Biclonal light chain gammopathy with aberrant CD33 expression in secondary plasma cell leukemia

Plasma cell leukemia is a rare neoplastic proliferation of circulating plasma cells. Clonal proliferations of plasma cells, such as in plasma cell leukemia or plasma cell myeloma, are typically characterized by production of a monoclonal heavy and/or light chain immunoglobulin. We present a case of a secondary plasma cell leukemia arising from plasma cell myeloma with dual expression of lambda and kappa light chains along with aberrant expression of CD33, CD20, and dim CD56. This case emphasizes the importance of recognizing aberrant immunophenotypes in plasma cell leukemias and represents the first reported case of biclonal light chain expression in a secondary plasma cell leukemia.     

Biclonal IgM gammopathy in chronic lymphocytic leukemia

The association of chronic lymphocytic leukemia (CLL) with serum paraproteinemia (ie, monoclonal immunoglobulin production and secretion) is well known. We, however, could find only three previous reports of CLL where multiple serum paraproteins were encountered. We describe a case of biclonal gammopathy in CLL, involving IgM/kappa and IgM/lambda, with each paraprotein reaching serum levels of approximately 10 g/L (1 g/dL). Using immunohistochemical techniques, we identified two morphologically similar lymphocyte populations, which could be stained for either mu and kappa or mu and lambda. The peripheral blood contained a majority of mu/kappa-containing cells (kappa/lambda = 17.5:1), while the bone marrow only contained a modest excess of cells staining for mu/kappa (kappa/lambda = 2.4:1). The clinical significance and prognosis of biclonal IgM gammopathies is uncertain, since so few cases have been reported. Our patient has now been followed up for more than four years.     

Kappa light chain glomerulosclerosis in multiple myeloma

Kappa light chains were demonstrated by immunofluorescence microscopy in the renal basement membranes of 6 of 10 patients with multiple myeloma subjected to kidney biopsy. Nodular glomerulosclerosis was present in 2 of these patients, but the remainder showed only minor light microscopic abnormalities. Deposition of kappa light chains in renal basement membranes may be a frequent cause of kidney disease in multiple myeloma. This deposition may be detected with electron microscopy by the demonstration of granular dense transformation of basement membranes. Occasionally there is systemic vascular deposition of kappa light chains which may be difficult to distinguish from amyloid but lacks a fibrillar character. The tissue effects of light chains in multiple myeloma seem likely to be more extensive than their deposition in renal tubules. There appears to be a greater tendency for kappa light chains to accumulate in renal and systemic basement membranes, but the mechanisms governing this deposition are unknown.     

Biclonal gammopathy (IgG kappa and IgG lambda) in a patient with non-Hodgkin's lymphoma

We report a case of non-Hodgkin's malignant lymphoma with biclonal gammopathy (IgG kappa and IgG lambda) involving both serum and urine. Detailed immunologic studies of the tumor disclosed two morphologically indistinguishable clones of cells that were responsible for the production of the two monoclonal immunoglobulins. This, to our knowledge, is the first documented case of a biclonal gammopathy involving a single heavy-chain class with both kappa and lambda light chains in a non-Hodgkin's lymphoma. Lesions resembling lymphomas must not be assumed to be inflammatory simply because the cells express both kappa and lambda antigens.     

Fibrillary glomerulopathy secondary to light chain deposition disease in a patient with monoclonal gammopathy

The pathologic manifestations of renal diseases related to monoclonal plasma cell dyscrasia include light chain deposition disease, the AL type of amyloidosis, and myeloma cast nephropathy. Light chain deposit disease (LCDD) is an uncommon condition in which monoclonal light chains are deposited in the glomeruli, tubules, and vessels causing varying degree of damage. We report a case of LCDD coincident with fibrillary glomerulonephropathy (FGN) in a 73-yr-old man with a diagnosis of monoclonal gammopathy of undetermined significance who presented with progressive renal insufficiency and mild proteinuria. The serum kappa light chain level was markedly raised. Immunofluorescent stains showed IgG along with C3 and kappa staining in glomeruli, but lambda staining was negative. Electron microscopic studies revealed diffuse punctuate-type deposits along the subendothelial areas. There were also scattered randomly oriented fibrils with a mean fibril thickness of 15-25 nm seen mainly in the glomerular mesangium, consistent with FGN. The congo red stain was negative on the histologic section. The present case illustrates that LCDD can progress to develop FGN in a patient with monoclonal gammopathy.     

