Despite being classically associated with Hodgkin lymphoma, reed sternberg cells (RSLCs) can also be found in other lymphoproliferative disorders and can pose diagnostic challenges. The presence of RSLCs in the tissue often leads to the diagnosis of nodular sclerosing Hodgkin lymphoma, but they can also be seen in follicular lymphoma, rheumatoid arthritis, B cell chronic lymphocytic leukemia and anaplastic large cell lymphoma. Therefore, a correct lymphoma classification is important for the appropriate therapy of these diseases.
The classic histological features of RSLCs are abundant slightly basophilic or amphophilic cytoplasm and rounded or oblong nucleus with prominent eosinophilic inclusion-like nucleoli, giving them a distinctive “owl’s eye” appearance. The cells may be mononucleated or multinucleated. Mononuclear variants of RSLCs are termed mummified cells and have condensed cytoplasm and pyknotic reddish nuclei. The identification of RSLCs is essential for the diagnosis of Hodgkin lymphoma, and the absence of this finding has very high negative predictive value.
Hodgkin lymphoma is classified according to World Health Organization criteria, with five different World Health Organization (WHO) subtypes: nodular sclerosing hodgkin lymphoma (cHL); lymphocyte predominate Hodgkin lymphoma (LPHL); diffuse large B cell lymphoma (DLCL); B cell non-Hodgkin lymphoma, low-grade (B-NHL) and high-grade (B-CLL). RSLCs are associated with all of the WHO subtypes.
RSLCs are often present as neoplastic sheets or scattered throughout the tissue. In follicular lymphomas, they can be found within or between neoplastic follicles and can form distinct neoplastic clusters that are differentiated from neoplastic centroblasts by their characteristic immunoglobulin heavy chain gene rearrangements and by expression of the marker protein CD10. In some follicular lymphoma cases, RS-like cells may express CD10, and they can sometimes be miscounted as centroblasts, particularly when examining enlarged tissue sections after formalin retraction. However, if the samples are adequately sized and morphologic guidelines are followed, the differentiation of neoplastic RS-like cells from centroblasts can be accomplished using strict morphologic criteria.
To identify genes expressed exclusively by HL RS-like cells, supervised clustering of RNA from four HL RS-cell lines was performed with a gene set composed of naive and memory B cells, follicular lymphoma (FL), burkitt lymphoma and diffuse large cell lymphoma (DLCL). The expression of 27 genes was significantly upregulated in the HL RS-cells compared to the collection of other B cells.
Several of these genes have previously been shown to have a role in B-cell functions, such as immune regulation, signaling and cell proliferation. Further, RT-PCR analysis on microdissected tumor cells from three of the four HL RS-cell lines confirmed that these genes were indeed regulated by reed sternberg cells. Among these, PRAME, IPL, Fer and Rab13 are novel genes that have only been reported to be expressed by neoplastic Reed-Sternberg cells. These findings provide new insight into the molecular basis of reed sternberg cell proliferation and suggest novel targets for therapeutic intervention in cHL, FL and other hematologic malignancies that feature RS-like cells.
