Nefropatías secundarias a paraproteína: perfil clínico a partir de hallazgos histológicos

Background: One of the devastating consequences of monoclonal gammopathies is the development of end-stage kidney disease, which can be prevented with an early diagnosis. Renal involvement can be secondary to saturation of paraproteins with intratubular precipitation or the glomerular deposition of paraproteins with secondary inflammation and destruction. These conditions can also be associated with monoclonal gammopathies that do not meet hematological treatment criteria, called monoclonal gammopathies of renal significance (MGRS). Aim: To report a retrospective analysis of patients who underwent a renal biopsy and whose final diagnosis was a form of monoclonal gammopathy. Material and Methods: We reviewed the clinical and laboratory features and response to treatment of 22 patients aged 63 ± 12 years (55% women) with a pathological diagnosis of a nephropathy associated with paraproteinemia. Results: The most common hematological diagnosis was amyloidosis in 50% of patients, followed by cast nephropathy. The predominant clinical presentations were proteinuria (without nephrotic syndrome) and nephritic syndrome. Classic criteria such as erythrocyte sedimentation rate > 100 mm/h and protein-albumin gap were unusual. Serum light chain quantification was the test with the best yield to detect paraproteins. Conclusions: In this group of patients, light chains tend to affect the kidney more commonly than heavy chains. The prognosis of multiple myeloma is much worse than MGRS.

Paraproteínas: claridad en la nebulosa / Paraproteins: a review

Hematological neoplasms are tumors of cells in different states of maturation and differentiation. Since monoclonal gammopathies (MG) refer to B mature lymphocyte neoplasms, lymphogenesis should be well known. We must keep in mind that the last stage of maturation of these lymphocytes is the plasma cell. This is how a MG could appear in the context of a plasma cell neoplasm, such as multiple myeloma or amyloidosis, but also in relation to a lymphoma. A monoclonal peak is produced by mature B lymphocytes or plasma cells that secrete a monoclonal protein (Immunoglobulin), and represents a MG. But it must be emphasized that, in the correct clinical context, a hypogammaglobulinemia can represent a MG as well. Another important point is the understanding and interpretation of requested tests, such as protein electrophoresis (PEP), immunofixation (IFx) or serum free light chains (sFLC). The current MG screening panel includes these three studies (PEF, IFx, sFLC), although a simpler panel measuring PEF and sFLC has also been proposed, but not yet formally validated. Therefore, screening done only with PEP is insufficient.

Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis based on a case reports systematic survey / Solitary plasmacytoma of the jaws: therapeutical considerations and prognosis based on a case reports systematic survey

Abstract Introduction: Solitary plasmacytoma is a rare malignant tumor of plasma cells with no evidence of systemic proliferation. There are two known subtypes: extramedullary solitary plasmacytoma and solitary bone plasmacytoma. The etiology is still unknown. Both lesions present a risk of progression to multiple myeloma. A number of approaches have been used for treatment of solitary plasmacytoma. Objective: To carry out a systematic review of the case reports described in the literature, focusing on therapeutic and prognostic aspects. Methods: A search of clinical case reports was performed in the PubMed database using Mesh Terms related to "plasmacytoma" under the following criteria: type of study (case report), articles in English language, conducted in humans, with no publication date limits. Results: Of the 216 articles found, only 21 articles met the pre-established inclusion criteria. Conclusion: The occurrence of solitary bone plasmacytoma in the bones of the face is a rare condition prevalent between the 4th and 6th decades of life, located in the posterior region of the mandible in most cases. Histopathological examination and systemic investigation are mandatory for confirmation of diagnosis.

