fibrin and Lymphoma--Large-B-Cell--Diffuse

Fibrin-associated large B-cell lymphoma is a rare microscopic-sized tumor, typically representing an unexpected finding at sites rich in chronic fibrin deposition. It is associated with Epstein-Barr virus, and has been reported to occur in a wide variety of anatomic sites and clinical scenarios. We report a case arising in a thyroid hyperplastic nodule, only the second case reported in this location. Notably, this is only the fourth case of fibrin-associated large B-cell lymphoma that is not associated with Epstein-Barr virus. We provide a literature review on the clinico-pathological characteristics and outcome of this newly characterized indolent lymphoma type, which has only recently been separated out from the pathologically similar but highly aggressive large B-cell lymphoma associated with chronic inflammation.

Topics: Epstein-Barr Virus Infections; Fibrin; Herpesvirus 4, Human; Humans; Hyperplasia; Lymphoma, Large B-Cell, Diffuse; Thyroid Nodule

In recent years, the features of lymphomas associated with chronic inflammation, referred to as diffuse large B-cell lymphoma (DLBCL) associated with chronic inflammation (DLBCL-CI), have been elucidated. DLBCL-CI is an aggressive lymphoma occurring in the context of long-standing chronic inflammation and showing an association with Epstein-Barr virus. Fibrin-associated diffuse large B-cell lymphoma (F-DLBCL) was suggested as a new and unusual form of DLBCL-CI in the most recent version of the World Health Organization classification. From the perspective of genetics, DLBCL-CI was associated with frequent TP53 mutation, MYC amplification and complex karyotypes, but cases of F-DLBCL behaved indolently and showed a relatively lower genetic complexity. In the central nervous system (CNS), several examples of DLBCL-CI and F-DLBCL have been reported. As with DLBCL-CI outside the CNS, DLBCL-CI in the CNS is an aggressive lymphoma. However, the clinical outcome of F-DLBCL in the CNS is good. Immunohistochemistry for p53 and c-Myc in DLBCL-CI and F-DLBCL in the CNS showed similar findings of those outside the CNS. However, one aggressive case showed transitional genetics and morphology between F-DLBCL and DLBCL-CI. These findings suggest that some cases of F-DLBCL in the CNS might have the potential to progress to DLBCL-CI.

Topics: Aged; Aged, 80 and over; Central Nervous System Neoplasms; Disease Progression; Fibrin; Humans; Inflammation; Lymphoma, Large B-Cell, Diffuse; Mutation; Proto-Oncogene Proteins c-myc; Tumor Suppressor Protein p53

Topics: Atrial Fibrillation; Epstein-Barr Virus Infections; Fibrin; Herpesvirus 4, Human; Humans; In Situ Hybridization, Fluorescence; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Myxoma; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-bcl-6

Topics: Fibrin; Humans; Lymphoma, Large B-Cell, Diffuse; Mutation; PTEN Phosphohydrolase

Fibrin-associated diffuse large B-cell lymphoma (fibrin-associated DLBCL) is a very rare subtype of Epstein-Barr virus (EBV)-associated DLBCL that usually develops within fibrin-rich lesions such as cardiac myxoma, chronic hematoma, thrombus, pseudocysts or cysts, prosthetic devices or breast implants. The pathogenesis as well as the clinicopathologic features of this usually indolent lymphoproliferative disorder, which are based on the analysis of a relatively limited number of cases, are still poorly known. Herein, we report a case of fibrin-associated DLBCL that was incidentally found within a multinodular goiter, a location not yet reported to our knowledge. Our findings not only illustrate further the specific nature of this peculiar lymphoproliferative disorder but also allow some interesting comments on its pathogenesis.

