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1.
Am J Hematol ; 98(2): 264-271, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36588407

RESUMO

Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full-blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familial monoclonal gammopathy, the Intergroupe Francophone du Myélome identified 318 families with at least two confirmed cases of monoclonal gammopathy. There were 169 families with parent/child pairs and 164 families with cases in at least two siblings, compatible with an autosomal transmission. These familial cases were compared with sporadic cases who were matched for age at diagnosis, sex and immunoglobulin isotype, with 10 sporadic cases for each familial case. The gender distribution, age and immunoglobulin subtypes of familial cases were unremarkable in comparison to sporadic cases. With a median follow-up of 7.4 years after diagnosis, the percentage of MGUS cases having evolved to MM was 3%. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Paraproteinemias , Criança , Humanos , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Paraproteinemias/genética , Paraproteinemias/complicações , Mieloma Múltiplo/patologia , Prognóstico , Aberrações Cromossômicas
3.
J Clin Exp Hematop ; 62(4): 273-278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36575005

RESUMO

Lymphoplasmacytic lymphoma (LPL) usually involves bone marrow (BM) and sometimes lymph nodes and spleen. LPL presenting as a hepatic mass lesion is extremely rare, with only one case reported in the English literature. A 70-year-old Japanese female presented to us with a right hypochondriac mass with tenderness. Computed tomography (CT) revealed a 14 cm-sized bulky hepatic mass. Laboratory findings showed a normal white blood cell count of 4.1×109/L with 4% plasmacytoid lymphocytes; normocytic anemia, Hb 9.4 g/dL; high soluble IL-2 receptor level, 2,290 U/mL; and elevated IgG, 10,306 mg/dL. Furthermore, IgG-κ monoclonal protein was detected. 18F-fluorodeoxyglucose-positron emission tomography/CT revealed abnormal uptake in the liver mass; left supraclavicular, parasternal, abdominal, and left inguinal lymph nodes; and bilateral lung bases. Magnetic resonance imaging showed no bone lesions. BM aspiration and liver biopsy showed predominant infiltration of small lymphocytes admixed with plasmacytoid lymphocytes and plasma cells. In the liver specimen, lymphoepithelial lesions were not observed. The small lymphocytes were positive for CD20, CD79a, and bcl-2, and negative for CD5, CD10, cyclin D1, and IRTA1; plasma cells in BM were positive for CD19, CD45, IgG, and κ-chain, and negative for CD20, and CD56. MYD88 L265P mutation, reported in approximately 40% of non-IgM LPL cases, was not detected in the liver specimen and BM cells. The frequency is lower than that of typical IgM LPL. These findings led us to a diagnosis of LPL with IgG-κ paraproteinemia. The patient underwent four courses of R-CHOP and two courses of Bendamustine-R. Partial remission was achieved.


Assuntos
Linfoma de Células B , Paraproteinemias , Macroglobulinemia de Waldenstrom , Humanos , Feminino , Idoso , Rituximab , Imunoglobulina G
4.
Int J Mol Sci ; 23(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36555090

RESUMO

Multiple myeloma (MM) is a monoclonal gammopathy characterized by biological heterogeneity and unregulated proliferation of plasma cells (PCs) in bone marrow (BM). MM is a multistep process based on genomic instability, epigenetic dysregulation and a tight cross-talk with the BM microenvironment that plays a pivotal role supporting the proliferation, survival, drug-resistance and homing of PCs. The BM microenvironment consists of a hematopoietic and a non-hematopoietic compartment, which cooperate to create a tumor environment. Among the non-hematopoietic component, mesenchymal stromal cells (MSCs) and osteoblasts (OBs) appear transcriptionally and functionally different in MM patients compared to healthy donors (HDs) and to patients with pre-malignant monoclonal gammopathies. Alterations of both MSCs and OBs underly the osteolytic lesions that characterize myeloma-associated bone disease. In this review, we will discuss the different characteristics of MSCs and OBs in MM patients, analyzing the transcriptome, the deregulated molecular pathways and the role performed by miRNAs and exosome in the pathophysiology of MM.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Paraproteinemias , Humanos , Mieloma Múltiplo/patologia , Medula Óssea/metabolismo , Plasmócitos/metabolismo , Paraproteinemias/patologia , Gamopatia Monoclonal de Significância Indeterminada/patologia , Microambiente Tumoral
5.
Ann Intern Med ; 175(12): ITC177-ITC192, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36508741