Resumo: Introdução: O plasmocitoma solitário é um tumor maligno raro de células plasmáticas sem evidência de proliferação sistêmica e engloba dois subtipos: plasmocitoma solitário extramedular e plasmocitoma solitário ósseo. A etiologia ainda é desconhecida. Ambas as lesões apresentam risco de progressão para mieloma múltiplo. Uma série de abordagens tem sido usada para seu tratamento. Objetivo: Realizar uma revisão sistemática da literatura com enfoque nos aspectos terapêuticos e prognósticos. Método: Realizou-se uma busca de relatos de caso clínico na base de dados PubMed com termos de busca relacionados com "plasmocitoma" sob os seguintes critérios: tipo de estudo (relato de caso), artigos na língua inglesa, estudos realizados apenas em humanos, sem limites de data de publicação. Resultados: Dos 216 artigos encontrados, apenas 21 preencheram os critérios de inclusão pré-estabelecidos. Conclusão: A ocorrência de plasmocitoma solitário ósseo nos ossos da face é uma condição rara prevalente entre a 4a e a 6a décadas de vida, localizada na região posterior de mandíbula na maioria dos casos. O exame histopatológico e a investigação sistêmica são mandatórios para confirmação do diagnóstico.

Association between left ventricular function and paraprotein type in patients with multiple myeloma

BACKGROUND/AIMS: Multiple myeloma (MM)–associated cardiac damage, particularly according to the type of monoclonal (M) protein has not been elucidated. We sought to investigate relationship between elevated serum M protein levels and echocardiographic indices of cardiac structure and function in patients with MM. METHODS: We evaluated a total of 184 consecutive MM patients who underwent echocardiography for bone marrow pre-transplant screening. Serum levels of intact immunoglobulin M protein and free light chain kappa/lambda (FLC-κ/-λ) were measured. RESULTS: One hundred thirty-nine patients were non-light chain MM (non-LCMM) and 45 patients belonged to LCMM. In patients with non-LCMM, significant correlations were found between serum M protein and left atrial volume index (LAVi; r = 0.720, p < 0.0001), E/e’ (r = 0.511, p < 0.0001), and systolic pulmonary arterial pressure (r = 0.485, p < 0.0001). In patients with LCMM, log-transformed FLC-λ (log-λ) was correlated with left ventricular ejection fraction (LVEF, r = –0.536, p = 0.010), left ventricular (LV) end-systolic dimension (r = 0.500, p = 0.018), and LV end-systolic volume (r = 0.444, p = 0.038). On multivariate analyses, hematocrit and serum M protein were independent predictors of LAVi in patients with non-LCMM. In patient with LCMM, FLC-λ isotype was only found to be an independent determinant of LVEF. CONCLUSIONS: An increase in serum M protein was associated with LV diastolic dysfunction, whereas an increase in serum FLC-λ concentration showed a negative correlation with the echocardiographic parameters of LV systolic function. These findings also suggest that serum M protein has different effects on LV function according to the type of paraproteins in patients with MM.

Association between left ventricular function and paraprotein type in patients with multiple myeloma

BACKGROUND/AIMS: Multiple myeloma (MM)–associated cardiac damage, particularly according to the type of monoclonal (M) protein has not been elucidated. We sought to investigate relationship between elevated serum M protein levels and echocardiographic indices of cardiac structure and function in patients with MM. METHODS: We evaluated a total of 184 consecutive MM patients who underwent echocardiography for bone marrow pre-transplant screening. Serum levels of intact immunoglobulin M protein and free light chain kappa/lambda (FLC-κ/-λ) were measured. RESULTS: One hundred thirty-nine patients were non-light chain MM (non-LCMM) and 45 patients belonged to LCMM. In patients with non-LCMM, significant correlations were found between serum M protein and left atrial volume index (LAVi; r = 0.720, p < 0.0001), E/e’ (r = 0.511, p < 0.0001), and systolic pulmonary arterial pressure (r = 0.485, p < 0.0001). In patients with LCMM, log-transformed FLC-λ (log-λ) was correlated with left ventricular ejection fraction (LVEF, r = –0.536, p = 0.010), left ventricular (LV) end-systolic dimension (r = 0.500, p = 0.018), and LV end-systolic volume (r = 0.444, p = 0.038). On multivariate analyses, hematocrit and serum M protein were independent predictors of LAVi in patients with non-LCMM. In patient with LCMM, FLC-λ isotype was only found to be an independent determinant of LVEF. CONCLUSIONS: An increase in serum M protein was associated with LV diastolic dysfunction, whereas an increase in serum FLC-λ concentration showed a negative correlation with the echocardiographic parameters of LV systolic function. These findings also suggest that serum M protein has different effects on LV function according to the type of paraproteins in patients with MM.

