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Upper respiratory tract involvement is common in patients with granulomatosis with polyangiitis (GPA), but malignancies should be kept in mind in the differential diagnosis. A 68-year-old man was referred to rheumatology to investigate for GPA after nasal excisional biopsy. After careful radiologic and pathologic assessment, he was diagnosed with peripheral Tcell lymphoma, nasal type. This is a rare case of Tcell lymphoma in a patient who was referred as GPA.
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Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) subtype characterized by overexpression of CCND1 and SOX11 genes. It is generally associated with clinically poor outcomes despite recent improvements in therapeutic approaches. The genes associated with the development and prognosis of MCL are still largely unknown. Through whole transcriptome sequencing (WTS), we identified mRNAs, lncRNAs, and alternative transcripts differentially expressed in MCL cases compared with reactive tonsil B-cell subsets. CCND1, VCAM1, and VWF mRNAs, as well as MIR100HG and ROR1-AS1 lncRNAs, were among the top 10 most significantly overexpressed, oncogenesis-related transcripts. Survival analyses with each of the top upregulated transcripts showed that MCL cases with high expression of VWF mRNA and low expression of FTX lncRNA were associated with poor overall survival. Similarly, high expression of MSTRG.153013.3, an overexpressed alternative transcript, was associated with shortened MCL survival. Known tumor suppressor candidates (e.g., PI3KIP1, UBXN) were significantly downregulated in MCL cases. Top differentially expressed protein-coding genes were enriched in signaling pathways related to invasion and metastasis. Survival analyses based on the abundance of tumor-infiltrating immunocytes estimated with CIBERSORTx showed that high ratios of CD8+ T-cells or resting NK cells and low ratios of eosinophils are associated with poor overall survival in diagnostic MCL cases. Integrative analysis of tumor-infiltrating CD8+ T-cell abundance and overexpressed oncogene candidates showed that MCL cases with high ratio CD8+ T-cells and low expression of FTX or PCA3 can potentially predict high-risk MCL patients. WTS results were cross-validated with qRT-PCR of selected transcripts as well as linear correlation analyses. In conclusion, expression levels of oncogenesis-associated transcripts and/or the ratios of microenvironmental immunocytes in MCL tumors may be used to improve prognostication, thereby leading to better patient management and outcomes.
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Linfocitos Infiltrantes de Tumor , Linfoma de Células del Manto , ARN Largo no Codificante , Adulto , Humanos , Carcinogénesis , Linfocitos T CD8-positivos/metabolismo , Linfoma de Células del Manto/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , Factor de von Willebrand , Secuenciación del Exoma , Linfocitos Infiltrantes de Tumor/metabolismo , Biomarcadores de Tumor/genética , PronósticoRESUMEN
Follicular lymphoma (FL) is the second most frequent non-Hodgkin lymphoma accounting for 10-20% of all lymphomas in western countries. As a clinically heterogeneous cancer, FL occasionally undergoes histological transformation to more aggressive B cell lymphoma types that are associated with poor prognosis. Here we evaluated the potential of circulating cell-free DNA (cfDNA) to improve the diagnosis and prognosis of follicular lymphoma patients. Twenty well-characterized FL cases (13 symptomatic and 7 asymptomatic) were prospectively included in this study. Plasma cfDNA, formalin-fixed paraffin-embedded (FFPE) tumor tissue DNA, and patient-matched granulocyte genomic DNA samples were obtained from 20 treatment-naive FL cases. Ultra-deep targeted next-generation sequencing was performed with these DNA samples by using a custom-designed platform including exons and exon-intron boundaries of 110 FL related genes. Using a strict computational bioinformatics pipeline, we identified 91 somatic variants in 31 genes in treatment-naive FL cases. Selected variants were cross-validated by using PCR-Sanger sequencing. We observed higher concentrations of cfDNA and a higher overlap of somatic variants present both in cfDNA and tumor tissue DNA in symptomatic FL cases compared to asymptomatic ones. Variants known to be associated with FL pathogenesis such as STAT6 p.D419 or EZH2 p.Y646 were observed in patient-matched cfDNA and tumor tissue samples. Consistent with previous observations, high Ki-67 staining, elevated LDH levels, FDG PET/CT positivity were associated with poor survival. High plasma cfDNA concentrations or the presence of BCL2 mutations in cfDNA showed significant association with poor survival in treatment-naive patients. BCL2 mutation evaluations in cfDNA improved the prognostic utility of previously established variables. In addition, we observed that a FL patient who had progressive disease contained histological transformation-associated gene (i.e. B2M and BTG1) mutations only in cfDNA. Pre-treatment concentrations and genotype of plasma cfDNA may be used as a liquid biopsy to improve diagnosis, risk stratification, and prediction of histological transformation. Targeted therapies related to oncogenic mutations may be applied based on cfDNA genotyping results. However, the results of this study need to be validated in a larger cohort of FL patients as the analyses conducted in this study have an exploratory nature.
