SINONASAL T-CELL LYMPHOMA IN THE DIFFERENTIAL-DIAGNOSIS OF LETHAL MIDLINE GRANULOMA USING IN-SITU HYBRIDIZATION FOR EPSTEIN-BARR-VIRUS RNA

''Lethal midline granuloma'' of the upper airways generally encompasse s T-cell lymphoma and Wegener's granulomatosis in Western populations. Treatment and outcome for each is different, but their pathological d istinction may not always be possible on routine biopsy specimens. Wit hin a defined population between 1947 and 1994, we found 12 cases of p rimary sinonasal T-cell lymphoma, all with a CD20-, CD3+ immunophenoty pe in paraffin sections. We studied the occurrence of the Epstein-Barr virus RNA EBER1 using colorimetric in situ hybridization (ISH) with a n oligoprobe. All available biopsy specimens from each patient were hy bridized to detect the presence of EBER1 in relation to the phase of l ymphoma progression. In addition, ISH was performed on 23 cases of non specific rhinitis and 10 cases of Wegener's granulomatosis to determin e the specificity of the method in the differential diagnosis of infla mmatory/ulcerative lesions. In ten cases of lymphoma, initial biopsy s pecimens showed the early phase with minimal lymphocytic atypia (''pol ymorphic reticulosis''). Four of these (including one recurrence) had been missed by experienced pathologists, resulting in a diagnostic del ay of 2 to 8 yr. The remaining two cases were in the late phase, i.e., malignant grade atypia was apparent in the initial biopsy specimen, a nd neither was misdiagnosed as being benign. All hybridizable lymphoma sections, regardless of phase of development, gave a strong ISH signa l easily detected at low magnification in 50 to 100% of tumor cells. S cattered positive cells were usually present even in necrotic areas. I n contrast, no case of Wegener's granulomatosis or nonspecific rhiniti s produced a true hybridization signal. We conclude that a negative EB ER1 ISH provides strong evidence against T-cell lymphoma in the differ ential diagnosis of lethal midline granuloma in our population. Conver sely, a strong ISH signal for EBER1 in immunohistochemically determine d T-cell infiltrates within sinonasal tissues provides strong support for the presence of lymphoma.