Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.

BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

Better resource utilisation and quality of care for ovarian cancer patients using internet-based pathology review.

BACKGROUND: The current literature indicates that a considerable number of patients in ovarian carcinoma clinical trials have histopathological diagnoses in conflict with inclusion criteria. It has been suggested that specialised pathology review prior to randomisation should become the standard procedure in study protocols. We hypothesised that our new, internet-based high-throughput infrastructure would be capable of providing specialised pathology review within 10 working days (w.d.). METHODS: Patients scheduled for the AGO OVAR17 ovarian carcinoma chemotherapy trial were registered for expert pathologic case review using a new internet-based central pathology review platform prior to randomisation. All original slides were requested from local pathologists. Slides were scanned and uploaded to a secured internet server. A network of experienced gynaecological pathologists was connected to the server through a custom-designed software platform. If deemed necessary by the expert pathologists, immunohistochemistry was available through a collaborating pathology lab. RESULTS: A total of 880 patients with an original diagnosis of ovarian epithelial carcinoma were registered for expert pathology review from October 2011 to July 2013. For case review, five gynaecopathologists from Austria, Switzerland and Germany were available online. Median number of w.d. required to complete the whole process from patient registration to transmission of final review diagnoses was 4 (range 2-31) (w.d.), and in 848 out of 880 (97.5%) cases, it amounted to ⩽10 w.d. In 2.5% (n=22) of cases, a major diagnostic discrepancy of potential clinical relevance was found leading to exclusion from the chemotherapy trial. CONCLUSIONS: Our results show that the use of a new internet-based infrastructure makes timely specialised case review, prior to patient randomisation feasible within ⩽10 w.d. Our new approach helped to protect against overtreatment with chemotherapy of patients with ovarian borderline tumours and inadequate treatment of patients with ovarian metastases, as a result of their inappropriate entry into a clinical trial designed for patients with primary ovarian carcinoma.

King-Devick Test reference values and associations with balance measures in high school American football players.

The King-Devick test appears to be a promising tool in screening for concussions. However, limited evidence exists on the baseline associations between the K-D test and age and baseline screening tools used after concussion. Additionally, there are no published reference values for the K-D test in high school football players. The K-D test, the Balance Error Scoring System, and the Limits of Stability (LOS) test were administered to 157 high school football players. Additionally, a subsample of 62 participants completed the test twice to examine the reliability of K-D test. There was no relationship between the K-D test and the BESS, or the reaction time and directional control of LOS test. Students aged between 16 and 18 years demonstrated faster K-D test performance compared to students between 13 and 15 years of age. However, there was no association between K-D test and history of concussion. The reliability of the K-D test was (ICC2,1 = 0.89), and the minimal detectable change was 6.10 s. Normative reference values for high school football players are presented in this study.

Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2).

BACKGROUND: Gastro-oesophageal adenocarcinomas rarely metastasize to the central nervous system (CNS). The role of the human epidermal growth factor receptor 2 (HER2) in patients with these cancers and CNS involvement is presently unknown. PATIENTS AND METHODS: A multicentre registry was established to collect data from patients with gastro-oesophageal adenocarcinomas and CNS involvement both retrospectively and prospectively. Inclusion in the study required a predefined clinical data set, a central neuro-radiological or histopathological confirmation of metastatic CNS involvement and central assessment of HER2 by immunohistochemistry (IHC) and in situ hybridisation (ISH). In addition, expression of E-cadherin and DNA mismatch repair (MMR) proteins were assessed by IHC. RESULTS: One hundred patients fulfilled the inclusion criteria. The population's median age was 59 years (interquartile range: 54-68), of which 85 (85%) were male. Twenty-five patients were of Asian and 75 of Caucasian origin. HER2 status was positive in 36% (95% CI: 26.6-46.2) of cases. Median time from initial diagnosis to the development of brain metastases (BMets) or leptomeningeal carcinomatosis (LC) was 9.9 months (95% CI: 8.5-15.0). Median overall survival from diagnosis was 16.9 months (95% CI: 14.0-20.7) and was not related to the HER2 status. E-cadherin loss was observed in 9% of cases and loss of expression in at least one DNA MMR proteins in 6%. CONCLUSIONS: The proportion of a positive HER2 status in patients with gastro-oesophageal adenocarcinoma and CNS involvement was higher than expected. The impact of anti-HER2 therapies should be studied prospectively.

[Serous ovarian tumors]. / Seröse Tumoren des Ovars.

