Gamma heavy-chain disease: defining the spectrum of associated lymphoproliferative disorders through analysis of 13 cases.
Gamma heavy-chain disease (gHCD) is defined as a lymphoplasmacytic neoplasm that produces an abnormally truncated immunoglobulin gamma heavy-chain protein that lacks associated light chains. There is scant information in the literature regarding the morphologic findings in this rare disorder, but cases have often been reported to resemble lymphoplasmacytic lymphoma (LPL). To clarify the spectrum of lymphoproliferative disorders that may be associated with gHCD, this study reports the clinical, morphologic, and phenotypic findings in 13 cases of gHCD involving lymph nodes (n=7), spleen (n=2), bone marrow (n=8), or other extranodal tissue biopsies (n=3). Clinically, patients showed a female predominance (85%) with frequent occurrence of autoimmune disease (69%). Histologically, 8 cases (61%) contained a morphologically similar neoplasm of small lymphocytes, plasmacytoid lymphocytes, and plasma cells that was difficult to classify with certainty, whereas the remaining 5 cases (39%) showed the typical features of one of several other well-defined entities in the 2008 WHO classification. This report demonstrates that gHCD is associated with a variety of underlying lymphoproliferative disorders but most often shows features that overlap with cases previously reported as "vaguely nodular, polymorphous" LPL. These findings also provide practical guidance for the routine evaluation of small B-cell neoplasms with plasmacytic differentiation that could represent a heavy-chain disease and give suggestions for an improved approach to the WHO classification of gHCD.
Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Shannon
S
Bieliauskas
Raymond R
RR
Tubbs
Chris M
CM
Bacon
Camellia
C
Eshoa
Kathryn
K
Foucar
Sarah E
SE
Gibson
Steven H
SH
Kroft
Aliyah R
AR
Sohani
Steven H
SH
Swerdlow
James R
JR
Cook
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002999:Clone Cells; D015897:Comorbidity; D020732:Cytogenetic Analysis; D005260:Female; D006362:Heavy Chain Disease / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007142:Immunoglobulin gamma-Chains / Q000097:blood* / Q000235:genetics; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008221:Lymphoid Tissue / Q000378:metabolism / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D012737:Sex Factors; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D008258:Waldenstrom Macroglobulinemia / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D007142:Immunoglobulin gamma-Chains