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PubMed1991

Ki-1+ anaplastic large-cell lymphoma of T-cell origin in an HIV-infected patient.

Non-Hodgkin's lymphomas (NHL) are part of the spectrum of disease associated with HIV infection. However, there are only occasional reports of NHL of T-cell origin in HIV-infected patients. A previously asymptomatic HIV-infected man, who was seronegative for human T-lymphotropic virus type I antibodies, developed a high-grade peripheral T-cell lymphoma of anaplastic large-cell type which was Ki-1 + (CD30 +), HLA-DR+, epithelial membrane antigen +, CD25 +, CD71 +, CD2 + and CD5 +. Pan-B markers CD19 and CD22 and histiocytic marker CD68 were negative. At diagnosis the patient had 0.3 x 10(9)/l T-helper lymphocytes. The response to chemotherapy was dramatic and the patient is alive and disease-free 18 months after treatment. A review of previously described peripheral T-cell lymphomas in HIV-positive individuals is performed, and we conclude that the spectrum of neoplasms in such cases is probably broader than originally thought.

Adult↗

PubMed1994

The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin.

The expression of the murine double minute-2 (MDM2) gene, the product of which binds to and inactivates p53, was studied in 60 patients with B-cell chronic lymphocytic leukemia (B-CLL) or non-Hodgkin's lymphoma (B-NHL). Northern blot analysis showed that the level of MDM2 gene expression was low in normal human B-cells, whereas 17 of the patients (28.3%) with B-CLL or NHL had more than 10-fold higher levels of MDM2 gene expression than that observed in normal B cells. Immunohistochemical analysis confirmed MDM2 overexpression at the cellular protein level. MDM2 gene overexpression was found more frequently in patients with the low-grade type of lymphoma (56.5%) than in those with intermediate-/high-grade types (10.8%) (P = .001). Moreover, MDM2 overexpression was found significantly more frequently in patients at advanced clinical stages. Simultaneous analysis of p53 gene mutation showed that three patients had both MDM2 gene overexpression and p53 gene mutation. The results of the present study suggest that MDM2 gene overexpression may play an important role in the tumorigenicity and/or disease progression of CLL and low-grade lymphomas of B-cell origin.

Adult↗

PubMed2002

Epstein-barr virus-associated non-Hodgkin's lymphoma of B-cell origin, Hodgkin's disease, acute leukemia, and systemic lupus erythematosus: a serologic and molecular analysis.

Parallel studies of (a) patients with Epstein-Barr virus (EBV)-associated peripheral T-cell proliferative disease/lymphomas and (b) a group of patients with a prolonged fever from other causes were conducted at Songklanagarind University Hospital from 1997 through 2000. (Reports on EBV-associated peripheral T-cell and NK-cell proliferative disease/lymphomas have been published elsewhere) In this study, the authors identified 58 patients; 14 were non-Hodgkin's lymphoma of B-cell origin (NHL-B), 8 were Hodgkin's disease, 6 were acute leukemia, 9 were systemic lupus erythematosus (SLE), and 21 were patients with other diseases. Serologic tests for the EBV infection, the study of EBV genome in circulating non-T-cells (CD3-cells) and T-cells (CD3+ cells), and the EBV-RNA study in the tumor cells were performed. EBV internal repeat-1 region (IR-1) in peripheral blood CD3+ cells was detected in 10 of 14 patients (71.5%) with NHL-B, 3 of 8 patients (37.5%) with Hodgkin's disease, 1 of 6 patients (16.7%) with acute leukemia, 4 of 9 patients (44.5%) with SLE, and was not detected in any of the 21 patients with other diseases. Anti-viral capsid antigen-IgG was significantly elevated in hematologic malignancy patients with EBV IR-1 genome in the peripheral blood CD3+ cells when compared to hematologic malignancy patients with a negative result, whereas there was no significant difference in anti-EBV nuclear antigen among these two groups. EBV-RNA expression in tumor cells by in situ hybridization was detected in 4 of 13 patients (31%) with NHL-B (all showed EBV IR-1 genome in peripheral blood CD3+ cells), and 3 of 5 patients (60%) with Hodgkin's disease (only two showed EBV IR-1 genome in peripheral blood CD3+ cells). These data support the theory that chronic EBV infection is often found in association with cases of NHL-B, Hodgkin's disease, acute leukemia, and SLE.

Adolescent↗

PubMed1984

Single cell origin of multilineage colonies in culture. Evidence that differentiation of multipotent progenitors and restriction of proliferative potential of monopotent progenitors are stochastic processes.

