An 89-year-old Japanese man was admitted to this hospital for persistent fever for over 1 month and pancytopenia (a white blood cell count of 1700 /μL with 46 % neutrophils, 33 % lymphocytes, 7 % atypical lymphocytes, and 14 % monocytes, a hemoglobin level of 8.4 g/dL, and a platelet count of 11.9 × 10/μL). A lymphoid neoplasm was suspected because of his markedly elevated soluble interleukin-2 receptor level of 16,709 U/mL, but computed tomography revealed no lymphadenopathy or hepatosplenomegaly. An 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan showed disseminated FDG uptake only in the bone marrow (Fig. 1).

Fig. 1
figure 1

This 18F-fluorodeoxyglucose positron emission tomography scan shows disseminated FDG uptake in the bone marrow without evidence of the involvement of other organs. Focal weak FDG uptake in the liver and the spleen was considered to be within normal range

Specimens of bone marrow aspiration and trephine biopsy showed hypercellular bone marrow and large binucleated or multinucleated cells resembling Reed-Sternberg (RS) cells, which were found sparsely in a background of small- to intermediate-sized lymphocytes and activated histiocytes (Fig. 2a). Bone marrow fibrosis was also seen. Immunostaining was carried out for various markers, including CD3, CD4, CD8, CD15 (Fig. 2b), CD20 (Fig. 2c), CD30 (Fig. 2d), CD45 (Fig. 2e), CD56, PAX5 (Fig. 2f), ALK, granzymeB, and BOB.1 (Fig. 2g), and nuclear staining for Epstein-Barr virus encoded RNA was performed by in situ hybridization (EBER-ISH). RS-like cells were positive for CD30, CD45, PAX5 and BOB.1. More specifically, a subset of the tumor cells was positive for BOB.1 but negative for the other antigens and EBER-ISH. The lymphocytes around the tumor cells were predominantly CD8-positive T-cells.

Fig. 2
figure 2

Reed-Sternberg-like cells, indicated by arrows, are found sparsely in the bone marrow (a Hematoxylin and Eosin staining). These cells are negative for CD15 (b) and CD20 (c) but positive for CD30 (d), CD45 (e) and PAX5 (f). Some neoplastic cells are positive for BOB.1 (g). (Original magnification of all panels, ×400)

Southern blot analysis of the bone marrow did not reveal clonal rearrangements of the joining heavy chain immunoglobulin. On the other hand, polymerase chain reaction (PCR) of immunoglobulin heavy chain gene locus using DH and JH consensus primers demonstrated a monoclonal amplification product. Furthermore, cytogenetic study of the bone marrow showed an abnormal karyotype of 46,XY,del(3)(p?) in four of the 20 cells analyzed. Finally, the diagnosis of primary bone marrow large B cell lymphoma was established.

Descriptions of primary bone marrow lymphoma (PBML) in the literature have been limited, and its diagnostic criteria have not been established. Because our patient did not show any evidence of organ involvement, other than bone marrow assessed by CT and PET scan, the diagnosis of PBML was thought to be reasonable.

In theory, RS-like cells should be interpreted carefully because they are not specific for Hodgkin lymphoma (HL) and have been found not only in cases of other malignancies, such as non-HL, carcinomas and sarcomas, but also in reactive processes. In the current case, HL was ruled out because the RS-like cells were negative for CD15 and EBER-ISH but positive for CD45 and BOB.1.

A further question regarding the current case was the origin of the tumor cells and this was thought to be B lymphocytes, based on the positivity for PAX5 immunostaining, clonal immunoglobulin heavy chain gene rearrangement detected by PCR analysis and negativity for NK/T-cell markers.