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Acute myeloid leukaemia M0: haematological, immunophenotypic and cytogenetic characteristics and their prognostic significance: an analysis in 241 patients.

Haematological, immunophenotypic and cytogenetic characteristics were analysed in 241 patients with acute myeloid leukaemia (AML) M0, including 58 children. Children < 3 years and adults between 60 and 70 years of age were most frequently affected. Immunophenotyping showed a heterogeneous phenotype. Anti-myeloperoxidase was positive in about half of the patients. Cytogenetic data were available from 129 (54%) patients. A normal karyotype was found in only 24%. Most of the abnormalities were unbalanced and the chromosomes 5, 7, 8 and 11 were the most frequently affected. Survival data were available from 152 treated patients (63%). The median overall survival for all patients was 10 months, 20 months for children (n = 36), 10 months for the young adult group (n = 50) and 7 months for the elderly patients (n = 66) (P = 0.09). Karyotype was not a prognostic factor influencing survival. AML M0 shows the immunological characteristics of early progenitor cells, but the expression of the different markers and cytogenetic abnormalities is heterogeneous. The prognosis is poor compared with other de novo AML and similar to that of AML with multilineage dysplasia or AML following myelodysplastic syndromes.

Adolescent↗

Lymphomatoid papulosis type A: clinical, morphologic, and immunophenotypic study.

BACKGROUND: Lymphomatoid papulosis (LyP) is a cutaneous clonal or polyclonal Ki-1 + T-cell lymphoproliferative disorder, morphologically resembling Ki-1 + anaplastic large cell lymphomas (Ki-1 + ALCL) or Hodgkin's disease (HD). Lymphomatoid papulosis usually has a characteristic benign clinical course with remissions and relapses of the cutaneous eruptions. METHODS: The authors studied three patients with LyP. In each case the diagnosis was established based on the typical clinical history and presentation of the cutaneous lesions as well as the morphologic and immunophenotypic findings. RESULTS: In all three cases the skin biopsies showed a polymorphic, nonepidermotropic, dermal lymphocytic infiltrate, composed of small lymphocytes and fewer large, atypical cells. The large cells were positive for the activation markers CD30 (Ki-1) and CD45R (leukocyte common antigen), and were negative for the HD marker CD15 (Leu MI). CONCLUSIONS: In most cases, LyP can be distinguished from Ki-1 + ALCL and HD on the basis of clinical, morphologic, and/or immunophenotypic findings. We emphasize the importance of the recognition of LyP as a clinicopathologic entity and the awareness of dermatologists, oncologists, and surgical pathologists in differentiating LyP from other primary cutaneous Ki-1 + lymphoproliferative disorders (Ki-1 + ALCL and HD). The prognosis of cutaneous Ki-1 + ALCL and HD is usually different from LyP and requires a different therapeutic approach.

Adult↗

Morphological, immunophenotypical and electrophysiological properties of resting microglia in vitro.

Morphological, immunophenotypical and electrophysiological properties were investigated in isolated cultured murine microglia before and after exposure to astrocyte-conditioned medium (ACM). Following application of ACM, microglial cells underwent a dramatic shape transformation from an amoeboid appearance to a ramified morphology. In parallel to morphological changes, a downregulation of macrophage surface antigens was observed in microglia exposed to ACM. Staining intensities for major histocompatibility complex (MHC) class II molecules and for the adhesion molecules leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) were significantly decreased in ramified microglia 5 days after exposure to ACM. In microglial cells treated daily with ACM over a period of 5 days, the smallest staining intensities for all surface antigens as well as the smallest ramification index as a measure for the highest degree of ramification were determined. In addition, upregulation of delayed rectifier K + currents was observed in microglia exposed to ACM for 1 day or treated daily with ACM for 5 days. In contrast, untreated amoeboid microglia or ramified microglia analysed 5 days after exposure to ACM did not express delayed rectifier K + currents. Analyses of the resting membrane potential and expression levels and properties of inward rectifier K + currents did not reveal any differences between untreated and ACM-treated microglia. It is suggested that electrophysiological properties of microglia do not strongly correlate with the morphology or the immunophenotype of microglial cells.