Skeletal scintigraphy with technetium diphosphonate in multiple myeloma--a comparison with skeletal x-ray

Twenty-one patients with multiple myeloma were examined in close time relation with skeletal X-ray survey and bone scanning using technetium diphosphonate. Results indicate that X-ray is superior to bone scan in detecting myelomatous bone lesions. Approximately twice as many lesions were detected by X-ray as by bone scan. An exception to this general finding is the lumbar spine and rib cage, in which the two methods are equally reliable. Thus, a negative bone scan does not exclude the possibility of a myelomatous bone lesion.     

Simultaneous AL-type amyloid and light chain deposit disease in a liver biopsy: a case report

A 57-year-old male caucasian presented with a peripheral neuropathy which had an autonomic component. Clinical examination revealed hepatomegaly and laboratory tests showed derangement of liver function tests and IgG lambda myeloma. Biopsy of the liver was performed. Histological examination revealed AL-type amyloid in the hepatic arteries and a perisinusoidal deposit of diastase resistant, periodic acid-Schiff positive material which did not react in the same way as the arterial deposit, giving no apple green birefringence when stained with Congo red. Immunohistochemistry showed the material to consist of lambda light chains. Electron microscopy confirmed that the material did not have the ultrastructural characteristics of amyloid. A diagnosis of light chain deposit disease concurrent with vascular AL-type amyloid was made.     

Bilateral styloid chain ossification: case report

The styloid chain is defined as the styloid process of the temporal bone, the stylohyoid ligament and the lesser cornua of the hyoid bone. Unusually long, incidental bilateral styloid chain ossification is described. This paper is presented for its unusual incidence, unusual length, the presence of ossification rather than calcification and its embryological correlation. Brief mention is made on the embryology and clinical significance of this condition.     

Serum free light chain analysis in multiple myeloma and plasma cell dyscrasias

After the development of a reliable method to detect free light chains in serum, several investigations have been conducted to explore their importance in plasma cell dyscrasias (PCD). Detection of monoclonal proteins is very important in the diagnosis and management of PCD, which include a broad spectrum of diseases such as multiple myeloma and also benign, premalignant disorders like monoclonal gammopathy of undetermined significance. The aim of this article is to summarize the recent studies and to highlight the importance of free light chain analysis in the diagnosis of PCD, its prognostic value and role in the management of this group of diseases.     

Immunoquantitation of free light chain immunoglobulins: applications in multiple myeloma.

A single radial immunodiffusion (RID) assay for the free lambda (lambda) and kappa (kappa) light chain (LC) immunoglobulins was developed for study of clinical samples of serum, urine, and bone marrow of patients with multiple myeloma. Using highly specific rabbit anti-LC sera, we were able to quantitate: (a) free serum LC after fractionating the serum sample using an Amicon ultrafiltration chamber equipped with an XM100A diaflow membrane and an 125I-LC standard for calculating filtration efficiencies, (b) directly, Bence Jones (BJ) proteins in the urine, and (c) the in vitro LC synthesis by myeloma plasma cells obtained from bone marrow aspirates. The median values of free LC levels in sera (n = 12), urines (n = 25), and marrow culture synthetic rates (n = 17) were 116.2 mg/dl, 0.775 g/day and 15.3 pg/plasma cell/day, respectively. These data were useful in initial evaluation of patients and serial follow-up studies. The assays have also been of use in our research on the determination of total body tumor mass in patients with BJ multiple myeloma.     

Serum free light chain analysis in multiple myeloma and plasma cell dyscrasias

After the development of a reliable method to detect free light chains in serum, several investigations have been conducted to explore their importance in plasma cell dyscrasias (PCD). Detection of monoclonal proteins is very important in the diagnosis and management of PCD, which include a broad spectrum of diseases such as multiple myeloma and also benign, premalignant disorders like monoclonal gammopathy of undetermined significance. The aim of this article is to summarize the recent studies and to highlight the importance of free light chain analysis in the diagnosis of PCD, its prognostic value and role in the management of this group of diseases.     

