Nodal T/NK-cell lymphoma of nasal type: a clinicopathological study of six cases

Aims:  To investigate the clinicopathological features of six unusual cases of nodal CD56+ and Epstein–Barr virus (EBV)+ T/natural killer (NK)-cell lymphoma, a putative nodal counterpart of nasal NK/T-cell lymphoma (nodal T/NK-cell lymphoma of nasal type) in comparison with nasal NK/T-cell lymphoma with secondary lymph node involvement ( n  = 24) and peripheral T-cell lymphoma (PTCL) of cytotoxic molecule (CTM)+ and EBV+ type ( n  = 21).
Methods and results:  All cases of nodal T/NK-cell lymphoma of nasal type exhibited diffuse infiltration of pleomorphic medium-sized to large tumour cells, reminiscent of those in CTM+ EBV+ PTCL. The tumour cells had a typical phenotype of nasal NK/T-cell lymphoma: CD2+, CD3ε+, CD4−, CD5−, CD56+, T-cell intracellular antigen-1+, granzyme B+, perforin+ and EBV+. However, four of six cases demonstrated clonal T-cell receptor γ-gene rearrangement on polymerase chain reaction analysis, unlike nasal NK/T-cell lymphoma. Comparison of clinical parameters and overall survival among the three groups demonstrated only minor differences.
Conclusions:  Nodal T/NK-cell lymphoma may occupy the grey zone between extranodal nasal-type NK/T-cell lymphoma and nodal CTM+ PTCL in a spectrum of NK to T-cell lymphomas that are EBV+. The close relationship between NK/T-cell lymphomas and cytotoxic T-cell lymphomas was also substantiated.     

Primary natural killer/T-cell lymphomas of the oral cavity are aggressive neoplasms

Thirty-four cases of primary non-Hodgkin’s lymphoma of the oral cavity were investigated for their clinical findings, histopathological features, immunophenotypes and association with Epstein-Barr virus (EBV). Four cases (12%) were natural killer/T-cell lymphomas, 3 (9%) were T-cell lymphomas and 27 (79%) were B-cell lymphomas. Compared with T- and B-cell lymphomas, NK/T-cell lymphomas had a male predominance (M:F 4:0), and most presented as ulceration of the palate and/or maxillary gingiva. Histologically, the lesions showed diffuse infiltration of medium-sized or large lymphoid tumour cells. Angiocentricity and/or angioinvasion were found in all 4 cases. The immunophenotypes of the NK/T-cell lymphomas were CD3+, CD43+, CD45RO+, CD56+ and TIA-1+. EBV was detected in 2 NK/T-cell lymphomas by in situ hybridization (ISH) and polymerase chain reaction (PCR) methods, and was not detected in T- and B-cell lymphomas. The survival rate of patients with NK/T-cell lymphoma was zero, but the survival rates for patients with T-cell and B-cell lymphomas were 67% and 38%, respectively. It appears that NK/T-cell lymphomas of the oral cavity have a predilection for originating in the palate and maxillary gingiva and are aggressive neoplasms. EBV positivity might be associated with more aggressive behaviour. Received: 21 January 1999 / Accepted: 14 April 1999     

Expression of cyclin-dependent kinase 6 (cdk6) and frequent loss of CD44 in nasal-nasopharyngeal NK/T-cell lymphomas: comparison with CD56-negative peripheral T-cell lymphomas