Topics: Epstein-Barr Virus Infections; Fibrin; Goiter; Herpesvirus 4, Human; Humans; Lymphoma, Large B-Cell, Diffuse

Topics: CD4 Antigens; Female; Fibrin; Humans; Immunophenotyping; Lymphoma, Large B-Cell, Diffuse; Middle Aged

Fibrin-associated diffuse large B cell lymphoma (FA-DLBCL) is a rare Epstein-Barr viruspositive B cell lymphoma that is nonmass-forming, does not directly produce symptoms, and is incidentally discovered on histological examination of tissues excised for other reasons. Despite overlap in morphologic and immunophenotypic features with aggressive B cell neoplasms, FA-DLBCL shows an excellent clinical outcome, even with surgical excision alone. We report an extremely rare occurrence of FA-DLBCL found in association with a metallic implant on revision arthroplasty of the knee. This report also illustrates the need for an integrated multidisciplinary approach for accurate diagnosis and avoidance of overtreatment.

Topics: Aged; Arthroplasty; Female; Fibrin; Humans; Knee Joint; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged

Topics: Aged; Brain Neoplasms; Fibrin; Hematoma, Subdural; Humans; Lymphoma, Large B-Cell, Diffuse; Male

Topics: Breast Implants; Epstein-Barr Virus Infections; Fibrin; Herpesvirus 4, Human; Humans; Incidental Findings; Inflammation; Lymphoma, Large B-Cell, Diffuse

Topics: Breast Implants; Breast Neoplasms; Diagnosis, Differential; Female; Fibrin; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Anaplastic; Middle Aged

Topics: Epstein-Barr Virus Infections; Fibrin; Hematoma; Herpesvirus 4, Human; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoproliferative Disorders; T-Lymphocytes

Topics: Aged; Atrial Fibrillation; Female; Fibrin; Heart Neoplasms; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Myxoma

Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is a rare Epstein-Barr virus (EBV) positive lymphoproliferative disorder included in the current World Health Organization (WHO) classification. It arises within fibrinous material in the context of hematomas, pseudocysts, cardiac myxoma or in relation with prosthetic devices. In these clinical settings the diagnosis requires an high index of suspicion, because it does not form a mass itself, being composed of small foci of neoplastic cells. Despite overlapping features with diffuse large B-cell lymphoma associated with chronic inflammation, it deserves a separate classification, being not mass-forming and often following an indolent course.. A 64-year-old immunocompetent woman required medical care for cerebral hemorrhage. Computed Tomography (CT) angiography identified an aneurysm in the left middle cerebral artery. A FA-DLBCL was incidentally identified within thrombotic material in the context of the arterial aneurysm. After surgical removal, it followed a benign course with no further treatment.. The current case represents the first report of FA-DLBCL identified in a cerebral artery aneurysm, expanding the clinicopathologic spectrum of this rare entity. A complete literature review is additionally made.

Topics: Biopsy; Computed Tomography Angiography; Epstein-Barr Virus Infections; Female; Fibrin; Herpesvirus 4, Human; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged

Topics: Aged; Female; Fibrin; Humans; Kidney Neoplasms; Lymphoma, Large B-Cell, Diffuse; Neoplasm Proteins; Tomography, X-Ray Computed

Topics: Fibrin; Heart Neoplasms; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Myxoma

Topics: Aged, 80 and over; Arachnoid; Arachnoid Cysts; Diagnosis, Differential; Fibrin; Humans; Intracranial Hemorrhages; Lymphoma, Large B-Cell, Diffuse; Male

Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to define their clinicopathologic spectrum and compare features with typical cases of DLBCL-CI. Median age was 55.5 years with a M:F ratio of 3. In all 12 cases, the lymphoma was an incidental microscopic finding involving atrial myxomas (n=3), thrombi associated with endovascular grafts (n=3), chronic hematomas (n=2), and pseudocysts (n=4). All cases tested were nongerminal center B-cell origin, type III EBV latency, and were negative for MYC rearrangements and alternative lengthening of telomeres by FISH. Most showed high CD30, Ki67, and PD-L1, and low to moderate MYC and p53 expression. Among 11 patients with detailed follow-up, 6 were treated surgically, 3 with cardiac or vascular lesions had persistent/recurrent disease at intravascular sites, and 4 died of causes not directly attributable to lymphoma. Reports of previously published fibrin-associated cases showed similar features, whereas traditional DLBCL-CI cases with a mass lesion had significantly higher lymphoma-associated mortality. Fibrin-associated EBV+ large B-cell lymphoma is clinicopathologically distinct from DLBCL-CI, warranting separate classification. Most cases, particularly those associated with pseudocysts, behave indolently with the potential for cure by surgery alone and may represent a form of EBV+ lymphoproliferative disease rather than lymphoma. However, primary cardiac or vascular disease may have a higher risk of recurrence despite systemic chemotherapy.

Topics: Adult; Aged; Biomarkers, Tumor; Case-Control Studies; Chronic Disease; Epstein-Barr Virus Infections; Female; Fibrin; Follow-Up Studies; Humans; Immunohistochemistry; Inflammation; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prognosis

Cardiac lymphomas are rare, and the spectrum of pathologic features is not well defined. We encountered an unusual case of cardiac lymphoma residing within a presumed thrombus. To place such cases in context, we reviewed all cardiac lymphomas presenting to a large US cardiovascular medicine referral center during a 30-year period. A total of 14 cardiac lymphomas were identified, and these included 6 primary cardiac lymphomas (PCLs) and 8 lymphomas secondarily involving cardiac structures. Upon review, 3 of the PCLs were confirmed to be diffuse large B-cell lymphoma, not otherwise specified, involving the myocardium. The other 3 cases of PCL lacked myocardial invasion and showed lymphoma cells embedded in fibrin thrombus. Acute inflammation was not evident. These lymphomas presented in immunocompetent male individuals and involved either a prolapsed myxomatous mitral valve, a pseudomyxoma from the left atrium, or a thrombus arising in a synthetic aortic root graft. All 3 consisted of large atypical lymphocytes expressing a nongerminal center B-cell immunophenotype. Two cases were positive for Epstein-Barr virus (latency type III), but none demonstrated human herpes virus-8 latent nuclear antigen. No systemic disease was found at presentation or during follow-up. In our experience, fibrin-associated large B-cell lymphoma arising in the heart represents a substantial proportion of PCL. These lymphomas appear to represent an underrecognized variant of diffuse large B-cell lymphoma with favorable outcome. Further study is needed to understand their natural history.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Coronary Thrombosis; Epstein-Barr Virus Infections; Female; Fibrin; Heart Neoplasms; Herpesvirus 4, Human; Humans; Immunocompetence; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Myocardium; Treatment Outcome

An immunocompetent 29-year-old male presented with an embolic stroke from an unusual primary cardiac lymphoma. The cardiac lesion consisted of a polypoid, left atrial, mural fibrin thrombus with anaplastic tumor cells lining the surface of the clot. Histologic, immunophenotypic, and molecular characterizations were consistent with a diagnosis of CD30+ large B-cell lymphoma with anaplastic cytology. While tumor emboli from invasive primary cardiac lymphomas have been reported, this noninvasive fibrin thrombus-associated lymphoma appears to be unique and previously unreported.

Topics: Adult; Diagnosis, Differential; Fibrin; Heart Atria; Heart Neoplasms; Humans; Immunophenotyping; Intracranial Embolism; Ki-1 Antigen; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Myxoma; Platelet Count; Stroke; Ultrasonography