Animals↗

Functional and immunophenotypic characteristics of isolated CD105(+) and fibroblast(+) stromal cells from AML: implications for their plasticity along endothelial lineage.

BACKGROUND: In vitro cultures of BM cells from newly diagnosed patients with AML displayed a defective BM stromal compartment, with a reduced number of fibroblast-colony-forming unit (CFU-F: 1 +/- 1.25 SD) and a decreased proliferative ability. The purposes of our study were: 1). to select BM mesenchymal stem cells (MSC) and BM-derived stromal cells (BMDSCs) from AML patients at diagnosis and from healthy subjects, using an immunomagnetic system and either anti-CD105 or anti-fibroblast MAbs; 2). to study the immunophenotypic and functional properties of freshly isolated and cultured mesenchymal cells; 3). to test the in vitro plasticity of the selected cells to differentiate towards an endothelial phenotype. METHODS: Fresh mononuclear cells obtained from BM of 20 patients newly diagnosed with AML and from eight healthy subjects were selected by using anti-fibroblast and anti-CD105 MAbs. Freshly isolated cells were analyzed, characterized by flow cytometry using a wide panel of MAbs and seeded in long-term culture medium to assess CFU-F formation. The level of confluence after 30 days and functional capacity in a long-term colony-forming cell culture (LTC-CFC) were tested. Furthermore, the cultured selected cell populations were assayed for their ability to differentiate into an endothelial-like cell phenotype with the addition of vascular endothelial growth factor (VEFG) and endothelial cell growth supplement (ECGS). RESULTS: In normal subjects the selection produced an increase of the CFU-F number of 2.6-fold with anti-fibroblast MAb and 2.7-fold with the anti-CD105 MAb. Anti-fibroblast and anti-CD105 MAb selection from AML BM cells resulted in a statistically significant greater count of CFU-F that was respectively 10.6-fold (P = 0.04) and 14.4-fold (P = 0.00001) higher in comparison with the unselected AML samples. Interestingly, in 80% of AML samples immunoselection was also able to restore the capacity of the CFU-F to proliferate and form confluent stromal layers. The isolation of those layers sustained the proliferation and differentiation of hematopoietic stem cells in the LTC-CFC. The phenotypic profile of cultured BMDSCs was different from that of the freshly isolated cells, and changed in relation to the culture conditions: CD105+ selected cells cultured with VEGF and ECGS expressed endothelial markers, a finding that suggests that this cell subpopulation may have the potential to differentiate toward an endothelial-like phenotype. DISCUSSION: We report that immunomagnetic selection represents a valid tool for the selection of BM mesenchymal cells in samples obtained from both healthy subjects and patients with AML. This technique was able to rescue two functional and immunophenotypic compartments related to two different selected populations. In particular, the CD105+ cells isolated in AML displayed, after stimulation with VEGF and ECGS, the ability to change towards an endothelial-like cell phenotype, thus revealing an unexpected plasticity. Both CD105+ and fibroblast+ cells once successfully isolated might represent sources of mesenchymal cells populations useful for in vitro investigations and, above all, as therapeutic devices.

Adult↗

Storage and transportation of lymphoid tissue for immunophenotyping.

Immunoperoxidase staining of frozen sections is a cost-effective technic for immunophenotyping cells of lymphoid tissue. Because this procedure is not performed in many institutions, a simple method to transport fresh tissue to centers performing these studies is required. Tissues in saline at refrigerator temperature may be successfully transported. In addition, in order to minimize laboratory expenses, lymphoid tissue can be kept refrigerated in saline until permanent sections are examined and immunodiagnostic procedures become necessary. In this study reproducible immunophenotyping of 12 samples of lymphoid tissue stored up to seven days was achieved.

Antibodies, Monoclonal↗

Immunophenotypic analysis of peripheral blood leukocytes at different stages of HIV infection. An analysis of asymptomatic, ARC, and AIDS populations.

