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Osteoclast-like giant cell tumor of the pancreas: immunophenotypic similarity to giant cell tumor of bone.

An immunophenotype was performed on an osteoclast-like giant cell tumor of the pancreas using a panel of antibodies to epithelial and leukocyte antigens. Several antibodies to cytokeratin and carcinoembryonic antigen were negative in the tumor. Osteoclast-like cells were positive for CD4, CD13, CD45, CD68, CD71, and vimentin, but negative for lysozyme and HLA-DR. Mononuclear tumor cells were positive for CD4, CD11c, CD13, CD14, CD45, CD68, CD71, HLA-DR, and vimentin, but negative for lysozyme. The phenotype is similar to that previously described for giant cell tumor of bone. The osteoclast-like cell phenotype is also similar to that reported for normal osteoclasts. The findings support a nonepithelial origin for osteoclast-like giant cell tumor of the pancreas, and suggest a derivation similar to giant cell tumor of bone.

Biomarkers↗

B-zone small lymphocytic lymphoma: a morphologic, immunophenotypic, and clinical study with comparison to "well-differentiated" lymphocytic disorders.

The pathologic, immunologic, and clinical features of five cases of B-zone small lymphocytic lymphoma (BZSLL), characterized by a nondestructive growth pattern with a selective and complete replacement of the B-zone areas of lymph nodes, were examined. These findings were compared with those of 13 cases of intermediate differentiated lymphoma/mantle zone lymphoma (ILL/MZL) and 20 cases of typical small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). B-zone SLL was characterized histologically by a deceptively benign pattern at a low magnification, the lymph node architecture being substantially preserved, in contrast to the ILL/MZL and SLL/CLL cases, in which complete effacement of the normal architecture usually could be observed. Moreover, in BZSLL the cellular population was rather uniform and lacked either a prolymphocytic component or the small-cleaved lymphoid cells often seen in SLL/CLL and ILL/MZL cases, respectively. The phenotypic profile of the BZSLL clonal cell population studied by the immunoperoxidase method and by single- and double-labeling flow cytometric analyses (SIg+, CD19+, CD20+, CD21+, CD22+, CD24+, CD35+, CD37+, CD74+, CD45+, CD45R+, MB2+, HLA-DR+, Leu-8+, CD9+/-, CDw75+/-, CD5-/+, CD23-/+, CD10-, FMC7-, PCA-1-, CD25-, CD38-, CD43-, CD3-) appeared to be fairly homogeneous and sufficiently distinct from that of ILL/MZL, based on the absence of FMC7 and CD38 molecules, and from that of SLL/CLL due to significantly stronger expression of SIgs (P less than .05), the higher reactivity with anti-CD9 and -CD22 antibodies (P less than .05), the lower reactivity with anti-CD5 and -CD23 antibodies (P less than .05), and the absence of CD25 determinants. Several clinical features of patients with BZSLL, including age group, advanced stage disease, and high frequency of bone marrow and peripheral blood involvement, were similar to those found in the other patients with ILL/MZL and SLL/CLL, but none of the BZSLL patients had an absolute lymphocyte count higher than 15.0 x 10(9)/L at presentation. Based on the architectural pattern, cytologic features, immunophenotypes, and hematologic findings, we conclude that BZSLL is an unusual variant of SLL that is primary in the lymph nodes and should be distinguished from ILL/MZL and CLL.

Adult↗

Immunophenotypic characterization of the cell infiltrate in five cases of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease).