Lymphomas involving the nasal and nasopharyngeal region mainly include CD56-positive natural killer (NK)/T-cell lymphomas, CD56-negative peripheral T-cell lymphomas (PTL), and B-cell lymphomas. Among these, the CD56-positive lymphoma, presumably of an NK/T-cell nature, is frequently seen in Asian, Mexican, and South American patients. NK cells are proposed to be closer developmentally to T cells than to other lymphoid cells, because bipotential common progenitor cells of NK/T-cell lineage have been isolated. In this study, we collected 47 cases of nasal lymphoma and investigated the phenotypic difference between NK/T-cell lymphoma and PTL by examining the pattern of the developmentally differentially expressed molecules cdk6 (cyclin-dependent kinase 6), CD44, CD117, and by examining the rearrangement of the T-cell receptor gene (TcR-GR). cdk6, an essential regulator of the cell cycle in G1 progression, was over-expressed in a subset of cortical thymocytes, but absent in mature thymocytes. In contrast, CD44, a glycosylated adhesion molecule, was absent in cortical thymocytes, but present in mature thymocytes and peripheral activated T cells. We found both over-expression of nuclear cdk6 (n-cdk6) and frequent absence of CD44 in nasal CD56-positive NK/T-cell lymphomas, in contrast to most nasal CD56-negative PTL, which were CD44-immunoreactive with weak or no expression of n-cdk6. Almost all tested cases of NK/T-cell lymphoma displayed a germ-line configuration of TcR, without evidence of gene rearrangement. Thus, there seems to be a useful distinction between the classical NK/T type of nasal lymphoma (CD56+/n-cdk6+/CD44-/TcR-GR-) and PTL (CD56-/n-cdk6-/CD44+/TcR-GR+) involving the nasal region. The presence of Epstein-Barr virus does not seem to be a good marker for distinguishing between NK/T lymphoma and PTL involving the nasal region.     

Prevalence of Epstein–Barr virus associated with nasal lymphoma in patients attending the regional hospital of Valdivia,Chile, between 1987 and 2005

Epstein–Barr virus (EBV) is a ubiquitous herpes virus with a widespread infection in the world's adult population. EBV has been associated with human malignancies, mainly the nasal type NK/T cell lymphoma. The disease is more frequent in Asian than in Western countries. However, there are few studies from Latin American countries. The aim of this study was to determine the prevalence of EBV in patients with nasal lymphomas diagnosed in the Regional Hospital of Valdivia, southern Chile, during 1987–2005. Immunohistochemistry was done on paraffin sections using anti‐CD3ε, anti‐CD20, and anti‐CD56. The presence of small ribonucleic acids (RNAs) of EBV was detected in paraffin sections by in situ hybridization using oligonucleotides targeting EBV‐encoded small RNAs. The present study revealed a prevalence of 27.7% of Hodgkin's lymphomas and 72.3% of non‐Hodgkin's lymphomas. From the latter group, there was a prevalence of 2.9% (10 cases) of nasal lymphoma. From these 10 cases, 6 (60%) were NK/T cell lymphomas, nasal type; 1 case (10%) was a T‐cell phenotype; and 3 cases (30%) were B‐cell phenotype. The prevalence was higher than reports from Western countries, but lower than the reports from Asian countries. These results agreed with previous reports suggesting that EBV is strongly associated with T lymphomas. This study contributes new epidemiological data on EBV in Chile. J. Med. Virol. 82: 825–828, 2010. © 2010 Wiley‐Liss, Inc.     

Histological and immunophenotypic profile of nasal NK/T cell lymphomas from Peru: high prevalence of p53 overexpression.

Nasal NK/T-cell lymphoma is a unique form of lymphoma highly associated with Epstein-Barr virus (EBV). These lymphomas are rare in Western populations and much more prevalent in some Asian and Latin American countries. Although there are several sizable studies from Asian countries, the same is not true from South America. The aim of this study was to analyze a series of 32 cases of nasal T-cell lymphoma from Peru and to further extend the characterization of this disease. Immunohistochemistry was performed on paraffin sections using the following antibodies: CD20 (L26), CD45RO, CD3, Ki67, CD57, CD56, TIA-1, bcl-2, and p53. The presence of EBV was investigated with immunohistochemical analysis for latent membrane protein (LMP)-1 and in situ hybridization using an antisense riboprobe to EBER 1. The 32 patients included 18 men and 14 women (M:F ratio, 1.2:1), with a median age of 43 years (11 to 72). Three categories were identified: (1) Nasal NK/T cell lymphomas (28 cases): The morphology ranged from small or medium-sized cells to large transformed cells. Necrosis was present in 86% of the cases, and angioinvasion was seen in 36% of the cases. All cases were positive for CD45RO, CD3, and for TIA-1. CD56 was positive in 21 of 27 cases (78%), and CD57 was negative in all cases. EBER 1 positivity was identified in most of the tumor cells in 27 of 28 cases (96%), including the six cases in which CD56 was negative. Overexpression of p53 was detected in 24 cases (86%). (2) Blastic NK cell lymphoma (1 case): The neoplastic cells resembled those of lymphoblastic lymphoma. CD56 and CD45RO were positive; TIA-1, TdT, and EBER-1 were negative. (3) Peripheral T-cell lymphoma (PTCL) unspecified (3 cases): CD56, TIA-1, and EBER-1 were negative. Nasal lymphomas from Peru with a T cell phenotype are predominantly EBV-associated NK/T cell lymphomas, similar to those described in Asian countries. The expression of CD56, TIA-1, and EBER-1, in combination, are very useful markers for the diagnosis of nasal NK/T cell lymphoma in paraffin-embedded tissue. The differential diagnosis of T-cell lymphomas in the nasal region should include rare cases of PTCL unspecified and the blastic variant of NK cell lymphoma. P53 is overexpressed in 86% of the cases. The significance of this finding with regard to clinical behavior and prognosis remains to be determined.     

