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Home , Cryoglobulinemia, Plasmacytoma

Experimental 27, 7-12, 2005 (March) 7 Exp Oncol 2005 27, 1, 7-12 UP-DATE ON SOLITARY AND ITS MAIN DIFFERENCES WITH P. Di Micco1,*, B. Di Micco2 1Thrombosis center, Instituto Clinico Humanitas, Milan, Italy 2Clinical Chemistry, University of Sannio, Benevento, Italy

Solitary plasmacytoma is . It is a localized bone disease and for this reason it is different from multiple myeloma (systemic plasma cell neoplasm). Sometimes, solitary plasmacytoma precedes a following multi- ple myeloma. Clinical findings of solitary plasmacytoma are related to the univocal localization on damaged bone, while laboratory findings could be similar to multiple myeloma (i.e. M component, kidney dysfunction, blood calcium alterations, increased β-2-microglobulin). However, during a solitary plasmacytoma, laboratory findings could not be present contemporaneously such clinical complications (i.e. , immunological disorders with a trend toward infectious disease and/or autoimmunity, neurological disorders, haematological disorders, amyloidosis, POEMS syndrome). These raise the reason because solitary plasmacytoma has better prognosis compared to multiple myeloma. Key Words: solitary plasmacytoma, multiple myeloma.

General information damages are principally related to light chains and are Plasmacytoma, a clonal neoplastic disorder of bone quickly eliminated representing the Beence-Jones pro- marrow that originates from plasma cells, the last mat- tein in the urine [9, 10]. Moreover, immunoglobulin pro- uration stage of B lymphocytes [1-2], may appear as duced by plasmacytoma may be insoluble if cold tem- three different diseases: multiple myeloma (systemic perature is present, so causing a [5, disease), extramedullary plasmacytoma and solitary 11], in particular if a chronic C viral hepatitis is associ- plasmacytoma (localized bone disease) [3]. Solitary ated [5, 12]; kidney failure may result from reduced plasmacytoma may be an isolated disease or the first immunoglobulin elimination in the urine [9]. Amyloido- manifestation of a following multiple myeloma [4]. The sis may be also a consequence of light chains produc- isolated form of plasmacytoma seems to have a better tion by plasmacytoma [13]. prognosis [4, 5], while in case of subsequent multiple Rarely we may observe a non-secretory plasmacy- myeloma the prognosis is different [6]. Usually, clonal toma [14], in which κ and λ chains are intracytoplasmat- plasma cells involved in plasmacytoma produce a ic and may be detected by immunofluorescence [15]. κ λ monoclonal immunoglobulin as well as and light New insights on aetiology chain [7, 8]. A quantitative assay of plasma monoclonal The aetiology of plasmacytoma is still unknown and immunoglubulin may be performed during a plasma- although different pathways and stimuli seem to be in- cytoma and may also reflect tumor growth [9]. Com- volved. Recently several hypothesis has been under- monly this described alteration may appear as mono- lined, including a possible role of viral [5, 9]. A γ β α clonal spike in area, area or rarely in 2 area on viral chronic, clinical or subclinical infection, in fact, has serum electrophoresis [10]. In case of light chain pro- been often researched to understand its possible role duction patient’s immunoelectrophoresis in serum and as oncological risk factor in newly induced lymphoprolif- urine might reveal the clonal activity [8]. erative disease other than cytogenetics (e.g. deletion of During solitary plasmacytoma, plasma cells monoclonal chromosome 13q) [16]. In particular, virus proliferation is localized in , bone pain, bone has been often suggested to play a role in pathophysiol- destruction and pathological fractures represent the most ogy of lymphoproliferative [17–20]. High common clinical sign of the disease [3, 5]. Moreover, bone HCV seroprevalence, in fact, was revealed in patients damages may also be responsible for alteration of blood affected by B-cell non-Hodgkin’s [20, 21]: calcium levels [3], but this alteration is more frequent in these data has been also confirmed by the presence of multiple myeloma than in solitary plasmacytoma. HCV in bone marrow [22]. Moreover, HCV seropreva- Clinical complications during plasma cells disorders lence has been also identified in bone marrow of pa- are related also to immunoglobulin production which is tients affected by multiple myeloma so underlying one responsible for a relative (specific more time the role of HCV infection as risk factor for de- antigen immune response seems to be reduced during velopment of several haematological malignancies [23]. plasmacytoma) and kidney damages [1, 3, 9]. Kidney Lymphotropic action of HCV is related to its binding on Received: January 4, 2005. protein expressed on lymphocyte surface, named CD *Correspondence: E-mail: [email protected] 81 [20, 24]. However, further study should confirm epi- Abbreviations used: POEMS syndrome — polineuropathy, orga- demiological data because HCV seroprevalence seems nomegaly, endocrinopathy, multiple myeloma and skin changes. to be higher in some countries than others [25]. 