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CPUs typically operate at a voltage which is higher than what is strictly required, using voltage margins to account for process variability and anticipate any combination of adverse operating conditions. However, these worst-case scenarios occur rarely, if ever, thus the operating voltage is overly pessimistic resulting in excessive power dissipation which leads to decreased performance under power capping. In this paper, we investigate the impact of reducing voltage margins beyond the nominal level on the efficiency of CPU power capping mechanisms, for three commercial systems, two Applied Micro ARMv8 micro-servers (X-Gene2 and X-Gene3) and an Intel x86-64 (Xeon E3). We show that CPU power capping at reduced voltage margins compared with Intel's RAPL and Dynamic Frequency Scaling (DFS) mechanisms results in performance improvement by up to 64% and 24% on average, respectively. In combination with state-of-the-art thread packing, the reduction of CPU voltage margins results in 36%, 33% and 27% performance improvement compared with RAPL and DFS for the Xeon E3 and the X-Gene processors, respectively. Also, we validate the robustness of our approach with a set of long-running experiments and show that significant energy gains can be achieved even when considering the cost of checkpointing and recovery in large-scale systems. IEEE

La tasa de mortalidad en pacientes con enfermedad celiaca (EC) excede a la de la poblacion general lymphoma como consecuencia de una mayor incidencia de neoplasias: adenocarcinoma de intestino delgado, carcinoma escamoso de orofaringe y de esofago y, especialmente, linfomas no Hodgkin (LNH)1. Smedby et al2 han calculado los cocientes estandarizados de incidencia (numero de linfomas observados en cada categoria entre el numero esperado) de 6,6 para los LNH como grupo, 2,2 para los de celulas B, 51 para los de celulas T, 21 para los primarios extranodales de intestino y 3,6 para los de origen no intestinal. A pesar de que el linfoma de celulas T asociado a enteropatia (LTE) es el tipo de linfoma con un riesgo relativo mas elevado en pacientes con EC, su baja incidencia hace que, en conjunto, el resto de los LNH sean mas frecuentes en pacientes con EC. Describimos una enferma con dolor abdominal a la que diagnosticamos una EC y un LTE. Mujer de 59 anos, con antecedentes de anemia ferropenica y osteoporosis, que consulta por dolor abdominal

Fundamento El sindrome hipereosinofilo (SHE) es un grupo heterogeneo de procesos raros caracterizados por un aumento prominente y sostenido de eosinofilos en sangre y dano organico. Se deben excluir otras causas de hipereosinofilia. Avances recientes en biologia molecular y citogenetica han permitido caracterizar diferentes subtipos. Se describe un caso de la variedad linfoide. Paciente Varon filipino de 46 anos que consulta por lesiones cutaneas, fiebre, conjuntivitis, adenopatias y eosinofilia prominente. Resultados El estudio de poblaciones linfocitarias en sangre periferica revela una poblacion aberrante de linfocitos T (LT) CD3-CD4+ productora de interleucina 5 (IL-5). Se confirmo la clonalidad del TCR mediante PCR. Conclusiones La variedad linfoide del SHE esta caracterizada por una expansion clonal de LT no maligna que produce IL-5, de comportamiento indolente, pero que puede evolucionar a linfoma T periferico. Se describe el primer caso de variedad linfoide publicada en nuestro pais y se revisan las caracteristicas de esta variedad.

Resume Dans le cadre de la prevention exercee par les services de PMI (Promotion de la sante de la mere et de l'enfant), le depistage des troubles des conduites ne peut etre isole d'une approche globale du developpement de l'enfant, considere dans son contexte et son histoire. Au-dela de la reconnaissance d'un symptome qui peut reveler une pathologie sous-jacente, il convient de s'interroger sur une demarche de prevention plus predictive que prevenante qui tend a enfermer les enfants dans un destin trace par leur capital genetique et leur milieu. Plus que d'etouffer les symptomes des enfants, il est urgent de chercher la cause profonde de troubles qui temoignent avant tout d'un probleme de societe.

Transformation of CLL into a large cell lymphoma has an incidence of 3-5%. We have studied 101 cases of CLL treated with fludarabine over a 10-year period (1990-2000) and observed a 12% incidence of transformation. In six of 12 patients, transformation was documented within 4 months following treatment with fludarabine. Pathological material, available in nine cases, was investigated for latent EBV by staining for LMP-1 by immunohistochemistry and EBERs-1 and 2 by in situ hybridisation. LMP-1 and EBERs were demonstrated in three of the nine samples. In two cases there was a different pattern of immunoglobulin gene rearrangement in the transformed cells assessed by PCR (FR3 fragment) compared to the original CLL clone. One of these two cases showed evidence of latent EBV. The other seven cases, of which two were EBV positive, showed identical pattern of Ig gene rearrangement in both the CLL and the transformed cells. We suggest that the relatively high incidence of transformation in this series may be due to immunosuppression mainly related to fludarabine, although other agents and prior therapies may have also contributed.

El sindrome de Churg-Strauss es una enfermedad multisistemica caracterizada por la presencia de rinitis alergica, asma y eosinofilia periferica1. Los organos mas frecuentemente afectados son el pulmon (90-100%) y la piel (51-70%), junto con la afectacion del sistema nervioso periferico en forma de mononeuritis multiple (66-76%)1,2. Las manifestaciones musculoesqueleticas son posibles durante la fase activa de la enfermedad, siendo mas raras en otros momentos1. La afectacion muscular en forma de miositis en un sindrome de Churg-Strauss es inusual, habiendose publicado solo 3 casos hasta la fecha como forma de presentacion clinica3—5. Presentamos el caso de un paciente con clinica indicativa de polimiositis como primera manifestacion de un sindrome de Churg-Strauss.

