MIST1—a Novel Marker of Plasmacytic Differentiation

Abstract

Currently available plasma cell markers include CD138 and CD38. However, CD38 is not specific to plasma cells. It is also expressed by many epithelial cells and other hematopoietic cells. In addition, rare CD138-negative PCNs may be exceedingly difficult to diagnose. MIST1 is a transcription factor expressed by mouse and human neoplastic and non-neoplastic plasma cells. Our goals were to compare MIST1 expression to CD38/CD138 in neoplasms with plasmacytic differentiation, assess reactivity in normal samples and nonplasmacytic cell lineages, and to determine whether MIST1 is expressed in CD138-negative PCNs. Eighty-five neoplasms with plasma cell differentiation [marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), plasmablastic lymphoma (PB), plasma cell neoplasm (PCN)] and 2 non-neoplastic cases (normal marrow) were tested with MIST1 immunohistochemistry. CD138/38 expression for each case was compared with MIST1 reactivity. Plasma cells were MIST1 positive in all cases interrogated. CD38 and/or CD138 expression was reviewed in all cases and found to be concordant in 46/47 (97.8%) of tested cases, with the exception of 1 case of PB that showed MIST1 positivity and no CD138 expression. All other cell lineages were negative, with the exception of MZL and LPL, in which MIST1 highlighted a subset of the lymphocytes, with plasmacytic differentiation. MIST1 is a sensitive and specific marker of plasmacytic differentiation. CD138+ plasma cells expressed MIST1 in all tested cases; however, 1 PB showed MIST1 positivity and no CD138 expression, suggesting MIST1 may be useful in certain CD138-negative cases. In MZL and LPL, MIST1 highlights a subset of the lymphocytes in lymphomas with plasmacytic differentiation.