Aggressive NK-cell leukemia with hemophagocytosis in a Caucasian patient

Abstract

Aggressive natural killer (NK) cell leukemia (ANKL) is a rare neoplasm characterized by a rapid course of disease and poor prognosis. Secondary hemophagocytic lymphohistiocytosis (sHLH) and coagulatory dysfunctions are frequently observed [1]. ANKL is mostly prevalent in Asian populations, whereas it is very rarely seen in European countries [2–5]. Here, we present a case of ANKL with sHLH in a 39-year-old Caucasian male. The patient was referred to our hospital due to fatigue, fever, epistaxis, and recurrent infections. He presented with a hepatosplenomegaly, but no sign of enlarged lymph nodes. The blood count showed leucocytes of 1.55 (reference range: 3.90–9.90) × 109/L, hemoglobin (Hb) of 118 (135–175) g/L and platelets of 41 (140–440) × 109/L. The lactate dehydrogenase (LDH) was elevated to 3922 (0–250) U/L and ferritin showed a pronounced increase to > 40,000 (50–360) μg/L. In the peripheral blood smear, several mediumto large-sized lymphocytes with fine to coarse azurophilic and deep-blue granules were detected (Fig. 1a). In the bone marrow cytology, 12% of all nucleated cells were classified as atypical lymphocytes with distinct granules and about the half of them with a prominent nucleolus. The flow cytometric analyses of the peripheral blood and the bone marrow revealed a population of cells positive with CD56, CD2, CD38, and cytoplasmic (c)CD3, but negative with surface (s)CD3 (Fig. 1c and d). In the peripheral blood, this cell population comprised about 15% of all leucocytes, in the bone marrow about 7% of all nucleated cells. In the trephine biopsy of the bone marrow, lymphocytes with the expression of CD56, perforin, granzyme B and Epstein–Barr virus-encoded small RNA (EBER) were detected. The latter indicated an infection with Epstein-Barr virus (EBV), which was confirmed by a high EBV copy number in the PCR. Moreover, in the bone marrow cytology, several hemophagocytes were observed (Fig. 1b). In this case, the diagnostic workup was guided by the presence of the distinctly granulated lymphocytes. The morphological characteristics of the malignant cells in ANKL can be diverse, ranging from large cells with irregular nuclei to cells resembling large granular lymphocytes (LGL) [6]. We detected CD56bright/CD16neg cells, which are typical for ANKL [7]. These cells mainly derive from poorly differentiated NK cells, mature NK cells are usually CD16bright [7]. Furthermore, our patient was positive for CD2 and cCD3, but not for sCD3. This is consistent with the findings in most ANKL cases [7]. Morphologically, besides the malignant lymphocytes, bone marrow hemophagocytosis was the most remarkable finding. We diagnosed sHLH by calculating the H-Score, which comprises nine parameters [8]. Our patient received chemotherapy including asparaginase, methotrexate, dexamethasone and etoposide. Two months after the initiation of the therapy, a 0.3% residual infiltration of malignant NK cells in the bone marrow was detected by flow cytometric immunophenotyping. The patient felt subjectively well and negated further treatment. Subsequently, he developed a DIC and sepsis and succumbed to the disease one week later. This case demonstrates the unfavorable characteristics of ANKL. The rarity of this entity in Western countries may leave clinicians unaware of its possible occurrence. * Simon Michaelis [email protected]