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Introduction: The use of the antifibrinolytic agent tranexamic acid has positive effects on bleeding control, but our knowledge is still limited regarding how fibrinolysis suppression changes the process of bone formation and the quality of bone. Because of the several side effects of systemic tranexamic acid, topical usage has been established in several procedures. This study aimed to investigate the effect of local tranexamic acid on vertebral fusion by using macroscopic, radiologic, and microscopic techniques. We also attempted to determine the safe dose range in case some doses had negative effects on fusion. Methods: Twenty-eight Wistar albino rats underwent intertransverse fusion. All rats were randomized into four groups: groups treated with local tranexamic acid doses of 1 mg/kg (D1), 10 mg/kg (D10), and 100 mg/kg (D100) and the control group with no drug (D0). At the end of the eighth week, all rats were sacrificed for evaluation in terms of palpation, mammography, and histopathologic analysis. Results: The manual palpation results presented with lower fusion rates in D10 and D100 groups than in the control group. Radiological examination results were significantly higher in the control group. The histopathologic examination revealed no significant differences between groups in the percent of new bone formation. Conclusions: Our results showed that local administration of tranexamic acid reduced the quality and stability of fusion without a delay in bone formation. However, doses of 1 mg/kg did not reduce the stability in the palpation test. Our findings suggest that 1 mg/kg dose is a critical threshold above which tranexamic acid reduced the bone healing process of fusion and that surgeons should consider the doses of local tranexamic acid during surgery.
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Objective: Multiple myeloma (MM) is a malignant condition characterized by the accumulation of malignant plasma cells. Although MM remains incurable, the survival of MM patients has improved considerably due to the application of autologous stem cell transplantation, novel agents, and advanced treatment strategies. This study aimed to determine the cytogenetic characterization and bone marrow (BM) features of Turkish patients with MM. Materials and Methods: Eighty-five MM patients were admitted to Dokuz Eylül University Hospital in Turkey. BM samples of these MM patients were subjected to cytogenetic analyses at diagnosis and during therapy as a part of therapeutical and clinical evaluation. A complete cytogenetic study was performed using the G-banding technique. Fluorescence in situ hybridization (FISH) analysis was performed using cytoplasmic immunoglobulin. The degree of BM fibrosis was determined using reticulin histochemical staining. We determined the percentage of BM plasma cells based on the extent of CD38 staining. Results: Eighty-five MM patients were retrospectively identified between 2015 and 2021. The median age was 63 (38-90) years. Of the 85 patients, 60 (70.6%) were male and 25 (29.4%) were female. Seventy-two (84.7%) cases had BM fibrosis at the time of diagnosis. The most common was grade 2 fibrosis, recorded in 35 cases (41.2%). About 72.9% of the patients showed more than 50% plasma cells. FISH analysis indicated the presence of abnormal chromosomes in 37% (32/85) of the patients. The most frequent abnormality was Immunoglobulin heavy-chain (IGH) translocation (21.3%). Conclusion: Subgroup analysis of IGH mutations is crucial in the identification of high-risk MM patients. We believe that our study will contribute to the determination of BM biopsy and cytogenetic features of MM patients in our country.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Médula Ósea/patología , Análisis Citogenético/métodos , Femenino , Fibrosis , Humanos , Inmunoglobulinas , Hibridación Fluorescente in Situ/métodos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Mieloma Múltiple/terapia , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
Human herpes virus-8 (HHV-8) is linked to four lymphoproliferative diseases: primary effusion lymphoma, HHV-8 positive multicentric Castleman disease (MCD), HHV-8 positive diffuse large B cell lymphoma and HHV-8 positive germinotropic lymphoproliferative disorder (GLPD). The diagnosis of HHV-8 associated lymphoproliferative diseases is quite challenging because each entity is rare and has a wide morphological spectrum. Our aim is to emphasize the overlapping histopathological features of MCD and GLPD as well as to underline the importance of clinicopathological correlation in case these two entities cannot be distinguished by pathological examination. We present here a case of an 82-year-old male patient who was examined for weight loss and multiple lymphadenopathy. Histopathological examination of the axillary lymph node revealed lymphoid follicle structures of varying shapes and sizes, including some atrophic germinal centers. Plasmablast-like cells were notable in some of these areas. HHV-8 and Epstein Barr Virus (EBV) positivity were noted in some of these cells and in a small number of cells in the mantle zone. Based on these findings; a diagnosis of "HHV-8 and EBV positive lymphoproliferative disease" was established. Since HHV-8 positive MCD and GLPD have similar histopathological features, it may not be possible to distinguish these two entities by histopathological examination only. At this point, the importance of clinicopathological correlation becomes more evident, especially in the determination of the treatment protocol to be applied to the patient.