Therapeutic outcome of Epstein-Barr virus positive T/NK cell lymphoma in the upper aerodigestive tract

Expression of the natural killer (NK) cell antigen CD56 is uncommon in malignant lymphoma, but when it is, it is almost exclusively of the non-B cell lineage and show a preference for the nasal and nasopharyngeal region. T/NK cell lymphoma is known to be aggressive and refractory to treatment. It is highly associated with the Epstein-Barr Virus (EBV), but clinical investigations are rarely reported, that is until recently. We report here, on the clinical features and therapeutic outcomes of patients with T/NK cell lymphomas and its association with EBV. We reviewed fifty-four cases with peripheral T cell lymphomas in the upper aerodigestive tract between Jan. 1987 and Aug. 1998 from the Severance Hospital, Yonsei University College of Medicine. The diagnosis of T/NK cell lymphoma was made according to the expression of the NK cell markers, CD56 antigen and cytoplasmic CD3epsilon, in tumor specimens, by immunohistochemistry. Epstein-Barr early region (EBER) RNA was detected using in situ hybridization on paraffin-embedded sections. Among the 54 cases with malignant lymphomas occurring in the upper aerodigestive tract, 20 had T/NK cell lymphoma (37%). The primary sites of T/NK cell lymphomas were the nasal cavity, 12 cases (60%), the tonsils, 4 cases (20%), the nasopharynx, 2 cases (10%), and the oropharynx, 2 case (10%). There were no differences between the features, at diagnosis or therapeutic modalities for patients with T/NK cell lymphoma and non-T/NK cell lymphoma. The complete remission rate of T/NK cell lymphomas was lower than non-T/NK cell lymphomas (65% vs 85%, p=0.02). The overall survival of T/NK cell lymphomas was 13 months (1-74 month), which was significantly lower than non-T/NK cell lymphomas [60.6% with a median follow up of 22 months (1-101 month, p=0.02)]. Disease free survival of T/NK cell lymphomas was 22 months (4-66 month), significantly lower than non-T/NK cell lymphomas [73.8% with a median follow up of 22 months (2-95 month), p=0.04]. The overall survival rates for T/NK cell lymphomas were significantly lower than for EBV positive non-T/NK cell lymphomas (p=0.018). EBER RNA was detected in the paraffin-embedded tissue sections of all T/NK cell lymphomas, compared to only 17.6% (6 of 34 cases) for non- T/NK cell lymphomas. In conclusion, as patients with T/NK cell lymphomas showed poor clinical outcomes, and a high association with EBV positivity, clinical trials with more investigational therapeutic strategies, and further research into the relationship of EBV infection with pathogenesis of T/NK cell lymphoma is warranted.     

Classification of cell lineage and anatomical site, and prognosis of extranodal T-cell lymphoma – natural killer cell, cytotoxic T lymphocyte, and non-NK/CTL types

