natural killer ( nk)/t - cell lymphoma is the most common subtype of primary nasal lymphoma1 ) .
nasal nk / t cell lymphoma is a very aggressive form of lymphoma , with over 50% of the tumors showing involvement of the adjacent alveolar bones , hard palate , orbits , nasopharynx and an association with an extensive soft - tissue mass2 ) .
relapse patterns of nasal nk / t cell lymphoma after treatment have not been systematically evaluated , and mediastinal nodal relapse at a controlled primary site has not been previously reported . here
we report a case of mediastinal single nodal relapse of a nk / t cell lymphoma , detected by positron emission tomography ( pet ) and confirmed pathologically , which was removed completely with surgery using video - assisted thoracoscopy ( vats ) .
a previously healthy 40-year - old korean male was admitted to asan medical center , seoul , korea , in december 2003 with symptoms of nasal obstruction and fever . a radiological examination of the paranasal sinus disclosed a soft tissue mass in the left middle meatus and associated obstructive sinusitis in the left maxillary sinus ( figure 1 ) .
a rhinoscopic examination revealed an irregular , and partly ulcerated protruding mass occupying the nasal cavity .
a punch biopsy showed the presence of extensively necrotic tissue with a few viable foci of sheets of atypical medium- to large - sized lymphocytes with irregularly shaped nuclei .
the tumor cells were positive by immunostaining for cd3 , cd 56 , cytotoxic granule marker tia-1 , and uchl-1 ( cd45ro ) , but negative for cd20 , cd79a , cd4 , and cd8 .
in situ hybridization showed the presence of epstein - barr virus in the majority of the tumor cell nuclei .
the patient was diagnosed with an extranodal cd 56 + nasal nk / t cell lymphoma . to evaluate the disease status , computed tomography ( ct ) , bone marrow aspiration and biopsy , and pet
fluorine-18 fluorodeoxyglucose ( fdg ) pet showed a focal hypermetabolic lesion with a 4.8 maximal standardized uptake value ( suv ) in the left nasal cavity , but no abnormally hypermetabolic lesions in the chest or abdomen ( figure 2 , figure 3a ) .
all of these findings were consistent with a stage ieb nasal nk / t cell lymphoma .
hematological levels were hemoglobin 12.8 g / dl , hematocrit 36.9% , platelet count 17210/mm , and white blood cell count 4,200/mm ( 66% neutrophils , 29% lymphocytes , 5% monocytes , and 0.5% eosinophils ) .
all blood chemistry findings were normal , except for a slightly elevated lactate dehydrogenase level of 379 iu / l ( normal range 120 - 250
iu / l ) . a cytological examination of the cerebrospinal fluid showed no abnormalities .
the patient was treated with three cycles of chemotherapy , consisting of cyclophosphamide , doxorubicin , vincristine , and prednisolone ( chop ) , followed by 28 fractions of local radiation therapy to the primary site , with a total dose of 5,040 cgy . in april 2004 ,
about one month after completion of the radiation therapy , fdg pet - ct revealed a newly developed focal hypermetabolic lesion with a maximal suv of 3.6 in the aorto - pulmonic nodal station .
there were no abnormal findings at other sites , except for post - radiation sinusitis and thyroiditis ( figure 3b ) .
microscopically , the node showed numerous histiocytes and epithelioid granulomas and scattered medium - sized cd56-positive lymphocytes in the paracortex ; the nuclei of these cells were positive for epstein - barr virus .
the tissue specimen of the mediastinal lymph node showed histology similar to that of the nasal mass ( figure 4a - d ) .
thirty - five months after the initial diagnosis and thirty months after the initial relapse , the patient is still alive , without any evidence of further relapse .
an extranodal nk / t cell lymphoma is characterized by extensive mucosal ulceration and angiocentric or angiodestructive lymphomatous infiltration .
these tumors have an immunophenotype of nk / t cell neoplasms , including expression of cytoplasmic cd 3 epsilon and cd56 , and many are positive for ebv3 , 4 ) .
these nk cell lymphomas show a geographic predilection , in that they are more common in asian regions such as hong kong , japan , and korea , and in latin american countries including mexico , peru , and guatemala5 - 7 ) .
