Heavy chain disease.
ABSTRACT The heavy chain diseases (HCDs) are rare B-cell malignancies that are distinguished by the production of a monoclonal immunoglobulin heavy chain (HC) without an associated light chain by the malignant B-cells. There are three types of HCD defined by the class of immunoglobulin (Ig) HC produced: IgA (alpha-HCD), IgG (gamma-HCD), and IgM (mu-HCD). Alpha-HCD is the most common and occurs most commonly as intestinal malabsorption in a young adult from a country bordering the Mediterranean Sea. Treatment consists of antibiotics and improved nutrition and hygiene. Surgery is occasionally required for patients with bulky masses at risk for bowel perforation. If there is no response to antibiotics or if aggressive non-Hodgkin's lymphoma (NHL) is diagnosed, the patient should be treated with chemotherapy. Gamma- and mu-HCD are rare and essentially are found in patients with a B-cell NHL that produces an abnormal Ig heavy chain. These patients occasionally may be diagnosed with a monoclonal gammopathy of undetermined significance (MGUS). Patients with MGUS with NHL should be administered chemotherapy. Screening the serum and urine of patients with lymphoplasmacytoid NHL would likely identify more patients with gamma- or mu-HCD.
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ABSTRACT: Heavy chain diseases are rare B-cell disorders that are characterized by an overproduction of abnormal and structurally incomplete monoclonal immunoglobulin (Ig) heavy chains and are devoid of light chains. We describe a case of a 62 year-old African-American woman with a long history of poorly controlled type 2 diabetes and subsequent probable diabetic nephropathy, hypertension, and recent onset of peripheral neuropathy involving all extremities. Routine laboratory testing revealed a distinct beta spike by urine protein electrophoresis (UPEP). No serum abnormality was noted on serum protein electrophoresis (SPEP). Serum and urine immunofixation demonstrated an IgG heavy chain protein devoid of any corresponding light chains. IgG subclasses identified IgG1 as the predominant IgG component but when we added all the subclasses, the sum, 683.4 mg/dL, failed to come close to our total IgG of 1,770 mg/dL. Therefore, a urine IgG subclass determination was performed in-house and we identified a subclass 3 gamma chain. In conclusion, we portray a patient with an underlying monoclonal gamma heavy chain disease (HCD) who presented with a complex medical history. The evaluation of IgG subclasses in the context of a HCD may be limited by the capability of the test to recognize the particular IgG fragment.Journal of Clinical Laboratory Analysis 02/2008; 22(2):146-50. · 1.36 Impact Factor
- Leukemia & lymphoma 06/2012; · 2.40 Impact Factor
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ABSTRACT: 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.The American journal of surgical pathology 01/2012; 36(4):534-43. · 4.06 Impact Factor