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PubMed1994

Induction of plasmacytomas with silicone gel in genetically susceptible strains of mice.

BACKGROUND: Plasmacytomas can be induced in high frequency in susceptible strains of mice by the intraperitoneal introduction of plastics or paraffin oils, including the chemically defined oil pristane (2,6,10,14-tetramethylpentadecane). These materials persist in the peritoneal cavity, where they induce chronic inflammation during the long periods before plasmacytomas develop. Such plasmacytomas appear to arise from B cells carrying chromosomal translocations that affect c-myc transcription. PURPOSE: Because silicone gels are in widespread medical use and share many of the characteristics of other materials known to be inducers of plasmacytomas, we wished to determine their capacity to induce plasmacytomas in mice. METHODS: In a series of parallel experiments, corn oil, pristane, silicone oil (dimethylpolysiloxane), or silicone gel from commercially obtained mammary implants was injected intraperitoneally into plasmacytoma-susceptible BALB/cAnPt-A and congenic BALB/cAnPt.DBA/2-Idh1-Pep3 mice, as well as into plasmacytoma-resistant C57BL/6N, C3H/HeJ, DBA/2N, and (BALB/c x DBA/2)F1 mice. Mice were examined at least once every 2 weeks for signs of abdominal tumor or weight loss and screened every 4-6 weeks for peritoneal plasmacytoma cells by peritoneal lavage. Tissues were examined by histologic and immunohistochemical techniques. Metaphase chromosome spreads were made from ascitic plasmacytomas without Colcemid treatment, and metaphase plates were G-banded according to standard techniques. The t(12;15) or t(6;15) translocation chromosomes were identified under the microscope in at least five metaphase plates of high banding quality. Mice were autopsied 125-400 days after the injection of test material. Gas chromatography and mass spectrometry were utilized to determine the composition of the silicone oil and silicone gel used in the injections. RESULTS: The silicone gels tested induced plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA/2-Idh1-Pep3 mice. Neither corn oil used as a control nor 1000-centistoke or 12,500-centistoke dimethylpolysiloxane induced plasmacytomas in these mice. The plasmacytomas were transplantable in syngeneic hosts. Cytogenetic studies of 41 silicone-induced plasmacytomas showed that 30 had t(12;15) translocations, eight had t(6;15) translocations, and three had no translocations. CONCLUSIONS: The silicone gels used in mammary implants, which contain a complex mixture of different siloxanes, induced peritoneal plasmacytomas in genetically susceptible mice. Silicone gels provide new chemically defined materials that are effective inducers of plasmacytomas in BALB/cAnPt-A and BALB/cAnPt.DBA/2-Idh1-Pep3 mice. Further studies will be required to determine which of the components of these gels are the active materials.

Animals↗
PubMed1984

Osteosclerotic plasmacytoma of maxillary bone (orbital floor).

Plasma cell neoplasms have been classified as multiple myeloma, solitary plasmacytoma and extramedullary plasmacytoma. They are usually considered as osteolytic lesions of bone except for the rare occurrence of osteosclerotic lesions. This paper describes the first reported osteosclerotic plasmacytoma of the maxillary bone and orbital floor. The difficulties in establishing a diagnosis and the relationship to other plasma cell neoplasms are discussed. Osteosclerotic plasmacytomas are a rare variant of plasma cell tumors which usually produce osteolytic lesions rather than bony sclerosis. Sixty-eight patients with the osteosclerotic variant have appeared in the world literature, with an overall incidence of about 1 per cent in a large series of plasma cell neoplasms (Dreidger and Pruzanski, 1979). There have been only six previous cases of solitary osteosclerotic plasmacytomas reported (Morley and Schweiger, 1964; Roberts et al., 1974; Rodriguez et al. 1976; Rushton, 1965; Schneinker, 1938; Brigham Medical Review, 1961) involving spine, sternum, or rib. None have previously been reported in the head and neck area. Plasma cell tumors have been classified into multiple myeloma, solitary plasmacytomas of bone, and extramedullary plasmacytomas. Multiple myeloma is a disseminated plasma cell malignancy characterized by the production of homogeneous immunoglobulins (whole or fragments) which appear in the serum and urine. Plasma cell tumors can also occur as solitary plasmacytomas, usually in bone, but also in soft tissue. With time, most solitary plasmacytomas develop disseminated disease with all the characteristics of multiple myeloma (Wiltshaw, 1976). Extramedullary plasmacytomas arise in soft tissue rather than bone, and primarily occur in the head and neck region. Clinically, they remain localized and less frequently develop into disseminated myeloma.