BACKGROUND—Most low grade gastric lymphomas arising from the mucosa associated lymphoid tissue (MALT) are related to Helicobacter pylori colonisation. Cases with disease limited to the stomach can be cured after H pylori eradication and remain in remission for years. In contrast, high grade lymphomas of the stomach, although also related to H pylori, do not usually respond to eradication treatment. CASE REPORT—A 36 year old patient was referred from another hospital with a diagnosis of a low grade gastric MALT lymphoma associated with H pylori. The patient was in stage I and while waiting for the biopsies to be reviewed H pylori eradication therapy was given as the first step of treatment. Review of the biopsies showed a high grade immunoblastic lymphoma with areas of low grade gastric MALT lymphoma (high grade gastric MALT lymphoma or diffuse large B cell lymphoma with areas of MALT type lymphoma of the WHO classification). The patient received no further treatment but has been closely followed up for 32 months with sequential endoscopies to obtain biopsies for histological studies, H pylori cultures, and polymerase chain reaction analysis of the IgH gene. RESULTS—After H pylori eradication the patient had a complete histological response that has been maintained for 32 months. Monoclonal IgH gene rearrangement persisted for 32 months. CONCLUSION—The response of this patient indicates the possibility that some cases of high grade gastric MALT lymphoma (possibly patients in stage I with a superficial or limited disease) may still be responsive to H pylori antigenic drive and may be cured with eradication therapy. Prospective studies should be performed to identify patients with high grade gastric MALT lymphomas that may respond to eradication therapy and be spared of other more aggressive treatments. Keywords: mucosa associated lymphoid tissue; lymphoma; gastric lymphoma; immunoblastic lymphoma; Helicobacter pylori

B lymphocytes that infiltrate the thyroid (Thy-B cells) in Graves' patients appear to be implicated in the pathophysiology of this disorder. The goal of the present study was to examine the nature of these Thy-B cells. To this end, Thy-B lymphocytes were isolated from surgical thyroidal samples, and their phenotype was determined by using mouse monoclonal antibodies (mAb) directed against a wide variety of surface markers, followed by flow cytometry multicolor analysis. The results show that most Thy-B cells (approximately 60%) exhibited IgM(+) IgD(low to -) surface immunoglobulin (Ig) profile, whereas the minor cell fraction (approximately 30%) consisted of switched IgG(+) memory B lymphocytes. Thy-B cells expressed low levels of CD5, CD23, and CD62L, which distinguished them from the resting B-cell pool, the major B-cell subset in the blood. In addition, they lacked CD38, CD10, and CD71, characteristic molecules for the germinal center B lymphocytes. In addition, Thy-B lymphocytes showed peculiar patterns both of adhesion molecules (CD62L(-), CD44(intermediate)), and of activation molecules (CD69(+), CD80(+), and, in part, CD95(+)). Taken together, these results suggest that the Thy-B lymphocyte subset consists of a combination of IgM(+) B cells resembling marginal zone B lymphocytes, and isotype-switched memory B cells.

BACKGROUND: Recently lymphomas arising primarily in serosal surfaces have been found in patients with advanced acquired immunodeficiency syndrome (AIDS), but they very rarely seem to occur in human immunodeficiency virus (HIV)-negative patients. Studies on a subset of these lymphomas suggested that they represent a distinct entity associated with Kaposi's sarcoma-associated herpesvirus or human herpesvirus 8 (HHV-8). CASE: An 83-year-old, HIV-negative male was admitted to the hospital with a massive pleural effusion. Abdominal and chest computed tomographic scanning was normal. Cytologic analysis of the pleural effusion revealed a large cell, non-Hodgkin's lymphoma. Polymerase chain reaction analyses on genomic DNA from the pleural effusion demonstrated the presence of HHV-8 sequences in the absence of Epstein-Barr virus. CONCLUSION: It is possible and advantageous to diagnose body cavity-based lymphoma with a combination of cytologic, immunocytochemical and molecular studies of the pleural effusion in conjunction with clinical and radiographic information.

The present report analyses the distribution of 30-base pair (bp) latent membrane protein-1 (LMP-1) oncogene deletions in 24 cases of Epstein-Barr virus (EBV)-positive paediatric Hodgkin's disease (HD) and 39 normal controls. The 30 bp deletion was identified in 19/24 paediatric HD cases (79.2%), of which seven (29.2%) showed the deleted fragment alone, whereas in the remaining 12 (50%) it was accompanied by the nondeleted fragment. Conversely, the deletion was found in 8/22 (36.4%) EBV-positive healthy children, in two (9.1%) of whom the deleted fragment was alone, and was coinfecting with the nondeleted fragment in the other six (27.3%). The LMP-1 deletion was significantly associated with paediatric HD, both including dual infections (P=0.006) or excluding them (P=0.01). Type 2 EBV was carried by 25% of HD children, whereas all controls harboured type 1 EBV. The 30 bp deletion was present in all the paediatric HD specimens that contained type 2 EBV, suggesting that a deleted type 2 EBV strain may be more tumourigenic than a nondeleted type 2 EBV strain. These findings indicate that EBV strains carrying a 30 bp deletion in the third exon of the LMP-1 oncogene may have a more important role in the pathogenesis of paediatric HD than full-length EBV strains. Dual infection by LMP-1 deleted and nondeleted EBV strains is a frequent event both in healthy children and in the paediatric HD population.