Marginal zone lymphoma with monoclonal immunoglobulin: three cases report and literatures review / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical features and treatment in patients of marginal zone lymphoma (MZL)with monoclonal immunoglobulin (McIg).</p><p><b>METHODS</b>The clinical data of MZL patients with McIg, including 3 cases diagnosed and treated in Beijing Anzhen Hospital from Jan 2007 to Dec 2014 were retrospectively studied, meanwhile 36 patients searched from literatures were reviewed.</p><p><b>RESULTS</b>Of a total of 39 patients, the ratio of male and female was 1.05∶1 with an average age of 65.1± 12.3 years old. 28 cases (71.8%)were with mucosa associated lymphoid tissue lymphomas (MALTL), 9 cases (23.1% )with nodal marginal zone lymphoma, and 2 cases (5.1%)with splenic marginal zone lymphoma. Nine cases (23.1% )were in the early stage, 30 cases (76.9%)in the advanced stage. The common initial symptom was non-mass lesions (65.5%), such as skin purpura, peripheral neuropathy; 13 patients (33.3% )were accompanied by autoimmune phenomenon, and most were with Sjogren's syndrome. Among MALTL patients, the common primary lesion was in non- gastrointestinal tract (17 cases, 60.7%). Most of patients with McIg were one with McIgM (82.0%); the others with McIgA, Mcκ-light chain, McIgG and double McIg. The level of plasma McIgM was (25.55±21.31)g/L, which was higher in advanced stage patients than in early stage ones [(29.85±20.60)g/Lvs (3.23±2.95)g/L,P= 0.008]. The complete remission (CR)rate was 56.0% and the overall response rate (ORR)92.0%, respectively in 30 patients treated by chemotherapy. At a median follow- up of 10 months, the 3- year progression free survival and the 3-year overall survival were 44.7% and 76.5%, respectively. The rates of ORR and CR in the patients received rituximab- included regimen were seemly better than those without rituximab one (100.0%vs 78.6%, 63.6%vs 50.0%;P>0.05), but no statistic differences were found. The CR rate in patients with McIgM was significantly higher than that with non- McIgM (P=0.026). The plasma McIgM level decreased after chemotherapy (P=0.002).</p><p><b>CONCLUSION</b>The MZL with McIg, perhaps a kind of unique subtype, usually occurred in 60 years or older patients. It was often diagnosed in patients of advanced stage and susceptible to autoimmune phenomenon. MALTL in non- gastrointestinal tract was more prone to find McIg. In MZL patients with McIg, McIgM was more common and other McIg rare. Rituximab-included regimen produced a better therapeutic response.</p>

Crystalline podocytopathy and tubulopathy without overt glomerular proteinuria in a patient with multiple myeloma

Crystalline nephropathy is a rare yet well-known condition associated with multiple myeloma and other light chain–secreting disorders. Paraproteins that are resistant to proteolysis crystallize within proximal tubular cells and cause light-chain proximal tubulopathy, which presents clinically as Fanconi syndrome. Podocytes are rarely affected, and the crystalline inclusions within podocytes are typically precipitated, yielding significant glomerular proteinuria. Here we report a case of extensive crystalline inclusions primarily within podocytes and proximal tubules that presented only with Fanconi syndrome and renal insufficiency. Despite the presence of extensive crystalline inclusions in podocytes and diffuse foot process effacement, the patient had no clinical evidence suggestive of podocyte injury.

Sospecha diagnóstica de mieloma múltiple en atención primaria: reporte de un caso / Multiple myeloma suspected in primary care: case report

