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Fibrosarcoma mimicking plasmacytoma or carcinoma: an ultrastructural study of 4 cases.

Because the fibroblast has a remarkable capability of phenotypic modulations, reflected in both morphologic and immunohistochemical (IHC) changes, ultrastructural studies are mandatory to identify the variants of fibroblasts. Myofibroblasts or histiofibroblasts are such examples, demonstrating chimeric ultrastructural features of fibroblastic cells in common with smooth muscle cells or with histiocytes, respectively. The presence of epithelioid fibroblastic cells sharing morphologic features with epithelial or plasma cells has not been yet characterized. The authors identified 4 cases of fibrosarcomas (FS) characterized by an unusual phenotype and associated with peculiar ultrastructural findings. The electron microscopic (EM) findings were correlated with the histologic appearance and immunoprofile. All tumors were located in the extremities, 3 in soft tissues and 1 in the bone. By light microscopy 2 cases were composed predominantly by round uniform cells with a striking plasmacytoid appearance. One case mimicked carcinoma, composed predominantly by epithelioid cells and scattered giant tumor cells. The fourth case showed a mixture of plasmacytoid-like and epithelioid cells. By IHC, tumor cells were positive for vimentin and in 2 cases also for epithelial membrane antigen. Kappa/lambda light chain and cytokeratins markers were negative. By EM all 4 tumors showed in addition to classic features of fibroblasts, unusual epithelial-type features, such as secretory granules of "neurosecretory-type" (3 cases), rudimentary cell junctions (3 cases), microvilli (2 cases), and lumen-like structures (1 case). One plasmacytoid-type tumor showed finely granular extracellular deposits. The study describe 4 examples of fibrosarcomas with unusual features at the ultrastructural level, which are associated microscopically with a peculiar phenotype, mimicking plasmacytoma or carcinoma. These findings broaden the spectrum of fibroblastic cell variants in neoplasia.

Adult↗

Misleading imaging features of intracranial dural plasmacytoma: report of two cases.

Dural plasmacytomas are very rare and often disregarded in the differential diagnosis of more common lesions of the convexity. We report two cases. Both patients exhibited headache as a main symptom. Computed tomography and magnetic resonance showed a homogeneously enhanced lesion without calcification and without bone involvement.

Diagnosis, Differential↗

Solitary plasmacytoma in the setting of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is an intriguing disorder characterized by the accumulation of specialized dendritic cells called Langerhans cells in several diverse tissues and body sites. It has been cited in numerous case reports to be associated with a wide variety of malignant neoplasms. Although many hypotheses have been suggested, the basis for such associations remains essentially unknown. We describe another association here that to our knowledge has not been reported thus far: a solitary plasmacytoma occurring at a site of previous involvement by LCH. This constitutes a new addition to the now fairly lengthy list of malignant neoplasms that have been reported to occur in the setting of LCH. The possible reasons for such an association are discussed along with a brief review of LCH.

Aged↗

Cavernous sinus involvement by extramedullary plasmacytoma of the sphenoid sinus. An argument for the use of adjuvant chemotherapy.

A 63-year-old man with cavernous sinus involvement from extramedullary plasmacytoma (EMP) of the sphenoid sinus is described. Transient resolution of retro-orbital headache and continued progression of the locally extensive tumor were noted after chemotherapy was given following a poor response to 5400 cGy of local irradiation. To determine whether adjunctive chemotherapy will improve the outcome of these particular patients, we propose that a randomized trial comparing radiotherapy to chemoradiation be conducted.

Aged↗

High dose therapy with autologous stem cell transplantation for solitary bone plasmacytoma complicated by local relapse or isolated distant recurrence.

We report three patients with solitary bone plasmacytoma (SBP) who developed either local recurrence within the radiotherapy field or an isolated distal recurrence and who were treated with high dose therapy supported by autologous stem cell transplantation. All patients remain without evidence of disease for 4-10 years after the procedure. High dose therapy may be of value and require further study in patients with SBP who develop local or distant failure.

Adult↗

The requirement of an adherent cell substratum for the growth of developing plasmacytoma cells in vivo.

