Plasma cell dyscrasias: current status

This is a review of the current status of the monoclonal gammopathies (plasma cell dyscrasias). We begin with the recognition of a monoclonal protein in serum and urine. We briefly discuss the differential diagnosis of the monoclonal gammopathies. Clinical and laboratory findings as well as the management of multiple myeloma are addressed. Future approaches for the treatment of myeloma are provided. The variant forms of multiple myeloma, including smoldering myeloma, plasma cell leukemia, nonsecretory myeloma, IgD myeloma, osteosclerotic myeloma, solitary plasmacytoma of bone, and extramedullary plasmacytoma, are briefly reviewed. Diagnosis and treatment of Waldenstr?m's macroglobulinemia are presented. The recognition and differential diagnosis of the heavy-chain diseases (gamma, alpha, and mu) are included. Monoclonal gammopathy of undetermined significance ("benign" monoclonal gammopathy) is presented in detail. Amyloidosis is not included in this review.     

Criteria for the classification of monoclonal gammopathies,multiple myeloma and related disorders: a report of the International Myeloma Working Group

Summary. The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is ≥ 30 g/l and/or bone marrow clonal cells ≥ 10% but no r elated o rgan or t issue i mpairment (ROTI)(end-organ damage), which is typically manifested by increased c alcium, r enal insufficiency, a naemia, or b one lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (± recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.     

Gastrointestinal bleeding as initial presentation of extramedullary plasma cell neoplasms: A case report and review of the literature

BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and treatment.CASE SUMMARY Our aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the literature with the view to consolidate and discuss information about diagnosis and management of this rare entity. In addition to our case, a literature search(Pub Med database) of case reports of extramedullary plasma cell neoplasms manifesting as upper gastrointestinal bleeding was performed. Twenty-seven cases of extramedullary plasmacytoma(EMP) involving the stomach and small bowel presenting with upper gastrointestinal bleeding were retrieved. The majority of patients were males(67%). The average age on diagnosis was 62.7 years. The most common site of presentation was the stomach(41%), followed by the duodenum(15%). The most common presenting complaint was melena(44%). In the majority of cases, the EMPs were a secondary manifestation(63%) at the background of multiple myeloma(26%), plasmablastic myeloma(7%) or high-grade plasma cell myeloma(4%). Oesophagogastroscopy was the main diagnostic modality and chemotherapy the preferred treatment option for secondary EMPs.CONCLUSION Despite their rare presentation, upper gastrointestinal EMPs should be considered in the differential diagnosis of patients with gastrointestinal bleeding especially in the presence of systemic haematological malignancy.     

Rare pancreas tumor mimicking adenocarcinoma: Extramedullary plasmacytoma

Neoplastic proliferation of plasma cells is called plasma cell dyscrasias, and these neoplasms can present as a solitary neoplasm or multiple myeloma. Extramedullary plasmacytoma, in particular pancreatic plasmacytoma, is a rare manifestation of multiple myeloma. Although computerized tomography is useful for the diagnosis of extramedullary plasmacytoma, there are no specific radiologic markers that distinguish it from adenocarcinoma. Histological confirmation by biopsy is necessary for accurate diagnosis and management of the tumor. Endosonography is the most sensitive method for the diagnosis of pancreatic tumors, and the use of fine needle aspiration by endosonography is associated with a lower risk for malignant seeding and complications. Here, we report a case of pancreatic plasmacytoma in newly identified multiple myeloma as diagnosed by endosonography. Endosonography is a reliable and rapid method for the diagnosis of extramedullary plasmacytoma. Therefore, endosonographic fine needle aspiration should be the first choice for histological evaluation when pancreatic plasmacytoma is suspected. Ideally, the pathology would be performed at the same site as endosonographic biopsy.     

