Pattern of Epstein-Barr virus association in childhood non-Hodgkin's lymphoma: experience of university of malaya medical center

The pattern of childhood non-Hodgkin's lymphoma (NHL) usually differs in adults. The most common subtypes are lymphoblastic, Burkitt's and anaplastic large cell lymphoma. Recent data indicate that a higher risk of developing lymphoma is associated in children of certain ethnic origins. The difference is probably related to the underlying etiological factors of these diseases, and Epstein-Barr virus (EBV) is a strong candidate. The present study aims to determine the disease pattern of childhood lymphomas in the University Hospital Kuala Lumpur, for a direct comparison to the reported data of adults from the same medical center. A total of 69 and 34 childhood NHL and Hodgkin's lymphomas, respectively, were retrieved. The most common subtypes were lymphoblastic (23 cases), Burkitt's (25 cases) and anaplastic large cell lymphomas (9 cases). Epstein-Barr virus association was more prevalent in B-cell (23%) than T-cell (12%) lymphomas. The most common EBV-associated tumor was Burkitt's lymphoma, and there was an increased risk of EBV association for Burkitt's lymphoma in Chinese patients. In conclusion, the pattern of childhood lymphoma in Malaysia is relatively similar to children elsewhere in the world. The EBV association of B- and T-NHL differs between children and adults from the same medical center because of differences in the subtype composition in these two age groups.     

Immunophenotypic analysis of non-Hodgkin's lymphomas in Chinese. A study of 75 cases in Hong Kong

The cell surface markers of 75 cases of non-Hodgkin's lymphoma were studied on cryostat sections using a panel of monoclonal antibodies. Forty-nine cases (65.3%) were found to express a B-cell phenotype, 23 cases (30.7%) a T-cell phenotype, 1 case (1.3%) a histiocytic phenotype and 2 cases (2.7%) no demonstrable surface markers. Follicular lymphoma accounted for only 10.7% of the cases. Most B-cell lymphomas expressed IgM-lambda or IgM-IgD-lambda, but a few failed to express surface immunoglobulin. Among the 23 cases of T-cell lymphoma, 22 were of peripheral T-cell type; most were of helper-cell (T4) phenotype and a significant number expressed J5 (CALLA) and I2 (HLA-DR). The present study shows that the percentage of T-cell lymphoma in Chinese is higher than in Caucasians, but lower than in Japanese. However, when the age-adjusted incidence of non-Hodgkin's lymphoma is considered, the incidence rates of T-cell lymphoma in Hong Kong Chinese and Japanese in areas non-endemic for adult T-cell lymphoma/leukemia are similar; the incidence in Americans is similar or slightly lower. The major difference between the races is that B-cell lymphoma, particularly the follicular type, is much rarer in Asians than Americans.     

Study of vimentin expression in non-Hodgkin's lymphoma using paraffin sections.

Human non-Hodgkin's lymphomas were studied by means of an avidin-biotin complex immunoperoxidase method using several monoclonal antibodies against the intermediate filament protein, vimentin. The study cases were 61 B-cell lymphomas (including 2 plasmacytomas) and 30 T-cell lymphomas (including 8 cases of mycosis fungoides). Twelve of the 61 B-cell lymphomas were positive for vimentin, and were composed of extrafollicular-center cells such as immunoblastic and plasmacytoid cells. On the other hand, lymphomas of follicular center cell origin were negative for vimentin. All cases of T-cell lymphoma except for 14 (all of 9 AILD-type lymphomas, all of 4 lymphoblastic lymphomas and one diffuse mixed small/large lymphoma) were positive for vimentin. Although vimentin expression appeared to be influenced by various conditions such as the proportion of T- and B-cell subsets, or B-cell proliferation rate, follicular center cells were constantly negative for vimentin.     

