Fortunately, most small cell predominant or lymphohistiocytic variants of anaplastic large-cell lymphoma are ALK+, as a diagnosis of ALK– anaplastic large-cell lymphoma with variant histology would be particularly difficult; large CD30+ hallmark type cells must be present with a preferential distribution of the CD30+ large cells around blood vessels.131 In ALK– anaplastic large-cell lymphoma with a null phenotype (and genotype), immunostains to exclude other tumours such as Hodgkin lymphoma (HL), carcinoma and acute leukaemia must be performed (Table 6). This evidence concerns the gene TNFRSF8 and anaplastic large cell lymphoma.