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Infecciones por Virus de Epstein-Barr , Infecciones por Herpesviridae , Herpesvirus Humano 8 , Trastornos Linfoproliferativos , Anciano de 80 o más Años , Enfermedad de Castleman , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/patología , Herpesvirus Humano 4 , Humanos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/patología , MasculinoRESUMEN
Intraocular lymphomas are among the rare malignancies that present with a wide variety of clinical manifestations. Differential diagnosis can be very troublesome due to its mimicking nature, insidious disease onset, and partial treatment response to steroids. The most important step in diagnosis is a high index of suspicion. Signs of the disease are now easier to detect using multimodal imaging techniques. In this case series, we reviewed the clinical characteristics of two women aged 70 and 71 years and a 72-year-old man with intraocular lymphoma and described their multimodal imaging findings in detail. Bilateral eye involvement was present in all three cases at our first ophthalmological examination. While the disease first presented with ocular involvement in two of the three cases, ocular involvement was detected seven years after initial heart involvement in one patient. All three patients had diffuse large B-cell lymphomas (one diagnosed with retinal biopsy, one with conjunctival biopsy, and the remaining with stereotactic brain biopsy). Intraocular lymphoma should be diagnosed and treated using a multidisciplinary approach, and we share our experience in this case series.
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Neoplasias del Ojo , Linfoma Intraocular , Neoplasias del Ojo/diagnóstico , Femenino , Angiografía con Fluoresceína , Humanos , Linfoma Intraocular/diagnóstico , Masculino , Retina , Tomografía de Coherencia ÓpticaRESUMEN
BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a rare multisystemic idiopathic fibroinflammatory disorder. The rare form of IgG4-RD with isolated thorax involvement is called immunoglobulin G4-related respiratory disease (IgG4-RRD). IgG4-RRD, which is reported in a limited number of cases in the literature, can be categorized into four types on the prevalent chest computed tomography (CCT) findings: solid nodular, round-shaped ground-glass opacity, alveolar interstitial, and bronchovascular. Solid nodular form of IgG4-RRD with mass-like lesions is sporadic and described in the literature with a small number of case reports. OBJECTIVES/METHODS: We aim to present the radiologic, pathologic, and clinical findings of three cases of IgG4-RRD mimicking lung cancer. RESULTS: In all three patients, IgG4-RRD occurred with mass-like lesions in the thorax. In case-1 and 2, CCT showed multiple, nodular lesions and multiple mediastinal lymph nodes. On positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro- D-glucose integrated with computed tomography (18F-FDG PET/CT), the masses showed increased 18F-FDG uptake in case-2 and 3. The gold standard histopathological verification for IgG4-RRD was provided for all cases. CONCLUSIONS: IgG4-RD is an immune-mediated condition comprised of a collection of disorders that share particular pathologic, radiologic, serologic, and clinical features. Isolated IgG4-RRD is rarely seen and is available in the literature as case reports. IgG4-RRD, which can make lung involvement in different patterns, rarely appears with mass-like lesions. Still, IgG4-RRD must be considered in the differential diagnosis of mass lesions detected in CCT. Laboratory, radiological, and histopathological findings of the disease should be evaluated together for an accurate diagnosis.