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     

Immunohistological subtypes of non-Hodgkin's lymphoma in Hong Kong Chinese

One hundred and four unselected cases of non-Hodgkin's lymphoma (NHL) in adult Chinese patients in Hong Kong were typed, using monoclonal and conventional antibodies, by immunoenzymatic labelling methods on cryostat sections or cell smears. The total included 69 cases (66%) of B-cell and 26 (25%) of T-cell tumours. The diffuse large cell (centroblastic or immunoblastic) types formed the largest proportion (44.9%) of B lymphomas. Of 26 cases of T-cell lymphoma 25 were of peripheral type; of these 25, the most frequent subtype (42.3%) was the immunoblastic lymphadenopathy-like lesion. Although there were 9 pleomorphic T-cell lymphomas, none of the patients presented with the adult T-cell leukemia/lymphoma syndrome. The incidence of T-cell lymphomas in our population is not markedly higher than that of western countries, but there are some interesting differences in the types of T-cell lymphomas that are commonly seen.     

The World Health Organization classification of malignant lymphoma: incidence and clinical prognosis in HTLV-1-endemic area of Fukuoka

New insights into the pathogenesis of lymphoid malignancies have been gained through novel genetic, molecular and immunological techniques. A new classification system for lymphoid malignancies, known as the new World Health Organization (WHO) classification, has been proposed recently based on these findings. The relative incidence of the subtypes of malignant lymphoma is known to differ according to geographic location. Adult T-cell leukemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukemia virus type 1 (HTLV-1), and the Kyushu islands are an HTLV-1 endemic area. To clarify the relationship between the histological classification and prognosis of lymphoid malignancies, we reclassified previous cases in our department and summarized our previous reports using the WHO classification. Of 933 cases of lymphoid malignancies, 471 (50%) were B-cell lymphoma, 396 (42%) T/natural killer (NK)-cell lymphoma and 41 (4%) Hodgkin lymphoma (HL). Analysis of clinical outcome showed favorable prognosis for HL, intermediate for B-cell lymphoma and poor prognosis for T-cell lymphoma. Among B-cell lymphomas, the commonest type was diffuse large B-cell lymphoma (n = 281; 60%). Marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) was diagnosed in 82 cases (17%), follicular lymphoma in 52 (11%) and mantle cell lymphoma in 24 (5%). Other less common lymphomas were Burkitt lymphoma (n = 9; 2%) and lymphoblastic lymphoma (n = 5; 1%). Using overall survival rates, the various B-cell lymphoma types could be divided into three broad groups for prognostic purposes: (i) low-risk group comprising follicular lymphoma and MALT; (ii) intermediate-risk group comprising diffuse large B-cell lymphoma and Burkitt lymphoma; and (iii) high-risk group comprising mantle cell lymphoma and lymphoblastic lymphoma. Among the T/NK-cell lymphomas, the commonest type was ATLL (n = 191; 48%), followed by peripheral T-cell lymphoma, unspecified (n = 83; 21%), angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) (n = 38; 10%), anaplastic large cell lymphoma (ALCL) (n = 22; 6%). Less common types were lymphoblastic lymphoma (n = 17; 4%), nasal and nasal-type NK/T-cell lymphoma (n = 17; 4%), mycosis fungoides (MF) (n = 9; 2%) and other rare types. With respect to clinical prognosis, T/NK-cell lymphomas fell into three groups: (i) relative low-risk group comprising ALCL, AILD, MF and lymphoblastic lymphoma; (ii) relative intermediate-risk group comprising NK/T-cell lymphoma and unspecified lymphoma; and (iii) extremely high-risk group comprising ATLL. Among the lymphoblastic lymphomas, B-cell type and T-cell type lymphomas exhibited different clinical outcomes. We conclude that the histological, phenotypic and genotypic classification of the new WHO system should be beneficial for the clinical approach to these tumors.     

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.     

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.     