RESUMO

Monoclonal gammopathy of undetermined significance (MGUS) is of considerable clinical importance to primary care physicians given its high prevalence in the general population. MGUS has a variable but lifelong risk for progression to hematologic cancer, such as multiple myeloma, Waldenström macroglobulinemia, or light-chain amyloidosis. In addition, MGUS has been associated with several nonmalignant yet symptomatic disorders that require therapy directed toward eliminating the monoclonal gammopathy. Thus, it is important not only to understand the essentials of diagnosing and monitoring patients with MGUS but also to recognize when to refer patients with MGUS to a specialist.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Paraproteinemias , Macroglobulinemia de Waldenstrom , Humanos , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/terapia , Progressão da Doença
8.
BMC Vet Res ; 18(1): 384, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36324112

RESUMO

BACKGROUND: Multiple myeloma (MM) is an uncommon neoplasm in cats. There is no established standard of treatment due to the rare occurrence of this disease in cats. Bortezomib is a proteasome inhibitor that serves as the first-line drug for MM in humans, but its effectiveness currently is unknown in feline MM. We present here the case report of a feline MM that exhibited a favorable response to bortezomib. CASE PRESENTATION: The case was an 11-year-old non-castrated male domestic cat with light-chain MM presenting with clinical symptoms (anorexia, fatigue, and vomiting), mild azotemia, and pancytopenia. The cat failed on melphalan with prednisolone (MP), so bortezomib (Velcade) was initiated on Day 88. A total of 6 cycles of the treatment was performed, with each treatment cycle consisting of twice-weekly subcutaneous administration for 2 weeks followed by a 1-week rest. The dose of bortezomib was 0.7 mg/m2 for first week and 1.0 mg/m2 for second week in the first cycle. A dose of 0.7 mg/m2 was used for subsequent cycles. Prednisolone was used concomitantly in the first 2 cycles. Following treatment with bortezomib, clinical symptoms disappeared and a decrease in serum globulin and recovery of pancytopenia were noted. A monoclonal gammopathy, overproduction of serum immunoglobulin light chain, and Bence-Jones proteinuria that existed at diagnosis were undetectable on Day 123. A monoclonal gammopathy also was not detectable at the end of the bortezomib treatment (Day 213). Anorexia, fatigue, and marked bone marrow toxicity were experienced when bortezomib was administrated at a dose of 1.0 mg/m2, while no recognizable toxicity was observed at a dose of 0.7 mg/m2 throughout the treatment period. The case was placed on follow-up and there was no evidence of relapse as of Day 243. CONCLUSIONS: Bortezomib was effective and durable for the treatment of this case of feline MM after failure with MP. Bortezomib was well-tolerated in this cat at a dose of 0.7 mg/m2, but not at 1.0 mg/m2. Bortezomib appears to be a drug worthy of further study for the treatment of feline MM.