Blood leukocytes from 51 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related syndrome (ARC) were immunophenotyped with the use of monoclonal antibodies and flow cytometry. The patients were placed into four clinically defined groups: HIV-positive asymptomatic (HIV+/A, 8); persistent generalized adenopathy (14); Kaposi's sarcoma (12); and opportunistic infections (17). Immunophenotypes were compared between groups. Statistically significant differences were seen in absolute lymphocyte counts, total T-cells, helper/inducer T-cells, the helper inducer subset of CD4+ lymphocytes, the suppressor inducer subset of CD4+ lymphocytes, activated helper T-cells, and natural killer cells. CD8+ cells and subsets were not statistically different between groups, possibly obscured by large ranges, but median values suggested differences. Results indicate a pattern of increasing or decreasing numbers of certain subpopulations as HIV infection progresses.

AIDS-Related Complex↗

Immunophenotyping of acute leukemias using paraffin-embedded tissue sections.

In a study of 55 patients with either acute lymphoid leukemia (ALL; 25 cases) or acute myeloid leukemia (AML; 30 cases), paraffin-embedded bone marrow particle sections were examined with a panel of monoclonal and polyclonal antibodies reactive toward lymphoid and myeloid-associated antigens, using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. All cases were previously classified according to the French-American-British (FAB) Co-operative Group, and cases of ALL were immunophenotyped by flow cytometry. Results indicated that myeloid-associated antibodies (Mac 387, KP 1 [CD68], antielastase, antilactoferrin, and antilysozyme) did not react with any case of ALL, M1-AML, or M6-AML, whereas at least one of these antibodies reacted with 20 of 21 (95%) cases of M2, M3, M4, and M5-AML. Anti-glycophorin C marked cases of M6-AML, whereas anti-CD3 labeled T-cell ALL. None of the antibodies tested specifically identified cases of B-cell ALL. The authors conclude that use of a selected panel of antibodies on paraffin-embedded bone marrow particle sections may be of value in the diagnosis and immunophenotypic classification of many cases of acute leukemias.

Acute Disease↗

Genotypic and immunophenotypic characterization of two human light chain-only B-cell non-Hodgkin's lymphomas.

Two atypical human non-Hodgkin's lymphomas (NHLs) that exhibited unusual genotypic and in situ immunophenotypic abnormalities are described. Immunophenotypically, both NHLs lacked surface Ig heavy chains. With the exception of the MB2 B-cell-associated antigen, no B- and T-cell differentiation antigen was detected in case 1. NHL 2 failed to show evidence of clonality by immunohistochemical analysis but revealed the presence of many B-lymphocytes with an abnormal phenotypic profile: CD19+, CD20+, CD22+, kappa-, lambda-, CD9-, CD10-, CD21-, and CD24-. Genotypic analysis indicated that both lymphomas derived from anomalously matured pre-B-cells that had rearranged the lambda or kappa light chain genes but not the Ig heavy chain gene. The neoplastic cells of the two NHLs resemble the light chain-only B-cells recently discovered, following Epstein-Barr virus immortalization, in the human bone marrow. The authors' data confirm, therefore, the existence of the light chain-only B-cells in the human hematopoietic compartment. Moreover, their results emphasize the conclusive role of the immunogenotypic analysis in defining clonality, lineage, and maturation abnormalities of such atypical NHLs.

Adult↗

Lymphoid infiltrates of the orbit and conjunctiva. A morphologic and immunophenotypic study of 99 cases.