The aim of the present study was to analyze in a series of 24 HIV-positive Hodgkin's disease (HD) patients the morphological and immunological features, the presence of rearrangements in the immunoglobulin heavy chain (IgH) gene, expression of the Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1), and the existence of deletions in the intracytoplasmic domain of the LMP-1 gene. The results obtained were compared with those from a parallel series of 56 patients with ordinary HD. Briefly, comparison of the two series showed a predominance of unfavorable histological subtypes in HIV-positive HD patients. The mixed cellularity subtype was more frequent in HIV-positive than in HIV-negative HD patients: the difference in percentage was statistically significant (p = 0.04). Neoplastic cell-rich cases were significantly more frequent (p = 0.40) in HIV patients (59%) than in ordinary HD patients (34%). In 25% of HIV-infected and in 14% of ordinary HD patients, the neoplastic cells were CD20+, a difference that was not statistically representative. Clonal IgH rearrangements were detected in 33% of HIV-infected patients and in 23% of ordinary HD patients, a nonsignificant difference. LMP-1 expression was detected in 100% of HIV-positive patients and in 57% of ordinary HD patients (p = 0.004). A 30-base-pair deletion in the carboxy-terminal domain of the LMP-1 gene was found in 16 of 18 HIV-infected patients (89%), whereas it was identified in only 8 of 25 ordinary HD patients (32%) (p = 0.008). In conclusion, HD in HIV-infected patients as compared with HD in HIV-negative individuals is associated with morphological features of aggressivity, with a higher frequency of neoplastic cells, and with constant LMP-1 expression. The fact that LMP-1 is expressed in all HIV-infected patients suggests that EBV plays an etiological role in the pathogenesis of HIV-associated HD. Furthermore, the presence of EBV strains carrying deletions near the 3' end of the LMP-1 gene in the majority of cases may be related with the morphological and clinical aggressivity of HD in immunocompromised patients.

Hypereosinophilic syndromes (HSS) are a rare group of heterogeneous disorders characterized by prominent and persistent eosinophilia and organ dysfunction. Secondary causes of eosinophilia must be excluded. Recent advances in molecular biology and cytogenetics have permitted the characterization of different subsets of hypereosinophilic syndrome. We describe a patient with the lymphocytic variant.A 46-year old male Philippine patient presented skin lesions, fever, red eyes, enlarged lymph nodes and marked eosinophilia.Lymphocytic phenotyping by flow cytometry analysis was performed on peripheral blood and an aberrant population of T lymphocytes CD3-CD4+ producing interleukin 5 was found. TCR gene rearrangement using PCR amplification confirmed T cell clonality.The lymphocytic variant of the hypereosinophilic syndrome is a primitive lymphocytic disorder characterized by a non-malignant T cell population expansion producing eosinophilopoietic cytokines, with an indolent clinical course but that can transform into a peripheral T lymphoma. We report the first case of such a variant published in our country and review the characteristics of this variety.

PROPÓSITO: Revisar los hallazgos citohistopatológicos, inmunohistoquímicos y moleculares del tumor de células pequeñas redondas (DSRCT). MATERIAL Y MÉTODOS: Varón de 18 años con masa intraabdominal epigástrica. RESULTADOS: Tumoración constituida por una proliferación en nidos y difusa de células pequeñas indiferenciadas sobre estroma desmoplásico, con formación de rosetas, inmunorreactivas para citoqueratinas, vimentina, desmina y enolasa y la fracción WT1 de la proteína EWS/WT1. El estudio molecular demostró la traslocación t(11;22)(p13;q12). CONCLUSIONES: La formación de rosetas y las áreas sólidas han sido descritas en otros casos de DSRCT. El producto quimérico puede detectarse mediante RT-PCR, Southern-blot, Western-blot e inmunohistoquímica. El estudio citológico está especialmente indicado en el diagnóstico de recidivas. El diagnóstico diferencial debe incluir el grupo de tumores indiferenciados de células pequeñas y redondas.

Background: Helicobacter pylori infection is associated with low-grade gastric MALT lymphoma, and available data support that the eradication of the H. pylori can cause histological regression of the lymphoma. Patients and methods. Nine patients with low-grade gastric MALT lymphoma were treated with amoxicillin, metronidazole, and omeprazole for 14 days in a prospective study. Patients were followed up with sequential endoscopy, mapping gastric biopsies, and molecular studies with PCR amplification of the IgH gene in order to assess the response to H pylori eradication and the evolution of the histological and molecular responses. Results: H. pylori was eradicated in all patients and reinfections were not demonstrated. After H. pylori eradication treatment, the lymphoma regressed both endoscopically and histologically in eight of the nine patients (88.8%). In four of the eight histologically cured patients, no clonal band was detected by PCR; in the remaining four patients: PCR identified a clonal band, which disappeared in all patients after a mean of 12 ± 4 months. No clonal band was detected by the PCR analysis in any of the eight patients with histological regression after a median of 7 ± 6 months (range 1-20). The seven followed-up patients have a persistent clinical and histological remission after a median of 14 ± 5 months. Conclusions: (1) Low-grade gastric MALT lymphoma can be histologically cured with eradication therapy for H pylori. (2) After histological regression, PCR amplification of the IgH gene can identify an eventually persisting clonal population. (3) Sequential histological and molecular studies are essential for the assessment of the evolution of the lymphoma. (4) The clonal population tends to disappear, but its disappearance may be delayed for months. (5) Patients with histological regression but with a persistent clonal band should not be treated unless the lymphoma can be histologically demonstrated. All these observations suggest that gastric lymphoma can be effectively cured, but the ultimate fate of these patients is unknown until long-term follow-up studies are available.

