Abdominal "Heaviness".

Abstract

To the Editor: An 86-year-old man presented with complaints of right upper quadrant pain for 3 to 4 months, associated with nausea and vomiting, and unintentional 10- to 15-pound weight loss. He denied fever, diarrhea, constipation, or gastrointestinal bleeding. He had a cholecystectomy for gallstones in the past. He denied smoking, alcohol, or illicit drug abuse. Physical examination was notable for pallor and hepatosplenomegaly. Laboratory examination showed pancytopenia (hemoglobin 9.4 g/dL, normal 14–18 g/dL; white blood cell count 2.9 k/μL, normal 4.8–10.8 k/μL; platelets 33 k/μL, normal 160–410 k/μL). The anemia was normocytic normochromic. Reticulocyte count was low for the degree of anemia (1.3%, normal 0.5–1.5%). Lactate dehydrogenase was 354 U/L (normal 125–220 U/L), aspartate aminotransferase was 42 U/L (normal 4–35 U/L), alanine aminotransferase was 64 U/L (normal 6–55 U/L), alkaline phosphatase was 878 U/L (normal 40–150 U/L), total bilirubin was 1.2 mg/dL (normal 0.2–1.3 mg/dL), total proteins were 5.7 g/dL (normal 6.4–8.3 g/dL), albumin was 3.3 g/dL (normal 3.4–4.8 g/dL), and globulin was 2.4 g/dL (normal 2.9–4 g/dL). Calcium, renal function, and coagulation tests were normal. Anemia workup was negative for hemolysis and notable for anemia of chronic disease. Vitamin B12, folate, and thyroid function tests were normal. Viral hepatitis screen was negative. Autoimmune markers such as double-strand deoxyribonucleic acid, antihistone, rheumatoid factor, anticardiolipin, complements, anti-Ro, anti-La, anti-RNP, anti-smooth muscle, antimitochondrial, and antiplatelet antibodies were negative, but antinuclear antibody was positive. Extensive infectious examination, tumor markers, and human immunodeficiency virus were negative. Serum electrophoresis revealed a broad band in the beta region, with a beta of 19.0% (normal 9.8–15.6%). Immunofixation of serum protein revealed the presence of monoclonal gamma heavy chain without any corresponding kappa or lambda light chains. Abdominal computed tomography showed hepatosplenomegaly with retroperitoneal and mesenteric lymphadenopathy. Bone marrow biopsy for evaluation of pancytopenia showed 10% to 20% cellularity with trilineage hematopoiesis. Liver biopsy showed the liver parenchyma to be infiltrated by a polymorphous population of cells comprising lymphocytes, plasmacytoid lymphocytes, histiocytes, and eosinophils, with rare plasma cells. Immunohistochemical study revealed that lymphocytes were highlighted by 79A, CD20 (partial), PAX-5 (partial), and MUM-1. These cells were positive for immunoglobulin (Ig)G and negative for kappa and lambda, IgA, IgD, IgM, and IgG4. Taken together, the morphological, immunophenotyping, and immunofixation findings were consistent with gamma heavy chain disease. He was started on chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisone and was doing well after one cycle. Heavy chain diseases (HCDs) are a group of B-cell lymphoplasmacytic disorders characterized by production of monoclonal immunoglobulins by neoplastic cells. These immunoglobulins are truncated proteins and do not have light chains attached to them, owing to deletion of the CH1 domain of the heavy chain, a domain that helps bind to light chains. They have been described as involving the three major immunoglobulin classes: α-HCD (IgA), γ-HCD (IgG), and μ-HCD (IgM). α-HCD is the most common and has a uniform presentation. In contrast, the other two have variable presentations. γ-HCD is a serologically determined entity with a variety of clinicohistological features. Franklin and colleagues first described it in 1964. The median age of diagnosis is 68, with a clear female to male predominance.1 γ-HCD has been divided into three broad categories: disseminated lymphoproliferative disease (DLPD), localized proliferative disease (LPD), and no apparent proliferative disease (NAPD). DLPD most commonly presents with lymphadenopathy and hepatosplenomegaly. LPD commonly presents with cutaneous involvement. Individuals with NAPD often have an underlying autoimmune condition.2 In individuals presenting with pancytopenia and organomegaly, serum and urine electrophoresis (SPEP/UPEP) should be part of the diagnostic examination. The monoclonal spike on SPEP is seen in the beta region. On immunofixation, there is presence of monoclonal heavy chains in the absence of light chains. Bone marrow biopsy usually shows increase in plasma cells, lymphocytes, or plasmacytoid lymphocytes similar to findings of Waldenström's macroglobulinemia. Bone involvement is rare. γ-HCD must be excluded in all individuals diagnosed with a lymphoplasma cell disorder. Treatment depends on the clinical picture. In asymptomatic individuals, no therapy is indicated. Individuals with progressive disease or high-grade non-Hodgkin lymphoma have been successfully treated with combination chemotherapy with cyclophosphamide, vincristine, and prednisone with or without doxorubicin, as the man described herein. Rituximab can be used in CD20-positive cases. Localized extramedullary plasmacytomas can be treated surgically or with radiation. Median duration of survival has been reported to be 7.4 years.1 The amount of serum γ heavy chain protein tends to correlate with disease activity. Conflict of Interest: Written and oral consent was received from the subject to submit this case report to be considered for publication. Author Contributions: Pallavi: acquisition of data, concept of design, manuscript analysis, interpretation of data, preparation of manuscript. Sponsor's Role: None.