Due to their minority among the non-Hodgkin lymphomas, classification of extranodal T-cell lymphomas, including those of the natural killer (NK) cell type, has long been controversial and unclear, and the clinical outcome is not well clarified. Recently, new well-defined disease entities have been described based on tumor cell biology combined with anatomical site, clinical features, Epstein-Barr virus (EBV) status, and cell lineage as determined by immunophenotype and genotype. Cytological features are usually not specific, and there are no morphologic correlates with the classification of extranodal T/NK-cell lymphomas. From a human T-cell lymphotropic virus type 1 (HTLV-1) endemic area in Japan, we report here the analysis of 144 cases of extranodal T-cell lymphoma, from which fresh tissues were available. As the clinicopathological features were known, we simply reclassified the cases according to cell lineage and anatomical site. The extranodal T-cell lymphomas were classified into three types on the basis of cell lineage: (1) natural killer cell (NK) type [sCD3-, CD56+, T-cell receptor gene (TCR) germline], (2) cytotoxic T lymphocyte (CTL) type [sCD3+, TIA-1+, TCR rearranged, CD8+/-, CD4-/+], and (3) non-NK/CTL type [sCD3+, TIA-1-, TCR rearranged, CD4+/-, CD8-/+]. In addition to cell lineage, the anatomical site and clinical features were added for subclassification. NK type tumors (35 cases) included the lymphoblastic type, nasal/nasal-type NK lymphoma, and NK leukemia. The CTL type (46 cases) included anaplastic large cell lymphoma (ALCL), cutaneous type, intestinal, gamma delta T-cell type, and an unspecified type. The non-NK/CTL type (63 cases) included adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides (MF), and an unspecified type. With the exception of ATLL and MF, most extranodal T-cell lymphomas had a cytotoxic phenotype of NK type or CTL type and were often associated with EBV infection. MF and the unspecified type within the non-NK/CTL tumors, with the exception of ATLL, had a favorable prognosis. However, NK and CTL types, with the exception of ALCL, were associated with a poor prognosis. Our results indicate that anatomical site and cell lineage are useful predictors of clinical outcomes of extranodal T-cell lymphomas.     

Testicular natural killer/t-cell lymphoma,nasal type,of true natural killer-cell origin

The majority of primary testicular lymphomas are of B-cell type. Other primary lymphomas are rarely encountered in the testes. Natural killer (NK)/T-cell lymphomas of nasal type are aggressive extranodal lymphomas associated with Epstein-Barr virus infection that are usually encountered in the upper aerodigestive tract. They also occur in the skin, soft tissue, and colon. Primary testicular NK/T-cell lymphomas are rarely reported. We describe the case of a 66-year-old Korean man who presented with right-sided painless testicular enlargement and underwent radical orchiectomy. Histologic examination revealed an angiocentric and angioinvasive infiltrate of medium to large tumor cells with moderately abundant pale pink cytoplasm and folded and indented pleomorphic nuclei. Paraffin immunohistochemical studies showed positivity of the tumor cells for CD45, TIA-1, granzyme B, CD56, and CD3 epsilon. In situ hybridization showed diffuse positivity for Epstein-Barr virus-encoding RNA. The results of gene rearrangement studies for the gamma chain of the T-cell receptor were negative. The results of paraffin immunohistochemical studies for CD20, CD8, CD45RO, beta f1, and ALK-1 were negative. An extensive workup showed no evidence of lymphoma outside the testes. We report a rare case of primary testicular NK/T-cell lymphoma of the nasal type of true NK-cell origin.     

Intestinal T-cell and natural killer-cell lymphomas in Taiwan with special emphasis on 2 distinct cellular types: natural killer-like cytotoxic T cell and true natural killer cell

