ST. LUKE'S Hospital clinicopathologic conference: plasma cell myeloma with amyloidosis of bone marrow and bronchopneumonia.
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Amyloidosis↗
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Results for “MYELOMA, PLASMA CELL”
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In vitro cytotoxic response to human myeloma plasma cells by peripheral blood leukocytes from patients with multiple myeloma and benign monoclonal gammopathy.
Peripheral blood leukocytes (PBL) from myeloma patients were studied for their capacity to lyse plasma cells from myeloma patients, benign monoclonal gammopathy (BMG) patients, and nonneoplastic disease patients. Plasma cells were isolated from bone marrow, labeled with 51Cr, and cultured with PBL isolated from patients with myeloma, BMG, or nonneoplastic disease, as well as normal individuals. PBL from patients with multiple myeloma demonstrated responses to autologous or allogeneic myeloma plasma cells. Optimum conditions for cytotoxic response included a responder-to-stimulator ratio of 1:1 and an effector-to-target ratio of 20:1. PBL from normal individuals or patients with BMG failed to demonstrate this response. However, PBL from BMG patients, but not normal individuals, could be induced to kill myeloma plasma cells (but not nonmyeloma plasma cells) by simultaneous stimulation with allogeneic lymphocytes and myeloma plasma cells.
Arthritis, Rheumatoid↗
Phagocytic, lambda light chain, plasma cell myeloma.
A case of phagocytic, lambda light chain, plasma cell myeloma was characterized by its clinical, morphologic, cytochemical, immunologic, and cell kinetic features. A 40-year-old man presented with Coombs-negative hemolytic anemia, hepatosplenomegaly, lytic bone lesions, lambda light chain monoclonal gammopathy, and infiltration of the bone marrow by dysplastic plasma cells, 10% of which demonstrated phagocytosis of erythroid cells. Electron microscopy demonstrated myeloma cells with prominent cytoplasmic microfilaments and erythroid cells in intracytoplasmic vacuoles. The myeloma cells did not phagocytose staphylococci in vitro. Phagocytic and nonphagocytic myeloma cells were tartrate-sensitive, acid-phosphatase positive, alpha-napthyl butyrate esterase negative, and did not form E rosettes or EAox(IgG) rosettes. The tumor cells were Tdt, Ia antigen, and SIg negative. Immunofluorescent staining for cytoplasmic light chains showed a monoclonal lambda pattern in nonphagocytic myeloma cells, and a probable monoclonal lambda pattern in phagocytic myeloma cells. These findings characterize the neoplasm as a monoclonal proliferation of differentiated plasma cells with the capability of erythrophagocytosis. Erythrophagocytosis by myeloma cells may have been responsible for the hemolytic anemia. The tritiated thymidine labeling index (LI%) was high (8%), suggesting a poor prognosis, despite a dramatic initial response to chemotherapy.
Adult↗
Plasma cell myeloma--new biological insights and advances in therapy.
