Extranodal natural killer/T-cell lymphoma, nasal-type

A 51-year-old previously healthy man, an ex-smoker, was admitted to the authors' medical department with a 3-month history of dry cough; intermittent fever; painless, ulcerated cutaneous lesions over the trunk and limbs (Figure 1); and progressive weight loss. He was of Greek descent. His medical history was remarkable for nasal polyps, which were surgically removed 15 years earlier. Initially, he had been treated with antibiotics, without improvement. Several days before admission, chest radiography revealed pulmonary infiltrates in the left lower lobe. On admission, physical examination revealed a well-orientated man in mild distress, with inspiratory rhonchi at the lower part of the left lung and scattered erythematous nodules of variable size, some of which were ulcerated. Laboratory values were notable for leukopenia, 3.3 x 10(9)/L; total protein, 5.9 g/dL; globulin, 2.2 g/dL; serum glutamic oxaloacetic transaminase, 86 IU/L; serum glutamic pyruvic transaminase, 71 IU/L; and lactate dehydrogenase, 519 U/L. Computed tomograph (CT) of the chest showed multiple alveolar opacities bilaterally (Figure 2). Fiberoptic bronchoscopy did not reveal any important pathologic findings. Results of bronchial biopsy, cytology of bronchoalveolar lavage, washing, brushing, and sputum following bronchoscopy were negative. CT of the brai and sinonasal area revealed an abnormal low-density mass in the left nasal area. CT findings of the abdomen were negative, as were results of a bone marrow biopsy. There was no evidence of immunosuppression. The differential diagnosis, considering the evidence described, included granulomatous or infectious diseases, angiocentric lymphoproliferative lesions, and lymphomas. Biopsy of a skin lesion showed lymphoproliferative infiltration of the dermis with a follicular and angiocentric growth pattern and regional epidermal necrosis. Immunohistochemical stains showed that the tumor cell were positive for CD56 and CD3 (cytoplasmic positivity) and expressed the cytotoxic proteins T-cell intracellular antigen and granzyme B (Figure 3) They lacked TdT, CD34, CD7, CD8, TCL-1, and CD123. Findings from an in situ hybridization study for Epstein-Barr virus were negative. Give this result, molecular analysis ofT-cell receptor (TCR) gene rearrangements was performed using polymerase chain reaction-based TCR-gamma gene, wit negative results. The morphology and the immunophenotype were consistent with natural killer/T-cell lymphoma, nasal-type. Nasal involvement must be first excluded to proceed to the diagnosis of nasal-type natural killer-cell lymphoma. Indeed, histologic examination of the nasal mass revealed its polypoid nature. Thus, the authors were led to the diagnosis of extranodal extranasal natural killer/T-cell lymphoma, nasal-type, CD56-positive, Ep stein-Barr virus-negative, TCR-negative. The patient received combination chemotherapy and completed 4 cycles of cyclophosphamide, doxorubicin vincristine, and prednisone every 14 days for 2 months. Skin lesions improved, and there was no fever soon after the initiation of therapy. Reevaluatio after the fourth cycle, however, disclosed pulmonary infiltrations as well as leukemic infiltration of the central nervous system. The patient had receive systemic salvage chemotherapy and intrathecal infusions of methotrexate. Although the lung lesions had diminished at that time, the patient develope paraplegia, his clinical course rapidly deteriorated, and he eventually died.