In this paper, we report analysis of differentiation in human hemopoietic colonies derived from a single cell. Cord blood mononulear cells and panned My-10 antigen-positive bone marrow and cord blood cells were plated in methylcellulose medium containing erythropoietin and conditioned medium. Initially, we performed mapping studies to identify candidate colony-forming cells. Subsequently, using a micromanipulator, we transferred single cells individually to 35-mm dishes for analysis of colony formation. Cellular composition of the colony was determined by identifying all of the cells in the May-Grunwald-Giemsa stained preparation. Of 150 single candidate cells replated, 63 produced colonies. The incidences of single lineage colonies included 19 erythroid, 17 monocyte-macrophage, and 9 eosinophil colonies. There were 18 mixed hemopoietic colonies consisting of cells in two, three, four, and five lineages in varying combinations. In some instances, we noted the predominance of one lineage and the presence of very small populations of cells in a second or third lineage. These results provide evidence for the single-cell origin of human multilineage hemopoietic colonies, and are consistent with the stochastic model of stem cell differentiation in man. They also indicate that restriction of the proliferative potential of committed progenitors is a stochastic process.

Bone Marrow Cells↗

PubMed1994

Morphological and immunohistochemical support for the interstitial cell origin of oestrogen-induced kidney tumours in the Syrian golden hamster.

The oestrogen-induced kidney tumour of the Syrian golden hamster has been extensively used not only as a model for renal carcinogenesis, but also for hormonal carcinogenetic studies. In spite of all the different approaches, its histogenesis remains unresolved. The two classical hypotheses are an epithelial origin (in the proximal convoluted tubules) or a mesenchymal-blastemal origin (in the interstitial cells). In the present study two types of preneoplastic lesions were seen: tubular dysplasia and interstitial cell hyperplasia. The first neoplastic stage consisted of interstitial or blastemal cells aggregated in the form of microscopic nodules (tumourlets). In the more advanced tumours the blastemal pattern was the more predominant, but we also observed other patterns of epithelial, mesenchymal or neural types. These findings were confirmed by ultrastructural analysis, which revealed blastemal-epithelial transitions and mesenchymal and mesonephric features, as well as the presence of neurosecretory granules. The paucity of immunohistochemical studies on these tumours led us to apply a panel of the most frequently used antibodies in diagnostic pathology to 36 cases of our series. There was co-expression of cytokeratins and vimentin, which were the most intensely stained, together with S-100 protein. Further positivities were seen for carcinoembryonic antigen, desmin, neuron-specific enolase and HNK-1. These results lend support to the revised, new histological classification confirmed by the ultrastructural findings, allowing us to postulate a tumoural origin in the renal interstitial cells, which may be nephrogenic undifferentiated cells that possess an epithelial, mesenchymal and neuroectodermal phenotype.

Animals↗

PubMed1990

[A case report of phylloides tumor of the prostate: review of the literature and analysis of bizarre giant cell origin].

A case of phylloides tumor of the prostate in a 58-year-old male is presented. The tumor was composed of columnar cystic folds and pleomorphic stromal elements including bizarre giant cells. Electron microscopic examination, which was performed using specimens embedded in paraffin blocks, revealed that the bizarre giant cells originated from the smooth muscle. The postoperative course was uneventful, with no evidence of local recurrence or metastasis for more than 2 years after operation.

Giant Cells↗

PubMed1997

S-100 protein is a differentiation marker in thyroid carcinoma of follicular cell origin: an immunohistochemical study.

S-100 protein, a dimer of S-100 alpha and S-100 beta subunits (S-100 alpha and S-100 beta), is widely distributed in human tissue, and several papers describing S-100 protein expression in follicular cells of the thyroid have been published. In the present study, 105 cases of thyroid carcinoma (of which 96 were papillary, four follicular, two undifferentiated, and three medullary) were analyzed immunohistochemically for the expression of S-100 protein, S-100 alpha, S-100 beta, and thyroglobulin. In papillary carcinoma, 188 lesions were studied and classified into well differentiated types (56 papillary, 45 follicular) and poorly differentiated types (41 trabecular, four solid, eight squamoid, three tall, and one insular), because the histological structure of each tumor was heterogeneous. The percentage of lesions which expressed positively for S-100 protein and S-100 alpha, respectively, according to type were: papillary, 96 and 99%; follicular, 96 and 100%; trabecular, 95 and 100%; solid, 50 and 50%; squamoid, 50 and 75%; and tall, 33 and 100%. The insular type was negative for both. For papillary carcinoma, well differentiated lesions showed stronger S-100 alpha expression than poorly differentiated lesions. S-100 alpha expression was weaker in follicular and undifferentiated carcinoma than in papillary carcinoma. Medullary carcinoma also expressed S-100 alpha. S-100 beta was positive in lesions that expressed S-100 alpha strongly. Expression of S-100 protein and S-100 alpha protein correlated with thyroglobulin synthesis in the follicular cells. It was concluded that S-100 protein, mainly S-100 alpha, exists in thyroid follicular cells, that it exists in higher quantity in most of the well differentiated lesions but in lower quantity in poorly differentiated or undifferentiated lesions, and that S-100 protein, especially S-100 alpha, is a differentiation marker in carcinoma of thyroid follicular cell origin.

