title: Sinonasal T-cell lymphoma in the differential diagnosis of lethal midline granuloma using in situ hybridization for Epstein-Barr virus RNA.
abstract: "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.
authors.affiliation: Department of Pathology, University Hospital, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Dictor
authors.forename: A
authors.initials: A
authors.lastname: Cervin
authors.forename: O
authors.initials: O
authors.lastname: Kalm
authors.forename: E
authors.initials: E
authors.lastname: Rambech
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003937:Diagnosis, Differential; D005260:Female; D006103:Granuloma, Lethal Midline / Q000175:diagnosis* / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D017403:In Situ Hybridization; D016399:Lymphoma, T-Cell / Q000175:diagnosis* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D010255:Paranasal Sinus Neoplasms / Q000175:diagnosis* / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis* / Q000235:genetics
chemical_list: D012367:RNA, Viral