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PubMed2001

Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study.

OBJECTIVE: Intracranial plasmacytomas are rare lesions that can arise from the calvarium, dura, or cranial base and exhibit a benign course unless associated with myeloma. Attention has recently been focused on the role of the cell adhesion molecules CD56 and CD31 in the pathogenesis of myeloma. No such information is available for intracranial plasmacytomas and myeloma-associated lesions. METHODS: We investigated the relationship between CD56 and CD31 expression, intracranial location, and progression to myeloma for a series of nine intracranial plasmacytomas (three dural, one calvarial, and five cranial base lesions). These parameters were also correlated with proliferation indices, as assessed by MIB-1 immunostaining of the histological sections. A single pathologist (AO) performed immunohistochemical analyses and reviewed all slides. RESULTS: Intracranial plasmacytomas presented more commonly in female patients (89%). The three dural lesions were CD56- and CD31-negative and exhibited MIB-1 staining of less than 10%; no patient developed myeloma or recurrence. Of the five cranial base lesions, three were CD56-positive, none was CD31-positive, and two exhibited MIB-1 labeling of more than 45%, with plasmablastic morphological features. Compared with other intracranial plasmacytomas, five of five patients with cranial base lesions developed bone marrow biopsy-proven myeloma (P < 0.05) within 8 months. The calvarial lesion was CD56- and CD31-positive, and the patient developed myeloma soon after diagnosis. Both of the two highly proliferative plasmablastic lesions recurred, one after gross total resection without radiotherapy and the other after a biopsy and 2000-cGy radiotherapy. CONCLUSION: Among intracranial plasmacytomas, cranial base location was the strongest predictor of the development of multiple myeloma. Expression of the cell adhesion molecules CD31 and CD56 was not predictive of outcome. Extramedullary dural-based lesions were CD56-negative and were not associated with myeloma. A high proliferation index and plasmablastic morphological features were predictive of a short time to recurrence and aggressive behavior. We recommend 4050- to 5040-cGy fractionated radiotherapy for all intracranial plasma cell neoplasms and gross total resection for non-cranial base lesions.

Adult↗

PubMed1993

Selective expression of intracisternal A-particle genes in established mouse plasmacytomas.

Mouse plasmacytomas generally express higher levels of RNA transcripts from endogenous intracisternal A-particle (IAP) proviral elements than do lipopolysaccharide-stimulated normal lymphocytes. Lymphocytes express a limited and highly characteristic set of IAP elements (lymphocyte-specific [LS] elements). In this study, we examined whether LS elements are expressed at higher levels after transformation of the cells and/or whether new IAP elements are activated. The IAP elements expressed in plasmacytoma MPC11 were characterized by sequence analysis of 22 cDNA clones. The long terminal repeats (LTRs) of the tumor cDNAs proved to be highly related in sequence. None of the clones was of the LS cDNA type. The MPC11 LTRs were five- to sixfold more active than an LS cDNA LTR when tested for promoter activity by transfection into plasmacytoma cells. The LTRs of the tumor-derived cDNAs contained a canonical ATF core sequence (ATF-PC), while the LS cDNAs contained an altered sequence (ATF-LS). An ATF-PC oligonucleotide probe detected multiple IAP transcripts on Northern (RNA) blots of RNA from several plasmacytoma but gave no reaction with RNA from stimulated B lymphocytes. In contrast, an ATF-LS probe detected higher levels of RNA in lymphocyte than in tumor RNAs. Thus, expression of IAP elements in transformed B cells is selective for a different set of regulatory sequence variants than those expressed in normal B cells. Other oligonucleotide probes representing LS- and PC-specific sequence variants detected multiple common hypomethylated IAP proviral loci in three independently derived plasmacytomas. Overall, the results show that established plasmacytomas exhibit a characteristic pattern of IAP proviral hypomethylation and regulatory sequence selection.

Animals↗

PubMed2005

Insertion of Myc into Igh accelerates peritoneal plasmacytomas in mice.

