Challenges of CD30 expression and its impact on targeted treatment responses in non-Hodgkin lymphoma: New perspectives for evaluation and validation.

Cluster of differentiation 30 (CD30) is an important diagnostic marker for classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL), where its expression is predominant. Reports indicate various levels of expression across different lymphoma types. Brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate (ADC), has received approval for clinical use in patients with cHL and ALCL, demonstrating remarkable efficacy. However, in other subtypes of non-Hodgkin lymphoma (NHL) that also express CD30, other than ALCL, the response to BV has been observed across a spectrum of CD30 expression levels by immunohistochemistry (IHC). The cause of this is multifactorial, such as the intra and interlesional heterogeneity of CD30 expression in tumor samples, the alternative secondary mechanisms of action of BV, and the IHC methodology, which is based on a semi-quantitative assay with limitation to detect lower levels of CD30 expression. In this review, we describe the current expert consensus and guidelines for evaluating CD30 expression by IHC in lymphoma biopsies, discuss ongoing controversies, and provide new perspectives on the direction of evaluation and validation of CD30 expression in the future.