Adenocarcinoma, Follicular↗

PubMed1998

Establishing germ cell origin of undifferentiated tumors by identifying gain of 12p material using comparative genomic hybridization analysis of paraffin-embedded samples.

An estimated 10% of adult cancer patients present with undifferentiated carcinoma. The diagnosis of germ cell tumor (GCT) in such patients can be difficult but has important implications for patient management. Male testicular GCT is characterized by an isochromosome 12p, i(12p), or additional 12p material, in some cases restricted to the 12p11.2-p12.1 region. A gain of 12p material can indicate that a tumor, which may not be present in the testis, is of germ cell origin. Formalin-fixed, paraffin-embedded samples are the most widely available material for diagnostic analysis and retrospective studies. We have compared the identification of 12p gain in snap-frozen samples with corresponding paraffin-embedded material from three clearly defined testicular GCTs using comparative genomic hybridization analysis. In this preliminary study, paraffin-embedded tumor samples of uncertain histogenesis from seven patients were then analyzed. Tumor samples from three of these patients showed a gain of 12p material, and in one patient, gain was restricted to the 12p11.2-p12 region. The clinical picture and response to therapy were generally consistent with the 12p status, though lack of 12p gain may not exclude a diagnosis of GCT.

Adenocarcinoma↗

PubMed1985

Improved synthesis of 2'-deoxyformycin A and studies of its in vitro activity against mouse lymphoma of T-cell origin.

7-Amino-3-(2'-deoxy-beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine (2'-deoxyformycin A) was synthesized from formycin A by a sequence consisting of (i) 3',5'-cyclosilylation with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane, (ii) 2'-acylation with phenoxythiocarbonyl chloride and 4-(N,N-dimethylamino)pyridine, (iii) N-trimethylsilylation with hexamethyldisilazane, (iv) reduction of the 2'-O-phenoxythiocarbonyl group with tri-n-butyltin hydride, and (v) desilylation with tetra-n-butylammonium fluoride. 2'-Deoxyformycin A was a potent inhibitor of the in vitro growth of S49 lymphoma, a murine tumor of T-cell origin. The IC50 of 2'-deoxyformycin A against S49 cells was 10-15 microM, whereas that of 2'-deoxyadenosine (dAdo) under the same conditions (72-h incubation in medium containing heat-inactivated horse serum) was 180 microM. In the presence of 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) to block intracellular adenosine deaminase (ADA) activity, 2'-deoxyformycin A and dAdo both gave IC50's of 5-10 microM. When assayed against a mutant S49 subline lacking adenosine kinase (AK) or a subline with a combined deletion of AK and deoxycytidine kinase (dCK), 2'-deoxyformycin A in combination with 10 microM EHNA was inactive at concentrations of up to 50 microM. Similar lack of activity against kinase-deficient cells was shown by formycin A. Thus, phosphorylation of 2'-deoxyformycin A appears to be required for biological activity and is probably catalyzed by AK rather than dCK. 2'-Deoxyformycin A and related 2'-deoxyribo-C-nucleoside analogues of the purine type may be of interest as potential T-cell specific cytotoxic agents.

Adenosine Kinase↗

PubMed1982

Report of a case of non-Hodgkin's lymphoma of large multilobated cell type with B-cell origin.

Large multilobated nuclei lymphoma is a rare entity that is characterized morphologically by large neoplastic elements with prominent nuclear lobations and clinically by a predilection for extranodal sites and a favorable prognosis. According to the data collected to date, the neoplasia is thought to be of T-cell origin. The authors describe the clinical, morphologic and immunohistochemical findings of a case of non-Hodgkin's lymphoma with large multilobated nuclei that showed a definite B-lymphocyte origin.

Aged↗

PubMed1989

Malignant lymphomas of follicular centre cell origin in 14 pigs.