Retrospective study of 82 cases of canine lymphoma in Austria based on the Working Formulation and immunophenotyping

In human beings the prevalence of different non-Hodgkin's lymphoma (NHL) subtypes varies according to geographical region. The aim of this study was to classify canine lymphomas in Austria and to compare the results with those of similar studies in other countries. Eighty-two NHLs were classified according to their morphology (based on the Working Formulation) and their immunophenotype (determined with anti-T-cell and anti-B-cell antibodies). Forty-two (51.2%) were of B-cell subtype, 24 (29.3%) of T-cell subtype, and 16 (19.5%) remained unclassified, because of either negative labelling (9/16) or immunoreaction with both antibodies (7/16). Diffuse lymphomas predominated (99%) over follicular lymphomas, while intermediate grade lymphomas (61%) outnumbered high-grade lymphomas (23.2%) and low grade lymphomas (13.4%). The most common subtype was the diffuse large cell lymphoma (40.2%), followed by the large cell immunoblastic lymphoma (13.4%) and the diffuse small lymphocytic lymphoma (13.4%). Follicular large cell lymphoma and small noncleaved cell lymphoma were uncommon (1.2%). Generally, these findings accord with those of similar studies in Western Europe, making the existence of specific risk factors in Austria unlikely.     

Clinicopathological analysis of 501 non-Hodgkin's lymphomas in Korea according to the revised European-American classification of lymphoid neoplasms

AIMS: The clinical relevance of the Revised European-American Classification of Lymphoid Neoplasms (REAL) is still debated. To test the clinical validity of the REAL classification in Korea, where the incidence of T-cell lymphoma is higher, we investigated the clinicopathological features of non-Hodgkin's lymphoma (NHL) from Korea Cancer Center Hospital. METHODS AND RESULTS: Five hundred and one patients with NHL were reclassified according to the REAL classification and clinicopathologically analysed. Immunophenotypically, B-cell lymphoma accounted for 67.9% and T- and NK-cell type for 30.5%. Approximately 48.5% of cases were forms of diffuse large B-cell lymphoma (DLBCL), while only 5.4% were follicular lymphoma. Peripheral T-cell lymphoma unspecified (PTCL-U; 10.8%) and angiocentric lymphomas (11.8%) comprised the majority of T-cell lymphomas. Most of the angiocentric lymphomas presented with localized nasal/nasopharyngeal or tonsillar primaries. All peripheral T-cell lymphomas (PTCL) showed a significantly low overall survival compared to DLBCL (P = 0.02, log rank). Overall survival rates for DLBCL and PTCL-U were also significantly different (P = 0.0043, log rank), though for DLBCL and angiocentric lymphoma there was no significant difference (P = 0.2142, log rank). Angiocentric lymphoma, however, was characterized by a shorter median survival time than DLBCL (54 months vs. 96 months). Among DLBCL patients according to the REAL classification, overall survival was significantly better in nonimmunoblastic type (intermediate-grade, WF-F,G) as compared to large cell immunoblastic type (high-grade, WF-H) (log rank, P < 0.001). The morphological distinction of the immunoblastic and nonimmunoblastic among DLBCL of the REAL classification bears significant prognostic relevance worthy of further consideration. CONCLUSION: We conclude that lineage assignment (T vs. B) in the REAL classification is a clinically important distinction, but that it is necessary to subdivide the broad category of DLBCL.     

Frequent alteration of MDM2 and p53 in the molecular progression of recurring non-Hodgkin's lymphoma

AIMS: Recurrence of non-Hodgkin's lymphoma with or without transformation is often associated with increased clinical drug resistance and poor prognosis indicating molecular progression. The study addresses the currently poorly understood molecular mechanisms underlying relapsing non-Hodgkin's lymphoma. METHODS AND RESULTS: We have analysed sequential biopsies from 42 non-Hodgkin's lymphoma patients immunohistochemically for p53 alterations (based on p53 and p21Waf1 expression), as well as for expression of MDM2, p27Kip1 and cyclin D3. Relapse of follicle centre lymphoma was associated with p53 alterations as 5/6 (83%) follicle centre lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. Of these cases, three showed transformation to diffuse large B-cell lymphoma. p53 alteration was also associated with relapse of de novo diffuse large B-cell lymphoma and T-cell non-Hodgkin's lymphoma, as 2/5 (40%) diffuse large B-cell lymphomas and 3/9 (33%) T-cell non-Hodgkin's lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. No indolent non-Hodgkin's lymphoma case showed MDM2 over-expression at diagnosis, whereas 4/5 (80%) transformed diffuse large B-cell lymphomas developed MDM2 over-expression. CONCLUSION: Our data are consistent with the notion that p53 alterations are important for the histological transformation of follicle centre lymphoma. However, the data also suggest that relapsing follicle centre lymphomas without overt transformation often have p53 alterations and increased risk of transformation, and that relapse of de novo diffuse large B-cell lymphomas and T-cell non-Hodgkin's lymphomas is associated with p53 alterations. Furthermore, our results are consistent with an association of MDM2 over-expression with histological transformation of both follicle centre lymphoma and marginal zone B-cell lymphoma.     

