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B-1a cell origin of the murine B lymphoma line BCL1 characterized by surface markers and bacterial reactivity of its surface IgM.

B cells are divided into two categories: conventional or B-2B cells and B-1B cells, the latter of which are distinguished by their different ontogeny. B cell lymphoma 1 (BCL1), the first-reported case of a spontaneously developed mouse B-lymphoma, expresses CD5, surface IgM, Mac-1, CD43 and low level of B220, and is likely to have B-1a cell origin. However, antigens recognized by IgM produced by the BCL1 cells (BCL1-IgM) have not been identified. Here, we demonstrate that BCL1-IgM reacts with Escherichia coli (E. coli). Our initial finding that several recombinant proteins expressed in E. coli bound to BCL1-B20 prompted us to examine the possibility that BCL1 cells may bind E. coli. Indeed, BCL1 cells bound fluorescein-labeled E. coli. To elucidate the structure on the BCL1 cells responsible for E. coli-binding, we produced a monoclonal antibody capable of inhibiting BCL1 binding to E. coli. The antibody recognizes an idiotypic epitope on the BCL1-IgM. Moreover, polyclonal antibody against IgM and secreted BCL1-IgM purified from the supernatants inhibited BCL1 binding to E. coli. Finally, transfection of non-lymphoid cells with cDNA of heavy and light chains of BCL1-IgM conferred the cells ability to bind E. coli. These results clearly indicate that BCL1-IgM bind E. coli and suggest that BCL1 lymphoma is a typical B-1 cell-derived lymphoma, characterized not only by the surface phenotype, but also by the reactivity of its IgM with commensal bacteria.

Animals↗

[Cell origin of 18 patients with non-T, non-B acute lymphoblastic leukemia].

Cell surface markers of 18 patients with non-T, non-B acute lymphoblastic leukemia (ALL) were analysed with a panel of monoclonal antibodies (McAbs) by indirect immunofluorescence. The results showed that the cells of 13/18 patients originated from immature B cell or B progenitors. The cells of 12/18 patients expressed B cell antigens (CD 19+ or CDw 40+). It was suggested that antibodies directed to these two surface markers could help each other in the diagnosis of ALL of B cell origin. Diagnosis might be further improved if anti-CD19 and CDw 40 McAb be used at the same time. CD 9 antigen was expressed on immature B cell surface. 13/14 patients with B-CLL did not react with anti-CD 9, but 14/18 with non-T, non-B ALL were positive. Cells of 7/18 patients expressed CALLA (CD 10), HLA-DR and CD 19/CDw 40, but did not express T cell associated antigens (CD1, CD2, CD3, CD7), so CALLA(+)-ALL also belongs to B cell lineage.

Adult↗

Bcl-2, Bcl-6 and CD10 expression in cutaneous B-cell lymphoma: further support for a follicle centre cell origin and differential diagnostic significance.

BACKGROUND: Primary cutaneous follicle centre cell lymphomas (PCFCCLs) are the most common type of cutaneous B-cell lymphoma. There is ongoing discussion on the origin of the neoplastic B cells in these PCFCCLs, and consequently on their relation to the groups of primary cutaneous marginal zone B-cell lymphomas (PCMZLs) and nodal follicular lymphomas. OBJECTIVES: To define better the neoplastic B cells in PCFCCLs, and to find out if differences in the expression of the antiapoptopic protein Bcl-2, and Bcl-6 and CD10, molecules which are normally expressed by the neoplastic B cells in nodal follicular lymphomas, might have diagnostic or prognostic significance in cutaneous B-cell lymphoproliferative disorders. METHODS: Pretreatment biopsies of well-defined groups of PCFCCL (n = 24), PCMZL (n = 14), primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg; n = 19), secondary cutaneous follicular lymphoma (n = 3) and cutaneous pseudo-B-cell lymphoma (n = 6) were investigated by immunohistochemistry for expression of Bcl-2, Bcl-6 and CD10. RESULTS: The PCFCCLs consistently expressed Bcl-6, whereas CD10 and Bcl-2 were expressed in only one and two of 24 cases, respectively. In contrast, PCMZLs were always negative for Bcl-6 and CD10, but were Bcl-2 positive, whereas skin and lymph node localizations of secondary cutaneous follicular lymphomas consistently expressed all of Bcl-2, Bcl-6 and CD10. Reactive follicle centre cells in pseudo-B-cell lymphomas expressed Bcl-6 (six of six cases) and CD10 (five of six cases), but not Bcl-2. PCLBCL-leg was Bcl-6 positive and CD10 negative in all cases, irrespective of clinical outcome, and strongly expressed Bcl-2 protein in all but two cases. CONCLUSIONS: The results of the present study provide further support for the follicle centre cell origin of both PCFCCL and PCLBCL-leg, and indicate that staining for Bcl-2, Bcl-6 and CD10 can serve as an important adjunct in the differential diagnosis of cutaneous B-cell lymphoproliferative disorders.