Rarepancreas tumormimickingadenocarcinoma:Extramedullary plasmacytoma简

Neoplastic proliferation of plasma cells is called plasma cell dyscrasias, and these neoplasms can present as a solitary neoplasm or multiple myeloma. Extramedullary plasmacytoma, in particular pancreatic plasmacytoma, is a rare manifestation of multiple myeloma. Although computerized tomography is useful for the diagnosis of extramedullary plasmacytoma, there are no specific radiologic markers that distinguish it from adenocarcinoma. Histological confirmation by biopsy is necessary for accurate diagnosis and management of the tumor. Endosonography is the most sensitive method for the diagnosis of pancreatic tumors, and the use of fine needle aspiration by endosonography is associated with a lower risk for malignant seeding and complications. Here, we report a case of pancreatic plasmacytoma in newly identified multiple myeloma as diagnosed by endosonography. Endosonography is a reliable and rapid method for the diagnosis of extramedullary plasmacytoma. Therefore, endosonographic fine needle aspiration should be the first choice for histological evaluation when pancreatic plasmacytoma is suspected. Ideally, the pathology would be performed at the same site as endosonographic biopsy.     

Light chain restriction analysis of bone marrow plasma cells in patients with MGUS or ''solitary'' plasmacytoma: diagnostic value and correlation with clinical course

Twenty-eight patients with a diagnosis of 'solitary' plasmacytoma or with gammopathy but with nondiagnostic morphologic examination of the bone marrow were investigated using a short-term bone marrow culture technique which enriched for the plasma cell fraction. The percentage of monotypic plasma cells in these plasma cell enriched cultures was correlated with the subsequent clinical course. The majority of patients with plasmacytoma and a significant number of those with gammopathy but with otherwise non-diagnostic investigations were found to have a monoclonal plasma cell component of greater than 20%. There was a significant correlation between the percentage of monoclonal plasma cells as detected by bone marrow culture and subsequent progression to disseminated myeloma. These results indicate that early bone marrow involvement can be detected by means of plasma cell culture prior to morphologic identification of marrow plasmacytosis and that short-term plasma cell culture distinguishes patients with early, low bulk myeloma from those with monoclonal gammopathy of uncertain significance (MGUS).     

Russell body gastritis

A 63-year-old woman who presented with chest and back pain underwent an upper gastrointestinal endoscopy which revealed elevated legion in the antrum mucosa. Histologic examinations of gastric biopsies were showing monoclonal proliferation plasma cells containing Russell bodies. Differential diagnosis from B-cell lymphoma and plasmacytoma is difficult, because of monoclonality. Molecular analyses of immunoglobulin heavy chain (IgH) gene demonstrated that gene rearrangement was negative. Thus, diagnosis of Russell body gastritis was made. The Giemsa stains were also showing infection of Helicobacter pylori (H.pylori). After eradication therapy for H.pylori, follow-up upper gastrointestinal endoscopy was performed. She then recovered.     

Solitary pleural plasmacytomas manifested as a massive pleural effusion without evidence of monoclonal gammopathy

Abstract:   The majority of extramedullary plasmacytomas involve the upper respiratory tract but only a few are associated with serum monoclonal gammopathy. Most extramedullary plasmacytomas respond to local radiotherapy and have a better prognosis than multiple myeloma. Solitary plasmacytomas, involving the pleura, are very rare. This case report describes a patient with a solitary extramedullary plasmacytoma involving the pleura, and no evidence of serum, urine or pleural fluid paraproteins. Diagnosis was made by strongly positive immunohistochemical stains with CD38, CD138 and MUM-1 of the pleural tumour. The response to both radiotherapy and chemotherapy was poor and the patient died shortly after diagnosis.     

Monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic disorder with serum monoclonal immunoglobulin less than 30 g/l. It preferentially affects elderly patients; MGUS prevalence is about 1% in the general population and about 10% in patients aged over 80 years. MGUS diagnosis is based on elimination of other causes of serum monoclonal immunoglobulin, particularly multiple myeloma. Within the 20 years following diagnosis of MGUS, about 25% of patients will evolve towards myeloma or other malignant lymphoproliferative disorder. No factor has been identified to date which can efficiently predict this evolution. Recent data concerning immunophenotype, cytogenetics and molecular biology of plasma cells demonstrate the link between MGUS and multiple myeloma. MGUS clearly appears now as a plasma cell monoclonal pathology with reduced malignity. Soon, new biological data would help to discriminate patients with MGUS who will remain asymptomatic life-long from those who will evolve towards malignant lymphoproliferative disorder.     

