An Unusual Cause of Lymph Nodes Enlargement

Case Report 

A 61-year-old man was referred for the evaluation of diffuse lymphadenopathy and nephrotic syndrome. He presented with dyspnea and dysphonia and had lost 16 kg in the last 4 months. On physical examination, lower limbs edema, bilateral parotidomegaly, and diffuse bulky lymph nodes were noted. Biological tests results revealed hepatic cholestasis (γ-glutamyltransferase 249 UI/L, normal <45 UI/L; alkaline phosphatase 190 UI/L, normal <135 UI/L) with normal transaminases (aspartate aminotransferase 39 UI/L, normal <45 UI/L; alanine aminotransferase 10 UI/L, normal <65 UI/L), increased lactate dehydrogenase (650 UI/L, normal <390 UI/L) and C-reactive protein (30 mg/L, normal <8 mg/L), and hypoalbuminemia (25 g/L). Blood cell and platelet count, serum creatinine, and blood coagulation test results were normal. Monoclonal immunoglobulin (Ig)-M lambda protein was detected in the serum (11 g/L). Nephelometric assay for free light chain serum concentration showed an abnormal λ/κ light chain ratio (81/9.6). Proteinuria was 3.5 g/day and was composed of lambda light chain (4%) and albumin. Serologic test results for hepatitis C and B, and human immunodeficiency virus were negative. After an exhaustive workup, no sign of active tuberculosis was detected. A thoracic computed tomography scan revealed bulky and compressive calcified mediastinal lymph nodes and subcutaneous calcifications (Figure 1, Figure 2), also present on plain x-ray films (Figure 3). An abdominal computed tomography scan showed diffuse calcified retroperitoneal lymph nodes, hepatosplenomegaly, and muscular calcifications. A biopsy of a cervical lymph node, and subsequently a kidney biopsy, disclosed the presence of Congo red positive deposits of AL-amyloidosis in the absence of granuloma or tumoral cells (Figure 4). A bone marrow biopsy showed a lymphoplasmacytic infiltration consistent with a WM. The diagnosis of systemic AL-amyloidosis related to WM was made. The electrocardiogram was normal, and echocardiography showed increased wall thickness (15 mm) with normal serum troponin and NT-pro-brain-natriuretic peptide. The electromyogram showed asymptomatic sensorimotor axonal and demyelinating peripheral neuropathy. Amyloidosis extension workup revealed heart, liver, spleen, kidney, peripheral nerve, pleural, lymph nodes, and skin involvement. Treatment with corticosteroids and chemotherapy was ineffective. Dyspnea worsened, and a cardiorespiratory arrest occurred leading to the death of the patient.

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Figure 1. Thoracic computed tomography scan, transverse section: Mediastinal mass due to bulky and compressive calcified mediastinal lymph nodes (arrows). Note the presence of axillary subcutaneous calcifications (arrows).

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Figure 2. Thoracic computed tomography scan, coronal section: bulky and compressive calcified mediastinal lymph nodes (arrows), and axillary subcutaneous calcification (arrows).

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Figure 3. Plain limb x-ray film: presence of widespread subcutaneous calcifications.

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Figure 4. Cervical lymph node biopsy. Light microscopy. Presence of Congo red positive deposits of AL-amyloidosis in the absence of any granuloma or tumoral cell. Immunofluorescence study shows the exclusive presence of λ light chains in the absence of κ light chains.

Discussion 

The case presented is remarkable in regard to 2 aspects. First, light chain amyloidosis (AL type) is a rare complication in patients with WM, occurring in only 2.2% of patients.1 WM is a malignant disorder of the blood and lymph system, accounting for 2% of all hematologic malignancies. It is the result of a lymphoplasmacytic proliferation leading to the secretion of a monoclonal IgM. It remains unknown why AL-amyloidosis is more frequently the result of a monoclonal IgG component (ie, multiple myeloma) than a monoclonal IgM component (ie, WM).

Second, AL-amyloidosis is rarely revealed by massive lymphadenopathy. Although lymph node involvement has been reported in 3% to 30% of patients with all types of amyloidosis, amyloidosis remains an unusual cause of generalized massive lymphadenopathy.2, 3 It may be related to systemic amyloidosis or localized amyloidosis (20% of the cases)2 and seems to be more frequent in the setting of AL-amyloidosis compared with AA-amyloidosis.4 Calcifications are noted in up to 20% of lymph node amyloidosis cases5 and have been reported in amyloid deposits in the lungs, adrenals, liver, ovaries, kidneys, or skin and muscle, as in the present case. Calcifications are probably related to the capacity of amyloid fibrils to chelate calcium, leading to the deposition of amorphous calcified matrix within amyloidosis.6

In conclusion, practitioners should be aware that diffuse large lymphadenopathy may reveal amyloidosis.