Because of different patterns of molecular changes, a dualistic model of serous tumors is now assumed with serous borderline tumors (SBT) and low-grade serous carcinomas (LGSC) on one side and high-grade serous carcinomas (HGSC) on the other. The clinical course and the type of treatment of SBT and LGSC depend crucially on whether they are associated with extraovarian manifestations. So-called invasive implants of SBT correspond morphologically to LGSC. The MD Anderson grading system has become established for the distinction between LGSC and HGSC, HGSC shows a wide range of growth patterns, including a transitional epithelial-like type. Carcinosarcomas can be interpreted as HGSC variants. Considering the new theory that all serous neoplasms of the ovary, peritoneum and fallopian tubes are derived from the tubal fimbria, the term "ovarian carcinoma" seems no longer appropriate.

Prognostic and predictive value of TOPK stratified by KRAS and BRAF gene alterations in sporadic, hereditary and metastatic colorectal cancer patients.

BACKGROUND: Our aim was to investigate the prognostic and predictive value of the oncogenic MAPKK-like protein T-cell-originated protein kinase (TOPK) stratified by KRAS and BRAF mutations in patients with sporadic, hereditary and metastatic colorectal cancer (CRC) treated with anti-EGFR therapy. METHODS: Immunohistochemistry (IHC) for TOPK was performed on four study groups. Group 1 included two subgroups of 543 and 501 sporadic CRC patients used to test the reliability of TOPK expression by IHC. In Group 2, representing an additional 222 sporadic CRCs, the prognostic effect of TOPK stratified by KRAS and BRAF was assessed. The prognostic effect of TOPK was further analysed in Group 3, representing 71 hereditary Lynch syndrome-associated CRC patients. In Group 4, the predictive and prognostic value of TOPK was analysed on 45 metastatic patients treated with cetuximab or panitumumab stratified by KRAS and BRAF gene status. RESULTS: In both sporadic CRC subgroups (Group 1), associations of diffuse TOPK expression with clinicopathological features were reproducible. Molecular analysis of sporadic CRCs in Group 2 showed that diffuse TOPK expression was associated with KRAS and BRAF mutations (p<0.001) and with poor outcome in patients with either mutation in univariate and multivariate analysis (P=0.017). In hereditary patients (Group 3), diffuse TOPK was linked to advanced pT stage. In metastatic patients treated with anti-EGFR therapy (Group 4), diffuse TOPK expression was linked to dismal outcome despite objective response to treatment (P=0.01). CONCLUSIONS: TOPK expression is an unfavourable prognostic indicator in sporadic patients with KRAS or BRAF mutations and also in patients with metastatic disease experiencing a response to anti-EGFR therapies. The inhibition of TOPK, which could benefit 30-40% of CRC patients, may represent a new avenue of investigation for targeted therapy.

[Development of a soft tissue ulcer after long-term peridural infusion]. / Entwicklung eines Weichteilulkus nach periduraler Langzeitinfusion.

Local anaesthetic agents (LA) in clinical concentrations have the potential for tissue toxicity, although this is rarely observed in clinical practice. The case of a 74-year-old female patient (BMI 16.8 kg/m(2)) with a metastasising bronchial carcinoma is reported, who suffered from severe back pain due to tumour infiltration. For pain management a tunnelled continuous thoracic peridural catheter (PC) was placed and a mixture of bupivacaine 0.49%, morphine 0.0036% and clonidine 0.0001% was infused at 3 ml/h. After 8 weeks of continuous infusion an ulcer developed in the soft tissue close to the thoracic spine containing whitish crystalline material (CM). A computed tomography examination revealed a subcutaneously displaced PC with extensive fluid collection reaching down to the sacrospinalis muscle. Histologically an unreactive necrosis with enclosed CM of unknown etiology was found. The result of the chemical analysis of the deposits demonstrated bupivacaine, morphine and sodium chloride. It is concluded that the soft tissue ulcer was probably caused by precipitation of the LA mixture.

Is sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp identical to inflammatory pseudotumour? Report of 16 cases.