The Detection of Pancreatic and Retroperitoneal Plasmacytoma Helped to Diagnose Multiple Myeloma: A Case Report

Multiple myeloma is characterized by the neoplastic proliferation of a single clone of plasma cells producing a monoclonal protein. However, the involvement of pancreas is a rare event. We herein report a rare case of pancreatic plasmacytoma, which was detected before the diagnosis of multiple myeloma.An 83-year-old male was referred to our hospital for further evaluation of obstructive jaundice and a pancreatic mass. A contrast-enhanced computed tomography (CT) scan revealed solid masses with homogenous enhancement in the pancreatic head and retroperitoneum. The histological findings of the retroperitoneal mass obtained by CT-guided biopsy showed multiple sheets of atypical plasma cells, which were positively immunostained for CD79a, CD138, and the κ light chain. Serum immunoelectrophoresis detected M-component of immunoglobulin A-κ, and the histological findings of the bone marrow revealed an abnormally increased number of atypical plasma cells with irregular nuclei and cytoplasmic vacuolation. The patient was therefore diagnosed to have multiple myeloma involving the pancreas and retroperitoneum. Although chemotherapy was performed, the patient died 6 months after the diagnosis.The pancreatic plasmacytoma was detected before the multiple myeloma in the present case. It is difficult to diagnose a pancreatic plasmacytoma without a history of multiple myeloma and related disease.     

Primary Gastric Plasmacytoma: A Morphological and Immunohistochemical Study of Five Cases

Five cases of primary gastric plasmacytoma were studied histopathologically and immunohistochemically. Plasmacytoid cells proliferated diffusely in the propria mucosa, almost preserving the structure of gastric glands. Occasionally, intranuclear inclusions, giant cells, and needle-shaped crystalline inclusions were observed. The neoplastic nature could be suspected on the basis of these histological findings. Immunohistochemically, three cases were positive for IgM and two for IgA. IgM positivity was more commonly observed in the gastric plasmacytoma than in multiple myeloma. Another immunohistochemical study demonstrated that LN-1 negativity and anti-EMA antibody positivity might be an indicator to differentiate gastric plasmacytoma from other types of gastric lymphoma. Four cases of early-stage gastric plasmacytoma have been followed for 5-12 yr. No recurrence has been observed so far. These cases suggest that gastric plasmacytoma has a relatively good prognosis.     

IgM myeloma: a report of four cases

IgM myeloma is a rare disease, accounting for approximately 0.5% of multiple myelomas (MM). Here we report four cases of IgM multiple myeloma. Two were diagnosed in advanced clinical stages with multiple osteolytic lesions, leading to hypercalcemia in one patient. Bone marrow morphology showed a variable degree of infiltration with mainly mature plasma cells. An immunophenotypic analysis performed in one case showed expression of CD38 and monoclonal cytoplasmatic immunoglobulin. Interphase fluorescence in situ hybridization performed in one case did not reveal any aneuploidies or deletions of the retinoblastoma, P16, or P53 tumor suppressor genes. While one patient with a smoldering IgM myeloma did not need specific therapy, the others received cytotoxic treatment based on standard chemotherapy for MM. The outcomes were one stable disease, one sustained complete remission, and one progressive disease. All four patients were alive 1 year after diagnosis. One died due to progressive disease after 31 months. We conclude that IgM myeloma shares clinical and histological features with other MM rather than with Waldenstr?m's macroglobulinemia, which is most commonly diagnosed in cases with IgM monoclonal gammopathy. Since MM and Waldenstr?m's macroglobulinemia differ in prognosis and treatment strategies, the two disease entities should be distinguished based on clinical criteria, bone marrow morphology, and immunophenotypic analysis.     