Malignant lymphomas of follicular centre cell (FCC) origin in 14 pigs are described. Seven cases were classified as abdominal type according to the distribution of the neoplastic lesions and the residual cases were of the general type. Most cases were composed of mixed populations of large and medium-sized neoplastic cells and the growing pattern varied from partially follicular to diffuse. The neoplastic cells often showed necrosis, to which macrophages reacted. A part of the neoplastic cells had cytoplasmic immunoglobulin M (CIgM) or cytoplasmic immunoglobulin G (CIgG). The histological features of swine FCC lymphomas are discussed.

Abdominal Neoplasms↗

PubMed2001

Association of primary pleural effusion lymphoma of T-cell origin and human herpesvirus 8 in a human immunodeficiency virus-seronegative man.

We describe a case of an 87-year-old human immunodeficiency virus (HIV)-negative man who developed a primary pleural lymphoma without any identifiable tumor mass associated with human herpesvirus 8 (HHV-8) infection. A large T-cell lymphoma was diagnosed based on morphologic, immunophenotypic, and molecular findings. The HHV-8 DNA sequences were detected using specific polymerase chain reaction amplification in the lymphomatous effusion. Study of the patient's serum confirmed the HHV-8 infection. This case report displays the characteristic features of HHV-8-related body cavity-based lymphoma/primary effusion lymphoma previously reported in HIV-seronegative patients, except that it is of T-cell origin. Whether this case may be included or not within the primary effusion lymphoma entity, the association of a pleural T-cell non-Hodgkin lymphoma with HHV-8 infection raises the question of the possible occurrence of T cells as the target of malignant transformation associated with HHV-8 infection.

Aged↗

PubMed1995

CDKN2 gene deletion is not found in chronic lymphoid leukaemias of B- and T-cell origin but is frequent in acute lymphoblastic leukaemia.

Homozygous deletions of the cyclin-dependent kinase 4 (CDK4) inhibitor gene CDKN2 (p16, MTS1) have been demonstrated to occur frequently in human cancer cell lines of different origin. However, in most primary tumours the frequencies of CDKN2 deletions are not well defined. We studied primary samples of 100 patients with lymphoid leukaemias [B-lineage acute lymphoblastic leukaemia (ALL), n = 23; T-ALL, n = 7; B-cell chronic lymphocytic (B-CLL) or prolymphocytic (B-PLL) leukaemia, n = 50; T-CLL/T-PLL, n = 20] using fluorescence in situ hybridization (FISH) with eight overlapping cosmid clones covering the region on chromosome band 9p21 containing CDKN2. We did not observe any CDKN2 deletions in the 70 patients with chronic lymphoid leukaemias of B- or T-cell origin. Of the 23 patients with B-lineage ALL, one (4%) exhibited a CDKN2 deletion: in this patient, two clones were detected, one exhibiting a hemizygous and the other a homozygous deletion. On chromosome banding analysis, four patients with B-lineage ALL had a 9p aberration, whereas all CDKN2 copies were retained. In contrast, six of the seven (86%) patients with T-ALL exhibited CDKN2 deletions (homozygous, n = 4; hemizygous, n = 2). We conclude that hemizygous or homozygous deletions of the CDKN2 gene occur at high frequency in T-ALL and at low frequency in B-lineage ALL, supporting the role of this gene as a tumour suppressor, especially in T-ALL. However, from our data there is no evidence that CDKN2 is involved in the pathogenesis of chronic lymphoid leukaemias of B- or T-cell origin.

Adolescent↗

PubMed1997

Acute myelogenous leukaemia with t(8;21) translocation of normal cell origin in mosaic Down's syndrome with isochromosome 21q.

We report a 13-year-old girl with Down's syndrome (DS) having a mosaic karyotype of 46,XX/46,XX, -21,+i(21q), who developed acute myelogenous leukaemia (AML) (FAB M1). The t(8;21) translocation generating a AML1/MTG8 chimaeric gene of her blasts was demonstrated by cytogenetic analysis and reverse transcription-polymerase chain reaction. Interestingly, the leukaemic clone with t(8;21) did not have isochromosome 21q, indicating that the blasts were of normal cell origin. These findings suggest that, in older patients with DS, 21 trisomy cells have no greater predisposition to develop AML than normal karyotypic cells.

Adolescent↗

PubMed1998

Determination of cell origin after marrow transplantation in canines by polymerase chain reaction and quantitation of the ZFY/ZFX genes.

