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2.
Intern Med J ; 39(8): 550-3, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19732202

ABSTRACT

The coexistence of chronic active hepatitis C with cryoglobulinemia and B-cell lymphoma has been presented in numerous case reports. However, the combination of these conditions with T-cell lymphoma has never been described before. We present the case of a patient who suffered chronic active hepatitis C, cryoglobulinaemia and B-cell lymphoma and was later complicated by cutaneous T-cell lymphoma (CTCL).


Subject(s)
Cryoglobulinemia/complications , Hepatitis C, Chronic/complications , Lymphoma, B-Cell/complications , Lymphoma, T-Cell, Cutaneous/complications , Adult , Bone Marrow Neoplasms/complications , Bone Marrow Neoplasms/virology , Cryoglobulinemia/virology , Female , Hepatitis C, Chronic/diagnosis , Humans , Kidney Neoplasms/complications , Kidney Neoplasms/diagnosis , Kidney Neoplasms/virology , Liver Neoplasms/complications , Liver Neoplasms/virology , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/virology , Lymphoma, T-Cell, Cutaneous/virology , Skin Neoplasms/complications , Skin Neoplasms/virology
7.
Ann Hematol ; 84(3): 188-91, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15042315

ABSTRACT

Lymph node infiltration by monoclonal plasma cells can occur either in aggressive forms of myeloma or may represent regional extension of extramedullary plasmacytomas, whereas lymph node plasmacytoma presenting as a solitary extramedullary plasmacytoma is very unusual. We report two cases of lymph node plasmacytomas without systemic disease diagnosed after surgical excision. Clinical remission was achieved after local radiotherapy although one patient relapsed with multifocal extramedullary plasmacytomas 20 months after radiotherapy.


Subject(s)
Plasmacytoma/pathology , Abdominal Neoplasms/pathology , Aged , Humans , Male , Middle Aged , Neoplasm Invasiveness , Plasma Cells/pathology , Plasmacytoma/diagnosis , Plasmacytoma/therapy , Retroperitoneal Neoplasms/pathology , Tomography, X-Ray Computed
8.
Hematol Oncol ; 22(4): 159-68, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15991268

ABSTRACT

The aim of the study was the evaluation of anti-angiogenic activity of the combination of intermediate doses of thalidomide and dexamethasone in patients with refractory/relapsed myeloma. Twenty-five patients were included in the study. Microvessel density (MVD) was evaluated in marrow biopsies before and after treatment. Serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), tumor necrosis factor-alpha (TNF-alpha), which have angiogenic potential and interleukin-6 (IL-6), IL-1beta, soluble IL-6 receptor (sIL-6R), and transforming growth factor-beta (TGF-beta) which are involved in the disease biology, were measured before treatment and then every 2 weeks for 8 weeks. Pretreatment levels of MVD, VEGF, b-FGF, IL-6, sIL-6R were increased in the patients compared to controls. The overall response rate to therapy was 72%. The administration of the combined regimen produced a significant reduction in MVD in responders. However, an increase in serum levels of VEGF, b-FGF, IL-6, sIL-6R was observed post-treatment in responders. In contrast, serum levels of TNF-alpha, TGF-beta, IL-1beta did not differ between patients and controls and remained unchanged during the study. These results suggest that the combination of thalidomide plus dexamethasone is an effective treatment for myeloma reducing MVD marrow levels but not serum levels of angiogenic cytokines or cytokines implicated in myeloma biology.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow/blood supply , Cytokines/blood , Multiple Myeloma/drug therapy , Neoplasm Proteins/blood , Neovascularization, Pathologic/blood , Aged , Dexamethasone/administration & dosage , Female , Fibroblast Growth Factor 2/blood , Humans , Interleukin-1/blood , Interleukin-6/blood , Male , Middle Aged , Multiple Myeloma/blood , Multiple Myeloma/pathology , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/etiology , Receptors, Interleukin-6/blood , Salvage Therapy , Solubility , Thalidomide/administration & dosage , Treatment Outcome , Tumor Necrosis Factor-alpha/analysis , Vascular Endothelial Growth Factor A/blood
9.
Ann Hematol ; 81(12): 732-5, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12483371

