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1.  Morphology and immunophenotype of canine cutaneous histiocytic tumours with particular emphasis on diagnostic application 
This study evaluated the morphology and immunohistochemistry of 85 canine cutaneous histiocytic tumours. The tumours were classified morphologically as either canine cutaneous histiocytomas (71 tumours) or canine cutaneous histiocytic sarcomas (14 tumours). The immunohistochemical analysis was conducted on paraffin sections using an antibody panel (against MHCII, CD18, CD79αcy, CD3 and E-cadherin). Histochemical staining with toluidine blue and Gomori silver impregnation was also performed. A follow-up was conducted via surveys. The histiocytic origin of the tumour cells was confirmed in 65 of the canine cutaneous histiocytomas and in 4 of the canine cutaneous histiocytic sarcomas. The tumours that had been misdiagnosed as canine cutaneous histiocytomas included plasmacytomas, epitheliotropic T-cell lymphomas and undetermined entities. The tumours misdiagnosed as canine cutaneous histiocytic sarcomas included plasmacytomas and non-epitheliotropic T-cell lymphomas, but the majority of them remained undetermined. The canine cutaneous histiocytomas showed MHCII, CD18 and E-cadherin expression, but in several of the tumours, the expression of CD18 or E-cadherin was confirmed in only a small percentage of the tumour cells. The regressing canine cutaneous histiocytomas showed increased T- and B-lymphocyte infiltration, a decreased mitotic index, transport of the MHCII molecules from the cytoplasm to the cell membrane and loss of E-cadherin expression in the tumour cells. The canine cutaneous histiocytic sarcomas showed both high morphological diversity and expression of MHCII and CD18. Two of the evaluated histiocytic sarcomas also showed expression of E-cadherin. In conclusion, immunohistochemistry, including analysis of MHCII, CD18 and the lymphocytic markers CD3 and CD79, should be performed for the diagnosis of canine cutaneous histiocytic tumours. The expression of E-cadherin in canine cutaneous histiocytic sarcomas suggests an origin of the tumour cells among Langerhans cells.
PMCID: PMC4330462  PMID: 25563490
Canine cutaneous histiocytoma; Histiocytic sarcoma; MHCII; CD18; E-cadherin; Regression
2.  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
3.  Phlegmasia caerulea dolens secondary to pelvic plasmacytoma and left femoral deep vein thrombosis☆ 
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.
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.
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.
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.
PMCID: PMC3785849  PMID: 23959409
Phlegmasia caerulea dolens; Deep vein thrombosis; Myeloma
4.  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.
PMCID: PMC502182  PMID: 7962610
5.  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.
PMCID: PMC3938377  PMID: 24626671
Multiple myeloma; Plasmacytoma; Skin manifestations
6.  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.
PMCID: PMC3130982  PMID: 21738502
Central venous catheter; Multiple myeloma; Extramedullary plasmacytoma; Subcutaneous plasmacytoma metastasis
7.  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
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.
PMCID: PMC3573150  PMID: 23420663
plasmacytoma; skull; diagnosis; therapy
9.  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
10.  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.
PMCID: PMC3821948  PMID: 24260722
11.  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.
PMCID: PMC500398  PMID: 8675729
12.  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.
PMCID: PMC2975009  PMID: 21060710
Pancreatic plasmacytoma; Jaundice; Endoscopic ultrasound-guided fine needle aspiration
13.  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.
PMCID: PMC3195345  PMID: 22084694
14.  Primary plasmacytoma of the testicle: a case report 
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.
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.
PMCID: PMC3198716  PMID: 21968163
15.  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.
PMCID: PMC3782939  PMID: 24086882
Fine needle aspiration cytology; Solitary plasmacytoma; Skull
16.  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.
PMCID: PMC3952166  PMID: 24634714
Plasmacytoma; Endosonography; Pancreatic mass; Multiple myeloma; Fine needle aspiration
17.  Solitary Bone Plasmacytoma Progressing into Retroperitoneal Plasma Cell Myeloma with No Related End Organ or Tissue Impairment: A Case Report and Review of the Literature 
Turkish Journal of Hematology  2014;31(3):286-289.
Solitary bone plasmacytomas and plasma cell myeloma are clonal proliferations of plasma cells. Many patients with solitary bone plasmacytomas develop plasma cell myeloma on follow-up. We present a case of a 70-year-old man who presented with fracture and a lytic lesion in the subtrochanteric region of the left femur and was assigned a diagnosis of solitary bone plasmacytoma. He received local curative radiotherapy. However, 4 months later his serum M protein and β2-microglobulin levels increased to 2.31 g/dL and 5.965 mg/L, respectively. He complained of abdominal fullness and constipation. Ultrasound and non-contrast CT imaging revealed multiple retroperitoneal masses. Colonoscopic examination was normal. Biopsy of the a retroperitoneal mass confirmed it to be a plasmacytoma. Repeat hemogram, blood urea, serum creatinine, skeletal survey, and bone marrow examination revealed no abnormalities. This is an unusual presentation of plasma cell myeloma, which manifested as multiple huge extramedullary retroperitoneal masses and arose from a solitary bone plasmacytoma, without related end organ or tissue impairment and bone marrow plasmacytosis. The patient succumbed to his disease 8 months after the appearance of the retroperitoneal masses. This case highlights the importance of close monitoring of patients diagnosed with solitary bone plasmacytoma with increased serum M protein and serum β2-microglobulin levels, so that early therapy can be instituted to prevent conversion to plasma cell myeloma.
PMCID: PMC4287030  PMID: 25330522
Solitary bone plasmacytoma; Retroperitoneal plasma cell myeloma; Related end organ or tissue impairment; Bone marrow plasmacytosis
18.  Primary isolated extramedullary plasmacytoma of colon 
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.
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.
PMCID: PMC1871591  PMID: 17470287
19.  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.
PMCID: PMC364815  PMID: 8246961
20.  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.
PMCID: PMC524229  PMID: 15520864
21.  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
22.  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
23.  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.
PMCID: PMC2805200  PMID: 19507209
24.  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.
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.
PMCID: PMC2610331  PMID: 19016727
25.  Disease recurrence in a transplant kidney in a patient with extramedullary plasmacytoma 
Renal transplantation in patients with malignancy is controversial. Renal transplantation is generally not considered for patients with multiple myeloma (MM) because of their extremely poor prognosis. There are few reports of MM recurrence among kidney transplant recipients. We present a case of disease relapse of plasmacytoma in a transplanted kidney. We present a patient with extramedullary plasmacytoma, who responded well to chemotherapy and underwent allogenic renal transplantation. He relapsed after 4 years with progression to extramedullary plasmacytoma. Despite minimal clinical symptoms, the patient had developed myeloma cast nephropathy and acute renal failure. His renal failure settled after excision of tumor. Extramedullary plasmacytoma as a mode of relapse is highly unusual. Experience of renal transplantation in MM is limited. In the literature, the recurrence of MM is mentioned as a severe complication with a poor graft prognosis. Extramedullary plasmacytoma as a mode of relapse is highly unusual. It should not be considered as a contraindication for transplantation. Renal transplantation for patients with end stage renal disease (ESRD) due to MM is possible. But large prospective studies are needed to develop a strategy for preventing multiple myeloma recurrence.
PMCID: PMC3009442  PMID: 21206716
Cast nephropathy; disease recurrence; plasmacytoma

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