Search

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral (mature) T-cell lymphoma (PTCL) caused by human T-cell leukaemia virus type 1 (HTLV-I). HTLV-I is prevalent in Japan, the Caribbean, Romania, and certain regions of Africa and Latin America. Taiwan is a country non-endemic for HTLV-I infection, with a low seroprevalence rate at 0.058-1.72%. ATLL shows diverse clinical manifestations and histology with several clinical variants including acute, lymphomatous, chronic, and smoldering.

Aims Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon complication associated largely with textured implants. It is important that the symptoms associated with BIA-ALCL are recognised and that robust pathways are in place to establish the diagnosis. The aim of this paper is to review what is known of the incidence of the disease, current thoughts on pathogenesis, patterns of presentation and pathological features to provide standard guidelines for its diagnosis. Methods and results Systematic review of the literature via PubMed covering cases series, modes of presentation, cytological, histological and immunohistochemical features and disease outcome. Since 1997, 518 cases throughout 25 countries have been registered on the American Society of Plastic Surgeons PROFILE registry, with an estimated risk for women with an implant of one to three per million per year. It most frequently presents as a late-onset accumulation of seroma fluid, sometimes as a mass lesion. The neoplastic cells are highly atypical, consistently strongly positive for CD30, with 43-90% also positive for EMA, and all are ALK-negative. Behaviour is best predicted using a staging system for solid tumours. Conclusion BIA-ALCL is a rare but important complication of breast implants. While characterised by CD30-positive neoplastic cells this must be interpreted with care, and we provide pathological guidelines for the robust diagnosis of this lesion as well as the most appropriate staging system and management strategies. Finally, in order to generate more accurate data on incidence, we recommend mechanisms for the routine central reporting of all cases.

Aims The aims of this study were to review our 5-year experience with clinical FISH testing for TP63 rearrangements using both TP63 break-apart (BAP) and TBL1XR1/TP63 dual-fusion (D-FISH) probes to evaluate the frequency of TP63 rearrangements and the distribution of TBL1XR1 vs. alternate partner loci, and to assess whether both probe sets are necessary in all cases undergoing FISH testing. Methods and results A retrospective review of the Mayo Clinic cytogenetic database identified 470 patients evaluated by FISH testing for TP63 rearrangements in formalin-fixed paraffin-embedded (FFPE) tissue using both BAP and D-FISH probes. Of these, 25 (5.3%) had TP63 rearrangements. All samples were being investigated for anaplastic large-cell lymphoma or other T cell lymphoma subtypes. A TBL1XR1 partner was identified by D-FISH in 12 (48%) of 25 cases. All cases positive by TBL1XR1/TP63 D-FISH were also positive by TP63 BAP FISH. Conclusion This is the largest series of TP63 rearrangements to date. The frequency of positive results among cases referred to a large reference laboratory for TP63 FISH testing was 5.3%. Approximately half of TP63 rearrangements have a TBL1XR1 partner. TP63 BAP FISH testing is sufficient for up-front testing of FFPE tissue samples. However, because of the genomic proximity of the TP63 and TBL1XR1 loci, we recommend reflex TBL1XR1/TP63 D-FISH testing in positive and equivocal cases.

AIMS The programmed death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumour cells escape from immune control. PD-L1 immunohistochemistry is a useful predictor of immunotherapy response, but is still not used widely in the diagnostic setting. Here we describe results using PD-L1 immunohistochemistry during routine diagnostics in lymphoma. METHODS AND RESULTS Ninety-one lymphoproliferative disease cases sharing tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells with and without Epstein-Barr virus (EBV) association were investigated by immunohistochemistry for PD-L1 (clone SP142). PD-L1 expression was present in more than 5% of tumour or non-malignant HRS-like cells in 100% of EBV+ classical (C) Hodgkin lymphoma (HL) (n = 10) and EBV-negative nodular sclerosis CHL (n = 8); 40% of EBV+ diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS) (n = 20); and 4% of nodal peripheral T cell lymphoma of follicular helper T cell type (PTCL-TFH) (n = 22). In contrast, nodular lymphocyte-predominant HL (n = 4), lymphocyte-rich CHL (n = 6), EBV+ hyperplasia (n = 8), plasmablastic lymphoma (n = 3) and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (n = 5) seldom exhibited PD-L1 in their large cells. Assessing PD-L1 positivity in tumour and non-malignant large cells was helpful in differentiating between CHL versus nodal PTCL-TFH (P

