Retroperitoneal follicular dendritic cell sarcoma presenting as secondary amyloidosis.
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Adult↗
Biomedical subjects
L V Abruzzo
Publications and source records attributed to L V Abruzzo.
Identifying differentially expressed genes in cDNA microarray experiments.
A major goal of microarray experiments is to determine which genes are differentially expressed between samples. Differential expression has been assessed by taking ratios of expression levels of different samples at a spot on the array and flagging spots (genes) where the magnitude of the fold difference exceeds some threshold. More recent work has attempted to incorporate the fact that the variability of these ratios is not constant. Most methods are variants of Student's t-test. These variants standardize the ratios by dividing by an estimate of the standard deviation of that ratio; spots with large standardized values are flagged. Estimating these standard deviations requires replication of the measurements, either within a slide or between slides, or the use of a model describing what the standard deviation should be. Starting from considerations of the kinetics driving microarray hybridization, we derive models for the intensity of a replicated spot, when replication is performed within and between arrays. Replication within slides leads to a beta-binomial model, and replication between slides leads to a gamma-Poisson model. These models predict how the variance of a log ratio changes with the total intensity of the signal at the spot, independent of the identity of the gene. Ratios for genes with a small amount of total signal are highly variable, whereas ratios for genes with a large amount of total signal are fairly stable. Log ratios are scaled by the standard deviations given by these functions, giving model-based versions of Studentization. An example is given.
Analysis of Variance↗
A novel four-color PCR assay to assess T-cell receptor gamma gene rearrangements in lymphoproliferative lesions.
We describe a novel 4-color polymerase chain reaction (PCR) assay combined with GeneScan analysis to assess for T-cell receptor gamma chain gene (TCRgamma) rearrangements and evaluate its usefulness in 86 lymphoproliferative lesions. In this assay, each variable region (Vgamma) family primer is 5' end-labeled with a different fluorescent dye, allowing determination of the Vgamma family involved in each TCRgamma rearrangement. PCR products were analyzed by capillary electrophoresis. We detected clonal TCRgamma rearrangements in 60 (98%) of 61 T-cell lymphomas, 2 (15%) of 13 B-cell lymphomas, and 3 (25%) of 12 reactive lesions. These results compared favorably with conventional PCR methods using denaturing gradient gel electrophoresis, which revealed clonal TCRgamma rearrangements in 37 (90%) of 41 T-cell lymphomas, 1 (25%) of 4 B-cell lymphomas, and 2 (25%) of 8 reactive lesions. This 4-color PCR assay is at least equivalent to conventional PCR methods and is convenient, allows accurate size determination of TCRgamma rearrangements, and identifies the specific Vgamma family involved, providing more specific information about TCRgamma rearrangement.
Gene Rearrangement↗
Hepatosplenic gamma/delta T-cell lymphoma in bone marrow. A sinusoidal neoplasm with blastic cytologic features.
We report 8 cases of hepatosplenic T-cell lymphoma (HSTCL) involving bone marrow and correlate histologic findings with disease progression. Immunophenotypic analysis demonstrated mature, aberrant gamma/delta T-cell immunophenotypes. Isochromosome 7q was identified in 4 cases; 1 case showed the t(7;14)(q34;q13). Seven of 7 cases tested had monoclonal TCR gamma gene rearrangements. The initial diagnostic bone marrow biopsy specimens were hypercellular with a frequently subtle, predominantly sinusoidal infiltrate of atypical small to medium-sized lymphoid cells. In all cases, aspirate smears at diagnosis and in subsequent specimens contained malignant cells that resembled blasts, some with fine cytoplasmic granules. With progression, the pattern of HSTCL in bone marrow biopsy specimens became increasingly interstitial, and the neoplastic cells became larger. In aspirate smears, the proportion of blasts increased. Seven patients died; 1 was lost to follow-up. Autopsy performed on 1 patient demonstrated malignant cells within vascular channels in all organs sampled, with relatively little tumor formation, resembling intravascular lymphoma at these sites. HSTCL often can be recognized in bone marrow by its unique combination of a sinusoidal pattern in core biopsy specimens and blastic cytology in aspirate smears.
Adolescent↗
Cytogenetic findings in mantle cell lymphoma cases with a high level of peripheral blood involvement have a distinct pattern of abnormalities.