BACKGROUND: In order to follow the course of bone marrow engraftment in dogs, and to determine the presence, and percentage, of donor-derived cells in other canine tissues, a simple and fast method of determining cell origin after sex-mismatched bone marrow transplantation was developed. METHODS: Using universal primers, fragments from genomic DNA corresponding to ZFX and ZFY genes were amplified by polymerase chain reaction. A restriction fragment length polymorphism, combined with densitometric analysis, was then used to distinguish and quantitate ZFY and ZFX sequences. Unknown samples were analyzed against standards of known mixtures of male and female DNA. RESULTS: Canine ZFY and ZFX genes were clearly resolved after amplification, digestion with HaeIII, and denaturing polyacrylamide gel electrophoresis. Microchimerism could be detected in male and female dog DNA samples derived from a range of fresh and frozen tissues including spleen, testicle, and the central nervous system. The levels of chimerism determined using this method were in either agreement with results obtained by karyotyping or more sensitive, with a detection limit of 0.4% compared with 1-2%. CONCLUSIONS: Polymerase chain reaction/restriction fragment length polymorphism detection of the ZFY and ZFX genes was found to be simple, accurate, and reliable for assessing engraftment in dogs. When compared with cytogenetic analysis, this method was found to be faster to perform, more capable of detecting lower levels of microchimerism, and useful for detecting donor-derived cells in stored specimens and in tissues other than peripheral blood or bone marrow.

Animals↗

PubMed1984

Confirming evidence for the clonal development and stem cell origin of Philadelphia chromosome-negative chronic myelogenous leukemia.

A 74-year old woman with Ph1-negative chronic myelogenous leukemia (CML) and heterozygous for glucose-6-phosphate dehydrogenase (G6PD) was studied. Both A and B types of G6PD were found in skin. In contrast, white blood cells and platelets showed only a single G6PD type A. These results provide further evidence that Ph1-negative CML has a stem cell origin and develops clonally.

Aged↗

PubMed2000

Carcinosarcoma with rhabdoid features of the urinary bladder in a 2-year-old girl: possible histogenesis of stem cell origin.

A case of carcinosarcoma of the urinary bladder in a 2-year-old girl is reported. The tumor, measuring 34 x 20 x 18 mm, was located in the peri-trigone area of the urinary bladder with polypoid features. Histologic examination revealed transitional cell carcinoma at the tumor surface with downward invasion. Concurrently, a sarcomatous area was found beneath the carcinoma, with these two different malignant components sharing on apparent transition without distinct boundaries. Sarcomatous components included immature round cells focally showing rhabdoid features. No rhabdomyomatous component was observed. Immunohistochemistry disclosed vimentin and cytokeratin-double positive cells at the transposition between carcinoma and sarcomatous components. In addition, ultrastructural analysis revealed that the epithelial cells had a distinct junctional complex, and the sarcomatous cells occasionally had a meshwork of cytoplasmic intermediate filaments, indicating bidirectional cytodifferentiation to epithelial and mesenchymal elements. The extremely young age at which this case of carcinosarcoma occurred suggests that the tumor may be of mesodermal stem cell origin.

Carcinosarcoma↗

PubMed1992

Establishment of a new Hodgkin's cell line (HD-70) of B-cell origin.

A new Hodgkin's cell line, designated HD-70, was established from the peripheral blood of a 69-year-old man with Hodgkin's disease of nodular sclerosing type. The cell line grows in a single cell suspension and has a doubling time of 28 hours. The cells have a round or irregular nucleus or multiple nuclei in relatively abundant cytoplasm that is positive for acid phosphatase, alpha-naphthyl butyrate esterase, and periodic acid-Schiff stains. HD-70 cells are positive for CD30 (Ki-1/Ber-H2), CD15 (Leu-M1), and CD71 (OKT9) antigens and contain cytoplasmic immunoglobulin (Ig) (A, kappa). Southern blot analysis showed that the cells have Ig heavy and kappa light chain gene rearrangement and lack T-cell receptor gene rearrangement. Chromosome analysis disclosed that the cells have a human karyotype with complicated abnormalities, including a 14q+. Heterotransplantation of the HD-70 cell line into newborn hamsters treated with antilymphocyte serum produced massive tumors with remarkable fibrosis and collagen band formation. These tumors displayed histologic features similar to those of the nodular sclerosing type tumor of the patient. Such fibrosis production and collagen band formation in heterotransplanted tumors suggest that a certain cytokine that induces fibrosis might be produced by HD-70 cells. This cell line may be useful for understanding the biology and pathogenesis of Hodgkin's disease.

Aged↗