Assuntos
Doenças do Gato , Mieloma Múltiplo , Pancitopenia , Paraproteinemias , Humanos , Gatos , Masculino , Animais , Bortezomib/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/veterinária , Mieloma Múltiplo/diagnóstico , Pancitopenia/veterinária , Anorexia/veterinária , Recidiva Local de Neoplasia/veterinária , Paraproteinemias/tratamento farmacológico , Paraproteinemias/veterinária , Prednisolona/uso terapêutico , Fadiga/veterinária , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Doenças do Gato/tratamento farmacológico
9.
Rinsho Ketsueki ; 63(10): 1379-1385, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-36351643

RESUMO

There is currently no evidence that a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine might be associated with the development of autoimmune hemolytic anemia or disease progression in patients with mature B-cell neoplasm. Our patient was a 71-year-old man with indolent mature B-cell neoplasm who had been monitored for many years without treatment. After receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine, he developed severe warm autoimmune hemolytic anemia. Although steroid therapy improved his anemia, he continued to develop IgM-monoclonal gammopathy, renal insufficiency, and splenomegaly. He was diagnosed with splenic marginal zone lymphoma after undergoing splenectomy. The splenectomy improved the patient's symptoms. We assessed his SARS-CoV-2 specific antibody response, but the patient's serologic response to the vaccine was impaired. In patients with mature B-cell neoplasm, a non-specific immune response after vaccination might be associated with paraneoplastic syndromes.


Assuntos
Anemia Hemolítica Autoimune , Vacinas contra COVID-19 , COVID-19 , Leucemia Linfocítica Crônica de Células B , Linfoma de Células B , Paraproteinemias , Neoplasias Esplênicas , Idoso , Humanos , Masculino , Anemia Hemolítica Autoimune/etiologia , Anemia Hemolítica Autoimune/complicações , Vacina BNT162 , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Imunoglobulina M , Leucemia Linfocítica Crônica de Células B/complicações , Linfoma de Células B/tratamento farmacológico , Paraproteinemias/complicações , SARS-CoV-2 , Neoplasias Esplênicas/complicações
11.
PLoS One ; 17(10): e0276048, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36315502

RESUMO

PURPOSE: To determine prevalence of paraproteinemic keratopathy (PPK) among patients with monoclonal gammopathy (MG). To evaluate interrelation between corneal and hematological parameters in patients with PPK. METHODS: Fifty-one patients with monoclonal gammopathy of undetermined significance (n = 19), smoldering multiple myeloma (n = 5) or multiple myeloma (n = 27) were prospectively included in this study. Best-corrected visual acuity, slit-lamp biomicroscopy, Scheimpflug tomography, in-vivo confocal laser scanning microscopy, optical coherence tomography and complete hematological workup were assessed. RESULTS: We identified n = 19 patients with bilateral corneal opacities compatible with PPK. PPK was newly diagnosed in 13 (29%) of 45 patients with a primary hematological diagnosis and in n = 6 patients without previous hematological diagnosis. The most common form was a discreet stromal flake-like PPK (n = 14 of 19). The median level of M-protein (p = 0.59), IgA (p = 0.53), IgG (p = 0.79) and IgM (p = 0.59) did not differ significantly between the patients with and without PPK. The median level of the FLC κ in serum of patients with kappa-restricted plasma cell dyscrasia was 209 mg/l in patients with PPK compared to 38.1 mg/l in patients without PPK (p = 0.18). Median level of FLC lambda in serum of patients with lambda-restricted plasma cell dyscrasia was lower in patients with PPK compared to patients without PPK (p = 0.02). CONCLUSION: The PPK was mostly discreet, but its prevalence (29%) was higher than expected. Median level of the monoclonal paraprotein was not significantly higher in patients with PPK compared to patients without PPK. Our results suggest a lack of correlation between morphology and severity of the ocular findings and severity of the monoclonal gammopathy. TRIAL REGISTRATION: German Clinical Trial Register: DRKS00023893.


