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1.  Adenopathy and Extensive Skin Patch Overlying a Plasmacytoma (AESOP) Syndrome 
Adenopathy and extensive skin patch overlying a plasmacytoma is a very rare syndrome featuring a red-to-brown, violaceous skin patch along with a plasmacytoma. Only 11 case reports exist in the literature. Skin biopsies from the cutaneous patch overlying the plasmacytoma exhibit a dermal vascular hyperplasia with increased surrounding dermal mucin. Radiation therapy is used to treat and cure the plasmacytoma.
PMCID: PMC3509886  PMID: 23198009
2.  Phlegmasia caerulea dolens secondary to pelvic plasmacytoma and left femoral deep vein thrombosis☆ 
INTRODUCTION
Phlegmasia caerulea dolens (PCD) is a clinical syndrome caused by venous obstruction leading to peripheral limb ischaemia. It can ultimately lead to venous gangrene, amputation or death in 25% of cases.
PRESENTATION OF CASE
A 52-year-old man with a background of myeloma developed PCD secondary to an obstructing plasmacytoma and left femoral vein deep vein thrombosis (DVT). These were treated with combined radiotherapy and anticoagulation, with resolution of the patient's symptoms. His recovery was complicated by the development of heparin-induced thrombocytopenia (HIT) and cutaneous vasculitis.
DISCUSSION
Both plasmacytoma and DVT are recognised complications of myeloma. This is, to our knowledge, the first description of these phenomena in combination causing PCD. The combination of venous stasis from the obstructing plasmacytoma and hypercoagulability from the underlying myeloma may have contributed to clot formation. A multifaceted treatment approach was required which aimed at improving venous flow via radiotherapy to the plasmacytoma and dissolving the obstructing clot with anticoagulant therapy.
CONCLUSION
PCD has a high mortality and morbidity. Recognition is important to avoid an incorrect diagnosis of arterial occlusion and inappropriate surgical intervention. Treatment must be focused on removing the offending causes.
doi:10.1016/j.ijscr.2013.07.010
PMCID: PMC3785849  PMID: 23959409
Phlegmasia caerulea dolens; Deep vein thrombosis; Myeloma
3.  Different guises of plasmacytoma--from skin to bone. 
Journal of Clinical Pathology  1994;47(10):951-953.
A case is reported of a patient with plasmacytoma which assumed different clinicopathological features over seven years. The tumour first presented as a subcutaneous mass which was misdiagnosed as anaplastic carcinoma. Complete response to radiotherapy ensued but recurrence took the form of an intracerebral tumour. Further complete response to "palliative" corticosteroids was followed by osseous lesions three years later, when the diagnosis of plasmacytoma was confirmed. This report illustrates the highly variable clinicopathological presentations of plasmacytoma, including the rare primary cutaneous manifestation.
Images
PMCID: PMC502182  PMID: 7962610
4.  Case for diagnosis*  
Anais Brasileiros de Dermatologia  2014;89(1):173-174.
Cutaneous involvement associated to multiple myeloma varies from 5 to 10% of cases and is infrequently recognized. Cutaneous metastatic plasmacitomas are rare. We present the case of a 72-year-old man with multiple myeloma in complete remission since 2 years ago with cutaneous tumors on the trunk and face. A cutaneous biopsy was consistent with plasmacytoma. The patient was treated with melphalan, prednisolone and radiotherapy. Despite optimal therapeutic response of the lesions, the disease progressed, with the appearance of new extra-cutaneous plasmocytomas. The cutaneous metastatic plasmocytomas were the first sign of progression of the disease.
doi:10.1590/abd1806-4841.20142431
PMCID: PMC3938377  PMID: 24626671
Multiple myeloma; Plasmacytoma; Skin manifestations
5.  Subcutaneous Plasmacytoma Metastasis Precipitated by Tunneled Central Venous Catheter Insertion 
Case Reports in Oncology  2011;4(2):315-322.