Aims The immunohistopathological features of lesions involving the bone marrow (BM) were examined in patients with anaplastic large-cell lymphoma (ALCL) to identify the most useful markers for the detection of BM involvement in ALCL. Methods and results A total of 80 patients with ALCL were enrolled, of whom 15 (18.8%) showed BM involvement. Anaplastic lymphoma kinase-negative (ALK–) patients (n = 11) showed a nodular BM involvement pattern more frequently than ALK+ patients (n = 4; 72.7% versus 25.0%, P = 0.095). Patients with interstitial BM involvement were more frequently ALK+ than those with nodular BM involvement (50.0% versus 11.1%, P = 0.095). CD30 positivity was the strongest indicator of the presence of BM lesions, regardless of the BM involvement pattern. The application of CD30 in cases without morphological evidence of BM involvement detected subtle BM involvement by ALCL in 13.7% of cases, which were predominantly ALK+. Conclusions The immunohistopathological features of BM lesions in patients with ALCL differ according to ALK status and BM involvement pattern. CD30 is the most useful marker for the identification of BM lesions in ALCL patients and should be employed in all ALCL patients without exception, especially ALK+ cases.

McKelvie P A, Thompson P A & Tam C S (2012) Histopathology 61, 212–233 Peripheral T cell and natural killer (NK) T cell lymphomas: a clinicopathological study from a single Australian centre Aims: Using pathological and clinical review, to identify all cases diagnosed as peripheral T cell and natural killer (NK) T cell lymphoma over 10 years from one metropolitan Australian hospital. Methods and results: Subtyping was performed using World Health Organization (WHO) 2008 criteria and a comprehensive immunohistochemical panel. Clinical data including follow-up were obtained. There were 47 cases, including 11 peripheral T cell lymphomas, not otherwise specified (NOS), nine extranodal NK T cell lymphomas, nasal type (eight nasal), eight primary cutaneous anaplastic large cell lymphomas, seven angioimmunoblastic T cell lymphomas, three anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphomas, four ALK-negative anaplastic large cell lymphomas, three enteropathic T cell lymphomas and two subcutaneous panniculitis-like T cell lymphomas. Follow-up of 46 of 47 cases (median time 45 months) revealed that 50% (23 of 46) of patients died. Five-year survival rates were: peripheral T cell lymphoma, NOS 39%; angioimmunoblastic T cell, 43%; nasal NK T 67%; ALK-negative anaplastic large cell lymphoma 67% (at 2 years); ALK+ anaplastic large cell lymphoma 33%; subcutaneous panniculitis-like T cell lymphomas 100%; primary cutaneous anaplastic large cell lymphoma 86%; and enteropathic T cell lymphoma 33% (at 1 year). One patient with Lennert lymphoma suffered four late cutaneous relapses. Conclusions: This first Australian clinicopathological series of peripheral T cell and NK T cell lymphoma shows epidemiological and survival data similar to those for Europe and North America.

Aims: Aberrant histone acetylation has been associatedwith malignancy and histone deacetylase (HDAC) inhib-itorsare currentlybeing investigatedinnumerousclinicaltrials. So far, the malignancy most sensitive to HDACinhibitors has been cutaneous T-cell lymphoma (CTCL).The reason for this sensitivity is unclear and studies onHDAC expression and histone acetylation in CTCL arelacking. The aim of this study was to address this issue.Methods and results: The immunohistochemical expres-sion of HDAC1, HDAC2, HDAC6, and acetylated H4 wasexamined in 73 CTCLs and the results related to histo-logical subtypes and overall survival. HDAC1 was mostabundantly expressed (P < 0.0001), followed by HDAC2;HDAC6 and H4 acetylation were equally expressed.HDAC2 (P = 0.001) and H4 acetylation (P = 0.03)were significantly more common in aggressive thanindolent CTCL subtypes. In contrast, no differences wereobserved for HDAC1 and HDAC6. In a Cox analysis,elevated HDAC6 was the only parameter showingsignificant influence on survival (P = 0.04).Conclusions: High expression of HDAC2 and acetylatedH4 is more common in aggressive than indolent CTCL.HDAC6 expression is associated with a favorableoutcome independent of the subtype.Keywords: acetylation, cutaneous T-cell lymphoma, histone deacetylases, histone H4, immunohistochemistry, survivalAbbreviations: ALCL, anaplastic large cell lymphoma; BSA, bovine serum albumin; CR, complete response;CTCL, cutaneous T-cell lymphoma; HAT, histone acetyltransferase; HDAC, histone deacetylase; HR, hazard ratio;MF, mycosis fungoides; NOS, not otherwise specified; PR, partial response; PTL, peripheral T-cell lymphoma;SS, Se´zary syndrome; TBS, Tris-buffered saline