Introducción: El mieloma múltiple (MM) es una neoplasia hematológica caracterizada por una proliferación clonal de células plasmáticas que genera una disfunción multiorgánica, con daño a nivel óseo, siendo una importante causa de morbimortalidad en estos pacientes. Presentación del caso: Mujer de 69 años, hipertensa tratándose con enalapril hace 10 años, operada de un prolapso genital en el año 2015, con antecedentes de fallecimiento de un hijo a los 30 años por un cáncer no especificado, refirió cuadro de un año de evolución caracterizado por oligoartralgias en extremidades inferiores, con predominio derecho, además de baja de peso de aproximadamente 5 kg en 4 meses. En atención primaria se solicitó exámenes que revelaron anemia moderada normocítica-normocrómica y velocidad de eritrosedimentación de 125 mm/hora, por lo cual, se derivó a Hospital de Puerto Montt. Durante hospitalización, se realizó biopsia de médula ósea que informó células plasmáticas que representaban más del 90% de los elementos medulares evaluables. Electroforesis de proteínas en sangre destacó banda de aspecto monoclonal en zona gamma de 7.9 g/dl. Frotis de eritrocitos con rouleaux positivo, proteínas totales de 13.1 g/dl y calcio corregido de 10.6 mg/dl. Se confirmó MM, iniciándose tratamiento con talidomida, melfalán y prednisona, además de bifosfonato y analgesia, con controles mensuales en policlínico de Hematología. Discusión: El MM es una enfermedad incurable, por ello el diagnóstico precoz en atención primaria es fundamental para dirigir los esfuerzos terapéuticos hacia la remisión de la enfermedad y mejoría de la calidad de vida.

ntroduction: Multiple myeloma (MM) is a hematological neoplasm characterized by clonal proliferation of plasma cells that generates multiple organ dysfunction, with bone damage, which it's an important cause of mortality in these patients. Case report: F69 year old woman with hypertension treated with enalapril from 10 years ago, with history of a genital prolapse surgery in 2015, and refers the death of a 30 years old son for an unspecified cancer. She had a 1 year evolution of symptoms characterized by oligoartralgias in lower extremities, predominantly right, in addition to 5 kg weight loss in 4 months. In Primary Care tests were requested, showing: moderate anemia normocytic- normocromic, erythrocyte sedimentation rate 125 mm/hour. Then, she was referred to Hospital of Puerto Montt to complete the study. Hospitalized, bone marrow biopsy was performed and showed more tan 90% of plasma cells. Blood protein electrophoresis, showed monoclonal band in gamma zone of 7.9 g/dl. Smears erythrocyte rouleaux positive, measurement of total proteins of 13.1 g/dl, corrected calcium of 10.6 mg/dl. MM suspicion was confirmed, starting treatment with thali-domide, melphalan and prednisone plus bisphosphonate and analgesia, with monthly checks of hematology polyclinic. Discussion: The MM is an incurable disease, so early diagnosis in Primary Care is essential to direct therapeutic efforts toward disease remission and improved quality of life.

Distribución de tipos de paraproteínas en una muestra de enfermos con mieloma múltiple / Distribution of types of paraproteins in a sample of patients with multiple myeloma

Introducción: el mieloma múltiple (MM) es una enfermedad caracterizada por una proliferación monoclonal de inmunoglobulinas que representa aproximadamente el 15 por ciento de las hemopatías malignas. Métodos: se realizó un estudio de la distribución de las clases, sub clases y tipos de cadenas ligeras de inmunoglobulinas en 285 enfermos con el diagnóstico de MM. Se emplearon tres métodos: electroforesis de proteínas en suero para la detección de la inmunoglobulina monoclonal o paraproteína, electroforesis de inmunofijación y doble inmunodifusión para identificar las clases, sub clases y tipo de cadenas ligeras. Resultados: se encontraron 206 enfermos (72.28 por ciento) con MM IgG; 73 (25.62 por ciento) con MM IgA y 6 (2.1 por ciento) con MM IgM. La distribución de sub clases de IgG fue: 130 casos (63.11 por ciento) IgG1, 43 (20.87 por ciento) IgG2, 21 (10.19 porciento) IgG3 y 12 (5.83 por ciento) IgG4; y la de sub clases de IgA fue de 59 enfermos (80.82 por ciento) IgA1 y 14 (19.18 por ciento) IgA2. Del total de enfermos 187 (65.61 por ciento) mostraron cadenas ligeras tipo kappa y 98 (34.38 por ciento) tipo lambda. Conclusiones: los datos obtenidos en nuestro estudio permitieron identificar la frecuencia de distribución de las clases, subclases y cadenas ligeras en una muestra de enfermos con MM