Female↗
PubMed1985

Inhibition of plasmacytoma development in BALB/c mice by indomethacin.

Indomethacin given continuously in the drinking water (20 micrograms/ml) to BALB/cAn pi mice during the latent period of pristane-induced plasmacytoma development dramatically reduced the plasmacytoma incidence from 34.9 to 2.2%. Additionally, indomethacin given from day 0 to 120 or begun as late as 60 d after a single injection of 1.0 ml pristane was also highly effective in reducing the development of plasmacytomas. Indomethacin treatment did not prevent the formation of a peritoneal inflammatory exudate or peritoneal oil granulomatous tissue, although it had a mild inhibitory effect on the intensity of the cellular inflammation, particularly after extensive treatment of greater than 100 d. Indomethacin treatment reduced the incidence of arthritis by 50%. A major effect of indomethacin treatment was a reduction in the appearance of microscopic plasmacytomas that appear in the oil granuloma before plasmacytomas can be detected by routine sampling of the peritoneal exudate. Between days 116 and 181, 16 of 20 mice given 0.5 ml pristane were found to have foci of plasmacytoma cells, while only 2 of 20 indomethacin-treated mice had foci-containing plasmacytoma cells. The number of mice with microscopic foci in the pristane-treated group greatly exceeded the expected incidence of plasmacytomas (22%) at this dose of pristane. The growth of primary plasmacytomas in transplant that is dependent on the pristane-conditioned peritoneal environment was not inhibited by indomethacin treatment. The role of indomethacin in inhibiting plasmacytoma development was not established; two possibilities are that it inhibits production of mutagenic and tissue destructive oxidants by inflammatory cells, and it inhibits prostaglandin synthesis and intracellular production of oxidant biproducts.

Animals↗
PubMed1977

Tumor immunity to murine plasma cell tumors. III. Detection of common and unique tumor-associated antigens on BALB/c, C3H, and NZB plasmacytomas by in vivo and in vitro induction of tumor-immune responses.

Tumor-associated antigens (TAA) were demonstrated on plasmacytomas derived from BALB/c, NZB, and C3H mouse strains, by in vivo and in vitro techniques. By immunizing the appropriate F1 hybrid mice with these tumors, it was possible to show that all the plasmacytomas expressed cross-reactive tumor-associated transplantation antigens. When cytotoxic lymphocytes (CL) were induced in vitro by the coculturing of syngeneic or F1 hybrid spleen cells with irradiated plasmacytoma cells, "shared" and "unique" plasmacytoma TAA were demonstrable. This was accomplished by inducing CL in vitro against one syngeneic plasmacytoma and assaying for lytic activity on a range of 51Cr-labeled BALB/c, NZB and C3H plasmacytoma cells in vitro. In a second in vitro assay, unlabeled plasmacytoma cells were tested for their ability to inhibit the lysis of a particular 51Cr-labeled plasmacytoma, with the use of CL induced in vitro against it. The possibility that these TAA were "self" antigens was excluded by demonstrating in the inhibition assay that they were not present on T lymphomas and spleen cells of the same strain, and that CL "autosensitized" in vitro could not significantly lyse 51Cr-labeled plasmacytoma cells in vitro. From both in vivo and in vitro studies of immunity to these tumors, it was concluded that any one plasmacytoma line possesses multiple TAA of both shared and unique types.

Animals↗
PubMed1984

[Chromosome translocations and the activation of C-myc oncogene in mouse plasmacytomas].

Plasmacytomas can be induced in BALB/c mice by three different agents: (1) Mineral oil, (2) Solid plastics such as diffusion chambers, and (3) Abelson murine leukemia virus plus pristane. We examined chromosome aberrations in mouse plasmacytomas induced by each of the three agents. Most of plasmacytomas showed the specific translocations of chromosomes between either No. 12 and No. 15 or No. 6 and No. 15. These chromosome translocations were common to all plasmacytomas induced by different agents. The specific breakpoints were at 12F2 where IgH genes appear to locate, and 6C2 where kappa light chain genes might be located, and 15D2/3 where c-myc oncogene appears to locate. However, we have found very recently a few plasmacytomas which have no translocations of chromosomes. The subregion (s) of one copy of chromosome 15 which is called D1:D2 appears to be deleted in these plasmacytomas. In the next study, we examined the relationship of chromosomal aberrations to the activation of c-myc oncogene. Not only the plasmacytomas with chromosome translocations, but also the translocation-negative plasmacytomas showed the either rearrangement or germline type of c-myc DNA. Rearranged c-myc transcript was found only in plasmacytomas with the 12;15 translocation. However, not all plasmacytomas belonging to this group expressed the altered c-myc RNA transcript. Our experiments indicated that the germline type c-myc RNA was 2.4 kb and the rearranged c-myc RNA was mostly 1.8 kb in length. Concerning the c-myc DNA, the germline type was 21 kb and the rearranged type of c-myc DNA was estimated, mostly, to be 14 kb by EcoRI digestion.