DNA-Binding Proteins↗

Epidermal Langerhans cells are derived from cells originating in bone marrow.

Langerhans cells constitute a morphologically well characterised subpopulation (3--8%) of mammalian epidermal cells which, in contrast to the bulk of epidermal cells, bear Fc-IgG and C3 receptors, express immune response-associated (Ia) antigens and function as antigen-presenting cells and allogeneic stimulatory cells to primed T lymphocytes. The ontogeny of Langerhans cells has been a subject of considerable debate since their discovery. Although some studies suggest that Langerhans cells are of mesenchymal as opposed to neural or melanocytic origin, direct evidence for this has not been presented. In this study we demonstrate that, after 3 weeks, most of the Langerhans cells (LC) in parenteral skin which had been transplanted on to F1 hybrids were of recipient origin whereas keratinocytes remained of donor origin; this indicates that the LC are derived from a mobile pool of cells. Furthermore, in studies of skin from radiation-induced bone marrow chimaeric animals we found that, depending on the strain combination, up to 80% of the epidermal LC were derived from the bone marrow of the donor animals.

Animals↗

Memory T cells originate from adoptively transferred effectors and reconstituting host cells after sequential lymphodepletion and adoptive immunotherapy.

Adoptive transfer of tumor-specific effector T cells induces regression of advanced tumors and induces a long term memory response; however, the origin of this response has not been clearly defined. In this study Thy1.2+ mice bearing advanced MCA-205 tumors were treated with sublethal total body irradiation, followed by adoptive transfer of congenic Thy1.1+ T cells that had been sensitized to tumor in vivo and then activated ex vivo with anti-CD3, IL-2, and IL-7. Splenocytes were recovered >140 days after the initial therapy, and the L-selectinlow memory cell subset was separated into host Thy1.2+ and transferred Thy1.1+ cells and restimulated ex vivo. Both adoptively transferred Thy1.1+ cells as well as reconstituted host Thy1.2+ cells could specifically eliminate MCA-205 pulmonary metastases. Interestingly, hosts with partial responses followed by tumor recurrence nevertheless harbored memory cells that could be isolated and numerically amplified ex vivo to regenerate potent effector function. Memory cells were recovered after adoptive transfer into lymphodepleted nontumor-bearing hosts, indicating that they were not dependent on continued Ag exposure. These experiments establish that rapid ex vivo expansion of tumor Ag-primed T cells does not abrogate their capacity to become long-lived memory cells. Moreover, immune-mediated tumor regression coincident with lymphoid reconstitution produces another wave of host memory cells. These data suggest an approach to rescuing antitumor immune function even in hosts with long-standing progressive tumor through restorative ex vivo activation.

Animals↗

Mismatch repair gene expression in malignant lymphoproliferative disorders of B-cell origin.

We investigated mismatch repair (MMR) gene expression in 31 lymphoid tissue specimens and bone marrow aspirates with malignant lymphoproliferative disorders of B-cell origin (25 cases of lymphoma and six cases of plasma cell myeloma). A multiplex RT-PCR assay was employed to assess the relative expression of the hMSH2, hMLH1 and hPMS1 genes, as compared to beta-actin, which was used as an internal control of gene expression. MSH2 was further evaluated at the protein level by immunohistochemistry. The findings were compared to those of a control group of lymphoid tissue specimens without evidence of malignancy (n = 6). Changes in MMR gene expression were observed in 10 out of 31 cases of the study group (32%). All three MMR gene transcripts were low in two out of six plasma cell myelomas, which had extensive bone marrow infiltration by neoplastic cells. The hMSH2 transcript was present in all cases of lymphoma, while the expression of hMLH1 and hPMS1 was significantly low in some large B-cell lymphomas (four and five out of 14 cases, respectively) and in mantle cell lymphomas of the blastoid type (two out of two cases). No MMR gene aberrations were found in seven cases of B-cell lymphocytic leukemia and two cases of mantle cell lymphoma of centrocyte-like type. These findings demonstrate that the expression rates of the hMSH2, hMLH1 and hPMS1 genes differ among various types of B-cell lymphoproliferative disorders, and suggest that MMR gene expression may be related to the natural history of these neoplasms. This study identified a higher incidence of MMR gene aberrations in lymphoma types characterized by aggressive biologic behavior, as compared to neoplasms with a more indolent course.