Quantitation of the monoclonal plasma cell component in bone marrow from patients with serum paraproteinemia and nondiagnostic marrow morphology

Twenty-one patients with serum monoclonal gammopathy but lacking acceptable morphological evidence of myelomatosis were studied with reference to the degree, if any, of monoclonal plasma cell expansion in aspirated marrow samples, enriched for plasma cells and analysed with respect to light chain distribution. Four of these patients had a biopsy-proven plasmacytoma of bone. Bone marrow aspirated from sites distant to the tumor showed clear evidence of infiltration by monoclonal plasma cells in two of the cases studied; the other two patients had normal results. Of the 17 other cases, 14 showed evidence of a monoclonal plasma cell component qualitatively concordant with the serum paraprotein as one would expect. These cases could be subdivided into those with myeloma (six cases) and those with monoclonal gammopathy of undetermined significance (eight cases) on the basis of conventional biochemical and radiological criteria. Three of the 17 patients, however, did not show evidence of monoclonal plasma cell infiltration, despite the presence of lytic lesions. It is important to recognize this minority group that simulates myeloma but that may well reflect alternative pathology that has not been identified.     

Outcome after autologous stem cell transplantation for multiple myeloma in patients with preceding plasma cell disorders

A third of patients with multiple myeloma (MM) have a preceding diagnosis of plasma cell proliferative disorder (PCPD), mostly monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM) or plasmacytoma. While autologous stem cell transplantation (SCT) improves survival in MM, it is not clear if patients with preceding PCPD have a different outcome. We identified 151 patients with preceding PCPD from among 804 patients undergoing SCT, and their outcomes were compared. The response rates, including complete responses, were similar between the groups. Patients with a preceding diagnosis of MGUS had longer time to progression (TTP; 27·5 months vs. 17·2 months, P  = 0·01), and longer overall survival (OS) from transplant (80·2 months vs. 48·3 months, P  = 0·03) compared to those with de novo myeloma. However no differences were seen among those with a preceding diagnosis of SMM or plasmacytoma in terms of TTP or OS from transplant when compared to those with de novo myeloma. Multivariate analysis indicated that the presence of MGUS prior to myeloma was prognostic for post-transplant relapse independent of other known risk factors. Patients with pre-existing MGUS prior to myeloma diagnosis have a better outcome following HDT, reflecting more indolent disease and a favourable biology than those presenting with de novo myeloma.     

伴单克隆免疫球蛋白血症的淋巴瘤——附3例报告及文献复习

目的:探讨伴单克隆免疫球蛋白血症的淋巴瘤患者的临床特征。方法:对3例伴单克隆免疫球蛋白血症的淋巴瘤患者的临床资料进行回顾性分析。结果:3例患者分别诊断为小淋巴细胞淋巴瘤(B细胞性)(B-SLL)、慢性淋巴细胞白血病(CLL)和脾边缘区淋巴瘤(SMZL),检查血清免疫球蛋白分别为单克隆IgG-kappa型、IgM-kappa型和Kappa型;临床表现均有贫血和肝脾肿大。结论:伴单克隆免疫球蛋白血症的淋巴瘤诊断需根据淋巴结和骨髓的病理学、血清免疫球蛋白、外周血或骨髓细胞免疫分型、融合基因综合判断;应注意与多发性骨髓瘤、原发性巨球蛋白血症的鉴别。     

A case of extramedullary plasmacytoma in the mediastinum]