Aims: The Revised European American Lymphoma classification uses the term Hodgkin's-like anaplastic large cell lymphoma (HD-like ALCL) for borderline cases with features of both anaplastic large cell lymphoma (ALCL) and classical Hodgkin's lymphoma (HL). The aim of this study was to clarify the association between cytotoxic molecule (CM) expression and clinical outcome in HD-like ALCL. Methods and results: Subjects were 59 patients with HD-like ALCL, defined by nodal presentation without mediastinal bulky lesions, T- or null-cell phenotype, CD30+ anaplastic lymphoma kinase (ALK)– phenotype and by confluent sheets or nodules of large cells mimicking classic Hodgkin and Reed–Sternberg cells. We evaluated the presenting features and prognosis of subjects on categorization into two defined groups, namely CM (TIA1 and/or granzyme B)-positive (n = 21) and CM-negative (n = 38). The series consisted of 18 women and 41 men ranging from 16 to 88 years of age (median 59 years). The CM+ group had poorer disease-specific survival than the CM– group (P = 0.02) despite the absence of differences in other clinical characteristics. Multivariate analysis confirmed that CM expression was an independent prognostic factor, in contrast to phenotypic categorization (T-cell vs. null-cell group), which had no prognostic impact on disease-specific survival. Conclusion: CM expression is predictive of prognosis in HD-like ALCL.

AIMS Protein kinase C (PKC) beta is an important regulator of lymphoid survival and its expression has been shown to be altered in lymphomas. The aim was to determine the expression of PKC beta(2) in various subtypes of lymphoproliferative diseases by immunohistochemistry. METHODS AND RESULTS One hundred and forty archival samples representing various subtypes of lymphoproliferative diseases were analysed. Certain subtypes, such as mantle cell, lymphocytic or follicular lymphoma, were found to express PKC beta(2) in > 90% of the samples. In follicular lymphomas, the follicular lymphomatous areas were constantly labelled, whereas residual germinal centres remained negative. In follicular hyperplasia, PKC beta(2)+ cells were found in the mantle and marginal zones. Most angioimmunoblastic T-cell lymphomas, lymphoblastic T-cell lymphomas and marginal zone/mucosa-associated lymphoid tissue (MALT) lymphomas were labelled with anti-PKC betaII antibody, but the pattern of expression was more heterogeneous in these subtypes. A minority of diffuse large B-cell lymphomas were stained and most plasma cell malignancies were negative. None of the cases of Hodgkin's disease and anaplastic large cell lymphoma expressed PKC beta(2). CONCLUSIONS PKC beta(2) expression varies significantly among lymphoproliferative diseases. In our series, the highest level of expression was found in mantle cell lymphomas and chronic lymphocytic lymphoma.

Distinguishing angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified, using morphology, immunophenotype and molecular genetics Aims: To identify distinguishing histological, immunophenotypic and molecular genetic features between angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma (PTL). Methods: Nodal T-cell lymphomas examined (n =137), included AITL (n = 89), PTL (n = 22), anaplastic large cell lymphoma (n = 16) and 'AITL/PTL indeterminate' (n = 10) with overlapping features between AITL and PTL, showing morphology typical of AITL but lacking follicular dendritic cell expansion. Immunohistochemistry for CD3, CD20, CD21 and CD10, in situ hybridization for Epstein-Barr virus encoded RNA (EBER) and polymerase chain reaction for T-cell and B-cell clonality analysis were performed. Results: Of the AITLs, 74/89 showed typical morphology, whereas 15/89 showed hyperplastic follicles. AITL and 'AITL/PTL indeterminate' showed a polymorphous infiltrate and prominent vascularity in all cases. In both groups, CD10 was present in the majority and clear cells and EBER positivity were specific (but not universal) features lacking in PTL. Detection of T-cell clonality was significantly higher in AITL (90%) compared with PTLu (59%). Conclusions: Clear cells and EBV infection (when present) are useful distinguishing features and CD10 a sensitive and specific marker of AITL. Hyperplastic follicles are present in a significant minority of AITL. AITL/PTL indeterminate probably falls within the spectrum of AITL rather than PTL.

