Lymphoplasmacytic Lymphoma and Marginal Zone Lymphoma in the Bone Marrow: Paratrabecular Involvement As an Important Distinguishing Feature

Abstract

Lymphoplasmacytic lymphoma and marginal zone lymphoma in the bone marrow: paratrabecular involvement as an important distinguishing featureAssia Bassarova, Gunhild Tr¿en, Signe Spetalen, Francesca Micci, Anne Tierens, DelabieAbstractLymphoplasmacytic lymphoma (LPL) is a neoplasm of small B-lymphocytes, lymphoplasmacytoid and plasma cells involving bone marrow and sometimes lymph nodes and spleen. Lymphoplasmacytic lymphoma is often accompanied by Waldenström macroglobulinemia. Since the original description, Waldenström macroglobulinemia has become recognized as a distinct clinicopathological entity defined by serum IgM paraprotein and bone marrow involvement by lymphoplasmacytic lymphoma. Since serum IgM paraprotein in itself is not specific and can be seen in a variety of small B-cell lymphoproliferative disorders, notable chronic lymphatic leukemia and marginal zone lymphoma, as well as in rare cases of myeloma, the diagnosis of Waldenström macroglobulinemia rests largely upon the proper diagnosis of LPL in the bone marrow. The differential diagnosis between bone marrow involvement by lymphoplasmacytic lymphoma (LPL) and marginal zone lymphoma (MZL) is challenging because histology and immunophenotype of both diseases overlap. The diagnosis may be helped by demonstrating the MYD88 L265P mutation, seen in most LPL. However, the mutation is also present in MZL, although at a lower frequency.To better define the distinguishing features of LPL we studied a series of bone marrow trephine biopsies of 59 patients with Waldenström’s macroglobulinemia (WM) without extramedullary involvement and compared the findings with bone marrow biopsies from 23 patients with well-characterized MZL who also had bone marrow involvement. H&E and immunoperoxidase-stained sections of bone marrow trephine biopsies as well as flow cytometry and classical cytogenetics performed on aspirations were reviewed. The study was complemented with MYD88L265P mutation analysis on the bone marrow trephine biopsies of all patients.The features are summarized in Table 1. The most distinguishing features of LPL with respect to MZL were focal paratrabecular involvement (p<0.001), the presence of lymphoplasmacytoid cells (p<0.001), Dutcher bodies (p<0.001), increased numbers of mast cells (p<0.001) and the MYD88L265P mutation (p<0.001). Other features such as sinusoidal infiltration and immunophenotype were not distinguishing.Table 1Summary of the pathology features of lymphoplasmacytic and marginal zone lymphoma in bone marrow trephine biopsiesLymphoplasmacytic lymphomaMarginal zone lymphomapInfiltration pattern*Paratrabecular Nodular non-paratrabecular Paratrabecular and non-paratrabecular Intrasinusoidal Diffuse37% (10/27) 0% (0/27) 56% (15/27) 37% (10/27) 0% (0/27)0% (0/16) 75% (12/16) 0% (0/16) 37% (6/16) 25% (4/16)<0,001 <0,001 <0,001 1 0,015CytologySmall lymphoid cells Plasmacytoid cells Plasma cells Dutcher nuclear inclusions Mast cells100% (59/59) 100% (59/59) 93% (55/59) 90% (53/59) 87% (49/56)100% (23/23) 0% (0/23) 78% (18/23) 0% (0/23) 9% (2/23)- <0,001 0,108 <0,001 <0,001Immunophenotype of the lymphomaCD20 CD138 (plasma cells) CD5 CD23 IgK IgL IgM IgG Focal CD21+ or CD23+ follicular dendritic cell network in the stroma100% (59/59) 88% (50/57) 21% (12/52) 29% (15/51) 81% (48/59) 19% (11/59) 97% (57/59) 3% (2/59) 20% (10/51)100% (23/23) 80% (12/15) 0% (0/23) 13% (5/23) 26% (5/19) 10% (2/19) 64% (7/11) 0% (0/11) 48% (11/23) - - 0,014 0,580 - - - - 0,024MYD88 L265P mutation96% (45/47)20% (3/15)0,001*the analysis was only performed on bone marrow trephine biopsies showing less than 66% lymphoma infiltrationIn conclusion, LPL can reliably be distinguished from MZL in the bone marrow by using a combination of pathology characteristics. In contrast to other studies, our findings stress the diagnostic importance of paratrabecular infiltration in LPL. DisclosuresNo relevant conflicts of interest to declare.