Primary amyloidosis associated with IgD-lambda M-proteinemia

We describe here a case of primary AL amyloidosis associated with IgD monoclonal gammopathy of undetermined significance. A 73-year-old man was referred to our hospital with suspected multiple myeloma due to renal failure and urinary Bence Jones protein. Although serum electrophoresis revealed IgDlambda monoclonal protein, the bone marrow did not showed plasma cell proliferation. Systemic bone survey disclosed no lytic bone lesions. Because the patient had macroglossia and multiple ecchymosis in the face and neck, primary amyloidosis was suspected. Skin biopsy revealed extensive deposition of amyloid which was positively stained by Congo red dye. A diagnosis of primary AL amyloidosis associated with IgD monoclonal gammopathy was made. The patient was also complicated renal failure that eventually needed hemodialysis. To our knowledge, this is the first report of primary AL amyloidosis associated with IgD monoclonal gammopathy with undetermined significance.     

Low IgE monoclonal gammopathy level in serum highlights 20-yr survival in a case of IgE multiple myeloma

This report describes the diagnosis, follow-up, and problems measuring serum immunoglobulin E (IgE) levels in a case of IgE myeloma with 20-yr survival. Serum and urine protein electrophoresis, immunofixation, and the N Latex IgE test were used to characterize the monoclonal proteins. The diagnosis of multiple myeloma in a 56-yr-old man was based on 5.4 g/24 h of monoclonal free lambda chain in urine and bone marrow findings of 23.5% plasma cells (19% mature and 4.5% atypical). IgE lambda monoclonal protein in serum measured 506,000 microg/L (210 833 IU/mL). The lack of other clinical findings of multiple myeloma places this case in the category of 'smoldering or indolent myeloma'. Measurement of serum IgE levels was complicated by the need to predilute serum to avoid antigen excess. Following chemotherapy, the patient went into clinical remission, eventually dying of complications of emphysema. This case expands the recognized clinical spectrum of IgE multiple myeloma.     

A neuron specific enolase-producing multiple myeloma

A 53-year-old woman was admitted to our hospital with left chest-wall pain. Computed tomography scans showed a homogenous mass on the left chest-wall with pleural effusion. Laboratory data showed anemia, hypercalcemia, and high levels of serum IgG. An IgG-lambda monoclonal protein was detected with serum immunoelectrophoresis. In addition, the serum level of neuron specific enolase (NSE) was elevated. A chest-wall tumor biopsy and a bone marrow aspiration revealed diffuse proliferation of atypical plasma cells, which were positive for cytoplasmic CD38 and IgG-lambda. The patient was diagnosed as having IgG-lambda type multiple myeloma with a chest-wall plasmacytoma. Immunostaining revealed diffuse NSE staining in the cytoplasm of the atypical plasma cells. These findings suggested that the myeloma cells produced NSE. The left chest-wall tumor and bone marrow myeloma cells disappeared following several courses of chemotherapy and radiotherapy and the serum levels of IgG and NSE also normalized. No recurrence of the multiple myeloma was seen after an autologous peripheral blood stem cell transplantation. This is the second report of an NSE-producing multiple myeloma. Interestingly, our case has similar clinical phenotypes with the previously reported case, such as chest-wall plasmacytoma, pleural effusion and hypercalcemia.     

Monoclonal gammopathy of undetermined significance. Natural history in 241 cases

Two hundred forty-one patients with a monoclonal protein in the serum but initially no evidence of multiple myeloma, macroglobulinemia, amyloidosis or lymphoma were followed up for more than five years. At the conclusion of the studies the patients were classified as follows: Group 1, patients without significant increase in monoclonal protein, 57 per cent; group 2, patients with more than 50 per cent increase in monoclonal serum protein or development of monoclonal urine protein, 9 per cent; group 3, patients who died without five-year serum studies, 23 per cent; and group 4, patients in whom myeloma, macroglobulinemia or amyloidosis developed, 11 per cent. Initially, the hemoglobin level, size of serum monoclonal protein peak, number of plasma cells in the bone marrow and levels of normal immunoglobulins were not significantly different among the four groups. The median interval from recognition of the monoclonal protein to diagnosis of multiple myeloma was 64 months, of macroglobulinemia 103 months and of amyloidosis 92 months. A significant increase of the monoclonal protein or development of myeloma, macroglobulinemia or amyloidosis occurred in 18 per cent of the patients with monoclonal immunoglobulin G(IgG), in 28 per cent with immunoglobulin A (IgA) and in 25 per cent with immunoglobulin M (IgM). Retrospective analysis of age, sex, presence of organomegaly, hemoglobin level, size and type of serum monoclonal protein peak, presence of small amounts monoclonal light chain in the urine, serum albumin level, levels of uninvolved immunoglobulins, IgG subclass and level of plasma cells in the bone marrow did not show how to distinguish initially between stable benign disease and progressive disease. Therefore, periodic reexamination of patients with monoclonal gammopathy is essential.     

