Biomedical subjects

I Anagnostopoulos

Publications and source records attributed to I Anagnostopoulos.

At least 19 recordsLinked to original sources

PubMed2007

[The morphologic variants of KSHV/HHV 8-associated lymphoproliferations].

KSHV/HHV 8 infection is associated with primary effusion lymphoma, multicentric Castleman disease (MCD) and MCD-associated plasmablastic lymphoma. We report the case of an HIV-infected male with Kaposi sarcoma, MCD in the lymph node and development of a KSHV/HHV 8-associated plasmablastic lymphoma in the liver. Immunohistochemistry revealed an HHV 8 infection of plasmablasts showing cytoplasmic IgM/lambda expression. To the best of our knowledge, liver infiltration by a MCD-associated HHV 8 positive plasmablastic lymphoma has not been documented previously. The differential diagnosis is discussed.

Adult↗

PubMed2006

[Oral EBV-associated diffuse large B-cell lymphomas in HIV-negative immunocompromised patients].

BACKGROUND: Diffuse large B-cell lymphomas (DLBCL) are non-Hodgkin's lymphomas (NHL) and with a prevalence of 30-40% they comprise the most frequent NHL in adults. Although their etiology is still unknown, a virus induction, especially by the Epstein-Barr-virus (EBV), is the subject of discussion. Patients with congenital or acquired immunodeficiency are primarily afflicted. PATIENT 1: A 39-year-old female patient developed an EBV-associated DLBCL of the plasmablastic subtype in the maxillary alveolar ridge in the region of teeth 11 and 21 after 24 years of immunosuppressive therapy with azathioprine due to myasthenia gravis. Clinically the lesion presented as a localized acute necrotizing periodontitis that was resistant to symptomatic therapy. After polychemotherapy the disease is in complete remission until today. PATIENT 2: A 56-year-old male patient developed an EBV-associated DLBCL of immunoblastic variant of the right maxillary edentulous alveolar ridge in the posterior region 7 weeks after heart transplantation and immunosuppressive therapy with azathioprine and cyclosporine A. Clinically, a soft, nonpainful, swelling measuring 1.5x0.5x0.5 cm with a central ulceration was evident. The tumor was excised followed by local radiation therapy. No recurrence was noted during a 15-year-follow-up. DISCUSSION: The presented clinical cases demonstrate the increased risk of occurrence of oral malignant B-cell lymphomas as adverse effects of immunosuppressive therapy. The demonstration of EBV in the tumor cells in both cases underlines the involvement of this virus in the pathogenesis of oral DLBCL arising in the setting of an immunodeficiency as has been shown previously in patients with HIV. CONCLUSIONS: Due to the varying and often nonspecific clinical appearance of oral DLBCL, an early biopsy and work-up by an institute specialized in hematopathology is essential for diagnosis, because these tumors may disseminate in early stages.

Adult↗

PubMed2006

Different T-bet expression patterns characterize particular reactive lymphoid tissue lesions.

AIMS: To investigate T-bet expression profiles in various lymphoid tissue diseases caused by intracellular pathogens and to compare them in disorders without an infective aetiology. Murine and in vitro experiments have shown that the expression/induction of T-bet, the master regulator of Th1 differentiation, can be achieved by obligate intracellular pathogens and high interferon (IFN)-gamma levels. METHODS: Lymph node biopsies were analysed immunohistochemically employing single and double labelling for T-bet and CD20, CD4, CD8 and CD30 detection. RESULTS: In disorders associated with high IFN-gamma levels and intracellular pathogens (infectious mononucleosis, HIV-associated lymphadenopathy, cat-scratch disease, and toxoplasmic lymphadenitis), T-bet-expressing CD4 cells were accompanied by significant numbers of T-bet-positive CD8 and B cells. A similar profile was also found in histiocytic necrotizing (Kikuchi) lymphadenitis, a disease of unknown cause. In contrast, T-bet expression in disorders without an infective aetiology was observed in only a small portion of lymphocytes. CONCLUSIONS: Increased T-bet expression does not only identify intracellular infections in lymphoid tissue associated with high IFN-gamma levels, but also implies that, under these conditions, it becomes induced in B cells, which apparently support the Th1 response. T-bet expression in Kikuchi lymphadenitis underscores the hypothesis that it is caused by an intracellular microorganism.