" nasal " nk / t cell lymphomas are classified as lesions confined within the nasal cavity and nasopharynx , whereas " nasal - type " nk / t cell lymphomas are lesions involving sites outside the nasal cavity / nasopharynx , such as the oral cavity , palate , larynx , tonsil , skin , soft tissues , and the visceral organs4 , 8 , 9 ) .
the prognosis for patients with primary non - hodgkin 's lymphoma of the nasal cavity is poor , and the rates of distant metastasis and local relapse are high .
the 5-year overall survival and disease - free survival rates for 102 patients with stage ie nasal nk / t cell lymphoma have been recently reported to be 71.7% and 60.9% , respectively10 ) .
outcomes of 262 extranodal nk / t cell lymphomas were recently used to develop a prognostic model of these tumors , with new prognostic factors including b symptoms , stage , lactate dehydrogenase ( ldh ) level , and regional lymph node status11 ) . according to this model
, our patient , who had b symptoms and an elevated ldh level , is in group 3 ( two risk factors ) . because of
the low incidence and geographic occurrence of these tumors , a systematic evaluation of the treatment for nasal nk / t cell lymphomas has not been fully performed .
therefore , the optimal therapy for nasal nk / t - cell lymphoma has not yet been established .
although a prospective randomized trial about optimal treatment has not been performed , several retrospective studies have shown radiotherapy to be superior to chemotherapy alone for stage i / ii disease12 , 13 ) .
some studies report that the addition of chemotherapy to radiotherapy does not appear to confer any survival benefit in early stage patients13 , 14 ) .
consequently radiotherapy , either as the initial treatment or as part of the chemotherapy regimen , is presently the mainstay of a treatment program for early stage nk / t cell lymphoma .
the patient in this case was treated with three cycles of chemotherapy , followed by in field radiation therapy as and initial treatment program .
secondary lymph node involvement is rarely encountered until late in the course of disease15 ) . in the patient described here , we diagnosed mediastinal relapse promptly using pet , a highly sensitive diagnostic tool for various cancers that can detect increased glucolytic activity of neoplasms16 ) .
pet is usually performed to diagnose and stage tumors and to monitor response to therapy17 ) . although ct is frequently performed for patients with lymphoma , it is less sensitive for small tumor foci .
following treatment of a lymphoma , ct can reveal residual masses or enlarged lymph nodes , which may or may not contain a viable tumor18 , 19 ) .
lymphoma evaluation using ct is primarily dependent on the size and morphologic criteria used to differentiate a malignant from a reactive lymph node .
the patient described here had a single mediastinal lymph node of 1 cm in size .
evaluation by ct alone , without pet , would have made the diagnosis difficult and would have affected the decision in deciding whether the patient should have been further evaluated by the use of vats .
various techniques can be used to perform diagnostic mediastinal biopsies , the most widely used being the use of percutaneous fine - needle aspiration , cervical mediastinoscopy , parasternal mediastinotomy , open biopsy through a thoracotomy , and more recently vats20 ) .
vats is currently indicated not only for diagnostic procedures , but also for its versatility , permitting other surgical treatments at the same time .
mediastinoscopy is still the most widely used procedure for mediastinal lymph node biopsy , but access to the aorticopulmonary window may be difficult and is limited by the aorta and left main bronchus .
however , vats makes it possible to reach all lymph node stations , including the posterior subcarinal , paraesophageal , and prevertebral stations20 ) .
the potentially aggressive behavior of relapsed nk / t - cell lymphomas makes early and correct pathological diagnosis and prompt treatment important .
the patient described here developed a single mediastinal nodal relapse one month after initial treatment of the nasal nk / t cell lymphoma , and was diagnosed and treated using pet and vats .
this patient is still alive 35 months after the initial diagnosis and 30 months after the initial relapse without any evidence of further relapse .
 a nasal nk / t cell lymphoma is a very aggressive form of lymphoma 
 . patterns of relapse after treatment have not been systematically evaluated , and mediastinal nodal relapse at a primary site has never been documented . 
 we describe here a 40-year old man who presented with a nasal obstruction caused by a protruding mass that was identified as a nasal nk / t cell lymphoma . 
 the initial work - up , including chest and abdominopelvic computed tomography ( ct ) and positron emission tomography ( pet ) , showed no regional or distant metastasis . 
 a ct scan performed following three cycles of chemotherapy with cyclophosphamide , doxorubicin , vincristine , and prednisolone ( chop ) showed that the mass had nearly disappeared . 
 radiation therapy undertaken following chemotherapy was given to the primary site . 
 however , pet performed following radiotherapy revealed a single mediastinal lymphadenopathy , with no evidence of residual tumor in the nasal cavity . 
 a biopsy using video - assisted thoracoscopy ( vats ) showed the presence of a recurrent nk / t cell lymphoma with an immunophenotype identical to that of the primary nasal lymphoma . 
 an additional three cycles of chop chemotherapy were administered , and the patient remains alive , with no evidence of disease 30 months after the initial relapse . 
 these findings indicate that early detection with pet and prompt surgical excision with the use of vats can lead to successful treatment of a relapsed nasal nk / t cell lymphoma . 
INTRODUCTION
CASE REPORT
DISCUSSION