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PubMed2004

Extramedullary plasmacytoma: report of two cases with uncommon presentation.

Lymph node infiltration by monoclonal plasma cells can occur either in aggressive forms of myeloma or may represent regional extension of extramedullary plasmacytomas, whereas lymph node plasmacytoma presenting as a solitary extramedullary plasmacytoma is very unusual. We report two cases of lymph node plasmacytomas without systemic disease diagnosed after surgical excision. Clinical remission was achieved after local radiotherapy although one patient relapsed with multifocal extramedullary plasmacytomas 20 months after radiotherapy.

Abdominal Neoplasms↗

PubMed1987

Serum-free medium for growth factor-dependent and -independent plasmacytomas and hybridomas.

A serum-free medium was developed for culture of plasmacytomas and hybridomas that are dependent upon or independent of the presence of specific P388D1-derived polypeptide growth factors. Possibly due to the stringency of requirements for culturing such plasmacytomas, a highly advantageous combination of components was developed. The medium, SFM, contains RPMI 1640, beta-mercaptoethanol, Hepes buffer, reduced glutathione (GSH), selenite (Se), pyruvate, transferrin, albumin, soybean lipids, and low density lipoproteins. A cooperative effect of GSH and Se is observed. SFM supports the continuous, prodigious growth of every B cell line tested, including a variety of the plasmacytomas, hybridomas, myeloma fusion partners and lymphoma cell lines, as well as the macrophage-like cell line P388D1. All of the B cell lines grow equally as well in SFM as in serum-containing medium. Hybridoma lines from mouse-mouse and rat-mouse fusions continue to produce monoclonal antibodies which can then be purified in a single-step procedure. The cells can be cloned out and frozen down in SFM. In addition, the medium is highly effective for establishment of plasmacytoma cell lines from some transplantable plasmacytomas, including early generation tumors.

Animals↗

PubMed1997

Primary plasmacytoma of lymph nodes.

Primary plasmacytoma of the lymph nodes is very rare, and there are fewer than 20 reported cases. These cases appeared to have a better prognosis than other extramedullary plasmacytomas, with rare recurrence and no progression to myeloma after treatment. To better characterize the clinicopathological features and the pathogenesis of primary plasmacytoma of the lymph nodes, we reviewed our consultation files and retrieved seven such cases. The age of presentation ranged from 39 to 76 years (median age, 59 years), with three women and four men. The clinical follow-up varied from 1 to 14 years. All patients presented with enlarged lymph nodes and had an indolent clinical course, except for one patient with slow progression and increasing numbers of bone marrow plasma cells. Five patients were treated with excision only and two with excision and chemotherapy. None of the patients had recurrence or developed multiple myeloma. All cases showed immunoglobulin light chain restriction, four with monotypic lambda and three with monotypic kappa. One patient had extensive nodal amyloid deposition. Four cases had monoclonal heavy chain expression, three with monoclonal immunoglobulin (Ig) G and one with monoclonal IgM. All cases were negative for CD20 and CD43, and six cases expressed CD79a. Overexpression of p53 and bcl-2 was not detected by immunostaining in any of the cases. Epstein-Barr viral (EBV) RNA was not detected in all seven cases by in situ hybridization, and no Kaposi's sarcoma-associated herpesvirus (KSHV) DNA sequences were detected by polymerase chain reaction in five cases. Our results confirm a more favorable outcome and rare progression to multiple myeloma in primary nodal plasmacytomas after excision or chemotherapy. The results of oncoprotein and viral studies suggest that the pathogenesis of primary nodal plasmacytoma may not be due to bcl-2- and p53-associated changes or viral-induced changes by EBV and KSHV.

Adult↗

PubMed2004

[Epstein-Barr virus-associated cutaneous plasmacytoma post-solid organ transplantation].

BACKGROUND: Post-transplantation lymphoproliferative disorders develop in 1 to 10p. 100 of organ transplant recipients and are frequently associated with Epstein-Barr virus (EBV). Among post-transplantation lymphoproliferative disorders, plasmacytoma with cutaneous involvement is exceptional. Association with EBV has been rarely reported in post-transplantation plasmacytomas and the latency type of EBV has never been characterized. We report 2 new cases of cutaneous monotype EBV-related plasmacytomas. CASE-REPORTS: Clinical presentation was a sub-cutaneous tumor on the thigh in the first case and an ulcerated nodule of the leg in the second case, occurring respectively 7 and 8 years after organ transplantation (liver transplantation and heart transplantation). In both lesions, tumor cells exhibited lambda light chain restriction and the association with EBV was confirmed using immunohistochemistry and in situ hybridization. The expression of EBV genes in tumor cells demonstrated type III latency. DISCUSSION: The classification of post-transplantation lymphoproliferative disorders is not well defined and some authors retain 3 categories. Among the latter, plasmacytomas have been rarely described. Cutaneous involvement is reported in 4 cases and an association with EBV in only 2 cases without description of viral latency. Clinical and histological features of post-transplantation plasmacytomas appear polymorphic. We report EBV-association in both cases, with a type III latency clearly demonstrated in one case, as has been reported in other lymphoproliferative diseases in patients with congenital or acquired immunodeficiency. We also discuss various possible therapeutic strategies for post-transplantation lymphoproliferative disorders.

