History and Physical Examination
It has been suggested that approximately 25% of patients with γ–heavy chain disease (HCD) present with localized disease, whereas two thirds exhibit disseminated disease, including medullary and extramedullary involvement, with the remainder showing gammopathy only. [11] Patients with disseminated γ-HCD present with a lymphomalike illness that includes lymphadenopathy, splenomegaly, and hepatomegaly, and often involves progressive weakness, fatigue, and intermittent fevers. Hepatosplenomegaly is present in 60% of patients.
Lymphadenopathy is present at the onset in approximately two thirds of patients with disseminated disease. It commonly involves cervical, axillary, thoracic, and abdominal nodes. It also involves the Waldeyer ring and mesenteric lymph nodes, often leading to an edematous tongue and soft palate. Lymphadenopathy becomes more pronounced as the disease progresses. Other features may include parotid gland tenderness, soreness of the tongue, autoimmune hemolytic anemia, and purpura. Skeletal involvement and hypercalcemia are rare but kidney, adrenal, and central nervous system lymphoid infiltration have been reported postmortem.
The course of γ-HCD varies from an asymptomatic presence of a nonprogressive monoclonal heavy chain in serum or urine that occasionally resolves spontaneously, to a rapidly progressive illness. A small percentage of γ-HCD exhibits a phase of monoclonal gammopathy of undetermined significance (MGUS). Most patients with progressive disease eventually succumb to bacterial infections. A series of 23 patients reported a median survival of 7.4 years. [5]
Signs and symptoms of γ-HCD are variable but include the following:
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Fevers are frequently recurrent and resemble that of lymphoproliferative disorders.
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Malaise may be secondary to the disease state itself or to anemia. Mild anemia is universal in patients with disseminated γ-HCD.
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Dysphagia is usually caused by edema of the soft palate, secondary to progressive lymphadenopathy of the Waldeyer ring. This edema may also lead to tongue soreness.
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Recurrent upper respiratory tract infections develop because of impaired humoral and cellular immunity, although other factors also can contribute, including lymphoid hyperplasia of the oropharynx that can reduce clearance of airway pathogens.
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Abdominal pain can be present and is caused by splenomegaly (see the image below), hepatomegaly, and/or abdominal lymphadenopathy.
The margins of this massive spleen were palpated easily preoperatively. Medially, the 3.18-kg (7-lb) spleen crosses the midline. Inferiorly, it extends into the pelvis.
Causes
The causes of γ-HCD are unknown. Approximately 25% of γ-HCD patients have a history of an autoimmune disorder, as follows [10] :
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Rheumatoid arthritis (most frequent)
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Sjögren syndrome
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Systemic lupus erythematosus
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Myasthenia gravis
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Autoimmune cytopenias (eg, immune thrombocytopenia)
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The margins of this massive spleen were palpated easily preoperatively. Medially, the 3.18-kg (7-lb) spleen crosses the midline. Inferiorly, it extends into the pelvis.
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Lateral radiograph of the skull. This image demonstrates numerous lytic lesions, which are typical for the appearance of widespread myeloma.
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Bone marrow biopsy specimen.
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Bone marrow biopsy specimen in fixative solution.
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Bone marrow aspiration and biopsy slides before staining.
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Histology of eosinophilic granuloma.
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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.