A 80-year-old man was admitted to our hospital for examination of a mediastinal mass. Chest CT showed a 6 x 9 cm mass in the left anterior mediastinum. The left main bronchus and pulmonary artery were invaded by the mass. Bronchoscopic examination showed compression of the left main bronchus by the mass and enlarged lymph nodes. The left upper lobe and lingular bronchi were almost occluded. The overlying mucosa was invaded by tumor tissue. Microscopic findings of specimen obtained by transtracheal biopsy showed plasma cells of various sizes were at different stages of differentiation. Immunohistochemical staining revealed IgA monoclonality. Whole-body bone scan and bone marrow aspiration excluded multiple myeloma and a diagnosis of extramedullary plasmacytoma was made. Serum protein electrophoresis showed an IgA monoclonal gammopathy. Immunoelectrophoresis of the serum revealed an IgA kappa monoclonal component. These suggested that tumor cells were producing monoclomal IgA kappa light chain. Radiotherapy was effective in reducing the size of the plasmacytoma, and serum IgA reverted to normal. A 67-Ga scan showed strongly increased uptake in the left anterior mediastinum. Chest CT after radiotherapy showed that the decreased mass had an extrapleural sign against the mediastinal pleura. We determined that the origin of the plasmacytoma was probably the mediastinum. We reported a rare case of extramedullary plasmacytoma in the mediastinum.     

PRIMARY GASTRIC PLASMACYTOMA OF RAPID GROWTH PRESENTING; WITH UPPER GASTROINTESTINAL BLEEDING

We report a new case of primary gastric plasmacytoma. The presenting symptom wass upper gastrointestinal bleeding, and the diagnosis was made preoperatively by means of gastroscopically obtained biopsy material. The demonstration of a single type of IgA-κ inmunoglobulin in plasma cells infiltrating the gastric antrum is considered conclusive evidence of its neoplastic nature. Endoscopieally, the gastric plasmacytoma progresses from a benign antral ulcer (0.5 cm in diameter) to an ulcerated mass (7 cm in diameter) in an 8-wk period, suggesting rapid tumoral growth of a kind not described in the revised literature.     

The evolving use of serum free light chain assays in haematology

Over the last few years new immunoassays have emerged that allow the measurement of free immunoglobulin light chains (FLCs) in serum to a level of 2-4 mg/l and provide a much greater sensitivity than older methods, such as immunofixation, which is able to detect FLCs at a minimum concentration of 100-150 mg/l. The new FLC assay has enabled the detection of monoclonal protein in some patients with non-secretory myeloma and amyloidosis that were previously undetectable. FLC measurements are quantitative, correlating with disease activity, and are an advance in monitoring light chain only multiple myeloma, AL amyloidosis, non-secretory and oligo-secretory multiple myeloma. Serum FLC concentrations also reflect the disease course in the majority of myeloma patients producing intact monoclonal immunoglobulin proteins and have been incorporated into the new response criteria. The rapid half life of lambda and kappa free light chains means that FLC assays may provide a more rapid indication of the response to treatment but their clinical utility in this setting needs further study. An abnormal FLC ratio has been shown to be a risk factor for progression of monoclonal gammopathy of undetermined significance, smouldering myeloma and solitary plasmacytoma of bone and is prognostic in multiple myeloma.     

超声技术在胃间质瘤诊断和治疗中的应用

胃间质瘤是消化系统常见的间叶组织肿瘤,临床表现包括腹痛、肠梗阻、消化道出血、腹部包块等,组织学上具有非定向分化特性,超声技术在其诊断和治疗中起着重要的作用,本文就其应用现状作一综述.     

Gastric Epithelioid Leiomyosarcoma: A Curable Gastric Neoplasm

This is the first case report of the preoperative diagnosis of a gastric epithelioid leiomyosarcoma by percutaneous needle biopsy. Preoperative diagnosis facilitated curative surgical resection. Patients may present without symptoms or may report symptoms of peptic ulcer disease or gastrointestinal bleeding. Upper gastrointestinal series is the most useful radiological tool for detecting these lesions. Ultrasound and CT play a useful role in documenting the origin of these large masses, as well as their spread. Endoscopy is being used with increasing frequency, but because these are submucosal lesions diagnosis cannot easily be made through the endoscope. Pathologically, these tumors can be subdivided histologically into a benign epithelioid leiomyoma and two varieties of malignant epithelioid leiomyosarcoma. Prognosis correlates with histological features. Complete surgical resection is the treatment of choice. Chemotherapy or radiotherapy have no proven efficacy in treating epithelioid leiomyosarcoma. Unlike most other gastric malignancies, a favorable prognosis follows successful resection.