We compared conventional cytogenetic findings in mantle cell lymphomas (MCLs) having an absolute peripheral lymphocytosis of more than 10,000/microL (>10 x 10(9)/L) at diagnosis ("leukemic"; n = 30) with those in cases having no or minimal lymphocytosis ("nodal"; n = 19). Only cases positive for t(11;14) were included for study. Forty-six cases (94%) had abnormalities in addition to t(11;14). The most frequent abnormalities involved chromosome 13 (26 cases [53%]), followed by chromosomes 1, 3, 7, 8, 9, 10, 12, 15, 17, and 21 (11-18 cases [22%-37%]). There was no difference in the number of aberrations between the 2 groups. Abnormalities of chromosomes 17, 21, and 22 were more frequent, and breakpoints involving 8q24, 9p22-24, and 16q24 were found exclusively in leukemic MCL. Chromosome 17 aberrations involved were structural (breakpoints involving 17p13, 17p11.2, 17q) in leukemic MCL but were only numeric in nodal MCL. Thus, leukemic MCL differs from nodal MCL in their cytogenetic profiles, which may contribute to the clinical presentation.
Adult↗
Primary paratesticular lymphoma: a report of 2 cases and review of literature.
Non-Hodgkin lymphoma arising in the paratesticular organs without testicular involvement is rare. In most previously reported cases, the classification systems that were used are now outdated and/or immunologic studies were not done. We report the clinical and pathologic features of 2 cases of non-Hodgkin lymphoma arising in the epididymis and the spermatic cord. Patient 1 was a 35-year-old man who presented with a painless scrotal mass. Patient 2 was a 61-year-old man who presented with a right inguinal mass. Orchiectomy performed in both patients revealed a mass confined to the epididymis in patient 1 and to the spermatic cord in patient 2. Histologic examination in both cases revealed diffuse large cell lymphoma, and immunohistochemical studies supported B-cell lineage. Subsequent staging studies showed no other site of disease in patient 1 and an isolated mass anterior to the right psoas muscle in patient 2. Malignant lymphoma involving testicular adnexal structures without involvement of the testis is extremely uncommon. To our knowledge, only 6 cases confined to the epididymis and 12 cases confined to the spermatic cord have been reported previously.
Adult↗
Primary follicular large cell lymphoma of the testis in a child.
Primary follicular lymphoma of the testis in childhood is extremely rare. To our knowledge, only 5 cases have been reported to date. We report a case in a 6-year-old boy who presented with painless right scrotal enlargement. Right radical orchiectomy revealed a follicular large cell lymphoma with diffuse areas confined to the testis and epididymis, clinical stage IE. Immunohistochemical stains demonstrated that the neoplastic cells were of B-cell lineage, positive for CD10, CD20, CD79a, and BCL-6. Staining for CD21 accentuated networks of dendritic reticulum cells within the nodules. The cells were negative for BCL-2, p53, and T-cell antigens. There was no evidence of the t(14;18) detected by polymerase chain reaction. The data suggest that follicular lymphoma of the testis in children has a different pathogenesis than follicular lymphoma in adults.
Antineoplastic Combined Chemotherapy Protocols↗
Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines.
BACKGROUND: Human cancer cell lines grown in the presence of the cytotoxic agent mitoxantrone frequently develop resistance associated with a reduction in intracellular drug accumulation without increased expression of the known drug resistance transporters P-glycoprotein and multidrug resistance protein (also known as multidrug resistance-associated protein). Breast cancer resistance protein (BCRP) is a recently described adenosine triphosphate-binding cassette transporter associated with resistance to mitoxantrone and anthracyclines. This study was undertaken to test the prevalence of BCRP overexpression in cell lines selected for growth in the presence of mitoxantrone. METHODS: Total cellular RNA or poly A+ RNA and genomic DNA were isolated from parental and drug-selected cell lines. Expression of BCRP messenger RNA (mRNA) and amplification of the BCRP gene were analyzed by northern and Southern blot hybridization, respectively. RESULTS: A variety of drug-resistant human cancer cell lines derived by selection with mitoxantrone markedly overexpressed BCRP mRNA; these cell lines included sublines of human breast carcinoma (MCF-7), colon carcinoma (S1 and HT29), gastric carcinoma (EPG85-257), fibrosarcoma (EPF86-079), and myeloma (8226) origins. Analysis of genomic DNA from BCRP-overexpressing MCF-7/MX cells demonstrated that the BCRP gene was also amplified in these cells. CONCLUSIONS: Overexpression of BCRP mRNA is frequently observed in multidrug-resistant cell lines selected with mitoxantrone, suggesting that BCRP is likely to be a major cellular defense mechanism elicited in response to exposure to this drug. It is likely that BCRP is the putative "mitoxantrone transporter" hypothesized to be present in these cell lines.