Extramedullary plasmacytomas are tumors of monoclonal plasma cells arising within soft tissue that uncommonly occur in multiple myeloma patients. While sporadic development of these tumors at cutaneous trauma sites, including venous catheter access sites, has been reported, interventional radiologists seldom encounter this disease. Herein, we describe a case of metastatic subcutaneous plasmacytoma precipitated by tunneled central venous catheter insertion in a male patient undergoing stem cell therapy for treatment of multiple myeloma. In addition, we review the identification, diagnostic pitfalls, pathogenesis, and treatment of this rare entity.
doi:10.1159/000330044
PMCID: PMC3130982  PMID: 21738502
Central venous catheter; Multiple myeloma; Extramedullary plasmacytoma; Subcutaneous plasmacytoma metastasis
6.  Inhibition of plasmacytoma development in BALB/c mice by indomethacin 
The Journal of Experimental Medicine  1985;161(5):996-1012.
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.
PMCID: PMC2187607  PMID: 3989472
7.  Restricted Immunoglobulin Variable Region (Ig V) Gene Expression Accompanies Secondary Rearrangements of Light Chain Ig V Genes in Mouse Plasmacytomas 
The Journal of Experimental Medicine  1999;190(10):1405-1416.
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 (VL) and heavy (VH) 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 VH-J558 family; and (c) secondary rearrangements occur at the light chain level with at least three plasmacytomas expressing both κ and λ 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.
PMCID: PMC2195694  PMID: 10562316
V(D)J rearrangement; plasmacytoma; allelic exclusion; polyreactivity; V gene usage
8.  Solitary plasmacytoma of the skull: Two case reports 
Oncology Letters  2012;5(2):479-482.
Solitary plasmacytoma of the skull is rare and few cases have been reported in the English literature. Plasmacytoma of the skull has a wide spectrum of pathology, including a quite benign, solitary plasmacytoma (SPC), and an extremely malignant, multiple myeloma (MM) at the two ends of the spectrum. The prognosis for solitary plasmacytoma of the skull appears to be good when it can be diagnosed on strict criteria. The clinical features of solitary plasmacytoma of the skull are complex and not easily identified, resulting in a high misdiagnosis rate. A comprehensive examination and analysis which includes radiological examination, immunoglobulin, biochemistry, test for Bence Jones protein in the urine and bone marrow is needed for correct diagnosis. If the skull lesion is isolated, with accompanying marked swelling in the area and tenderness, plasmacytoma must be considered as a possibility for the cause of solitary skull masses. Two cases of solitary plasmacytoma of the skull lesions were retrospectively reviewed, in which a comprehensive examination was used in order to predict the clinical course of solitary plasmacytoma of the skull. The patients received postoperative radiation and/or chemotherapy. Survival following surgery was longer than 2 years for patient 1, and patient 2 is alive at the 18-month follow-up.
doi:10.3892/ol.2012.1046
PMCID: PMC3573150  PMID: 23420663
plasmacytoma; skull; diagnosis; therapy
9.  Pancreatic and Gastric Plasmacytoma Presenting with Obstructive Jaundice, Diagnosed with Endoscopic Ultrasound-Guided Fine Needle Aspiration 
Case Reports in Gastroenterology  2010;4(3):410-415.
Pancreatic plasmacytoma is a rare disorder which may present with obstructive jaundice. Only eighteen cases have been reported in the English language literature. We present the first case of pancreatic plasmacytoma and gastric plasmacytoma diagnosed with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). A 75-year-old male with a known history of multiple myeloma presented with obstructive jaundice and a pancreatic mass. A concomitant gastric mass due to gastric plasmacytoma was seen. The diagnosis was established via EUS-FNA of the pancreatic mass. Pancreatic plasmacytoma should be suspected in patients with a history of myeloma. EUS-FNA is a safe and effective modality in the diagnosis of pancreatic plasmacytoma. Radiation therapy should be the first-line of therapy in treating pancreatic plasmacytomas.
doi:10.1159/000321050
PMCID: PMC2975009  PMID: 21060710
Pancreatic plasmacytoma; Jaundice; Endoscopic ultrasound-guided fine needle aspiration
10.  POEMS Syndrome Presentation with an Abscess within the Plasmacytoma—A Rare Case Report 
ISRN Hematology  2011;2011:173164.
