Natural killer cell lymphoblastic lymphoma/leukemia
Natural killer cell lymphoblastic lymphoma/leukemia is an acute leukemia of ambiguous lineage according to the WHO 2008 classification (2). Repeat contrast-enhanced whole body CT and bone marrow biopsy revealed no lymphomatous involvement outside the CNS and high dose intravenous methotrexate treatment was initiated. Her condition was complicated by left cerebellar hemisphere hematoma, which was treated with surgical removal and ventriculoperitoneal shunting. Following this complication the patient never fully regained consciousness and died 4 months later of sepsis.
Primary central nervous system lymphoma (PCNSL) accounts for less than 5% of primary CNS tumors (9). Natural killer (NK) cell derived lymphomas involving the brain are extremely rare and are more likely to extend from the nasal cavity than be PCNSL (3). A small subpopulation of NK lymphomas/leukemias may appear morphologically and immunophenotypically to derive from immature NK cells and are referred to as blastic NK lymphoma/leukemia (BNKLL) (1). These BNKLLs have been reported to affect the skin, lymph nodes, bone marrow and peripheral blood and less commonly the tonsils, spleen and paranasal sinuses (1, 10). Although secondary CSF involvement by BNKLL has been described before, this is the first report of blastic NK leukemia/lymphoma (BNKLL) to present as PCNSL (1).
With a median age of presentation at 50 years, blastic BNKLLs have been reported in children as young as 14 y-o occurring 4 times more commonly in males (10). An initially relapsing course resembling multiple sclerosis has been described before in PCNSL patients (8). Brainstem infiltration is among the least common localizations of PCNSL lesions (4). The radiological features of PCNSLs may sometimes also resemble demyelinating disease (5). Primary CNS lymphoma lesions typically exhibit a homogenous pattern of gadolinium enhancement. In a series of 100 immunocompetent patients with PCNSL, gadolinium enhancement was present in all but one case (7). The rare occurrence of PCNSLs with non- enhancing lesions may delay diagnosis, as in this case of BNKLL, in which mild ventricular gadolinium enhancement only became evident for the first time 17 months from initial presentation. CSF analysis may support the diagnosis of clinically and radiologically typical PCNSL cases, but in this BNKLL case CSF examination with cytology and flow cytometry at three different occasions over 6 months was unrevealing and otherwise helpful mainly in excluding infectious causes (4). EBV latency, which has been implicated in the pathogenesis of PCNSL primarily in immunocompromised patients, was negative, consistent with previous reports indicating lack of an association between BNKLL and EBV (10). TdT expression in the absence of TCR and immunoglobulin gene rearrangement commonly seen in BNKLL is of unknown significance but has been associated with better prognosis (10).
Due to lack of evidence-based data regarding the optimal treatment of BNKLL, high dose intravenous methotrexate was chosen for being the cornerstone of treatment for PCNSLs (4). Mitoxantrone did not appear to exert a beneficial effect given the clinical and radiological worsening during the two monthly courses of the drug. Microbleeds in lymphomatous lesions are a scarce radiological finding in immunocompetent patients with PCNSL. Clinically significant bleeding is very rare and thought to be associated with aberrant angiogenesis, as suggested by increased VEGF expression in PCNSL lesions (6).
In conclusion, BNKLL is a histological type of natural killer cell derived malignancies of unknown aetiology and poor outcome. Our case indicates for the first time that BNKLL may affect exclusively the CNS and may exhibit less typical clinical and radiological features than those described for PCNSLs. Increased awareness and clinical suspicion of less common histological types including BNKLL is essential in order to start treatment early and improve survival.
Contributed by Elli Kontogeorgi, Dimitrios Papadopoulos, Eirini Zafeiropoulou, George Karagkounis, Theodore Argyrakos, George Stranjalis, Dimitra Rontogianni, Dimitrios Karakalos