Primary intestinal lymphomas are rare, especially the T-cell and natural killer (NK)-cell types. Enteropathy-type T-cell lymphoma (ETL) is the most characteristic of the intestinal T-cell and NK-cell lymphomas (ITNKLs) defined in the World Health Organization classification. However, typical ETL is rare in nonendemic areas for celiac disease, which include Taiwan. With the exception of ETLs, ITNKLs comprise heterogeneous subtypes such as anaplastic large cell lymphoma, nasal-type NK/T-cell lymphoma and peripheral T-cell lymphoma, unspecified. Furthermore, the literature results with respect to the association between Epstein-Barr virus (EBV) and ITNKL are contradictory. To define the clinicopathological features of primary ITNKLs and develop a better understanding of their relationship with EBV in Taiwan, therefore, we investigated a sample of 11 patients based on the new World Health Organization classification using immunostaining, in situ hybridization for EBV detection, and polymerase chain reaction (PCR) for evaluation of T-cell receptor clonality. In conclusion, 2 distinct groups of primary ITNKLs were identified in our Taiwanese sample. The 6 group A cases were non-EBV-associated ETLs, prevalent in the jejunum and/or ileum. They were composed of monotonous round-ovoid medium-sized nuclei and had little pale cytoplasm. The immunophenotypes of these tumors were consistently CD3+, CD4-, CD8+, CD56+, T-cell intracellular antigen 1+, and Epstein-Barr early region- and monoclonal for T-cell receptor PCR, which indicated NK-like cytotoxic T-cell origin. The 5 group B cases were EBV-associated nasal-type NK/T-cell lymphomas prevalent in the ileum or cecum of younger patients. The neoplastic cells had polymorphous medium to large angulated nuclei and moderate cytoplasm, with immunologic phenotypes of CD4-, CD8-, variable cytoplasmic CD3varepsilon+, CD56+, T-cell intracellular antigen 1+, and Epstein-Barr early region 1+, and germ line PCR result for T-cell receptor, which indicated true NK-cell origin. The grave prognoses for the 2 groups did not differ significantly.     

Three cases of extranodal NK/T-cell lymphoma of the nasal type diagnosed by nasal brush cytology

Extranodal natural killer (NK)/T-cell lymphoma of the nasal type is a rare type of malignant lymphoma that is most common in Asian countries. Here we describe cytomorphologic, immunocytochemical, and molecular cytochemical features of three cases of NK/T-cell lymphoma of the nasal type diagnosed by nasal brush cytology. Cytomorphologic findings common among the three cases included the presence of several cell types, including nasal cavity epithelial cells, histiocytes, phagocytic histiocytes, and lymphoid cells, within a necrotic background. Suspected lymphoma cells were medium to large lymphoid cells possessing light blue and abundant cytoplasm. A characteristic feature of these cells was the presence of the tongue-like projections of cytoplasm from one or both sides of the cells. We believe these intriguing cytologic findings are indicators of NK/T-cell lymphoma of the nasal type. Azurophilic granules were observed in all cases, ranging from extremely fine granules to large granular lymphocyte (LGL)-like granules. Immunocytochemical and molecular cytochemical analyses showed staining for natural killer cell antigen CD56 as well as cytotoxic granule-associated proteins granzyme B7 (GrB7) and T-cell-restricted intercellular antigen-1 (TIA-1). EBV (Epstein-Barr virus) encoded small RNAs (EBER) positivity was shown by in situ hybridization, and no rearrangement of the TCRgamma gene was observed. Comparison between cytobrush and cotton swab methodology showed that cytobrush resulted in more cell-rich specimens than did cotton swabs, suggesting that nasal brush cytology with cytobrush is most useful in the diagnosis of NK/T-cell lymphoma of the nasal type.     

EBV viral load in tumor tissue is an important prognostic indicator for nasal NK/T-cell lymphoma

We retrospectively studied 19 cases of nasal NK/T-cell lymphoma for various potential prognostic factors and performed real-time quantitative polymerase chain reaction for Epstein-Barr virus (EBV) viral load in tumor tissue. Patients with a low EBV viral load (<1 copy per cell) more frequently survived for more than 2 years compared with patients with a high EBV viral load (>/=1 copies/cell) (7/7 vs 3/9; P = .014; Fisher exact test). Furthermore, the patients with low EBV viral loads had a better overall survival than patients with high viral loads (50% accumulative survival: not reached vs 4-5 months; Kaplan-Meier survival analysis; P = .049). In contrast, the overall survival of the patients did not correlate with the extent of lesion, age, stage, necrosis, histologic subtypes, CD56 expression, or angiocentric or angiodestructive growth pattern. Our findings suggest that the EBV viral load in tumor tissues is a useful indicator for predicting outcome of nasal NK/T-cell lymphoma.     