CD30-positive primary cutaneous lymphoproliferative disorders include several entities with differing clinical presentation but overlapping histological features, including lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma (C-ALCL). DUSP22-IRF4 locus translocation is present in 20-57% of C-ALCLs, and has also been described in a series of 11 lymphomatoid papulosis patients, where it was associated with a particular biphasic histological pattern, including pagetoid reticulosis-type epidermal infiltration. We aimed to study whether the presence of this translocation may define distinctive histological features in C-ALCL.We collected three cases of C-ALCL with histological features similar to those described in the new variant of lymphomatoid papulosis with 6p25.3 rearrangement. We studied their histological features and immunophenotype, using a panel of antibodies against CD30, TCR-βF1, TCR-γ, CD4, CD8, CD20, Ki-67 and ALK. FISH analyses were performed using an IRF4-DUSP22 break-apart probe for the study of the 6p25.3 rearrangement. FISH results were positive in the three cases, which all showed distinctive histological and immunohistochemical features: a diffuse dermal infiltrate of atypical medium-to-large cells, and marked epidermotrophism with small, atypical intra-epidermal lymphocytes.Our findings suggest that the presence of 6p25.3 rearrangement might be related to this particular biphasic pattern.

45% 5-year survival). In multivariate analysis of overall survival time, performed in the combined group of ALK-negative nodal mature T-cell lymphomas, only age and the International Prognostic Index (IPI) remained independent prognostic parameters, while lymphoma subtype (ALCL versus PTCL-NOS versus AILT) gave no additional information. CONCLUSIONS: The distinction between ALK-negative ALCL and PTCL-NOS or AILT is of limited clinical relevance as they show comparable poor prognosis. In these lymphoma subtypes, only age and the IPI are of significant prognostic value.

Aims The ALK p80 chimeric protein is thought to be up-regulated as a result of the t(2;5) as classically seen in anaplastic large cell lymphoma. However, rhabdomyosarcomas (in particular, the alveolar subtype) have also been noted to show expression of this protein. This study set out to examine ALK expression in a large number of rhabdomyosarcomas. Methods and results Eighty-three cases of rhabdomyosarcomas and 16 cases of malignant mixed mullerian tumours with a rhabdomyosarcomatous component were retrieved from the archives of the Department of Anatomical Pathology for the period 1983-2001. The sections were stained with polyclonal ALK antibody. There were 52 male and 30 female patients. In one case, the gender of the patient was not indicated. The ages ranged from 1 week to 77 years. The most common site was the head and neck region, followed by the pelvis and extremities. Thirty-one cases were of the alveolar subtype while 40 cases were embryonal. There were four mixed embryonal/alveolar, six pleomorphic and two unclassifiable rhabdomyosarcomas. Fourteen of the 31 (45%) alveolar rhabdomyosarcomas stained positively for the ALK protein, while only six of the 40 embryonal (15%) cases showed positivity. One case each of the mixed embryonal/alveolar, pleomorphic and unclassified cases was also immunopositive. The rhabdomyosarcomatous component in the malignant mixed mullerian tumours was positive in four of the 16 cases. Conclusion We conclude that a proportion of alveolar rhabdomyosarcomas (in particular) exhibit ALK protein expression. However, ALK expression is not restricted to this subtype. An extension of this study is to determine if this over-expression is as a result of the t(2;5) translocation.