Animals↗
PubMed2002

Secondary extramedullary plasmacytoma involving the pancreas.

Extramedullary plasmacytoma is a rare variant of plasma cell tumor involving organs outside the bone marrow. The vast majority of extramedullary plasmacytomas present as a secondary tumor of systemic myelomatosis of the bone marrow. We experienced a patient with extramedullary plasmacytomas of the head and tail of the pancreas presenting as secondary masses from extramedullary plasmacytoma of the maxillary sinus that had been treated 5 years previously. A 38-year-old Japanese man had undergone radiation therapy for an extramedullary plasmacytoma of the maxillary sinus 5 years before the current presentation. He experienced severe upper abdominal pain in November 1999, when laboratory data showed elevation of the serum amylase level. Computed tomography showed two isodensity masses, in the head and tail of the pancreas. Angiography showed two hypervascular masses, one in the head and the other in the tail of the pancreas, and encasement of the portal vein trunk junction. Laparotomy was performed, with the tentative diagnosis of extramedullary plasmacytoma of the pancreas, in order to obtain a definite diagnosis. Intraoperative biopsy revealed that the two pancreatic masses were extramedullary plasmacytomas. External radiation therapy was performed after the operation. When a pancreatic mass is noticed in patients with a history of plasmacytoma, secondary extramedullary plasmacytoma of the pancreas should be considered as a differential diagnosis.

Adult↗
PubMed1983

Increased expression of myc-related oncogene mRNA characterizes most BALB/c plasmacytomas induced by pristane or Abelson murine leukemia virus.

RNA blots of poly(A)-containing RNA from normal livers and spleens and from a number of transplantable hematopoietic and lymphoid BALB/c tumors, including early and late generation plasmacytomas, were hybridized with probes for four onc genes. abl RNA was abundant only in those tumors producing Abelson virus, bas RNA was found in approximately equal amounts in normal tissues and plasmacytomas, and myb RNA was absent in normal liver and plasmacytomas. Normal liver and spleen RNA showed faint traces of myc hybridization, but myc RNA was increased in most plasmacytomas. In one plasmacytoma, TEPC 1165, a particularly abundant amount of myc RNA was found, principally as a 3.5-kilobase band. In the other plasmacytomas, bands of 2.4- or 1.8-kilobase myc RNA were found. Southern blots of DNA from tumors that contained 2.4-kilobase or larger myc RNA showed myc hybridization to an EcoRI fragment of about 21 kilobase pairs, similar to the myc band in normal DNA. EcoRI digests of DNA from two tumors that expressed myc RNA of 1.8 kilobases showed an additional smaller myc band, suggesting that the myc gene is rearranged in these plasmacytomas. The basis for increased myc gene transcription in plasmacytomas is not understood, but the evidence suggests that different mechanisms may be operating in different plasmacytomas. Apparently, neither myc gene amplification nor myc gene rearrangement is required for increased myc transcription.

Abelson murine leukemia virus↗
PubMed1997

Previously hidden chromosome aberrations in T(12;15)-positive BALB/c plasmacytomas uncovered by multicolor spectral karyotyping.

The majority of BALB/c mouse plasmacytomas harbor a balanced T(12;15) chromosomal translocation deregulating the expression of the proto-oncogene c-myc. Recent evidence suggests that the T(12;15) is an initiating tumorigenic mutation that occurs in early plasmacytoma precursor cells. However, the possible contribution of additional chromosomal aberrations to the progression of plasmacytoma development has been largely ignored. Here we use multicolor spectral karyotyping (SKY) to evaluate 10 established BALB/c plasmacytomas in which the T(12;15) had been previously detected by G banding. SKY readily confirmed the presence of this translocation in all of these tumors and in three plasmacytomas newly identified secondary cytogenetic changes of the c-myc-deregulating chromosome (Chr) T(12;15). In addition, numerous previously unknown aberrations were found to be scattered throughout the genome, which was interpreted to reflect the general genomic instability of plasmacytomas. Instability of this sort was not uniform, however, because only half of the tumors were heavily rearranged. Seven apparent hot spots of chromosomal rearrangements (40% incidence) were identified and mapped to Chrs 1B, 1G-H, 2G-H1, 4C7-D2, 12D, 14C-D2, and XE-F1. Two of these regions, Chr 1B and Chr 4C7-D2, are suspected to harbor plasmacytoma susceptibility loci; Pctr1 and Pctr2 on Chr 4C7-D2 and as yet unnamed loci on Chr 1B. These results suggest that secondary chromosomal rearrangements contribute to plasmacytoma progression in BALB/c mice. To evaluate the biological significance of these rearrangements, SKY will be used in follow-up experiments to search for the presence of recurrent and/or consistent secondary cytogenetic aberrations in primary BALB/c plasmacytomas.