Adaptor Proteins, Signal Transducing↗

The involvement of adult stem cells originated from bone marrow in the pathogenesis of pterygia.

Pterygium is a proliferative disease. Recent research has reported that stem cells are involved in the pathogenesis of various proliferative diseases, including solid tumors and diabetic proliferate vitreoretinopathy. In previous literature, we hypothesized that adult stem cells originated from bone marrow were involved in the pathogenesis of pterygium. We proved this by immunohistochemical staining with various stem cell markers. The staining showed adult stem cells in the pterygium. c-kit positive cells were observed primarily in the stroma, and some cells were also found in the basal epithelium. AC133 and CD34 positive cells were primarily found in the basal epithelium and were ovoid shaped, similar to the c-kit cells. However, some cells were found in vascular endothelium. STRO-1 positive cells were found mainly in the stroma and were spindle shaped. In recurrent pterygium, cells were more scattered and the expression pattern was denser. Therefore, we suggest a new theory of pterygium pathogenesis. Inflammation caused by environmental factors triggers the abnormal production of some growth factors and cytokines in order to recover from cellular damage. If these healing signals are excessive, limbal basal cells will be changed to abnormally-altered pterygial cells. The excessive wound healing process and remnant altered cells result in recurrence using the same mechanism.

AC133 Antigen↗

"Cercariform" cells: a clue to the cytodiagnosis of transitional cell origin of metastatic neoplasms?

The "cercariform" cell is described as a distinct cytomorphologic clue that may be helpful in the diagnosis of metastatic transitional cell neoplasms, particularly low grade. This cell has a nucleated globular body and a cytoplasmic process with a nontapering, flattened, bulbous or fishtail-like end. The cercariform cell corresponds to intermediate cells in histologic and ultrastructural preparations of normal urothelium. The cercariform appearance is the result of pseudostratification of both normal and low-grade neoplastic urothelium. The unique features of cercariform cells make them readily distinguishable from neoplastic squamous cells as well as spindle cells of mesenchymal origin.

Adult↗

Dendritic cell origins: puzzles and paradoxes.

In the present review, a series of studies on the origins of dendritic cells of mice and humans are summarized. Several subsets of mature dendritic cells found in vivo are described and these may correspond to distinct lineages. There is evidence that some dendritic cells are myeloid-derived and that others are lymphoid-derived. The different ways of generating dendritic cells are examined and an attempt to reconcile the differences seen using mouse and human culture models is made. The particular case of Langerhans cells is discussed and an historical overview of the biology of the plasmacytoid T cells, which may represent a distinct 'lymphoid-related' dendritic cell lineage, is given. It is concluded that three or four different pathways lead to the development of different subtypes of dendritic cells.

Animals↗

Remodeling of suspended small intestinal submucosa venous valve: an experimental study in sheep to assess the host cells' origin.

PURPOSE: To investigate the origin of host cells during remodeling of small intestinal submucosa (SIS) square stent-based bicuspid venous valves (VVs). MATERIALS AND METHODS: Suspended VVs (SVVs) were developed by suspending VVs within bare square stents so the valve elements would not contact the vein wall after deployment. Eight SVVs were placed within the intrahepatic and infrahepatic inferior venae cavae (IVCs) of four adult female sheep. Eight standard VVs were implanted in the external jugular veins of these animals for comparison. At 5 weeks after placement, the devices were examined for stability and patency and the animals were killed. Gross, histologic, and scanning electron microscopic (SEM) examinations were performed. RESULTS: Follow-up spot radiographs and venography showed no migration of the devices, venous occlusion, or thrombus formation. All SVVs were intact without contact with the IVC wall. Six VVs were competent and two were slightly tilted with some reflux. Histologic study showed remodeling of SVVs and VVs with newly formed collagen fibers; fibroblasts and inflammatory cells were found penetrating the SIS leaflets and endothelial cells on the surface. SIS neovascularization was also present. There was no difference regarding SIS remodeling between SVVs and the free part of VV leaflets. The VV leaflets' bases were thicker compared to their free parts (P <.01). SEM examination showed endothelial cells on both sides of the SVVs and VVs. Endothelialization of the SVV central leaflet surfaces and both surfaces of the VV leaflets was more complete than that of the peripheral surfaces of the SVV leaflets. CONCLUSION: SIS-based valve remodeling occurs independently of vessel wall contact by recruitment of cells directly from the circulation.