Most of the earlier clinicopathologic studies of orbital and conjunctival lymphoid infiltrates were done before the development of immunohistologic methods. In this study, we have examined 99 lymphoid infiltrates of the orbit and conjunctiva immunohistologically and correlated clinical and histologic features with immunophenotype. Sixty-six infiltrates expressed monotypic immunoglobulin; one case was immunoglobulin-negative, B-lineage; and 32 infiltrates expressed polytypic immunoglobulin. Using histologic criteria, 36 cases were malignant (35 monotypic; one immunoglobulin-negative, B-lineage), 44 were indeterminate (31 monotypic, 13 polytypic), and 19 were benign (all polytypic). Combining histologic and immunophenotypic criteria, 67 cases were diagnosed as malignant lymphoma. Seventy-six percent of the lymphomas were classified as low-grade according to the Working Formulation; small lymphocytic lymphoma (45%) was the most common histologic subtype. Cytologic atypia (p less than .0001) and Dutcher bodies (p less than .05) were found only in lymphomas. Similarly, bilateral involvement (p less than .05) and dissemination at time of presentation (p less than .001) occurred only in lymphomas. No other histologic or clinical features reliably distinguished lymphomas from benign orbital and conjunctival lymphoid infiltrates. Nineteen patients had a prior history of extraorbital malignant lymphoma, and eight patients had a history of pseudolymphoma. Patients with a history of malignant lymphoma more often presented with dissemination (p less than .001) and less often had the small lymphocytic subtype (p = .07) than patients without a history of lymphoma. However, not all patients with a history of extraorbital lymphoma had monotypic orbital and conjunctival infiltrates, and the incidence of monotypic orbital and conjunctival lesions in these patients was similar to that of the patients without a history of lymphoma. Patients with a history of pseudolymphoma always presented with localized disease (p less than .01) and more often had benign lesions (p = .08) as compared with patients without a history of pseudolymphoma. We conclude that the presence of either cytologic atypia or Dutcher bodies is a reliable criterion of malignant lymphoma in the orbit and conjunctiva. However, for one-third of the cases in this study, immunohistologic studies were the only means of distinguishing malignant from benign lymphoid infiltrates.

Conjunctiva↗

Primary large cell lymphoma of the mediastinum. A histologic and immunophenotypic study of 29 cases.

We studied the morphologic and immunologic features of 29 cases of primary nonlymphoblastic non-Hodgkin's lymphoma of the mediastinum. The patients ranged in age from 15 to 73 years, with a median of 32 years. The mean age for the 11 men (50 years) was significantly higher than that for the 18 women (32 years) (p less than 0.05). All had diffuse large cell lymphomas (six immunoblastic, 14 large cell not otherwise specified, six large cell noncleaved, one large cell cleaved, and two not subclassifiable). Sclerosis was prominent in 11 cases, none of them immunoblastic, and did not correlate with superior vena cava syndrome. The mean age (54 years) of patients with immunoblastic lymphomas was higher than that for patients with other subtypes (35 years) (p less than 0.02). Frozen-section immunoperoxidase staining disclosed monotypic immunoglobulin in 13 cases, with a high frequency of heavy-chain class switching (seven IgG, two IgA, four IgM). Sixteen cases were immunoglobulin negative; 14 of 15 cases expressed B-lineage antigens, and none expressed T-lineage antigens. Three of four cases showed immunoglobulin heavy- or light-chain gene rearrangement by the Southern blot technique. None showed rearrangement of the T-cell receptor beta-chain-gene constant region. There was no correlation between immunophenotype and morphologic subtype. The immunoglobulin-negative group was predominantly female (13 of 16 cases; p less than 0.02), and younger (mean age, 34 years versus 44 years; p = NS) than the immunoglobulin-positive group; however, the difference in age was not statistically significant. The actuarial 5-year survival was 57%, and there was no correlation between survival and either histologic subtype or immunophenotype. Mediastinal large cell lymphoma is a B-cell tumor, which frequently lacks immunoglobulin, may be primary in the thymus, has a predilection for young women, and can be cured with aggressive therapy.

Adolescent↗

Lymphocytic lymphoma of intermediate differentiation. Morphologic and immunophenotypic spectrum and clinical correlations.