The intraperitoneal injection of pristane (2,6,10,14-tetramethylpentadecane) produces an environment conductive to primary plasmacytoma growth in as few as 3 days. After pristane injection, the total free peritoneal cell population increases from a normal value of 1.55 X 10(6) to 5.28 X 10(6) and remains at this elevated level for at least 50 days. The adherent peritoneal cell population, composed of both mononuclear cells and polymorphonuclear leukocytes, is the primary source of this increase. In the pristane-conditioned peritoneum, these cells rapidly form a chronic granuloma on the peritoneal connective tissues. Daily subcutaneous treatment of mice with 0.5 mg of hydrocortisone beginning simultaneously with pristane injection prevents the increase in the peritoneal cell population, granuloma formation, d the production of a conditoned environment. In mice treated with hydrocortisone beginning 3 days after pristane injection, however, neither the peritoneal cell increase nor the production of a conditioned environment is prevented. The intraperitoneal injection of thioglycolate medium at 4-day intervals produces an elevation of the free adherent peritoneal cell population similar to pristane, but does not produce a granuloma or a conditioned environment. The intraperitoneal transfer of thioglycolate-induced adherent peritonel cells to mice treated with pristane and hydrocortisone simultaneously restores the production of a conditioned environment. These findings indicate that the adherent peritoneal cell population is responsible for the conditioning effect, and that the establishment of a resident population of these cells is necessary to produce conditioning.

Alkanes↗

Physiology of IgD. IV. Enhancement of antibody production in mice bearing IgD-secreting plasmacytomas.

Immune responses to trinitrophenylated hemocyanin (TNP-KLH), Ficoll (TNP-Ficoll), and Brucella abortus (TNP-BA) were examined in BALB/c mice bearing subcutaneous transplants of TEPC-1017 and TEPC-1033, the two known IgD-secreting BALB/c plasmacytomas. Both primary and secondary 19S and 7S splenic plaque-forming cell (PFC) responses in spleen to intravenously injected TNP-KLH were enhanced three to fivefold. Primary responses to TNP-Ficoll were 1.5-2 times higher than in control mice (particularly the 7S PFC response). Primary responses to TNP-BA were enhanced by TEPC-1017 but suppressed by TEPC-1033, while secondary responses to TNP-BA were enhanced three to sevenfold by both tumors. Intraperitoneal injections of ascites fluid from mice bearing TEPC-1017 or TEPC-1033, or of IgD isolated from such ascites fluid, caused a similar enhancement of the primary response to TNP-KLH, as did the tumor itself, particularly when injected approximately 1 wk before antigen injection. IgD-containing ascites fluid had no effect on the response of athymic (nu/nu) BALB/c mice to TNP-KLH. These findings suggest the existence of an IgD-responsive immunoregulatory T cell.

Animals↗

Subglottic plasmacytoma: the use of jet ventilation and contact Nd:YAG laser for tissue diagnosis.

Extramedullary plasmacytomas (EMP) constitute only 1% of all head and neck malignancies, with the vast majority occurring in the upper respiratory tract. The diagnosis of laryngeal EMP can be difficult since the symptoms are non-specific and the tumor usually mucosally covered. This paper discusses the successful combination of jet Venturi ventilation technique with suspension microlaryngoscopy and contact Nd:YAG laser for tissue diagnosis in a patient presenting with a large subglottic mass. Previous attempts using standard endotracheal intubation and forceps technique for biopsy failed to reach the diagnosis and resulted in significant bleeding from the biopsy site. A review of the disease and technique is presented.

Biopsy↗

Comparison of the mouse P(1)450 gene and flanking sequences from a MOPC 41 plasmacytoma and normal liver.