AIMS: To report 16 cases of sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp. METHODS AND RESULTS: Patients were selected in two phases. An initial group of seven patients was diagnosed with SANT based on the presence of angiomatoid nodules. Sheets of inflammatory fibrosis were found in three patients, resembling inflammatory pseudotumour (IPT); nine further cases of IPT were reviewed. Angiomatoid nodules were detected, leading to the diagnosis of SANT in all cases. The splenic mass (10-150 mm in diameter) was polycyclic, composed of multiple small nodules of loose connective tissue comprising myofibroblasts and a dense network of capillaries as well as some remnants of sinuses. Collagenous fibrosis surrounded them. Bands or large sheets of fibrosis, infiltrated by various inflammatory cells, particularly polytypic plasmacytes, resembling IPT, were present in 10 cases. CONCLUSIONS: SANT of the red pulp is a distinct benign pseudotumorous lesion of the spleen characterized by the presence of angiomatoid nodules. We observed such angiomatoid nodules in all our cases of splenic IPT, which were not follicular dendritic cell or myofibroblastic tumours. We therefore recommend careful examination for angiomatoid nodules in all suspected cases of splenic IPT.

Bilateral primary adrenal non-Hodgkin's lymphoma - a case report and review of the literature.

Primary adrenal non-Hodgkin's lymphoma (PAL) is a rare neoplastic disease. Clinical symptoms are often related to the presence of lymphoma or adrenal insufficieny. Diagnostic strategies include endocrine evaluation, imaging studies and histopathological examination. In case of suspicious PAL, percutaneous CT or US-guided needle biopsy is recommended to rapidly establish diagnosis before starting chemotherapy. We report about an 84-year-old male who presented with significant weight loss and chronic lumbar pain. Abdominal CT scans revealed bilateral masses highly suggestive of malignancy. After open bilateral adrenalectomy with abdominal lymphadenectomy, histological examination showed bilateral PAL. Five months after surgery, the patient died due to progressive tumor disease.

[Basal and myoepithelial phenotype of metastatic mammary carcinomas. A prognostic factor in the palliative situation?]. / Basaler und myoepithelialer Phänotyp des invasiven Mammakarzinoms. Prognostischer Faktor in der palliativen Situation?

AIMS: The aim of the present study was to evaluate the prognostic impact of basal and myoepithelial phenotype in breast carcinomas (BBC and MBC) in the palliative situation. METHODS: Paraffin-embedded material from 244 primary breast carcinomas of patients with subsequent metastatic disease was stained immunohistochemically for CK 5/6, CK14, smooth-muscle actin, p63, estrogen receptor and progesterone receptor. BBC was defined as positive for CK5/6 and/or CK14 and MBC as positive for SMA and/or p63. Clinical and pathological data were available for all patients and follow-up data for 96.3% (range 5 days-151 months). RESULTS: Until the end of the follow-up period 90.2% of patients died and 6.1% are still alive. Of the tumours 28.7% could be classified as BBC and 8.2% as MBC. Kaplan Meier analysis revealed a trend for reduced survival after first diagnosis of metastasis (OASM) for BBC and MBC. Differences in survival were significant for BBC (log-rank =5.0; p=0.025), but not for MBC. CK5/6+ and CK14+ double positive tumours (n=18; 7.4%) were identified as a subgroup of BBC associated with reduced OASM (log-rank=8,6; p=0.003). This subgroup, but not BBC or MBC was an independent negative prognostic factor in a multivariate analysis including age, typing, tumour size, grading, axillary nodes, HR, Her2/neu, site of first metastasis and disease-free interval. CONCLUSION: The association of BBC and MBC with reduced OASM in metastatic breast carcinomas is not independent from established prognostic factors. CK5/6+ CK14+ double positive tumours may be a subgroup of BBC with particularly unfavourable outcome.

Primary mediastinal anaplastic alk-1-positive large-cell lymphoma of T/NK-cell type expressing CD20.

We describe an unusual case of ALK-1-positive primary mediastinal lymphoma with the morphology of an anaplastic large-cell lymphoma (ALCL) of T/NK cell type but expressing CD20. This tumour had T/NK morphology and immunophenotype, as demonstrated by its expression of CD30, EMA, ALK-1, CD7 and TiA-1 and the lack of expression of B-cell markers other than CD20. The significance of such a co-expression of a B cell-associated antigen in a case of ALCL of T/NK cell type is discussed.

Characterization and removal of DNAPL from sand and clay layered media.