Epstein-Barr Virus Infections↗

PubMedDate not supplied

Solitary plasmacytoma of bone and soft tissues.

PURPOSE: To define the optimal treatment and outcomes for patients with solitary plasmacytoma of bone and soft tissue. METHODS: Review of the literature. RESULTS: Solitary plasmacytomas are uncommon and account for less than 5% of plasma cell neoplasms. Solitary plasmacytomas of bone (SPB) usually occur in the vertebra and skull and are more common than extramedullary plasmacytomas (EMP) that almost always arise in the head and neck and may spread to regional lymph nodes. The optimal treatment is moderate-dose radiotherapy (40-50 Gy) and occasionally surgery. Adjuvant chemotherapy does not improve survival. Patients with EMP have a relatively low risk of progressing to multiple myeloma and have improved survival compared with those who present with SPB. CONCLUSION: Solitary plasmacytoma is an uncommon neoplasm that often arises in the head and neck. Optimal treatment is moderate-dose radiotherapy. Prognosis is relatively good and is better for patients with EMP compared with those presenting with SPB.

Bone Neoplasms↗

PubMedDate not supplied

Plasmacytoma and upper airway obstruction.

Extramedullary plasmacytomas are hematologic malignancies that occur primarily in the head and neck region. They usually involve the submucosal lymphoid tissue of the nasopharynx or paranasal sinuses and present as soft tissue masses, but have not been previously reported to cause airway obstruction. In general, detection of plasmacytoma antedates the eventual development of the systemic hematologic malignancy, multiple myeloma, by months or years. We describe a unique case of acute upper respiratory tract obstruction secondary to compression by an extramedullary plasmacytoma occurring in the neck of a patient with history of long-standing multiple myeloma. Upper airway obstruction may be a manifestation of untreated plasmacytoma. It is imperative for otolaryngologists and head and neck surgeons to be familiar with this entity because total excision, as well as radiation therapy, for plasmacytomas can be curative in patients without underlying overt plasma cell dyscrasias.

Acute Disease↗

PubMed1978

Lymphocyte defect in plasmacytoma-bearing mice.

Multiple myeloma is often associated with humoral immunodepression in both man and mouse. When mice bearing the humorally immunodepressive plasmacytomas TEPC-183 and SPQC-11 were injected with SRBC, the rise of serum haemolysins was significantly less than that of non-tumour-bearing mice. Mice with the plasmacytomas MPC-11 and MOPC-315 have an antibody response similar to normal mice when injected with SRBC. Following immunization, normal mice and those bearing MPC-11 showed a 2- to 3-fold increase in total spleen lymphocytes. Mice bearing TEPC-183 or SPQC-11, the plasmacytomas causing an impaired antibody response, has significant increase in spleen lymphocytes under the same conditions. Mice bearing MOPC-315 had a very high initial count of spleen lymphocytes, which did not further increase upon immune stimulation.Incubation of lymphocytes from plasmacytoma-bearing mice with PHA did not produce an increase in TdR incorporation and in some cases even caused a decrease in TdR incorporation.Lymphocytes from mice bearing TEPC-183, SPQC-11, and MOPC-315 incorporated less TdR in response to LPS than did normal mice. On the other hand, mice bearing MPC-11 incorporated about as much TdR as did normal mice following LPS stimulation. Thus, the defect in the ability to respond to LPS in vitro correlated with the lack of an increase of spleen lymphocytes in mice bearing these tumours following antigenic stimulation in vivo.No immunodepressive properties of serum from mice with plasmacytoma could be detected.

Animals↗

PubMed2001

Localized amyloidosis and extramedullary plasmacytoma involving the larynx of a child.