The murine P(1)450 gene is inducible by foreign chemicals such as dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD). The induction process appears to involve binding of TCDD to the Ah receptor, interaction of the inducer-receptor complex with chromatin, and transcriptional activation of the P(1)450 gene. P(1)450 gene expression did not occur in the MOPC 41 plasmacytoma transplanted intra-abdominally in the BALB/c mouse. By Southern blot analysis, the P(1)450 gene restriction patterns are similar between MOPC 41 DNA and normal mouse liver DNA digested with Eco RI, Bam HI, or Hind III, suggesting there is no evidence for a gross chromosomal rearrangement in the tumor P(1)450 gene. The P(1)450 gene isolated from a genomic DNA library derived from the MOPC 41 tumor lacked the first exon and two-thirds of the first intron because of a rearrangement that presumably occurred during construction of the genomic DNA library. An unknown upstream segment of 2578 bases that had recombined with the remainder of the P(1)450 gene was sequenced and found to contain several repetitive sequences on both strands. The remaining 6272 bases of the P(1)450 gene (2532 bp of exons, 1969 bp of introns and 1771 bp of 3'-flanking region) are identical between the BALB/cJ-derived MOPC 41 and normal C57BL/6N mouse liver, with the exception of one CTTT repeat in the second intron. Hence, the BALB/c and C57BL/6 inbred mice, generally regarded as among the most divergent of Mus domesticus inbred laboratory strains, possess a P(1)450 gene and flanking region that exhibit greater than 99.9% similarity in nucleotide sequence.

Animals↗

Inhibition of cell division and antibody secretion by murine alpha/beta interferon: effects on plasmacytoma and hybridoma lymphoid cells.

Murine alpha/beta interferon (IFN) inhibited the growth of myeloma cells in vitro. Independently of the cell growth inhibition, IFN also reduced the number of antibody secreting myeloma cells as measured by haemolytic plaque assay. The sensitivity of both MOPC 315 plasmacytoma cells and 4F4 hybridoma cells varied, though not to the same extent, depending on the dose of IFN used and the duration of exposure. Inhibition of PFC activity was observed after one day of IFN treatment while inhibition of cell growth was not detected until Day 2 of incubation. A dose of 20 u/ml IFN had no effect on the growth rate of MOPC 315 cells but with 100 u/ml the inhibition of growth was virtually complete. In contrast, an inhibition of PFC activity was observed at all the concentrations tested. The cell growth and PFC activity of 4F4 hybridoma cells, on the other hand, were both inhibited by IFN when used at concentrations as low as 1.25 u/ml. Incubation with higher concentrations of IFN resulted in a progressive reduction in cell growth and PFC activity of 4F4 cells, however to a lesser degree of inhibition compared to that observed with MOPC 315 cells. For example, although virtually 70% of MOPC 315 PFC could be inhibited by culture for two days in the presence of 100 u/ml, it was necessary to use 1,250 u/ml IFN for 4 days incubation before the similar level of PFC inhibition was achieved with 4F4 cells. IFN treatment resulted in an increase in both cellular volume and protein content and this effect was prevented when IFN was previously neutralised by a specific antiserum. IFN-treated cells also showed an inhibition in the incorporation of 3[H]-thymidine but no alteration in the rate of utilization of 35[S]-methionine, when compared with an equal number of control cells.

Animals↗

Plasmacytoma arising in giant lymph node hyperplasia.

Giant lymph node hyperplasia (GLNH) is generally thought to represent a benign process. A patient with GLNH of the chest wall had part of the lymph node replaced by large nodules of infiltrating plasma cells, and a serum paraprotein of the IgG lambda type. A peroxidase-antiperoxidase immunocytochemical technic showed that the plasma cells within areas of typical appearing GLNH were polyclonal, whereas those making up the nodular infiltrates were monoclonal. The observation of a plasmacytoma arising in this lesion demonstrates the neoplastic potential of GLNH.

Humans↗

Murine plasmacytomas, carrier of the t(12;15) chromosomal translocation, develop from immature/mature B cells not from differentiated plasma cells.