Little is known about the nature of the large intrasinusoidal cells exhibiting cytophagocytosis, which are the histologic hallmark of sinus histiocytosis with massive lymphadenopathy (SHML) (Rosai-Dorfman disease). Using a broad panel of monoclonal and polyclonal antibodies, we analyzed the immunophenotype of the cell infiltrates in seven lymph node biopsy specimens from five cases of SHML. The SHML cells constantly expressed the S-100 protein, concanavalin agglutinin and peanut agglutinin lectins, and monocyte-macrophage-associated antigens CD 11c, CD 14, CD 33, CD 68, and LN 5. Labeling with other antimacrophage antibodies was extremely variable, with some (MAC 387, lysozyme) restricted to clusters of SHML cells and others (CD11b, CD 36, alpha-1-antichymotrypsin) staining only scattered cells. The CD 1a antigen was found on some cells in only one case, whereas HLA-DR and the HLA-DR-associated invariant chains were absent. The heterogeneity of SHML cell marker expression might be related to the local content of factors (eg, cytokines) capable of modulating the phenotype of monocytes and derived cells. All cases presented with huge amounts of medium-sized mononuclear cells accumulated in the sinuses and intersinusoidal tissue. These cells expressed the S-100-/CD 11b+/CD 11c+/CD 14+/CD 16+/CD 33+/CD 36+/lysozyme+/MAC 387+/HLA-DR+ phenotype. These recently immigrated monocytes might represent the immediate precursors of SHML cells.

Adolescent↗

KP1 (CD68)-positive large cell lymphomas: a histopathologic and immunophenotypic characterization of 12 cases.

CD68/KP1 antigen expression in a series of 298 non-Hodgkin's lymphoma (NHL) cases, including 41 cases of CD30/Ki-1-positive anaplastic large cell (Ki-1+ ALC) lymphomas, was examined. Among the cases in this series, 12 large cell NHLs, including five centroblastic (G group according to the Working Formulation) NHLs, three immunoblastic (H group) NHLs, and four Ki-1+ ALC lymphomas, were found to express KP1. By extensive immunophenotypic analysis and in situ hybridization, KP1-positive large cell lymphomas of the G and H groups were assigned a B-cell phenotype. The pattern of KP1 staining usually consisted of localized small to medium-sized cytoplasmic dots; only two cases showed diffuse fine granular reactivity. In two of the four Ki-1+ ALC lymphomas tumor cells failed to express a B- or T-cell phenotype and stained positively for lysozyme, whereas in the other two cases they showed a hybrid T/histiocytic, phenotypic profile. KP1 staining of Ki-1+ ALC lymphoma cells was usually intense and showed a diffuse granular cytoplasmic pattern; tumor cells also expressed the CD13 antigen and showed strong reactivity with the anti-CD68 EBM11 antibody. Our results suggest that certain subsets of large "blastic" B-cell lymphomas may simultaneously express the CD68/KP1 histiocyte-specific marker and other myeloid-associated antigens, indicating the necessity of using a multiparameter approach in the determination of cell lineage. Moreover, this study, which demonstrates that the expression of CD68/KP1 and CD30 antigens is not mutually exclusive, supports the view that a fraction of cases diagnosed as Ki-1+ ALC lymphomas (at least those with KP1 expression along with the lack of B- or T-antigen expression) represent true histiocytic lymphomas despite the Ki-1+ phenotype.

Adolescent↗

Adult rhabdomyoma of the head and neck: a clinicopathologic and immunophenotypic study.

Twenty-seven cases of adult rhabdomyoma (ARM) of the head and neck are reported. The 20 male and seven female patients ranged in age from 33 to 80 years (median age, 60 years). Symptoms included airway obstruction and a mass within the mucosa or soft tissue. Median tumor size was 3.0 cm (range, 1.5 to 7.5 cm). Seven patients (26%) presented with multinodular tumors and one tumor was multicentric. Follow-up was available in 19 cases and ranged from 2 months to 18.5 years after diagnosis (median, 6.0 years). Lesions recurred locally in eight cases (42%) 2 to 11 years after diagnosis (median, 6 years). One recurrence was multicentric. Histologically, ARM was composed of closely packed, large polygonal cells having abundant, eosinophilic, granular, or vacuolated glycogen-rich cytoplasm with focal cross-striations. Immunohistochemical stains confirmed skeletal muscle differentiation; the majority of tumors stained for myoglobin (21 of 21 tumors), muscle-specific actin (21 of 21 tumors), and desmin (19 of 21 tumors). Focal or rare immunoreactivity for vimentin (six of 17 cases), alpha-smooth muscle actin (17 of 20 cases), S-100 protein (14 of 21 cases), and Leu-7 (10 of 20 cases) also was detected. Cytokeratin, epithelial membrane antigen, glial fibrillary acidic protein, and CD68 antigen (with KP1) were not found. The characteristic histology and immunophenotype distinguish ARM from other lesions with which it is frequently confused, including granular cell tumor, hibernoma, oncocytoma, and paraganglioma. The expression of alpha-smooth muscle actin has not been reported previously in ARM; its presence could reflect aberrant expression of smooth muscle actin in skeletal muscle or possibly be a recapitulation of early skeletal muscle embryogenesis.