POEMS Syndrome is a rare cause of demyelinating and axonal mixed neuropathy. Plasmacytomas are usually seen in POEMS syndrome and can be osseous or extramedullary. Plasmacytomas presenting as an abscess has not been noted earlier. Our patient presented with localized hyperpigmented patch on the back and later developed progressive weakness in upper and lower limbs. Initially serum and urine protein electrophoresis were normal. The patient was thought to have Chronic Inflammatory Demyelinating Polyneuropathy and was treated accordingly without any improvement. Repeat serum protein electrophoresis showed monoclonal gammopathy. MRI of the back revealed an abscess in the paravertebral soft tissues reaching up to the skin. Needle biopsy was consistent with plasmacytoma. Later, he developed a purulent fungating lesion in the lower midback. Antibiotics were started and local resection was done followed by radiation. Pathology of the resected mass showed plasmacytoma extensively involving subcutaneous soft tissue and bone. The patient improved with the treatment. Cystic plasmacytomas and abscess within the plasmacytoma has not been reported earlier. Whether abscess formation is part of the disease spectrum due to infiltration of overlying tissue or is secondary to localized immunosuppression is unknown. Local treatment of a single plasmacytoma is useful in ameliorating systemic symptoms.
doi:10.5402/2011/173164
PMCID: PMC3195345  PMID: 22084694
11.  Radiation Therapy for Secondary Cutaneous Plasmacytomas 
Case Reports in Hematology  2013;2013:739230.
We are reporting a case of a 75-year-old man with multiply recurrent IgA-lambda multiple myeloma status post multiple rounds of chemotherapy, autologous stem cell transplantation, and palliative radiation therapy for diffuse bone lesions. Approximately 15 years after original diagnosis, he developed secondary cutaneous plasmacytomas of the right arm, right chest wall, and right upper back over the course of several months. He underwent palliative involved field 3D conformal photon or en face electron therapy concurrently with various chemotherapy regimens and achieved good to complete response with palliation of pain at the irradiated sites. He died of complications related to his disease approximately 7 months after developing skin lesions. The case presented is unique for dermal involvement of myeloma treated with palliative involved field radiation.
doi:10.1155/2013/739230
PMCID: PMC3821948  PMID: 24260722
12.  VS38 immunostaining in melanocytic lesions. 
Journal of Clinical Pathology  1996;49(3):205-207.
AIMS: To investigate the immunoreactivity of a range of melanocytic lesions, both benign and malignant, with the monoclonal antibody VS38. This was recently described as a marker of reactive/neoplastic plasma cells and, therefore, is useful in the diagnosis of plasmacytoma/myeloma and lymphomas with plasmacytic differentiation. This study was prompted by the recent observation that a plasmacytoid melanoma arising in the nasal cavity was strongly immunoreactive with VS38, which was therefore a potential source of major diagnostic error. METHODS: The Streptavidin-peroxidase complex technique was used on paraffin wax embedded sections of 167 melanocytic lesions. Diaminobenzidine (DAB) was used as chromogen for non-pigmented or lightly pigmented lesions and nickel/DAB for more heavily pigmented lesions. RESULTS: Positive immunostaining for VS38 was seen in 14.5% (10/69) of benign naevi (including 40% (four of 10) of Spitz naevi), 10.5% (two of 19) of dysplastic naevi/in situ melanomas, 92% (35/38) of primary cutaneous melanomas, 100% (four of four) of primary mucosal melanomas, 91.7% (33/36) of recurrent/metastatic melanomas, and 100% (one of one) of clear cell sarcomas of soft tissues. CONCLUSIONS: VS38 immunostaining is frequently positive in primary and recurrent/metastatic malignant melanoma and is also reactive less commonly with benign naevi. These results should be borne in mind when this recently described marker of normal/neoplastic plasma cells is used to identify tumour lineage, particularly in tumours arising at unusual sites, such as in the nasal cavity. The possibility of malignant melanoma should be actively considered and excluded in any undifferentiated tumour which shows VS38 immunoreactivity.
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PMCID: PMC500398  PMID: 8675729
13.  Mast cell–derived angiopoietin-1 plays a critical role in the growth of plasma cell tumors 
Journal of Clinical Investigation  2004;114(9):1317-1325.