Animals↗

Expression of the CEA gene family members NCA-50/90 and NCA-160 (CD66) in childhood acute lymphoblastic leukemias (ALLs) and in cell lines of B-cell origin.

The carcinoembryonic antigen (CEA) and the classical non-specific cross-reacting antigens (NCAs) belong to the CEA gene family which is part of the immunoglobulin superfamily. In normal hematopoiesis, CEA gene family members (CGMs) have only been reported on cells of myeloid and monocytic origin. In the present study, we analyzed 62 childhood acute lymphoblastic leukemias (ALLs) and seven surface immunoglobulin positive (sig+) B-cell lines for the expression of the CEA family members CEA, NCA-50/90, NCA-95, NCA-160, CGM1 and CGM7. We demonstrated that members of the CEA family were present in 76% of childhood ALLs of B- and T-cell origin. In ALLs of B-cell origin, 82% of the samples expressed at least one CEA subgroup member: 38% NCA-50/90 (CD66c), 31% NCA-160 (CD66a), and 13% both. Six of seven B-cell lines solely expressed NCA-160. In seven ALL of T-cell origin, sole NCA-160 expression was present in 29% of the cases. CEA and CGM1 were not expressed in childhood ALLs or in the sIg+ B-cell lines. In 15 ALLs and seven B-cell lines which could be analyzed for CGM7 expression, the antigen was not detected. NCA-95 was not expressed in 91% of the B-lineage ALLs, in T-lineage ALLs and in the B-cell lines. However, five B-lineage ALLs showed conflicting data on the binding patterns of two, on leukocytes specifically NCA-95 recognizing antibodies suggesting either expression of unknown forms of NCA-95 or NCA-50/90 or of a yet unknown member of the CEA family in these ALL cells. The expression of CEA subgroup members in childhood ALL cells might have prognostic impacts, as an inverse correlation exists between NCA expression on leukemic blasts and the risk factor white blood count at diagnosis.

Adolescent↗

Prognostic significance of CD30 (Ki-1/Ber-H2) expression in primary cutaneous large-cell lymphomas of T-cell origin. A clinicopathologic and immunohistochemical study in 20 patients.

The histologic and immunophenotypical features of 20 primary cutaneous large-cell lymphomas of T-cell origin were investigated and correlated with clinical data to obtain prognostically relevant criteria. Histologic evaluation, using the updated Kiel classification, showed that these large-cell lymphomas represent a morphologic spectrum, often making classification rather arbitrary. It is therefore concluded that the clinical relevance of histologic subtyping is limited for this group of lymphomas. Immunophenotypical studies revealed significant differences between CD30-positive and CD30-negative lymphomas. CD30-positive lymphomas generally presented with localized skin disease, and had a favorable prognosis (9 of 10 patients alive and in complete remission; median survival, 37 months). In contrast, CD30-negative lymphomas often presented with or rapidly developed generalized disease; all patients died of lymphoma (median survival, 17 months). These findings suggest that CD30 expression is an important prognostic parameter for this group of primary cutaneous large-cell lymphomas.

Antigens, CD↗

Monolayer culture of cells originating from a preimplantation bovine embryo.