8 Experimental Oncology 27, 7-12, 2005 (March)

Laboratory and instrumental data on solitary logical, immunological, haematological, infectious, plasmacytoma nephrological findings. Laboratory signs of solitary plasmacytoma are usu- Bone metabolism and pathological findings. Bone ally related to the immunoglobulin production, if secre- lysis and/or bone fractures are responsible for locali- tory component is present (i.e. monoclonal gammopa- zed pain of patients affected by solitary plasmacyto- thy in serum electrophoresis, light chains production ma. Bone pain, in fact, is the most common clinical detectable in serum and/or urine, cryoglobulinaemia), symptom of patients affected by plasma cells malig- blood calcium alterations, kidney dysfunction and se- nancy. Bone pain is prevalent during movements, while rum β-2-microglobulin levels [1, 9]. Moreover, β-2-mi- is infrequent during the night, like in bone metastatic croglobulin has also a relevant role in staging and prog- carcinoma. Bone lesions are induced by neoplastic cells nosis of multiple myeloma [9]. in bone marrow (i.e. neoplastic plasma cells) which re- Amyloidosis [13] and polyneuropathy, organomega- lease osteoclast activating factor, so inducing osteo- ly, endocrinopathy, multiple myeloma and skin changes clasts activation. Osteoclasts activity destroys the bone (POEMS syndrome) [26] may also be associated as structure and it seems not opposed by new bone for- complication of a secretory plasmacytoma. Usually pre- mation by osteoblasts. Glucocorticoids administration ferred bone localisations of solitary plasmacytoma are may stop this bone management (osteoclasts/osteo- sternum, skull, rib, jaw, humerus, femur, pelvis and in blasts imbalance) because it is due to cytokines re- these cases radiographic images show an unique coin lease by neoplastic plasma cells. lesion without peripheral edema, in particular if comput- In fact, an increase in vascular endothelial growth fac- β ed tomography is performed [9, 27]. However, in rare tor (VEGF), transforming growth factor beta 1 (TGF -1) cases also diffuse bone alterations are reported. and interleukin 6 (IL-6) levels have been found in patients Bone marrow aspirate and/or bone marrow biopsy affected by lymphoproliferative disorders [32, 33]. are normal in solitary plasmacytoma, while are usually Yet, increased levels of endostatin has also been diagnostic in multiple myeloma (presence of more than found in active phases of multiple myeloma, but its role 15% of neoplastic plasma cells) [9]; only localised bone should be further investigated in solitary plasmacyto- biopsy directed to damaged bone allows to identify ma [34]. neoplastic plasma cells and so a solitary plasmacyto- Furthermore, also osteopontin (OPN), an adhesive ma. Usually, solitary plasmacytoma is not related to a glycophosphoprotein produced by several cell types detectable M-component in serum electrophoresis, seem to be involved in plasmacytoma [35, 36]. Although while light chains could be produced [5]. Intracytoplas- OPN is produced by both osteoclasts and osteoblasts matic monoclonal immunoglobulin production could be it seems to play an important role on mechanical bone found in non-secretory plasmacytoma [14, 15]. remodelling in several conditions like accelerated bone Extramedullary solitary plasmacytoma is very rare loss conditions such as myeloma and bone metastasis and diagnosis could be checked out only with a locali- [35–37]. Serum OPN seems also to have a correlation β zed biopsy. Usually, we may have a solitary extrame- with -2-microglobulin levels, while there is no corre- dullary plasmacytoma localized on nasopharynx, na- lation with serum OPN levels and severity of bone mor- sal and gastrointestinal mucosa [28, 29], but also other bidity [36]. unusual sites are reported [30, 31]. Localised bone lesions may expand to the original