Immunohistochemical Labeling of Multiple Myeloma Oncogene 1/Interferon Regulatory Factor 4 (MUM1/IRF-4) in Canine Cutaneous Histiocytoma

Abstract

Multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF-4) immunohistochemistry (IHC) is mainly used for diagnostic confirmation of plasma cell tumors (PCTs) in dogs and cats. This article describes MUM1/IRF-4 IHC expression in 20 cases of canine cutaneous histiocytoma (CH) and compares it with 10 cutaneous or mucocutaneous PCTs and 5 cutaneous histiocytic sarcomas (HSs) submitted to the same IHC protocol. All histiocytomas had strong nuclear and variable cytoplasmic immunolabeling for MUM1/IRF-4, whereas all PCTs had strong nuclear and moderate cytoplasmic immunolabeling for MUM1/IRF-4. No MUM1/IRF-4 immunolabeling was detected in the HSs. Although not typically a diagnostic challenge, MUM1/IRF-4 expression may have to be used with caution or in conjunction with additional immunomarkers to differentiate among poorly differentiated round cell tumors, especially when a histiocytic or plasma cell origin is suspected.

Chromogenic in situ hybridization for the detection of lambda and kappa immunoglobulin light chains as a potential auxiliary diagnostic technique in canine plasmacytomas

“…4,25 In our study, a high percentage (96%) of PCTs were MUM1 positive, in agreement with previous reports (93.5-100%). 24,30 Given this high sensitivity, IHC for MUM1 is routinely used to confirm the plasma cell origin in canine tumors, often replacing the IHC for light chains. 12,24 However, the specificity of MUM1 for PCTs has recently been questioned by a study that demonstrated consistent expression of MUM1 in a series of 20 canine histiocytomas.…”

“…36 For this reason, distinguishing poorly differentiated PCTs from other round cell tumors may represent a diagnostic challenge. 30 Immunohistochemistry (IHC) for multiple myeloma oncogene 1 (MUM1) is widely used to confirm the diagnosis of PCTs in dogs. 24,30 MUM1 is a transcription factor involved in regulation of cell growth, especially B-cell differentiation.…”

“…30 Immunohistochemistry (IHC) for multiple myeloma oncogene 1 (MUM1) is widely used to confirm the diagnosis of PCTs in dogs. 24,30 MUM1 is a transcription factor involved in regulation of cell growth, especially B-cell differentiation. 13 Conventionally believed to be highly specific for canine PCTs, MUM1 expression has been demonstrated in cutaneous histiocytomas and in 21% of B-cell lymphomas.…”

“…13 Conventionally believed to be highly specific for canine PCTs, MUM1 expression has been demonstrated in cutaneous histiocytomas and in 21% of B-cell lymphomas. 24,30 Therefore, MUM1 should be used in conjunction with histiocytic (e.g., ionized calcium-binding adaptor molecule 1, Iba1) and lymphoid markers to distinguish some undifferentiated round cell tumors. 28,30 Canine PCTs are negative for the T-cell marker CD3, and variably positive for B-cell markers including CD79a (56-82%) and CD20 (19%).…”

“…24,30 Therefore, MUM1 should be used in conjunction with histiocytic (e.g., ionized calcium-binding adaptor molecule 1, Iba1) and lymphoid markers to distinguish some undifferentiated round cell tumors. 28,30 Canine PCTs are negative for the T-cell marker CD3, and variably positive for B-cell markers including CD79a (56-82%) and CD20 (19%). 24,28 The common leukocyte antigen CD45RA is frequently expressed (94%), although the positivity varies among tumors and in different tumor areas.…”