Animals↗
PubMed2005

Primary extramedullary plasmacytoma and multiple myeloma: phenotypic differences revealed by immunohistochemical analysis.

Primary extramedullary plasmacytomas are infrequent, typically solitary, plasma cell neoplasms that generally pursue an indolent clinical course but may, rarely, convert to multiple myeloma. Phenotypic differences between these two entities are not well defined. Twenty-eight cases of primary extramedullary plasmacytoma and 26 cases of both medullary (n = 17) and extramedullary (n = 9) multiple myeloma were analysed for the expression of proteins known to play a role in the biology of multiple myeloma. Immunohistochemistry was performed on paraffin wax sections using antibodies against cyclin D1, Bcl-2, Bcl-xL, p27, p21, p53, MIB1, CD20, and CD56. Twenty-three extramedullary plasmacytomas were localized in the upper aerodigestive tract, four in the lymph nodes, and one in the testis. There was a strong male predominance (M : F = 6 : 1). None of the patients died from the disease or progressed to multiple myeloma (mean follow-up 50 months). Nine patients developed local relapse and one patient's tumour evolved into a B-cell non-Hodgkin's lymphoma. In contrast to both intra- and extra-medullary multiple myeloma, extramedullary plasmacytoma showed absence of cyclin D1 (p < 0.001) and infrequent expression of CD56 (p < 0.001). Furthermore, extramedullary plasmacytomas were characterized by weaker staining for Bcl-2 protein and rare overexpression of p21 and p53. In comparison to extramedullary multiple myeloma, extramedullary plasmacytoma showed a more mature morphology and lower proliferation indices (p = 0.008). There was no association between the phenotypic parameters investigated and clinical outcome in extramedullary plasmacytoma. In summary, extramedullary plasmacytoma and multiple myeloma show significant immunophenotypic differences, some of which may be of both diagnostic utility and biological relevance.

Adult↗
PubMed1998

Plasmacytomas of the head and neck.

Plasmacytomas are rare tumors that often appear in the head and neck region and are characterized by a monoclonal proliferation of plasma cells. On both clinical presentation and pathologic examination these tumors may be confused with more common tumors of the head and neck. The purpose of this article is to review our experience with these rare neoplasms, with emphasis on clinical, pathologic, and therapeutic features. On retrospective chart review, we identified 20 patients with the diagnosis of plasmacytoma of the head and neck region at the Cleveland Clinic Foundation between 1976 and 1993. Records were reviewed with regard to initial symptoms, location of the neoplasm, diagnostic evaluation, treatment modalities, and survival. Of the 20 cases we identified, the tumor arose in the sinonasal/nasopharyngeal region in 11 (55%). Two cases (10%) represented medullary plasmacytomas, arising in the clavicle and presenting as supraclavicular masses. The mean follow-up was 60.2 months (range 6 to 131 months). In 15 of the 20 cases, immunohistochemistry staining for immunoglobulin light chain production was conducted. One of the two cases (50%) classified as medullary plasmacytoma demonstrated conversion to multiple myeloma, whereas only 2 of 18 cases of extramedullary plasmacytoma (11%) converted to multiple myeloma. The primary modality of treatment was radiation therapy with typical doses of 4500 to 6000 cGy. Kaplan-Meier survival estimates demonstrated 95% survival at 1 year, 82% survival at 5 years, and 10-year estimated survival of 72%. Plasmacytomas of the head and neck region are rare and on initial evaluation must be distinguished from multiple myeloma. The diagnostic evaluation includes appropriate radiologic and pathologic studies including immunohistochemistry. Despite the typical presentation as a locally destructive tumor, plasmacytomas are highly radiosensitive, and 70% to 80% survival may be obtained with the use of radiotherapy. Patients with plasmacytomas require long-term follow-up to detect conversion to multiple myeloma.

Adult↗
PubMed1999

Restricted immunoglobulin variable region (Ig V) gene expression accompanies secondary rearrangements of light chain Ig V genes in mouse plasmacytomas.