However, we report below the most common clini- point and may lead to compression signs, in particular cal associated to plasma cells if vertebrae are involved (e.g. ). ; it is also important underline that during a This is a really interesting aspect of patients affected solitary plasmacytoma only few of the following mani- by plasma cell disorders because, associated to sep- festations may be present and solitary plasmacytoma sis, bone damages and related symptoms may repre- diagnosis is often related only to a specific clinical eval- sent a common cause of medical emergencies. Fur- uation of a bone related symptom. thermore, bone lysis, also if localised, may result in calcium mobilisation from bone so leading sometimes General clinical data to hypercalcemia. Plasma cells neoplasm usually affects people in the Hypercalcemia. Hypercalcemia is related to calci- range of 50–80 years [5]. Relevant clinical signs of soli- um mobilisation from affected bone and may lead to tary plasmacytoma may be summarised in localised acute and/or chronic complications. Hypercalcemia, in bone pain and bone alterations confirmed by X-ray fact, is related only to bone damage related to osteo- examination showing joint alteration and/or well defined clast/osteoblast impaired activity and to pathological radiographic lesions and bone fractures [5, 9]. Howev- fractures, while parathormone and vitamin D3 seem not er, other clinical data may be referred and are related to be involved. Acute complications are principally rep- to the three pathophysiological mechanisms of the dis- resented by neurological disturbances such as lethar- ease: localised bone symptoms, M-component, alter- gy, , depression and confusion, while chron- ations in blood calcium levels. These findings confirm ic effects of hypercalcemia are related to kidney dam- that systemic complications may be present also in ages. However, hypercalemia is rare in case of solitary solitary plasmacytoma, not only in multiple myeloma. plasmacytoma, while it is more frequent in case of So, complications may be represented also by neuro- multiple myeloma. Experimental Oncology 27, 7-12, 2005 (March) 9

Kidney failure. Hypercalcemia contributes to kidney of serum viscosity compared to water and is related failure of patients affected by plasma cells disorders, in primary to the excess of paraprotein (i.e. principally particular if M-component (toxic effects of light chain immunoglobulin) production by neoplastic plasma cells production) and amyloidosis are also present. Hyper- such as full immunoglobulin or light chains. Hypervis- calcemia often leads to tubular damages such as Fan- cosity related symptoms could be summarised in head- coni syndrome characterised by glucose and amino- ache, visual disturbances, astenia, rethinopathy, sen- acids loss in the urine, defects to acidify urine and pro- sorial and mental confusion. teinuria. Proteinuria is related to the excess of light On the other hand also peripheral neurological dis- chains fallen on tubules, while it is a nonselective pro- orders may be present in patients with plasma cells teinuria if glomeruli are involved. Yet, glomerular de- disorders both to sensorial or motor function such as posit of amyloid, recurrent in the urinary tract spinal cord compression, radicular pain due to bone and filtration troubles related to the presence of light lesion expansion and its peripheral oedema and also chains are other factors inducing progressive kidney loss of bowel or bladder control. Yet, sensorial peri- failure. Increase in light chains production present in pheral nerves damages could be related to amyloid in- tubules leads to an overload resulting in the toxic neph- filtration inducing different types of sensorial mono-poly- rological effects of light chain production of patients af- neuropathy. Rarely we may have a peripheral nerves fected by plasmacytoma. ischemia due to autoimmune mechanism. Infectious disease and sepsis. Infections are com- Haematological disorders. is rarely present mon in patients affected by plasma cells disorders, in in solitary plasmacytoma because the disease dominant- particular if M-component is present. If we could ex- ly occurs in an isolated bone and does not involve the clude M-component we probably find a hypogamma- full bone marrow, so hematopoiesis has not been hos- globulinemia related to destruction/fall of normal anti- tile. However, when present, anemia is probably related bodies and to a down regulation of immunoglobulin pro- to hemolysis due