Multiple myeloma in humans is frequently associated with mast cell infiltration and neovascularization, which correlate directly with disease severity, but the mechanisms underlying this relationship remain unclear. Here, we report that primary murine mast cells express angiopoietin-1 (Ang-1) and low levels of VEGF-A but not Ang-2 and that 2 established murine plasmacytoma cell lines express high levels of VEGF-A but little or no Ang-1 or Ang-2. An in vivo angiogenesis assay using extracellular matrix components shows that mast cells and plasmacytoma cells, together, promote marked neovascularization composed of dilated vessels, which is prevented by neutralization of VEGF-A and Ang-1 but is only partially reduced by neutralization of either VEGF-A or Ang-1. Mast cells within extracellular matrix components express Ang-1, and recombinant Ang-1 together with plasmacytoma cells promotes extracellular matrix neovascularization similar to that induced by mast cells. A transplantation assay shows that primary mast cells accelerate tumor growth by established plasmacytoma cell lines and that neutralization of Ang-1 alone or with VEGF-A reduces significantly the growth of plasmacytomas containing mast cells. These results demonstrate that mast cell–derived Ang-1 promotes the growth of plasmacytomas by stimulating neovascularization and provide further evidence supporting a causal relationship between inflammation and tumor growth.
doi:10.1172/JCI200422089
PMCID: PMC524229  PMID: 15520864
14.  Interleukin-HP1, a T cell-derived hybridoma growth factor that supports the in vitro growth of murine plasmacytomas 
We have recently described the purification and NH2-terminal amino acid sequence of a T cell-derived hybridoma growth factor that was provisionally designated interleukin-HP1 (IL-HP1). Here we report that a T cell supernatant containing high titers of this hybridoma growth factor considerably facilitated the establishment of primary cultures of murine plasmacytomas. Most plasmacytoma cell lines derived from such cultures remained permanently dependent on IL-HP1-containing T cell supernatant for both survival and growth in vitro. These cell lines, however, retained their ability to form tumors in irradiated pristane- treated mice. Analytical fractionation of a T cell supernatant rich in IL-HP1 by either gel filtration, isoelectric focusing, or reversed- phase HPLC revealed the existence of only one plasmacytoma growth factor activity that strictly copurified with IL-HP1, strongly suggesting the identity of both factors. This conclusion was further supported by the finding that IL-HP1 purified to homogeneity supported the growth of both B cell hybridomas and plasmacytomas. For half- maximal growth, plasmacytomas, however, required a concentration of IL- HP1 of approximately 30 pM, which is approximately 200 times higher than that required by B cell hybridomas. A clear difference in the specificity of IL-HP1 and B cell stimulatory factor 1 (BSF-1) was demonstrated by the finding that IL-HP1-dependent plasmacytomas did not survive in the presence of BSF-1, whereas helper T cell lines that proliferated in the presence of BSF-1 failed to respond to IL-HP1.
PMCID: PMC2188283  PMID: 3493321
15.  High resolution banding analysis of the involvement of strain BALB/c- and AKR-derived chromosomes No. 15 in plasmacytoma-specific translocations 
Plasmacytomas were induced in (BALB/c X AKR 6;15) X BALB/c backcross mice where one of the BALB/c-derived chromosomes No. 15 was replaced by the AKR(6;15)-derived Robertsonian 6;15 chromosome. (BALB/c X AKR 6;15)F2 mice that were homozygous for Rb 6;15 were mated to BALB/c mice. Plasmacytomas were induced in the progeny by intraperitoneal injection of pristane. The cytogenetic marker permitted the distinctive identification of the two chromosome 15 homologues, including the distal segment involved in the plasmacytoma-specific translocations. 7 of the 10 plasmacytomas contained the typical t(12;15) translocation. The BALB/c-derived 15 chromosome served as the donor of the translocated segment in six of them. In the seventh, the Rb 6;15 chromosome of the AKR strain was the donor. The remaining three tumors contained the same type of intrachromosomal rearrangement. It arose by the pericentric inversion of the Rb 6;15 chromosome, leading to a variant plasmacytoma-associated rcpt (6;15) translocation. Unlike the usual 6;15 variant that arises by a reciprocal exchange between two separate chromosomes, it was generated by an exchange of the distal segments of a single chromosomal element. High resolution banding analysis of the tumors showed that all translocated breakpoints on chromosomes 15, 12, and 6 were identical with the previously described breakpoints characteristic for the typical 12;15 and the variant 6;15 translocation in murine plasmacytomas. It is known that the distal segment of chromosome 15 carries the c-myc oncogene (23). The PC- associated translocations cut across the 5'-exon of c-myc in the majority of the cases (24,26). The severed oncogene is transposed to the Ig-region on the recipient chromosome. Since the BALB/c strain is highly sensitive to PC-induction, we were interested to examine the question whether its chromosome 15 is preferred as the oncogene donor in AKR X BALB/c backcross mice that carry cytogenetically distinguishable 15 chromosomes. Our results show that this is not the case, since the same segment of the AKR-derived chromosome 15 could also serve in the same capacity. This is in contrast with T cell leukemogenesis where we have previously found that the trisomization- associated duplication of chromosome 15 occurred in a highly asymmetrical fashion, depending on the donor strain of No. 15 (9-11).