The many binding studies of monoclonal immunoglobulin (Ig) produced by plasmacytomas have found no universally common binding properties, but instead, groups of plasmacytomas with specific antigen-binding activities to haptens such as phosphorylcholine, dextrans, fructofuranans, or dinitrophenyl. Subsequently, it was found that plasmacytomas with similar binding chain specificities not only expressed the same idiotype, but rearranged the same light (V(L)) and heavy (V(H)) variable region genes to express a characteristic monoclonal antibody. In this study, we have examined by enzyme-linked immunosorbent assay five antibodies secreted by silicone-induced mouse plasmacytomas using a broader panel of antigens including actin, myosin, tubulin, single-stranded DNA, and double-stranded DNA. We have determined the Ig heavy and light chain V gene usage in these same plasmacytomas at the DNA and RNA level. Our studies reveal: (a) antibodies secreted by plasmacytomas bind to different antigens in a manner similar to that observed for natural autoantibodies; (b) the expressed Ig heavy genes are restricted in V gene usage to the V(H)-J558 family; and (c) secondary rearrangements occur at the light chain level with at least three plasmacytomas expressing both kappa and lambda light chain genes. These results suggest that plasmacytomas use a restricted population of B cells that may still be undergoing rearrangement, thereby bypassing the allelic exclusion normally associated with expression of antibody genes.

Amino Acid Sequence↗
PubMed1998

Solitary plasmacytoma of the skull: a case report.

Solitary plasmacytoma of the skull is very rare and only 35 cases have been reported in the English literature. It remains controversial whether solitary plasmacytoma of the skull is essentially identical with solitary plasmacytoma of bone or not. Solitary plasmacytoma of bone including solitary plasmacytoma of the skull is characterized by a radiologically solitary bone lesion, neoplastic plasma cells in the biopsy specimen, fewer than 5% plasma cells in bone marrow, less than 2.0 g/dl monoclonal protein in the serum when present and negative urine test for Bence Jones protein (monoclonal light chain). Solitary plasmacytoma of bone tends to disseminate or progress to multiple myeloma even as long as 7-23 years after presentation. We report the first case of solitary plasmacytoma of the skull in which both beta2-microglobulin for detection of early renal disturbance and neoplastic plasma cell labeling index for detection of DNA synthesis were examined in order to predict the clinical course of solitary plasmacytoma of the skull.

Female↗
PubMed1984

Specific chromosome translocation in pristane-induced plasmacytomas of NZB mice.

The karyotypes of 3 pristane (2,6,10,14-tetramethyl-pentadecane)-induced NZB mouse plasmacytomas producing IgA (plasmacytoma TEPC-3660), IgG3K (plasmacytoma TEPC-6583), and IgG2aK plus IgG3K (plasmacytoma TEPC-6906) were studied in early transplantation generations by the combined Hoechst 33258-quinacrine mustard banding method. The two IgG producers (TEPC-6583 and TEPC-6906) showed diploid chromosome number, whereas the IgA producer (TEPC-3660) showed hypotetraploid chromosome number. Banding analysis revealed that these 3 plasmacytomas consistently had the t(12;15) translocation with the specific breakpoints at 12F2 and 15D2. Taken together with the previous observation of t(12;15) in plasmacytomas of BALB/c and C3H mice, these results suggest that the t(12;15) is specific for murine plasmacytomas and that the putative gene(s) on the t(12;15) may participate in the genesis of murine plasmacytomas.

Animals↗
PubMed2001

Plasmacytoma of the larynx diagnosed by fine-needle aspiration cytology: a case report.

Extramedullary plasmacytoma is a rare lesion. The use of fine-needle aspiration for diagnosis of plasmacytoma has been described in a few sporadic reports. To the best of our knowledge, none of these reports described the cytologic findings from plasmacytoma of the larynx. We report on a case of laryngeal plasmacytoma in a 79-yr-old man diagnosed by fine-needle aspiration cytology. The patient had a history of a plasmacytoma involving the sixth thoracic vertebra diagnosed in 1996, which progressed to multiple myeloma in 1997. He received treatment in the form of local radiation to the skeletal vertebrae and chemotherapy. Two years later, the patient presented with a large neck mass. Computed tomography (CT) was done at an outside facility, and the radiologic impression was of a large right glottic carcinoma with invasion into the right thyroid cartilage. Because of the history of multiple myeloma, a fine-needle aspiration (FNA) biopsy was performed of the laryngeal mass. Cytologic examination demonstrated atypical plasma cells arranged in a dissociative fashion, consistent with a plasmacytoma. Although there are previous surgical pathology reports of laryngeal plasmacytoma, to the best of our knowledge, this is the first report of plasmacytoma of the larynx diagnosed by FNA cytology.

Aged↗