Histological and immunohistochemical characterization of extranodal diffuse large-cell lymphomas with prominent spindle cell features Aims: To describe five cases of diffuse large-cell lymphoma with prominent spindle cell components involving skin, nasal-ocular mucosa, and soft tissue. Because of the spindle cell morphology, such cases must be differentiated from true sarcomas arising in or metastasizing to soft tissue, skin, bone, lymph node, or other organs and sites. Methods and results: Formalin-fixed paraffin-embedded archival tissue from five consultation cases of diffuse large-cell lymphoma with prominent spindle cell features involving the skin, nasal-ocular mucosa, and soft tissue in three male and two female patients was studied by histology and immunohistochemistry. Clinicopathological findings were also reviewed for all the patients. By morphology, initial evaluation of the cases suggested spindle cell sarcoma in two cases, inflammatory pseudotumour in one case, large-cell lymphoma in another case, and one case was considered suspicious for malignant lymphoma. Immunohistochemistry demonstrated a B-cell lineage in four of the spindle cell lesions, with a diagnosis of primary cutaneous CD30+ anaplastic large cell lymphoma made for the fifth case. Four of five cases also showed actin reactivity. Conclusions: Although extremely rare, lymphomas with prominent spindle cell morphology can be encountered in daily surgical pathology practice, and should be included in the differential diagnosis of spindle cell lesions in skin and soft tissue. The observed actin reactivity in four of the five spindle cell lymphomas may lead to a misdiagnosis of leiomyosarcoma if lymphoid markers are not included in the immunohistochemical panel.

Aims: Primary lymphoma of the thyroid gland (PTL) is a relatively rare disease. During an 18-year period, 53 cases of primary non-Hodgkin’s lymphoma involving this extranodal site were seen at our institutions. The aims of this study were to evaluate the spectrum of PTLs using current lymphoma classification concepts and immunocytochemical markers, determine whether features of MALT-type lymphoma were evident in PTL, and if there was any clinical significance of such a finding. Methods and results: The cases were retrospectively studied clinically, histologically and immunohistochemically. The tumours were classified according to the Revised European‐American Lymphoma Classification of lymphoid malignancies (REAL classification). Thirty-eight patients were females, 15 were males and mean age at diagnosis was 66.3 years (range 38‐90). Three cases were low-grade marginal zone lymphomas (low-grade MALT-type lymphomas). There were 45 diffuse large B-cell lymphomas (DLBCL) of which there were 27 DLBCL-NOS and 18 high-grade MALT-type lymphomas. Within the diffuse large B-cell lymphoma (DLBCL) category, cases were subdivided into those without (DLBCL-NOS) and those with features of ‘highgrade’ MALT-type lymphoma based on presence of a low-grade component or large cell lymphoepithelial lesions (HG MALT-type lymphoma). In addition there were three follicle centre lymphomas, one anaplastic large cell lymphoma and one peripheral T-cell lymphoma. Twenty cases were stage IE, 18 stage IIE, and four stage IV. All patients with low-grade MALT-type lymphoma are alive without disease. The 5-year survivals for DLBCL-NOS and HG MALT-type lymphoma were 75% and 25%, respectively. Univariate analysis (log rank) among the DLBCLs showed stage (P< 0.001) and subtype (Pa 0.005) were associated with survival. Stage was associated with type of DLBCL, 65% of DLBCL-NOS being stage IE compared to 20% of HG MALT-type lymphomas. Conclusions: We conclude that primary thyroid lymphomas occur most commonly in elderly women and are frequently present in clinical stage IE and IIE. Low-grade MALT-type lymphomas are relatively uncommon but appear to have a favourable prognosis. DLBCL is the most common lymphoma and features of MALT can be seen in over one-third of cases. As a group, HG MALTtype lymphomas had a worse outcome than DLBCLNOS, primarily due to higher clinical stage at diagnosis. These two subtypes of DLBCL appear to be distinct clinical and histological entities.