Plasma cell myeloma is a more complex neoplasm than suggested by the relative uniformity of its dominant plasma cells, which represent the terminal stage of normal B-cell differentiation. Phenotypic, molecular, and cellular genetic data favor the presence of a myeloma stem cell early in hematopoietic development so that, as in chronic myelogenous leukemia (CML), a far distance exists between the primordial malignant cell that was the target of malignant transformation and the dominant clinical phenotype. Traces of pre-B, myeloid, and T cells are coexpressed with the mature B-cell phenotype, an occurrence unknown in normal B-cell differentiation. Analogous to CML, disease progression is marked by disease dedifferentiation, occasionally with cessation of myeloma protein production and development instead of extramedullary lymphomalike features with high LDH or myelodysplasia/acute myelogenous leukemia (AML) syndromes. The prognostic importance of serum LDH levels even in newly diagnosed myeloma suggests the early presence of tumor cells with "LDH phenotype," which, as a result of drug resistance and proliferative advantage, expand preferentially during disease progression. Further characterization of these cells may provide important clues about the ontogeny of multiple myeloma. Myeloma cells express many receptors for different biological signals that might be exploitable for therapy with immunotoxins or radioisotopes. Plasma cells and their precursors also produce a variety of cytokines, some of which have putatively autostimulatory functions (eg, IL-1, IL-5, IL-6) and/or are related to disease manifestations (eg, IL-1 and TNF-beta as OAF). The wealth of cellular expression by plasma cells provides clues for understanding the mechanisms of gene activation and the nature of abnormal growth and differentiation. The accuracy of prognostically relevant staging systems has been refined with the use of new quantitative parameters that reflect tumor mass (ie, serum B2M levels) and biology. Further studies of cellular and molecular biology (ie, CAL-LA, H-ras) may reveal those tumor cell features that define clinical entities, response to therapy, and long-term prognosis. The lack of a major advance in prognosis despite the use of more drugs and more intensive regimens justifies the continued use of standard melphalan-prednisone for patients with a highly favorable prognosis, for the very aged, and for those with a short life expectancy due to other major medical problems. However, a radical departure from standard practice is required to improve the prognosis for younger patients with poor risk features.(ABSTRACT TRUNCATED AT 400 WORDS)
B-Lymphocytes↗
Plasma cell myeloma of the mandible.
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Mandible↗
Heparin-like anticoagulant associated with plasma cell myeloma.
A 54-year-old man with plasma cell myeloma had sustained bleeding develop after prophylactic hip hemiarthroplasty. Routine coagulation studies revealed significant prolongation of the prothrombin time, activated partial thromboplastin time, and thrombin time. Further evaluation showed failure of the activated partial thromboplastin time to correct in a 1:1 mixture with pooled normal plasma, correction of the prolonged thrombin time by addition of protamine, and a normal reptilase time. A purified preparation of the immunoglobulin component of patient plasma produced the same pattern of coagulation abnormalities, suggesting the paraprotein possessed heparin-like anticoagulant activity. This appears to be a rare mechanism of bleeding diathesis in plasma cell myeloma.
Blood Coagulation↗
[Morphological and chemical considerations in prognosis of plasma cell myeloma].
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Blood Proteins↗
Renal symptomatology of plasma cell myeloma.
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Humans↗
Post-transplant plasma cell myeloma and polymorphic lymphoproliferative disorder with monoclonal serum protein occurring in solid organ transplant recipients.
Post-transplant lymphoproliferative disorders are mostly Epstein-Barr virus-related, B-cell tumors that develop as a consequence of immunosuppressive therapy in recipients of solid organ or bone marrow transplants. These disorders range from reactive, polyclonal plasmacytic hyperplasia to those that are morphologically and genotypically indistinguishable from typical non-Hodgkin's lymphomas. Plasma cell myeloma occurring after solid organ transplantation is rare. We report three plasma cell myeloma post-transplant lymphoproliferative disorder cases and one polymorphic, monoclonal post-transplant lymphoproliferative disorder case associated with a monoclonal serum protein. All three plasma cell myeloma post-transplant lymphoproliferative disorder cases had clinical, radiologic, and pathologic features of conventional plasma cell myeloma. The one polymorphic post-transplant lymphoproliferative disorder case was associated with an IgM monoclonal serum protein and was morphologically indistinguishable from a lymphoplasmacytic lymphoma. Three of the four cases, including the one polymorphic post-transplant lymphoproliferative disorder case, were positive for Epstein-Barr virus encoded small RNA by in situ hybridization. One patient died of plasma cell myeloma post-transplant lymphoproliferative disorder. The remaining three patients are alive: two are completely free of post-transplant lymphoproliferative disorder, and one has shown partial response to therapy. We compare the clinicopathologic features of these cases with those in the literature.
Aged↗
Progressive myeloma after thalidomide therapy in a patient with immature phenotype of myeloma (plasma) cells.
