A novel immunohistochemical classifier to distinguish Hodgkin lymphoma from ALK anaplastic large cell lymphoma

Abstract

Classical Hodgkin lymphoma and ALK À 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 490% for classical Hodgkin lymphoma and an unfavorable prognosis for anaplastic large cell lymphoma. Classical Hodgkin lymphoma and ALK À 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 À 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.

Biomarker and Histopathology Evaluation of Patients with Recurrent Glioblastoma Treated with Galunisertib, Lomustine, or the Combination of Galunisertib and Lomustine

“…We also attempted to stain for the presence of CCL22 in tumor tissue but were not able to establish a satisfactory staining protocol, which was based on previous work on lymphoma tissue [25]. Thus, it is not clear whether the high levels of CCL22 originate from the tumor or are produced systemically.…”

“…Furthermore, tumor specimens were stained for MDC/CCL22 [25]. The process of evaluation was based on the standard IHC staining developed at the neuropathology laboratory at the University Clinic of Heidelberg, Heidelberg, Germany [18].…”

PAX5-expressing ALK-negative anaplastic large cell lymphoma with extensive extranodal and nodal involvement

“…Molecular analysis has not been routinely used in clinical practice due to the lack of well-established markers to clarify ambiguous cases. Recently, Doring et al 39 explored gene expression data of microdissected tumour cells of both lymphomas, and found four genes strongly expressed in Reed-Sternberg cells (MDC/CCL22, CD83, STAT3, TUBB2B) that could distinguish Hodgkin from ALK − ALCL with reasonable accuracy in a test cohort of 44 patients.…”

Cutaneous localization of angioimmunoblastic T‐cell lymphoma may masquerade as B‐cell lymphoma or classical Hodgkin lymphoma: A histologic diagnostic pitfall

“…Nevertheless, ALCL are not associated with EBV. Interestingly, some pathologists have already established an imunohistochemical classifier based on expression of 4 proteins including CD83, MDC/CCL22, STAT3, and TUBB2B, helping to distinguish ALCL from cHL …”