Gene-targeted mice that contain a His6-tagged mouse c-Myc cDNA, Myc(His), inserted head to head into different sites of the mouse immunoglobulin heavy-chain locus, Igh, mimic the chromosomal T(12;15)(Igh-Myc) translocation that results in the activation of Myc in the great majority of mouse plasmacytomas. Mice carrying Myc(His) just 5' of the intronic heavy-chain enhancer Emu (strain iMyc(Emu)) provide a specific model of the type of T(12;15) found in a subset (approximately 20%) of plasmacytomas that develop "spontaneously" in the gut-associated lymphoid tissue (GALT) of interleukin-6 transgenic BALB/c (C) mice. Here we show that the transfer of the iMyc(Emu) transgene from a mixed genetic background of segregating C57BL/6 x 129/SvJ alleles to the background of C increased the incidence of GALT plasmacytomas by a factor of 2.5 in first-generation backcross mice (C.iMyc(Emu) N1). Third-generation backcross mice (C.iMyc(Emu) N3, approximately 94% C alleles) were hypersusceptible to inflammation-induced peritoneal plasmacytomas (tumor incidence, 100%; mean tumor onset, 86 +/- 28 days) compared with inbred C mice (tumor incidence, 5% on day 150 after tumor induction). Peritoneal plasmacytomas of C.iMyc(Emu) N3 mice overexpressed Myc(His), produced monoclonal immunoglobulin, and exhibited a unique plasma cell signature upon gene expression profiling on mouse Lymphochip cDNA microarrays. These findings indicated that the iMyc(Emu) transgene accelerates plasmacytoma development by collaborating with tumor susceptibility alleles of strain C and circumventing the requirement for tumor precursors to acquire deregulated Myc by chromosomal translocation.

Alleles↗

PubMedDate not supplied

Fine needle aspiration cytology in extramedullary plasmacytoma.

OBJECTIVE: Extramedullary plasmacytoma is a rare plasma cell neoplasm. It can occur as the sole manifestation of plasma cell neoplasm, as a metastasis from another extramedullary plasmacytoma, as a solitary plasmacytoma of the bone or as a consequence of multiple myeloma. These plasma cell tumors can occur anywhere and have to be differentiated from other neoplasms, infectious processes and chloroma. STUDY DESIGN: We report the findings of fine needle aspiration cytology (FNAC) in 18 patients with extramedullary plasmacytoma. In six patients extramedullary plasmacytoma was the initial presentation of plasma cell neoplasm. In the remaining 12 patients the tumors occurred under or after treatment of plasma cell disease. RESULTS: Eleven lesions were located in the skin, seven in the lymph nodes, one in the liver and another in the spleen. Two patients with known diagnoses of plasma cell disease were thought, before FNAC, to have an infection, and two had a histologic diagnosis of non-Hodgkin's lymphoma. In 13 of 18 patients, cytologic smears showed anaplastic plasma cells. CONCLUSION: FNAC is a front-line investigative procedure in diagnosing extramedullary plasmacytoma.

Adult↗

PubMed2002

Prognostic value of angiogenesis in solitary bone plasmacytoma.

Angiogenesis plays an important role in the biology of multiple myeloma (MM) and has prognostic importance in this disease. Solitary plasmacytoma is a localized plasma cell malignancy that progresses to MM in a significant number of patients. We examined if angiogenesis is increased in solitary plasmacytoma and if it can help identify patients likely to progress to myeloma. We studied angiogenesis in plasmacytoma biopsy samples and bone marrow biopsies from 25 patients. High-grade angiogenesis was present in 64% of plasmacytomas. In contrast, bone marrow angiogenesis was low in all patients. Patients with high-grade angiogenesis in the plasmacytoma sample were more likely to progress to myeloma and had a shorter progression-free survival compared with patients with low-grade angiogenesis (P =.02). Angiogenesis is increased in solitary plasmacytoma and is a significant predictor of progression to myeloma and provides further evidence of its importance in the pathogenesis of myeloma.

Adult↗

PubMed2000

Irradiation of genetically modified plasmacytoma vaccines results in upregulation of CD80 molecule expression, IL-2 production and higher therapeutic efficacy of the vaccines.