Nonsecretory Myelomatosis without Intracellular Immunoglobulin

A patient with multiple myeloma is reported with severe hypogammaglobulinaemia but without monoclonal immunoglobulin (M-component) in the serum or Bence Jones protein in the urine. In May-Grünwald-Giemsa stained bone marrow film 45 % of the cells resembled plasma cells. Marrow immunofluorescent studies showed no increase of immunoglobulin containing cells. Ultrastructural studies showed a large number of cells with a well developed rough endoplasmic reticulum and other morphological features characteristic for plasma cells.     

Amyloid arthropathy resembling seronegative rheumatoid arthritis in a patient with IgD-kappa multiple myeloma

A 67-year-old woman suffered from symmetrical polyarthralgia and multiple joint swelling simulating rheumatoid arthritis (RA). Laboratory examination showed negative results for rheumatoid factor, decreased levels of IgG, IgA, and IgM, and an increased level of IgD. Immunoelectrophoresis in her serum and urine revealed an IgD-kappa monoclonal component and Bence Jones protein (kappa), respectively. A bone marrow biopsy showed an excess of atypical plasma cells. A synovial biopsy revealed amyloid deposition composed of IgD-kappa. She was diagnosed with amyloid arthropathy (AmyA) secondary to IgD-kappa multiple myeloma. It is important to pay attention to AmyA due to multiple myeloma in patients with seronegative RA.     

The Physiopathological Significance of Benign Monoclonal Gammopathy: a Study of 64 Cases

Sixty-four patients with monoclonal protein in serum but initially without evidence of multiple myeloma, macroglobulinaemia, amyloidosis or lymphoma, were studied. Fifty patients (78%) were observed for a period exceeding 3 years. Based on the follow-up data the patients were classified into the following four groups: Group 1=patients with transient monoclonal gammopathy: 4.7%; Group 2 = patients without significant increase in monoclonal serum protein: 75%; Group 3 = patients with more than 50% increase in monoclonal serum protein: 14.1%; Group 4=patients in whom multiple myeloma developed: 6.2%. The mean interval from discovery of the serum monoclonal protein to evolution to multiple myeloma was 61 months. Retrospective analysis of age, sex, blood count, bone marrow picture, antigenic type and size of serum monoclonal proteins, presence of small amounts of homogeneous light chain in the urine, serum albumin level, levels of residual immunoglobulins, did not help to distinguish initially the patients in whom the monoclonal gammopathy evolved to multiple myeloma from patients in whom the disease remained benign and stable. The evolution to multiple myeloma had occurred abruptly after long periods of stable condition; and until this progression the follow-up data were similar to the patients with benign disease. The possible physiopathology of occurrence and evolution of benign monoclonal gammopathy is discussed.     

Multiple myeloma presenting with acquired factor VIII inhibitor

An initial presentation of hematological malignancies associated with autoantibodies is not common, and there is only one documented case of multiple myeloma presenting with acquired FVIII inhibitor for multiple myeloma. In this paper, we describe a second case of multiple myeloma who presented with acquired FVIII inhibitor. A 43-year-old woman was referred to our hematology unit for anemia and an elevated erythrocyte sedimentation rate. Two months before her admission, she had undergone an operation at a local hospital because of ovarian cyst rupture complicated by severe postoperative bleeding. Because coagulation tests had revealed a prolonged partial thromboplastin time which could not be corrected by a mixing test and a decreased FVIII level, a diagnosis of acquired FVIII inhibitor had been made. The patient was hospitalized in our unit for further evaluation. The erythrocyte sedimentation rate was 110 mm/h, serum albumin level 2.5 g/dL, globulin level 5.6 g/dL, and C-reactive protein 47.8 mg/L (0–6). Serum IgG was high, and serum protein electrophoresis showed a monoclonal spike in the gamma region. An IgG-kappa paraprotein was identified by immunofixation of the urine and serum. X-ray films of the bones revealed lytic areas in the skull, pelvis, and lumbar vertebrae. Bone marrow aspiration showed normal cellularity with 40% plasma cell infiltration. The patient was diagnosed with the IgG kappa type of multiple myeloma associated with acquired FVIII inhibitor. In patients presenting with severe bleeding, autoantibodies against FVIII should be considered for the differential diagnosis of bleeding. Clinicians should be alert to the presence of rare underlying neoplastic diseases such as multiple myeloma, in patients with acquired FVIII inhibitor.     

