Natural killer (NK) cell lymphomas are rare, and atypical features might lead to diagnostic pitfalls. This report describes an unusual patient in whom lymphoma occurred initially as isolated lymph node involvement, an exceptional presentation of an almost exclusively extranodal disease. Furthermore, during the terminal haemophagocytosis in the bone marrow, lymphoma cells lost the expression of the NK cell marker, CD56, making the histopathological diagnosis of bone marrow involvement difficult. This was resolved by in situ hybridisation for Epstein-Barr virus encoded small RNA, which detected occult bone marrow infiltration.

A 59 year old man presented with intermittent fever, night sweating, and left submandibular swelling. The submandibular lymph node biopsy showed partial replacement by a polymorphic infiltration of small to medium sized abnormal lymphoid cells with a prominent eosinophilic infiltrate. Focal angioinvasion by the abnormal lymphoid infiltrate was identified (fig 1A​1A,, B). The abnormal lymphoid cells were CD2⁺, surface CD3⁻, CD3⁺, and CD56⁺ (fig 1C​1C).). EBER was strongly positive on ISH (fig 1D​1D).). Polymerase chain reaction for the T cell receptor gene showed a germline configuration. These findings confirmed the diagnosis of NK cell lymphoma. To search for occult nasopharyngeal involvement, endoscopy of the nasopharynx with random biopsies was performed, but lymphoma was not seen. The serum lactate dehydrogenase concentration was increased to 640 U/litre (normal, < 400). Real time quantitative polymerase chain reaction¹¹ showed circulating plasma EBV DNA to be 1.4 × 10³ copies/ml at diagnosis. Further investigations showed no involvement of other anatomical sites. The diagnosis was therefore primary nodal NK cell lymphoma, Ann Arbor stage 1B. The patient achieved complete remission with three courses of combination chemotherapy, which was consolidated with local radiotherapy. He remained well until two years later when he developed a refractory left leg ulcer associated with enlarged left inguinal lymph nodes. Biopsy of the leg ulcer confirmed recurrent NK cell lymphoma. There was no apparent involvement of other sites. He received cisplatinum, high dose cytosine arabinoside, and dexamethasone, together with local irradiation to the leg ulcer. The response was poor, and despite chemotherapy, he developed persistent fever, hepatosplenomegaly, nodular lesions over the trunk and limbs, and pancytopenia (haemoglobin, 84 g/litre; platelets, 46 × 10⁹/litre; and white blood cell count, 1.2 × 10⁹/litre). Lactate dehydrogenase was extremely high at 5640 U/litre. Bone marrow aspiration showed scattered atypical lymphoid cells with prominent haemophagocytosis. Immunohistochemical analysis did not reveal CD56⁺ cells (fig 2A​2A–C),–C), although ISH showed multiple EBER positive lymphoid cells (fig 2D​2D).). Computerised tomography of the thorax and abdomen showed mediastinal lymphadenopathy and hepatosplenomegaly. He deteriorated rapidly and died. A postmortem examination was not permitted by the family.