Antigens, CD20↗

PubMed2006

Three coexisting lymphomas in one patient: genetically related or only a coincidence?

The simultaneous manifestation of different lymphomas in the same patient or even in the same tissue, defined as composite lymphoma, is very rare. The exceptional case of a patient who, presented with simultaneous manifestation of three different lymphomas after 30 years of successful treatment of a nodal T cell lymphoma is reported here. The three lymphomas were: (1) primary cutaneous marginal zone B cell lymphoma (MZBL); (2) nodal Epstein-Barr virus (EBV)-associated classic Hodgkin's lymphoma (cHL) of the B cell type; and (3) peripheral T cell lymphoma coexisting in the skin and cervical lymph node. Immunohistochemical and molecular analyses showed different clonal origins of EBV-negative cutaneous MZBL and EBV-positive B cell cHL and, in addition, the presence of the same clonal T cell population in the skin and lymph node. The simultaneous occurrence of three different, clonally unrelated lymphomas in one patient at the same time has not been reported yet.

Aged↗

PubMed2006

Dermatopathic lymphadenopathy: a differential diagnosis of enlarged lymph nodes in uremic pruritus.

BACKGROUND: In end-stage renal disease patients, the incidence of both infections and malignancies is increased leading to a higher incidence of peripheral lymphadenopathy. In the present work we describe a rare but probably underdiagnosed cause for enlarged lymph nodes in uremic patients. PATIENT: A 43-year-old male patient was admitted to our hospital with inguinal lymphadenopathy and pruritus. He turned out to be uremic due to focal segmental glomerulosclerosis (creatinine 4.5 mg/dl, MDRD creatinine clearance 12 ml/min). FINDINGS: Sonography revealed enlarged lymph nodes (up to 4 cm) with intact corticohilar border differentiation. After extirpation of an inguinal lymph node, histological examination established the diagnosis of dermatopathic lymphadenopathy. T cell lymphoma was excluded by PCR for T cell receptor-gamma rearrangements and subsequent GeneScan analysis. Intravenous fluid supplementation with subsequent decline of creatinine, UVB treatment, clemastine, and topical use of emollients led to a relief of the uremic pruritus and the lymph nodes' size normalized within 8 weeks. CONCLUSION: Dermatopathic lymphadenopathy refers to the reactive condition seen in lymph nodes that drain areas with disruption of the skin integrity, e.g. due to scratch marks. The present case report describes dermatopathic lymphadenopathy as a harmless cause of enlarged lymph nodes in uremic pruritus for the first time. This entity should be considered in the differential diagnosis of peripheral lymphadenopathy of unknown origin in patients with renal failure.

Adult↗

PubMed2005

T-bet expression patterns in coeliac disease, cryptic and overt enteropathy-type T-cell lymphoma.

AIMS: To clarify the distribution and lineage allocation of T-bet-expressing cells in coeliac disease (CD) and in enteropathy-type T-cell lymphoma (ETTCL). The detection of elevated levels of interferon-gamma, interleukin-18 and the key regulator of Th1 helper immune response T-bet in CD biopsies led to the view that CD is the result of a Th1 response to gluten. It remains unknown whether T-bet is expressed in cryptic and overt ETTCL. METHODS: Specimens from 20 patients with CD, five patients with cryptic and 10 patients with overt ETTCL were analysed by immunohistology employing single and double labellings for T-bet and CD4 or CD8 antigens. RESULTS: In CD specimens nearly all intraepithelial CD8 cells and many CD4 cells in the lamina propria expressed T-bet. Cryptic ETTCL showed T-bet expression in the intraepithelial neoplastic cells while T-bet+ CD4 cells in the lamina propria were rare. Overt ETTCL showed T-bet expression in cases with non-anaplastic morphology. In addition, a proportion of bystander T cells expressed T-bet. CONCLUSIONS: Morphological evidence proves that while T-bet orchestrates a CD4- and CD8-based Th1 reaction in CD, its expression shifts to the neoplastic intraepithelial compartment of cryptic ETTCL and becomes absent or lost in anaplastic overt ETTCL.