PMCID: PMC2187207  PMID: 6607313
16.  Primary plasmacytoma of the testicle: a case report 
Introduction
Extramedullary plasmacytoma is a rare plasma cell neoplasm. Plasmacytomas are most commonly found in the head and neck region, but can occur in many other locations. They rarely occur in the testis, and are commonly associated with concurrent multiple myeloma at the time of diagnosis. Isolated plasmacytoma of the testis is exceedingly rare, with few cases reported in the literature.
Case presentation
A 72-year-old Caucasian man presented with a painless testicular mass treated by orchiectomy. The mass was determined to be plasmacytoma on pathological examination. At the time of diagnosis, our patient did not have multiple myeloma, and is currently undergoing chemotherapy for treatment of his disease.
Conclusion
Isolated plasmacytoma of the testicle is a rare cause of testicular mass, and is seldom reported in the literature. Patients with this disease require careful monitoring because of their high risk of progression to multiple myeloma. The diagnosis of testicular plasmacytoma can be challenging for primary care doctors and urologic specialists. This condition should be in the differential diagnosis in elderly men.
doi:10.1186/1752-1947-5-494
PMCID: PMC3198716  PMID: 21968163
17.  Solitary Plasmacytoma of Skull: A Rare Cytological Diagnosis 
Solitary Plasmacytoma of the Skull (SPS) is very rare and only 35 cases have been reported in the English literature. It remains controversial whether a solitary plasmacytoma of the skull is essentially identical with a Solitary Plasmacytoma of Bone (SPB) or not. A solitary plasmacytoma of bone, which includes a 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 it is present and a negative urine test for Bence Jones protein (monoclonal light chain). A solitary plasmacytoma of bone tends to disseminate or progress to multiple myeloma, even as long as 7-23 years after its presentation.
doi:10.7860/JCDR/2013/5555.3259
PMCID: PMC3782939  PMID: 24086882
Fine needle aspiration cytology; Solitary plasmacytoma; Skull
18.  Rare pancreas tumor mimicking adenocarcinoma: Extramedullary plasmacytoma 
Neoplastic proliferation of plasma cells is called plasma cell dyscrasias, and these neoplasms can present as a solitary neoplasm or multiple myeloma. Extramedullary plasmacytoma, in particular pancreatic plasmacytoma, is a rare manifestation of multiple myeloma. Although computerized tomography is useful for the diagnosis of extramedullary plasmacytoma, there are no specific radiologic markers that distinguish it from adenocarcinoma. Histological confirmation by biopsy is necessary for accurate diagnosis and management of the tumor. Endosonography is the most sensitive method for the diagnosis of pancreatic tumors, and the use of fine needle aspiration by endosonography is associated with a lower risk for malignant seeding and complications. Here, we report a case of pancreatic plasmacytoma in newly identified multiple myeloma as diagnosed by endosonography. Endosonography is a reliable and rapid method for the diagnosis of extramedullary plasmacytoma. Therefore, endosonographic fine needle aspiration should be the first choice for histological evaluation when pancreatic plasmacytoma is suspected. Ideally, the pathology would be performed at the same site as endosonographic biopsy.