Antineoplastic Agents↗
A multidrug resistance transporter from human MCF-7 breast cancer cells.
MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 655-aa [corrected] member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.
ATP Binding Cassette Transporter, Subfamily G, Mem↗
Epstein-Barr virus-related posttransplantation lymphoproliferative disorder involving pancreas allografts: histological differential diagnosis from acute allograft rejection.
The clinical and pathological features of acute pancreas allograft rejection and involvement of the graft by posttransplantation lymphoproliferative disorders (PTLD) overlap. Because the treatment is diametrically opposite in these two types of lesions, an accurate diagnosis is essential. The histological features in pancreas allograft needle biopsy specimens (n=7) and pancreatectomies (n=4) from four patients with Epstein-Barr virus (EBV)-related PTLD were compared with the material from 14 patients who did not develop PTLD after 12 to 58 months of follow-up and whose biopsy specimens (n=10) and pancreatectomies (n=10) showed rejection-related heavy or atypical inflammatory infiltrates. Features typical of rejection included most (>75%) being of mixed small and large, activated-appearing T lymphocytes, a smaller component of mature plasma cells, and variable numbers of eosinophils. Cytologically atypical cells were always a minority (< 10%). The inflammation involved the septal spaces with proportional involvement of the exocrine tissue, veins, ducts, and arteries. The inflammation was particularly targeted against the acini and was associated with acinar cell damage. Features characteristic of PTLD were nodular and expansile infiltrates, composed of a significant proportion of atypical, plasmacytoid B cells (40% to 70% of the infiltrate); Reed-Sternberg-like cells were noted in two patients. The infiltrates involved the parenchyma randomly with no apparent affinity for the acinar tissue. Extensive infiltration of the peripancreatic soft tissues was common. Arterial walls were not involved in PTLD unless there was concurrent acute vascular rejection. Features identified in both conditions were foci of necrosis and infiltration of venous walls with associated endotheliitis. Samples with concurrent PTLD and acute rejection showed combinations of these features. In situ hybridization for EBER (Epstein-Barr-encoded RNAs) was positive only in the samples from patients with PTLD. Based on the assessment of morphological differences and the selective use of relatively simple ancillary techniques, PTLD can be correctly diagnosed even in small tissue samples such as needle biopsy specimens. An early diagnosis will lead to the appropriate treatment.
Acute Disease↗
Posttransplantation lymphoproliferative disorder associated with OKT3 and decreased antiviral prophylaxis in pancreas transplant recipients.
Between September 1994 and October 1995, we diagnosed and treated four cases of early onset posttransplantation lymphoproliferative disorder (PTLD) occurring within 62 days of pancreas transplantation. The development of PTLD was associated with both a significantly higher total muromonab-CD3 (OKT3) dose and a lack of ganciclovir/acyclovir prophylaxis, but it was not associated with the total dose of antithymocyte globulin or cytomegalovirus serostatus. All four patients were treated aggressively and survived without evidence of recurrent PTLD more than 1.5 years later. We conclude that the use of a high total dose of OKT3 puts pancreas transplant recipients at increased risk for early onset PTLD, while ganciclovir/acyclovir prophylaxis may help to prevent this disorder; however, if early onset PTLD does occur in these patients, aggressive therapy can lead to a favorable outcome.
Acyclovir↗
Primary hepatic low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) associated with primary biliary cirrhosis.
We describe a case of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the liver of a patient with early-stage primary biliary cirrhosis (PBC). The patient, a 62-year old woman, presented with abnormal liver function tests, a positive antimitochondrial antibody titer (1:160), and a liver mass. The resected mass, 6.0 x 5.0 x 4.0 cm, had the features of MALT-type lymphoma. The neoplastic cells were small lymphoid cells of B-cell lineage that surrounded reactive lymphoid follicles and infiltrated bile ductules to form lymphoepithelial lesions. The uninvolved liver had histologic evidence of early stage PBC, characterized by segmental duct destruction with granulomata and an inflammatory infiltrate in the portal triads composed of lymphocytes, plasma cells, and occasional eosinophils. A periportal lymph node showed histologic features of the hyaline-vascular type of Castleman's disease, without evidence of malignant lymphoma. Low-grade B-cell lymphomas of the MALT type rarely arise in the liver and, to our knowledge, have not been reported previously in association with PBC. The association in this case suggests that chronic antigenic stimulation as a result of PBC induced the accumulation of acquired MALT, which subsequently transformed to low-grade B-cell lymphoma.