The objective of this study was to establish a method by which trophectodermal cells originating from individual preimplantation bovine embryos could be perpetuated in monolayer culture. A single, Day-11 bovine embryo collected nonsurgically from a mixed-breed beef cow was cultured in Ham's F10 medium supplemented with fetal bovine serum, sodium pyruvate, insulin, and epidermal growth factor. After 13 d in culture the embryo had adhered to the surface of the plastic culture vessel and a monolayer covering 0.3 cm2 had developed in the manner of a tissue explant. The monolayer was successfully dispersed using trypsin-EDTA and the cells were passaged. Expansion to a 25-cm2 flask was achieved by the 4th passage. By passaging cultures at a dilution ratio of 1:2, cells were maintained for 38 passages before growth slowed. Transfers beyond the 44th passage were unsuccessful. The cell line, designated BE-13, was successfully frozen and thawed at the 9th, 12th, 15th, and 20th passages. The cell line contains both mono- and binucleate cells with a prominent rough endoplasmic reticulum characteristic of ruminant trophoblast cells. Susceptibility to eight bovine viruses was demonstrated. Such cell lines may provide inexpensive systems for the study of trophoblast metabolism and for investigation of the role of the trophoblast in the pathogenesis of selected bovine abortifacient diseases. Because of their range of viral susceptibility, these cells might also be useful for diagnostic purposes.

Animals↗

Inflammatory fibroid polyps of the gastrointestinal tract: evidence for a dendritic cell origin.

Inflammatory fibroid polyps (IFPs) are rare mesenchymal tumors of the gastrointestinal tract that consist of spindle-shaped stromal cells and an inflammatory infiltrate rich in eosinophils. Their etiology and histogenesis remain unknown. Based on previous reports of their immunoreactivity for CD34 and c-kit biomarkers, IFPs have been thought to be related to gastrointestinal stromal tumors (GISTs). After reviewing the current literature and examining IFPs at the light microscopic level, we evaluated a series of IFPs using an extensive panel of immunohistochemical and in situ hybridization markers in an effort to gain insight into their etiology and histogenesis and to determine their true relationship to GISTs. Sixteen routinely processed IFP specimens (14 gastric, 1 ileal, and 1 rectal) were immunohistochemically stained for antibodies to CD34, HMB-45, desmin, smooth muscle actin, calponin, h-caldesmon, anaplastic lymphoma kinase, S-100 protein, epithelial membrane antigen, c-kit (CD117), stem cell factor (SCF/N19 or kit ligand), p53, bcl-2, cyclin D1, and human herpesvirus-8 (HHV8). In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was also performed. Ten cases were further evaluated for the dendritic cell markers fascin, CD21, CD23, and CD35. Stromal cells were diffusely positive for CD34 and fascin in all (100%) cases, and these stromal cells were, in addition, immunoreactive for calponin and smooth muscle actin in 88% and 25% of cases, respectively. CD35 was also found to be focally reactive in the stromal cells. Cyclin-D1 was overexpressed in all (100%) IFPs. All other immunohistochemical markers and EBER were negative in the stromal cells. These findings suggest that the proliferating stromal cells in IFPs are of dendritic cell origin, with some cases also exhibiting myofibroblastic features. Absence of c-kit, SCF, and h-caldesmon immunoreactivity fails to support a relationship to GISTs. We also conclude that Epstein Barr virus and HHV8 are unlikely etiologic agents of IFPs. Overexpression of cyclin D1 in all cases suggests that a defect in cell-cycle regulation may be involved in the growth of IFPs.

Adult↗

Regulatory function of Thy-1-negative cells: V. A lymphokine of B cell origin (BEF) induces in vitro high antibody response in genetically selected low responder mice.

Studies were conducted on two lines of mice genetically selected, respectively, for high (AB/H) and low (AB/L) antibody production, in order to identify the mechanism by which genes involved in the selection express their functions. It was found that B cell-derived enhancing factor (BEF), a lymphokine of B cell origin which acts on T cells by preventing the activation of suppressor cells, is effective in inducing high responses in low responder mice, whereas it is ineffective in modulating antibody production in high responder mice. As a result, no difference was found between the responses of AB/H and AB/L mice when spleen cells were stimulated in vitro in the presence of BEF. AB/H and AB/L mice do not seem to differ in their B cell functions since no difference was found in the capacity of B cells of either line to synthesize antibodies in the presence of T cell-replacing factor (TRF), or to produce endogenous BEF. These data indicate that, at least in vitro, the character of general responsiveness of these two mouse lines mainly reflects differential reactivity of T suppressor cells. Since the two lines represent, respectively, the maximal and minimal responsiveness of an outbred population of animals, it is suggested that the individual difference in antibody response is related to individual differences of T suppressor cells in responding to the immunogen.

Animals↗

The greater glycan content of recombinant human thyroid peroxidase of mammalian than of insect cell origin facilitates purification to homogeneity of enzymatically protein remaining soluble at high concentration.