All cases of lymphocytic lymphoma of intermediate differentiation (IDL) referred to the National Cancer Institute were reviewed in order to define the histopathologic spectrum of the disease and to investigate morphologic and immunophenotypic features with potential prognostic relevance. Thirty-three cases were classified as IDL according to histologic criteria. Immunophenotypic analysis was performed in 27 cases, and clinical records were available for 22 patients. The median age was 58 years, and the male-to-female ratio, 3.4:1. All patients presented with stage III or IV disease, and five had extranodal presentations. Median survival was 56.3 months, with only three patients having a prolonged relapse-free survival (greater than 2 years). Morphologically, 14 cases were diffuse or only vaguely nodular; 18 cases showed a mantle zone pattern with naked germinal centers. There was a trend toward prolonged median survival for patients with the mantle zone (77.4 months, p = 0.098). The neoplastic population was composed of irregular or cleaved small lymphoid cells with a mitotic rate ranging from 5 to 62 per 20 high-power fields (hpf). A histologically distinctive variant with blastic cytologic features was identified (seven cases). The blastic variant was associated with a higher mitotic index (51.3 versus 19.0) and shortened survival (24.9 months). In contrast to the histologic progression often observed in follicular lymphomas, in no case was transformation to a large-cell or small noncleaved lymphoma observed. All cases had a mature B-cell phenotype demonstrating monoclonal Ig and B-cell surface antigens. Seventy-eight percent were CD5 positive; three of six CD5-negative cases presented in mucosal-associated extranodal sites. CD10 and CD25 were expressed in 52% and 44%, respectively, but did not show clinical correlations. The proliferative rate measured by Ki-67 positivity correlated with the mitotic index, but neither of these parameters had a statistically significant influence on survival.

Abdominal Neoplasms↗

The value of immunophenotyping on paraffin sections in the identification of T-cell rich B-cell large-cell lymphomas: lineage confirmed by JH rearrangement.

Immunophenotyping of lymphomas using paraffin-embedded lymphoid tissue, not previously distorted by frozen section, is useful in identifying the large neoplastic B cells that may be in the minority in T-cell rich B-cell lymphoma (TCRBCL). Even in cases in which frozen tissue sections are available, the improved morphology in unfrozen sections allows the proper classification of these lymphomas as large cell and identifies their B-cell lineage, which is important for clinical therapeutic studies. Seven cases initially believed to be diffuse mixed cell lymphoma of possible peripheral T-cell lineage showed the large cells to be immunoreactive with L-26 (pan B-cell marker) with the majority of smaller lymphocytes immunoreactive for UCHL-1 and Leu-22 (pan T-cell markers). K/lambda immunostaining on frozen sections was equivocal. In these cases, the diagnosis of large-cell lymphoma of B-cell lineage was confirmed by detection of immunoglobulin heavy- (all seven cases) and light- (six of seven cases) chain gene rearrangements, with germ-line configuration of the T-cell receptor beta-chain gene (all cases). Some cases of TCRBCL may not show detectable rearrangement of the immunoglobulin genes because of the low concentration of neoplastic cells in the samples submitted. The presence of rearrangements in these seven cases, however, supports the diagnosis of TCRBCL based on paraffin immunophenotyping when frozen tissue is not available or when molecular studies are not feasible. Although these seven cases are classified as large-cell lymphoma, an intermediate-grade lymphoma, the influence of the reactive T-cell population on the clinical behavior will require follow-up studies.

Adult↗

Characterization of a primary central nervous system atypical teratoid/rhabdoid tumor and derivative cell line: immunophenotype and neoplastic properties.

Primary central nervous system (CNS) atypical teratoid/malignant rhabdoid tumors (ATT/RhT) occur during early childhood and are almost invariably fatal. Expression of multiple phenotypes in ATT/RhT suggests the presence of an undifferentiated progenitor with the potential to differentiate along multiple lines. These properties have made it difficult to characterize the etiology and histogenesis of these tumors and complicate efforts to develop targeted therapies. This paper characterizes the immunophenotype of a human CNS ATT/RhT and describes the properties of a derivative cell line (Atrt95) which retained morphological and immunochemical characteristics of the parent tumor including diverse differentiation. Most tumor cells were strongly immunoreactive for glial fibrillary acidic protein, vimentin and A2B5. Scattered, large tumor cells that showed a rhabdoid phenotype were immunoreactive for synaptophysin. The morphology of cultured Atrt95 cells was heterogeneous, but often fit into 1 of 3 classes that appeared to correspond to cell populations observed within the parent tumor including: 1) tightly-packed small-cell colonies, 2) large, well-spread highly motile cells and 3) arrays of elongated cells. In vitro assays demonstrated that growth of the entire culture was anchorage-dependent but not serum-dependent. Transplantation of Atrt95 cells into the rat spinal cord resulted in tumor growth and CNS invasion. Preliminary cytogenetics study revealed complex aneuploidy but no apparent monosomy or deletions of chromosome 22. The immunophenotype of this neoplasm and derivative cell line is consistent with a primitive glioneuronal lineage and its in vitro characteristics are that of an invasive malignancy similar to the naturally occurring tumor. This unique cell line (Atrt95) provides a valuable model to study the biology and genetics of the CNS ATT/RhT.