In our experience with thalidomide treatment for refractory multiple myeloma (MM), most patients with progressive disease (PD) did not show an increase in M-protein despite the tumor burden of myeloma cells. This finding led us to suspect that proliferation of immature myeloma cells showing MPC-1(-)/CD49e(-) phenotype may be a sign of PD. We report the results of consecutive analysis of the phenotype of myeloma (plasma) cells in an MM patient with PD during treatment with thalidomide. The myeloma cells decreased by thalidomide therapy were mature (MPC-1(+)/CD49e(+)) and intermediate (MPC-1(+)/CD49e(-)) types. When the patient was in the PD state, extramedullary plasmacytoma was recognized without proliferation of myeloma cells in the bone marrow (BM). The phenotype of myeloma (plasma) cells in both of these locations was that of immature myeloma cells (MPC-1(-)/CD49e(-)), and they showed decreased intensity of CD38 expression. The level of immunoglobulin G (IgG) in serum was decreased, and myeloma (plasma) cells in BM did not increase in PD. Although these clinical features may not be specific to MM patients in PD undergoing treatment with thalidomide, we suggest that immature myeloma cells may be resistant to thalidomide.
Aged↗
Bone marrow mastocytosis associated with IgM kappa plasma cell myeloma.
An association between mastocytosis and monoclonal gammopathy is a relatively rare but well recognized clinical finding. In the majority of cases, however, overt myeloma or lymphoma is not detectable morphologically. Here we describe the case of a 51 year-old male patient first presenting with paresis of the right facial nerve and the serological finding of IgM kappa paraproteinemia. The patient did not have organomegaly, lytic bone lesions, or urticaria pigmentosa-type skin lesions. Histological examination of a trephine biopsy specimen revealed the unusual coexistence of plasma cell myeloma and mastocytosis. Immunohistochemically, plasma cells were found to exhibit a monotypic staining for Ig heavy chain mu and Ig light chain kappa, thus confirming their neoplastic nature. Mast cells showed prominent spindling and formed dense multifocal infiltrates, thus enabling the diagnosis of bone marrow mastocytosis. Immunohistochemically, mast cells expressed tryptase, chymase, and KIT (CD117). In addition, aberrant expression of CD25 on mast cells was detected, confirming the coexistence of a neoplastic mast cell-proliferative disorder. According to the WHO proposal for classification of hematopoietic malignancies, this unique case, showing the association of two very rare haematologic neoplasms, can therefore best be referred to as bone marrow mastocytosis associated with IgM kappa plasma cell myeloma (SM-AHNMD).
Antigens, CD↗
Nonsecretory plasma cell myeloma--becoming even more rare with serum free light-chain assay: a brief review.
CONTEXT: Nonsecretory plasma cell myeloma is characterized by an absence of detectable monoclonal protein in both the serum and urine. It is generally reported to comprise approximately 1% to 5% of all cases of plasma cell myeloma and, because of its rarity, requires a high index of suspicion and bone marrow biopsy to establish the diagnosis. OBJECTIVE: Review the diagnostic strategy when nonsecretory plasma cell myeloma is a clinical consideration in light of a relatively new serum free light chain assay. DATA SOURCES: Case study and review of the literature. CONCLUSIONS: Initial data using a recently developed nephelometric serum free light chain assay suggests that only about one fourth of nonsecretory plasma cell myeloma cases may be truly nonsecretory. The definition of nonsecretory plasma cell myeloma should be modified to exclude cases with evidence of clonality using the serum free light chain assay.
Agammaglobulinemia↗
Plasma cell myeloma marrow diagnosis including morphologic and phenotypic features.
This article emphasizes both the morphologic and phenotypic features of the bone marrow in plasma cell myeloma. It details the morphologic features of both trephine biopsies and marrow aspirations. It emphasizes the salient phenotypic features of marrow myeloma cells, in contrast with normal plasma cells. The myeloma cell phenotype is discussed from the perspective of both tissue section immunohistochemistry (IHC) and flow cytometry (FACS analysis). The specific criteria for myeloma diagnosis are discussed and illustrated in Figures 1-12. Finally, the emphasis is on the key morphologic and phenotypic diagnostic criteria of each of the plasma cell neoplasms.