ABSTRACT

Histiocytic necrotizing lymphadenitis (HNL), or Kikuchi-Fujimoto disease, is a benign, self-limited disease that predominantly occurs in women. The etiology remains undetermined, although a viral or autoimmune hypothesis has been suggested. The disease usually emerges with cervical lymphadenopathy with or without fever. The diagnosis can be confirmed only by histological findings of lymph node biopsy, characterized by necrosis and histiocytic infiltration without neutrophils. We report a case of a 28-year-old woman with a medical history of two episodes of unexplained pulmonary embolisms (3 and 2 years previously) who was admitted to our hospital because of unilateral cervical lymphadenopathy and mild fever that presented 1 week before admission. A diagnosis of HNL was performed by lymph node biopsy. In parallel, whereas the laboratory tests for inherited thrombophilia were negative, a progressive elevated titer of anti-beta(2) glycoprotein I (GPI) antibodies was established. Because of persistent fever, the patient received a short course of corticosteroid therapy and she recovered completely from the HNL after 2 months. It is noteworthy that to date the patient has displayed an elevated titer of anti-beta(2) GPI antibodies (18 months after the recovery from the HNL). Thus, considering the previous history of venous thrombosis and the presence of antiphospholipid antibodies, the diagnosis of primary antiphospholipid syndrome associated with HNL was made. To our knowledge, this is the first report in the literature describing antiphospholipid syndrome associated with HNL. Moreover, a brief literature review is provided with emphasis on the etiology, clinical course, and pathogenesis of this rare disease entity.


Subject(s)
Antiphospholipid Syndrome/complications , Histiocytic Necrotizing Lymphadenitis/etiology , Adrenal Cortex Hormones/therapeutic use , Adult , Antibodies, Antiphospholipid/blood , Antiphospholipid Syndrome/diagnosis , Female , Histiocytic Necrotizing Lymphadenitis/diagnosis , Histiocytic Necrotizing Lymphadenitis/drug therapy , Humans , Pulmonary Embolism/etiology , Treatment Outcome
10.
Am J Clin Pathol ; 116(4): 535-42, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11601138

ABSTRACT

Cyclin D1 expression was evaluated by immunohistochemical analysis and biotin-labeled in situ hybridization (ISH) in a series of 71 decalcified, paraffin-embedded bone marrow biopsy specimens from patients with multiple myeloma (MM). Cyclin D1 messenger RNA (mRNA) overexpression was detected by ISH in 23 (32%) of 71 cases, whereas cyclin D1 protein was identified by immunohistochemical analysis in 17 (24%) of 71 specimens. All cases that were positive by immunohistochemical analysis also were positive by ISH. Statistically significant associations were found between cyclin D1 overexpression and grade of plasma cell differentiation and between cyclin D1 overexpression and extent of bone marrow infiltration. Our findings demonstrate the following: (1) ISH for cyclin D1 mRNA is a sensitive method for the evaluation of cyclin D1 overexpression in paraffin-embedded bone marrow biopsy specimens with MM. (2) ISH is more sensitive than immunohistochemical analysis in the assessment of cyclin D1 expression. (3) Cyclin D1 overexpression in MM is correlated positively with higher histologic grade and stage.