Malignant lymphoma of the thyroid. A 30-year clinicopathologic experience and an evaluation of the presence of Epstein-Barr virus.

Lymphoma of thyroid is uncommon, and Epstein-Barr virus (EBV) is found in many lymphomas. We studied the clinicopathologic characteristics in Hong Kong Chinese and analyzed the presence of EBV in thyroid lymphomas by reviewing data collected during 3 decades. We studied EBV gene expression by in situ hybridization and immunohistochemistry. Primary thyroid lymphomas were found in 23 patients (diffuse large B-cell lymphoma, 18; marginal zone B-cell lymphoma, 4; plasmacytoma, 1), and secondary lymphomas were found in 9 patients (diffuse large B-cell lymphoma, 3; Burkitt lymphomas, 2; Burkitt-like lymphoma, 1; hairy cell leukemia, 1; nasal T-cell and natural killer cell lymphoma, 1; and intestinal T-cell lymphoma, 1). Primary thyroid lymphomas were large (mean, 7 cm), found commonly in older women, and often misdiagnosed as undifferentiated carcinomas. Fine-needle aspiration was not helpful for diagnosis. Fifteen patients had Hashimoto thyroiditis. A history of thyrotoxicosis was found in 3 patients, and coexistence of 3 diseases (papillary microcarcinomas, primary thyroid lymphoma, and Hashimoto thyroiditis) was found 4 patients. The 5-year survival rate for primary thyroid lymphoma was 53%. Combined surgery and radiotherapy seemed to be the best treatment. Secondary thyroid lymphomas often were asymptomatic. EBV messenger RNAs were detected in 1 primary and 1 secondary thyroid lymphoma. The EBV gene expression in primary thyroid lymphoma showed a type II latency pattern. Thyroid lymphomas in Chinese had important clinicopathologic features. EBV may have a role in a subset of cases.     

Lymphomas of the oral cavity: histology, immunologic type, and incidence of Epstein-Barr virus infection

The purpose of this study was to determine the histologic class and immunologic phenotype of lymphomas presenting initially in the oral cavity and whether this correlated to a high incidence of Epstein-Barr virus (EBV) infection as has been reported with lymphomas in the nasal cavity. Seventy-one cases of oral lymphomas from the oral pathology referral service were analyzed retrospectively. They were classified according to the Revised European American Lymphoma (REAL) classification system using routine immunohistochemistry. EBV infection was determined by detection of early viral RNA sequences (EBER) and latent membrane protein (LMP-1) expression. Only non-Hodgkin's lymphomas were observed, with a female predominance of 2:1. They were primarily of B-cell origin and histologically classified mainly as large B-cell type (68%); T-cell lymphomas were rare (8%). EBV infection was observed in 14% of the B-cell lymphomas, an incidence rate higher than that reported in studies of B-cell lymphomas not located in the oral cavity but not as high as that observed in pleomorphic T-cell lymphomas (all sites, 36%) or nasal cavity T-cell lymphomas (nearly 100%). Interestingly, EBV proliferation did not correlate with expression of either Bcl-2 or p53.     

