 2 cohorts: an RNA discovery set of 66 classic Hodgkin lymphoma cases (31 skeletal vs 35 nodal-only) and an immunohistochemistry cohort of 193 patients (27 skeletal). Skeletal involvement was classified on fluorodeoxyglucose positron emission tomography/computed tomography using predefined criteria. Gene expression profiling used the NanoString PanCancer Immune 770 panel; after filtering, 578 genes were analyzed. In silico immunophenotyping employed CIBERSORTx (LM22; 1,000 permutations). Multiplex immunohistochemistry quantified CD68, CD163, CD206, CD20, CD4, CD8, and FoxP3 by area fraction with predefined receiver operating characteristic–based cutoffs; survival was analyzed by Kaplan–Meier with log-rank testing and multivariable modeling.
Fifty-one genes were differentially expressed between skeletal and nodal-only disease (27 upregulated; 24 downregulated). Macrophage-associated genes were higher in skeletal disease—CD163 fold change 2.56, MRC1 (CD206) 2.48, SIGLEC1 1.99, MARCO 1.67—while B-cell genes were lower—MS4A1 (CD20) 0.42, CD19 0.48, PAX5 0.63, CD79A 0.52, CD79B 0.51. CIBERSORTx showed lower B-cell proportions and a trend toward higher M2 macrophages. Macrophage markers correlated positively with Ann Arbor stage.
Clinically, among patients treated with adriamycin, bleomycin, vinblastine, and dacarbazine, skeletal involvement was associated with inferior overall survival (5-year overall survival 71.3% vs 96.1%), with no difference in progression-free survival (PFS). "High protein expression levels of CD68 and CD163 were associated with poorer outcomes, whereas the opposite was observed for CD206, where high expression levels were linked with superior PFS," noted by Maja Dam Andersen of the Department of Haematology, Aarhus University Hospital, Aarhus, Denmark, and colleagues. In multivariable models, high CD68 remained independently adverse for overall survival (hazard ratio 8.54) and PFS (hazard ratio 2.59). High CD206 was associated with superior PFS but inferior overall survival.
The researchers reported no conflicts of interest.
