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.     

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.     

Monoclonal antibody HML-1 reactivity with adult T-cell leukaemia/lymphoma and other lymphomas

Human T-cell leukaemia/lymphoma virus type 1 (HTLV-1), a causative virus of adult T-cell leukaemia/lymphoma (ATLL), is known to be transmitted by breast-feeding. Using a monoclonal antibody HML-1 which labels human intestinal intra-epithelial T lymphocytes, we have immunohistochemically examined ATLL tissues in order to evaluate the possibility that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Previously this antibody was reported to react with intestinal T-cell malignant lymphomas but not with peripheral tumours, or any B-cell lymphomas. We investigated 181 patients with malignant lymphomas and found that 19 out of 113 ATLLs were positive for HML-1. T-cell malignant lymphomas excluding ATLL also reacted with HML-1 (7/24), but all the B-cell lymphomas 0/33) and non-neoplastic lymph node and skin lesions (0/10) were negative for HML-1. In patients with ATLL and other T-cell malignant lymphomas, the positivity level of HML-1 was relatively higher in stomach (3/7) and tonsil (2/6) than that in lymph nodes (15/100) and skin (8/47). We observed one HML-1 positive ATLL patient with tumour formation in the skin and lymphadenopathy and marked infiltration of the large intestine but minimal involvement of other organs. Although HML-1 was frequently expressed in gastric infiltration of ATLL, the level of positivity was too low in lymph nodes to support the hypothesis that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Some of the HML-1 positive ATLL cases co-expressed CD30. Furthermore, three of six cases of Ki-1 lymphoma (large anaplastic cell lymphoma) were positive for HML-1. We conclude that expression of HML-1 in ATLL reflects an activated state of the lymphoma cells, but not the intestinal origin of ATLL cells.     

Sinusoidal CD30-positive large B-cell lymphoma: a morphologic mimic of anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) has been recognized recently as a distinct clinicopathologic entity, restricted to a subset of CD30-positive diffuse large cell lymphomas of T/null lineage. Some of the characteristic features of ALCL, such as CD30 antigen expression and the presence of large pleomorphic lymphoid cells infiltrating lymph node sinuses, can be found rarely in diffuse large B-cell lymphomas. We collected 11 such cases, and their clinical, morphologic, and immunophenotypic features are reviewed. The age of the patients ranged from 36 to 82 years (mean, 63.2 years) with a male to female ratio of 1:1.2. All neoplasms were nodal with a sinusoidal infiltrative pattern, although four neoplasms also had foci of confluent growth. Eight tumors were composed predominantly of large pleomorphic cells with occasional Reed-Sternberg-like cells. The other three tumors had a higher proportion of large monomorphic lymphoid cells. Necrosis and admixed granulocytes were other common features. Immunophenotypically, all cases were positive for CD30 and CD20 or CD79a. All eight cases examined for anaplastic lymphoma kinase-1 immunoreactivity were negative. In situ hybridization for Epstein-Barr virus RNA was performed in eight cases; two were positive. Excluding one consultation case with no available clinical follow-up data, six patients died of the disease within 3 years and one had disease relapse within 1 year. We conclude that an unusual variant of diffuse large B-cell lymphoma can closely mimic ALCL. However, these neoplasms can be distinguished from ALCL by virtue of their B-lineage and lack of anaplastic lymphoma kinase-1 expression. Evidence of Epstein-Barr virus infection can be found in a small subset of these neoplasms.     

Primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma of the brain in a patient with acquired immunodeficiency syndrome

Anaplastic large cell lymphoma is a unique diagnostic subcategory of the T-cell lymphomas in the current World Health Organization classification. Representing approximately 3% of adult and 10% to 30% of childhood non-Hodgkin lymphomas, anaplastic large cell lymphoma classically consists of CD30+ large lymphoid cells with abundant cytoplasm and pleomorphic, often horseshoe-shaped or kidney-shaped nuclei. Among the reported nodal and extranodal sites of occurrence, the gastrointestinal tract and central nervous system have rarely been noted. We report a case of primary anaplastic lymphoma kinase-negative anaplastic large cell lymphoma in the brain of a 46-year-old patient with acquired immunodeficiency syndrome. T-cell lineage was confirmed by T-cell receptor gamma chain gene rearrangements using polymerase chain reaction, and extra copies of the anaplastic lymphoma kinase gene of chromosome 2 were demonstrated by fluorescence in situ hybridization analysis. To our knowledge, primary anaplastic large cell lymphoma of the brain has not previously been reported in acquired immunodeficiency syndrome.     