CD4 Antigens↗

PubMed2005

Effect of anti-CD 20 antibody rituximab in patients with post-transplant lymphoproliferative disorder (PTLD).

Post-transplant lymphoproliferative disorders (PTLD) are a life-threatening complication following solid organ transplantation. Treatment with rituximab, a humanized anti-CD20 monoclonal antibody, has proved to be a promising approach and shown a low toxicity profile. Between February 1999 and April 2002, we conducted a multicentre phase II trial investigating rituximab as single agent in 17 patients with PTLD. Transplanted organs were heart (n = 5), kidney (n = 4), lung (n = 4) and liver (n = 4). Patients were treated with four weekly doses of 375 mg/m(2) of rituximab. The mean follow-up time is 24.2 months. Histology was distributed in 10 diffuse large cell-, 2 marginal zone-, 1 Burkitt-like lymphoma, 1 Hodgkin-like PTLD and 3 polymorphic lymphoproliferations. Therapy was well tolerated and no severe adverse events were observed. The mean overall survival period is 37.0 months with 11 patients still living. In total, 9 patients (52.9%) achieved a complete remission, with a mean duration of 17.8 months. Partial remission was observed in 1 patient, minor remission in 2 patients, no change in 3 patients and 1 patient experienced progressive disease. Two patients relapsed, at intervals 3 and 5 months after obtaining complete remission. Rituximab proved to be well tolerated and effective in the treatment of PTLD.

Adult↗

PubMed2005

Plasmacellular differentiation in extranodal marginal zone B cell lymphomas of the ocular adnexa: an analysis of the neoplastic plasma cell phenotype and its prognostic significance in 136 cases.

AIM: To determine (a) the expression of plasma cell related antigens in extranodal marginal zone B cell lymphomas (EMZL) of the ocular adnexa; and (b) the prognostic value of plasmacellular differentiation in these tumours. METHODS: A consecutive case series of 136 ocular adnexal EMZL obtained from three ocular pathology centres over 20 years was analysed retrospectively. An extensive immunohistochemical panel, including the plasma cell related antigens VS38c, CD38, CD138, multiple myeloma oncogene-1-protein (MUM1/IRF4), and CREB binding protein (CBP) was performed. EMZL were defined as "plasmacellular differentiated" on the basis of morphological features, evidence of cytoplasmic immunoglobulin, negativity for BSAP/PAX5, and expression of at least one of the investigated plasma cell related antigens. Controls included normal or hyperplastic lymphatic tissues. Detailed clinical data were collected for most patients, and compared with the results of immunohistochemistry. The end points considered for statistical analysis were development of local tumour recurrence, development of systemic disease, and lymphoma related death. RESULTS: 57 (42%) of the 136 ocular adnexal EMZL showed a plasmacellular differentiation; 45 of these plasmacytoid cases were primary tumours. In contrast with most admixed normal plasma cells, which displayed co-expression of MUM1/IRF4, Vs38c, CD38, CD138, and CBP, the plasmacellular differentiated EMZL tumour cells demonstrated co-expression of all five plasma cell related antigens in only six of 57 (11%) plasmacellular differentiated ocular adnexal EMZL. The most commonly expressed plasma cell related antigen was MUM1/IRF4, immunoreactivity being seen in 56/57 (98%) plasmacellular differentiated EMZL examined. Although the association of plasmacellular differentiation in primary ocular adnexal EMZL and disseminated disease was statistically significant on univariate analysis (p = 0.042), this was weaker on multivariate analysis. CONCLUSION: Plasmacellular differentiated tumour cells in EMZL demonstrate an aberrant immune profile for plasma cell related antigens when compared with normal plasma cells. On multivariate analysis, plasmacellular differentiation in ocular adnexal EMZL was not significantly associated with local recurrence, the development of systemic disease, or with lymphoma related death.

ADP-ribosyl Cyclase↗

PubMed2004

Cutaneous T cell lymphoma and classic Hodgkin lymphoma of the B cell type within a single lymph node: composite lymphoma.