The pathology of NK-cell lymphomas and leukemias

Natural killer (NK) cell lymphomas and leukemias are a rare but clinically important group of neoplasms. Most of these tumors are aggressive, with a high rate of mortality. They include extranodal NK/T-cell lymphomas of nasal type and aggressive NK-cell leukemias. Both are Epstein-Barr virus (EBV) associated and show similar epidemiologic features. A closely related entity seen mainly in children is hydroa vacciniforme-like lymphoma, which also is EBV positive. EBV influences the pathophysiology of these tumors, through the induction of cytokines and chemokines. The differential diagnosis of NK-cell malignancies includes fulminant EBV-associated T-cell lymphoproliferative disorder, a condition referred to in the past as fatal infectious mononucleosis. Benign proliferations of NK cells can be seen in association with viral infection. The disease formerly referred to as blastic NK-cell lymphoma is now considered to be a malignancy derived from a dendritic cell precursor.     

NK-cell lymphoma with nodal presentation and expression of cutaneous lymphocyte-associated antigen

Nasal and nasal-type NK/T-cell lymphomas are predominantly extranodal tumors with a specific immunophenotype and a strong association with EBV. The cutaneous lymphocyte-associated antigen (CLA) is the homing receptor for skin-homing T cells and NK cells. In the literature, the prognostic impact of CLA expression in primary cutaneous T-cell lymphomas and nasal NK-cell lymphomas is contradictory. We present 2 non-nasal NK-cell lymphomas with nodal presentation. Both tumors showed the phenotype of CD3+ (cytoplasmic), CD5−, CD7−, CD16+, CD56+, cytotoxic molecules+, EBV+ (by in situ hybridization), and CLA+. They were polyclonal for T-cell receptor γ chain gene rearrangement, indicating an NK cell lineage. The aggressive course in these two patients suggested that in nasal and nasal-type NK-cell lymphomas, CLA expression might be an indicator of poor prognosis. More studies are needed to elucidate the prognostic impact of CLA expression in T cell and NK-cell lymphomas.     

Comparative analysis of NK/T-cell lymphoma and peripheral T-cell lymphoma in Korea: Clinicopathological correlations and analysis of EBV strain type and 30-bp deletion variant LMP1

Natural killer/T-cell lymphoma (NKTL) and peripheral T-cell lymphomas (PTCL) are prevalent in the Asian population and exhibit a high association with the Epstein-Barr virus (EBV). Moreover, differentiation of these two groups is often difficult and problematic. We investigated 35 cases of NKTL (22 nasal cases and 13 extranasal cases) and 30 cases of PTCL in terms of their clinical features, immunohistology, EBV positivity, EBV strain-type polymorphism and latent membrane protein 1 (LMP1) deletion variant distribution. Eighteen cases (82%) of nasal NKTL and seven (54%) of extranasal NKTL showed EBV positivity by EBV in situ hybridization. Fifteen cases (50%) of PTCL revealed EBV positivity. EBV strain type A was predominant in NKTL (18:5), and EBV strain types A and B were distributed evenly in PTCL (6:6). EBV-positive patients had significantly shorter survival than EBV-negative patients (P < 0.05), and EBV positivity correlated with advanced clinical stage (P < 0.05). Patients harboring type A EBV showed slightly poorer prognoses than those having type B, though it was not obviously statistically different (P = 0.07). The LMP1 deletion variant was prevalent in both NKTL (three wild-type LMP1, 15 deletion variants) and PTCL (three wild-type LMP1, eight deletion variants, two coexistent forms) patients, but did not have prognostic impact. Our results indicate that EBV acts as a negative prognostic factor in NKTL and PTCL, and that the intrinsic properties of a specific viral strain might influence the clinical behavior of these diseases.     

Characteristics of Epstein-Barr virus associated childhood non-Hodgkin’s lymphoma in the Republic of Korea

To analyze the clinicopathologic characteristics of childhood non-Hodgkins lymphoma (NHL) associated with Epstein-Barr virus (EBV), EBER in situ hybridization was performed in 80 cases of NHLs. EBER-positive lymphomas account for 25% (20/80) and include NK/T-cell lymphoma (6/6), aggressive NK-cell leukemia (1/1), peripheral T cell lymphoma (5/11), diffuse large B-cell lymphoma (5/14), hydroa-like T-cell lymphoma (1/1), marginal zone B-cell lymphoma (1/2), and post-transplantation lymphoproliferative disorder (1/1). Other types including 19 cases of Burkitts lymphoma were negative. For 9 EBER-positive cases, immunohistochemical staining for LMP-1, and EBNA-2 was performed to determine the EBV latency pattern. Two of nine EBER-positive cases expressed both LMP-1 and EBNA-2. Clinically, patients with EBV-positive B-cell lymphomas were cured with chemotherapy, whereas EBV-associated NK- and T cell lymphomas pursued fatal clinical course. In conclusion, EBVs infected in childhood NHLs are frequently associated not only with NK- and T- cell lymphomas but also large B-cell lymphomas.     