Extramedullary plasmacytoma of the larynx and localized laryngeal amyloidosis are 2 uncommon disease entities that are exceedingly rare in children. We report a case of a 12-year-old girl presenting with progressive hoarseness who was subsequently found to have extramedullary plasmacytoma coexisting with localized amyloidosis involving the larynx. Results from the immunohistochemical and molecular studies showed that the tumor cells of the plasmacytoma were monoclonal (kappa-restricted), strongly supporting their neoplastic nature. The biochemical nature of the amyloid deposits was also shown to be of kappa immunoglobulin light chain, suggesting the pathogenetic relationship between the plasmacytoma and amyloid deposition in the larynx of this patient. There was no other evidence of malignancy or amyloidosis elsewhere. On a follow-up period of 4 years, this patient was well and asymptomatic. We believe that this represents the first case in the literature showing the coexistence of extramedullary plasmacytoma and localized amyloidosis of the larynx in children. This case also supports the concept that localized laryngeal amyloidosis may be a manifestation of low-grade B-cell neoplasms.

Amyloidosis↗

PubMed1987

A plasmacytoma-specific factor binds the c-myc promoter region.

We used an electrophoretic mobility-shift assay to study proteins that bind to sequences in the 5' flanking region of the murine c-myc gene. By comparing the DNA-protein complexes formed with extracts from cells representing earlier stages of B-cell development with those from plasmacytomas, we identified a plasmacytoma-specific protein that binds to a region within the c-myc promoter. Five other regions of this promoter show extensive sequence-specific binding, but the binding is not clearly B-cell stage-specific. Methylation-interference and o-phenanthroline/copper-protection experiments identified a single plasmacytoma-specific protein binding site 290 base pairs 5' of the transcription start site P1. Homologues of a core sequence, d(AGAAAGGGAAAGGA), within the 25-base-pair binding site are found at three additional sites in the murine c-myc locus. The plasmacytoma-specific occurrence of this protein suggests that it may play a role in the transcriptional repression of the normal c-myc gene observed in plasmacytomas.

Animals↗

PubMed1992

Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice.

The mechanisms through which pristane or mineral oil can induce plasmacytomas in BALB/c or NZB mice are not fully understood, but involvement of interleukin 6 (IL-6), a growth factor for plasmacytomas and myelomas, has been strongly suggested. To clarify the role of IL-6 in plasmacytomagenesis, a human IL-6 cDNA was introduced into mouse germ lines under the transcriptional control of the murine major histocompatibility complex class I (H-2Ld) promoter. IL-6 transgenic mice of C57BL/6 origin developed a massive plasmacytosis but not plasmacytomas. However, introduction of BALB/c genetic background into IL-6 transgenic mice could generate monoclonal transplantable plasmacytomas with the chromosomal translocation t(12;15). These results provide firm evidence of the critical role of IL-6 in the plasmacytoma development.

Animals↗

PubMed1975

Alteration of immunoglobulin phenotype in cell culture-adapted lines of two mouse plasmacytomas.

Murine plasmacytomas can be adapted to continuous in vitro culture by alternate passage between culture and animal. We have found that the kinetics of adaptation reflect a selection for the growth of variant plasmacytoma cells. The inclusion of an altered immunoglobulin phenotype in such variant cells could explain the Ig-producing variants that we observed in two of six transplantable lines of plasmacytomas that were adapted to culture. The first variant, an IgM-producing cell line (104-76), was adapted from a transplanted line of MOPC 104E that had stopped producing IgM with binding specificity for alpha1-3 Dextran. Unlike MOPC 104E, the IgM of 104-76 contains kappa- instead of lambda-light chains and probably contains an altered or different mu-heavy chain. A second variant (352-57) was found in an IgG2b-producing tumor (MOPC 352) which was induced in a BALB/c mouse strain (CB-6) that carried Ig genes of the C57BL/Ka allotype. This cell line apparently switched from producing IgG2b molecules of the C57BL allotype (H9) and of a known idiotype to IgG1 molecules of the BALB/c allotype (F19) without the idiotype marker. The propagation of a biclonal plasmacytoma from the time of original tumor induction does not appear as a likely explanation for these results. Rather, we seem to be dealing with plasmacytoma variants or with the possible induction of secondary tumors of host origin.

Animals↗

PubMed1986

Increased susceptibility of old mice to plasmacytoma induction.

Because multiple myeloma is a malignancy that appears in aging humans, the murine plasmacytoma model was selected to investigate the association between tumor formation, age, and immunity. Plasmacytomas were induced in young, middle-aged, and old BALB/c mice by intraperitoneal injections of pristane. Old mice were more vulnerable than middle-aged mice who were more vulnerable than young mice to histopathologically documented plasmacytoma formation. The difference between old and young mice was significant (p less than .05). The increased frequency of plasmacytomas was associated with decreased in vitro immune parameters in pristane-treated mice compared with age-matched saline-treated controls. The decrease was especially marked with T cell responses (mitogenic responses to concanavalin A, phytohemagglutinin, or allogeneic spleen cells) and natural killer (NK) cell activity. It was less striking with the predominantly B-cell parameters of mitogenic response to lipopolysaccharide (LPS) and LPS-induced plaque-forming cells. These findings support the hypothesis that old mice have increased vulnerability to plasmacytoma formation because of diminished NK and T cell activities.