Important characterization and remediation techniques (e.g. partitioning tracer tests (PTT), cosolvent and surfactant flushing) have been developed over the years to deal with dense nonaqueous phase liquid (DNAPL) sources in the saturated zone. Unfortunately, subsurface media layering and heterogeneity pose a major challenge to the efficiency of these and other techniques that rely on flushing fluids through porous media. Using laboratory column experiments with both single media and layered-media columns and computer modeling of tracer breakthrough results, we examined the difficulty that layering poses to subsurface remediation and characterization techniques. Quantifying tetrachloroethylene (PCE) saturation in layered media was determined using PTT and effluent mass determinations. Conservative tracer breakthrough curves were used to determine permeability and the flow through layers before and after PCE contamination. The removal efficiency of alcohol flushing in the layered systems was also determined. Results showed that even a relatively simple layering with less than an order magnitude difference in permeability leads to difficulty in characterization and remediation using flushing technologies. These results suggest that much greater volumes of flushing solutions will be needed in heterogeneous environments to ensure adequate flushing of lower permeable lenses and layers.

Marginal zone lymphoma of both spleen and kidney displaying transformation into large B-cell lymphoma.

We report a case of simultaneous involvement of the spleen and the left kidney in a marginal zone lymphoma with a monotypic lymphoplasmacytic cell component, which transformed into a diffuse large B-cell lymphoma of the immunoblastic type. PCR showed that the small and large B-cell populations carried the same type of immunoglobulin heavy chain gene rearrangement. This type of rearrangement was detected in the spleen, the latero-aortic lymphadenopathy and the kidney demonstrating that it is the same lymphoma that affected both organs and the lymph nodes. Primary renal lymphoma is very rare and only a few cases of renal marginal zone lymphoma, MALT type, have been reported. Involvement of simultaneous multiple sites has been described in MALT type lymphoma, but splenic involvement secondary to renal MALT lymphoma seems to have never been observed. Nevertheless, in our case the huge size of the spleen associated with splenic hilar node involvement is consistent with primary splenic marginal zone lymphoma. The extension into latero-aortic lymph nodes of this lymphoma can explain secondary kidney involvement. The nodal Kaposi's sarcoma observed in this patient of Mediterranean origin was probably coincidental.

Interphase cytogenetic analysis of prostatic carcinomas by use of nonisotopic in situ hybridization.

To gain a better understanding of chromosomal aberrations in direct correlation with histology, we studied tumor material from 35 patients (36 regions) with primary prostate carcinoma by nonisotopic in situ hybridization. Nine biotinylated DNA probes were used on serial paraffin sections (centromer-specific probes for X, Y, 1, 7, 8, 10, 17, and 18, and a telomer-specific probe for 1p; ONCOR). Of the 324 hybridized sections, 94% were suitable for evaluation. In 34 of the 35 cases (35 of 36 regions) 1-8 chromosomal aberrations were detected. Chromosome X showed supernumerary centromer copies in 44% of cases. The probes for chromosomes 1, 1p, 10, and 18 demonstrated deletions in 25, 23, 40 and 58% of cases, respectively. Gains as well as deletions were present for Y, 7, 8, and 17 in 31, 25, 36, and 58% of cases, respectively. In 27% of cases discordant copy numbers of the centromer- and the telomer-specific probes for chromosome 1 were observed. No aberration which might be specific for prostate cancer could be established. The rate of aneusomy increased significantly with histological grade. Intratumoral heterogeneity of chromosomal aberrations was revealed in one case. Due to the higher sensitivity of nonisotopic in situ hybridization, aneusomic cases outnumbered cases with cytometrically determined DNA aneuploidy. In view of published results of metaphase preparations, the high frequency of aneusomy and some of the chromosomal aberrations detected by nonisotopic in situ hybridization were unexpected.

Initial lesions of classical Hodgkin's lymphoma of the nodular sclerosis type.

The necessity of correct diagnostics of initial lesions of Hodgkin's lymphoma is underlined. The correct assessment may relate of more than 90% of such observation to 90% of noduler sclerosis. The criteria similar to those of WHO are suggested for the differentiation with mixed-cell or lymphoid preponderance.

World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997.

PURPOSE: The European Association of Hematopathologists and the Society for Hematopathology have developed a new World Health Organization (WHO) classification of hematologic malignancies, including lymphoid, myeloid, histiocytic, and mast cell neoplasms. DESIGN: Ten committees of pathologists developed lists and definitions of disease entities. A clinical advisory committee (CAC) of international hematologists and oncologists was formed to ensure that the classification would be useful to clinicians. The CAC met in November 1997 to discuss clinical issues related to the classification. RESULTS: The WHO uses the Revised European-American Lymphoma (REAL) classification, published in 1994 by the International Lymphoma Study Group, to categorize lymphoid neoplasms. The REAL classification is based on the principle that a classification is a list of "real" disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one gold standard. The WHO Neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. At the CAC meeting, which was organized around a series of clinical questions, participants reached a consensus on most of the questions posed. They concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors, such as the International Prognostic Index. CONCLUSION: The WHO classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies.