to the excess of produced parapro- duction by non-neoplastic plasma cells. This action is teins. Granulocytopenia and thrombocytopenia are very probably exerted by a small population of regulatory rare and usually due to autoimmune mechanisms. cells. Moreover, the reduced immunoglobulin produc- On the other hand, molecular abnormalities may be tion of patients affected by plasmacytoma associated present on clotting activity. Haemorragic trends could to M-component has been also associated to a poor be observed if M-component binds clotting factors such response to polysaccaride [9]. For this rea- as clotting factor I, clotting factor II, clotting factor V, son we may have a susceptibility to infections in these clotting factor VII, clotting factor VIII or von Willenbrand patients and pneumonia and pyelonephritis are the most factor, so inducing an acquired disorders mimicking common type of infections described. Several bacteri- inherited deficiency. Laboratory findings may confirm al pathogens, grampositive and gramnegative, are in- this acquired disorders with different tests focused to volved in these cases and are responsible of recurrent identify quantitation of clotting factors and after to its pyelonephritis of patients affected by plasmacytoma. related impaired activity (adhesion molecules, aggre- Yet, recurrent pyelonephritis seem to be also responsi- gation defects, impaired thrombin/fibrin formation, pro- ble of progressive kidney dysfunction. Furthermore, se- longed prothrombin time, prolonged activated partial rious infection, if not well treated and/or if a timely diag- thromboplastin time) [9]. nosis has not been done could also lead to a sepsis and Thrombotic trends may also be observed in patients sepsis has been identified as one of the most common affected by plasma cells disorders and could be relat- cause of death of these patients being often associated ed firstly to the acquired present in ma- to the occurrence of disseminated intravascular coagu- lignancy which could have several mechanisms [41, lation (DIC) and then to septic shock [38, 39]. 42]. Yet, also anticardiolipin antibodies and/or Moreover, produced immunoglobulin may have also anticoagulant could be produced by neoplastic plasma a trend to fall at cold temperature so inducing a cryo- cells inducing a secondary antiphospholipids syndrome. globulinaemia [5, 11], in particular if a chronic HCV Other. The reason is unknown because plasma cell infection is present. Patients affected by cryoglobuli- proliferation in plasma cells tumor is located dominantly nameia often show also a positivity in bone marrow, while rarely involves lymphatic tissues that may be present as subclinical and asymptomatic such as lymph nodes, spleen and intestinal lymphatic positivity or may be responsible of clinical arthritis with zone, so lymphatic tissue involvement in solitary plas- joints’ involvement [40]. macytoma is very rare, but we may find it during compli- Neurological disorders. Neurologic symptoms rarely cation such as amyloidosis and/or POEMS syndrome. occur in solitary plasmacytoma patients and could be Amyloidosis. Amyloidosis is a disease character- related to several alterations found in myeloma patho- ised by extracellular deposition of a well identified pro- physiology. We have already underlined the role of hy- tein (i.e. amyloid). Amyloid deposition may occur in percalcemia inducing clinical neurological disorders several tissues and/or organs and may induce specific such as lethargy, weakness, confusion and strong de- and progressive organ dysfunction [43]. Also different pression. forms of amyloid have been reported and among them Yet, neurological symptoms could also be due to we may identify also a light chain (κ or λ) or β-2-micro- hyperviscosity. Hyperviscosity is defined on the basis globulinemia prevalence in its structure [44, 45]. Of 10 Experimental Oncology 27, 7-12, 2005 (March) course, we have previously underlined the role of both have a solitary plasmacytoma diagnosis after evalua- components (i.e. light chains and β-2-microglobuline- tion of progressive bone pain or after well identified mia) in pathophysiology of plasma cells , so M-component. So, surgical approach, if possible, is we may have amyloidosis as complication of such case often considered and usually allows a really diagnosis of plasmacytoma. Usually, in the daily clinical manage- of solitary plasmacytoma. Furthermore also radiothe- ment we may observe two different form of amyloido- rapy and are considered. Median