Nonspecific cutaneous xanthomas have been reported in a variety of lymphocytic neoplastic processes, but to date only three cases of xanthomatous lesions associated with monocytic leukaemias have been described. We now report a patient with a chronic myelomonocytic leukaemia (CMML) associated with these lesions. The clinical and immunohistochemical features do not correspond to any entity previously described and suggest that xanthomas are a cutaneous expression of the CMML. Blood monocytic dyscrasias may be associated with specific cutaneous changes, the most characteristic being the plum-coloured nodules of acute monocytic leukaemia. Nonspecific cutaneous xanthomas have been reported with a variety of leukaemias, lymphomas and myeloma,' but specific cutaneous xanthomatous lesions are rarely noted in association with monocytic leukaemia. A case of these lesions associated with a primary monocytic myeloproliferative disorder is now reported.

Transformation of CLL into a large cell lymphoma has an incidence of 3-5%. We have studied 101 cases of CLL treated with fludarabine over a 10-year period (1990-2000) and observed a 12% incidence of transformation. In six of 12 patients, transformation was documented within 4 months following treatment with fludarabine. Pathological material, available in nine cases, was investigated for latent EBV by staining for LMP-1 by immunohistochemistry and EBERs-1 and 2 by in situ hybridisation. LMP-1 and EBERs were demonstrated in three of the nine samples. In two cases there was a different pattern of immunoglobulin gene rearrangement in the transformed cells assessed by PCR (FR3 fragment) compared to the original CLL clone. One of these two cases showed evidence of latent EBV. The other seven cases, of which two were EBV positive, showed identical pattern of Ig gene rearrangement in both the CLL and the transformed cells. We suggest that the relatively high incidence of transformation in this series may be due to immunosuppression mainly related to fludarabine, although other agents and prior therapies may have also contributed.

Thyroid-infiltrating B (Thyr-B) lymphocytes are thought to play an important role in the pathogenic mechanisms underlying Graves' disease.In this study, a broad phenotypic analysis of these cells has been performed in 15 consecutive patients who underwent thyroidectomy.Data reveal the occurrence of two distinct types of Thyr-B cell infiltrates. Type 1 was present in most of the cases (10/15) and consisted of a combination of IgM+ IgD(low to-) B lymphocytes showing features of marginal zone B cells, and IgG+ classic memory B cells. In contrast, in 5 of the 15 cases, a second type of Thyr-B cell infiltrate occurred, exhibiting the profile IgM- IgD- CD44(low to-) CD38++ CD71+ CD95+. This phenotype is highly suggestive of germinal center (GC) B cells, a finding not always anticipated from routine histologic examination. The presence of these ectopic GC was closely associated with the elevated serum level of anti-thyroid peroxidase (TPO), but not with anti-thyrotropin receptor (TSHR), autoantibodies. Moreover, local active anti-thyroglobulin (Tg) antibody secretion was only detected in cultures of type 2 Thyr-B cells.These findings indicate that high titers of anti-TPO, but not anti-TSHR antibody, might be associated with intrathyroidal GC development.

We present the final band-merged European Large-Area ISO Survey (ELAIS) Catalogue at 6.7, 15, 90 and 175 μm, and the associated data at U, g′, r′, i′, Z, J, H, K and 20 cm. The origin of the survey, infrared and radio observations, data-reduction and optical identifications are briefly reviewed, and a summary of the area covered and the completeness limit for each infrared band is given. A detailed discussion of the band-merging and optical association strategy is given. The total Catalogue consists of 3762 sources. 23 per cent of the 15-μm sources and 75 per cent of the 6.7-μm sources are stars. For extragalactic sources observed in three or more infrared bands, colour-colour diagrams are presented and discussed in terms of the contributing infrared populations. Spectral energy distributions (SEDs) are shown for selected sources and compared with cirrus, M82 and Arp220 starburst, and active galactic nuclei (AGN) dust torus models. Spectroscopic redshifts are tabulated, where available. For the N1 and N2 areas, the Isaac Newton Telescope ugriz Wide Field Survey permits photometric redshifts to be estimated for galaxies and quasars. These agree well with the spectroscopic redshifts, within the uncertainty of the photometric method [∼ 10 per cent in (1 + z) for galaxies]. The redshift distribution is given for selected ELAIS bands and colour-redshift diagrams are discussed. There is a high proportion of ultraluminous infrared galaxies (log 10 of 1-1000 μm luminosity L ir > 12.22) in the ELAIS Catalogue (14 per cent of 15-μm galaxies with known z), many with Arp220-like SEDs. 10 per cent of the 15-μm sources are genuine optically blank fields to r′ = 24: these must have very high infrared-to-optical ratios and probably have z > 0.6, so are high-luminosity dusty starbursts or Type 2 AGN. Nine hyperluminous infrared galaxies (L ir > 13.22) and nine extremely red objects (EROs) (r - K > 6) are found in the survey. The latter are interpreted as ultraluminous dusty infrared galaxies at z ∼ 1. The large numbers of ultraluminous galaxies imply very strong evolution in the star formation rate between z = 0 and 1. There is also a surprisingly large population of luminous (L ir > 11.5), cool (cirrus-type SEDs) galaxies, with L ir - L opt > 0, implying A v > 1.

We present a retrospective series of 27 nasopharyngeal carcinomas, selected from those attended at Ramón y Cajal Hospital between 1977 and 1996, with the aim of review the role of the study of Epstein-Barr virus in the diagnostic process of nasopharyngeal carcinoma. Twenty-seven patients, ranging from 14 to 81 years, with an average age of 50 years were selected. Male/female ratio was 1,7. All but one case were Caucasian. A neck mass was the first symptom in 40% of cases, with a mean diagnostic delay of 17 months. Only 8 cases (23%) did not exhibit neck nodes at the moment of diagnosis. CT and MRI were essential to establish staging: 5 stage I, 7 stage II and 15 stage IV, due to regional extension and/or bone erosion. Radiotherapy was employed in all cases, helped by chemotherapy in 20% of them. With a mean follow-up of 62 months, 5-years survival was 32% (IC 14,06-52,09). Of 27 cases of nasopharyngeal carcinoma 4 were differentiated (type I), 2 moderately differentiated (type II) and 22 undifferentiated (type III). While LMP-1 was only expressed by 41% of cases, PCR detected Epstein-Barr virus genome in 26 cases (96%) and in situ hybridization for EBERs was positive in all cases. Thus, all nasopharyngeal carcinomas were related to Epstein-Barr virus. Expression of LMP-1 seemed to worse the prognosis of nasopharyngeal carcinoma.