Aims We investigated the phenotypic and cytotoxic characteristics of different types of peripheral T-cell and NK-cell lymphomas and correlated the findings of cytotoxic phenotype with Epstein–Barr virus (EBV) association. Methods and results Eighty cases of peripheral T-cell and NK-cell lymphomas, classified according to the REAL classification, were investigated for cytotoxic phenotype (by studying T-cell intracellular antigen-1 (TIA-1) expression immunohistochemically) and EBV association (by in situ hybridization for EBV-encoded small non-polyadenylated RNAs), and the results were correlated with the specific clinicopathological types and the immunophenotype with special emphasis on CD56 expression and CD4/CD8 status. Overall, 39/80 cases (49%) expressed TIA-1. Angiocentric lymphoma (23/24 cases; 96%), aggressive NK-cell leukaemia (‘large granular lymphocyte (LGL) leukaemia’) (3/3 cases; 100%), intestinal T-cell lymphoma (5/6 cases; 83%) and anaplastic large cell lymphoma (4/6 cases; 67%) were the major subtypes showing a cytotoxic phenotype. Only four of the 27 cases (15%) of peripheral T-cell lymphoma, unspecified, were TIA-1+ , while all the seven cases of angioimmunoblastic T-cell lymphoma, six cases of mycosis fungoides and one case of adult T-cell lymphoma/leukaemia were TIA-1−. Conclusions Within the group of peripheral T-cell and NK-cell lymphomas, angiocentric lymphoma, aggressive NK-cell leukaemia (‘LGL leukaemia’), intestinal T-cell lymphoma and anaplastic large cell lymphoma are the major subtypes displaying a cytotoxic phenotype. The relationships between the cytotoxic phenotype and EBV association, CD56 expression or CD4/CD8 status are secondary to the relationship between cytotoxic phenotype and specific lymphoma subtype.

Aims: We describe the clinicopathological features of eight cases of Ki-1 positive anaplastic large cell malignant lymphoma (Ki-1 ALCL) in which there was extensive infiltration by eosinophils and/or neutrophils in the absence of necrosis. Methods and results: The patients comprised four males and four females with an age range of 24–74 years. Five cases had originally been diagnosed as Hodgkin's disease and one as true histiocytic lymphoma. In all cases, there was massive infiltration by eosinophils and/or neutrophils sometimes to such an extent that malignant cells were obscured. Immunohistochemical staining was performed using the monoclonal antibodies CD30, CD15, CD45, CD20, CD3, CD45RO, epithelial membrane antigen (EMA), CAM5.2, vimentin and CD68. In all cases, tumour cells were strongly positive for CD30 but negative for CD15. One case was positive for CD45 but none expressed B or T-cell markers. Five cases were positive for vimentin and two for EMA. Three of seven patients in whom adequate clinical details were available had stage III or IV disease at presentation and four exhibited B symptoms. Four patients had a peripheral neutrophilia and one a peripheral eosinophilia. Conclusions: The study shows that an eosinophil and/or neutrophil-rich variant of Ki-1 ALCL exists, expanding the morphological spectrum of this tumour.

FAS/APO-1 (CD95) is a membrane glycoprotein belonging to the tumour necrosis factor/nerve growth factor receptor family, and which can trigger apoptosis in some lymphoid cell lines. Immunohistochemistry combined with Northern blotting allowed determination of the pattern of FAS/APO-1 expression in a series of Ki-1 [CD30] positive lymphoid malignancies, including 27 Hodgkin's disease and eight anaplastic large cell lymphomas. CD30 negative tumours used as controls included 27 B-cell non-Hodgkin's lymphomas. 14 T-cell non-Hodgkin's lymphomas, four reactive lymphadenitis, and non-lymphoid tissues. Immunohistochemistry, performed on frozen sections, revealed a strong FAS/APO-1 expression in 25 out of 27 (92%) Hodgkin's disease cases, predominantly in Reed Sternberg cells; 50 to 100% of the neoplastic cells in eight out of (100%) anaplastic large cell lymphoma cases were positive. In contrast, positive FAS/APO-1 immunostaining was observed only in 22 out of 41 (53%) CD30 negative non-Hodgkin's lymphomas. Northern blot analysis detected variable amounts of the FAS/APO-1 transcript in the immunohistochemistry-positive samples. These results suggest possible hyper-expression of FAS/APO-1 (CD95) in Hodgkin's disease and anaplastic large cell lymphomas.