Assuntos
Doenças da Córnea , Opacidade da Córnea , Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Paraproteinemias , Humanos , Doenças da Córnea/diagnóstico , Paraproteinemias/epidemiologia , Prevalência , Transtornos da Visão
12.
Klin Lab Diagn ; 67(10): 570-574, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36315171

RESUMO

Multiple myeloma (MM) is a malignant tumor occurring from plasma cells that produce an abnormal monoclonal immunoglobulin - a paraprotein. A distinctive feature of Bence-Jones myeloma is the excretion of monoclonal free light chains of immunoglobulins with 24h urine, and the absence of monoclonal intact immunoglobulins secretion. Comprehensive analysis of biochemical parameters in blood serum and 24h urine in patients with Bence-Jones multiple myeloma using electrophoretic and immunoturbidimetric methods to assess their sensitivity as biomarkers. 50 patients with a morphologically confirmed diagnosis of MM of the Bence-Jones immunochemical type were examined. 28 people without oncological diseases were examinedas a control. Detection of monoclonal secretion in blood serum and daily urine was performed by immunofixation electrophoresis on the Hydrasys 2 electrophoretic system (Sebia). The determination of free light chains of immunoglobulins (FLC) was performed by the immunoturbidimetric method (Binding Site) on an Advia 1800 analyzer (Siemens). Analysis of IgG, IgA, IgM, ß2-microglobulin and C-reactive protein was performed on Cobas 6000 analyzer (Roche). The median excretion of Bence-Jones protein in 24h urine of MM patients was 0.49 g/24h (0.06-2.45 g/24h). In the blood serum, in 86% of cases, the presence of paraproteinemia, represented by κ and λ type light chains of immunogloublins was detected. At the same time, the frequency of detection of monoclonal secretion in blood serum in Bence-Jones type λ myeloma was 95.7%, which was statistically significantly higher than the frequency of detection of monoclonal secretion of type κ - 77.8%. In patients with identified paraproteinemia, Bence-Jones protein excretion in daily urine (median 0.82 g/day) was statistically significantly higher than in patients without a monoclonal component detected in blood serum (median 0.04 g/24h). The levels of FLC in blood serum obtained by immunoturbidimetry in Bence-Jones myeloma of the corresponding type were higher than the reference levels in 100% of cases. The median level of κ-FLC reached 4358 mg/l, λ-FLC - 2225 mg/l, which was statistically significantly higher than the control levels. The median concentrations of IgG, IgA and IgM in patients with Bence-Jones myeloma were statistically significantly lower than in the control group, while the medians of ß2-microglobulin and C-reactive protein were significantly higher than in the control. Our investigation showed high diagnostic efficiency of electrophoretic and immunoturbidimetric analysis of monoclonal secretion in patients with Bence-Jones MM, while FLC analysis demonstrated maximum sensitivity. Bence-Jones MM revealed biochemical signs of secondary immunodeficiency and general inflammatory syndrome.


Assuntos
Mieloma Múltiplo , Paraproteinemias , Humanos , Mieloma Múltiplo/diagnóstico , Proteína C-Reativa , Proteína de Bence Jones/urina , Cadeias lambda de Imunoglobulina/urina , Anticorpos Monoclonais , Imunoglobulina G , Imunoglobulina A , Imunoglobulina M
13.
Sci Rep ; 12(1): 16994, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36216844

RESUMO

Monoclonal gammopathy has emerged as an important cause of renal injury. Since the clinicopathologic features related to monotypic monoclonal gammopathy of renal significance with IgM monoclonal gammopathy (IgM-MGRS) are poorly described and it is uncertain if intervention improves renal survival and mortality, we report a series of such patients, characterizing their clinicopathologic spectrum and outcomes. We retrospectively analyzed 38 patients referred to one medical center between 2009 and 2019 with detectable serum monoclonal IgM by immunofixation, performance of a bone marrow biopsy and kidney biopsy-proven MGRS. Of the 38 patients identified, about half patients were amyloidosis, followed by cryoglobulinemic glomerulonephritis. Patients were divided into two groups on the basis of their kidney pathology: amyloid and non-amyloid. Patients with non-amyloidosis were more likely to have renal dysfunction, hematuria, anemia and hypocomplementemia and κ light chain was predominant in this sub-group. Amyloid patients were more often treated with chemotherapy than the non-amyloid patients (P = 0.002). There were no significant differences between amyloid and non-amyloid patients in mortality (48% vs 29%, P = 0.467) and incidence of ESRD (19% vs 59%, P = 0.103). The incidence of ESRD was lower in patients treated with chemotherapy and/or ASCT, compared to those without chemotherapy (25% vs 57%, P = 0.049), and it was also lower in the hematologic responders than non-responders (10% vs 40%, P = 0.047). Our study confirmed a diverse variety of clinicopathological features and outcomes in patients with IgM-MGRS. Chemotherapy and/or ASCT and deep hematologic responses might improve renal prognosis.


