Polyclonal but Not Monoclonal PAX8 Is a Marker of Normal B Cells and B Cell Lymphomas, Including Most Classical Hodgkin Lymphomas: An Immunohistochemical Study
Katherine L Chandler, Elizabeth C Chastain, Diane Lawson, Kyle T Bradley. Emory University, Atlanta, GA
Background: The paired box (PAX) proteins are a family of transcription factors that have critical roles in embryogenesis, and have emerged as lineage-specific immunohistochemical markers. IHC for PAX2 and PAX5 is useful in identifying normal and neoplastic renal epithelial cells and B cells, respectively. IHC using a monoclonal (m) PAX8 antibody is sensitive and specific for renal, Mullerian, and thyroid tissues and neoplasms. A recent comprehensive study of PAX8 IHC using a polyclonal (p) antibody reported expression in these tissues as well as seminal vesicle, epididymis, pancreatic islet cells, and lymphoid cells, including 17 lymphomas, but not in other tissue types. Lymphomas included “both small and large cell types,” but no other description was provided (Mod Pathol 2011;24:751-64). We sought to further investigate the utility of PAX8 IHC in lymphoma.
Design: IHC using mPAX8 and pPAX8 antibodies was performed on two benign tonsils and 72 lymphomas of various types. Staining results were reviewed in the context of the H&E slide and other IHC stains.
Results: In benign tonsils and lymph nodes pPAX8 demonstrated strong nuclear staining in germinal center (GC) and mantle zone B cells and few interfollicular cells, in a pattern similar to CD20 and PAX5. T cells and plasma cells were negative. In cHL, H/RS cells were pPAX8-positive in 9/11 cases; staining intensity was slightly weaker than in normal B cells, essentially identical to PAX5 IHC (same 9/11 positive). pPAX8 was positive in 2/3 B-ALL and 44/44 B cell lymphomas of other types, including 12 FL (7 grade 1-2, 5 grade 3; centroblasts were negative in one grade 3 case), 8 DLBCL (4 GC, 4 non-GC), 4 TC/HRLBCL, 6 CLL/SLL, 6 extranodal MZL (plasmacytic cells were negative), 5 MCL, and 3 NLPHL. pPAX8 was negative in all 14 T cell neoplasms evaluated, including 4 T-ALL, 3 peripheral TCL, 4 ALCL, and 3 AITL. mPAX8 was negative in all lymphoid cells in 65 cases tested.
Conclusions: PAX8 (m and p) is uniformly negative in T cells, T cell lymphomas, and plasmacytic cells. pPAX8 is a sensitive and specific marker of normal B cells and B cell lymphomas (positive in 2/3 B-ALL, 9/11 cHL, and 44/44 other B cell lymphomas). However, mPAX8 is consistently negative in B cells, raising the possibility of cross-reactivity of the polyclonal antibody, possibly with PAX5, and suggests that PAX8 may not be a B-cell transcription factor. In routine clinical practice pPAX8 IHC may have greater utility than PAX5 due to its additional role in identifying renal, Mullerian, and thyroid neoplasms.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 226, Monday Morning