PB2155: B-CELL NON-HODGKIN’S LYMPHOMAS ASSOCIATED WITH AMYLOIDOSIS

Abstract

Background: Different types of B-NHLs (MZL, LPL, B-CLL/SLL, FL, MCL, DLBCL) may show plasmacytic differentiation and may produce AL amyloid locally or as a part of systemic amyloidosis. Case reports of coincidence of B-NHL and non-AL amyloidosis were also reported, therefore correct diagnostic workflow to type amyloid deposits should include three main steps 1. special histological staining (Congo red and/or Saturn red), 2. immunoprofiling and proteomic analysis (LMD-LC/MS). Nomenclature classification distinguishes 36 amyloidogenic proteins and more are expected (ISA 2020). Aims: Analysis of amyloid deposits irrespective of origin and localization is appealing for diagnostic and experimental precising which brings new insights in pathogenesis, classification and correct therapy due to a possibility of combination or hybrid amyloid deposits, and concurrent B-NHL may be detected. Methods: Amyloid deposits were detected in variable FFPE tissues stained with Congo red and/or Saturn red with consequent immunohistochemical analysis (IHC) and proteomic analysis with the use of laser capture microdissection and liquid chromatography/tandem mass spectrometry (LMD-LC/MS/MS). Concurent B-NHLs (excl. multiple myeloma, plasmocytoma and MGUS) were diagnosed due to characteristic morphology (HE, PAS, Giemsa), immunoprofile (primary antibodies with appropriate dilution - CD3, CD5, CD10, CD20, CD21, CD23, CD30, CD138, Bcl-2, Bcl-6, MUM1/IRF4, PAX5, cyclin D1 and/or SOX11, c-Myc, Ki67) and detected clonal rearrangement of IgVH (BIOMED-2). Results: In our file with 329 amyloid positive specimens concurent B-NHLs were found in 14 specimens. 7 specimens were signed as highly suspected for B-NHL with plasmacytic differentiation and immunoglobulin light chain restriction but without evidence of IgVH clonal rearrangement. The most common B-NHL associated with localised amyloidosis was ENMZL MALT-type (10 cases, 1 case with hybrid amyloidosis AL kappa/AH IgG1), in 4 specimens LPL was detected. In all cases with IHC and/or LCM-LC/tandem MS analysis AL type of amyloid was detected including 2 cases with hybrid amyloidosis AL/AH and AL/AApoAIV, and in 1 case local AL amyloid deposition was produced after a therapy for B-NHL. Summary/Conclusion: M-protein produced by B-NHL may be low or high according to a localised or systemic AL involvement resp., localised amyloid deposition is commonly associated with ENMZL MALT-type, both localised and systemic amyloidosis may be found out in LPL. Our category of highly suspected B-NHL with plasmacytic differentiation is literary sign as “AL amyloidosis with a localized B-cell neoplasia of undetermined significance” or as “AL amyloidosis with a an associated predominant kappa or lambda light chain expressing plasma cell population without evidence for clonality”. In our file (7 cases) only kappa/lambda immunohistochemically detected monotypy was recorded without an evidence of IgVH clonal rearrangement (somatic hypermutation of IgVH may be expected). The possibility of senescence evolution in B-NHL after a therapy may also bring local AL deposits (1 case in our cohort). Coincidence or association of non-AL amyloidosis (ATTRwt, ATTRv, AA and other) with B-NHL was described mainly in single case reports and extends the differential diagnosis. In a such cases both methods (IHC and LCM-LC/tandem MS) are suitable for correct amyloid typing, although LMD-LC/tandem MS brought more promising results than IHC.