It has been found previously that irradiated, IL-2 gene-modified plasmacytoma (X63-m-IL-2) vaccines are more efficient in the therapy of the parental (X63-Ag8.653) plasmacytoma than live plasmacytoma vaccines. In this communication, we have demonstrated that irradiation of murine IL-2-producing plasmacytoma vaccines resulted in upregulation of CD80 molecule expression and IL-2 production. The expression of MHC class I antigens was not altered. The upregulation of the CD80 membrane molecule expression in X63-m-IL-2 cells was higher after irradiation with 150 Gy than after irradiation with 50 Gy. Comparable upregulation of the CD80 molecule expression has also been demonstrated after irradiation of the parental murine X63-Ag8.653 plasmacytoma cells. The results indicate that upregulation of the CD80 molecule expression and enhanced IL-2 production in irradiated X63-m-IL-2 cells was responsible for the higher therapeutic effectiveness of the irradiated plasmacytoma vaccine.

Animals↗

PubMed2000

Chronic lymphocytic leukemia complicated by plasmacytoma originating from different clones.

In a woman with chronic lymphocytic leukemia (CLL), a plasmacytoma developed on the back region after four years. CLL cases complicated with plasmacytoma are rare. In the present case, the plasmacytoma showed kappa cytoplasmic immunoglobulin (Ig), and the CLL showed gamma lambda surface Ig. To reveal the clonal origin of CLL and plasmacytoma, we analyzed Ig gene rearrangements in the patient's peripheral blood and plasmacytoma. Ig gene DNA analysis confirmed the presence of different rearrangements in the heavy and light chain genes of CLL and plasmacytoma. These findings suggest that in this patient, the two B cell malignancies arose from expansion of two phenotypically and genotypically distinct clones.

Blotting, Southern↗

PubMed2000

Neuropsychological and magnetic resonance imaging abnormalities associated with a plasmacytoma of the frontal dura: a case report.

OBJECTIVE: The goal of this investigation was to describe the neuropsychological and magnetic resonance imaging (MRI) findings in a patient with an extramedullary plasmacytoma that extensively infiltrated the cerebral dura, especially over the frontal region. BACKGROUND: Extramedullary plasmacytomas are rare tumors that have been reported to involve the dura matter in only a small number of cases. In most of the reported occurrences, the dura plasmacytomas were successfully treated with a combination of surgery and irradiation, without prominent cognitive sequelae. METHOD: MRI of the brain and neuropsychological tests were conducted approximately 13 months after the patient underwent radiotherapy. In addition, measures of frontal lobe personality characteristics were obtained before and after radiotherapy. RESULTS: MRI findings revealed extensive enhancement around the anterior frontal lobes and prominent involvement of the anterior longitudinal fissure. Results from neuropsychological testing indicated mild to moderately impaired performance on tests of working memory, complex attention, and cognitive flexibility. Further, the patient reported experiencing personality changes consistent with frontal lobe dysfunction as part of the initial symptoms of the disease, which remained unchanged after treatment. CONCLUSIONS: Our findings are the first to describe cognitive sequelae of dural plasmacytomas. In addition, results from this case study reveal that plasmacytomas of the frontal dura produce personality changes similar to those observed in patients with significant frontal lobe injury. Finally, plasmacytomas that significantly infiltrate the frontal lobes may be insensitive to radiotherapy and result in residual cognitive and personality abnormalities.

Attention↗

PubMed2006

[Solitary plasmacytoma: a clinicopathologic and immunophenotypic analysis of 43 cases].

