IgM Expression on Paraffin Sections Distinguishes Primary Cutaneous Large B-cell Lymphoma, Leg Type From Primary Cutaneous Follicle Center Lymphoma

Abstract

In the World Health Organization (WHO) 2008 classification 2 main types of primary cutaneous large B-cell lymphomas (PCLBCLs) are distinguished: primary cutaneous follicle center lymphoma (PCFCL) and primary cutaneous large B-cell lymphoma, leg type (PCBCL-LT). PCFCL has a 5-year overall survival rate of 95%, and PCBCL-LT of approximately 50%. Expression profiling studies have shown higher RNA expression of the IgM heavy chain in PCBCL-LT compared with PCFCL. To find out whether this difference could also be demonstrated at the protein level, we performed immunohistochemical staining for B-cell receptor heavy and light chains on skin biopsies from 53 patients with PCFCL and 40 patients with PCBCL-LT. All 40 cases of PCBCL-LT consistently showed cytoplasmic staining for IgM, in 18 of them with coexpression of IgD. In contrast, only 5 of the PCFCL cases showed cytoplasmic staining for IgM and/or IgD, including all 3 PCFCLs presenting on the leg. Hence, staining for IgM on paraffin-embedded sections seems to be an additional tool for differentiating between the 2 entities in clinical pathology practice. Analogous to other nodal and extranodal large B-cell lymphomas, expression of IgM in PCLBCL seems to be related to an activated B cell-like phenotype. Finally, the expression of IgM (and IgD) in this type of lymphoma might imply defective class switch recombination.

The isotype of the BCR as a surrogate for the GCB and ABC molecular subtypes in diffuse large B-cell lymphoma

“…This correlation is consistent with a recent report where the expression of an IgM was associated with the worst prognosis in a large series of nodal DLBCL cases. 16 It is also consistent with the observation that this isotype predominates in rare and aggressive forms of lymphomas, such as primary central nervous system, 15 primary testicular 17 and primary cutaneous DLBCL, 18,19 which all have an ABC-like phenotype. 20 Isotype class switching in DLBCL P Ruminy et al…”

Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type: Diagnostic Considerations

“…10 In addition, PCFCLs usually lack BCL2, MUM-1, FOX-P1, and IgM; however, few cases may be positive for these markers. 10,14 Strong expression of CD10 and BCL2 is suggestive of cutaneous involvement by a systemic follicular lymphoma. 5,6 As in nodal follicular lymphoma, coexpression of BCL6 and BCL2 is abnormal and indicates a neoplastic process.…”

“…10 Interestingly, PCFCLs involving the leg tend to have a worse outcome 4,10 and are more likely to express BCL2, MUM-1, FOX-P1, and IgM. 10,14 Primary cutaneous follicle center lymphoma is composed of dermal infiltrates of follicle center cells, including centrocytes and centroblasts, without epidermal involvement. Centrocytes are characterized by irregular, twisted, or cleaved nuclei and, in occasional cases, they may take on a marked spindled morphology (Figure 2, A and B).…”

“…6,10 Additionally, a recent study 14 identified immunoglobulin M (IgM) as another sensitive marker of PCDLBCL-LT.…”

Best Practices in Diagnostic Immunohistochemistry: Workup of Cutaneous Lymphoid Lesions in the Diagnosis of Primary Cutaneous Lymphoma

“…42 IgM and HGAL as markers to aid in the differentiation between these 2 entities have been reported. [50][51][52] FOXP1 is shown to be expressed in most DLBCLs, leg type. 53 Primary Cutaneous Diffuse Large B-Cell Lymphoma, Other…”