Heavy Chain Deposition Disease: Clinicopathologic Characteristics of a Chinese Case Series.

RATIONALE & OBJECTIVE: Heavy chain deposition disease (HCDD) is a rare consequence of monoclonal immunoglobulin deposition disease that has not been well characterized in non-white populations. To explore the clinicopathologic characteristics and outcomes of HCDD in Chinese individuals, we report on a case series assembled in a single center in China. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 25 patients with biopsy-proven HCDD were studied retrospectively. RESULTS: 14 men and 11 women with an average age of 50.3 years were studied. The patients presented with hypertension (76%), edema (96%), anemia (84%), serum creatinine level > 1.2mg/dL (68%), nephrotic-range proteinuria (56%), and microscopic hematuria (80%). One (4%) patient had multiple myeloma diagnosed. Serum immunofixation electrophoresis showed that 10 of 21 (48%) patients were positive for monoclonal immunoglobulin. Hypocomplementemia of C3 was found in 68% of patients. Nodular mesangial sclerosis was identified in all patients by using light microscopy. Using immunofluorescence, all 25 patients had deposition of heavy chains of immunoglobulin G class (γ1, 13; γ2, 2; γ3, 6; γ4, 2; γ1 and γ4, 1; and γ2 and γ4, 1). During an average of 40.1 months of follow-up of 20 patients, 65% had improved kidney function, 10% had worsening kidney function, and 25% progressed to kidney failure. Mean values for kidney and patient survival were 37.8 and 40.1 months, respectively. Kidney survival was higher among patients who received chemotherapy. LIMITATIONS: Retrospective study, single-center experience. CONCLUSIONS: In this case series of HCDD in a single center in China, the heavy chain deposits seen in the kidney biopies of all individuals were of immunoglobulin G class. Chemotherapy improved kidney function, especially among individuals in an early stage of the disease.

A unique case of γ-heavy chain deposition disease characterized by concomitant deposition of γ2 and γ4 subclasses.

Heavy chain deposition disease (HCDD) is a rare entity. γ-HCDD is the predominant subtype and is characterized by glomerular and tubular deposition of a single γ-heavy chain subclass. To our knowledge, γ-HCDD with simultaneous deposition of two subclasses has not yet been described. A 39-year-old woman presented with hypertension, nephrotic syndrome, anemia, microscopic hematuria and progressive renal dysfunction. A light microscopic examination of renal biopsy specimens showed nodular glomerulosclerosis. Electron microscopy revealed electron-dense deposits along the glomerular and tubular basement membranes. Immunofluorescence microscopy showed positive glomerular and tubular staining for immunoglobulin G (IgG) and negative staining for κ and λ light chains. An analysis of the IgG subclass showed positive staining for both IgG2 and IgG4. We herein describe a unique case of γ-HCDD with concurrent deposition of two subclasses, presenting a new subtype to the disease spectrum.

Gamma heavy-chain disease: defining the spectrum of associated lymphoproliferative disorders through analysis of 13 cases.

Gamma heavy-chain disease (gHCD) is defined as a lymphoplasmacytic neoplasm that produces an abnormally truncated immunoglobulin gamma heavy-chain protein that lacks associated light chains. There is scant information in the literature regarding the morphologic findings in this rare disorder, but cases have often been reported to resemble lymphoplasmacytic lymphoma (LPL). To clarify the spectrum of lymphoproliferative disorders that may be associated with gHCD, this study reports the clinical, morphologic, and phenotypic findings in 13 cases of gHCD involving lymph nodes (n=7), spleen (n=2), bone marrow (n=8), or other extranodal tissue biopsies (n=3). Clinically, patients showed a female predominance (85%) with frequent occurrence of autoimmune disease (69%). Histologically, 8 cases (61%) contained a morphologically similar neoplasm of small lymphocytes, plasmacytoid lymphocytes, and plasma cells that was difficult to classify with certainty, whereas the remaining 5 cases (39%) showed the typical features of one of several other well-defined entities in the 2008 WHO classification. This report demonstrates that gHCD is associated with a variety of underlying lymphoproliferative disorders but most often shows features that overlap with cases previously reported as "vaguely nodular, polymorphous" LPL. These findings also provide practical guidance for the routine evaluation of small B-cell neoplasms with plasmacytic differentiation that could represent a heavy-chain disease and give suggestions for an improved approach to the WHO classification of gHCD.