We evaluated the association of nasopharyngeal carcinoma (NPC) and Epstein-Barr virus (EBV) in Spanish patients, and studied the expression of EBV products (latent membrane protein–1 [LMP-1] and ZEBRA proteins) by NPC cells and its possible prognostic value. In situ hybridization (ISH) for EBV-encoded nonpolyadenylated RNAs (EBERs) and immunohistochemical expression of LMP-1 and ZEBRA proteins by immunohistochemistry were examined in formalin-fixed, paraffin-embedded NPC specimens from 30 patients, and a survival analysis was done by the Kaplan-Meier method. We detected EBERs by ISH in 96.67% of the NPC cases, and detected expression of LMP-1 in 43.33% of the NPC cases and expression of ZEBRA protein in 6.67% of the NPC cases. We conclude that ISH for expression of EBERs is an adequate method for detection of EBV in NPC. LMP-1 is not frequently expressed in NPC cells (43.33%). Most NPC cells carry a latent EBV infection. LMP-1 expression might have worsened the prognosis of NPC in our series.

Most cases of gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphoma are associated with H. pylori. In localized disease (stage I), eradication of H. pylori can result in histologic regression of the lymphoma in 50% to 100% of the patients. Moreover, in half of the apparently cured patients a monoclonal rearrangement of the IgH gene can be demonstrated. However, data on the long-term outcome of the patients are scarce. We report the evolution of a series of patients followed-up since 1994 in order to evaluate the long-term outcome of the apparently cured lymphoma.From January 1994 to July 2000, 19 consecutive patients with stage I gastric low grade MALT lymphoma were sequentially studied in our hospital. They had all been diagnosed by endoscopy and had had a complete staging (including CT-scan, contrast X-ray of the small bowel, bone marrow biopsies, immunophenotyping of bone marrow and peripheral blood and, in the later years, endoscopic ultrasonography). Diagnosis required established histologic criteria for low grade MALT lymphoma in the samples obtained by endoscopy. The investigation of H. pylori status included histologic search, serology and breath test urea-(13)C. Only patients in stage I disease associated with H. pylori were included in the study. Patients received standard triple therapy for eradication of H.pylori and after treatment were sequentially followed-up with endoscopies performed every 2-3 months in the first year, every 6 months in the second year and then yearly. Post-treatment biopsies were obtained by endoscopy for histologic studies, H. pylori cultures and molecular studies. The criteria of Wotherspoon et al. were used for the histological evaluation. Molecular studies were performed with a polymerase chain reaction analysis of the IgH gene using semi-nested procedures with consensus primers for the V(H) (Fr3A/Fr2A) and J(H) (LJH and VLJH) regions.After the eradication treatment, 18 of the 19 patients (94.7%) achieved histologic regression of the MALT lymphoma that occurred after a mean of 4.6 months (range 2-19). In 11 of the 18 histologically cured patients (61%) a monoclonal rearrangement of the IgH gene was demonstrated. In 2 patients the monoclonality disappeared completely, but 9 of the 11 patients (82%) had either persistent (3 patients) or intermittently persistent (5 patients) monoclonality for as long as 64 months. None of the patients who achieved a histologic remission (either with or without monoclonality) relapsed after a mean follow-up of 37 months (range 2-78). Two patients were lost to follow-up and another patient died of a gastric carcinoma; the remaining 15 patients are still in histologic remission after a mean period of 43 months (range 5-78). Ten patients studied between 1994 and the end of 1996 are in remission after a mean of 59 months (range 33-78).In most cases of gastric low-grade MALT lymphoma in stage I eradication of H. pylori can produce histologic regression of the lymphoma and this regression can be maintained for years. However, IgH gene monoclonality can be detected and persists in most cases. Although this persistent monoclonality seems to indicate the presence of a latent lymphoma population, over a period of 6 years it has not so far influenced the outcome. These findings indicate that in cases of localized gastric low-grade MALT lymphoma associated with H. pylori, the first step of treatment should be eradication of the H. pylori; however, a close and long follow-up is essential to determine the ultimate outcome of these patients and the possible significance of the persistent monoclonality.

We present a retrospective series of 16 cases of undifferentiated squamous carcinoma in cervical metastatic nodes of unknown primary. We review their clinical and radiological evaluation in search of a possible primary tumor, their response to treatment and the eventual development of a primary tumor. Furthermore, we study the presence of Epstein-Barr virus in the metastases as a predictor of their nasopharyngeal origin, in relation to the finding of primary lesions in the nasopharynx during further follow-up of the cases.

Recently lymphomas arising primarily in serosal surfaces have been found in patients with advanced acquired immunodeficiency syndrome (AIDS), but they very rarely seem to occur in human immunodeficiency virus (HIV)-negative patients. Studies on a subset of these lymphomas suggested that they represent a distinct entity associated with Kaposi's sarcoma-associated herpesvirus or human herpesvirus 8 (HHV-8).An 83-year-old, HIV-negative male was admitted to the hospital with a massive pleural effusion. Abdominal and chest computed tomographic scanning was normal. Cytologic analysis of the pleural effusion revealed a large cell, non-Hodgkin's lymphoma. Polymerase chain reaction analyses on genomic DNA from the pleural effusion demonstrated the presence of HHV-8 sequences in the absence of Epstein-Barr virus.It is possible and advantageous to diagnose body cavity-based lymphoma with a combination of cytologic, immunocytochemical and molecular studies of the pleural effusion in conjunction with clinical and radiographic information.