Introduction: multiple mieloma (MM) is a disease characterized by a monoclonal proliferation of immunoglobulins representing approximately 15 percent of malignant hemopathies. Methods: the distribution of classes, subclasses and light chains of monoclonal immunoglobulins was studied in 285 patients with MM. Three methods were used: serum protein electrophoresis for the detection of monoclonal immunoglobulins or paraproteins, immunofixation electrophoresis and double immunodiffusion to identify classes, subclasses and light chain types. Results: 206 patients (72.28 percent) with IgG MM, 73 (25,62 percent) with IgA MM, and 6 (2,1 percent) with IgM MM were found. The distribution of IgG subclasses was: 130 cases (63,11 percent) IgG1; 43 (20,87 percent) IgG2; 21 (10,19 percent) IgG3: and 12 (5,83 percent) IgG4. Distribution of IgA subclasses was: 59 patients (80,82 percent) IgA1 and 14 (19,18 percent) IgA2; 187 patients (65,62 percent) showed kappa light chains and 98 (34,38 percent) were lambda. Conclusions: the data obtained in our study allowed us to identify the frequency of distribution of classes, subclasses and light chains in a sample of patients with MM

Artifactual Hyperbilirubinemia due to Paraprotein Interference in a Case of Multiple Myeloma / 임상검사와정도관리

When analyzing samples containing paraproteins, various interference effects are encountered in the clinical laboratory. Precipitation of paraproteins mostly interferes with the assays that use photometric detection. Herein, we present a case of a patient with multiple myeloma who had paraproteins and spuriously elevated total bilirubin levels (31.1 mg/dL), which were measured by using Roche total bilirubin assay on the Modular DPE (Roche Diagnostics, Switzerland) chemical analyzer. The total bilirubin concentration reduced from 31.1 mg/dL to 1.5 mg/dL, when tested after three fold dilution of the sample on Modular DPE chemical analyzer.

Prognostic significance of serum immunoglobulin paraprotein in chronic lymphocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the incidence of serum immunoglobulin (Ig) paraprotein in chronic lymphocytic leukemia (CLL), and to explore its clinical associated laboratory features and prognostic implication.</p><p><b>METHODS</b>Serum protein electrophoresis and immunofixation electrophoresis were performed by automatic electrophoresis apparatus to identify serum Ig paraprotein. Immunonephelometry was used to measure serum Ig levels.</p><p><b>RESULTS</b>Out of 101 CLL patients, serum Ig paraprotein detection was found in 20 (19.8%) cases, 13 (12.9%) patients with IgG paraprotein, 7 (6.9%) patients with IgM paraprotein and 1(1.0%) patient with IgA paraprotein. Among these 20 cases, 1 patient had both IgG and IgM paraprotein, 2 patients had both κ and λ light chains. The incidence of serum IgG paraprotein was high in the group of advanced Binet stage (P = 0.032) and high level of thymidine kinase 1 (TK1) (P = 0.013). The incidence of serum IgM paraprotein was high in the group of advanced Binet stage (P = 0.037), high level of TK1 (P = 0.017) and cytogenetic abnormalities of del(11q22.3) (P = 0.006). With a median follow-up of 30 months (range 1 - 101 months), 66 patients received therapy after initial diagnosis. Survival analysis showed that the patients with serum Ig paraprotein had significantly shorter treatment-free survival (TFS) times than the patients without serum Ig paraprotein (P = 0.024). And the patients with serum IgM paraprotein had significantly shorter treatment-free survival (TFS) times than the patients without serum Ig paraprotein (P = 0.013). However, serum Ig paraprotein or IgM paraprotein was not independent prognostic factor.</p><p><b>CONCLUSION</b>Serum Ig paraprotein can be detected in a subset of patients with CLL, which could be of value as a prognostic factor in CLL.</p>

Platelet Dysfunction in a Patient with Multiple Myeloma: A Case Report with a Literature Review / 대한내과학회지

Multiple myeloma is a monoclonal plasma cell proliferation disorder with various symptoms and signs caused by paraproteinemias. Among these signs, a bleeding tendency is one of the major fatal causes. However, significant severe bleeding is rare in most cases. In this study, we report a case of multiple myeloma in a patient who had a severe recurrent bleeding tendency due to platelet dysfunction caused by paraproteins. After being treated with therapeutic plasma exchange and chemotherapy, the patient's monoclonal protein level decreased and the bleeding stopped.