The leukocyte integrin Mac-1 (CD11b/CD18) and the urokinase receptor (uPAR, CD87) mediate complementary functions in myelomonocytic cells. Both receptors promote degradation of fibrin(ogen) and also confer adhesive properties on cells because Mac-1 and uPAR bind fibrin and vitronectin, respectively. Staining of lung biopsy specimens from patients with acute lung injury indicated that fibrin and vitronectin colocalize at exudative sites in which macrophages bearing these receptors accumulate. Because of the parallel roles and physical proximity of Mac-1 and uPAR, the capacity of these receptors to functionally interact was explored. Induction of Mac-1 and uPAR expression on monocytic cell lines by transforming growth factor- beta 1 and 1.25-(OH)2 vitamin D3 conferred urokinase and uPAR-dependent adhesion to vitronectin, which was further promoted by engagement of Mac-1. Vitronectin attachment promoted subsequent Mac-1-mediated fibrinogen degradation threefold to fourfold. In contrast, enhancement of uPAR occupancy by exogenous urokinase or receptor binding fragments thereof inhibited Mac-1 function. Addition of urokinase progressively inhibited Mac-1-mediated fibrinogen binding and degradation (maximal inhibition, 91% +/- 14% and 72% +/- 15%, respectively). Saturation of uPAR with urokinase also inhibited binding of the procoagulant Mac-1 ligand, Factor X. These inhibitory effects of uPAR were reproduced in fresh monocytes, cultured monocytic cells, and in Chinese hamster ovary (CHO) cells transfected with both human Mac-1 and human uPAR. These data show that the procoagulant and fibrinolytic potential of monocytic cells is co-ordinately regulated by ligand binding to both Mac-1 and uPAR and identify uPAR as a regulator of integrin function. Vitronectin-enhanced fibrin(ogen) turnover by Mac-1 may operate as a salvage pathway in the setting of urokinase and plasmin inhibitors to promote clearance of the provisional matrix and subsequent healing.

Topics: Animals; Blood Coagulation; Calcitriol; CD18 Antigens; Cell Adhesion; CHO Cells; Cricetinae; Factor X; Fibrin; Fibrinogen; Fibrinolysis; Humans; Leukemia, Monocytic, Acute; Lung; Lung Injury; Lymphoma, Large B-Cell, Diffuse; Macromolecular Substances; Macrophage-1 Antigen; Macrophages; Monocytes; Neoplasm Proteins; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Recombinant Proteins; Transfection; Transforming Growth Factor beta; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator; Vitronectin

Fibrin deposition is characteristic of inflammatory diseases. The monocytes is central to the inflammatory response and can affect fibrinolysis by expression of urokinase (u-PA) and plasminogen activator inhibitor types 1 and 2 (PAI-1 and PAI-2, respectively). This study examines whether thrombin, which promotes fibrin deposition, can contribute to fibrin persistence by modulating expression of proteins of the fibrinolytic system. Monocytes were isolated from human peripheral blood and analyzed for PAI-2, PAI-1, and u-PA antigens by enzyme-linked immunosorbent assay (ELISA). Monocytes responded to thrombin by increased expression of PAI-2 in a dose- and time-dependent manner, with maximal synthesis at a concentration of 1 U/mL to 10 U/mL. This trend was also evident for PAI-1, which was present at much lower levels. Thrombin and lipopolysaccharide (LPS) stimulated comparable levels of PAI-2, studied at the antigen and mRNA level. The dose effet of LPS on PAI-2 and PAI-1 was found to differ from that of thrombin. The level of u-PA was undetectable by ELISA and zymography in all samples. Thrombin stimulates PAI-2 synthesis by human monocytes, therefore creating an imbalance in the fibrinolytic system. This may contribute to persistence of fibrin, deposited during inflammation.

Topics: Fibrin; Fibrinolysis; Gene Expression Regulation; Humans; Inflammation; Lipopolysaccharides; Lymphoma, Large B-Cell, Diffuse; Monocytes; Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 2; Thrombin; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator

Nonmalignant lymphoid tissue and tissue from patients with nodular sclerosis, Hodgkin's disease, and large cell lymphocytic lymphoma was examined by immunohistochemical techniques for the occurrence in situ of components of coagulation and fibrinolysis reaction pathways. Staining for material interpreted as fibrinogen was observed in abundance in both malignant and reactive lymphoid tissue. Fibrin also occurred to a variable extent but focally in all tissues. Components of coagulation pathways, including tissue factor, factor VII, factor X, and factor XIII ("a" subunit), were restricted to tissue macrophages. Double-labeling techniques revealed fibrin in direct apposition to tissue macrophages. We conclude that fibrinogen and fibrin occur in both benign and malignant lymphoid tissue and that the transformation of fibrinogen to fibrin is attributable to macrophage-initiated thrombin formation. We postulate that both systemic and local hypercoagulability associated with these disorders may be attributable to macrophage activation resulting in expression of procoagulant activity.