Peripheral T/NK-cell lymphoma: a report of the IXth Workshop of the European Association for Haematopathology

AIMS: In April 1998, The European Association for Haematopathology organized the IXth workshop on peripheral T-cell and NK-cell lymphomas and leukaemias. The workshop focused on unusual subtypes of these rare malignancies, allowing evaluation of the recently published WHO classification of neoplastic diseases of the lymphoid tissues. METHODS AND RESULTS: One-hundred and three cases were centrally immunophenotyped and hybridized for EBER1/2 of Epstein--Barr virus. All cases were reviewed by a panel of experienced haematopathologists and classified according to the new WHO classification for lymphoid neoplasms. Three cases were considered as precursor T-cell and 95 cases as peripheral T/NK-cell lymphoma/leukaemia. Although the cases represented a selected series of unusual cases, the following conclusions could be made: (i) Most lymphomas except the hepatosplenic gamma/delta T-cell lymphomas showed a rather broad morphological spectrum, with differences both between and within individual tumours. (ii) This heterogeneity was also reflected by the immunophenotype, for instance a variable expression of CD30 was found in many enteropathy type T-cell lymphomas. (iii) Exceptions in phenotype were regularly found in almost all categories, indicating that phenotype should not be the final determining factor in classification. (iv) The great majority of T-cell lymphomas expressed the alpha/beta T-cell receptor, with the exception of all but one hepatosplenic T-cell lymphomas and a few other extranodal peripheral T cell lymphomas. (v) Malignancies of precursor cells, blastic NK-cell lymphoma/leukaemia, adult T-cell lymphoma/leukaemia and most AIL-type T-cell lymphomas did not express cytotoxic molecules such as TIA1 and granzyme-B. In contrast, all five aggressive NK/T-cell lymphomas/leukaemias, a single case of large granular lymphocyte leukaemia and 40 of 47 primary extranodal lymphoma/leukaemias expressed these molecules. In hepatosplenic gamma/delta T-cell lymphoma, five of six cases showed expression of TIA1 but not of granzyme-B. (vi) Seven tumours developed after organ-transplant, four cases being EBV-positive. No distinct phenotype could be attributed to these cases. CONCLUSIONS: Most peripheral T/NK cell lymphomas could be categorized as distinct entities as described in the recently proposed WHO classification for lymphoid neoplasms.     

结外鼻型NK/T细胞淋巴瘤中EB病毒潜伏膜蛋白1基因30 bp碱基缺失的检测意义及其与预后的关系

目的 比较结外鼻型NK／T细胞淋巴瘤和鼻咽部慢性炎症和扁桃体炎中EB病毒潜伏膜蛋白（LMP）1基因30bp碱基缺失的检出率,初步探讨结外鼻型NK／T细胞淋巴瘤中LMP1缺失型的检出意义及其与预后的关系。方法 通过聚合酶链反应（PCR）检测55例结外鼻型NK／T细胞淋巴瘤和19例鼻咽部慢性炎症和扁桃体炎中EB病毒LMP1基因30bp的缺失情况,结合随访资料进行分析。结果 结外鼻型NK／T细胞淋巴瘤中LMP1野生型和野生为主型9例,LMP1缺失型和缺失为主型46例;鼻咽部慢性炎症和扁桃体炎中LMP1缺失型和缺失为主型16例。LMP1缺失型和缺失为主型的检出率在NK／T细胞淋巴瘤与鼻咽部慢性炎症和扁桃体炎病例间差异无统计学意义（P〉0．05）。结外鼻型NK／T细胞淋巴瘤中LMP1野生型和野生为主型病例比缺失型和缺失为主型病例预后好。结论 不能简单地将LMP1缺失型作为结外鼻型NK／T细胞淋巴瘤的致病因素,但也不能完全否定其促进该淋巴瘤演进的作用。