Pseudohyperphosphatemia in a Patient with Multiple Myeloma

Hyperphosphatemia is an unusual manifestation in patients with multiple myeloma without a significantly reduced glomerular filtration rate. Serum phosphate may be falsely elevated when a large amount of paraproteins is present in the serum, because ultraviolet light absorbance is elevated with the phosphomolybdate ultraviolet assay, which is most commonly used for serum phosphate measurement. This pseudohyperphosphatemia can be confirmed by deproteinization of the serum of patients. We report a case of multiple myeloma presenting with spurious hyperphosphatemia revealing pseudohyperphosphatemia by deproteinization of serum using sulfosalicylic acid.

Clinical Significance of Serum Osteopontin in Patients with Multiple Myeloma / 대한진단검사의학회지

BACKGROUND: Angiogenesis and osteoclastogenesis are increased in the bone marrow of multiple myeloma (MM) patients in parallel with the tumor progression. Osteopontin (OPN) is a multifunctional protein that is involved in angiogenesis and bone destruction and, eventually, in tumor progression in MM. OPN is known to increase in MM patients as the disease progresses and bone is destroyed. We studied the clinical usefulness of OPN as a monitoring marker for treatment response in patients with MM. METHODS: We obtained 70 serial sera from 27 MM patients and 14 sera from healthy individuals. OPN was measured by a sandwich ELISA method. The hospital records were reviewed, and the clinically important markers for monitoring the treatment response, such as monoclonal component, immunoglobulin, free light chain, and hemoglobin, etc, were analyzed together with OPN levels. RESULTS: There was no significant difference in OPN levels between MM patients and healthy controls. OPN showed no significant correlations with the markers used for monitoring of treatment response such as M component, immunoglobulin, and free light chain levels. There was no difference in OPN levels between the 3 groups classified by the amount of M component. In addition, OPN levels showed no compatible changes to the treatment response of MM patients. CONCLUSIONS: Although OPN has been known to have an important role in the formation and progression of MM by involving angiogenesis and bone destruction, our results show that OPN is not valuable as a clinical marker for monitoring the treatment response in MM patients because of inconsistency in its levels in MM patients.

Liposomal daunorubicin and dexamethasone as a treatment for multiple myeloma: the DD Protocol

CONTEXTO E OBJETIVO: A daunorrubicina lipossomal tem sido usada no tratamento em várias doenças hematológicas malignas, incluindo mieloma múltiplo (MM). O objetivo deste estudo foi avaliar a eficácia, efeitos colaterais e toxicidade da daunorrubicina lipossomal and dexametasona no Protocolo DD. TIPO DE ESTUDO E LOCAL: Estudo prospectivo, realizado nos hospitais Sírio Libanês, São Camilo, Brasil e no Hospital Alemão Oswaldo Cruz. MÉTODOS: 20 pacientes com MM ativo receberam daunoxome (25-30 mg/m²/dia) por três dias consecutivos, mensal, por quatro meses (total de quatro ciclos), e dexametasona, 10 mg a cada seis horas por quatro dias consecutivos (dia 1 - 4, 9 - 12 e 17 - 20), também mensal. RESULTADOS: A mediana entre o diagnóstico e o início do protocolo DD foi de 13 meses. Quinze pacientes receberam alguma quimioterapia anterior ao protocolo DD. Uma redução maior que 50% do pico monoclonal sérico foi observada em seis paciente após o primeiro ciclo do DD (30%), em seis pacientes após o segundo ciclo (30%), em quatro pacientes após o terceiro ciclo (20%) e em quatro pacientes não houve redução (20%). No início do protocolo, 17 pacientes (85%) apresentavam anemia e em 12 destes pacientes (70%) a anemia foi corrigida. Doença progressiva foi observada em três pacientes (15%), um apresentava resposta mínima, quatro pacientes (20%) apresentaram resposta parcial e 12 (60%) apresentaram resposta completa. A toxicidade hematológica foi aceitável.Toxicidade em trato gastrointestinal foi leve, consistindo em náusea (10%) e anorexia (15%), sem episódios de vômito. CONCLUSÃO: Este tratamento apresentou uma baixa toxicidade, uma boa taxa de resposta e pode ser usado previamente ao transplante de medula óssea autogênico.