Dysregulation of the c-myc gene by chromosomal translocation in >95% of murine plasmacytomas (MPCs) is an obligatory requirement for the transformation of B lymphocytes into MPCs. However, it is still unknown whether sIg+ B cells or differentiated plasma cells are the legitimate precursor cells from which MPCs develop. To address this question, C.B-17 scid/scid (SCID) mice were reconstituted with splenic surface Ig-positive (sIg+) B lineage cells originating from BALB/cRb6.15 (B/cRb6.15) or human IL-6 transgene-congenic BALB/cRb8.12 mice (B/cRb8.12 IL-6-Tg). Six of 80 SCID mice reconstituted with B/cRb6.15 sIg+ B cells developed MPCs after pristane (2,6,10,14-tetramethylpentadecane) treatment followed by Abelson murine leukemia virus (A-MuLV) infection (incidence 7.5%) and four of 40 after pristane treatment alone (incidence 10%). Similarly, in 20 SCID mice reconstituted with B/cRb8.12 IL-6-Tg splenic sIg+ B cells the MPC incidence was 10%. Karyotype analysis revealed that all the translocations were of typical t(12;15) type and all tumors carried the Rb6.15 or Rb8.12 marker chromosome, indicating their donor cell origin. In contrast, none of the 48 SCID mice reconstituted with plasma cells obtained from the lymph nodes of B/cRb8.12 IL-6-Tg mice developed MPCs when treated either with pristane plus A-MuLV (20 mice) or with pristane alone (28 mice), although the transferred plasma cells were still functional in the recipient SCID mice 6 months after transfer. The findings indicate that the malignant transformation triggered by Ig/myc juxtaposition occurs more in immature (sIgM+) and/or mature (sIgM+/sIgD+, sIgG+ and sIgA+) B cells than in differentiated G0 or cycling plasma cells. We inferred that immature and/or mature B cells and not differentiated plasma cells are most likely the principal source of precursor cells from which the typical t(12;15) MPCs develop.

Animals↗

Alteration of cell-surface antigenicity of the mouse plasmacytoma. I. Immunologic characterization of surface antigens masked during successive transplantations.

Alterations of membrane antigenicity of IgA-synthesizing plasmacytoma cells (58-8) induced in a BALB/c mouse were investigated with rabbit antisera against 58-8 transplanted from 7-8 generations (anti-58-8) and mouse antisera against H-2d (anti-H-2d). The 58-8 cells transplanted (TP) for 8 generations (TP8), showed moderate susceptibilities to anti-58-8 [cytotoxicity index (CI) = 72%] and to anti-H-2d (Cl = 30-40%). At TP12, the susceptibility to anti-58-8 remained (tCl approximately 50%) but there was none to anti-H-2d (Cl = 0-10%). After TP13, 58-8 cells had detectable reactivity neither with anti-58-8 nor with anti-H-2d before proteolysis. However, antigenicity was demonstrated after treatment of cells with proteases: Anti-58-8 and anti-H-2d became cytotoxic to pronase-treated 58-8 (P-58-8) and these cytotoxic reactivities of antisera could be completely absorbed with P-58-8- but not with "intact" 58-8. Anti-H-2d absorbed with P-58-8 had no cytotoxicity to BALB/c spleen cells. Absorption of anti-H-2d with BALB/c spleen cells did not show any measurable cytotoxicity to P-58-8. Appearance of antigenicity after proteolysis was transient and reversible. When P-58-8 was incubated in vitro, susceptibilities to antisera were decreased. Actinomycin D and puromycin inhibited the loss of susceptibility; these metabolic inhibitors suppressed the "masking" of antigenic determinants with protein-like material(s). In early generations (TP8), 58-8 cells were susceptible to antiserum to bone marrow-derived lymphocytes (anti-B) and complement. The cells completely absorbed the cytotoxicity of anti-B against spleen cells. After additional transplantations (TP14, TP30), susceptibilities to anti-B were no longer detectable and no removal of the cytotoxicity was shown, though the cells were pretreated with pronase. Anti-B failed to kill MOPC-31C.

Animals↗

Growth characteristics of MOPC-315 plasmacytoma and response to anticancer agents.

