A 56-year-old male presented to the emergency department with a 1-month history of feeling unwell with abdominal pain, night sweats, anorexia, and weight loss. A right iliac fossa mass was detected on ultrasonography. CT scan demonstrated mediastinal, extensive retroperitoneal, and abdominal lymphadenopathy, together with a 7-cm mass in the region of the cecum.
Blood results revealed normal hemoglobin, a white cell count of 29.8 × 109/L, neutrophils of 15 × 109/L, and platelets of 121 × 109/L. The lactate dehydrogenase was markedly raised at 9,647 IU/L. The blood film demonstrated medium- to large-sized mononuclear cells with basophilic cytoplasm, vacuolation, and multiple nucleoli. Peripheral blood immunophenotyping revealed the abnormal cells (25–30% of all cells) to be positive for CD19, CD10, and lambda light chain and negative for CD5 and CD23.
The bone marrow aspirate showed large abnormal lymphoid cells with variation in cell and nuclear size. These cells had basophilic cytoplasm with multiple vacuoles and multiple small basophilic nucleoli (Fig. 1a–c). Immunophenotype of the bone marrow aspirate revealed a B-cell population that was positive for CD19, CD20, CD79a, CD10, CD24, CD27, CD81, FMC7, surface Ig, and lambda light chain. A bone marrow trephine biopsy showed replacement by sheets of medium- to large-sized lymphoid cells. These cells showed mild nuclear irregularity and granular chromatin and multiple small nucleoli (Fig. 1d,e). The tumor cells were positive for CD20 (Fig. 1f), CD10 (Fig. 1g), B-cell lymphoma (BCL)6 (focal; Fig. 1h), BCL2 (Fig. 1i), CD38 (Fig. 1j), and MUM1 (Fig. 1k) and were negative for CD44, TdT, cyclin D1, CD5, CD43, and EBER. Ki-67 was expressed in >95% of cells (Fig. 1l).
G-banded chromosome analysis revealed the presence of t(8;14)(q24;32) that was confirmed by FISH to be IGH-MYC fusion positive (Fig. 1m). A subclone carrying a der(2)t(2;7)(p1?3;q?11.2) (Fig. 1n) was negative for an IGK rearrangement by FISH (not shown). A further subclone had add(13)(q34), and FISH demonstrated that the additional material of unknown origin had replaced the distal part of chromosome 13, resulting in loss of the green telomeric signal (Fig. 1o). FISH using probes for IGH/BCL2 and BCL6 showed normal signal patterns (not shown).
A diagnosis of BCL, unclassifiable with features intermediate between diffuse large BCL and Burkitt lymphoma, or BCLU (DLBCL/BL), was made. This is currently a provisional entity in the WHO 2008 classification . In contrast to BL, cases of BCLU (DLBCL/BL) have an admixture of medium- and large-sized cells, and more often have additional cytogenetic abnormalities (MYC-Complex karyotype). A proportion of cases harbor BCL2, BCL6, or CCND1 translocations, in addition to carrying a MYC translocation, comprising the so-called “double-hit” lymphomas . This latter subgroup has a particular dismal prognosis with a median survival of 4–6 months; patients are often refractory to therapy, and remissions are short lived. Morphology, immunohistochemistry, and molecular markers may further help distinguish this entity from BL . Though conventional cytogenetics and FISH did not detect a BCL2 rearrangement in our patient, BCL2 expression was detected on trephine sections. Although accurate diagnosis and distinction from BL is challenging, it is crucial for appropriate prognostication and management of this condition.
In keeping with the highly aggressive nature of BCLU (DLBCL/BL) disease, our patient developed acute kidney injury as a result of spontaneous tumor lysis syndrome for which he was treated with fluids and rasburicase. He was transferred to the intensive care unit and required hemofiltration, subsequent intubation, and ventilation. Emergency chemotherapy with mitoxantrone and prednisolone were administered with little response. Despite subsequent treatment with Rituximab-chemotherapy and organ support, on day 3 of chemotherapy he continued to deteriorate and died of disease progression and multiorgan failure.