Animals↗

Ovarian atypical proliferative (borderline) mucinous tumors: gastrointestinal and seromucinous (endocervical-like) types are immunophenotypically distinctive.

Ovarian atypical proliferative (borderline) mucinous tumors of gastrointestinal and seromucinous types are considered subtypes within the mucinous tumor category despite the presence of distinctive clinicopathologic features that seromucinous tumors share with pure serous tumors. Immunophenotypic differences have not been extensively investigated. Immunohistochemical studies were performed to compare the expression patterns of cytokeratins 7 and 20 (CK7, CK 20), estrogen and progesterone receptors (ER, PR), CA-125, mesothelin, and WT-1 in 28 tumors of gastrointestinal type and 12 tumors of seromucinous type. Both gastrointestinal and seromucinous type tumors had a high frequency of CK7 expression (93% and 100%, respectively). The gastrointestinal type tumors were characterized by frequent expression of CK20 (86%) and CDX2 (39%), infrequent expression of CA-125 (11%) and mesothelin (7%), and lack of expression of ER, PR, and WT-1. In contrast, the seromucinous type tumors were characterized by frequent expression of ER (100%), PR (67%), CA-125 (92%), and mesothelin (83%), infrequent expression of WT-1 (8%), and lack of expression of CK20 and CDX2. The gastrointestinal and seromucinous types of atypical proliferative mucinous tumors are immunophenotypically distinctive tumors. The former are characterized by expression of markers of gastrointestinal-type differentiation (CK20 and CDX2), whereas the latter are characterized by expression of "müllerian-type" markers (ER, PR, CA-125, and mesothelin). Expression of the latter markers in the seromucinous tumors, which also are expressed in pure serous tumors, and lack of expression of gastrointestinal-type markers, combined with the clinicopathologic features these tumors share with pure serous tumors, support the concept that this subtype is more closely related to serous than gastrointestinal type mucinous tumors and justify the designation "seromucinous."

Adenocarcinoma, Mucinous↗

Borrelia burgdorferi-associated lymphocytoma cutis: clinicopathologic, immunophenotypic, and molecular study of 106 cases.

Lymphocytoma cutis (LC) is considered as the stereotypical example of the cutaneous B-cell pseudolymphomas. It can be induced by various antigenic stimuli including arthropod bites, vaccination, and drugs among others. In endemic regions, Borrelia burgdorferi is the principal causative agent for LC. We studied retrospectively 108 biopsies from 106 patients (male : female, 48 : 58; mean age, 44.6; median, 51.5; range, 3-81) with B. burgdorferi-associated LC retrieved from the files of the Department of Dermatology of the University of Graz (Austria). Only cases with a B. burgdorferi etiology (typical locations, positivity of serologic and/or polymerase chain reaction (PCR) tests, clinical history) were included in the study. Lesions were located on the nipple (63 cases), earlobe (18 cases), genital region (9 cases), and trunk or extremities (16 cases). PCR analysis of B. burgdorferi DNA was positive in 54 of 80 cases tested (67.5%). In 47 cases, we could retrieve data on serologic examination for B. burgdorferi antibodies performed at the time of diagnosis of LC. Positivity was found in 45 patients (IgG+/IgM+, 5 cases; IgG+/IgM-, 37 cases; IgG-/IgM+, 3 cases; IgG-/IgM-, 2 cases). Histology revealed dense lymphoid infiltrates with prominent germinal centers (GCs) in all cases. Atypical morphologic and/or immunophenotypic features of the GCs were commonly observed. In 5 cases, due to confluence of large follicles, the histopathologic pattern simulated that of a large B-cell lymphoma. PCR analysis of the IgH gene rearrangement performed in 33 cases showed a polyclonal pattern in 31 cases and a monoclonal band in 2. In summary, B. burgdorferi-associated LC can present with misleading histopathologic, immunophenotypic, and molecular features, and integration of all data is necessary for a correct diagnosis.