OBJECTIVE: To investigate the clinicopathologic and immunophenotypic features of solitary plasmacytoma and discuss the diagnosis and differential diagnosis of the tumor. METHODS: Clinicopathological study and follow up study were made on 43 cases of solitary plasmacytoma, including 24 cases of extramedullary plasmacytoma (EMP) and 19 cases of solitary plasmacytoma of bone (SPB). Immunohistochemical staining was performed by SP method using antibodies CD20, CD79a, PC, Ig kappa, Ig lamda, IgA, IgD, IgE, IgG and IgM. RESULTS: Rgarding EMP, the male/female ratio is 2.5 to 1, the age ranges from 3 to 70 years (mean 49). Clinically, the neoplasms of 22 cases were located in nasal cavity or nasosinus, 2 cases were located in lung and tonsil respectively. Rgarding SPB, the male/female ratio is 1:1, the age ranges from 36 to 72 years (mean 53). Clinically, the neoplasms of 8 cases were located in vertebrae, 3 cases in pelvis, 6 cases in clavicle, rib and femur respectively, 2 case in radius and tibia respectively. Histopathological examination revealed tumor cells diffuse infiltration with necrosis and ulceration; the well-differentiated tumor cells were similar to the normal plasmacyte in shape; the poorly-differentiated tumor resembled centroblasts; there were a few interstitial tissues with plenty of vessels or formation of blood lakes; and there was deposition of amyloid materials. Immunophenotypic analysis showed that all tumor cells were positive for CD79a and negative for CD20; that plasma cell marker (VS38C) was expressed in 41 cases; that light chain restriction was detected in all 43 cases( 31 for lamda and 12 for kappa), and that heavy chain expression was detected in 39 for IgG, 1 for IgA, 2 for both IgG and IgM, and 1 for IgA/IgG. CONCLUSION: The special histopathology in this group of solitary plasmacytomas is presented. The well-differentiated tumors should be distinguished from reactive plasmacytosis and MALT. And, when poorly-differentiated solitary plasmacytomas were tentatively diagnosed, large cell lymphoma, melanoma and poorly differentiated carcinoma should be considered in differential diagnosis.

Adolescent↗

PubMed1990

[Diagnosis and treatment of solitary plasmacytoma].

Solitary plasmacytomas are rare tumours. We report our experience from 25 solitary osseous and 18 solitary extramedullary plasmacytomas. 41 patients were given high voltage radiotherapy, usually 40 Gy in 20 fractions. Two patients with extramedullary plasmacytoma developed generalized disease, while ten patients with osseous plasmacytoma developed myelomatosis. Extramedullary plasmacytomas are usually cured by adequate local treatment, while in solitary osseous plasmacytomas the prognosis is more dubious.

Adult↗

PubMed1978

[Light-chain plasmacytoma with reversible renal insufficiency after intravascular application of thorotrast (author's transl)].

Thirty-three years after intravascular injection of Thorotrast, a light-chain plasmacytoma with hypercalcemia and renal insufficiency was diagnosed in a 60-year-old man. The question of causal relation between Thorotrast deposit and plasmacytoma is discussed. The accumulated radiation load to the bone-marrow as caused by thorium dioxide deposition amounts to circa 3000 rem. According to casuistic and epidemiological communications, induction of plasmacytomas by external X-irradiation may be regarded as possible. A distinct increase in myeloproliferative diseases but only small numbers of plasmacytomas are reported in extensive epidemiological Thorotrast studies. From combination of results of the three most comprehensive epidemiological Thorotrast studies is obtained a numerical ratio of 1:5 for the spontaneous rate against the number of plasmacytomas observed. Identical correlations are yielded by investigations at Hiroshima and Nagasaki. Hence it is to be supposed that also plasmacytomas can be induced by thorotrastosis of the reticulohistiocytic system.

Acute Kidney Injury↗

PubMed1993

Retroviral enhancer insertion 5' of c-myc in two translocation-negative mouse plasmacytomas upregulates c-myc expression to different extents.

Essentially all murine plasmacytomas have deregulated c-myc expression that is typically brought about by chromosomal translocations between the c-myc/Pvt-1 locus and one of the immunoglobulin loci. ABPC 22 and RFPC 2782 are BALB/c plasmacytomas that lack chromosomal translocations yet have Southern blot evidence of c-myc gene rearrangements. In this report we show that proviral integrations 5' of the c-myc gene can deregulate c-myc expression in mouse plasmacytomas. Analysis of DNA sequences 5' of the c-myc genes from both tumors demonstrated that rearrangements were caused by retroviral integrations 5' of c-myc exon 1. The proviral insertion in RFPC 2782 was associated with a high steady-state c-myc mRNA level comparable to that seen in plasmacytomas with typical translocations. An analogous proviral insertion in ABPC 22 was associated with a c-myc RNA level that was only 38% of that of RFPC 2782. Nuclear run-on studies of c-myc transcription showed that ABPC 22 has both a lower rate of transcription and a greater degree of transcriptional attenuation than RFPC 2782. DNA sequencing of the long terminal repeat of each tumor provirus showed that the ABPC 22 provirus harbors a deletion of one of the two direct repeats in the viral enhancer, whereas both repeats are present in the RFPC 2782 provirus. These data indicate that maximum LTR enhancer effectiveness in plasmacytomas in vivo requires the presence of both LTR direct repeats. The documentation of the low level of steady-state c-myc mRNA in ABPC 22 supports the notion that deregulated c-myc expression, even at low steady state levels, is effective in supporting the development of plasmacytomas.