doi:10.4253/wjge.v6.i3.99
PMCID: PMC3952166  PMID: 24634714
Plasmacytoma; Endosonography; Pancreatic mass; Multiple myeloma; Fine needle aspiration
19.  Primary isolated extramedullary plasmacytoma of colon 
Background
Extramedullary plasmacytoma is an uncommon entity that most commonly involves nasopharynx or upper respiratory tract. Involvement of the gastrointestinal tract occurs in approximated 10% of cases. Isolated primary plasmacytoma of colon is rare and only 7 well documented cases have been reported in the literature.
Case presentation
We present a case of 42 year male who presented with diarrhea. Multiple colonic strictures were found on investigation. Colonoscopic biopsy was not helpful in making any specific diagnosis. Patient underwent subtotal colectomy. Isolated primary colonic plasmacytoma was found on histopathological examination.
Conclusion
Plasmacytoma is known to occur in extra osseous sites. Primary colonic plasmacytoma, however, is a rare clinical entity. Primary colonic plasmacytoma may have varying clinical presentations including multiple colonic strictures that may mimic colonic tuberculosis or inflammatory bowel disease. Although these cases are rare, treating physician as well as radiologist, and pathologist should be aware of this entity.
doi:10.1186/1477-7819-5-47
PMCID: PMC1871591  PMID: 17470287
20.  Selective expression of intracisternal A-particle genes in established mouse plasmacytomas. 
Molecular and Cellular Biology  1993;13(12):7439-7446.
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.
Images
PMCID: PMC364815  PMID: 8246961
21.  Alteration of immunoglobulin phenotype in cell culture-adapted lines of two mouse plasmacytomas 
The Journal of Experimental Medicine  1975;142(4):998-1010.
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.
PMCID: PMC2189950  PMID: 51902
22.  Skeletal Plasmacytoma: Progression of disease and impact of local treatment; an analysis of SEER database 
Background
Previous reports suggest an as yet unidentifiable subset of patients with plasmacytoma will progress to myeloma. The current study sought to establish the risk of developing myeloma and determine the prognostic factors affecting the progression of disease.
Methods
Patients with plasmacytoma diagnosed between 1973 and 2005 were identified in the SEER database(1164 patients). Patient demographics and clinical characteristics, treatment(s), cause of death, and survival were extracted. Kaplan-Meier, log-rank, and Cox regression were used to analyze prognostic factors.
Results
The five year survival among patients initially diagnosed with plasmacytoma that later progressed to multiple myeloma and those initially diagnosed with multiple myeloma were almost identical (25% and 23%; respectively). Five year survival for patients with plasmacytoma that did not progress to multiple myeloma was significantly better (72%). Age > 60 years was the only factor that correlated with progression of disease (p = 0.027).
Discussion
Plasmacytoma consists of two cohorts of patients with different overall survival; those patients that do not progress to systemic disease and those that develop myeloma. Age > 60 years is associated with disease progression. Identifying patients with systemic disease early in the treatment will permit aggressive and novel treatment strategies to be implemented.
doi:10.1186/1756-8722-2-41
PMCID: PMC2759950  PMID: 19778427
23.  Endoscopic Endonasal Transsphenoidal Resection of Solitary Extramedullary Plasmacytoma in the Sphenoid Sinus with Destruction of Skull Base 
Solitary extramedullary plasmacytomas are isolated plasma cell tumors of soft tissue that typically do not metastasize. They are rare and account for 4% of all plasma cell tumors. To our knowledge, only 14 cases of solitary extramedullary plasmacytomas in the sphenoid sinus have been reported. A 32-year-old man presented to our department with complaint of ocular pain in the right eyeball and diplopia. Physical and neurological examinations revealed intact and prompt direct and indirect light reflexes in both pupils and limitation of extraocular muscle movement seen with the lateral gaze of the right eyeball. Magnetic resonance imaging suggested the presence of mucocele or mycetoma, therefore surgical resection was performed with endoscopic endonasal transsphenoidal approach. Histopathology was consistent with plasmacytoma. Systemic work-up did not show any evidence of metastasis and the sphenoid sinus was the sole tumor site, and therefore the diagnosis of solitary extramedullary plasmacytoma was confirmed. We report a rare case of solitary extramedullary plasmacytoma in the sphenoid sinus with successful treatment using the endoscopic endonasal transsphenoidal resection and adjuvant radiotherapy.