Age Factors↗

PubMed2005

CD56-positive small round cell tumor: osseous plasmacytoma manifested in osteolytic tumors of the iliac bone and femora.

Monoclonal gammopathy of undetermined significance does not overexpress cluster of differentiation (CD) 56, but plasma cell myeloma frequently overexpressed it. However, plasma cell leukemia and extramedullary plasmacytoma usually down-regulate CD56 expression. Plasmacytoma, especially 'solitary plasmacytoma of bone', is difficult to diagnose as plasma cell neoplasm, because it occasionally appears similar to other bone tumors, both clinically and pathologically, and is rarely accompanied by monoclonal protein in the serum or urine. The present case was a patient with an osteolytic 'small round cell tumor' of the iliac bone, which also invaded the femora. An immunohistopathological finding of CD56 expression played a key role in making a diagnosis. The definitive diagnosis of plasmacytoma was made based on the electron microscopic findings. The plasma cells which infiltrated her sternum showed the same restriction to kappa light chain expression in their cytoplasms as that of the iliac bone tumor cells, but did not express CD56. Locally infiltrating osteolytic bone tumors should be examined for surface immunoglobulin light chains as well as CD56 expression when plasmacytoma is suspected.

Adult↗

PubMed1975

Genetics of susceptibility to plasmacytoma induction. I. BALB/cAnN (C), C57BL/6N (B6), C57BL/Ka (BK), (C times B6)F1, (C times BK)F1, and C times B recombinant-inbred strains.

Plasmacytomas were found in 58% of 373 BALB/cAnN (C) mice given three 0.5-ml doses of mineral oil (Bayol F or light mineral oil) or 2,6,10,14-tetramethylpentadecane (pristane) ip. The incidence of plasmacytomas in C57BL/6N (B6), C57BL/Ka (BK), (C times B6)F1 and (C times BK)F1 was 6.4, 0, 11.5, and 16.5%, respectively. The plasmacytomas occurred in old B6 mice, in contrast to their early appearance in strain C mice. The incidence of plasmacytomas in mineral oil-treated or pristane-treated C times B recombinant-inbred (Rl) strain mice was 28.3% in C times BD, 17.5% IN C times BE, 36.5% IN C times BG, 0% in C times BH, 2.9% in C times Bl, 48% in C times BJ, and 4.3% in C times BK. C times BD, C times BG, and C times BJ strains were considered susceptible to plascytoma induction by mineral oil or pristane; C times BE had a low susceptibility, and C times BH, C times Bl, and C times BK were resistant. The results suggested that there were only a few gene difference between C and B6 or BK that determined susceptibility or resistance to plasmacytoma induction, and that B6 and BK have at least one dominant resistance gene. The distribution pattern of susceptibility and resistance in the C times B Rl strains suggested the presence of a resistance gene on chromosome 9, linkage group II.

Age Factors↗

PubMed1994

Identification of a locus control region in the immunoglobulin heavy-chain locus that deregulates c-myc expression in plasmacytoma and Burkitt's lymphoma cells.

In murine plasmacytoma and human Burkitt's lymphoma cells, one allele of c-myc is translocated into one of the immunoglobulin loci, resulting in a characteristic pattern of deregulated c-myc transcription. Translocation events between c-myc and the IgH locus segregate c-myc and the IgH intron enhancer to different reciprocal products in all plasmacytomas and in most Burkitt's lymphoma cells, suggesting that an additional element(s) capable of affecting c-myc expression over a large and variable distance must exist in the IgH locus. The region 3' of the IgH C alpha gene contains four tissue-specific and cell stage-specific DNase I hypersensitive sites (HSs), two of which map to the late B cell-specific 3' C alpha enhancer. We report here that DNA sequences comprising the two other 3' C alpha HSs contain potential protein-binding motifs for trans-activators commonly associated with immunoglobulin enhancers and that these sites can function as cell stage-specific enhancers in transient B cell assays. A DNA fragment containing all four HSs (HS1234) synergistically activates c-myc transcription in plasmacytoma and Burkitt's lymphoma cells in transient assays and induces high-level transcription, a promoter shift from P2 to P1, and an increase in readthrough transcription in stable transfections. Furthermore, plasmacytoma clones stably transfected with a HS1234-linked c-myc construct express c-myc in a position-independent, copy number-dependent manner. These results suggest that HS1234 may function as a locus control region (LCR), deregulating c-myc expression in t(15;12) plasmacytomas, as well as potentially contributing to aspects of normal IgH chain expression.