Animals↗

PubMed1997

[Multiple extramedullary plasmacytomas from the whole respiratory system].

Extramedullary plasmacytoma occurs most commonly in the upper respiratory tract, but rarely develops in the lung. We have recently studied an unusual case of multiple extramedullary plasmacytomas, presumably preceding localized myelomatous bone lesions. This rather unique case is, to the best of our knowledge, the first documented report of widespread multiple extramedullary plasmacytomas confined to a single organ system. A 50-year-old man was hospitalized for assessment of bilateral hilar masses on a chest radiograph. An open lung biopsy specimen was obtained, revealing plasmacytoma of the lung. Biopsy specimens from the nasal fossa also demonstrated plasma cell tumor. Moreover, a bronchoscopy revealed that the both main-stem bronchi appeared to be involved by hemorrhagic tumorous lesions. However, a biopsy could not be done because of the high risk of bleeding. Electrophoresis revealed an IgA (kappa) type M-component (2.8 g/dl) in the serum and kappa type Bence Jones proteins (0.5 g/day) in the urine. The clinical course of the present case accurately corresponds to multiple extramedullary plasmacytomas with a localized bone involvement, but not to extensive extramedullary disease associated with aggressive multiple myeloma. The occurrence of multiple extramedullary plasmacytomas confined to the respiratory system may be due to an endobronchial metastatic process or to a multicentric autochthonous process.

Bence Jones Protein↗

PubMedDate not supplied

An unusual sellar mass--solitary plasmacytoma.

OBJECTIVE: To describe a case of solitary intrasellar plasmacytoma in a patient with a preoperative diagnosis of a nonfunctioning pituitary adenoma. METHODS: A case of a solitary intrasellar plasmacytoma is presented, in which the clinical and laboratory findings are detailed and the response to treatment is discussed. Pertinent reports from the literature are reviewed. RESULTS: A 53-year-old woman came to the neurology clinic with complaints of frontal headaches and intermittent blurry vision. Physical examination showed no remarkable findings. Computed tomography revealed an enhancing sellar and suprasellar mass, with extension into the sphenoid and cavernous sinuses. The patient had a preoperative diagnosis of a clinically nonfunctioning pituitary adenoma and underwent transsphenoidal resection. The biopsy specimen was heavily infiltrated with abnormal plasma cells, which stained exclusively for lambda light chain immunoglobulins. An extensive investigation failed to show evidence of multiple myeloma. In view of these findings, the diagnosis of solitary extramedullary plasmacytoma was made. Postoperatively, the patient received radiotherapy to the pituitary and has remained free of disease for 7 years. Review of the world literature disclosed only 17 previous reports of patients in whom a solitary plasmacytoma or multiple myeloma first appeared as a sellar mass. In each case, the plasmacytoma mimicked a clinically nonfunctioning pituitary adenoma. CONCLUSION: Parasellar plasmacytomas are often mistaken for a nonfunctioning pituitary adenoma. The diagnosis is difficult to make in the absence of overt systemic myeloma. Nevertheless, normal pituitary function associated with severe destruction of the pituitary fossa, cranial neuropathies, and diabetes insipidus are clues that the primary lesion is outside the pituitary gland itself. The current patient is unique in terms of prolonged survival in the absence of systemic myeloma. Perhaps those patients with progression of disease did not have extramedullary tumors because such lesions rarely progress to overt myelomatous disease.

Journal Article↗

PubMed1993

Discordant LFA-1/ICAM-1 expression in a case of secondary plasma cell leukemia associated with subcutaneous plasmacytoma.

