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.

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.