The histological, immunophenotypic and clinical features of 19 primary cutaneous anaplastic large cell lymphomas (cutaneous ALCL) were compared with those of 18 primary nodal anaplastic large cell lymphomas (nodal ALCL) of T-cell or null cell type. Although cutaneous ALCL and nodal ALCL had identical morphological features, differences in surface marker expression and clinical behaviour were found. Immunophenotypical differences concerned the expression of epithelial membrane antigen (82% of the nodal ALCL were positive v. none of the cutaneous ALCL) and the cutaneous lymphocyte antigen (HECA-452), a possible skin-homing receptor on cutaneous T-lymphocytes (most tumour cells in 44% of cutaneous ALCL cases were positive, whereas nodal ALCL showed expression of HECA-452 on only few tumour cells (< 25%) in 18% of cases tested). Loss of T-cell markers was more pronounced for nodal ALCL. Patients with cutaneous ALCL were generally older (median 61 years) than patients with nodal ALCL (median 24 years) and, in contrast to the latter group, did not show bimodal age distribution. Survival after 4 years, using lymphoma-related death as an end-point, differed significantly between cutaneous ALCL and nodal ALCL; 92% for cutaneous ALCL and 65% for nodal ALCL (P = 0.04). The better survival of cutaneous ALCL patients could not be ascribed to differences in age, stage or initial mode of treatment. These data indicate that differences in immunophenotype and clinical behaviour exist between morphologically identical primary cutaneous and primary node-based ALCL. They indicate that the primary site is an important prognostic factor in predicting the clinical outcome of ALCL.

We describe 13 cases of a peculiar lymphoid tumour containing very large numbers of reactive histiocytes. The tumours occurred in young patients (mean age 14.8 y) who presented with systemic symptoms and superficial lymphadenopathy. Microscopic examination revealed a diffuse effacement of lymph node structure due to the presence of histiocytes intermingled with a variable number of anaplastic large lymphoid cells. The latter, in some cases, were isolated, while in others they were arranged in clusters or were diffusely present in residual sinuses. The large anaplastic cells expressed the activation markers CD30 (Ki-1), CD25 (interleukin-2 receptor), CD70 (Ki-24) and Ki-27, as well as varying combinations of T-associated molecules. The histiocytes expressed lysozyme and the CD11b (C3bi-R), CD11c (p150, 95) CD14, CD68 (KPI) and Ber-Mac3 antigens. Double staining with the antibody Ki-67 demonstrated that the proliferating components were the CD30-positive cells and not the histiocytes. T-cell receptor beta gene rearrangements were shown in three cases tested. The patients responded well to aggressive chemotherapy and nine are still alive, eight in complete remission. It is suggested that the tumour represents a well-defined clinico-pathological entity originating from activated T-lymphocytes.

Aims : Undifferentiated nasopharyngeal non-keratinizing carcinoma (UNPC), formerly known as lymphoepithelioma, frequently metastasizes at an early stage to regional lymph nodes and, thus, may be difficult to distinguish from Hodgkin's lymphoma (HL) or anaplastic large cell lymphoma (ALCL). CD30 expression is a useful diagnostic stain in both HL and ALCL, but its expression in UNPC deserves clarification. The aim of this study was to evaluate CD30 expression in UNPC and lymphoepithelioma-like carcinoma (LELC) from other anatomic locations and compare it with ALCL and squamous cell carcinoma (SCC). Methods and results : CD30 immunoreactivity was examined in 38 cases of primary or metastatic UNPC, six cases of LELC, 10 cases of SCC and seven cases of ALCL. CD30 immunoreactivity was observed in four of 38 (10.5%) cases of UNPC. CD30 staining was absent in all cases of LELC (0/6) and SCC (0/10). All cases of ALCL (7/7) were strongly positive for CD30. Conclusions : The majority of cases of UNPC are immunohistochemically negative for CD30; however, a small subset of cases expresses CD30 antigen. These findings provide additional evidence that CD30 expression is not restricted to neoplasms of lymphoid origin. This should be taken into consideration when interpreting CD30 immunohistology and the possibility of UNPC.

By in situ hybridization with EBER oligonucleotides and immunohistochemistry with anti-latent membrane protein 1 (LMP1) antibody, we compared the detection rate of Epstein-Barr virus (EBV) in Hodgkin's disease and anaplastic large-cell lymphomas in children. Among the 13 cases of Hodgkin's disease tested, 7 (54%) were found to be EBV associated (EBER transcripts +, LMP1 +). None of the 11 cases of ALC lymphomas was found to contain EBV genomes or gene products. This may indicate that EBV is not a pathogenic agent in anaplastic large-cell lymphomas in children in comparison to Hodgkin's disease.