Assuntos
Amiloidose , Nefropatias , Falência Renal Crônica , Linfoma de Células B , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Amiloidose/patologia , Humanos , Imunoglobulina M , Rim/patologia , Nefropatias/patologia , Falência Renal Crônica/complicações , Linfoma de Células B/patologia , Gamopatia Monoclonal de Significância Indeterminada/complicações , Paraproteinemias/complicações , Prognóstico , Estudos Retrospectivos
14.
Eur Rev Med Pharmacol Sci ; 26(18): 6777-6786, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36196726

RESUMO

OBJECTIVE: Bence Jones proteinuria (BJP) refers to monoclonal free immunoglobulin light chains detected in urine, deriving from the clonal expansion of plasma cells in the bone marrow in patients with plasma cell dyscrasias, associated with monoclonal gammopathies of uncertain origin. This review summarizes routinely diagnostic procedures to assess BJP highlighting critical steps of pre-analytical, analytical, and post-analytical phases. QUALITATIVE AND QUANTITATIVE METHODS: The best option for BJP detection is the first morning void urine sample and immunofixation electrophoresis detection technique (IFE) the recommended method, with the employment of specific polyvalent antisera. Other qualitative tests for a quick evaluation of BJP are currently available. Densitometric analysis performed on the 24-hour urine is the recommended method to quantify BJP. To overcome the 24-hour collection, it is possible to use morning urine sample and correlate the assessed value of BJP to creatininuria. In addition to the traditional ones, we here reviewed screening methods currently used to avoid false negatives and reduce the time around test (TAT), together with immunochemical quantification methods for increased sensitivity, after checking BJP by IFE. Mass spectrometry emerges as a new challenge in the determination of BJP. CONCLUSIONS: The employment of different based-assays methods may be useful for diagnostic purposes to improve the accuracy of BJP monitoring in monoclonal gammopathies.


Assuntos
Neoplasias , Paraproteinemias , Proteína de Bence Jones/urina , Humanos , Soros Imunes , Cadeias Leves de Imunoglobulina , Paraproteinemias/diagnóstico , Proteinúria/diagnóstico
15.
Ann Hematol ; 101(12): 2627-2631, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36194257

RESUMO

Acquired von Willebrand syndrome (AVWS) is a rare hematologic disorder characterized by quantitative or qualitative defects of von Willebrand factor (vWF), a protein crucial for normal hemostasis. AVWS has been described in association with several pathologic entities with varied mechanisms. Among these, lymphoproliferative disorders are the most common, with monoclonal gammopathy of undetermined significance (MGUS) being the most frequently reported. AVWS in this setting is commonly associated with the development of bleeding that is clinically challenging to manage due to accelerated clearance of vWF, limiting the utility of many conventional treatment modalities such as DDAVP or vWF/FVIII. We report a case of a 43-year-old male who was sent to our institution for new-onset easy bruising and laboratories concerning for von Willebrand disease (vWD). Further diagnostic workup revealed evidence of an IgG monoclonal gammopathy and findings suggestive of vWF inhibition. Ultimately, he was found to have monoclonal gammopathy of clinical significance (MGCS)-associated AVWS refractory to conventional treatment but responsive to lenalidomide and dexamethasone. This case suggests that lenalidomide may be suitable for patients with AVWS secondary to MGCS.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Doenças de von Willebrand , Masculino , Humanos , Adulto , Doenças de von Willebrand/complicações , Doenças de von Willebrand/tratamento farmacológico , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/tratamento farmacológico , Fator de von Willebrand/metabolismo , Lenalidomida/uso terapêutico , Paraproteinemias/complicações , Paraproteinemias/tratamento farmacológico , Paraproteinemias/diagnóstico
16.
BMC Med Genomics ; 15(1): 203, 2022 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-36138464