doi:10.3340/jkns.2009.46.2.156
PMCID: PMC2744026  PMID: 19763219
Plasmacytoma; Sphenoid sinus; Endoscopic surgical resection
24.  Tumor-associated macrophages infiltrate plasmacytomas and can serve as cell carriers for oncolytic measles virotherapy of disseminated myeloma 
American journal of hematology  2009;84(7):401-407.
In multiple myeloma, some of the neoplastic plasma cells are diffusely dispersed among the normal bone marrow cells (bone marrow resident), whereas others are located in discrete, well-vascularized solid tumors (plasmacytomas) that may originate in bone or soft tissue. Interactions between bone marrow-resident myeloma cells and bone marrow stromal cells (BMSCs) are important determinants of myeloma pathogenesis. However, little is known of the factors sustaining myeloma growth and cell viability at the centers of expanding plasmacytomas, where there are no BMSCs. Histologic sections of 22 plasmacytomas from myeloma patients were examined after immunostaining. Abundant CD68+, CD163+, S100-negative macrophage infiltrates were identified in all tumors, accompanied by scattered collections of CD3+ T lymphocytes. The CD68+ tumor-associated macrophages (TAM) accounted for 2– 12% of nucleated cells and were evenly distributed through the parenchyma. The TAM generally had dendritic morphology, and each dendrite was in close contact with multiple plasma cells. In some cases, the TAM were strikingly clustered around CD34+ blood vessels. To determine whether cells of the monocytic lineage might be exploitable as carriers for delivery of therapeutic agents to plasmacytomas, primary human CD14+ cells were infected with oncolytic measles virus and administered intravenously to mice bearing KAS6/1 human myeloma xenografts. The cell carriers localized to KAS6/1 tumors, where they transferred MV infection to myeloma cells and prolonged the survival of mice bearing disseminated human myeloma disease. Thus, TAM are a universal stromal component of the plasmacytomas of myeloma patients and may offer a promising new target for therapeutic exploitation.
doi:10.1002/ajh.21444
PMCID: PMC2805200  PMID: 19507209
25.  Plasmacytoma of bone, extramedullary plasmacytoma, and multiple myeloma: Incidence and survival in the United States, 1992−2004 
British journal of haematology  2008;144(1):86-94.
Summary
Population-based plasmacytoma incidence and survival data are sparse. We analyzed incidence rates (IRs), IR ratios (IRRs), and 5-year relative survival for plasmacytoma overall and by site – bone (P-bone) and extramedullary (P-extramedullary) – in the Surveillance, Epidemiology and End Results (SEER) Program (1992−2004). For comparison, we included cases of multiple myeloma (MM) diagnosed over the same time period in SEER. Incidence of MM (n=23,544; IR 5.35/100,000 person-years) was 16-times higher than plasmacytoma overall (n=1,543; IR=0.34), and incidence of P-bone was 40% higher than P-extramedullary (p<0.0001). The male-to-female IRRs for P-bone, P-extramedullary, and MM were 2.0, 2.6, and 1.5, respectively. For plasmacytoma and MM, IRs were highest in Blacks, intermediate in Whites, and lowest in Asian/Pacific Islanders. Compared with Whites, the Black IR was ∼30% higher for P-extramedullary and P-bone and 120% higher for MM. IRs for all neoplasms increased exponentially with advancing age, less prominently at older ages for plasmacytoma than MM. Distinct age, gender, and race incidence patterns of plasma cell disorders suggest underlying differences in clinical detection, susceptibility, disease biology and/or aetiologic heterogeneity. Five-year relative survival for P-bone, P-extramedullary, and MM varied significantly by age (<60/60+ years), supporting age-related differences in disease burden at presentation, disease biology, and/or treatment approaches.
doi:10.1111/j.1365-2141.2008.07421.x
PMCID: PMC2610331  PMID: 19016727

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