There is a strong association (approximately 95%) of endemic Burkitt's lymphoma with Epstein-Barr virus (EBV), whereas the association is weak for the sporadic form occurring in Western countries (approximately 15%). In the Middle East, North Africa and South America, 60–80% of Burkitt's lymphomas harbour EBV. These epidemiological differences suggest that either the endemicity of EBV or socio-economic conditions, or both, may influence the pathogenetic role of EBV in Burkitt's lymphoma. Since only meagre data are available on Asians, this study was performed to address this issue by studying cases from Hong Kong, where EBV seroconversion occurs in the first few years of life but the socio-economic conditions approach those of Western countries. In situ hybridization for EBV encoded RNAs (EBERs) was performed on paraffin sections of 18 cases of Burkitt's lymphoma. Labelling of the neoplastic cells was detected in five cases (27.7%). In contrast, among 54 cases of B-cell lymphomas of various subtypes studied for comparison, signals for EBER were detected in only one case each of T-cell-rich large B-cell lymphoma, anaplastic large cell lymphoma and Reed-Sternberg-like cells occurring in B-cell chronic lymphocytic leukaemia/small lymphocytic lymphoma. The strong labelling with oligo-dT probe (which hybridized with the polyadenylated ends of mRNA) in all cases suggested that the negative results were genuine and not due to poor preservation of RNA in the tissues. Thus, among B-cell neoplasms occurring in Chinese, Burkitt's lymphoma shows a statistically stronger association (P < 0.01) with EBV than with other types of B-cell lymphoma. The available data also suggest that the socio-economic status of the country rather than exposure to EBV at an early age is the crucial factor determining the role of EBV in the genesis of Burkitt's lymphoma.

Five antibodies, MT1 (CD43), UCHL1 (CD45RO), OPD4, poly-CD3 and beta F1, were assessed for their reactivity with 50 archival cases of T-cell lymphoma in formalin-fixed paraffin-embedded tissue. All cases had been previously characterized as T-cell lymphomas, and the histological types included 14 cases of small cerebriform lymphoma, six cases of angioimmunoblastic lymphadenopathy-like T-cell lymphoma, four cases of T-zone lymphoma, five cases of pleomorphic small cell lymphoma, 12 cases of pleomorphic medium and large cell lymphoma, four cases of anaplastic large cell lymphoma, two cases of T-lymphoblastic lymphoma and three cases of enteropathy-associated T-cell lymphoma. UCHL1 and MT1 showed reactivity with the highest percentage of cases (94 and 86% respectively) but lack absolute specificity for T-cells, especially in high-grade lymphomas. Poly-CD3 is highly specific for T-cells, and stained neoplastic cells in almost 80% of the cases. beta F1 stained the lowest percentage of cases (40%). UCHL1 and poly-CD3 together identified 98% of cases, and this combination is recommended for the diagnosis of T-cell lymphomas in paraffin sections.

The CD30 antigen has been reported as the immunophenotypic hallmark of a recently described category of non-Hodgkin's lymphoma, termed anaplastic large cell lymphoma. From a series of approximately 500 lymphomas, 17 cases showing typical anaplastic features have been identified. They were strongly labelled by monoclonal antibodies recognizing CD30 (Ki-1 or BerH2). However, 36 other lymphomas, mainly high-grade, of non-anaplastic cytology also expressed CD30, either diffusely or focally, with a staining pattern identical to that seen in anaplastic large cell lymphomas. This clearly suggests that such lymphomas cannot be identified solely on the basis of being high-grade non-Hodgkin's lymphomas showing CD30 positivity. From the present results, the distinction between the anaplastic and non-anaplastic types would be better made with antibodies to epithelial membrane antigen than to CD30. Clinical data, available for 48 of the patients (16 with anaplastic large cell lymphomas and 32 with non-anaplastic) revealed no significant differences with regard to age at presentation, sex or clinical signs. A short-term follow-up study of 25 patients revealed that for the first 2 years after diagnosis there were no significant differences in patient survival between anaplastic large cell lymphoma, other CD30+ high-grade lymphomas and all high-grade non-Hodgkin's lymphomas considered together. These findings, which must be confirmed by larger studies, suggest that in a general lymphoma clinic there is probably little justification for differentiating anaplastic large cell lymphomas or CD30+ lymphomas from other high-grade non-Hodgkin's lymphomas.