The world health organization classification of malignant lymphomas in japan: incidence of recently recognized entities. Lymphoma Study Group of Japanese Pathologists

New insights into the immunology and genetics of malignant lymphomas have allowed the recognition of new entities and the refinement of previously recognized disease categories. The relative incidence of these subtypes of malignant lymphoma is also known to differ according to geographic location. In order to clarify the current status of malignant lymphomas in Japan and the relative incidences of their subtypes, 3194 patients were classified according to the new World Health Organization (WHO) classification. Among these were 3025 cases (94.71%) of non-Hodgkin's lymphoma (2189 cases (68.53%) of B-cell lymphoma, 796 cases (24.92%) of T-cell lymphoma) and 141 cases (4.41%) of Hodgkin's lymphoma. The incidences of the major subtypes of non-Hodgkin's lymphoma were 33.34% for diffuse large B-cell lymphoma, 8.45% for marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, 8.05% for plasma cell myeloma, 7.45% for adult T-cell leukemia/lymphoma (ATLL), 6.7% for follicular lymphoma, 6.67% for peripheral T-cell lymphoma of unspecified type, 2.79% for mantle cell lymphoma, 2.6% for nasal and nasal-type T/NK cell lymphoma, 2.35% for angioimmunoblastic T-cell lymphoma, and 2.35% for precursor B-cell lymphoblastic leukemia/lymphoma, in decreasing order. The other subtypes comprised less than 2%, mainly precursor T-cell lymphoblastic lymphoma/leukemia (1.72%), anaplastic large-cell lymphoma of T- and null-cell types (1.53%), and B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (1.31%). The incidence of ATLL was influenced by its high percentage (19.20%) in the south-western Japanese island, Kyushu, an endemic area of human T-cell leukemia virus type 1 (HTLV-1), but which appeared to be lower than that in a previous study. The nodular sclerosis and mixed cellularity types of Hodgkin's disease occupied 1.78% and 1.63%, respectively. These data are distinct from those in Western countries and similar in several ways to those in the East, although the relatively high rate of ATLL was attributed to the geographical difference in the etiologic factor, HTLV-1.     

Distribution and ZAP-70 expression of WHO lymphoma categories in Shanxi, China: a review of 447 cases using a tissue microarray technique.

This study aims to assess the distribution of lymphoma subtypes in Shanxi, China, according to the World Health Organization (WHO) classification, and to compare the relative distribution with other areas of the world. H&E-stained tissue sections from the archives of the Shanxi Tumor Hospital, China, were reviewed and 447 cases with sufficient materials were selected for detailed study. A panel of antibodies and probes was assembled, including antibodies to ALK1, bcl-6, CDs 1alpha, 3, 4, 5, 7, 8, 10, 15, 20, 23, 30, 43, 56, 68, 79alpha, and 99, cyclin D1, EMA, kappa, lambda, LMP1, PAX5, TdT, Vs38C and ZAP70, plus EBER RNA probe by in situ hybridization. The 447 lymphoma cases, subtyped according to the WHO classification, were assembled in triplicate into 11 tissue microarrays and examined with the panel of markers described. Among the 447 cases, 385 (82.6%) were confirmed to be non-Hodgkin lymphomas (NHL) and 62 (13.9%) were Hodgkin lymphomas of classic type (CHL). Of the NHL cases, 68.6% were B-cell lymphomas and 30.6% T/NK-cell lymphomas. Histiocytic neoplasms accounted for only three cases (0.8%). Diffuse large B-cell lymphomas (DLBCL) were the most common subtype (35.1%), followed by peripheral T-cell lymphomas unspecified (PTun, 12.0%), extranodal marginal zone B-cell lymphomas (MALT lymphomas, 11.7%), follicular lymphomas (FL, 8.6%), T-lymphoblastic lymphomas (T-LBL, 7.0%), anaplastic large cell lymphomas (ALCL, 4.2%), B small lymphocytic lymphomas (B SLL, 3.6%), and mantle cell lymphomas (MCL, 2.6%). Of 263 B-cell neoplasms, 105 (39.9%) expressed immunoglobulin light chain, including 52 kappa and 53 lambda, detectable in paraffin sections. The incidence of DLBCL was similar to many Western countries and Asia. The frequency of FL was, however, much lower than the usual pattern in Western countries, although NK/T-cell lymphomas were more common (30.6%), similar to other countries in Asia, including Japan and Korea. With regard to markers of EBV infection, 8 of 385 (2.1%) NHL cases gave positive findings by both in situ hybridization (EBER RNA) and immunohistochemistry (LMP-1), whereas 24 (6.2%) expressed only the EBER and 12 (3.1%) expressed only LMP-1. EBV positivity was found in 24 of 119 (20.2%) T and NK cell lymphomas, in 20 of 263 (7.6%) B cell neoplasms, and in 37 of 62 (59.7%) CHLs. In CHLs there was complete concordance of results by both in situ hybridization (EBER RNA) and immunohistochemistry (LMP-1) procedures. ZAP70 was detected in most T cell-lineage disorders (61.4%) and also in a subset of B small lymphocytic lymphomas (50%). However, ZAP-70 was expressed in a minority of other types of B-cell lymphomas, including precursor B-cell acute lymphoblastic leukemia (25%), diffuse large B-cell lymphoma (26.7%), follicular lymphoma (15.2%), and lymphoplasmacytic lymphoma (9.1%). Immunohistochemical analysis represents an effective method for assessing ZAP-70 expression and reveals that a variety of B-cell malignant neoplasms express ZAP-70, albeit at low frequency.     