Enfermedad por depósito de cadenas ligeras. Experiencia en nuestro medio / No disponible

La enfermedad por depósito de cadenas ligeras (EDCL) es una entidad rara, caracterizada por el depósito de un solo tipo de cadena ligera en la membrana basal del riñón. Puede asociarse a una discrasia de células plasmáticas, aunque en ocasiones no se detecta patología hematológica y se denomina idiopática. Suele manifestarse como una insuficiencia renal severa con proteinuria nefrótica, no tiene tratamiento claramente establecido y el pronóstico es malo. El objetivo de este trabajo es analizar las características de los casos de EDCL diagnosticados en nuestro medio. Se identifican 6 casos, todos entre 1999 y 2005 de un total de 640 biopsias realizadas en ese periodo, 4 mujeres y 2 varones, media de 57 años. Se detectó un mieloma en 3 pacientes(50%). La insuficiencia renal aguda o de rápida evolución fue la presentación clínica más frecuente (66%) junto con proteinuria nefrótica (66%). Todas las biopsias mostraban engrosamiento de la membrana basal tubular y depósito lineal de cadenas kappa en la misma. La lesión glomerular más frecuente fue la glomérulo esclerosis nodular (83%).En un caso la afectación fue exclusivamente túbulo intersticial con cilindros tubulares asociados. Se trataron 3 pacientes,2 con mieloma. Requirieron diálisis 5 pacientes: 3 con EDCL idiopática con un tiempo medio desde el diagnóstico hasta recibir la misma de 7 días, y 2 con mieloma que tardaron una media de 46 días en requerir diálisis. Fallecieron 4 pacientes, 2 con mieloma. El tiempo de seguimiento hasta el exitus fue de 13 semanas para los pacientes con mieloma y de 110 semanas para el resto. Conclusión, la EDCL parece mas frecuente de lo publicado y se asocia a mieloma en la mitad de los casos. Se presenta con daño renal severo y la evolución renal y del paciente es mala (AU)

The Light chain deposition disease (LCDD) is a strange entity characterized by the deposition of only one type of light chain in the renal tubular basement membranes. It can be associated to a plasmacell dyscrasia, however, it can occur in the absence of any detectable hematological disorder and it is called idiopathic LCDD. The clinical manifestation is renal insufficiency and nephrotic proteinuria, it does not have a clearly fixed treatment and has a severe prognosis. The aim of this work is to analyse the characteristics of the LCDD cases diagnosed within our environment. Six cases were identified, all of them between 1999 and 2005,from a total amount of 640 renal biopsies performed during this period, 4 women and 2 men, average age of 57. Multiple myelomain 3 patients was detected (50%). The acute renal failure or rapidly progressive renal insufficiency was the most frequent clinical presentation (66%) together with nephrotic proteinuria (66%). All the biopsies showed tubular basement membranes thickening and kappa chains with a linear distribution within the same. The most frequent glomerular pathological finding was the nodular sclerosing glomerulopathy (83%). In one of the cases the affectation was exclusively tubular interstitial with tubular casts. 3 patients were treated, 2 with multiple myeloma. 5 patients needed dialysis: 3 with idiopathic LCDD within an average time of 7 days from the diagnosis to its reception, and 2 with myeloma, who started needing dialysis in an average of 46 days. 4 patients died, 2 of them with myeloma. The monitoring time until the death was 13 weeks for the patients with myeloma and 110 weeks for the rest. Conclusion: The LCDD seems to be more frequent than what has been published and it is associated to the myeloma in half of the cases. It appears together with severe renal insufficiency and the patient's and renal prognosis is poor (AU)

Detection rate and clinical significance of monoclonal gammopathy in different age groups in the population of Northern Jutland, Denmark.

