Pulmonary Extranodal Marginal Zone Lymphoma Of MALT Type Associated With Pulmonary Amyloidosis - Two Case Reports

Light chain (AL) amyloidosis is typically a systemic disease resulting from the malignant production and deposition of immunoglobulin light chain fragments in various tissues. Pulmonary AL amyloidosis is uncommon but can be seen concomitantly with non-Hodgkin lymphoma (NHL) as one of two distinct syndromes. In the more common presentation, a NHL, typically lymphoplasmacytic lymphoma or extranodal marginal zone lymphoma, produces a measurable serum/urine M-protein or light chain resulting in a systemic AL amyloidosis. There have also been sporadic reports of a less common, nodular form of pulmonary AL amyloidosis due to peritumoral amyloid deposition in patients with pulmonary extranodal marginal zone lymphoma of MALT type. This latter association is probably under-recognized. Here we present two cases from our institution with important diagnostic and therapeutic implications.

A 60 year old male was found to have bilateral pulmonary nodules. A percutaneous biopsy of the largest lesion in the left perihilar region revealed a MALT lymphoma. He was treated with eight cycles of R-CVP with a partial response. Significant residual disease led to further treatment with radioimmunotherapy using ibritumomab tiuxetan but without additional radiographic improvement. Due to concerns about the persistence of multiple pulmonary nodules, the original diagnostic biopsy was stained with Congo red to reveal amyloid deposition. No measurable monoclonal protein was present in the serum or urine. He has been observed now for an additional 4 years without evidence of progression.

This patient has pulmonary amyloidosis in a nodular pattern in conjunction with a pulmonary MALT lymphoma. Pathologic review has shown the individual pulmonary nodules to be composed of both lymphoma and amyloid. The decrease in the size of the nodules with initial chemotherapy indicates a response to therapy, likely of the lymphoma component. The lack of response to typically effective additional therapy and the stability of the nodules over an extended period of time lead us to conclude that the residual nodules are likely to be primarily composed of amyloid. The initial lack of recognition of the amyloid component was disadvantageous and made determination of treatment response difficult.

A 37 year old male with HIV was found to have multiple pulmonary nodules. Pulmonary wedge resection revealed an extranodal marginal zone lymphoma of MALT type and amyloidosis that was confirmed as AL type by laser dissection and mass spectroscopy. Initial PET/CT demonstrated widespread FDG-avid lymphadenopathy and non-FDG-avid pulmonary nodules. There was no other evidence of systemic amyloidosis. The patient has been treated with three cycles of bendamustine and rituximab. Restaging PET/CT has shown a decrease in FDG-avid lymphadenopathy but no significant improvement in the size or number of pulmonary nodules. His chemotherapy is being continued.

This patient has pulmonary AL amyloidosis in association with a stage IV extranodal marginal zone lymphoma. At first glance, the patient appears to have had a discordant response to initial treatment. However, the diagnosis of amyloidosis allows us to determine that his lymphoma has responded to therapy and the lack of response seen in the lungs is likely due to the presence of persistent amyloid. If the diagnosis of pulmonary amyloidosis was not made or known, this may have been mistakenly considered as refractory disease resulting in an unnecessary change in therapy.

The association between pulmonary amyloidosis and extranodal marginal zone lymphoma of MALT type may be more prevalent than previously recognized. All cases of pulmonary MALT lymphoma should be carefully examined for evidence of amyloid deposition. If proven, imaging studies, serum/urine electrophoresis and serum free light chain studies and organ assessments will help to determine whether the amyloid is a nodular form due to local deposition of light chain fragments or a systemic amyloidosis secondary to NHL. The former has a better prognosis than its systemic counterpart since the amyloidosis is typically localized to the lungs, has a more indolent course and is unlikely to involve other organs. As the above cases highlight, assessment of lymphoma response is greatly complicated by the concurrent presence of amyloid and PET/CT may be particularly useful in this scenario.

No relevant conflicts of interest to declare.