Subject(s)
Bone Marrow/pathology , Cyclin D1/genetics , Gene Expression , Immunohistochemistry , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Antigens, CD20/analysis , Biopsy , Biotinylation , Cell Differentiation , Female , Humans , Immunoglobulin kappa-Chains/analysis , Immunoglobulin lambda-Chains/analysis , In Situ Hybridization , Male , Middle Aged , Multiple Myeloma/chemistry , Neoplasm Staging , Paraffin , Plasma Cells/pathology , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Tissue Embedding
12.
Mod Pathol ; 14(2): 62-71, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11235907

ABSTRACT

Mantle cell lymphoma (MCL) is characterized by the chromosomal translocation t(11;14), which involves rearrangement of the bcl-1 proto-oncogene to the immunoglobulin heavy chain gene and results in overexpression of cyclin D1 mRNA. In this study, we evaluated the diagnostic relevance of three methods that may be helpful in the diagnosis of MCL: in situ hybridization (ISH) and a stringent reverse transcriptase-polymerase chain reaction (RT-PCR) protocol for cyclin D1 mRNA, and immunohistochemistry for cyclin D1 protein. The study group included 37 paraffin-embedded specimens (25 from lymph nodes and 12 from extranodal tissues) from 30 patients. MCL diagnosis was performed according to the Revised European-American Classification of Lymphoid Neoplasms. Twenty-nine patients with non-MCL lymphoproliferative disorders comprised the control group. Biotin-labeled ISH was performed in 28 cases of MCL, 24 (86%) of which were found to be positive. As shown by ISH in extranodal tissues, cyclin D1 mRNA was present not only in neoplastic lymphoid cells, but in other cell types as well. For this reason, RT-PCR results were considered reliable for MCL diagnosis only on informative material (from tissues that do not normally express cyclin D1); this method was evaluated as positive in 16 of 18 (89%) MCL cases. Cyclin D1 immunopositivity was present in 20 of 29 (69%) MCL cases. No members of the control group were found to express cyclin D1 mRNA by either ISH or RT-PCR under the stringent conditions used. In conclusion, stringent RT-PCR for cyclin D1 expression can be helpful in MCL diagnosis in paraffin-embedded material from lymph nodes. ISH is a sensitive method for cyclin D1 mRNA detection; its sensitivity is superior to that of cyclin D1 immunohistochemistry and similar to that of the stringent RT-PCR used. ISH is very specific as well, clearly more specific than RT-PCR, because it allows the correlation of molecular findings with morphology. This method can be applied on all types of paraffin-embedded tissues and provides an accurate tool for MCL diagnosis.


Subject(s)
Cyclin D1/genetics , In Situ Hybridization , Lymphoma, Mantle-Cell/diagnosis , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Cyclin D1/analysis , DNA, Neoplasm/analysis , Humans , Immunohistochemistry , Lymph Nodes/chemistry , Lymph Nodes/metabolism , Lymph Nodes/pathology , Lymphoma, Mantle-Cell/genetics , Lymphoma, Mantle-Cell/pathology , Paraffin Embedding , Proto-Oncogene Mas , RNA, Neoplasm/analysis
13.
Pathol Res Pract ; 196(8): 573-5, 2000.
Article in English | MEDLINE | ID: mdl-10982021

ABSTRACT

Multiple primary malignancies of the uterus are extremely rare. We report a case of endometrial adenocarcinoma and cervical large B-cell lymphoma occurring simultaneously in a 64-year-old woman with uterine bleeding. Adenopathy, hepatosplenomegaly or bone marrow infiltration were not found. Both malignant neoplasms mentioned above were diagnosed incidentally on the specimen (total hysterectomy with bilateral salpingo-oophorectomy) removed for uterine leiomyomas.


Subject(s)
Adenocarcinoma/pathology , Endometrial Neoplasms/pathology , Lymphoma, B-Cell/pathology , Lymphoma, Large B-Cell, Diffuse/pathology , Neoplasms, Multiple Primary/pathology , Uterine Cervical Neoplasms/pathology , Female , Humans , Middle Aged
14.
Lab Invest ; 72(4): 405-10, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7723278

