Should the Reporting of Bone Marrow Positivity for Amyloid Be Revised?: A Critical Assessment Based on 66 Biopsies From a Single Institution

Abstract

Context.— Amyloidoses are rare but heterogeneous disorders for which diagnosis is contingent upon the detection of deposits by Congo red stain and amyloid protein typing determines the treatment options. Objective.— To address the reporting of bone marrow (BM) involvement by amyloid in relation to the spatial distribution of deposits and to explore whether the location of deposits may have clinical relevance. Design.— We examined 66 BM biopsies positive for amyloid with regard to the location and type of amyloid, the percentage and clonality of plasma cells, other organ involvement, and relevant clinical information. Results.— In 21 cases, amyloid deposits involved BM stroma, whereas 45 cases were nonstromal. All cases of stromal involvement were typed as AL amyloidosis (or presumed AL), whereas nonstromal involvement was associated with at least 3 types of amyloidosis: AL, ATTR, and AA. The initial diagnosis of amyloidosis was made in a BM specimen in 21 of 66 cases (31.8%). Plasma cells ranged from 1% to 80% (mean, 13.4%; median, 8%; <10% in 44 of 66 specimens [66.6%]) and were monoclonal in 58 of 66 cases (87.8%), and in 54 of 66 cases (81.8%) amyloid deposits were documented in at least one other organ. Conclusions.— This study demonstrates that there is significant heterogeneity in the spatial distribution of amyloid in BM biopsy specimens with medullary, extramedullary, purely vascular, or combined involvement. Whereas stromal deposits were associated exclusively with AL, nonstromal and purely vascular deposits were seen in at least 3 types of systemic amyloidosis (AL, AA, and ATTR). We discuss the reporting of BM biopsy tissue positivity for amyloid deposits.

The Pathology of Amyloidosis in Classification: A Review

“…While biopsy of a target organ (kidney, heart) is most sensitive if amyloid is clinically suspected, a less invasive biopsy is recommended, such as abdominal fat biopsy and bone marrow biopsy [50][51][52][53][54][55][56]. The sensitivity of fat in amyloid detection is amyloid-type dependent, ranging from 70-90% in AL and 67% in ATTRv to only 14% in ATTRwt [53].…”

“…While, in the routine pathology stain H&E, amyloid has a nonspecific appearance as extracellular “amorphous” deposits, early deposits may be inconspicuous. Hence, a Congo red stain should be examined to rule out early amyloid and not just to confirm a suspicion of amyloid based on H&E. The sensitivity of the Congo red stain may be greatly enhanced by combining it with fluorescence microscopy [50, 51] (Fig. 2a, b).…”

“…Bone marrow biopsy is routinely performed for the diagnosis/follow-up of patients with most hematologic disorders. The reported overall sensitivity of this procedure for amyloid detection is ∼60% and may be the basis of a first-time diagnosis of amyloidosis in up to one-third of patients [6, 51, 58, 59]. In bone marrow biopsies selected for Congo red stain because of light chain restriction, increased plasma cells, MGUS, clinical suspicion, or prior diagnosis of amyloidosis in other tissues, amyloid was detected in 10.5% [51].…”

“…The reported overall sensitivity of this procedure for amyloid detection is ∼60% and may be the basis of a first-time diagnosis of amyloidosis in up to one-third of patients [6, 51, 58, 59]. In bone marrow biopsies selected for Congo red stain because of light chain restriction, increased plasma cells, MGUS, clinical suspicion, or prior diagnosis of amyloidosis in other tissues, amyloid was detected in 10.5% [51]. Bone marrow biopsy findings in non-AL patients, may also be useful since there is evidence that at least AA, ATTR, and ALECT2 may be associated with vascular and/or extramedullary deposits of amyloid [21, 26, 51, 60].…”

“…In bone marrow biopsies selected for Congo red stain because of light chain restriction, increased plasma cells, MGUS, clinical suspicion, or prior diagnosis of amyloidosis in other tissues, amyloid was detected in 10.5% [51]. Bone marrow biopsy findings in non-AL patients, may also be useful since there is evidence that at least AA, ATTR, and ALECT2 may be associated with vascular and/or extramedullary deposits of amyloid [21, 26, 51, 60]. The sensitivity of bone marrow biopsy in ATTRv has been reported as 41%, while in ATTRwt it is reported as 30% [53].…”