SUMMARY Human MM is a haematologic disorder characterized by the accumulation of malignant plasma cells (PC), primarily in the bone marrow (BM). Although these cells characteristically home to the BM, in recent years several groups have detected the presence of related malignant B cells in the peripheral blood (PB) which could be implicated in the progression and spread of the disease. However, the proportion and origin of these clonotypic circulating B cells is still controversial. In this study, using a triple-staining flow cytometric procedure and a whole blood lysis method, PB B lineage cells could be divided into two populations according to their distinct repertoires of cell adhesion molecules and B cell antigens in untreated MM patients. The results show that: (i) the percentage and the absolute number of PB CD19+ B cells were decreased in MM patients compared with controls; (ii) the quantity and percentage of B cell antigens (CD20, CD22, CD24, DR, CD138) and adhesion molecules (β1- and β2-integrins, CD44, CD54, CD56, CD61 and CD62L) expressed by these PB CD19+ cells of MM patients and healthy subjects were similar and all of them were virtually polyclonal cells; (iii) a very minor circulating CD19− CD38++ CD45−/dim subset was also detected which expressed CD138 (B-B4) (high intensity), monoclonal cytoplasmic immunoglobulin (cIg), and was negative for pan-B antigens (CD19, CD20, CD24, DR), surface immunoglobulin (sIg) and several adhesion molecules such as CD62L, CD18 and CD11a; this CD19−CD38++ CD45−/dim CD138++ subset was not found in normal blood and exhibited a phenotypic profile which was closely related to that of malignant BM plasma cells, with the exception of the CD56 antigen. Polymerase chain reaction (PCR) analysis of IgH clonotypic rearrangements confirmed these results. We postulate that, in MM patients, circulating B lineage cells may be divided into two different categories: polyclonal CD19+ B cells and a very minor proportion of clonal CD138++ PC that escape from the BM.

The aim of the present study was to explore the diagnostic value of the immunophenotypic analysis of bone marrow mast cells (BMMC) in indolent systemic mast cell disease (SMCD) patients. For that purpose, a total of 10 SMCD patients and 19 healthy controls were analyzed. Our results show that BMMC from SMCD are different from normal BMMC with regard to both their light scatter and immunophenotypic characteristics. Accordingly, forward light scatter (FSC), side (90 degrees) light scatter (SSC), and baseline autofluorescence levels were higher in BMMC from indolent SMCD patients than they were in control subjects. From the immunophenotypic point of view, the most striking findings were the constant expression of CD2 (P = .0001), CD25 (P = .0001), and CD35 (P = .06) molecules by BMMC from SMCD patients, markers that were absent from all normal controls. In contrast, CD71, absent in BMMC from indolent SMCD, was positive in BMMC from normal subjects. Although, slight differences between BMMC from SMCD patients and normal controls were found in several other markers, they did not reach statistical significance. In conclusion, our results show that simultaneous assessment of FSC/SSC and reactivity for the CD117, CD2, CD25, CD33, and CD35 forms the basis for the immunophenotypic characterization of BMMC from SMCD in adults and should be integrated with clinical and morphologic studies for the diagnosis of the disease.

AIM: To investigate the possibility of a correlation among microvessel density, p53 overexpression, and apoptosis in invasive breast carcinoma. METHODS: Microvessel density was analysed in 105 cases of invasive breast carcinoma by immunohistology using antifactor VIII related antibody. The results were correlated with the immunohistochemical expression of p53 and the apoptotic index, detected using the in situ end labelling of fragmented DNA method (TUNEL). Assessment was made with a CAS 200 image analyser. All these studies were performed on formalin fixed, paraffin wax embedded tissue sections of tumour samples. RESULTS: The mean (SD) microvessel count was 47.2 (51.1), with a range from 7 to 250. Thirty five (33%) carcinomas showed overexpression of p53 protein. The apoptotic index of tumours ranged from 0.0 to 28.0, with a mean (SD) of 1.7 (3.2). The results showed that there was a significant inverse correlation between microvessel density and p53 expression (p = 0.04; odds ratio, 0.37). In contrast, no correlation was identified between the microvessel density and apoptotic index. CONCLUSIONS: These results suggest that in invasive breast carcinoma the p53 overexpression phenotype downregulates tumour neoangiogenesis, as does the wild-type of p53 protein. In addition, they suggest that apoptosis and neoangiogenesis in these tumours are independent processes.

The aims of this study are to evaluate the frequency of clonal immunoglobulin heavy chain gene rearrangements in paraffin-embedded samples of Hodgkin's disease (HD) with use of the polymerase chain reaction method and to correlate the molecular findings with the histologic and immunocytochemical features. DNA extracts from paraffin-embedded sections from 212 HD samples were used for amplification of the IgH gene by use of framework 2 and framework 3 region primers. Immunohistochemical studies were performed on paraffin sections by use of monoclonal antibodies for CD20 and latent membrane protein-1 and polyclonal antibody for CD3. With use of both primer combinations, monoclonality was detected in 18.7% of lymphocyte-predominant HD cases and in 32.2% of classical HD cases. These results suggest that immunoglobulin heavy chain gene clonal rearrangements are relatively frequent in classical HD. In addition, the statistical analyses of the genotypic and immunocytochemical data revealed that the detection of B-cell populations is significantly associated with the expression of CD20 on HRS cells. There was, however, no correlation between the histologic subtype, the percentage of HRS cells, the presence of latent membrane protein-1 expression, and the molecular analysis results.