ABSTRACT

BACKGROUND: Histologic examination of bone marrow is important in establishing diagnoses among chronic myeloproliferative disorders (CMPD). Only a few studies, however, have compared cytogenetic or molecular genetic findings to histopathology in CMPD. Diverging results on the presence of the Ph1-translocation in patients with myelofibrosis have been reported. EXPERIMENTAL DESIGN: Cytogenetic studies and molecular analysis of the bcr gene were performed in bone marrow cells of patients with CMPD simultaneously with histopathologic examination of plastic-embedded bone marrow biopsies. RESULTS: The Ph1-chromosome was found in 120/128 (93%) cases with histopathologic diagnosis of chronic myeloid leukemia (CML), including a notable proportion of cases with an increase of megakaryocytes and/or myelofibrosis; the latter was associated with a significant increase of chromosome aberrations, in addition to Ph1. Among those additional changes in myelofibrosis of Ph1-positive CML were del (13q) and t(1;11) in one case each. A bcr gene rearrangement was detected in 92% (24/26) of the CML cases examined. All other groups of CMPD, comprising cases of myelofibrosis and unclassifiable cases, were Ph1-negative by both cytogenetics (n = 102) and molecular analysis (n = 18). Karyotype changes associated with myelofibrosis in various CMPD concerned mainly balanced translocations involving 1p36 and 11q11, deletions of 5q13-34, 3p, 11q23, 13(q12,q22), and 20q12 as well as gain of 1q and trisomy 3, 8, 19, or 21. In histologically unclassifiable CMPD, karyotyping provided additional information for the differential diagnosis. CONCLUSIONS: The correlation of cytogenetic findings and histopathologic features is helpful in confirming or supporting histopathologic diagnoses and in characterizing new marker chromosomes in CMPD.


Subject(s)
Gene Rearrangement , Karyotyping , Molecular Biology , Myeloproliferative Disorders/genetics , Myeloproliferative Disorders/pathology , Protein-Tyrosine Kinases , Proto-Oncogene Proteins/genetics , Aged , Cell Count , Chromosome Aberrations , Chromosome Disorders , Chromosome Mapping , Chronic Disease , Humans , Megakaryocytes/pathology , Middle Aged , Primary Myelofibrosis/pathology , Proto-Oncogene Proteins c-bcr , Translocation, Genetic
15.
Pathologe ; 16(1): 41-5, 1995 Jan.
Article in German | MEDLINE | ID: mdl-7886013

ABSTRACT

The histopathological classification of chronic myeloproliferative disorders can be supported by applying cytogenetics and molecular genetics to the analysis of bone marrow or blood cells, as demonstrated in 253 cases evaluated. The Philadelphia translocation (9;22) is the most important genetic parameter, being specific for chronic myeloid leukemia. Conventional methods for the detection of the t(9;22) are karyotyping and Southern blot analysis of the bcr gene. The newly established technique of fluorescence in situ hybridization (FISH) allows visualization of bcr-abl fusion even in non dividing cells. Molecular cytogenetics for t(9;22) yield results that are rapid and reliable as well as easily quantifiable.


Subject(s)
Chromosome Aberrations , Myeloproliferative Disorders/genetics , Protein-Tyrosine Kinases , Biopsy , Blotting, Southern , Bone Marrow/pathology , Chromosomes, Human, Pair 22 , Chromosomes, Human, Pair 9 , Diagnosis, Differential , Fusion Proteins, bcr-abl/genetics , Gene Rearrangement , Genes, abl/genetics , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Myeloproliferative Disorders/pathology , Philadelphia Chromosome , Polycythemia Vera/genetics , Polycythemia Vera/pathology , Primary Myelofibrosis/genetics , Primary Myelofibrosis/pathology , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-bcr , Thrombocythemia, Essential/genetics , Thrombocythemia, Essential/pathology , Translocation, Genetic/genetics
16.
Pathologe ; 15(5): 286-91, 1994 Oct.
Article in German | MEDLINE | ID: mdl-7824438

ABSTRACT

The value of cytogenetics performed simultaneously with histopathology was evaluated in patients with myelodysplastic syndrome (MDS). Clonal karyotype changes of the bone marrow cells supporting the histological diagnosis were found in 38/69 cases (55%). The chromosome aberrations, especially complex changes, were significantly correlated to distinct histopathological findings such as atypias of the haematopoietic cell lines and myelosclerosis. Complex karyotype changes were further associated with short survival of the MDS patients. Our results demonstrate that cytogenetic analyses are helpful in supplementing the histopathological diagnoses. Recent developments in molecular cytogenetics even allow the detection of chromosomal aberrations in non-dividing cells from cytological preparations or tissue sections which may become available for routine diagnosis.