Composite lymphomas are defined as two unrelated, morphologically and genetically distinct lymphomas occurring at the same point in time within the same tissue or organ. Since their original definition, several composite lymphomas have been reported exclusively based on morphological grounds. However, with the application of immunohistological and molecular biological techniques it has become evident that many so called "composite" lymphomas do not fulfil the necessary criteria, because they merely represent two different morphological phenotypes of the same malignant clone. This report describes the manifestation of a true composite lymphoma within a single cervical lymph node, which is composed of a cutaneous T cell lymphoma and a classic Hodgkin lymphoma of B cell type--a very rare finding indeed.

Aged↗

PubMed2003

Receptor revision of immunoglobulin heavy chain genes in human MALT lymphomas.

BACKGROUND/AIMS: Rearrangement of immunoglobulin gene segments, leading to B cells with functional receptors, is thought to be largely restricted to developing immature B cells in bone marrow. However, accumulating evidence suggests that mature B cells occasionally modify their antigen specificity by VH segment replacements during the germinal centre reaction to enhance antigen affinity, or to overcome self reactive antigen receptors. Although malignant B cells maintain the features of their normal counterparts in most instances, to date, such replacements have not been described for human B cell lymphomas. METHODS: Rearranged immunoglobulin heavy chain genes from two extranodal marginal zone B cell lymphomas were amplified, cloned, and sequenced. Sequences with identical CDR3 regions were selected and aligned to each other and public databases. RESULTS: VH replacements were seen in two extranodal marginal zone B cell lymphomas. In line with the hypothesis that in mature B cells these replacements are associated with active somatic hypermutation, in addition to VH replacement, different mutation patterns were seen in the revised VH portions. In the remaining common 3'-VH regions, these mutations could be used to establish a phylogenetic relation between the sequences, rendering the possibility of artefactual chimaeric polymerase chain reaction products very unlikely. CONCLUSIONS: These results support the view that VH replacements are a further mechanism for reshaping antigen affinity and specificity, and indicate that these receptor modifications are not restricted to normal and reactive germinal centre B cells, but may also occur in close association with the development of malignant B cell lymphomas.

Base Sequence↗

PubMed2003

[Classification and differential diagnosis of B-cell lymphomas].

The standard for the pathological identification of B-cell lymphomas is the World Health Organization (WHO) classification, which integrates tumor morphology, immunophenotype, recurrent genetic abnormalities and clinical features. The lymphoma entities defined in this classification are derived from virtually every stage of normal B-cell differentiation. This classification which has gained wide acceptance has proven useful in patient management and treatment. Novel findings based on gene expression profiling have however started to reveal that not all described entities are entirely molecularly homogeneous. This report describes distinct examples of the more common B-cell lymphomas along with the pathogenetic models and gives some information on the novel gene expression profiling data.

Burkitt Lymphoma↗

PubMed2002

Molecular genetic diagnosis of a primary central nervous system T cell lymphoma.

Primary central nervous system T cell lymphomas are rare tumors. Histologically, they may be indistinguishable from other entities like inflammatory processes. In such cases, molecular genetic verification of clonal T cell receptor (TCR) gene rearrangements is an indispensable diagnostic tool. Here we present a case where identification of TCR beta and gamma gene rearrangements by polymerase chain reaction was used to differentiate between a vasculitis and a primary CNS T cell lymphoma, which has profound consequences for therapy management and outcome.

Adult↗

PubMed2002

Expression of the progesterone receptor and progesterone- metabolising enzymes in the female and male human kidney.

Due to high binding affinity of progesterone to the human mineralocorticoid receptor (hMR), progesterone competes with the natural ligand aldosterone. In order to analyse how homeostasis can be maintained by mineralocorticoid function of aldosterone at the MR, especially in the presence of elevated progesterone concentrations during the luteal phase and pregnancy, we investigated protective mechanisms such as the decrease of free progesterone by additional binding sites and progesterone metabolism in renal cells. As a prerequisite for sequestration of progesterone by binding to the human progesterone receptor (hPR) we demonstrated the existence of hPR expression in female and male kidney cortex and medulla at the level of transcription and translation. We identified hPR RNA by sequencing the RT-PCR product and characterised the receptor by ligand binding and scatchard plot analysis. The localisation of renal hPR was shown predominantly in individual epithelial cells of distal tubules by immunohistology, and the isoform hPR-B was detected by Western blot analysis. As a precondition for renal progesterone metabolism, we investigated the expression of steroid-metabolising enzymes for conversion of progesterone to metabolites with lower affinity to the hMR. We identified the enzyme 17alpha-hydroxylase for renal 17alpha-hydroxylation of progesterone. For 20alpha-reduction, different hydroxysteroid dehydrogenases (HSDs) such as 20alpha-HSD, 17beta-HSD type 5 (3alpha-HSD type 2) and 3alpha-HSD type 3 were found. Further, we detected the expression of 3beta-HSD type 2 for 3beta-reduction, 5alpha-reductase (Red) type 1 for 5alpha-reduction, and 5beta-Red for 5beta-reduction of progesterone in the human kidney. Therefore metabolism of progesterone and/or binding to hPR could reduce competition with aldosterone at the MR and enable the mineralocorticoid function.

