Intravascular large B‐cell lymphoma cells in the bone marrow smear preparation

Abstract

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of extranodal large B-cell lymphoma characterized by the growth of lymphoma cells only within the lumina of small vessels in the various organs (Swerdlow et al, 2008). Because of its rarity and its variety of the clinical presentations, the definite diagnosis of IVLBCL often requires long time with repeated applications of biopsy on the various organs. Bone marrow is demonstrated to be one of the affected organs (Masaki et al, 2009) and a diagnostic site in IVLBCL (Murase et al, 2007). However, the detection of lymphoma cells within the lumina of small vessels and/or sinuses in the bone marrow biopsy specimen is not necessarily guaranteed because, at least in part, the quantity of specimen yield by a single painful procedure is not large. We show characteristic morphology of IVLBCL cells in the May-Grünwald Giemsa (MG)-stained bone marrow smear preparation, which could be one of the useful features for the diagnosis of IVLBCL. From February 2006 through April 2010, 11 patients were clinically diagnosed as having intravascular lymphoma in our institute. In the retrospective analysis, five out of the 11 patients fulfilled the following presentations for the definite diagnosis of IVLBCL: (i) the proposed clinical diagnostic criteria for IVLBCL (Masaki et al, 2009), (ii) the characteristic accumulation of 18[F]-fluorodeoxyglucose (FDG) in the positron emission tomography (PET)/computed tomography (CT) (Miura & Tsudo, 2010) and (iii) the existence of atypical lymphoid cells within the lumina of small vessels in the biopsy specimens (Asada et al, 2007). In the examination of MG-stained bone marrow smear preparation, four out of the five patients presented with an involvement of IVLBCL cells (Table I). Among the four patients, the IVLBCL cells demonstrated similar unique morphological features in the three patients (Fig 1, Case #2, #3 and #5). The IVLBCL cells are large-sized cells with basophilic cytoplasm, vacuoles in the cytoplasm, not fine chromatin in the nuclei. Cell aggregates were found in two out of the three patients (Fig 1, Case #2 and #5). May-Grünwald Giemsa (MG)-stained bone marrow smear preparation of three intravascular large B-cell lymphoma (IVLBCL) patients. (Case #2) 64-year-old man. (Case #3) 74-year-old woman. (Case #5) 57-year-old woman. All three patients fulfilled the proposed clinical diagnostic criteria of IVLBCL, showed the characteristic features in 18[F]-PET/CT examination and existence of atypical lymphoma cells within the lumina of small vessels in the random skin biopsy specimens. The IVLBCL cells demonstrated a similar unique morphological feature in all three patients showing large-sized cells with basophilic cytoplasm, vacuoles in the cytoplasm, not fine chromatin in the nuclei. Cell aggregates were found in two out of the three patients (Case #2 and #5). Bone marrow is one of the initial sites of histological examination for the diagnosis of lymphoma. Biopsy specimen of bone marrow is reported to be useful for the diagnosis of IVLBCL (Masaki et al, 2009). In our retrospective analysis, however, the existence of lymphoma cells within the lumina of small vessels and/or sinuses in the hematoxyline-eosin (HE)-stained bone marrow biopsy specimen was confirmed in none of the patients with definite diagnosis of IVLBCL (Table I). Regarding the discrepancy between the previous reports and our results, we would speculate that there are methodological differences in detection of lymphoma cells such as the quantity of biopsy specimen yield, the number of biopsy specimen sections reviewed and the use of immunohistochemical analysis. On the other hand, the preparation of MG-stained smear of bone marrow aspirate is a relatively uniform procedure. In our analysis, the involvement of IVLBCL cells in the bone marrow smear was observed in four out of the five patients in which multiple accumulations of FDG in the bones were confirmed in the PET/CT examination (Table I). Three out of the four patients presented with IVLBCL cells with a similar unique characteristic morphology in the MG-stained bone marrow smear preparation (Fig 1). We would like to suggest that lymphoma cells shown here are one of the patterns of IVLBCL cells and that further investigations including 18[F]-FDG-PET/CT and/or random skin biopsy should be applied actively to make an early diagnosis of IVLBCL for such patients.