Adult↗

Immunophenotype of blast cells in acute myelofibrosis.

The immunophenotype of peripheral blood blast cells from six patients with acute myelofibrosis was studied using a panel of monoclonal antibodies directed against granulocytic, erythroid, megakaryocytic and lymphoid antigenic determinants. In all patients most of the blast cells were labeled with anti-HLA-DR and with the early myelomonocytic antibodies My7 (CD13), My9 (CD33) and B1-3C5 (CD34) (3/3). In three cases, platelet antibodies Edu3 (CD41) and GPIIIa (CD61) reacted with about 30% of blast cells. TdT was positive in two out of six samples studied. Lymphoid markers T3 (CD3), Leu9 (CD7), J5 (CD10), B4 (CD19) and B1 (CD20) were negative in all cases. These results suggest that blast cells are mainly of immature myelocytic origin. However, the coexistence of megakaryoblasts cannot be ruled out in the cases with a proportion of cells that are positive with Edu3 and GPIIIa antibodies.

Acute Disease↗

Histologic, immunophenotypic and genotypic analyses of bone marrow trephines from patients with non-Hodgkin's lymphoma.

Marrow involvement in 20 patients with non-Hodgkin's lymphoma (NHL) were studied by histology, immunophenotypic and genotypic methods. Eighteen of these trephines were histologically involved with recognizable lymphomatous infiltrates and five of these were the primary disease site. In the remaining two cases (with histologically involved lymph nodes) the trephines were uninvolved with tumour. Three B-cell cases expressing surface immunoglobulin (sIg) and/or CD37 and one case not analysed phenotypically showed Ig gene rearrangements. The two remaining cases with B NHL showed no gene rearrangements, however, in one of these the trephine was histologically uninvolved with tumour. Twelve out of 14 T-cell cases were characterized by variable or absent expression of one or more T-cell antigens from the tumour population, one case was negative for all T-cell antigens and the remaining case was not histologically involved with tumour. All three lymphoblastic lymphomas and only 4/11 peripheral T-cell lymphomas (PTCL) cases revealed T-cell receptor (TcR) gene rearrangements. One of the latter cases also exhibited Ig JH gene rearrangements. This study demonstrates the usefulness of bone marrow trephines (BMT) in histologic, phenotypic and genotypic analyses. However, although genotypic data confirm clonality in B NHL and the lymphoblastic lymphomas there was genotypic heterogeneity within the PTCL group.

Antigens, CD↗

S-phase DNA content and aneuploidy of immunophenotypic defined subpopulations in acute myeloid leukemia determined by multi-parameter flow cytometry.