RESUMO

BACKGROUND: Next-generation sequencing (NGS) detects somatic mutations in a high proportion of plasma cell dyscrasias (PCD), but is currently not integrated into diagnostic routine. We correlated NGS data with degree of bone marrow (BM) involvement by cytomorphology (BMC), histopathology (BMH), and multiparameter flow cytometry (MFC) in 90 PCD patients. METHODS: Of the 90 patients the diagnoses comprised multiple myeloma (n = 77), MGUS (n = 7), AL-amyloidosis (n = 4) or solitary plasmocytoma (n = 2). The NGS panel included eight genes CCND1, DIS3, EGR1, FAM46C (TENT5C), FGFR3, PRDM1, TP53, TRAF3, and seven hotspots in BRAF, IDH1, IDH2, IRF4, KRAS, NRAS. RESULTS: Mutations were detected in 64/90 (71%) of cases. KRAS (29%), NRAS (16%) and DIS3 (16%) were most frequently mutated. At least one mutation/sample corresponded to a higher degree of BM involvement with a mean of 11% pathologic PC by MFC (range, 0.002-62%), and ~ 50% (3-100%) as defined by both BMC and BMH. CONCLUSIONS: The probability of detecting a mutation by NGS in the BM was highest in samples with > 10% clonal PC by MFC, or > 20% PC by BMC/ BMH. We propose further evaluation of these thresholds as a practical cut-off for processing of samples by NGS at initial PCD diagnosis.


Assuntos
Paraproteinemias , Proteínas Proto-Oncogênicas B-raf , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação , Paraproteinemias/genética , Paraproteinemias/patologia , Plasmócitos/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Fator 3 Associado a Receptor de TNF/genética
17.
JAMA Dermatol ; 158(10): 1205-1206, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36069819

RESUMO

A woman in her late 70s with a history of immunoglobulin A monoclonal gammopathy of unknown significance presents with a tender, draining lesion of the central face. What is your diagnosis?


Assuntos
Abscesso , Paraproteinemias , Humanos , Abscesso/diagnóstico
18.
Cancer Epidemiol Biomarkers Prev ; 31(12): 2192-2198, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36126958

RESUMO

BACKGROUND: Both multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance (MGUS), occur twice as often within Black compared with White populations, suggesting that racial disparities lie within the development of MGUS. Nonetheless, MGUS has been studied mainly in White cohorts; the study that first described the natural history of MGUS was conducted in 97.3% White Olmsted County, Minnesota. METHODS: We determined the prevalence of MGUS among 386 Black South African (SA) men >30 years at Chris Hani Baragwanath Hospital in Johannesburg. We conducted serum protein electrophoresis and free light chain quantification to define MGUS by the same criteria as the Olmsted County studies. We also investigated the association between MGUS and various clinical factors, including human immunodeficiency virus (HIV) infection and smoking. RESULTS: We found the prevalence of MGUS to be 8.03% [95% confidence interval (CI), 5.32-10.74], nearly 1.6-fold higher than in the White Olmsted County male population. In a univariable logistic regression model, MGUS was associated with HIV status (OR, 2.39; 95% CI, 0.95-5.49), but in an adjusted model that included body mass index and cigarette use, the association was not statistically significant. Those who were current (vs. never) cigarette smokers were more likely to have MGUS in both univariable (OR, 5.60; 95% CI, 2.16-17.42) and multivariable models (OR, 4.49; 95% CI, 1.63-14.56). CONCLUSIONS: The prevalence of MGUS in Black SA men is substantially higher than in White populations and may be associated with HIV status and cigarette use. IMPACT: Racial disparities in MGUS exist and may be associated with potentially modifiable risk factors.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Paraproteinemias , Masculino , Humanos , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Gamopatia Monoclonal de Significância Indeterminada/complicações , Prevalência , África do Sul/epidemiologia , Paraproteinemias/epidemiologia , Paraproteinemias/complicações , Cadeias Leves de Imunoglobulina , Fatores de Risco
19.
Am J Hematol ; 97(10): 1337-1347, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36054609