Systemic amyloidosis associated with IgD-λ multiple myeloma

We describe here a case of systemic amyloidosis associated with IgD multiple myeloma. A 59-year-old man was admitted to our hospital in April 2009, because of macroglossia and swelling in both wrists and fingers. He had difficulty moving his limbs and was aware of peripheral neuropathy. Skin biopsy revealed extensive deposition of amyloidosis, which was positive by Congo red staining. Laboratory findings were as follows: serum electrophoresis revealed IgD λ monoclonal protein, and Bence-Jones protein was detected. Monoclonal IgD protein had a concentration of 727 mg/dl, and a bone marrow aspiration revealed 49.6% of plasma cells. These findings led to a diagnosis of IgD multiple myeloma with systemic amyloidosis. The patient was treated with MP (melphalan and methylprednisolone), high-dose dexamethasone and VAD therapy (vincristine, adriamycin and dexamethasone), but systemic amyloidosis progressed, and his general condition deteriorated. Coexistence of IgD multiple myeloma and systemic amyloidosis is rare, and accumulation of case reports is needed to gain a better understanding of this condition.     

A case of malignant lymphoma concomitant with multiple myeloma

A 75-year-old woman was referred to us because of cough, high fever and skin erythema in April 1999. Malignant lymphoma (diffuse mixed cell type) was previously diagnosed in 1990 and she achieved complete remission after treatment with a series of CHOP regimen treatments. In 1998, multiple myeloma (IgG lambda type) was diagnosed and she was treated with a combination of melphalan and prednisolone. On physical examination, superficial lymphadenopathy and skin erythema were noted. Biclonal gammopathy (IgG kappa/lambda) was shown in serum, and Bence Jones protein in urine. Computed tomography showed pleural effusion and swelling of paraaortic lymph nodes. The bone marrow examination showed an increased number of abnormal plasma cells (19.2%) and no evidence of lymphoma. Left axillary lymph node biopsy revealed that she had non-Hodgkin's lymphoma (immunoblastic lymphadenopathy-like T cell lymphoma). She was treated with the CHOP regimen at reduced doses for both diseases. The lymphoadenopathy reduced after 6 courses of CHOP and 4 courses of CHOPE (CHOP + VP16), however, she had bone pain on November 1999 and received treatment with MCNU-VMP (MCNU + VDS + L-PAM + PSL). Her rib pain improved, but she died of systemic infection of herpes zoster virus. We report here a rare case of malignant lymphoma concomitant with multiple myeloma.     

Nodular liver lesions involving multiple myeloma： A case report and literature review

We report a case of a 62-year old woman admitted to our hospital for multiple nodular metastatic liver lesions found by ultrasonography in a regular medical examination. Routine laboratory tests were normal. PET-CT showed multiple bone lesions and nodular liver lesions. Liver biopsy revealed nodular infiltration of multiple myeloma with positive staining of kappa light chain. Further investigation of bone marrow aspiration, immunofixation and immunoelectrophoresis of serum protein, urine test for Bence-Jones protein, 132-microglobulin in serum and urine confirmed the diagnosis. The patient also coinfected with hepatitis C virus （HCV）. With six cycles of chemotherapy with VAD schedule, she achieved complete remission. In this report, a literature review of liver lesions involving multiple myeloma is also provided.     

