Primary natural killer NK/T-cell lymphoma, nasal type, of the central nervous system.
Extranodal natural killer (NK)/T-cell lymphoma of nasal type (NKTCL) is a malignant disorder of cytotoxic NK or, rarely, T-cells, associated with Epstein-Barr virus (EBV) infection. These tumors usually occur as destructive midline facial lesions but primary involvement of extra-nasal sites has been reported (1). The "extra-nasal" NKTCL cases do not differ histologically from their nasal counterparts but exhibit a more aggressive clinical behavior (1, 4). Although secondary involvement of the central nervous system has been described (6), primary NKTCLs in the CNS are very rare and a handful of previous cases have been reported in detail (2, 3, 5, 7, 9). Primary NKTCLs of the CNS affect preferentially the cerebral hemispheres (2, 3, 5, 9) but a single case affecting the cauda equina has been reported (7). The occurrence of NKTCL of the CNS seems to be independent from the immune status or the ethnic background of the patients. The median age of onset of NKTCL in the CNS is about 50 years. The cytological spectrum of tumor cell in NKTCL is broad: the tumor cells may show variable nuclear size (ranging from small to large), nuclear morphology (unfolded, folded or angulated), chromatin appearance (vesicular or dense) and presence or absence of evident nucleoli. Apoptosis and interspersed inflammatory cells are frequently found.
NKTCL cells are positive for CD2, CD56, as well as CD3ε and negative for CD5 (1, 4). It is also positive for Granzyme B, Perforin and TIA-1 (1, 4). The immunophenotype of extranasal cases is similar to that observed in nasal cases, except for a higher percentage of CD30 expressing cells. The invariable association of extranodal NKTCL with EBV suggests a pivotal pathogenic role for this virus infection in the pathogenesis of this lymphoma subtype (1-5, 8).
The differential diagnoses comprise other types of malignant lymphoma in particular T-cell lymphomas. The TCR gene is in germline configuration in the majority of cases (1). As in our case, only a small group of NKTCLs shows clonal TCR rearrangements, suggesting that they represent tumors related to cytotoxic T-cells. Interestingly the T-cell origin seems to be more common in NKTCLs of the CNS (3-5, 8) than in extranodal cases affecting other organs.
NKTCLs of the CNS are associated with short survival and poor response to standard therapies (1-5, 8). Adjuvant treatment strategies as well as radiotherapy, applied in patient with primary nasal cavity NKTCL, may be used also for the therapy of CNS cases. The patient here reported received systemic chemotherapy (high doses of methotrexate) after the neuropathological diagnosis. After two cycles of chemotherapy, the control MRI of the brain did not reveal disease recurrence. However, due to scarce renal compliance to chemotherapy, the treatment was suspended. The patient refused further therapeutic options.
In conclusion, NKTCL, an aggressive neoplastic disorder with distinctive histopathological features and unfavorable clinical course, has to be considered in the differential diagnosis of primary CNS lymphomas.
Contributed by Marco Gessi MD, Udo Kellner MD, Harald Stein MD, Torsten Pietsch MD