Nonspecific cutaneous xanthomas have been reported in a variety of lymphocytic neoplastic processes, but to date only three cases of xanthomatous lesions associated with monocytic leukaemias have been described. We now report a patient with a chronic myelomonocytic leukaemia (CMML) associated with these lesions. The clinical and immunohistochemical features do not correspond to any entity previously described and suggest that xanthomas is are a cutaneous expression of the CMML.

To assess the non-cutaneous involvement in primary B-cell non-Hodgkin's lymphoma (NHL) of the skin.Data from 45 patients with B-cell NHL of the skin were retrospectively analysed. The patients were diagnosed on histologic and immunocytochemical grounds between June 1977 and July 1993, and 14 cases were selected for their exclusively cutaneous initial involvement. Initial treatment, response to therapy, disease-free survival characteristics of relapse and therapeutic sequence were evaluated in every case.Cutaneous involvement presented as nodules or patches, on a single location, in 12 cases, or disseminated, in 2 others. No prognostic factor could be identified, and complete remission was attained in all cases. Cutaneous relapse was seen in 7 patients after 4 to 108 months since diagnosis. Extracutaneous dissemination was not seen in any case, and 13 patients are alive and disease-free. A 90 year-old woman died of toxic complications.The clinical facts reported here confirm the not too aggressive behaviour of certain B-cell cutaneous NHL, probably related with their origin on the skin itself.

Aims-To analyse the latent membrane protein-1 (LMP-1) gene in a series of patients with Epstein-Barr virus (EBV) positive LMP expressing ordinary and HIV associated Hodgkin's disease to detect possible genetic alterations and particularly the existence of deletions near the 3' end of the gene.Methods-Expression of the EBV LMP-1 was assessed using immunohistochemistry in 186 cases of Hodgkin's disease and 31 cases of HIV associated Hodgkin's disease. Genomic DNA was extracted from frozen lymph node biopsy specimens from 25 cases of Hodgkin's disease and 11 of HIV associated Hodgkin's disease, all of whom expressed the LMP-1 protein within diagnostic Hodgkin and Reed-Sternberg (HRS) cells, and amplified by polymerase chain reaction (PCR) using primers specific for the different LMP-1 regions.Results-LMP-1 expression was observed in 106 of 186 Hodgkin's disease cases and in all 31 HIV associated Hodgkin's disease cases. Molecular analysis of the LMP-1 gene showed a high degree of genetic heterogeneity in the carboxy-terminal domain compared with the prototype B95-8 EBV strain, specially in the patients with HIV associated Hodgkin's disease. Variation in the size of the repeated region was found in 17 of 25 Hodgkin's disease and nine of 11 HIV associated Hodgkin's disease cases. Deletions of 30 base pairs near the 3' end of the gene were detected in all cases of HIV associated Hodgkin's disease and in six Hodgkin's disease. In one case of Hodgkin's disease a larger deletion was observed. In all patients with LMP-1 deletion mutants, 50-90% of the diagnostic HRS cells expressed the LMP-1 protein.Conclusions-The presence of the 30 base pair deletion in all cases of HIV associated Hodgkin's disease supports previous studies that reported aggressive histological and clinical behaviour in tumours harbouring this deletion. This deletion may prolong the half-life of the protein which would explain the high levels of LMP-1 expressing HRS cells in those cases carrying LMP-1 deletions. That the 30 base pair deletion was present in all of the HIV associated Hodgkin's disease specimens suggests that impairment of immune function is a stringent requirement for the expansion of malignant cells infected by EBV strains containing the deleted LMP-1 gene.

We have correlated histologic type of Hodgkin's disease, degree of Hodgkin and Reed-Sternberg cell infiltration, percentage of Hodgkin and Reed-Sternberg cell positivity for latent membrane protein, immunophenotype of Hodgkin and Reed-Sternberg cells, and immunoglobulin heavy chain (IgH) gene rearrangements detected by polymerase chain reaction (PCR) in 56 unselected Hodgkin's disease cases. Two protocols were used for amplification of IgH gene using Fr2 or Fr3 V-region primers, in conjunction with nested primers directed to the JH region. PCR products were run on polyacrylamide gels. Immunohistochemical studies were performed on paraffin sections using monoclonal antibodies for CD20 and latent membrane protein, and polyclonal antibody to CD3. Using both primer combinations we detected a definitive clonal band in 23.2% of the Hodgkin's disease cases. Clonal IgH rearrangements were detected in 23.6% of nodular sclerosis type and in 28.5% of mixed cellularity type. Using a highly sensitive method such as PCR, more than 20% of unselected cases of Hodgkin's disease were found to contain B-cell clonal proliferations, but there was no correlation between histological and immunological parameters and molecular analysis results.