Adolescent↗

Lymphomatoid papulosis followed by large-cell lymphoma: immunophenotypical and genotypical analysis.

The immunophenotype and genotype of atypical cells in skin and lymph node infiltrates were investigated in a patient with lymphomatoid papulosis (LyP) complicated by anaplastic large-cell lymphoma of the lymph nodes. The large atypical cells in both skin and lymph nodes displayed an almost identical immunophenotype, i.e. CD30+ and CD25+. Southern blot analysis for T-cell receptor beta-chain gene rearrangement revealed an identical gene configuration in DNA extracted from skin and lymph node. Our results strongly support the hypothesis that clonal populations of T cells arising in cutaneous LyP lesions may undergo malignant transformation, spread into regional lymph nodes, and give rise to secondary malignant lymphomas, such as anaplastic large-cell lymphoma.

Adult↗

Rearrangements of the RAR-alpha gene in acute promyelocytic leukaemia: correlations with morphology and immunophenotype.

We have used genomic probes which specifically recognize DNA rearrangements of the RAR-alpha locus on chromosome 17q21 in patients with acute promyelocytic leukaemia (APL) and acute myeloid leukaemia (AML) subtypes. Molecular data were examined in comparison with morphological and immunophenotypic characterization at diagnosis in 20 hypergranular FAB M3 cases, five microgranular APL (M3v), 51 non-M3 AML and 12 myeloid CML blast crises. Rearrangements of the RAR-alpha locus were only detected in 23/25 APL cases and in none of the other FAB subtypes analysed. Surface marker characterization showed a consistent immunophenotypic profile--HLADR negative, CD9 and CD13/33 positive--in all M3 and M3v cases. Neither HLADR negativity nor CD9 positivity were associated with RAR-alpha rearrangements in non M3 AML. Our data indicate that RAR-alpha gene rearrangements are relevant diagnostic features of both M3 and M3v, and may prove useful molecular marker for follow-up analysis in APL patients.

Acute Disease↗

Leu 7+ (HNK-1+) cells. I. Selective compartmentalization of Leu 7+ cells with different immunophenotypes in lymphatic tissues and blood.

In the present immunohistochemical studies, Leu 7+ (HNK-1+, human natural killer and killer) cells were found to occupy preferentially germinal centres of follicles in lymph nodes and tonsils. Leu 7+ cells were also present in germinal-like zones of spleen follicles and in mantle zones of hyperplastic thymus follicles and varied in localization in lymph nodes involved in different types of follicular centre cell-derived malignant lymphomas. Most of the Leu 7+ cells in the follicles expressed the Leu 3 (helper/inducer) marker. Double staining studies of tonsil sheep erythrocyte-rosetting and peripheral blood mononuclear cell suspensions showed that two main, mutually complementary, subpopulations of Leu 7+ cells could be distinguished in both cases, namely Leu 7+/Leu 4+ (subdivided into Leu 2+ (suppressor/cytotoxic) and Leu 3+) and Leu 7+/Leu 4-, including mostly cells with OKM 1 (myelomonocytic) characteristics. Thus, in the tonsil cell suspension the cells with Leu 7+ Leu 3+/OKM 1- immunophenotype strongly predominated, whereas among peripheral blood mononuclear cells Leu 7+Leu 2+/OKM 1- and Leu 7+/OKM 1+ immunophenotypes were mostly observed.

Antibodies, Monoclonal↗