We examined the growth characteristics and response to anticancer agents of the murine plasmacytoma MOPC-315, a rapidly growing and widely disseminating tumor syngeneic in BALB/c mice. The doubling time for the tumor was approximately 24 hours, and about 1 in 100 cells was tumorigenic. We developed a spleen colony assay for the clonogenic component of the tumor and used it to define the dose-response relationships for various anticancer agents, including melphalan, cyclophosphamide, 1,3-bis(chloroethyl)-1-nitrosourea, 5-fluouracil, gamma-radiation, methotrexate, methylprednisolone, cytosine arabinoside, and vincristine.

Animals↗

Control of a murine plasmacytoma with doxorubicin-cisplatin: dependence on circadian stage of treatment.

In anticipation of the development of clinical chronotherapy and in order to pick clinical test times for doxorubicin and cisplatin trials, two large studies were performed on rats bearing a transplanted plasmacytoma. The circadian timing of each of two anticancer drugs given at precisely equal dose intensities was expected to improve therapeutic benefit over conventionally given (time-unqualified) treatment. In each chronotherapeutic study, maximal benefit and minimal toxic effects were found when cisplatin was administered in the middle to latter part of the daily activity (dark) span, while doxorubicin was administered near the end of the daily resting (light) span for these nocturnally active rodents living on a 12-hour-12-hour or 8-hour-16-hour light-dark schedule. This was true whether doxorubicin or cisplatin was given first and whether there was a lag of only a few hours or a few days between the administration of these two agents.

Animals↗

Translocation affects normal c-myc promoter usage and activates fifteen cryptic c-myc transcription starts in plasmacytoma M603.

Plasmacytoma M603 contains one normal, nontranslocated c-myc gene and one translocated c-myc gene in which c-myc exon 1 is juxtaposed with the immunoglobulin heavy chain enhancer and c-myc exons 2 and 3 are juxtaposed with C alpha. We find that steady-state c-myc RNA levels are 2-4 fold elevated in M603 relative to normal liver or spleen and that these transcripts originate predominantly if not exclusively from the translocated c-myc gene. Although both promoters on the nontranslocated c-myc gene are repressed, the proximal promoter, P1, is active on the translocated 5' c-myc region which is juxtaposed with the immunoglobulin heavy chain enhancer. The 3' portion of the translocated c-myc gene is transcribed from fifteen cryptic start sites and spliced at aberrant donor and acceptor splice sites, thereby generating a mixture of transcripts with different, abnormal 5' untranslated regions. Although the reason that translocation activates the cryptic c-myc starts in M603 is not completely understood, we show that truncation of the c-myc gene is not sufficient to activate cryptic transcription sites.

Animals↗

Analysis of cleavage products of DNA repair enzymes and other nucleases. Characterization of an apurinic/apyrimidinic specific endonuclease from mouse plasmacytoma cells.

We have developed a strategy by which the nature of phosphodiester bond breaks produced by various DNA-repair endonucleases and also other nucleases, can be characterized. A purified apurinic/apyrimidinic (AP) specific endonuclease from a permanently established mouse plasmacytoma cell-line (MPC-11) has been examined with respect to the exact incision site generated at the baseless site. By the aid of enzymatic treatment with calf intestinal phosphatase, the 3'-phosphatase activity of T4-polynucleotide kinase, chemical modification with piperidine in addition to the Maxam-Gilbert sequencing procedure, followed by separation on a DNA-sequencing gel, the nature of the cleaved phosphodiester bond, both 3' and 5' to the cleavage site, has been established. The AP-specific endonuclease investigated was classified as a class II AP-endonuclease according to the four possible classes of AP-endonuclease with respect to the termini produced. By use of this technique each single damaged and cleaved site can be investigated separately.

Animals↗

Direct evidence for intrastrand DNA inversion of kappa immunoglobulin gene segments in two murine plasmacytomas.

The products of kappa immunoglobulin gene recombination have been characterized in two murine plasmacytomas to examine the relationship between V-J products and reciprocal elements. By cloning, sequencing, hybridization, and application of the polymerase chain reaction, we have established the direct relationship of the kappa recombination products in these cells. The results provide stronger support for the intrastrand mechanism of kappa gene recombination as well as demonstrating a role for secondary, corrective recombinations.

Amino Acid Sequence↗