All serum protein electrophoresis performed in the period 1 May 1979-30 April 1982 in the county of Northern Jutland, Denmark, were studied to find the annual detection rate and the clinical significance of a monoclonal gammopathy (MG) in different age groups. A monoclonal gammopathy was found in 325 persons (185 males and 140 females). The average annual detection rate of MG per 100,000 individuals increased with age in both sexes (p less than 0.01, Kolmogorov test). The lowest and highest detection rate for males/females were 2.8/3.3 (age group less than 50 years) and 236.8/100.3 (age group greater than or equal to 80 years) per 100,000 individuals, respectively. Monoclonal gammopathy was associated with a B-cell malignancy in 28 percent (95% confidence limits 23.9-32.4%) of the persons irrespective of sex and age.

Alpha chain disease in the Thai man.

A 61-year-old Thai man presented with a history of chronic diarrhoea of 1-2 years duration. Stool examination revealed a heavy parasitic infection. Several anthelminthics were given without benefit, despite disappearance of the intestinal parasites. Serum protein studies revealed abnormal alpha heavy chain. Two courses of cyclophosphamide, vincristine and prednisolone were followed by a brief remission in his symptoms. A 21 day course of tetracycline was then given, resulting in an improvement in his condition. He is still symptom free nine months after confirmation of the diagnosis, without any further treatment. Serum protein studies should be included in laboratory investigations of a patient with chronic diarrhoea.

Two cases of alpha chain disease from Nigeria.

The first two cases of alpha chain disease from Central Africa are reported from Nigeria. Both patients show the classical features of the disease with diffuse involvement of the small bowel and malabsorption. The patients were lost to follow-up but died soon after diagnosis.

Alpha-chain disease in an Englishman.

Eighty cases of the gastro-intestinal form of alpha-chain disease had been reported up to the time of writing this communication (September 1975). All patients were non-Caucasians. This report presents a case of this in an Englishman who became ill whilst working the tropics. His clinical features and response to therapy were entirely in line with the other cases so far reported.

[The geography of leukemias and hematosarcomas]. / La géographie des leucémies et des hématosarcomes

The geography of leukemias and haematosarcomas is comprised of two parts 1) The study of geographic lymphomas, Burkitt tumor, and alpha heavy chain disease. 2) The general geography of leukemias and haematosarcomas a) leukemias: variations of frequency according to the country, variations of the frequency of different forms of leukemia, temporal variations b) haematosarcomas, increased frequency in hot countries, unequal distribution of Hodgkin's disease in children and adults. Geography of animal and human leukemias. First description of "ethnologic hematology".

Alpha-chain disease and related small-intestinal lymphoma: a memorandum.

Primary intestinal lymphomas are remarkably frequent in the Mediterranean region and South-West Asia. They are usually found in young persons from the lower socio-economic strata of the population. These conditions sometimes present a premalignant phase characterized by plasmacytic infiltration of the small intestine. It has been reported that early treatment of cases with antibiotics is followed by complete remission, suggesting that some environmental factors may be responsible for the disease. Some patients have an abnormal alpha-chain protein in their serum. This Memorandum reviews the present knowledge of the clinical, immunological, epidemiological, and therapeutic aspects of this condition.

Alpha chain disease: immunoglobulin abnormalities, pathogenesis and current concepts.

The laboratory findings upon which the diagnosis of alpha chain disease relies and the main results of immunochemical, structural and biosynthetic studies of the pathological immunoglobulin are reviewed briefly. The pathogenesis of the disease is discussed in view of its possibly non-malignant nature at the early stage and of its peculiar geographic distribution, suggesting the triggering role of an intestinal micro-organism.

Immunochemical, clical, and pathological features of alpha-chain disease.

Making the diagnosis of alpha-chain disease in the laboratory is difficult. Immunologic and structural characteristics of the abnormal protein were shown in results of cellular studies. There are clinicopathological features associated with the protein abnormality. The peculiar geographic origin of patients affected with alpha-chain disease and the possible reversibility of the hyperplastic process at its early stage lead to some considerations of cause.