Gamma Heavy Chain Disease: A Morphologic and Immunophenotypic Study of 10 Cases Including Bone Marrow, Lymph Nodes, and Spleen.
Shannon Bieliauskas, Chris Bacon, Kathryn Foucar, Sarah Gibson, Steven Kroft, Camellia Eshoa, Steven H Swerdlow, James R Cook. Cleveland Clinic, OH; Newcastle Univ., Newcastle Upon Tyne, United Kingdom; Univ. of New Mexico, Albuquerque; Univ. of Pittsburgh, PA; Medical College of Wisconsin, Milwaukee; Columbia St. Mary's Hospital, Milwaukee, WI
Background: Gamma heavy chain disease (γHCD) is defined as a lymphoplasmacytic neoplasm that produces an abnormally truncated IgG heavy chain (HC) protein that lacks associated light chains (LCs). There is scant information in the literature regarding the detailed morphologic findings in this rare disorder, although cases are reported to often resemble lymphoplasmacytic lymphoma (LPL). This study reports the clinical, morphologic and immunophenotypic findings in 10 cases of γHCD.
Design: Bone marrow (BM) biopsies (n=10), lymph nodes (LN) or extramedullary biopsies (n=7), and spleens (n=3) from 10 patients (pts) with serum IgG HC without LCs were reviewed.
Results: The median age was 55 (range 39-77 yrs) and 9 pts were female. 6 had a history of autoimmune disease and 2 had coexisting clonal LGL disorders. 6 pts displayed similar morphologic features in LN and spleen: architectural effacement by a diffuse and/or interfollicular proliferation of predominantly plasmacytoid cells, plasma cells (PCs) and histiocytes. By IHC, PCs were IgG+ and LC- in 8 cases, 1 case showed weak cytoplasmic monotypic LC, and 1 case was LC restricted by ISH but LC- by IHC. 4 cases resembled typical examples of IgM+ LPL/WM, SMZL, splenic diffuse red pulp small B-cell lymphoma, or MGUS, with at least a subset of neoplastic cells being IgG+ LC-. BM biopsies included 1 with an overt B-cell lymphoma (IgM+ LPL) and 4/7 cases had few LC- B-cells noted by flow cytometry. In 1 case, PCs were 13% with clearly identified CD138+IgG+ LC- forms, while the remainder showed up to 10% PCs that appeared predominantly polytypic, although LC- PCs were difficult to exclude.
Conclusions: Extramedullary γHCD most commonly is a proliferation of predominantly plasmacytoid cells and PCs. Careful attention to IHC to identify LC- PCs and correlation with immunofixation data is critical to making this diagnosis. Most cases do not resemble the classic forms of LPL/WM, but there is overlap with cases reported as "vaguely nodular, polymorphous” LPL versus marginal zone lymphoma. Importantly, there is morphologic heterogeneity and at least some cases resemble typical examples of other entities, suggesting that the γHCD abnormality may be acquired in multiple lymphoproliferative disorders rather than representing one homogeneous entity.
Tuesday, March 1, 2011 9:00 AM
Platform Session: Section B, Tuesday Morning