Topics: Adolescent; Adult; Aged; Factor VII; Factor VIII; Factor X; Female; Fibrin; Fibrinogen; Fibrinolysis; Hodgkin Disease; Humans; Immunohistochemistry; Leukemia, Lymphocytic, Chronic, B-Cell; Lymph Nodes; Lymphoid Tissue; Lymphoma, Large B-Cell, Diffuse; Macromolecular Substances; Macrophages; Male; Middle Aged; Sclerosis; Thromboplastin

Factor XIII A subunit was detected in U937 cells and human alveolar macrophages by immunohistology and Western blotting. U937 cells synthesize factor XIII A subunit de novo under serum-free, platelet-free conditions, as indicated by 35S-methionine labeling and immunoprecipitation. Thrombin-dependent activity was demonstrated to account for 98% of the total transglutaminase activity in U937 cells (1.5 micrograms per 0.5 X 10(6) cells/mL). Intact U937 cells and alveolar macrophages and homogenates from these cells cross-linked fibrin to form gamma-gamma and alpha-polymers. Factor XIII A was detected on the surface of intact U937 cells and macrophages by flow cytometry and 125I-labeling and immunoprecipitation. Cell surface expression of factor XIII A was augmented in the presence of several soluble macrophage activators; however, no concurrent increase in its biosynthesis was observed. The presence and cell surface expression of factor XIII A subunit within macrophages suggest new pathways by which these cells may function in clotting and in the remodeling of the extracellular matrix during inflammation and wound healing.

Topics: Blood Coagulation; Cell Line; Extracellular Matrix; Factor XIII; Fibrin; Histiocytes; Humans; Immunoelectrophoresis; Lymphoma, Large B-Cell, Diffuse; Macrophages; Membrane Proteins; Neoplasm Proteins; Pulmonary Alveoli; Transglutaminases

Topics: Adult; Aged; Chronic Disease; Disseminated Intravascular Coagulation; Factor V; Factor VII; Female; Fibrin; Fibrinogen; Gaucher Disease; Hodgkin Disease; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Middle Aged; Organ Size; Plasminogen; Polycythemia Vera; Prothrombin Time; Spleen; Splenectomy; Splenomegaly

Topics: Adult; Aged; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysis; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Middle Aged; Multiple Myeloma; Myeloproliferative Disorders; Plasminogen; Trypsin Inhibitors

Topics: Animals; Cell Transformation, Neoplastic; Collagen; Connective Tissue; Cysts; Dose-Response Relationship, Drug; Fibrin; Hepatic Veins; Injections, Subcutaneous; Kupffer Cells; Liver; Liver Diseases; Liver Neoplasms; Lymphatic System; Lymphoma, Large B-Cell, Diffuse; Male; Microscopy, Electron; Mitosis; Monocytes; Rats; Rats, Inbred Strains; Sarcoma, Experimental; Trypan Blue

Topics: Adolescent; Adult; Agammaglobulinemia; Aged; Albumins; Animals; Antigens; Biological Evolution; Child; Child, Preschool; Fibrin; Goats; Hodgkin Disease; Humans; Immune Sera; Immunodiffusion; Immunoglobulin G; Infant; Infant, Newborn; Leukemia, Lymphoid; Lymphocytes; Lymphoid Tissue; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Middle Aged; Proteins; Solubility; Thymoma; Thymus Gland; Transferrin

Topics: Blood Cells; Fibrin; Hodgkin Disease; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Neoplasms; Sarcoma