20-Hydroxysteroid Dehydrogenases↗

PubMed2001

Analysis of BCL-6 mutations in classic Hodgkin disease of the B- and T-cell type.

BCL-6 is essential for germinal center formation and thus for affinity maturation of immunoglobulin (Ig) genes by somatic mutations. The 5'-noncoding region of the BCL-6 gene is even a target for the mutation machinery. Translocations of the BCL-6 gene to heterologous promoters and mutations of its 5'-noncoding regulatory region were reported to be potential mechanisms for deregulating BCL-6 expression and for playing a role in the genesis of non-Hodgkin lymphoma. In line with this hypothesis is the observation that B-cell lymphoma with somatic mutations, such as diffuse large B-cell lymphoma and follicular lymphoma, also carry BCL-6 mutations, some of which are recurrently detectable. Classic Hodgkin disease (cHD) is also derived from B cells with high loads of somatic mutations and thus a further candidate for BCL-6 mutations. To determine the presence and potential role of BCL-6 mutations in cHD, the 5'-noncoding BCL-6 proportion of single Hodgkin and Reed-Sternberg (HRS) cells from 6 cases of cHD and 6 cases of HD-derived cell lines was analyzed. All B-cell-derived HD cases and cell lines harbored BCL-6 mutations. In contrast, both T-cell-derived HD cases and cell lines were devoid of BCL-6 mutations. With only one exception, there were no lymphoma-specific recurrent BCL-6 mutations detected, and BCL-6 protein was absent from the HRS cells of most cases. In conclusion, (1) somatic BCL-6 mutations are restricted to cHD cases of B-cell origin, and (2) the BCL-6 mutations represent mostly irrelevant somatic base substitutions without consequences for BCL-6 protein expression and the pathogenesis of cHD.

5' Untranslated Regions↗

PubMed2001

Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription.

In contrast to the tumor cells (L&H cells) of lymphocyte predominant Hodgkin disease (LPHD), Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin disease (cHD) are unable to transcribe immunoglobulin, despite the presence of rearranged immunoglobulin genes. Although initial studies have suggested crippling immunoglobulin gene mutations to be the cause of absent immunoglobulin expression in cHD, recent work of our group has demonstrated an impaired activation of the immunoglobulin promoter as a superior mechanism. As immunoglobulin transcription is mainly regulated by the B-cell transcription factors Oct2 and BOB.1/OBF.1, we analyzed 35 cases of LPHD, 32 cases of cHD, and 2 Hodgkin disease cell lines for the expression of these transcription factors and also in parallel for immunoglobulin expression. Our results demonstrate an absence of Oct2 and/or BOB.1/OBF.1 in cHD and a striking overexpression of Oct2 in LPHD. Immunoglobulin expression was lacking in cHD but present in LPHD. Furthermore, the reintroduction of BOB.1/OBF.1 and Oct2 into cultured HRS cells restored the activity of cotransduced immunoglobulin promoter constructs. Our findings dismiss the concept that the different immunoglobulin expression in cHD and LPHD is due to disrupting mutations of immunoglobulin V genes in cHD but is most likely due to a down-regulation of Oct2 and/or BOB.1/OBF.1. This study further revealed Oct2 as a new and valuable marker for the identification of L&H cells and their distinction from HRS cells. The impairment of immunoglobulin transcription with a down-regulated synthesis of Oct2 and BOB.1/OBF.1 is the first established general recurrent defect found in HRS cells.

Cell Line↗

PubMed2001

Analysis of single EBER-positive and negative tumour cells in EBV-harbouring B-cell non-Hodgkin lymphomas.