Extended versus involved fields irradiation combined with MOPP chemotherapy in early clinical stages of Hodgkin's disease.

From 1976 to 1981, 335 patients with untreated Hodgkin's disease, clinical stages I, II, and IIIA, have been treated by MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) chemotherapy, three to six cycles according to the prognostic factors, combined with radiotherapy. Irradiation was always performed after the first three cycles of chemotherapy, and was randomized between extensive radiotherapy, ie, mantle and paraaortic areas for supradiaphragmatic presentations, and radiotherapy restricted to the involved areas. No significant difference was observed between the two randomized branches for the disease-free survival (86% after six years in the involved field branch v 90% in the extended field branch), and none for the overall survival. Most of the relapses occurred in nonirradiated areas in the first group, and in irradiated areas in the second. Relapses were especially frequent in the IIE stages with pulmonary extension; extranodal relapses occurred with osseous and cutaneous localizations. Two cases of secondary leukemia were observed after three- or six-cycle MOPP plus radiotherapy limited to the involved areas.

Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: The aims of this study were as follows: (1) to analyze clinical, histopathologic characteristics, treatment outcome, and prognostic factors of patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same therapeutic trial. PATIENTS AND METHODS: Eighty-nine FLCL patients who were histologically reviewed and who received an intensive chemotherapy regimen according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell DLCL patients included in the same protocol. RESULTS: After intensive induction treatment, 59 patients (67%) achieved a complete remission [CR]. Estimated 5-year survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%. Prognostic factors associated with shorter FFP were age greater than 60 years (P = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH) level (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03), bone marrow involvement (P = .04), and high expression of bcl-2 protein (P = .05). When compared with B-cell DLCL patients, FLCL patients were younger (P = .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04), more advanced clinical stages (P < .001), and more bone marrow involvement (P = .02). No significant difference was observed between FLCL and DLCL patients for response to therapy (67% v 67% of CR), 5-year overall survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival (39% v 43%). CONCLUSION: FLCL patients have a favorable response rate and survival when treated with intensive chemotherapy. Their outcome is similar to that of B-cell DLCL patients, and a long-term FFP is observed for a substantial number of patients. Some adverse prognostic factors (including those of the International Prognostic Index, bone marrow involvement, and beta-2 microglobulin) have been identified to define a subset of patients who require other therapeutic approach.

Burkitt-like lymphomas in AIDS patients: characterization within a series of 103 human immunodeficiency virus-associated non-Hodgkin's lymphomas. Burkitt's Lymphoma Study Group.

PURPOSE: Burkitt-like lymphoma (BLL) is a tumor with morphologic features intermediate between Burkitt's lymphoma (BL) and large-cell lymphoma, but its relationship with these lymphomas is currently unclear. We have therefore analyzed its characteristics within a large series of human immunodeficiency virus (HIV)-associated lymphomas. MATERIALS AND METHODS: Clinical, histologic, immunophenotypic, and molecular analyses were performed on 103 patients with AIDS lymphomas. RESULTS: Nineteen cases (18.4%) were identified as BLL. They were monoclonal B-cell proliferations, as evaluated by immunoglobulin (Ig) gene rearrangement analyses, and had rearrangement of the c-myc oncogene in 68% of cases but not the bcl-2 gene, in contrast to a previous study on non-HIV-associated BLL. This molecular pattern was therefore identical to that of typical BL, suggesting that they represented tumors of similar origin. However, some features could clearly differentiate BLL from BL and were similar to those seen in the diffuse large-cell immunoblastic lymphomas (DLC-IBL) group. These included a greater frequency of Epstein-Barr Virus (EBV) infection (79% v 48%, P = .04), an upregulation of CD39 (50% v 0%, P = .0007) and CD70 (75% v 15%, P = .003) activation antigens and of the CD11a/LFA-1 adhesion molecule (83% v30%, P = .05), and, finally, a lower CD4 count (mean, 119/microL v 270/microL, P = .04). CONCLUSION: BLL is a frequent entity among AIDS lymphomas and should be considered as a morphologic variant of BL in the context of severe immunodepression that occurs in HIV-infected patients.