Primary CD30-positive cutaneous T-cell lymphomas and lymphomatoid papulosis frequently express cytotoxic proteins

AIMS: To analyse the relationship between expression of cytotoxic proteins, histopathology and the CD30 status in primary cutaneous T-cell disorders, we investigated the expression of TIA-1, granzyme B and perforin in CD30 negative and CD30 positive cutaneous T-cell lymphomas (CTCL) and lymphomatoid papulosis (LP). METHODS AND RESULTS: We studied 26 cases of CTCL and 12 cases of LP for the expression of TIA-1, granzyme B and perforin which are granule-associated proteins of cytotoxic lymphocytes involved in the mechanism of apoptosis. We showed that most cases (10/13) of CD30 negative pleomorphic lymphomas expressed cytotoxic proteins only in scattered, apparently reactive lymphocytes, the exception being one CD8+ CTCL and two gammadelta subcutaneous 'panniculitis-like' T-cell lymphomas. We also showed that at least one cytotoxic protein was expressed in a proportion of neoplastic cells in 77% (10/13) of CD30+ T-cell lymphomas (3/4 pleomorphic and 7/9 anaplastic) and in a proportion of atypical cells in 75% (9/12) of LP. CONCLUSIONS: Our findings show a strong correlation between the CD30 phenotype and the expression of cytotoxic proteins in primary CTCL. In addition, these results provide further evidence for an overlap between lymphomatoid papulosis and cutaneous CD30+ pleomorphic and anaplastic lymphomas. These entities, which belong to the spectrum of CD30 positive cutaneous T-cell lymphoproliferations, appear to be derived from cytotoxic cells.     

Peripheral T-cell lymphoma in childhood. A clinicopathological study of six cases

A review of the pathological material from 42 children with non-Hodgkin's lymphoma seen over a 44 month period revealed 10 large cell tumours. Of these, six were classified as peripheral T-cell lymphoma, an entity rarely reported in childhood. Three patients were boys and three girls (median age 9.5 years), and extranodal presentation was a feature of two patients. Five had high-grade tumours; of these, three were classified as large cell anaplastic, Ki-1 positive and two as pleomorphic large cell. The remaining patient had a low-grade tumour of angioimmunoblastic type. T-cell subsets were examined in three cases and showed the following phenotypes: CD4-, CD8-; CD4+, CD8-; CD4-, CD8+. Three of the patients with high-grade tumours died, with a mean survival of 22 weeks. The remaining patients are alive and clinically disease-free for between 10 and 24 months after treatment.     

Immunoreactivity of B-cell markers (CD79a, L26) in rare cases of extranodal cytotoxic peripheral T- (NK/T-) cell lymphomas.

The monoclonal antibodies L26 (CD20) and CD79a are very useful reagents for the immunohistochemical assessment of B-cell lineage in lymphoproliferative disorders. Although very few CD20-positive peripheral T-cell lymphomas (PTL) have been reported, comprehensive analyses of CD79a reactivity in extranodal PTL and NK/T-cell lymphomas have not been performed previously. This study investigated CD79a (clone JCB117) and CD20 reactivity in 94 extranodal non-B-cell lymphomas (enteropathy-type intestinal T-cell lymphoma [n = 52], nasal NK/T-cell lymphoma [n = 11], and primary cutaneous PTL [n = 31]) and in 17 cases of nodal PTL, unspecified. In four cases (enteropathy-type intestinal T-cell lymphoma [n = 3] and nasal NK/T-cell lymphoma [n = 1]), the majority of tumor cells stained for CD79a (all CD20 negative) and one cutaneous PTL, unspecified, was CD20 positive (CD79a negative). Extensive immunophenotyping and polymerase chain reaction-based molecular analyses revealed that all five B-cell marker-positive extranodal lymphomas had a cytotoxic phenotype and did indeed represent monoclonal peripheral T-cell proliferations. To minimize the risk of misinterpretation of lymphoma cell lineage, especially in cases of extranodal, lymphoproliferative disease, we suggest the use of both CD79a and CD20 in combination with a panel of antibodies reactive to T cells, such as betaF1 and CD5, and to T cells and NK cells, such as CD3, CD2, CD56, and TIA-1.     