In situ hybridization for Epstein-Barr virus (EBV) encoded small nuclear RNAs (EBERs) is the method of choice for the detection of EBV infection at the single cell level. With the application of this technique it was shown that non-Hodgkin's lymphomas of B-cell type may be associated with an EBV infection of tumour cells. Interestingly, in many EBV-positive cases, only a proportion of the tumour cell population has been found to be EBER-positive. To clarify whether EBV is absent or whether EBER gene expression is downregulated in EBER-negative tumour cells, single EBER-positive and negative tumour cells were isolated from paraffin sections from four B-cell non-Hodgkin's lymphoma cases with partial EBER expression in the neoplastic cells. These single cells were then screened for the presence of EBV DNA by a nested single cell PCR. EBV DNA was undetectable in all but one of the 86 EBER-negative cells, whereas in the EBER-positive cells EBV-specific DNA amplificates could be generated following single cell PCR. This finding prompts the conclusion that the inability to detect EBERs in a proportion of tumour cells is not due to a down-regulation of gene expression but to a real absence of EBV from these cells. This partial absence of EBV is thought to be caused by a loss of the EBV episomes during cell division, rather than by infection of only a proportion of the tumour cells.

Cell Separation↗

PubMed2001

Extranodal mantle cell lymphoma mimicking marginal zone cell lymphoma.

AIM: We report a case of mantle cell lymphoma masquerading as a marginal zone cell lymphoma. METHODS AND RESULTS: In the initial manifestation in the palatine tonsils, the neoplastic cells were found to grow exclusively within the marginal zones of secondary follicles which showed a preserved mantle zone. The few immunostains performed showed a B-cell phenotype including an immunoglobulin light chain restriction. The extranodal manifestation, the growth pattern, and the immunophenotype led to the diagnosis of an extranodal marginal zone B-cell non-Hodgkin's lymphoma (NHL). The specimen from the relapse occurring 8 months later exhibited diffuse monomorphous cells co-expressing B-cell antigens and CD5, CD43 and cyclin D1, leading to the diagnosis of mantle cell lymphoma. Re-investigation of the initial biopsy revealed that the neoplastic cells within the marginal zones had a mantle cell lymphoma immunophenotype expressing cyclin D1, the immunoglobulin heavy chains IgD and IgM and partly CD5. Both lesions harboured identical clonal immunoglobulin gene rearrangements proving that they represented different manifestations of the same lymphoma. CONCLUSION: This case emphasizes the importance of broad immunohistological investigation of B-cell NHLs involving the marginal zone.

Antigens, CD↗

PubMed2001

Neuroendocrine differentiation is a relevant prognostic factor in stage III-IV colorectal cancer.

OBJECTIVE: To determine the prognostic relevance of neuroendocrine differentiation in colorectal cancer. METHODS: The survival of 116 patients with colorectal cancer of stages III (n = 59) and IV (n = 57) was correlated with the extent of neuroendocrine differentiation. Chromogranin A and synaptophysin were used as neuroendocrine markers. Based on the degree of immunoreactivity for these markers, tumours were classified as 0 (no expression of neuroendocrine markers), 1 (< 2% cells staining positive for neuroendocrine markers) and 2 (> 2% cells staining positive for neuroendocrine markers). Patients were followed up for more than 5 years or until death. RESULTS: Seven of 59 (11.8%) stage III cancers and 13/57 (22.8%) stage IV cancers belonged to group 2. The 96 patients of groups 0 and 1 lived for 48.9 months, whereas the 20 patients of group 2 survived for only 18.6 months (Kaplan-Meier survival curves, P < 0.001). The difference was most striking in stage III disease with 79.4 months' survival for combined groups 0 and 1, and 38.9 months' survival for group 2 (P < 0.01). Using the multivariate Cox regression model, the presence of more than 2% of cells with neuroendocrine differentiation was found to be an independent prognostic parameter for stage III and IV disease. No correlation was observed between neuroendocrine differentiation and tumour location, grade, depth of invasion or stage. CONCLUSION: Neuroendocrine differentiation is often seen in colorectal cancer. It is an independent prognostic factor in stage III-IV colorectal cancer.

Adenocarcinoma↗