Structural studies on thyroid peroxidase (TPO), a major thyroid autoantigen, require milligram amounts of pure protein. We found that the human TPO ectodomain (amino acid residues 1-848) generated in insect cells did not remain in solution at high concentrations after affinity purification. In contrast, the TPO ectodomain secreted by mammalian (Chinese hamster ovary) cells, although generated to a lesser extent (1 vs. 8 mg/liter), remained in solution at high concentration (10 mg/ml) after purification to homogeneity. This purified material was well recognized by TPO autoantibodies, but lacked enzymatic activity. We attempted to restore activity by culturing the Chinese hamster ovary cells in the presence of added heme. TPO enzymatic activity was clearly detected in conditioned medium from cells cultured in hematin and hemin, but not in protoporphyrin IX (all at 1 mg/liter). Heme prosthetic group incorporation into affinity-purified TPO was highest for hematin and hemin, but unchanged for protoporphyrin IX (OD 410/280 nm ratios of 0.25, 0.23, and 0.14, respectively). Enzymatic activity was now evident with hemin (mean +/- SE, 27.2 +/- 2.6; n = 3; guaiacol units/mg protein), hematin (24.1 +/- 1.6), and, to a lesser extent, protoporphyrin IX (3.6 +/- 0.2). Culturing cells in 20 mg/liter hematin, the maximum concentration tolerated, increased enzymatic activity even further (45.6 +/- 0.6 guaiacol units/mg protein). All purified TPO preparations were homogeneous on PAGE and of similar size (105 kDa). Enzymatic deglycosylation showed a complex carbohydrate contribution of 13 kDa (unlike the 2.3 kDa in insect cell TPO). In conclusion, this is the first report on the purification to homogeneity of recombinant human TPO of mammalian cell origin. Unlike TPO generated in insect cells, mammalian TPO remains soluble at high concentration, possibly because of its greater carbohydrate content. This enzymatically active, recombinant human TPO may be useful for future structural studies.

Animals↗

The B cell IgM Fc receptor: further evidence for the B cell origin of "null" chronic lymphocytic leukemia.

Fifty-three cases of chronic lymphocytic leukemia (CLL) were studied for the presence of the B cell IgM Fc receptor (Fc microR) using an aggregated IgM reagent. Restricted surface immunoglobulin, using conventional immunofluorescent techniques and FACS analysis, was detected in 43 cases (81%). The cells in the remaining ten cases (19%) expressed negligible surface immunoglobulin (slg-) and did not form E rosettes (E-), but this "null" subset clearly expressed the B cell Fc microR. The coincident membrane expression of the B1 antigen and the la-like antigen, as well as serial studies showing surface membrane light chain acquisition (in one patient), provided additional evidence for the B cell origin of this slg-E- subset. This subgroup of CLL appears to correspond phenotypically to a normal counterpart at a stage of B cell differentiation between the pre-B cell and the slgM+ early B cell. The B cell Fc microR appears to be a consistent and potentially useful marker for sl gE ("null") CLL.

Antigens, Surface↗

Intratumoral microvascular density in malignant lymphomas of B-cell origin.

Sections of surgical lymph-node biopsies of four types of malignant non-Hodgkin's lymphoma of B-cell origin (B-NHL) classified according to the R.E.A.L. terminology or lymphadenitis were immunostained in order to demonstrate endothelial CD34 (QBEnd 10) and to determine the microvascular density and vessel-size distribution using an interactive image-analysis technique. Only microvessels displaying a cross-sectional area corresponding to a diameter of between 3.2 and 34.6 microm were included. The intratumoral microvascular density (iMVD) was found to be significantly higher in chronic lymphatic leukaemia (CLL, n = 13) compared with the clinically more aggressive mantle cell lymphoma (MCL, n = 9) and diffuse large B-cell lymphoma (DLBCL, n = 14). iMVD in CLL was also higher than in the follicular neoplastic parts (FL FOLL) of follicular lymphoma (FL, n = 16). In FL FOLL the microvessel density was, moreover, significantly lower than in the surrounding non-neoplastic FL tissue. In lymphadenitis (LA, n = 10) the iMVD was higher than in DLBCL, FL FOLL and MCL. The data suggest that future studies focusing on the relationship between iMVD and the clinical outcome within each particular NHL group should be carried out in order to verify whether iMVD is a prognostic factor in NHL, as it is in carcinomas.

Humans↗