Clinical Course and Pathological Findings in a Series of Patients with Aggressive Natural Killer (NK) Cell Leukemia

NK cell leukemia is a rare, malignant proliferation of NK cells associated with Epstein Barr Virus (EBV). The World Health Organization (WHO) defines NK cell leukemia based on a blood film showing pancytopenia, and circulating leukemic cells, which are positive for CD2, cytoplasmic CD3, CD56, and cytotoxic molecules. The neoplastic cells may have a wide range of appearances, including cells that resemble large granular lymphocytes, highly atypical cells with abundant cytoplasm, and azurophilic granules. Reported cytogenetic abnormalities have included 6q deletion, 11 q deletion and losses of 7p and 17p.

Previous publications in the medical literature have been limited to case reports, mostly from Asian centers.

We conducted a retrospective chart review of all aggressive NK cell leukemia diagnoses at an academic medical center, from 2008–2012.

We identified 4 cases of aggressive NK cell leukemia. The median age at diagnosis was 57 years. 3 out of 4 cases were male, and 3 of 4 were associated with EBV infection. All patients presented clinically with cytopenias, one patient had an elevated white blood cell count, 31 × 10 ⁹per liter with the others presenting with pancytopenia. All had constitutional symptoms (including fever and night sweats) at diagnosis. 2/4 cases had extramedullary involvement, including splenomegaly and lymphadenopathy. One patient presented with hemophagocytic lymphohistiocytosis. 2/4 patients had CNS involvement. All had a large proportion of circulating neoplastic cells (12–80%).

The blood film examination in all cases demonstrated large, pleomorphic neoplastic cells. Most (3/4) had distinct nucleoli and 1/4 had large azurophilic granules in the cytoplasm. The immunohistochemistry profile showed positivity for cytoplasmic CD3, CD56 and CD7 in all cases. 3/4 cases were positive for CD11c. 2/4 patients had unique complex karyotypes including chromosome 3p duplication, deletion of 16q, addition 1p, trisomy 7, trisomy 8, isochrome 17q and near tetraploid karyotype.

All patients received treatment with various chemotherapeutic protocols; however none received radiation therapy, or stem cell transplantation. 2/4 cases achieved a short remission. All patients had poor clinical outcomes with median survival of 12 months (range 2–19 months), which is consistent with prior reports.

This case series serves to confirm the typical clinical presentation, and poor prognostic outlook, of patients with aggressive NK cell leukemia. This rare malignancy was previously described only in individual case reports. In our patient population, we noted complex, novel cytogenetic findings. Our study reaffirms the need for new therapeutic modalities to improve the poor prognosis for this disease.

No relevant conflicts of interest to declare.