One of the major limitations of DNA flow cytometry (FCM) in hematologic malignancies is the lack of information about the proliferation activity of subpopulations of the heterogeneous bone marrow (BM) compartment. We studied the S-phase DNA content of immunophenotypically defined BM subpopulations (CD2+; CD19+; CD2/CD19+; glycophorin-A+; CD14+; CD13+; CD33+ and CD13/CD33+) in 18 patients with acute myeloid leukemia (AML), including three patients with M6 AML. The results were compared with the findings in twelve normal BM aspirates. The measurements were performed using a special protocol for bivariate FCM of DNA content and surface immunofluorescence (s-IF). In patients with AML the proportion of BM cells expressing the myelomonocytic and monocytic markers (M1-M5 AML) or erythroid marker (M6 AML) was expanded. However, in many patients other subpopulations were 4% or higher permitting the calculation of their S-phase DNA. No essential differences in median S-phase DNA percentages of the distinct subpopulations were observed between normal and leukemic bone marrow though the ranges in AML patients were much wider. These data suggest that AML is not characterized by an increased nor a decreased proliferation activity, but rather by a situation of cell growth independent to the normal regulatory mechanisms. Additional information was obtained upon DNA aneuploidy using CD2+ or CD2/CD19+ cells as an intrinsic DNA standard which allowed us to define differences in the DNA index as small as 2% as aneuploid. This approach appeared suitable for detecting small-degree numerical chromosomal aberrencies, as found by cytogenetics, in 4/6 cases.

Adult↗

Relation of 5'-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia.

Ecto-5'-nucleotidase (ecto-5'NT) catalyzes the extracellular dephosphorylation of nucleotides like IMP. Cytoplasmic 5'NT (cyto-5'NT) and non-specific (e.g. acid- and alkaline) phosphatases (AP) regulate the intracellular degradation of nucleotides. High NT and AP activities might cause a resistance to the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We studied the relation between these enzymes and immunophenotype, drug resistance and prognosis in 77 children with acute lymphoblastic leukemia (ALL). Enzyme activities were assessed radiochemically; in vitro drug resistance was measured with the MTT assay. AP activities were higher in T-ALL and B-ALL than in precursor B-ALL. Cyto-5'NT activity was very low in all phenotypes and accounted for a significant proportion of total IMPase activity only in the very immature CD10- c mu- precursor B-ALL. CD10+ ALL cases with high ecto-5'NT activities showed a trend (p = 0.065) for a lower probability of continuous complete remission than those with a low activity. Ecto-5'NT activity was not related to in vitro drug resistance to 6-TG. A weak correlation was found between in vitro 6-TG resistance and cyto-5'NT and AP activities. We conclude that high ecto-5'NT activities do not cause a resistance to 6-thiopurines in childhood ALL. Some patients have high cyto-5'NT and AP activities associated with 6-thiopurine resistance.

5'-Nucleotidase↗

Immunophenotyping of childhood acute lymphoblastic leukemia in Saudi Arabia: second look.

Geographical variations in the incidence of disease are of considerable theoretical and practical importance. It has been claimed that the distribution of acute lymphoblastic leukemia (ALL) phenotypes in Saudi Arabia is different from that recorded in the Western literature. One hundred and twelve (112) patients under 15 years of age, diagnosed as ALL between January 1992 and May 1994 had immunophenotypes performed on their blast cells. Common ALL (cALL) together with pre-B-ALL, formed 86.5% of the total; B-cell 3%, T-cell 6% and null cell 4.5%. These figures are not significantly different from the Western literature. A previous claim from this institution in 1990, that both null and B-cell ALL were significantly increased compared with elsewhere, is not supported by the present figures. Age and sex distribution, and FAB classification, L1 77%, L2 20% and L3 3%, were also of the same order as described elsewhere and, in particular, there was no increase in the frequency of L3 subtype.

Adolescent↗

Immunophenotyping of acute lymphoblastic leukaemia in Madras, India.

At the Cancer Institute, Madras, India, we have performed immunophenotyping in 125 untreated cases of acute lymphoblastic leukaemia using a panel of 16 monoclonal antibodies and the avidin-biotin immunoperoxidase technique in a haematology autoanalyser (Technicon Hi system). Our results demonstrate a marked difference in the phenotypic pattern of ALL compared to Western countries, the predominant finding being a relative excess of T-ALL and a paucity of C-ALL cases. Age distribution of C-ALL reveals a peak at 2-6 years in paediatric ALL cases.

Adolescent↗

Acute leukemic transformation of myelodysplastic syndrome--immunophenotypic, genotypic, and cytogenetic studies.