肠道T细胞淋巴瘤中的EB病毒感染和T细胞内抗原1的表达

目的 探讨ＥＢ病毒感染在肠道Ｔ细胞淋巴瘤发病中的意义。方法 用ＥＢＥＲ１／２原位杂交及三步ＡＢＣ法免疫组织化学染色技术,观察２４例肠道Ｔ淋巴瘤患者中ＥＢ病毒感染及Ｑ细胞内抗原（ＴＩＡ－１）抗原表达情况,选用的抗体有ＴＬＡ－１,ＬＭＰ－１,ＣＤ３,ＣＤ２０,ＣＤ３０和ＣＤ４５ＲＯ等。     

High frequency of Epstein–Barr virus in Chinese peripheral T-cell lymphoma

Forty-two cases of Chinese T-cell lymphoma were studied for expression of Epstein–Barr virus (EBV) encoded RNA (EBER-1) and EBV latent membrane protein-1 (LMP-1) using in situ hybridization and immunohistochemistry, respectively. EBV was detected in tumour cells in 24/39 peripheral T-cell lymphomas (62%), comprising 18/27 pleomorphic, medium and large cell lymphomas (67%), 4/6 angioimmunoblastic lymphadenopathy-like lymphomas (67%), 2/2 Lennert's lymphomas, 0/2 anaplastic large cell lymphomas, and 0/2 T-zone lymphomas. EBV was not found in three T-lymphoblastic lymphomas. EBV was associated with 12/24 nodal (50%) compared with 12/15 extranodal (80%) peripheral T-cell lymphomas. In EBV positive nodal lymphomas, 9/12 cases (75%) contained less than 10% EBER positive tumour cells. In EBV positive extranodal lymphomas, 9/11 cases (82%) showed EBV gene expression in more than 50% of the tumour cells, and in five of these almost all tumour cells were positive. Lymphomas of the nasopharynx (mainly midline granuloma-type) showed EBER-1 expression in nearly all tumour cells. LMP-1 was detected in 19/23 EBER positive peripheral T-cell lymphomas (83%). Our results show that EBV is strongly associated with peripheral T-cell lymphomas in Chinese. An important role for the virus is suggested in lymphomas of the nasopharynx. The significance of EBV in T-cell lymphomas that contain only a minor population of virally infected tumour cells is currently unclear.     

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.     

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.     

Leukaemic phase of mantle zone (intermediate) lymphoma: its characterisation in 11 cases

Sixteen patients presented with B cell leukaemia (white cell count 26-269 x 10(9)/l) which could not be classified as chronic lymphocytic (CLL), prolymphocytic leukaemia, or follicular lymphoma in leukaemic phase. Eleven patients (10 men, one woman) corresponded histologically to intermediate (INT) or mantle zone lymphoma, and five, with less well defined features, were designated small lymphocytic lymphoma with cleaved cells. The blood films showed a pleomorphic picture with lymphoid cells of predominantly medium size with nuclear irregularities and clefts. The membrane phenotype of the circulating cells showed strong immunoglobulin staining and reactivity with CD5 and FMC7 in all cases tested; CD10 was positive in six out of nine cases. The membrane phenotype of two of the five cases of small lymphocytic lymphoma was close to those of B-CLL and three resembled INT lymphoma. Bone marrow trephine biopsy specimens showed a diffuse pattern of infiltration in INT lymphoma. The median survival of these patients was less than two years, suggesting that a leukaemic presentation is associated with poor prognosis. By combining data from histology, membrane markers, and peripheral blood morphology, the leukaemic phase of typical INT lymphoma can be defined in most cases.     