Gamapatía monoclonal de significado indeterminado (GMSI) en mestizos mexicanos: Experiencia de una sola institución / Monoclonal Gammopathy of Undetermined Significance (MGUS) in Mexican Mestizos: One Institution's Experience

La gamapatía monoclonal de significado indeterminado (GMSI) se define como la presencia de una proteína sérica monoclonal a una concentración de 3 g por decilitro o menor; sin proteína monoclonal en la orina o solamente cantidades moderadas de cadenas ligeras monoclonales, sin lesiones líticas óseas, anemia, hipercalcemia, ni insuficiencia renal relacionada a la pro teína monoclonal y con una proporción de células plasmáticas en la médula ósea de 10% o menor. En poblaciones caucásicas, la GMSI afecta a 3% de la población mayor a 70 años, en tanto que en mestizos mexicanos esta proporción es considerablemente menor (0.7%); por otro lado, de todas las para proteinemias monoclonales en México, la GMSI representa sólo 2.4%. En un total de 9081 pacientes estudiados en el Centro de Hematología y Medicina Interna de Puebla en un período de 20 años, se identificaron 11 pacientes con GMSI. La mediana de edad es de 70 años, con márgenes de 43 a 83. Los pacientes han sido vigilados por periodos que oscilan entre 6y 3270 días (mediana 308). Dos pacientes desarrollaron mieloma múltiple 308 y 1687 días después de haberse identificado la GMSI. La mediana de supervivencia (SV) del grupo no se ha alcanzado y la SV a 32 70 días es de 91%. Después de discutir causas potenciales de error como son la falta de reporte y varios sesgos, parece que la GMSI, al igual que otros padecimientos inmunoproliferativos malignos, es probablemente menos frecuente en mestizos mexicanos que en individuos de origen caucásico. Es posible que hacer estudios rutinarios para identificar esta condición permita diagnosticar más casos.

Monoclonal gammopathy of undetermined significance (MGUS) is defined as presence of serum monoclonal protein at a concentration of 3 g per deciliter or less, no monoclonal protein or only moderate amounts of monoclonal light chains in urine, absence oflytic bone lesions, anemia, hypercalemia, and renal insufficiency related with monoclonal protein, and with a proportion of plasma cells in bone marrow of 10% or less. In Caucasian population, MGUS affects about 3% of individuals > 70 years of age, whereas in Mexican mestizos this figure is substantially lower (0.7%); on the other hand, MGUS represents in Mexico only 2.4% of all monoclonal gammopathies. In a total of 9081 individuals studied prospectively at the Centro de Hematología y Medicina Interna de Puebla throughout a 20-year period, 11 patients with MGUS were identified. Median age was 70 years (range 43-83 years). Patients have been followed in periods ranging from 6 to 3270 days (median, 308 days). Two patients evolved into overt multiple myeloma at 308 and 1687 days after diagnosis of MGUS. Overall median survival (SV) of the group has not been reached, whereas3270 days overall SV is 91%. After discussing underreporting, biasing, and other confounding factors, it would seem that MGUS, like other monoclonal gammopathies, is les sfrequent in Mexican mestizos than in Caucasians. Routine screening studies to identify the condition should result in increased numbers of patients.

Excreción de proteínas de bajo peso molecular en pacientes con proteinuria a cadena liviana como marcadoras de disfunción renal / Protein excretion of low molecular weight in patients with proteinuria to light chain like marking of renal dysfunction

Se determinó la excreción urinaria de las proteínas de bajo peso molecular (PBPM) beta-2 mocroglobulina(B2m), proteína transportadora de retinol (RBP) y alfa-1 microglobulina(A1m), en 65 pacientes con cadenas livianas monoclonales (CLM) en orina y en 47 con distintas enfermedades renales (DER), para evaluar la utilidad clínica de su determinación y el efecto de la presencia de CLM. Se utilizó inmunonefelometría (Beckman) para la determinación de Kappa, lambda y A1m, inmunoturbidimetría (Roche) para B2m y ELISA para RBP (Randox). La A1m correlacionó con los valores de CLM (r=0.49, p <0.01) y RBP (r=0.33, p <0.05). Las medias de PBPM mostraron diferencia significativa entre ambos grupos (p < 0.05); también entre la presencia o no de insuficiencia renal (IR) (p<0.001). Para A1m la diferencia fue significativa entre pacientes con y sin IR ( p<0.05 para CLM y p < 0.01 para DER). El número de pacientes sin IR con excreción aumentada de A1m mostró diferencias entre CLM y DER ( 80% y 35.7% ; p<0.01). En pacientes con CLM la alta excreción de PBPM en presencia o no de IR indicaría una disfunción tubular. En pacientes con CLM sin insuficiencia renal, A1m podría constituir una herramienta para el diagnóstico precoz de nefrotoxicidad.