Biomarkers, Tumor↗
Immunophenotypic differentiation between neoplastic plasma cells in mature B-cell lymphoma vs plasma cell myeloma.
Some non-Hodgkin lymphomas show marked plasmacytic differentiation. In such cases, it may be difficult to differentiate these lymphoma from plasmacytoma or myeloma, especially with limited diagnostic material. However, there may be immunophenotypic differences in the plasma cells in these disorders that distinguish them. This study characterizes the immunophenotypes of neoplastic plasma cells in 41 cases of B-lineage non-Hodgkin lymphoma and compares them with those in plasma cell myeloma. We found that plasma cells in lymphoma were significantly more likely to express CD19, CD45, and surface immunoglobulin and less likely to express CD56 than those in myeloma. We further show that CD 19 and CD56 expression can be used reliably to distinguish these entities. Myeloma-associated osseous lesions and solitary plasmacytoma of bone showed myeloma-like immunophenotypes. However, some extramedullary plasmacytomas showed lymphoma-like phenotypes, suggesting that, in reality, they may represent non-Hodgkin lymphomas with extensive plasmacytic differentiation.
ADP-ribosyl Cyclase 1↗
Managing the complications of plasma cell myeloma.
Management of some diverse complications of plasma cell myeloma is reviewed with respect to prevention when possible and prompt treatment when necessary. A series of 102 patients from the Duke University Medical Center was surveyed to ascertain the approximate frequency with which renal failure, hypercalcemia, infection, hyperviscosity syndrome, and neurologic disorders occur. Selected patient studies and additional data from the literature emphasize aspects of these complications amenable to therapy aside from that directed at plasma cell growth.
Acute Kidney Injury↗
Plasma cell myeloma in unusually young patients: a report of two cases and review of the literature.
Two cases of plasma cell myeloma in unusually young patients are reported. One was a case of multiple myeloma involving the skull and ribs in a 23-year-old woman, the other of solitary myeloma of the tibia in a 21-year-old man. Both the cases were non-secretory myeloma; however, monoclonal immunoglobulins were demonstrated by immunohistochemical studies. Plasma cell myeloma in patients below the age of 30 years is extremely rare. Our literature search disclosed 20 well-documented cases of multiple myeloma and 25 cases of solitary myeloma in patients at or below the age of 30. Plasma cell myeloma may occur in young persons, so it should be considered in the pre-biopsy differential diagnosis when bone lesions radiologically consistent with myeloma are encountered in young patients.
Adult↗
Etoposide and ifosfamide for MP (melphalan and prednisolone)- and VAD (vincristine, adriamycin and dexamethasone)-resistant plasma cell myeloma: a case report.
A patient with plasma cell myeloma refractory to both MP (melphalan-prednisolone) and VAD (vincristine-adriamycin-dexamethasone) was treated with a combination chemotherapy consisting of VP-16, ifosfamide and dexamethasone (VID). A partial remission of 12-month duration was achieved. VID combination might be considered for myeloma patients who are refractory to both MP and VAD, and not eligible for high-dose melphalan with bone marrow transplantation.
Adult↗
Growth of a plasma cell myeloma in lathyritic mice.
Growth of a plasma cell myeloma (Adj PC-5) was studied in mice made lathyritic by the administration of beta-amino-proprionitrile (BAPN). The number of bones that had their medually cavities filled with tumor cells was notably decreased compared with tumor-bearing mice not treated with BAPN. Other aspects of tumor growth were the same. BAPN caused some retardation of tumor growth in the medullary cavity, but also caused osteoporosis and decreased tensile strength of collagen that allowed expansion of tumor growth outside the bones to proceed as usual. Additionally, the tumor-bearing mice showed some inhibition in their response to BAPN. This agrees with previous work that has shown that the response to BAPN treatment is greatest in animals that otherwise are healthiest.
Aminopropionitrile↗