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BACKGROUND: Differentiation of multiple myeloma (MM) from osteolytic metastatic (OM) bone lesions may be critical in patients with lytic bone lesions but can be challenging for radiologists. PURPOSE: To determine whether computed tomography (CT) can be used to distinguish between MM and other OM bone lesions. MATERIAL AND METHODS: In this retrospective study, 320 lesions of 207 patients diagnosed with MM or OM, based on biopsy or clinical examination, were evaluated. Eight qualitative features were evaluated by two radiologists blinded to the diagnoses. The chi-square and Fisher exact tests, and logistic regression analysis, were used to evaluate the relationships between the CT findings and diagnoses. RESULTS: High-density areas were more common in OM than MM lesions (85.2% and 19%, P < 0.001), as were perilesional sclerosis (38.9% vs. 13.2%, P < 0.001), heterogeneity (on non-contrast CT images, 60% vs. 19.1%, P < 0.001; on contrast enhanced CT images, 80.6% vs. 28.2%, P < 0.001), and ill-defined margins (34.6% vs. 9.1%, P < 0.001). Similarly, OM lesions showed high-density areas more than MM in evaluation of skeletal system subgroups (vertebrae, 93.8% vs. 29.8%, P < 0.0001; thoracic cage bones, 69.6% vs. 19.2%, P < 0.001; pelvic bones and sacrum, 84.8% vs. 7.7%, P < 0.001; peripheral skeletal bones, 81.5% vs. 8.3%, P < 0.001). Logistic regression analysis revealed that the presence of a high-density area in the lesion increased the probability of a metastasis 25.88-fold (R2 = 0.516, P < 0.001). CONCLUSION: MM and OM lesions can be differentiated by CT; OM lesions exhibit high- density areas.
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Neoplasias Óseas/diagnóstico por imagen , Mieloma Múltiple/diagnóstico por imagen , Osteólisis/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Densidad Ósea , Neoplasias Óseas/secundario , Huesos/diagnóstico por imagen , Distribución de Chi-Cuadrado , Medios de Contraste , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos , Esclerosis/diagnóstico por imagen , Adulto JovenRESUMEN
OBJECTIVE: Lipodystrophy represents a group of rare diseases characterized by loss of body fat. While patients with generalized lipodystrophy exhibit near-total lack of fat, partial lipodystrophy is associated with selective fat loss affecting certain parts of the body. Although classical familial partial lipodystrophy (FPLD) is a well-described entity, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants. METHODS: We have encountered 2 unique cases with complex phenotypes, generalized fat loss, and very low leptin levels that made the distinction between generalized versus partial lipodystrophy quite challenging. RESULTS: We present a 61-year-old female with generalized fat loss, harboring the heterozygous pathogenic variant p.R541P (c.1622G>C) on the LMNA gene. The discovery of the pathogenic variant led to correct clinical diagnosis of her muscle disease, identification of significant heart disease, and a recommendation for the implantation of a defibrillator. She was able to start metreleptin based on her generalized fat loss pattern and demonstration of the genetic variant. Secondly, we report a 40-year-old Turkish female with generalized fat loss associated with a novel heterozygous LMNA pathogenic variant p.K486E (c.1456A>G), who developed systemic B cell follicular lymphoma. CONCLUSION: Clinicians need to recognize that the presence of an LMNA variant does not universally lead to FPLD type 2, but may lead to a phenotype that is more complex and may resemble more closely generalized lipo-dystrophy. Additionally, providers should recognize the multisystem features of laminopathies and should screen for these features in affected patients, especially if the variant is not at the known hotspot for FPLD type 2.
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Objective: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). The treatment of older NHL patients has always been a struggle; however, treatment statistics have begun showing favorable results similar to those of younger DLBCL patients thanks to newer treatment protocols. Here, we analyze the progress of our own elderly DLBCL patients who were followed between 2000 and 2016 in our center. Materials and Methods: Eighty-seven DLBCL patients, who were diagnosed and treated in the Dokuz Eylül University Department of Hematology between 2000 and 2016, were included in this study. Median age was 72 (65-89) years and 13 (14.9%) patients were older than 80 years. Results: Median follow-up time was 19 months and 45 patients (51.7%) died during the follow-up period. Median overall survival (OS) was 55 months and median progression-free survival was calculated as 27 months. Sixty-three patients (72.4%) received standard R-CHOP therapy. Complete response was seen in 46 (52.9%) patients. The median survival time for patients who had complete response was 136 months (p<0.001); however, OS was not statistically different between older (>80 years) and younger patients (p=0.236). Conclusion: According to our findings, we think that being able to complete standard R-CHOP therapy is vital for the survival rate of elderly DLBCL patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Achilles tendon ruptures are characterized by a long recovery period, high re-rupture rate and late return to work. To overcome these difficulties and augment tendon repair, many agents have been used. AIMS: To determine the effect of autologous platelet rich plasma (PRP) in the treatment of Achilles tendon ruptures in rabbits. STUDY DESIGN: Animal experimentation. METHODS: The study included 14 New Zealand albino rabbits that were divided randomly into 2 groups, A and B, each containing seven rabbits. On day zero, all 28 Achilles tendons were tenotomized and repaired. In group A, the tendons were injected with PRP post-surgery, whereas those in group B were left untreated. On day 28, the right tendons in both groups were examined histopathologically via both light and electron microscopy, and the left tendons were subjected to biomechanical testing. RESULTS: The histological and biomechanical findings in both light and electron microscopy in group A were better than those in group B, but the difference was not significant. According to Tang's scale, the mean value in Group A was 3.57, while it was 3.0 in Group B. The mean value of Group A for the length of collagen bands was 48.09 nm while the mean value of Group B was 46.58 nm (p=0.406). In biomechanical tests, although stiffness values were higher in group A, the difference between groups was not significant. In addition, maximum load values did not differ between groups A and B. CONCLUSION: PRP had no effect on the healing process 28 days post-Achilles tendon rupture.