Lymphoma of the breast. A clinicopathologic study of primary and secondary cases

BACKGROUND: Primary lymphomas of the breast are rare, accounting for 1.7% to 2.2% of extranodal lymphomas and 0.38% to 0.7% of all non-Hodgkin lymphomas. Although secondary breast lymphomas are also rare, they represent the largest group of metastatic tumors of the breast. OBJECTIVES: To investigate the clinicopathologic and immunophenotypic characteristics of breast lymphomas, the relative frequency of primary and secondary mammary lymphomas, and in selected cases, the role of gene rearrangement analysis in diagnosis and staging of these lymphomas. RESULTS: We conducted a retrospective review of 22 cases of breast lymphoma diagnosed at William Beaumont Hospital, Royal Oak, Mich, during a 30-year period (1963-1994). Eleven of the 22 cases fulfilled the criteria for primary breast lymphoma; these cases represented 0.6% of all non-Hodgkin lymphomas seen in our hospital. Of the 11 cases, 5 were diffuse large B-cell lymphomas, 2 were follicle center lymphomas, 2 were marginal zone B-cell lymphomas (mucosa-associated lymphoid tissue type), 1 was a lymphoplasmacytoid lymphoma, and 1 was a peripheral B-cell neoplasm, unclassified. Using a panel of immunohistochemical stains (CD45RO, CD45RA, CD43, CD3, CD20, CD30, CD68, and HLA-DR), 8 cases demonstrated unequivocal B-cell phenotype and 3 cases had equivocal or weak staining patterns for B-cell markers. We identified no cases of T-cell lymphoma. Of 7 cases that had bone marrow biopsies for staging, 3 were positive morphologically for bone marrow involvement. Molecular analysis of B- and T-cell gene rearrangement was used to exclude bone marrow involvement in one case with bone marrow lymphoid aggregates and to confirm negativity in a case that was morphologically negative. Of the 11 secondary breast lymphomas, 5 were diffuse large B-cell lymphomas; 1 was diffuse large B-cell, primary mediastinal subtype; and 5 were follicle center lymphomas. CONCLUSIONS: Breast lymphomas represented 1.2% of all non-Hodgkin lymphomas in this study; the frequency of primary and secondary cases was equal. In both groups, right breast lesions were predominant, and the most frequent morphologic type was diffuse large B-cell lymphoma. Gene rearrangement analysis is helpful in selected cases to rule out bone marrow involvement, especially in older patients, in whom lymphoid aggregates are common.     

Venular endothelium binding molecules CD44 and LECAM-1 in normal and malignant B-cell populations. A comparative study

Summary Lymphocytes leave the blood via post-capillary venules by binding initially to their specialized endothelium. CD44 is a 80–90 kDa hyaluronate-binding glycoprotein involved in binding to endothelium of high endothelial venules (HEV). LECAM-1 is a 75–85 kDa glycoprotein with lectin activity interacting with human peripheral lymph node vascular addressin (PNAd) on HEV. This immunohistochemical study shows that CD44 and LECAM-1 are essentially coordinately expressed on B-lymphocytes. The mode and level of CD44/ LECAM-1 expression dissect the peripheral B-cell development into stages that are closely linked to morphologically defined B-cell compartments. Although statistically correlated in B-cell leukaemias (p<0.0009) and extranodal B-cell lymphomas (p<0.003), expression of both molecules was less stringently coordinated in 127 B-cell neoplasms examined. B-cell chronic lymphocytic leukaemia, hairy cell leukaemia and mantle zone lymphoma were CD44/LECAM-1 positive, thus corresponding to their reactive counterparts. Correspondingly, follicular centre cell-derived lymphomas were devoid of both markers. Conversely, CD44 and LEC-AM-1 were infrequently detectable in extranodal malignant B-cell neoplasms, irrespective of their maturational state. Presence versus absence of CD44 and LECAM-1, alone or together, determined neither the leukaemic versus aleukaemic state nor the nodal versus extranodal tumour-forming phenotype of a B-cell tumour.     

Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T-cell lymphomas

Degradation of the extracellular matrix by matrix metalloproteinases (MMPs) is a crucial step in tumour invasion and metastasis. In human carcinomas, tumour cell-fibroblast interactions (TFIs) have been demonstrated to play a role in the up-regulation of MMP levels in tumours, and emmprin is a surface molecule on tumour cells that stimulates nearby fibroblasts to produce MMP-1, 2, and 3. T-cell lymphomas frequently show extranodal organ involvement and skin invasion, but a role for TFIs in their invasion has not been examined in detail. This study investigated TFIs in T-cell lymphomas with special reference to emmprin expression and MMP production. Immunohistochemically, only germinal centre cells and some histiocytes expressed emmprin in non-neoplastic lymph nodes (ten cases), while all T-cell lymphomas [14 cases of adult T-cell leukaemia/lymphoma (ATLL), six cases of lymphoblastic lymphoma, seven cases of anaplastic large cell lymphoma, and nine cases of angio-immunoblastic T-cell lymphoma] expressed emmprin strongly and diffusely. FACS analysis of peripheral blood from normal individuals revealed that small fractions of B-cells, T-cells, and monocytes expressed emmprin, whereas emmprin-expressing T-cells were much increased in number, and expressed this protein to a higher level, in ATLL patients. In vitro co-cultures of emmprin-positive HTLV-1-transformed lymphocytes (MT-2) and emmprin-negative human fibroblasts enhanced the production of pro-MMP-2 (gelatinase A) and active MMP-2, compared with cultures of either cell type alone. This stimulation was inhibited by an activity-blocking peptide against emmprin. Moreover, in histopathological sections from patients with ATL skin involvement, MMP-2 was demonstrated in fibroblasts around infiltrating ATL cells, but not in fibroblasts in non-diseased areas. In conclusion, emmprin is overexpressed by T-lymphoma cells, when compared with normal counterparts, and facilitates MMP-2 production via interactions with fibroblasts, which could play a role in stromal invasion by lymphoma cells.     

CD5-positive diffuse large B cell lymphoma arising from a CD5-positive follicular lymphoma

Follicular lymphoma (FL) is a neoplasm originating from germinal centre cells, corresponding to 25-40% of non-Hodgkin's lymphomas. Transformation into diffuse large B cell lymphoma (DLBCL) occurs in about one-third of cases. CD5 is expressed in B-chronic lymphoid leukaemia/small lymphocytic lymphoma and mantle cell lymphoma, but can rarely be expressed in conjunction with CD10 in well-documented cases of FL. In this report one case of grade 1 FL is described, which transformed into a DLBCL 6 months after initial diagnosis, with both tumours expressing CD5. In both specimens, neoplastic cells were strongly positive for CD20, CD79a, bcl-2, bcl-6 and CD5 in virtually all cells. CD10 was strongly positive in initial specimens and weakly positive in the DLBCL. Investigation using the PCR confirmed the derivation of the DLBCL from the FL as they presented the same immunoglobulin heavy chain gene rearrangement and the same BCL2-J(H) break point.     

Usefulness of flow cytometry for differential diagnosis of precursor and peripheral T-cell and NK-cell lymphomas: analysis of 490 cases

Although various CD markers have been analyzed in T-cell and natural killer (NK)-cell lymphomas, the sensitivity and specificity of these phenotypic features have not been satisfactorily characterized. Flow cytometry (FCM) was used to determine the phenotypic pattern of 490 T/NK-cell lymphomas with the aid of a set of surface antigens (CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11c, CD16, CD19, CD20, CD25, CD30, CD34, and CD56). In data obtained from 319 patients, CD10 expression was detected in 57% of angioimmunoblastic T-cell lymphomas, CD30 in 93% of anaplastic large cell lymphomas, CD34 in 50% of lymphoblastic lymphomas, and CD56 in 100% of extranodal NK/T-cell lymphomas nasal type. A total of 92% of adult T-cell leukemia/lymphomas (ATLL) had expression of CD25 and downregulation of CD7. Of special interest is that 92 ATLL (50%) were CD4⁺CD7^-CD25⁺ phenotype while only four peripheral T-cell lymphoma unspecified (9%) and one (9%) cutaneous T-cell lymphoma had this phenotype. Phenotypic analysis using FCM was thus found to be useful for differential diagnosis of T-cell and NK-cell lymphomas.     

Heterogeneity of CD3 antigen expression in T-cell lymphoma

CD 3 antigen expression was studied in a series of 98 T-cell lymphomas, using polyclonal antibodies which recognize this molecule in routinely processed, paraffin-embedded, tissue. We identified 40 cases in which CD3 was present on only a proportion of the neoplastic cells. This phenomenon of heterogeneous CD3 expression was commonest in pleomorphic T-cell lymphomas (22/42 cases) and in CD30 (Ki-1)-positive lymphomas (5/11 cases), and was less frequently observed in mycosis fungoides (4/18 cases) and not seen in T-cell lymphoblastic lymphoma (0/9 cases). CD3 expression was often related to cell morphology, with CD3 antigen being present on the smaller neoplastic cells but absent from the larger ones. The diagnostic significance of these observations is that, on occasion, it may be possible to diagnose a lymphoma as being of T-cell origin in paraffin sections by demonstrating a minor subpopulation of CD3-positive neoplastic cells.