Lymphoid follicles are the main B-cell areas in peripheral lymphoid tissues. These structures commonly consist of germinal centre (GC) and mantle zone (MZ) regions. In the present work, human tonsillar B cells belonging to these two compartments were purified by a combination of density centrifugation and separation techniques involving the recognition by monoclonal antibodies of specific surface molecules followed by panning and magnetic bead selection. These purified populations were identified as GC and MZ cells by three different criteria: (1) GC cells showed the phenotype IgD- CD20+bright CD38+ CD44- and peanut agglutinin (PNA)+, and MZ cells were IgD+ CD20+dim CD38- CD44+ and PNA-; (2) morphologically, MZ cells appeared as small resting lymphocytes whereas GC cells consisted of large blastic cells of the germinal centre; (3) functionally, most GC, but not MZ, cells underwent apoptosis early in culture. The isolation of GC and MZ cells allowed the study of their proliferative response. As a result of these studies, GC cells were demonstrated to inhibit the proliferation of MZ cells in response to B-cell mitogens (Staphylococcus aureus Cowan I and anti-mu plus BCGF) in a concentration-dependent way; 50% inhibition was reached at a GC/MZ cell ratio of 1/2. This effect did not require GC-cell DNA synthesis since similar results were obtained with irradiated GC cells. Neither was it due to a non-specific toxic effect since GC cells did not alter the proliferative response of autologous T cells to mitogens (phytohaemagglutin and anti-CD3). The inhibition required cellular contact between GC and MZ cells, and was not restricted by histocompatibility barriers. These data suggest the possible existence of a new regulatory pathway within peripheral B-cell areas.

Pure red cell aplasia is manifested by unregenerative anemia with intense erythroid hypoplasia in the bone marrow and absolute reticulocytopenia. Its association with chronic myeloproliferative syndrome (CMS) is infrequent. The appearance of both processes may or may not be simultaneous and accidental association cannot be ruled out. Two cases of pure red cell aplasia were studied; one associated to Philadelphia positive chronic chromosome myeloid leukemia and the other associated to atypical CMS. In the first case no response was obtained with prednisone alone or associated to cyclophosphamide. In the second patient treatment with danazol was not efficient, however, corticotherapy produced a positive and maintained response. Treatment of pure red cell aplasia associated to CMS must be the same as that employed when this disease is presented as isolated or associated to other processes.

To investigate the results of the treatment of large-cell non-Hodgkin's lymphomas (LCNHL) with the MACOP-B chemotherapy protocol.20 patients with the following inclusion criteria were treated: LCNHL with a definite majority of large lymphoid cells and absence of previous therapy, HIV infection or severe underlying diseases.Three patients died during therapy and 15 (75%) achieved a complete remission. Actuarial survival after 36 months (0.66) was significantly better (p = 0.05) than that of a comparable historical series of LCNHL treated with CHOP (0.28). Age, stages III-IV, B symptoms, large lymphatic mass (LLM) and bone marrow infiltration did not negatively affect survival. The toxicity of the MACOP-B protocol was high: mucositis (65%), cytopenia (55%), neuropathy (40%), complications of steroid therapy (15%), and mortality directly related with therapy in 15%. Residual masses were found after therapy in 7% (70%) with BD, which were localized in lymphoid areas or in parenchyma (spleen and kidney). Surgical exploration showed that the residual masses were not tumoral in three cases, and in another three magnetic resonance suggested inactive disease.The MACOP-B protocol is highly effective for the treatment of LCNHL. The essential prognostic factor for survival in these NHL appears to be the cell composition with a great majority of large cells.

We report the case of a man with generalized osteosclerosis secondary to well-differentiated lymphocytic lymphoma. This finding is considered to be exceptional in this type of lymphoma, especially when other organs were not found to be involved. A year after the diagnosis was established the patient appeared to be in relatively good health. The radiological pattern showed no change from the original studies, nor was there any evidence of neoplastic involvement in any other location.

The experience of 22 Hodgkin's disease (HD) patients with human immunodeficiency virus type I (HIV) antibodies, collected from a cooperative study of six hospitals during 1984-1989 is presented. Young men (average age, 27.6 years) with a high incidence of intravenous drug abuse (86%) were found. The status of the HIV infection at diagnosis of HD was: four patients, acquired immune deficiency syndrome (AIDS); eight patients, persistent generalized lymphadenopathy (PGL); and ten patients, asymptomatic. The natural history of HD was unusual, with a high incidence of B symptoms (81%), advanced Stages III to IV (90%), bone marrow invasion (50%), cytopenias before treatment (45%), opportunistic infections (68%), and aggressive histologies. A decreased response to chemotherapy with poor marrow tolerance and a significant decrease in survival, 18 months, was observed. The AIDS and cytopenias pretreatment were associated with a shorter statistically significant survival, which defines the importance of immunodeficiency in HD prognosis. Complete remission after treatment was a factor that contributed to a longer statistically significant survival. The PGL or asymptomatic patients survived longer but also had a poor course, and five of them had AIDS criteria during evolution. A high incidence of HD in relation to non-Hodgkin's lymphoma (NHL) in patients with HIV infection in the six cooperating hospitals was found. Criteria for considering HD as an AIDS-associated lymphoproliferative disease in our environment are discussed.

Intracanalicular or intra-abdominal undescended testicles often present a difficult surgical problem, due to a vascular pedicle shortening that prohibits scrotal placement with a 1 stage orchiopexy. The division of spermatic vessels to properly place the testis in the scrotum solves the problem of the shortening of the vessels, but raises the question of whether the endocrine function and the potential for fertility are preserved. In the present study transection of spermatic vessels before arterial branch-off was done intra-abdominally in rats. Angiographic, patho-anatomic and hormonal evaluations have been made. Revascularization of the testicular artery through the vasal artery has occurred in all cases. The anastomotic circuit, however, does not always have the same functional value. The spermatogenic alterations suggest that fertility can be impaired in a significant percentage of cases. Spermatogenesis was quantified taking into account the mean tubular diameter and the situation of seminiferous epithelium, expressed as the percentage of tubules containing well-developed spermatogenesis. Plasma testosterone levels are in a low range. However, Leydig cell functional response to human chorionic gonadotropin stimulation is maintained in every case and so are plasma and pituitary luteinizing hormone levels, suggesting that plasma testosterone levels are high enough to maintain an adequate hormonal activity.