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BACKGROUND: Mast cell leukemia (MCL) is rare type of neoplasia with an incidence of 1% in a large series of 342 adult patients with systemic mastocytosis (SM). Chronic basophilic leukemia (CBL) is an extremely rare type of leukemia with appearance of 7 cases in the literature. CASE PRESENTATION: A 73 year-old female patient who presented with weaknes, had a prolonged duration of hematologic remission after treatment of her CBL by hydroxyurea (HU). Evolution of SM occurring as a second neoplasia concurrently with relapse of de novo CBL was demonstrated by mast cells (MCs) infiltration in the bone marrow (BM) biopsy and smear and increase in tryptase level. Transformation to MCL with simultaneous occurrance of accelerated phase of CBL were documented by the appearance of MCs in both BM and peripheral blood (PB) smears, antigen expressions detected by flow cytometry and spesific stains. Sequence analysis of c-kit gene revealed c-kit exon 11 K550N mutation. Undefined associations of MCL with different mast cell morphology, increase in IL-6 level and accelerated phase of de novo CBL was described. CONCLUSION: Elevations in CRP and IL-6 levels occurring with increases in basophil counts to high levels revealed that febrile episodes with abdominal pain seen in our patient were induced by increase in IL-6 levels released from neoplastic basophils. Neoplastic basophils with diffuse and coarse basophilic granules possibly mimic neutrophils with toxic granules and cause wrong characterization of neoplastic basophils as neutrophils by the automated blood cell counters and misleaded physicians.
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UNLABELLED: Acute lymphoblastic leukemia (ALL) is a pediatric malignancy associated with remissions and relapses. Common relapsing sitesare meninges, testis and ovary. Testicular scintigraphy is a highly specific modality used mainly in the differential diagnosis of testicular torsion and epidydimitis/epidydimo-orchitis. There is only one interesting image on leukemic infiltration with scrotal scintigraphy in the literature. The aim of this case presentation is to report that although the scintigraphic appearance of testicular torsion was observed in a patient with the diagnosis of ALL, testicular ALL infiltration was revealed in pathologic examination. CONFLICT OF INTEREST: None declared.
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Intravesical Bacillus Calmette-Guérin (BCG) is widely used as an adjuvant therapy in the treatment of non-muscle-invasive bladder cancer. BCG is generally well tolerated, though localized and systemic infectious complications may occur. Infection of the glans and inguinal adenopathy are rare local complications of intravesical BCG therapy. Traumatic urethral catheterization is one of the main causes. We report the case of a 75-year-old male who developed granulomatous balanitis and enlarged inguinal lymph nodes after five cycles of intravesical BCG treatment for transitional cell carcinoma of the bladder. Histology revealed giant cell granuloma. Oral antituberculous treatment was initiated with subsequent full recovery of penile lesions and adenopathy. Physicians who administer BCG must be familiar with the possible complications and their adequate management and should inform patients about the side-effects accordingly.
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Diffuse large B-cell infiltration of the skin includes mainly primary cutaneous follicle center lymphoma (PCFCL) with diffuse architecture and diffuse large B cell lymphoma (PCDLBCL), leg type. Differentiation of these lymphomas on morphology may be troublesome. Immunohistochemistry panel, including CD20, CD79a, bcl-6, bcl-2, MUM-1, FOX-P1 is mandatory. However, in minority of cases, these markers would not suffice. In order to search the value of another marker, IgM, 30 cases of PCFCL and 10 cases of PCDLBCL, leg type were included in the study. As suggested in a recent literature, our study denoted that expression of IgM was useful as an additional tool for differentiation.