The clinical and biological characteristics of myelodysplastic syndrome (MDS) in acute leukemic transformation were studied in 23 patients. All had myeloid transformation according to FAB criteria, but coexpression of lymphoid-associated antigens was detected in five of the 20 patients who underwent an immunophenotypic study. Rearrangement of the immunoglobulin heavy chain gene was also observed in one of the five patients who coexpressed lymphoid markers and that of the T-cell receptor beta chain gene in another one. None had pure lymphoid transformation. Clonal chromosomal abnormalities were noted in 12 (63%) of the 19 patients who underwent cytogenetic study, most commonly - 7 (six patients or 32%). In the 18 patients who underwent serial analyses both at MDS diagnosis and at acute transformation, seven (39%) underwent karyotypic evolution. The most common new or additional aberrations were +8 and +21. N-ras gene mutation was detected in two of the nine patients at acute leukemic transformation. The median interval from diagnosis of MDS to onset of acute transformation was 10 months (1-36 months). Patients with a normal karyotype at diagnosis had a significantly longer chronic phase duration than those with chromosomal abnormalities (median of 20 months vs. 5 months). However, all had a short survival time after diagnosis of acute leukemia, whether chromosomal anomalies were present or not.

Adolescent↗

8;20 chromosomal translocation in a case of acute leukemia. Cytogenetic, immunophenotypic, ultrastructural, and molecular characteristics.

An 8;20 chromosomal translocation was observed in the leukemia cells of a 3-year-old girl. To our knowledge, this is the first report of this translocation in de novo acute leukemia. This chromosomal defect was present in the leukemia cells at diagnosis and also at relapse, but remission bone marrow cells had the 46,XX karyotype. By morphologic and cytochemical criteria the leukemia was myeloid but these features were more lymphoid when the leukemia recurred. However, the immunophenotype was consistent with myeloid leukemia and did not change at relapse. No evidence for either immunoglobulin or TCR gene rearrangement was observed.

Biomarkers, Tumor↗

Immunophenotype of mitotic cells with clonal chromosome abnormalities demonstrating multilineage involvement in acute myeloid leukemia.

Eleven patients with acute myeloid leukemia (AML) were studied with a technique that simultaneously identifies cytogenetic abnormality and immunophenotype of the same mitotic cell. To determine the cell lineages with abnormal karyotypes, monoclonal antibodies in the alkaline phosphatase-antialkaline phosphatase (APAAP) detection procedure were used. The granulocytic/monocytic lineage was involved in the leukemic process in all 11 patients. In nine patients, we also detected abnormal karyotypes in the erythrocytic and/or megakaryocytic lineages. All four patients with secondary AML showed involvement of the granulocytic/monocytic, erythrocytic, and megakaryocytic lineages into the leukemic process, as compared with five of seven patients with de novo AML. One patient with trisomy 8 showed erythrocytic participation in the leukemic process, but in another the erythrocytic lineage had only normal karyotypes. Thus, in AML, the chromosome abnormalities apparently usually originate at the multipotent progenitor cell stage, since in addition to granulocytic/monocytic lineages, erythrocytic and/or megakaryocytic lineages were also involved. Some patients show involvement of granulocytic/monocytic lineages only, however, suggesting that the target cell belongs to a more mature committed progenitor cell stage.

Adult↗

Cell lineage involvement in four patients with myelodysplastic syndrome and t(1;7) or trisomy 8 studied by simultaneous immunophenotyping and fluorescence in situ hybridization.

Four patients with myelodysplastic syndrome (MDS), one with t(1;7) and three with trisomy 8, were studied by immunophenotyping and fluorescence in situ hybridization (FISH) to assess cell lineage involvement. The t(1;7) was detected using a biotin-labeled chromosome 1 centromere-specific DNA probe. This aberration was present in CD34-positive stem cells, the erythroid cell lineage (GPA+), and the granulocytic/monocytic (CD13+ and CD64+) cell lineages. We were not able to demonstrate the abnormality in the lymphoid cell lineages. In the patients with trisomy 8, the aberration was detected with chromosome 8 centromere-specific DNA probe or by chromosome in situ suppression hybridization (CISS) with a chromosome 8-specific library probe. The trisomy was detected in stem cells, erythroid precursor cells, megakaryocytes, and granulocytes/monocytes. In these MDS patients, the chromosome aberrations appear to occur only in cells of myeloid lineage.