Female↗
Quantitative measurement of telomerase activity in lymphadenopathy: correlation with histologic features and human immunodeficiency virus-1 infection.
Telomerase is a ribonucleoprotein that uses its internal RNA component as a template for synthesis of telomeric DNA on the ends of chromosomes after each round of cell division. It is expressed in approximately 90% of all human cancers tested to date, as well as in most immortal cell lines. Recently, telomerase activity was detected in normal proliferating lymphoid tissue and in non-Hodgkin's lymphomas (NHLs) by use of the telomeric repeat amplification protocol assay, a qualitative measure of telomerase activity. In this study, we modified the assay to measure quantitatively the telomerase activity in lymph node biopsy specimens obtained from patients with lymphadenopathy. The lymph nodes either contained benign reactive changes, were involved by NHL of B-cell lineage, or were involved by Hodgkin's disease. Telomerase activity was detected in all of our samples, benign as well as malignant. The levels of activity were unaffected by the patient's human immunodeficiency virus-1 status. Although the specimens involved by NHLs showed a range in telomerase activity from low to high, the levels did not correlate strictly with the histologic grade according to the Working Formulation. All of the cases of Hodgkin's disease also expressed telomerase activity, and the levels were similar regardless of histologic subtype. Our results showed that telomerase activity was expressed in both benign and malignant lymphoproliferative processes.
Biopsy↗
Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gammadelta T cell lymphoma.
Malignant lymphomas often have complex, nonrandom chromosomal abnormalities. Hepatosplenic gammadelta T cell lymphoma (gammadelta TCL) is an unusual post-thymic T cell lymphoma that primarily involves liver and spleen, often in young adult males. Few cases have had cytogenetic analysis. We report a consistent isochromosome 7q [i(7q)] abnormality in three cases of hepatosplenic gammadelta TCL, one with i(7q) as the sole abnormality at presentation. Three patients, 15-, 37- and 65-year-old males, presented with hepatosplenomegaly and fevers. Histopathologic, immunophenotypic, and molecular genetic studies supported the diagnosis. Spleen, liver, and bone marrow contained sinusoidal infiltrates of atypical lymphoid cells of T cell immunophenotype. PCR performed on two cases demonstrated clonal T cell receptor gamma gene rearrangements. Cytogenetic analysis of bone marrow showed i(7q) as the sole abnormality at presentation in one case. The second case showed i(7q) in addition to two normal chromosomes 7, and other structural and numerical abnormalities. The third case showed i(7q) and a deletion in the long arm of chromosome 11. These findings support the proposal that i(7q) represents the primary nonrandom cytogenetic abnormality in hepatosplenic gammadelta TCL, and plays a role in its pathogenesis.
Adolescent↗
Histologically discordant lymphomas with B-cell and T-cell components.
We describe the clinical, histologic, immunophenotypic, and genotypic features of five cases of histologically discordant lymphomas with B-cell and T-cell components. Three patients presented with B-cell lymphoma; T-cell lymphoma subsequently developed. One patient presented with T-cell lymphoma; B-cell lymphoma subsequently developed. One patient presented with synchronous B-cell and T-cell lymphomas. There were three men and two women. The median age at the initial diagnosis of lymphoma was 66 years. The mean interval between the development of the two lymphomas was 83 months. All patients died of disease. The mean survival was 96 months after the initial diagnosis of lymphoma and 14 months after the diagnosis of the histologically discordant lymphoma. Epstein-Barr virus was found in two cases--the B-cell lymphoma in the patient who presented with synchronous lymphomas, and the subsequent T-cell lymphoma in one of the patients who presented with B-cell lymphoma. Based on the results of immunophenotypic and genotypic analyses, these cases likely represent the occurrence of two distinct lymphoid neoplasms rather than histologic progression of the same neoplastic clone. Furthermore, a subset of these cases are Epstein-Barr virus-associated.
Adult↗
Enhancer activity of upstream hypersensitive site 2 of the chicken beta-globin cluster is mediated by GATA sites.