Epstein-Barr virus-associated B-cell lymphoproliferative disorders in angloimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified

Various patterns of Epstein-Barr virus (EBV)-associated B-cell lymphoproliferation occur in patients with immunodeficiency. We studied 17 cases of T-cell lymphoma displaying extensive EBV-driven B-cell lymphoproliferation or simultaneous/subsequent EBV-associated B-cell lymphoma. In 10 cases of angioimmunoblastic T-cell lymphoma, an uncommonly prominent population of EBV+ atypical, activated, focally confluent large transformed B cells was found in the background of T-cell lymphoma. In 4 cases, an EBV-associated B-cell neoplasm (3 diffuse large B-cell lymphomas, 1 plasmacytoma) occurred in patients with T-cell lymphoma. Three cases were composite lymphomas of a peripheral T-cell lymphoma, unspecified, combined with EBV-associated diffuse large B-cell lymphoma. The transformed B-cell population displayed EBV latency types 2 and 3. Monoclonal and oligoclonal B-cell populations were detected in 5 and 6 cases, respectively. Similar to other states of immunodeficiency, disease-related and therapy-induced immunosuppression in T-cell lymphoma may lead to a prominent EBV-associated B-cell lymphoproliferation and to EBV+ B-cell neoplasms.     

Primary lymphoma of the thyroid: a clinical, histological and immunohistochemical study of 20 cases

Twenty cases of malignant lymphoma arising in the thyroid gland were studied clinically, histologically and immunohistochemically. Nineteen cases were non-Hodgkin's lymphoma (15 diffuse and four follicular lymphoma) and one was a plasmacytoma. Immunohistochemical analysis of the lymphomas using paraffin-embedded sections disclosed that 17 lymphomas were B-cell type and two were T-cell type. The plasmacytoma was of IgG kappa type. The large majority of the lymphomas were associated with an underlying chronic thyroiditis. The 5-year survival rate of the patients was 70%. An unfavourable diagnosis was more likely when the tumour was diffuse rather than follicular, when it was of diffuse large cell type or of immunoblastic type and when there was cervical lymph node involvement.     

The prognostic significance of immunophenotype in high-grade non-Hodgkin''s lymphoma

The prognostic value of immunophenotyping lymphomas was assessed by studying 51 cases of high-grade non-Hodgkin's lymphoma for which long term clinical follow-up (14-28 years) was available. Using antibodies which identify T- and B-cell-related antigens in formalin-fixed, paraffin-embedded material, 43 were shown to be of B-cell and eight of T-cell phenotype. In terms of survival, cases of high-grade T-cell lymphoma fared significantly worse (P less than 0.05) than cases of high-grade B-cell subtype. These findings support the belief that T-cell lymphomas have a more aggressive clinical course than their B-cell counterparts.     

Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma.

