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Nasal T-lymphocyte/natural killer cell lymphomas (nT/NKLs) are a distinct group of neoplasms highly associated with Epstein-Barr virus (EBV), with a high prevalence in Asia but rare in Western countries. Recent studies indicate that these neoplasms are of cytotoxic T- or NK-cell derivation. Previous studies identifying a characteristic 30-base pair deletion within the 3' end of latent membrane protein-1 (del-LMP-1) in other EBV-associated lymphomas suggested a pathogenetic role for del-LMP-1 in those neoplasms. We examined 23 cases of nT/NKL from Mexico for expression of the cytolytic granular proteins TIA-1 and perforin (PRF), and for the presence of EBV by in situ hybridization (ISH). Polymerase chain reaction was performed to identify the EBV (EBNA-2) strain type and the status of the LMP-1 gene (del-LMP-1). Controls consisted of 11 sinonasal B-cell lymphomas (nBLs) and 30 reactive tonsils (RTs) from healthy Mexican individuals. The nT/NKLs expressed TIA-1 in 21 (91%) of 23 cases and PRF in 15 (65%) of 23 cases. In contrast, all of the nBLs were negative for TIA-1 and PRF. Twenty-two (96%) of 23 nT/NKLs were positive for EBV by ISH. In contrast, only 2 (18%) of 11 nBLs were positive for EBV by ISH. EBV strain Type A was identified in 21 (91%) of 23 cases, whereas strain Type B was present in 2 (9%) of the 23 nT/NKLs. A similar percentage (80%) of Type A was noted in 12 of the 15 RTs. del-LMP-1 was detected in 6 (26%) of 23 nT/NKLs, comprising 4 cases of Type A and 2 of Type B. del-LMP-1 was detected in 9 (45%) of 20 RTs. Our results indicated that TIA-1 and PRF were sensitive markers of nT/NKL. The presence of del-LMP-1 in comparable frequencies in the RTs and nT/NKLs suggested to us that this genotype was common in the Mexican population and argued against a definite pathogenetic role for del-LMP-1 in nT/NKL.

Extramedullary myeloid cell tumors (EMCTs) may be unsuspected clinically and difficult to recognize histologically. Fresh or frozen tissue is often not available for analysis. We studied 29 cases of EMCT using routinely fixed and processed paraffin-embedded tissue, an immunohistochemical method, and a panel of antibodies.We studied 29 patients with EMCTs: 22 males and 7 females, with a median age of 48 years (range, 5 to 80 years). Histologically, 9 tumors were well differentiated, 16 were poorly differentiated, and 4 were blastic.The Leder stain (napthol-ASD-chloroacetate esterase) was positive in 21 (77.7%) of 27 tumors. Immunohistochemically, the following antibodies reacted with the greatest number of cases: Leu-22 or MT1 (CD43) in 28 (96.6%) of 29, antilysozyme in 27 (96.4%) of 28, and antimyeloperoxidase (MP07) in 21 (91.3%) of 23 cases. Other myeloid lineage-associated antibodies were positive in a subset of cases: antineutrophil elastase (NP57) in 10 (62.5%) of 16, Leu-M1 (CD15) in 7 (46.6%) of 15, and Mac-387 in 6 (40.0%) of 15 cases. The well-differentiated EMCTs reacted with most myeloid-associated antibodies; poorly differentiated and blastic tumors were more often negative. The pan-leukocyte antibody LCA (CD45RB) reacted with 15 (60%) of 25 neoplasms. Three (16.6%) of 18 tumors contained numerous p53-positive cells, ranging from 10% to 50% of the tumor cell population. In 10 cases, exons 5 through 8 of the p53 gene were analyzed using the polymerase chain reaction and single-stranded conformational polymorphism analysis. Gel shifts consistent with mutations were identified in exon 8 of one tumor (10%) that exhibited abundant p53 immunostaining.Immunohistochemical studies using fixed, paraffin-embedded sections are very useful in the diagnosis of EMCTs. The most sensitive antibodies are anti-CD43, antilysozyme, and antimyeloperoxidase. Immunohistochemical methods are more sensitive than the Leder stain. We found p53 staining in a small subset of cases, in which we were able to confirm evidence of p53 gene mutation using the polymerase chain reaction and single-stranded conformational polymorphism analysis in one case; p53 gene mutations appear to be uncommon in EMCTs.