Relato de caso: nefropatia por depósito de cadeia leve de imunoglobulina secundária ao mieloma / Ligth-chain deposit disease secondary to myeloma

A nefropatia de cadeia leve é causada pela superprodução de cadeia leve de imunoglobulina pelos linfácitos B com deposição nas membranas tubulares e no glornérulo. A expressão clínica habitual é proteinúria, insuficiência renal e hipertensão arterial. A glomeruloscierose nodular é a alteração histológica mais freqüente. Relatamos um caso de nefropatia por cadeia leve de imunoglobulina secundário ao mieloma múltiplo, em que suspeitou-se do diagnóstico pelos achados à microscopia ótica, sendo depois confirmado pela imunofluorescência. O paciente já iniciou tratamento quimioterápico, sendo proposto a seguir o autotransplante de medula.

Paraproteins: a regional South Australian experience.

We have performed a systematic review of all new serum and urinary paraproteins detected over a six year period in an immunodiagnostic laboratory serving a population of 400,000 people. Clinical diagnoses and associated laboratory features were ascertained from a computerized laboratory database or from clinical notes. Over the period of study, serum or urine paraproteins were detected in 613 new patients. These consisted of 568 patients with serum paraproteins and 45 patients with urinary monoclonal free light chain (in the absence of a serum paraprotein). These paraproteins occurred more commonly in males and the frequency increased with age. Approximately 30% of the serum paraproteins and 60% of urinary monoclonal free light chain were associated with B cell lymphoproliferative disorders (multiple myeloma, plasmacytoma, Waldenstrom's macroglobulinemia, non-Hodgkins lymphoma, chronic lymphocytic leukemia, etc) with the remainder being labeled as monoclonal gammopathies of uncertain significance (MGUS). At clinical presentation, patients with lymphoproliferative disorders tended to have higher levels of paraprotein, B2 microglobulin, the presence of free urinary light chain and demonstrated molecular size heterogeneity of the paraprotein but there was considerable overlap. A good correlation was noted between paraprotein concentration and viscosity in most patients. In conclusion paraproteins were most frequently encountered in the context of a gammopathy of uncertain significance. Features which suggested lymphoproliferative disorders included higher levels of serum paraprotein (> 15 g/l), elevated levels of B2-microglobulin and the presence of urinary free high chain. However, as much overlap was seen with patients with MGUS, regular monitoring of paraprotein level is considered mandatory in the management of these patients.

A case of multiple myeloma with ascites / 대한내과학회지

Ascites is a rare complication of multiple myeloma. When it develops, it is usually associated with extensive liver infiltration with plasma cells, infectious peritonitis or myelomatous peritoneal infiltration. Ascites caused by peritoneal infiltration is even less frequent than others. The majority of previously reported cases were characterized by an IgA paraprotein and lack of skeletal lesions. This rare extramedullary complication of myeloma has been unresponsive to therapy and rapidly fatal. Therefore, it is important to recognize myeloma as a cause of ascites and the presence of ascites heralds a poor prognosis of myeloma. We recently experienced a case of myeloma with ascites and reviewed the relevant literature of human myeloma presenting with the triad of ascites, relative or absolute sparing of the skeleton, and an IgA paraprotein. A 76-year-old man was presented with ascites early in the course of myeloma. He had no evidence of intra-abdominal plasmacytoma and skeletal lesions. Myelomatous ascites was demonstrated by the monoclonal immunoglobulin of IgA type in ascitic fluid. He was treated by plasmapheresis due to hyperviscosity syndrome and VAD combination chemotherapy. He was discharged with the improved clinical condition.