British Journal of Radiology (2007) 80, e250-e252
© 2007 British Institute of Radiology
doi: 10.1259/bjr/56686654
CT appearances of amyloid lymphadenopathy in a patient with non-Hodgkin's lymphoma
C A Turner, MBBS, BSc, MRCP, FRCR
and
K Tung, BM, BCh, MA, FRCP, FRCR
Radiology Department, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
Correspondence: Dr Caroline A Turner, Radiology, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. E-mail: mandy1{at}doctors.org.uk
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Abstract
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Amyloidosis is a rare but recognized complication of non-Hodgkin's lymphoma (NHL). Most patients have evidence of irreversible systemic amyloid deposition associated with an extremely poor prognosis and, in the majority, a limited life expectancy. Lymphadenopathy secondary to amyloid infiltration is uncommon. We report an unusual case of massive amyloid lymphadenopathy related to underlying low-grade NHL, which has followed an indolent clinical course over the last 16 years. Lymphadenopathy in this patient showed unique imaging appearances with many of the enlarged nodes showing areas of diffuse low density, presumably related to amyloid deposition. Although imaging findings in amyloidosis are often non-specific and diverse, these particular features have not to our knowledge been previously described. When these radiological findings are present in the appropriate clinical setting, we suggest that the possible diagnosis of amyloidosis should be considered.
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Introduction
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A previously healthy man initially presented in 1990 at the age of 54 years with painless right cervical lymphadenopathy. He was otherwise systemically well. A lymph node biopsy demonstrated extensive amyloid infiltration adjacent to which were sheets of lymphocytes (Figure 1
). Immunophenotyping demonstrated that these lymphoplasmacytic lymphocytes were immunoglobulin M (IgM)-positive lymphoma cells with kappa (
) light chain restriction.
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Figure 1. Biopsy showing a malignant infiltrate of plasmacytoid lymphocytes with abundant production of amorphous eosinophilic material(pink), which is amyloid, virtually replacing the lymph node (x40; H&E stain).
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The nodal amyloid deposits stained with an anti- monoclonal antibody. Monoclonal IgM paraprotein was detected in the serum and a monoclonal Bence Jones protein was detected in the urine. Bone marrow trephine showed no evidence of amyloid or lymphoma infiltration.
At this stage a diagnosis was made of amyloid lymphadenopathy related to underlying lymphoplasmacytic non-Hodgkin's lymphoma (NHL) with an IgM -secreting clone. Over the next few years, the patient developed gradually progressive bulky generalized lymphadenopathy. Repeat lymph node biopsy in 1992 when there was no reduction in lymph node size following chemotherapy confirmed the presence of gross amyloid infiltration. The lymphadenopathy has been refractory to multiple chemotherapeutic regimes and also to local radiotherapy. At this time, other than pressure symptoms related to enlarged cervical and axillary lymph nodes, he remains well. He has no clear evidence of systemic amyloidosis, no progressive organ dysfunction and the underlying lymphoma remains stable 16 years after the initial presentation.
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Imaging findings
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Three separate CT examinations of the chest, abdomen and pelvis spanning 15 years (performed in 1990, 1996 and 2005) demonstrate extensive lymphadenopathy with only very minor progressive enlargement over this time period.
Within the mediastinum, there is large-volume low-density lymphadenopathy with some of the lymph nodes demonstrating flecks of calcification. There is bulky retroperitoneal and pelvic side-wall lymphadenopathy (Figures 2 and 3), in which the most striking feature is the low-density nature of the lymph nodes, which, although heterogeneous, are almost of fatty density. In both inguinal regions there are further enlarged lymph nodes of predominantly soft-tissue density but also some nodes showing areas of low density and/or calcification.
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Figure 3. CT images from(a) 1990 and (b) 2005 at comparable levels showing large low-density lobulated nodal masses along both pelvic side walls, with slightly more compression of the bladder (B) in the more recent study.
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Discussion
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Amyloidosis is a diverse condition caused by the pathological extracellular deposition and accumulation of an insoluble fibrillar protein, which demonstrates characteristic apple-green birefringence when stained with Congo red and viewed under polarized light. It is this protein component that determines the type of amyloidosis, which depends on the underlying disease. The vast majority of amyloidoses are either amyloid light chain (AL) or amyloid associated (AA) [1, 2].
AL amyloidosis, is often termed primary amyloidosis. In AL amyloidosis, the protein building block is a portion of the immunoglobulin light chain derived from plasma cells, and it is therefore usually associated with monoclonal B cell proliferation, as in this case report [1, 2].
In AA amyloidosis, also known as secondary amyloidosis, the protein component is the amino acid terminus of the acute phase protein serum amyloid, which is an acute phase reactant secreted by the liver in response to chronic inflammatory conditions. Examples of diseases associated with AA amyloidosis include rheumatoid arthritis, Crohn's disease, tuberculosis, bronchiectasis and chronic osteomyelitis [1].
The clinical presentation and imaging findings of amyloidosis are varied, particularly as amyloidosis often exists in combination with other disease processes as described, many of which may have their own radiological features [3, 4]. Biopsy is invariably required for diagnosis [4]. Amyloidosis may be localized or more commonly systemic and can manifest as a focal mass lesion or more diffuse soft-tissue thickening involving any part of the body [4]. It is a rare but recognized complication of NHL [5–7]. Although amyloidosis is able to infiltrate lymph nodes, amyloid lymphadenopathy is uncommon, occurring as a presenting feature in only 4% of patients with systemic amyloidosis [8]. In most reported cases of amyloid lymphadenopathy, patients have had irreversible systemic amyloidosis with a poor outcome, usually resulting in death [9].
Despite the relatively benign clinical course to date of the patient described in this report, his lymphadenopathy has been refractory to both local radiotherapy to nodes and cytotoxic treatment directed at the underlying plasma cell dyscrasia. This is consistent with reports documenting a limited response to the treatment of primary amyloidosis [8].
Amyloid fibrils have an affinity for calcium, and radiologically detectable calcified lymph node deposits are not an infrequent finding in both AL and AA amyloidosis [4]. CT examinations can demonstrate the presence of calcification in a number of abnormal enlarged nodes, likely to be related to amyloid deposition. This was also the case in our patient, in whom a number of enlarged nodes on CT showed calcification related to amyloid deposition. However, a previously unreported finding of diffuse low-density change within enlarged lymph node groups was a much more prominent feature in this case; we believe that this is also likely to be caused by AL deposits. The differential diagnosis of enlarged low-attenuation lymph nodes on CT includes pyogenic infection, Whipple's disease, metastatic disease following radiation and chemotherapy, tuberculosis and Mycobacterium avium-intracellulare. In our patient, there are no clinical features to suggest any such alternative diagnoses. Unfortunately, further more recent histology is unavailable and repeat biopsy cannot be justified clinically. Although acknowledging that histology in NHL can change with time and in response to treatment, in view of the fact that the CT images are similar and the histology unchanged both before and after chemotherapeutic intervention we feel that amyloidosis remains the underlying cause of these imaging appearances.
The incidence of amyloidosis is increasing [4], probably, at least in part, because of the improved treatment options for, and life expectancy of, patients with chronic diseases.
In the clinical context of a long-standing inflammatory condition or underlying plasma cell dyscrasia, we propose that the CT findings of diffuse low-density nodal enlargement should prompt the possible diagnosis of associated amyloidosis, as in this case.
Received for publication May 10, 2006.
Revision received July 24, 2006.
Accepted for publication July 31, 2006.
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References
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Abstract
Introduction