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Inmunoglobulina M/metabolismo , Linfoma Folicular/diagnóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Neoplasias Cutáneas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Diagnóstico Diferencial , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Linfoma Folicular/metabolismo , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patologíaRESUMEN
It is believed that viral infections and the hyperimmune reaction due to these infections are involved in the etiology of Kikuchi-Fujimoto Disease (KFD), a rare cause of fever of unknown origin. Axillary lymphadenopathy and neurologic involvement are rare in KFD. We present a patient diagnosed with KFD histopathologically during an investigation of the origin of fever and axillary lymphadenopathy. Subsequently, incidental sinus aspergilloma was diagnosed radiologically in the patient and acute disseminated encephalitis developed during follow-up. This report aims to draw attention to the co-existence of KFD and Acute Disseminated Encephalomyelitis, two diseases of which the origins are not clear.
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Encefalomielitis Aguda Diseminada/complicaciones , Encefalomielitis Aguda Diseminada/diagnóstico , Fiebre de Origen Desconocido/diagnóstico , Fiebre de Origen Desconocido/etiología , Linfadenitis Necrotizante Histiocítica/complicaciones , Linfadenitis Necrotizante Histiocítica/diagnóstico , Adulto , Femenino , HumanosRESUMEN
Matrix metalloproteinases (MMPs), and, in particular, gelatinases (MMP-2 and MMP-9), have been implicated in vascular cell proliferation and/or migration, contributing to intimal thickening, an essential stage in the development of atherosclerosis and restenosis following balloon angioplasty. Endothelin, a strong chemoatractant and mitogen, has been shown to promote smooth muscle cell proliferation and migration by activating MMPs via endothelin-A (ETA) receptors. The positioning of a soft silicon collar around the left carotid artery in rabbits results in intimal thickening. In this study, we investigate the possible role of gelatinases and the effect of a nonselective ETA/ETB receptor antagonist, TAK-044 (5 mg/kg body weight/day, subcutaneously [sc]), on these enzymes. Our results demonstrated that both MMP-2 and MMP-9 activities increased in response to collaring in placebo group, while treatment with TAK-044 significantly suppressed both gelatinase activities and proMMP-2 levels, and inhibited intimal thickening in collared arteries. These results suggest that either enhanced MMP expression or endothelin receptor antagonism may be involved in the formation of intimal thickening in this model.
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Enfermedad de la Arteria Coronaria/metabolismo , Antagonistas de los Receptores de Endotelina , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Péptidos Cíclicos/farmacología , Animales , Arterias Carótidas/efectos de los fármacos , Arterias Carótidas/enzimología , Enfermedad de la Arteria Coronaria/enzimología , Enfermedad de la Arteria Coronaria/etiología , Modelos Animales de Enfermedad , Activación Enzimática/efectos de los fármacos , Precursores Enzimáticos/metabolismo , Femenino , Gelatinasas/metabolismo , Masculino , Conejos , Túnica Íntima/anatomía & histología , Túnica Íntima/citología , Túnica Íntima/efectos de los fármacos , Túnica Íntima/metabolismoRESUMEN
Focal adhesion kinase (FAK) is a protein tyrosine kinase essential for intracellular regulatory events, such as cell growth, differentiation, migration and tumor metastasis. The aim of this study was to analyze the expression of FAK protein in a series of normal and neoplastic lymphoid tissues. An anti-FAK antibody was used to study the protein expression in paraffin-embedded samples of normal and neoplastic, hematolymphoid and non-hematolymphoid tissues by immunohistochemistry. In normal hematolymphoid tissue, the strongest expression of FAK was detected in germinal center and marginal-zone B cells; positive staining was also found in mantle zone B cells. In human lymphomas, FAK was expressed mostly in B-cell lymphomas and was predominantly negative in T-cell lymphoma. In Hodgkin lymphomas, FAK was found only in the neoplastic cells of lymphocyte predominant type, whereas the tumor cells of the classical form were FAK-negative. We demonstrate for the first time the expression of FAK in paraffin-embedded hematolymphoid tissue samples. Its differential expression in lymphomas may be of relevance for some B-cell neoplasms by using it as an additional marker to distinguish B- from T-lymphoblastic leukemia/lymphoma to further differentiate lymphocyte predominant from classical Hodgkin lymphoma.