Using immunohistochemical methods, we evaluated zeta-associated protein (ZAP)-70 expression in 341 cases of non-Hodgkin and Hodgkin lymphoma. In B-cell NHL, ZAP-70 was positive in five of six (83%) precursor B-lymphoblastic lymphoma, 11 of 37 (30%) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), five of 39 (13%) mantle cell lymphoma, one of 12 (8%) Burkitt lymphoma, and one of 12 (8%) nodal marginal zone B-cell lymphoma. In 22 cases of CLL/SLL, seven of nine (78%) with unmutated IgVH genes expressed ZAP-70, compared with one of 13 (8%) with mutated IgVH genes (P=0.0015 Fisher's exact test). ZAP-70 expression was not detected in diffuse large B-cell lymphoma (n=26), extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (n=24), follicular lymphoma (n=21), plasma cell myeloma/plasmacytoma (n=10), lymphoplasmacytic lymphoma (n=10), or splenic marginal zone lymphoma (n=6). In T/NK-cell NHL, ZAP-70 was positive in all extranodal natural killer (NK) / T-cell lymphoma, nasal-type (n=6) and enteropathy-type T-cell lymphoma (n=4), four of five (80%) subcutaneous panniculitis-like T-cell lymphoma, six of eight (75%) mycosis fungoides, three of five (60%) precursor T-lymphoblastic lymphoma, 10 of 17 (59%) peripheral T-cell lymphoma, two of four (50%) blastic NK-cell lymphoma, one of three (33%) T-cell prolymphocytic leukemia, 13 of 52 (25%) anaplastic large cell lymphoma, and one of six (17%) angioimmunoblastic T-cell lymphoma. Seven of 12 (58%) cutaneous CD30-positive lymphoproliferative disorders were also ZAP-70-positive. In Hodgkin lymphoma, ZAP-70 was negative in neoplastic cells in all cases tested. ZAP-70 staining in B-cell lymphomas and reactive T cells was predominantly nuclear with variable cytoplasmic staining. By contrast, ZAP-70 staining in T/NK-cell lymphomas was heterogeneous, and a shift from predominantly nuclear to predominantly cytoplasmic staining was observed, particularly in those neoplasms with high-grade morphology. In summary, ZAP-70 is expressed by many lymphoma types, correlates with immunoglobulin heavy-chain variable region gene mutational status in CLL/SLL, and can be detected reliably using immunohistochemical methods.     

A survey of Epstein-Barr virus gene expression in sporadic non-Hodgkin''s lymphomas. Detection of Epstein-Barr virus in a subset of peripheral T-cell lymphomas.

This study analyzes the association of Epstein-Barr virus (EBV) with non-Hodgkin's lymphoma (NHL) arising in patients without pre-existing overt immunodeficiency. The authors examined 201 lymphomas (105 high-grade B-cell, 82 peripheral T-cell, 7 high-grade non-B-cell, non-T-cell, and 7 hairy-cell leukemia) for EBV gene expression by immunohistologic procedures using monoclonal antibodies to EBV latent, immediate early, and replicative infection antigens. Transformation-associated EBV latent membrane protein 1 (LMP 1) was detected in 13 (6%) NHL, comprising 4 (4%) high-grade B-cell, 8 (10%) peripheral T-cell, and 1 non-B-cell, non-T-cell lymphomas. Anaplastic large-cell lymphoma of T-cell type was consistently LMP 1-negative. EBV nuclear antigen 2 was demonstrated in only three (1%) cases. Induction of replication as defined by expression of the immediate early BamHI Z leftward reading frame 1 (BZLF1) protein was detected in five cases, but early (EA) and late (VCA and MA) lytic cycle antigens were only found in two cases and in one case, respectively. The presence of EBV was confirmed by in situ DNA hybridization in 9 of 11 EBV antigen-positive lymphomas. This study shows the surprisingly frequent presence of EBV in peripheral T-cell NHL in European patients without pre-existing overt immunodeficiency. Interestingly, most sporadic B-cell NHL are not associated with the virus. Furthermore, the usefulness of selected monoclonal antibodies for the routine immunohistological diagnosis of EBV infection was confirmed.