RESUMO

There are numerous reports of cancers in Gaucher disease (GD) from mostly small single-center studies; however, precise risk estimates and cancer types involved have not been delineated. We conducted a study involving 2123 patients with GD type 1 (GD1) to assess the incidence of hematological malignancies, gammopathies, and solid tumors in an international observational study, the International Cooperative Gaucher Group Gaucher Registry (Clinicaltrials.gov: NCT00358943). Risk for cancer overall and for each type of malignancy was compared to the United States (US) population using the Surveillance, Epidemiology, and End Results database. Natural history of gammopathy was determined through assessing the progression from a diagnosis of monoclonal gammopathy of unknown significance (MGUS) to multiple myeloma (MM). Risk for hematological malignancies was more than four times higher than expected compared to the general population: non-Hodgkin lymphoma was approximately three times higher; MM was approximately nine times higher. Age-specific incidence rates of MGUS were unexpectedly high among younger patients. The 10-year cumulative incidence of MM after diagnosis of MGUS was 7.9%, comparable to the general population. Compared to the general US population, GD1 patients were at higher risk for solid malignancies of liver (2.9 times), kidney (2.8 times), melanoma (2.5 times), and breast (1.4 times). Colorectal, prostate, and lung cancer risks were lower than expected. These findings help advance care of patients with GD1 by supporting recommendations for individualized monitoring for malignancies and antecedents such as MGUS for MM and provoke important questions of the role of glucosylceramide and related sphingolipids in cancer biology.


Assuntos
Doença de Gaucher , Neoplasias Hematológicas , Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Paraproteinemias , Adulto , Doença de Gaucher/complicações , Doença de Gaucher/epidemiologia , Doença de Gaucher/patologia , Humanos , Masculino , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/patologia , Sistema de Registros , Risco
20.
Ann Diagn Pathol ; 61: 152028, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36055005

RESUMO

Idiopathic Systemic Capillary Leak Syndrome (ISCLS), also known as Clarkson's Syndrome, is due to primary fluid and protein leak across capillaries that leads to an accumulation of interstitial fluids and cardiovascular collapse from intravascular hypovolemia. Viral infections are a putative trigger of these episodes. ISCLS is typically associated with a monoclonal gammopathy. Here we present four patients with idiopathic systemic capillary leak syndrome. The cohort consists of three men and one woman who range in age from 55 to 72 years old. All of the patients had a monoclonal gammopathy. Two patients had viral triggers. Biopsies of normal skin were examined throughout all phases of the disease. During an acute attack, we identified perivascular mixed CD4+ and CD8+ T cell lymphocytic infiltrates in the superficial dermis. We observed significant microvascular deposits of C5b-9 and upregulation of type I interferon signaling in endothelium along with reduced serum levels of complement during very active disease. We also identified deposits of immunoglobulin along the dermal epidermal junction mirroring the monoclonal immunoglobulin isotype implicated in each patient. During a post treatment recovery or mild disease phase there was reduced inflammation and decreased amounts of C5b-9 and type I interferon expression. Sudden onset capillary leak syndrome reflects enhanced endothelial cell permeability as a unique form of endothelial injury mediated by the combined effects of complement pathway activation and upregulation of type I interferon signaling on endothelium.


Assuntos
Síndrome de Vazamento Capilar , Interferon Tipo I , Paraproteinemias , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/terapia , Complexo de Ataque à Membrana do Sistema Complemento , Biópsia
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