Non-secretory primary plasma cell leukemia with hyperammonemia

A 78-year-old man was admitted because of lumbago and chest pain. A diagnosis of non-secretory primary plasma cell leukemia was made based on the laboratory findings and his history. However, the plaque-forming cells assay of bone marrow cells revealed secretion of monoclonal immunoglobulin from the myeloma cells. Hyperammonemia was detected in the serum. Although the patient was treated with 4 courses of combination chemotherapy (vincristine, adriamycin, cyclophosphamide, methylprednisolone), he died of respiratory failure five months after diagnosis. Autopsy showed widespread multiple myeloma and prominent infiltration of myeloma cell in the sinusoid of the liver. Recently, there have been a few reports which increased the plasma ammonia concentration with multiple myeloma. This report strongly suggested that liver infiltration of myeloma cell caused hyperammonemia.     

Mandibular mass as the presenting manifestation of IgM myeloma in a 22-year-old man

 We report here the youngest known IgM myeloma patient to have presented with a mandibular mass. A 22-year-old Chinese man sought medical attention due to a mass over his right mandible that had been growing progressively for 6 months. A solitary osteolytic lesion in the right mandible was identified radiologically. Incisional biopsy revealed the presence of plasma cells of monoclonal origin, as evidenced by the exclusively positive staining of the kappa light chain. The diagnosis of multiple myeloma with mandibular involvement was confirmed by bone marrow examination. Further tests, including immunoglobulin electrophoresis and assay of the serum levels of kappa and lambda light chains, demonstrated that his myeloma was of the IgM, kappa subtype. The patient achieved a nonsustained partial response to six courses of melphalan and prednisolone therapy and palliative radiotherapy. Received: April 29, 1998 / Accepted: September 14, 1998     

Ectopic production of amylase by a non-producing type of multiple myeloma]

The patient was a 64-year-old woman who was admitted to our hospital because of lumbago. A diagnosis of multiple myeloma (non-producing type) was made, based on (1) the presence of multiple osteolytic lesions, (2) hypercellular marrow with 64.2% plasmacytoid malignant cells, (3) no monoclonal gamma-globulin was detected in the serum and urine, and (4) abnormal monoclonal gamma-globulin was also not detected in the cytoplasm and membranes of these malignant cells. After several courses of chemotherapy, a pleural effusion infiltrated by myeloma cells developed and the patient's serum contained a markedly increased amylase activity of salivary-type. Amylase activity was also detected in vitro in the supernatant of cultured myeloma cells established from the patient's pleural effusion. The presence of alpha-amylase in the myeloma cells, which were derived from pleural effusion, was demonstrated immuno-histochemically. These observations indicates that amylase was ectopically produced by these myeloma cells. Interestingly, 14 out of 20 metaphases in the cells derived from pleural effusion showed translocation of 1p22 near the region of 1p21, where the amylase gene was assigned.     

An autopsy case of IgE myeloma

An autopsy case of IgE myeloma, 85-year-old male is reported. He was admitted to our hospital on November 17, 1987 due to pain of left humerus. Osteolytic and osteoporotic foci were found in left humerus, ribs, spinal column and femurs. Complete blood countings were as follows: RBC 3.23 x 10(12)/L, Hb 11.3 g/dl, WBC 6.3 x 10(9)/L, platelet 173 x 10(9)/L. Blood smear showed red cell rouleaux formation without myeloma cells. Examination of bone marrow revealed hypoplasia with 52% myeloma cells which were stained with anti-IgE and antilambda antisera by peroxidase anti-peroxidase method. Total serum protein level was 7.7 g/dl. Monoclonal protein was observed at fast gamma-region by cellulose-acetate electrophoresis. On immunoelectrophoresis, this monoclonal protein made specific M-bow against anti-IgE and anti-lambda antisera. The IgE level in serum and urine were 7.8 x 10(6) IU/ml and 2.4 x 10(3) IU/ml by radio-immunoassay respectively. He was died owing to renal failure on September 7, 1988. Postmortem examination showed infiltration of myeloma cells in bone marrow, spleen, kidneys, lungs and generalized lymph nodes.     

Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia.