Animals↗

PubMed2005

Plasmacytoma relapses in the absence of systemic progression post-high-dose therapy for multiple myeloma.

Autologous (ASCT) and allogeneic stem cell transplantations (alloBMT) are well-established therapies for multiple myeloma. However, patients continue to relapse at a constant rate. We present here 15 out of 163 patients who underwent SCT and relapsed with plasmacytomas only without evidence of bone marrow disease progression (14/147 post-ASCT and 1/16 post-alloBMT). The median time from SCT to plasmacytoma relapse was 24 months. The sites of plasmacytoma included bone, skin, rectum, and testicles. Five patients were treated with local radiotherapy, while seven patients received a combination of radiotherapy and chemotherapy or thalidomide, and two patients received chemotherapy alone with or without thalidomide. The recipient of alloBMT was initially treated with VAD-chemotherapy and local radiotherapy followed by a mini-allograft from the original donor. Eleven patients died at a median of 10 months following diagnosis of the plasmacytoma. Four are still alive, 12-20 months post-plasmacytoma diagnosis. These cases of unconventional disease recurrence are likely to be seen due to sub-clinical seeding of tumour cells suggestive of the presence of an extramedullary (EM) clone of plasma cells with a high degree of chemoresistance. We also review all the available data in the literature for the optimal therapy for patients with isolated EM relapse.

Aged↗

PubMedDate not supplied

Huge IgD plasmacytoma in the abdomen presenting coagulation necrosis.

A 65-year-old Japanese woman was diagnosed in 1996 with a pathological fracture of the left femur caused by immunoglobulin D-type myeloma (IgD myeloma). She responded well to combination chemotherapy followed by irradiation. The patient experienced renal failure and became dependent on haemodialysis. In 1999, large plasmacytomas developed in the abdomen and left humerus. The abdominal tumour appeared to induce gastroduodenal ulcers and jejunal obstruction. We initiated irradiation therapy without chemotherapy to prevent further growth of the plasmacytoma, although treatment-resistant gastroduodenal ulcers developed. Continued blood loss from the gastroduodenal ulcers resulted in a deterioration in the patient's health, which prevented successful haemodialysis. An autopsy showed that the plasmacytoma had undergone coagulation necrosis. We conclude that the use of combination chemotherapy with topical irradiation was an acceptable treatment measure against IgD plasmacytoma; irradiation without chemotherapy was the most likely cause of the coagulation necrosis seen in the plasmacytoma at autopsy.

Abdominal Neoplasms↗

PubMed1997

Radiotherapy in the treatment of solitary plasmacytoma.

Solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are rare. High local control rates are reported with radiotherapy, although the optimal dose and extent of radiotherapy portals remains controversial. Between 1983 and 1993, 30 patients with solitary plasmacytoma were seen at the Regional Cancer Centre, Trivandrum, India. 23 patients had SPB and seven EMP. The mean age was 52 years and the male to female ratio 3.2:1. Diagnosis of SPB was confirmed by biopsy in 16 patients and tumour excision in seven. 20 patients received megavoltage radiotherapy to the bone lesion with limited margins, and one received chemotherapy. Two patients who underwent complete tumour excision received no further treatment. All seven patients with EMP received megavoltage radiotherapy, four following biopsy and three after tumour excision. Local control was achieved in all patients with SPB. Nine progressed to multiple myeloma and one developed a solitary plasmacytoma in another bone. Six patients with EMP achieved local control. Three later progressed to multiple myeloma and one had local relapse. Median time to relapse was 28 months in SPB and 30 months in EMP. 5-year overall survival rates were 82% and 57% for patients with SPB and EMP, respectively. The corresponding progression free survival rates were 55% and 50%, respectively. Age, sex, site of tumour, serum M protein and haemoglobin levels did not significantly influence progression free survival. The extent of surgery, radiotherapy dose or time to relapse were not significant prognostic factors. Radiotherapy appears to be an effective modality of treatment of solitary plasmacytoma. No dose-response relationship is observed, and high local control rates are achieved with limited portals. Progression to multiple myeloma is the commonest pattern of failure, although no prognostic factors for progression are identified. The role of chemotherapy in preventing disease progression needs further evaluation.

Adult↗