We observed a unique case of multiple myeloma that was transformed into plasma cell leukemia presenting with subcutaneous and soft tissue infiltrates. Subcutaneous and minor pelvic soft tissue plasmacytomas and the leukemic transformation were diagnosed in a 72-year-old woman after she had completed 9 months of chemotherapy for IgG kappa multiple myeloma. Immunophenotypic study revealed that leukemic cells in her peripheral blood were positive for ICAM-1 (CD54) but negative for LFA-1 alpha (CD11a) and LFA-1 beta (CD18), whereas infiltrating leukemic cells in the subcutaneous plasmacytoma of the left thigh were positive for LFA-1 alpha and LFA-1 beta but negative for ICAM-1. In addition, intermingling capillary endothelial cells were positive for ICAM-1. Extramedullary soft tissue plasmacytoma is uncommon in association with plasma cell tumors, and the exact mechanism of the development of plasmacytoma is not known. In the present case, however, the discordant expression of LFA-1/ICAM-1 adhesion molecules may have accounted for the distinct patterns of growth and the spread of the subcutaneous plasmacytoma through homing of the LFA-1 alpha+, LFA-1 beta+ leukemic cells to ICAM-1+ endothelial cells.

Aged↗

PubMed1990

Identification of consensus genes expressed in plasmacytomas but not B lymphomas.

We have combined subtractive cDNA and PCR technologies to construct and analyze a plasmacytoma minus a highly differentiated B lymphoma subtractive cDNA library. We detected no plasmacytoma-specific clones by hybridization with differential cDNA probes or the subtractive insert. However, random selection of 115 clones has identified 16 quantitatively subtractive and 39 qualitatively subtractive clones. From these clones we have identified 8 potentially interesting genes. One quantitatively subtractive clone (clone 315) identifies an mRNA that is expressed in most plasmacytoma cell lines, but is expressed at an approximately 10-fold lower level in B and pre-B lymphoma cell lines; preliminary evidence suggests that the expression of this gene is increased by IL-6. From the 31 unrelated qualitatively subtractive clones, we have identified two classes of genes that are expressed in one or none of 8 B lymphomas examined: 1) those expressed in most plasmacytoma and pre-B lymphoma cell lines (clone 70 and clone 260); and 2) those expressed in most plasmacytoma cell lines, but not in any of the ten pre-B lymphomas examined (clones 251, 289A, 289B, 326, 291).

Animals↗

PubMed1996

Plasmacytoma development in mice injected with silicone gels.

Silicone gels derived from commercially obtained implants induce plasmacytomas in 60-70% of highly susceptible BALB/cAn.DBA/2-Idh1-Pep3 congenic mice. In contrast, dimethylpolysiloxane (DMPS) silicone oils with viscosities of 5, 1000 and 12,500 cs fail to elicit these tumors. 1000 cs vinylmethylpolysiloxane is also inactive. Silicone gels, in contrast to the oils, induce a highly inflammatory silicone granuloma. Silicone gels contain chemical components not found in the oils. The chemical component responsible for inducing the permissive environment for plasmacytoma formation has not yet been identified. Silicone gels are well tolerated for long periods of time in mice without adverse effects other than plasmacytoma formation. The response to different gel preparations varies; some are associated with relatively rapid formation of plasmacytomas resembling that seen with pristane, while in others the plasmacytoma formation is extended nearly over a two year period.

Animals↗

PubMed1998

Solitary plasmacytoma in the thoracic spine. Two case reports.

Plasmacytoma of the spine is rather common, but solitary occurrence is not. We report two cases of solitary plasmacytomas in the thoracic spine. A 72 year old male and a 77 year old male presented with progressive paraparesis. In both cases, magnetic resonance images revealed tumors in the thoracic spine which predominantly occupied the posterior elements of the spine with compression of the spinal cord. Abnormal proteinuria and proteinemia were not detected. The tumors were removed and patients' symptoms improved, the tumors were diagnosed by histopathology to be plasmacytomas. Further neuroradiological studies suggested them to be single lesions, so that the final diagnosis was solitary plasmacytomas. Solitary plasmacytoma should be considered for diagnosis of single spinal lesion even without abnormal proteinemia or proteinuria.

Aged↗