Successful treatment of severe splenic lymphoma‑associated hemophagocytic syndrome by splenectomy and subsequent chemotherapy: A case report

Abstract

Hemophagocytic lymphohistiocytosis (HLH) represents a fatal immunopathology derived from excessive inflammatory reactions. In particular, lymphoma-associated hemophagocytic syndrome (LAHS) is associated with a dismal prognosis. The current study presented a challenging case of splenic LAHS. A 71-year-old man presented with fatigue and anorexia. Laboratory test results revealed anemia, thrombocytopenia, lactate dehydrogenase elevation and markedly elevated levels of ferritin (6,210 ng/ml) and soluble interleukin 2 receptor (sIL-2R; 11,328 U/ml). Abdominal computed tomography revealed marked splenomegaly, while fluorodeoxyglucose positron emission tomography revealed increased tracer uptake in the spleen. An elective splenectomy was performed, which led to the diagnosis of B-cell splenic lymphoma with transformation from indolent to aggressive lymphoma. Prior to the splenectomy, thrombocytopenia and hepatic dysfunction with rapidly progressing jaundice appeared, accompanying further elevation of ferritin (25,197 ng/ml) and sIL-2R levels (30,420 U/ml). On postoperative day 5, the patient was transferred to a tertiary care institution and corticosteroid pulse therapy was immediately initiated after establishing the diagnosis of LAHS. Liver dysfunction gradually recovered and subsequent chemotherapy resulted in complete remission with improved performance status. At eight months after the onset, the patient remains alive without any signs of residual lymphoma. Although splenic lymphoma typically manifests with low-grade lymphoma, it can transform into high-grade lymphoma associated with severe complications, such as HLH and multiple organ failure. In this case, splenectomy assisted in not only establishing the diagnosis but also in tumor cytoreduction before commencing chemotherapy. Through interdisciplinary collaboration, the patient was successfully treated by performing a timely splenectomy, followed by steroid pulse therapy and chemotherapy.

Keywords: hemophagocytic lymphohistiocytosis; hemophagocytic syndrome; lymphoma-associated hemophagocytic syndrome; splenectomy; splenomegaly.

Figure 1.

Preoperative abdominal CT. Dynamic contrast-enhanced CT in the (A) axial and (B) coronal planes revealed pronounced splenomegaly. No prominent lymphadenopathy was observed. CT, computed tomography.

Figure 2.

PET-CT scanning. PET-CT images reveal increased FDG uptake most prominently in (A) the spleen with a SUV-max of 16.7, followed by (B) a part of the right atrium (SUV-max of 6.8) and (C) the bone marrow (SUV-max of 4.2), with no significant FDG uptake in the liver. PET-CT, positron emission tomography-computed tomography; SUV-max, maximum standardized uptake value; FDG, ¹⁸F-fluorodeoxyglucose.

Figure 3.

Histopathological features of bone marrow biopsy. (A) HE staining shows the bone marrow is hypercellular, demonstrating a vaguely nodular appearance (scale bar, 200 µm). (B) Higher magnification shows an increase in small lymphoid cells interspersed with large cells (scale bar, 20 µm). (C) Clonality was confirmed through cytogenetic examination of T cell receptor γ chain Jγ rearrangement. (D) Gating on CD45-dimly positive cells in flow cytometry dot plots; the highlighted area represents a cell population where ~70% of the cells are CD19-positive, CD20-positive and CD10-negative. These cells exhibit unequivocal light chain restriction, also suggesting the presence of a clonal cell population. However, even with immunohistochemistry and flow cytometry, the findings are not sufficient to characterize the transition to large-cell lymphoma. HE, hematoxylin and eosin.

Figure 4.

Intra- and postoperative images from the open splenectomy. (A) Intraoperative view showing the spleen during the open procedure. Note the marked enlargement of the spleen (arrow). (B) Post-splenectomy operative view. (C) Gross appearance of the resected spleen (scale, 1 cm). The weight of the spleen was 1,100 g.

Figure 5.

Histopathological and immunohistochemical features of the excised spleen. (A) The normal architecture is effaced by diffuse processes with atrophic white pulp on HE staining (arrowheads; scale bar, 200 µm). (B) A higher magnification on HE staining shows diffuse proliferation of predominantly small, with occasional large cells. Aggregations of erythrocytes due to phagocytosis by macrophages can be observed (scale bar, 20 µm); cell classification was confirmed by immunohistochemical probing for CD68. (C) Sinusoidal and Billroth cord involvement is evident by CD8-positive (brown) sinus endothelial cells (scale bar, 20 µm), which were counterstained with Hematoxylin (Blue). (D) Immunohistochemical staining for CD68. The tissue section was strongly stained, highlighting the presence of macrophages (scale bar, 10 µm). HE, hematoxylin and eosin.

Figure 6.

Detailed treatment course of the patient. Line graph illustrating changes in key biochemical markers (T-Bil, AST, LDH, Ferritin and sIL-2R) over time, starting from the preoperative period. Note that a significant improvement is observed following steroid pulse therapy and subsequent chemotherapy for the lymphoma. The steroid administration was switched from intravenous injection of mPSL to oral intake of prednisolone on POD 14. T-Bil, total bilirubin (normal range, 0.3–1.2 mg/dl); AST, aspartate transaminase (normal range, 8–48 U/l); LDH, lactate dehydrogenase (normal range, 140–271 U/l); Ferritin (normal range, 15–500 ng/ml); sIL-2R, soluble interleukin 2 receptor (normal range, 122–496 U/ml); mPSL, methylprednisolone; POD, postoperative day; R-EPOCH, Rituximab, Etoposide, Prednisone, Oncovin, Cyclophosphamide and Hydroxydaunorubicin.