"
Lethal midline granuloma" of the upper airways generally encompasses
T-cell lymphoma and
Wegener's granulomatosis in Western populations. Treatment and outcome for each is different, but their pathological distinction may not always be possible on routine biopsy specimens. Within a defined population between 1947 and 1994, we found 12 cases of primary sinonasal
T-cell lymphoma, all with a CD20-, CD3+ immunophenotype in
paraffin sections. We studied the occurrence of the Epstein-Barr virus
RNA EBER1 using colorimetric in situ hybridization (ISH) with an oligoprobe. All available biopsy specimens from each patient were hybridized to detect the presence of
EBER1 in relation to the phase of
lymphoma progression. In addition, ISH was performed on 23 cases of nonspecific
rhinitis and 10 cases of
Wegener's granulomatosis to determine the specificity of the method in the differential diagnosis of inflammatory/ulcerative lesions. In ten cases of
lymphoma, initial biopsy specimens showed the early phase with minimal lymphocytic atypia ("
polymorphic reticulosis"). Four of these (including one recurrence) had been missed by experienced pathologists, resulting in a diagnostic delay 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, and neither was misdiagnosed as being benign. All hybridizable
lymphoma sections, regardless of phase of development, gave a strong ISH signal easily detected at low magnification in 50 to 100% of
tumor cells. Scattered positive cells were usually present even in necrotic areas. In contrast, no case of
Wegener's granulomatosis or nonspecific
rhinitis produced a true hybridization signal. We conclude that a negative
EBER1 ISH provides strong evidence against
T-cell lymphoma in the differential diagnosis of
lethal midline granuloma in our population. Conversely, a strong ISH signal for
EBER1 in immunohistochemically determined T-cell infiltrates within sinonasal tissues provides strong support for the presence of
lymphoma.