Subject(s)
Chromosome Aberrations/genetics , Karyotyping , Myelodysplastic Syndromes/genetics , Aged , Bone Marrow/pathology , Chromosomes, Human, Pair 8 , Female , Follow-Up Studies , Humans , Male , Middle Aged , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/pathology , Survival Rate
17.
Am J Clin Pathol ; 101(2): 123-9, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8116565

ABSTRACT

The histologic, hematologic, and morphometric findings of 40 patients positive for the human immunodeficiency virus (HIV) were compared statistically with those of 40 patients with primary myelodysplastic syndromes (MDS) and those of 32 HIV-negative patients with infectious diseases. The severity of anemia and the abnormalities of erythropoiesis in the group of HIV patients were less pronounced than in the group with MDS; megakaryopoiesis showed similarities only with the group of patients with infectious diseases, and characteristics of dysplasia were not observed. Granulopoiesis in MDS showed an increase of blasts in several cases; this was not found in any biopsy specimen from the HIV group. In addition, a statistically significant increase of monocyte-like cells and giant bands could be observed in the bone marrow of the HIV patients. The peripheral blood findings and bone marrow picture in the series of our HIV patients appeared to be related mainly to the influence of opportunistic infections, although a direct effect of the HIV itself could not be excluded.


Subject(s)
Bone Marrow/pathology , Communicable Diseases/blood , Communicable Diseases/pathology , HIV Infections/blood , HIV Infections/pathology , Myelodysplastic Syndromes/blood , Myelodysplastic Syndromes/pathology , AIDS-Related Opportunistic Infections/blood , AIDS-Related Opportunistic Infections/pathology , Acquired Immunodeficiency Syndrome/blood , Acquired Immunodeficiency Syndrome/epidemiology , Acquired Immunodeficiency Syndrome/pathology , Adult , Aged , Aged, 80 and over , Anemia/blood , Anemia/pathology , Communicable Diseases/epidemiology , Erythropoiesis/physiology , Female , HIV Infections/epidemiology , Hematopoiesis/physiology , Humans , Male , Megakaryocytes/pathology , Middle Aged , Myelodysplastic Syndromes/epidemiology , Retrospective Studies , Severity of Illness Index
18.
Ann Hematol ; 66(3): 117-22, 1993 Mar.
Article in English | MEDLINE | ID: mdl-8471656

ABSTRACT

The present study, based upon the retrospective evaluation of 352 patients with primary myelodysplastic syndrome (pMDS), revealed hypoplastic MDS in 42 patients (11.9%). Median age is similar in hypo- and normo-/hypercellular MDS (72.6 versus 70.7 versus 72.4 years). Hypoplastic MDS occurred significantly more often in women compared with normo- and hypercellular MDS. Sequential biopsies were performed in 14 patients, showing a persistence of hypoplasia over a period of up to 43 months. The proportion of patients showing mesenchymal reaction, especially an increase of mast cells, was significantly higher in hypoplastic MDS, whereas dysplastic features of hematopoiesis occurred less frequently and were of lower grade in comparison to normo-/hyperplastic MDS. Among the subgroup with hypoplastic bone marrow, the classification according to FAB criteria revealed 28 patients with RA (66.7%), three with RARS (7.1%), and eight with RAEB (19.0%), as well as one patient each with RAEB-T and CMMol (2.4% each), and one case which had to be reckoned among the category of unclassifiable MDS (2.4%). Median survival was 21.8 months for hypoplastic MDS, 26.9 months for normoplastic MDS, and 14.2 months for hyperplastic MDS. During follow-up, 14 patients (33%) with hypoplastic MDS developed acute nonlymphatic leukemia. Although not a constant finding, karyotype abnormalities involving particularly chromosome 7 seem to be associated with hypoplastic MDS. The results confirm the existence of a hypoplastic variant of MDS which seems to more frequently affect female patients, and which requires bone marrow biopsy for its accurate diagnosis.