Aged↗

Cytogenetic and immunogenotypic alterations of blast crisis cells in chronic myelogenous leukemia independently linked to immunophenotypic expression.

Chronic myelogenous leukemia (CML) is a disease of the hematopoietic stem cells, which can differentiate into either B-lymphoid or myeloid cells, because most of them develop either lymphoid or myeloid blast crisis. Immunophenotypic, genotypic, and cytogenetic analyses of 22 patients (24 episodes) with Philadelphia (Ph) positive CML in blast crisis were performed to determine the genetic alterations of the blast crisis cells. In B-lymphoid blast crisis, all the five patients had immunoglobulin heavy-chain (IgH) rearrangements and most of them showed normal karyotypes. Among the five patients, T-cell receptor (TCR) genes were rearranged at the following occurrence rates: 20% in TCR-beta, 60% in TCR-gamma, and 40% in TCR-delta chain genes. A high incidence of additional chromosome changes was noted in patients with B-lymphoid/myeloid-mixed blast crisis, but about 80% of them had rearranged IgH and about 40% had TCR rearrangements. In contrast, most of the patients with non-lymphoid blast crisis showed further chromosomal abnormalities, including +8, +19, i(17q), and double Ph, and most of them had germline configurations of IgH and TCR-gamma chain genes. Notably, only one patient (dual lymphoid and myelomegakaryoblast crisis) in this group exhibited IgH rearrangement, and TCR-beta and TCR-delta rearrangements were also rarely noted. Rearrangement of the IgH gene in CML blast crisis might be linked to expression of lymphoid markers, especially CD19.

Antibodies, Monoclonal↗

Immunophenotypic and genotypic characterization of lymphomatoid papulosis.

BACKGROUND: Lymphomatoid papulosis (LyP) is a chronic dermatosis that histologically resembles malignant lymphoma. Thus far, only a few cases of LyP have been characterized in detail with regard to immunophenotype, genotype, and karyotype. OBJECTIVE: Our purpose was to study seven patients with LyP and compare the results to those reported in the literature. METHODS: Skin biopsy specimens were analyzed by frozen section immunohistochemical and molecular biologic techniques. Cytogenetic analysis was also performed in three cases. RESULTS: The atypical lymphoid cells consisted of activated helper T cells; four of the seven patients had lesions with a detectable clonal T-cell population. A peripheral T-cell lymphoma developed in one patient before the emergence of a genotypically different LyP T-cell clone. Cytogenetic studies were abnormal in one case of LyP and normal in another, whereas the karyotype of the lymphoma was abnormal. CONCLUSION: LyP is a preneoplastic proliferation of activated helper T cells, which is often clonal and may regress and expand with the development of new LyP clones or lymphoma.

Adolescent↗

In vitro karyotypic and immunophenotypic characterisation of primitive neuroectodermal tumours: similarities to malignant gliomas.

Monoclonal antibody (Mab) mediated immunotherapy of brain tumours requires the identification of tumour-restricted cell surface antigens. We have characterised four primitive neuroectodermal tumours, which included pineoblastoma, medulloblastoma and ependymoblastoma cultures, that demonstrated in vitro evidence of malignant behaviour (anchorage-independent growth and nu/nu xenograft tumour formation). The cytogenetic findings ranged from normal G-banded and Q-banded karyotypes through mixed near-diploid/hyperdiploid. These cultures resembled the cell surface immunophenotypic spectrum of malignant gliomas. They were distinguished from normal glia in vitro by the expression of restricted fetal mesenchymal, neuronal, myoblastic, melanocytic, epidermal, chondrocytic, lymphoid and epithelial antigens. Certain antigens appeared sufficiently represented among central nervous system (CNS) neoplasms to afford potential targets for Mab-mediated immunotherapy.

Adolescent↗