Gamma Heavy Chain Disease Workup

Updated: Jan 17, 2017
  • Author: Guy B Faguet, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Laboratory Studies

Complete blood cell (CBC) count may reveal a mild normochromic-normocytic anemia, which develops in virtually all patients. The leukocyte count and differential cell count are usually normal, although leukopenia and leukocytosis may be present. Eosinophilia and thrombocytopenia, secondary to an autoimmune process or hypersplenism, can occur.

Peripheral blood smear may demonstrate eosinophilia, neutropenia, and lymphoid plasma cells. If present, rouleaux formation suggests a high serum level of ϒ-protein.

Measurement of the creatinine level is important because renal function occasionally decreases from nodular glomerulosclerosis, precipitated by deposition of the monoclonal heavy chains. [11] Hyperuricemia is common in patients with advanced disease.

Routine protein studies are performed. Serum protein electrophoresis (SPE) is variable but shows a monoclonal spike, with an electrophoretic mobility in the α-γ regions, which is detected in approximately 75% of patients. The remainder reveals either hypogammaglobulinemia or polyclonal hyperglobulinemia migrating in the β region of the spectrum. Urine electrophoresis often detects small amounts of ϒ-protein. [12] The Bence Jones heat test is usually negative.

Special protein studies (not universally available) include immunoelectrophoresis (IEP), immunofixation (IF), and rocket immunoselection of serum and urine. These tests, which identify and characterize the immunoglobulin class and subclass (in this case IgG1, IgG2, IgG3, and IgG4), are highly specialized tests beyond the scope of this overview. For details, readers are referred to two reviews of the subject. [13, 14]


Imaging Studies

Skeletal radiographs may show lytic lesions in approximately 10% of patients (see images below). Osteoporosis is rare.

Lateral radiograph of the skull. This image demons Lateral radiograph of the skull. This image demonstrates numerous lytic lesions, which are typical for the appearance of widespread myeloma.
Radiograph of the right femur. This image demonstr Radiograph of the right femur. This image demonstrates the typical appearance of a single myeloma lesion as a well-circumscribed lucency in the intertrochanteric region. Smaller lesions are seen at the greater trochanter.


Bone marrow biopsy with aspirate often reveals increased numbers of plasma cells, lymphocytes, and plasmacytoid lymphocytes but are sometimes normal. A marked increase in erythropoiesis is classic in cases associated with hemolytic anemia. Eosinophilia, mastocytosis, lymphocytosis, and other abnormalities have been noted but are rare. See the images below.

Bone marrow biopsy specimen. Bone marrow biopsy specimen.
Bone marrow biopsy specimen in fixative solution. Bone marrow biopsy specimen in fixative solution.
Bone marrow aspiration and biopsy slides before st Bone marrow aspiration and biopsy slides before staining.
Histology of eosinophilic granuloma. Histology of eosinophilic granuloma.

Lymph node biopsy can be valuable to exclude a gammopathy associated with amyloidosis, non-Hodgkin disease, or granulomatous disease.


Histologic Findings

See Procedures.