A case of isolated light chain deposition disease in the duodenum

Light chain deposition disease (LCDD) is a rare disorder associated with a clonal proliferation of plasma cells, which synthesize abnormal monoclonal immunoglobulin light chains. LCDD is characterized by systemic deposition of light chains in various organs, with the kidneys being most commonly affected. There have been few reports of isolated LCDD. We report a rare case of LCDD limited to a duodenal polyp. A 63-yr-old man visited our hospital for health screening without symptoms in 2009. On gastrofiberscopy, a duodenal polyp was observed. The biopsy showed diffuse infiltration by atypical plasma cells, which were positive for kappa-type light chains by immunohistochemistry. While the patient refused further management, we could find no evidence of recurrence until 2 yr after the initial diagnosis. It has been reported that isolated LCDD has relatively good prognosis compared to systemic LCDD. However, treatment for this disease has not been established yet.     

Bone marrow lambda-type light chain crystalline structures associated with multiple myeloma

Summary A 58-year-old man showed bone marrow crystalline structures associated with a lambda light chain producing multiple myeloma. Analysis and processing of electron images clearly displayed the periodic structure of the crystals. Immunochemistry suggested that they contained the whole or a fragmented constant portion of immunoglobulin.     

Association of plasma cell subsets in the bone marrow and free light chain concentrations in the serum of monoclonal gammopathy patients

This study investigated bone marrow plasma cell subsets and monoclonal free light chain concentrations in blood of monoclonal gammopathy patients. 54 bone marrow samples were stained by double immunofluorescence to enumerate cellular subsets making either intact monoclonal immunoglobulin or free light chains only. Blood taken at the same time was assayed for free light chains by an automated immunoassay. Patients were assigned to three cellular population categories: single intact monoclonal immunoglobulin (59%), dual monoclonal immunoglobulin and free light chain only (31%), or single free light chain only (9%). The median affected free light chain concentration of each group was 75 mg/l, 903 mg/l and 3320 mg/l, respectively, but with substantial overlap. In myeloma patients the difference in serum free light chain concentrations between patients with free light chain only marrow cells and those without was statistically significant. Serum free light chain levels >600 mg/l result mostly from marrow cells restricted to free light chain production.     

Myoinformatics report: myosin regulatory light chain paralogs in the human genome

On-line bioinformatics tools were used to identify and characterize all paralogs (intragenomic homologs) of muscle myosin regulatory light chains in the human genome. The initial search yielded 22 possible paralogs, but careful examination of supporting data eliminated most of these. Five paralogs were clearly identified with the tissue types (skeletal and cardiac muscles, smooth muscle, non-muscle cytoplasm) in which they are expressed. Sequence comparisons and phylogenetic analysis showed early divergence of a common ancestor of smooth muscle and non-muscle paralogs from a common ancestor of skeletal and cardiac muscle paralogs. An unusual sixth human paralog was very similar to the regulatory light chain of “superfast” myosin, which to date has been found only in cat. Finally, a unique and questionable “precursor lymphocyte” paralog was tentatively identified. Three-dimensional structural models of all seven human paralogs were constructed using the known structure of chicken fast skeletal muscle regulatory light chain as a template.     

IgG-kappa type multiple myeloma in alcoholic cirrhosis--a case report

Transition from polyclonal to monoclonal gammopathy resulted in myeloma in the course of cirrhosis is rare but of interest. We treated such a case of multiple myeloma of IgG-kappa type associated with alcoholic cirrhosis. The case was a 72-year-old Japanese male patient who was admitted because of ascites and edema. Physical examination and laboratory findings including liver histology were compatible with alcoholic cirrhosis. Serum electrophoresis revealed monoclonal hypergammaglobulinemia of IgG-kappa. Bence Jones protein in urine was positive. Bone scintigraphy and roentgenography revealed small punched out lesions in the skull. A bone marrow clot section showed marked infiltration of atypical plasma cells. From these findings multiple myeloma associated with alcoholic cirrhosis was diagnosed. On the basis of a review of the reported cases, the possible relationship between monoclonal gammopathy and chronic liver diseases was discussed.