Subject(s)
Bone Marrow/pathology , Myelodysplastic Syndromes/pathology , Adult , Aged , Aged, 80 and over , Biopsy , Chromosomes, Human, Pair 7 , Female , Hematopoiesis , Humans , Male , Middle Aged , Monosomy , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/mortality , Plasma Cells/pathology , Prognosis , Retrospective Studies , Survival Rate , Translocation, Genetic
19.
Article in English | MEDLINE | ID: mdl-8099457

ABSTRACT

The reliability of histopathological diagnosis in bone marrow specimens from patients with chronic myeloproliferative disorders (CMPD) was evaluated by correlating the histological findings with molecular genetic and cytogenetic analyses of the Ph1-translocation. A rearrangement of m-bcr was detected only in patients (28/30) diagnosed histologically as chronic myeloid leukemia (CML). This finding was supported by the presence of a Ph1-chromosome in 24/26 patients with CML examined. All the patients with other types of CMPD, including polycythemia vera (PV), primary thrombocythemia (PTH) and chronic megakaryocytic-granulocytic myelosis (CMGM), as well as those with unclassifiable CMPD (CMPD.UC) were Ph1-negative (n = 38). The histopathological discrimination of CML from Ph1-negative varieties of CMPD was also reliable for patients with myelofibrosis complicating CML, CMGM and CMPD.UC. The results demonstrate that bone marrow histopathology allows a reliable diagnosis of CML. This is in contrast with hematological data such as high platelet counts which show considerable overlapping in the various forms of CMPD.


Subject(s)
Bone Marrow/pathology , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/genetics , Protein-Tyrosine Kinases , Proto-Oncogene Proteins , Adult , Aged , Aged, 80 and over , Chronic Disease , Gene Rearrangement , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Middle Aged , Myeloproliferative Disorders/pathology , Oncogene Proteins/genetics , Philadelphia Chromosome , Proto-Oncogene Proteins c-bcr
20.
Anal Quant Cytol Histol ; 14(5): 391-7, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1299229

ABSTRACT

Elliptic Fourier analysis was applied to megakaryocyte nuclei in bone marrow biopsies from 15 patients with chronic myelocytic leukemia with megakaryocyte predominance and from 15 patients with chronic megakaryocytic granulocytic myelosis. To assess the reliability of this procedure, the biopsies were evaluated also by the semiautomatic measurement of nuclear area and form factor, and both methods were compared with respect to the degree of morphologic differences obtained between these two types of chronic myeloproliferative disorders (CMPDs). Discriminant analysis revealed correct reclassification of all cases both for elliptic Fourier analysis and for semiautomatic planimetry, whereas discriminant scores were much higher for Fourier analysis. Thus, simple planimetric features such as nuclear area and form factor, in contrast to Fourier analysis, are not able to detect the full degree of morphologic differences between megakaryocyte nuclei in different CMPDs. Elliptic Fourier analysis therefore seems to be a useful procedure for the accurate description of such complicated structures as megakaryocyte nuclei in CMPD.


Subject(s)
Cell Nucleus/ultrastructure , Megakaryocytes/ultrastructure , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/pathology , Analysis of Variance , Biopsy , Bone Marrow/pathology , Discriminant Analysis , Fourier Analysis , Humans , Image Processing, Computer-Assisted , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/pathology , Microscopy , Primary Myelofibrosis/diagnosis , Primary Myelofibrosis/pathology
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