A patient with primary plasma cell leukemia resistant to chemotherapy was treated for 2 months with daily intravenous injections of anti-interleukin-6 (IL-6) monoclonal antibodies (MoAbs). The patient's clinical status improved throughout the treatment and no major side effects were observed. Serial monitoring showed blockage of the myeloma cell proliferation in the bone marrow (from 4.5% to 0% myeloma cells in the S-phase in vivo) as well as reduction in the serum calcium, serum monoclonal IgG, and the serum C-reactive protein levels. The serum calcium and serum monoclonal IgG corrected by approximately 30%, whereas the C-reactive protein corrected to undetectable levels during treatment. No major side effects developed, although both platelet and circulating neutrophil counts decreased during anti-IL-6 therapy. A transient immunization was detected 15 days after the initiation of the treatment, which could explain the recovery of myeloma cell proliferation after 2 months of treatment (2% myeloma cells in the S phase). In conclusion, this first anti-IL-6 clinical trial demonstrated the feasibility of injecting anti-IL-6 MoAbs, and also a transient tumor cytostasis and a reduction in IL-6-related toxicities. It gave insight into the major biologic activities of IL-6 in vivo and may serve as a basis for further development of anti-IL-6 therapy in myeloma and other IL-6-related diseases.     

Primary hyperparathyroidism complicated by multiple myeloma

A patient with primary hyperparathyroidism and multiple myeloma did not have roentgenographic evidence of either disease, yet there was biochemical evidence for both diseases. Hyperparathyroidism was diagnosed by hypercalcemia and increased parathyroid hormone values. Multiple myeloma was diagnosed by serum gamma-globulin component of 2.74 g/dL with a monoclonal spike and bone marrow plasmacytosis of 31%. The serum IgA level was 2.22 g/dL and the IgG and IgM levels were normal. Serum and urine immunoelectrophoresis showed abnormal IgA and lambda arcs. Computed tomography of the neck localized a parathyroid adenoma that was found and removed at surgery.     

Clinical significance of a multiple myeloma cell line, derived from a case associated with hyperammonemia

Recently, there have been several reports describing patients with multiple myeloma complicated by consciousness disturbance due to hyperammonemia. Here we report a patient with multiple myeloma and hyperammonemia, who died after rapid progression of the disease. A 71-year-old man who had been diagnosed as having Bence Jones protein (kappa)-type multiple myeloma in 1996 was readmitted to our hospital in February 1997 because of worsening bone pain, renal dysfunction, and hypercalcemia. Bone marrow aspiration yielded an almost dry tap, and the bone marrow was found to be completely occupied by immature plasma cells. Although liver dysfunction was slight, the serum ammonia level was high and increased gradually. Despite treatment, the patient died due to cerebral embolism and progression of plasmacytic leukemia in October 1997. Peripheral blood sampled at the time of death showed a serum ammonia level of 204 micrograms/dl, and the myeloma calls were cultured using monolayered bone marrow stromal cells as feeder cells. This led to the successful establishment of a cell line. The level of ammonia in the supernatant was high, indicating that the cultured myeloma cells produced and released ammonia.     

Bence-Jones myeloma with pleural effusion: response to alpha-interferon and combined chemotherapy.

A 73-year-old female patient with myelomatous pleural effusions is described. She was admitted to our hospital with lumbago and emaciation. Laboratory findings revealed cytopenia and hypogammaglobulinemia. Immunoelectrophoresis demonstrated Bence-Jones monoclonal protein in the serum, but not in the urine. Bence-Jones myeloma was diagnosed by the bone marrow aspiration. Chest X-ray film, however, showed bilateral pleural effusions. Fluid cytology revealed numerous immature plasma cells, indicating pleural involvement. Intrapleural administration of alpha-interferon combined with systemic chemotherapy (oral melphalan-prednisolone with alpha-interferon im.) was successful in maintaining the resolution of pleural effusions. Intrapleural alpha-interferon administration seems to be effective in the management of myelomatous pleural effusions.     

Uncommon combination of multiple myeloma in three patients

The authors describe uncommon combinations of multiple myeloma in three men aged 83, 63 and 55 years. In patient no. 1 both diseases--pernicious anaemia and multiple myeloma IgG-kappa were detected simultaneously. In patient no. 2 Crohn's disease preceded multiple myeloma IgA-lambda by more than 30 years. In patient no. 3 Gaucher's disease preceded multiple myeloma with paraproteinaemia IgA-lambda and IgG-kappa by more than 10 years. The diagnosis was facilitated by examination of the bone marrow, immunochemical examination of serum and urine and X-ray examination of the skeleton. In all patients the development of the myeloma had an adverse effect on the general course of the disease and despite treatment it soon proved fatal. In the discussion views on the possible causal associations between these diseases are discussed.