Upstream of the chicken beta-globin gene cluster are four DNase I-hypersensitive sites (HS1-4). Hypersensitive sites located upstream of the mammalian beta-globin clusters have enhancer activity and mediate position-independent gene expression. In contrast, a region inside the chicken cluster has enhancer activity and mediates position-independent expression. Here we investigate the function of the chicken upstream sites, which are different from the mammalian ones in sequence, number, and distance from the genes. Each was tested for its effect on reporter gene expression in transfected primary erythroid cells. HS2 and HS3 (4.4 and 6.4 kilobases upstream of rho-globin) showed significant enhancer activity while HS1 and HS4 (1.6 and 11 kilobases upstream of rho-globin) did not. A 237-base pair region of HS2 contained the sequences necessary for enhancer activity. Proteins from erythroid extracts bound HS2 in seven different regions; six of these sites were characterized. GATA-1 bound to four of the sites. Each site contributed to the enhancer activity of HS2. Two other sequences bound proteins that may be related to Sp1 and erythroid krüppel-like factor. Surprisingly, mutations in these elements, which disrupted protein binding, did not affect enhancer activity. Thus, the observed enhancer activity of HS2 is due to the four GATA sites. The existence of multiple GATA sites in both chicken HS2 and the mammalian upstream sites may be due to evolution from a common element with preservation of only very short sequences or to convergent evolution. These observations highlight the crucial role for GATA proteins in globin regulation.
Amino Acid Sequence↗
Expression and regulation of macrophage inflammatory protein-1 alpha by murine alveolar and peritoneal macrophages.
A number of disease states are characterized by the accumulation of inflammatory cells at the site of tissue injury. Mononuclear phagocytes (M phi) represent key cellular mediators of inflammation via the production of regulatory and chemokinetic cytokines. One such cytokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha), has been shown to be one of the major inducible chemotaxins expressed from murine macrophage cell lines (RAW 264.7). We postulated that MIP-1 alpha is a major monocyte chemoattractant produced by resident M phi, and the magnitude of production of this chemotaxin may depend upon the specific population of M phi studied. To test this hypothesis, we isolated alveolar macrophages (AM phi) and peritoneal macrophages (PM phi) from CD-1 mice by bronchoalveolar and peritoneal lavage, respectively. Recombinant murine MIP-1 alpha accounted for significant neutrophil chemokinetic rather than chemotactic activity, as assessed by checkerboard analysis. LPS-stimulated AM phi-derived monocyte chemotactic activity (MCA) was significantly neutralized by specific rabbit anti-murine MIP-1 alpha serum. In contrast, PM phi-derived conditioned media failed to produce MCA attributable to MIP-1 alpha. The production of MIP-1 alpha was then characterized from both AM phi and PM phi. While unstimulated AM phi and PM phi failed to express MIP-1 alpha mRNA, both AM phi and PM phi challenged with lipopolysaccharide (LPS) expressed MIP-1 alpha mRNA in a time-dependent fashion.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
B-cell lymphoma after angioimmunoblastic lymphadenopathy: a case with oligoclonal gene rearrangements associated with Epstein-Barr virus.
We describe a patient with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), who subsequently developed large-cell immunoblastic lymphoma of B-cell immunophenotype. At the time of the initial diagnosis, histologic examination of an inguinal lymph node showed typical features of AILD, and there was no evidence of a monoclonal B-cell population by immunohistochemical analysis. In situ hybridization and Southern blot analysis for Epstein-Barr virus (EBV) were negative. At autopsy 2 years later, the patient had widespread lymph node and organ involvement by large-cell immunoblastic lymphoma of B-cell immunophenotype. Southern blot analysis performed on DNA extracted from lymph nodes, liver, and spleen showed two patterns of Ig heavy chain and kappa light chain gene rearrangements. The T-cell receptor beta chain gene was in the germline configuration. Analysis with an EBV terminal repeat region probe showed two clonal populations that paralleled the Ig gene rearrangement studies. Double-labeling immunohistochemistry and in situ hybridization confirmed the presence of EBV within the neoplastic B cells. The data support the hypothesis that EBV was not etiologically related to AILD in this case, and that EBV proliferation may occur after the onset of the disease. Further, the data suggest that some B-cell lymphomas that arise in the setting of AILD resemble EBV-associated B-cell lymphomas that arise in other immunodeficiency states.
Blotting, Southern↗