sur- sis during plasmacytoma: localised amyloidosis, in vival rate of a solitary plasmacytoma is longer than which only one or few tissues are damaged by amyloid patients with that with multiple myeloma [52, 53], be- protein, and systemic amyloidosis in which we may cause of the absence of diffused bone marrow alter- identify amyloid protein in several tissues. However, ations, and of reduced involvements of kidney damag- systemic amyloidosis commonly posesses an inherit- es and calcium metabolism. However, full clinical re- ed ground [46]. During amyloidosis we may observe mission is unusual. Prognosis of solitary plasmacytoma cardiac damages (perycarditis, dilatative cardiomyopa- could be worse if recurrence is present as in case of its thy, heath failure), liver disease (persistent aminotrans- evolution toward systemic disease (multiple myeloma) ferase elevation, hepatomegaly, liver fibrosis, portal hy- [9]. Also pharmacological toxicity should be considered pertension), skin alterations with several clinical mani- in patients treated with Melphalan and Prednisone pro- festations, acquired clotting deficiencies with a trend to tocol (those with acute , other oncological dis- hemorragic disorders, endocrinological disorders (seve- eases or sepsis (sepsis is a well known complication of ral type of thyroid dysfunction, thyroid cancer, chronic chemotherapy induced neutropenia) [54, 55]). pancreatic illness), chronic arthritis, central and periphe- REFERENCES ral neuropathy, gastroenterological disorders (macro- 1. William JW, Beutker E, Erslev AJ, Licthmann MA. glossia, intraoral masses on the oral mu- . New York: McGraw Hill, Inc, 1990; 1140–7. cosa [47], pancreatic disfunction, bowel localized dis- 2. Diebold J. World Health Organization classifica- function), nephrological disorders (in particular nephrotic tion of malignant . Exp Oncol 2001; 23: 101–3. syndrome) and rarely temporal giant cells arteritis [48, 3. Pisano JJ, Coupland R, Chen SY, Miller AS. Plas- 49]. Because both β-2-microglobulinemia and light macytoma of the oral cavity and jaws: a clinicopathologi- chains are produced during plasmacytoma’s natural cal study of 13 cases. Oral Surg Oral Med Oral Pathol history, reduction of their levels by plasmacytoma ther- Oral Radiol Endod 1997; 83: 265–71. apy (chemotherapy and/or radiotherapy) may improve 4. Knowling MA, Harwood AR, Bergsagel DE. Com- progression and outcome of amyloidosis. In particular, parison of extramedullary plasmacytoma with solitary and multiple plasma cell tumor of bone. J Clin Oncol 1983; a recent case report underlined a possible therapeutic 1: 255–62. support of chemotherapy in primary amyloidosis [50]. 5. Di Micco P, Niglio A, Torella R, Di Micco B. Soli- POEMS. The findings of POEMS syndrome are re- tary plasmacytoma of the jaw occurring in a elderly wom- lated to a progressive peripheral neuropathological dis- an affected by infection: a case report. order inducing continuous pain. However, POEMS rep- Tumori 2002; 88: 421–4. resents only a small subset of total peripheral neurop- 6. Ferrer AC, Ferrer AE, Fernandez IA, Pinzo BJ, athy present in plasmacytoma, so it is very rare a Ramos FV, Rancho TR. Solitary plasmacytoma of the POEMS diagnosis, in particular during a solitary plas- mandibole. Report of one case and review of the literature. macytoma. Unlike, in typical plasmacytoma patients A Otorrinolaringol Ibero Am 1995; 22: 609–18. affected by POEMS syndrome show frequently lym- 7. Huang JS, Ho YP, Ho KY, Wu YM, Chen CC, Wang CC, Tsai CC, Lin SF. Multiple myeloma with oral phatic tissues involvement such as lymph nodes swell- manifestation report of two cases. Kaoshiung J Med Sci ing, hepatomegaly and splenomegaly. However, also 1997; 13: 388–94. cardiomegaly has been shown in POEMS syndrome. 8. Cotticelli G, Di Micco P, Mastroianni M, Ciavattone A, Several endocrinopathy have been described in these Bartiromo D, Torella R. Long term survival of a young man patients and diabetes (described as type 2 diabetes) is with λ-IgD plasmacytoma. Exp Oncol 2003; 25: 313–4. frequent as thyroid disfunction, in particular secondary 9. Longo DL. Plasma cell disorders. In: Principles of hypothyroidism following an autoimmune thyroid dis- Internal Medicine. Harrison 15th Ed. New York: McGraw ease. Adrenal insufficiency is rarely noted, while hy- Hill Inc, 2001; 727–33. perprolactinemia has been often described and it is 10. Kadokura M, Tanio N, Nonaka M, Yamamoto S, secondary to the loss of hypothalamus inhibitory con- Kataoka D, Kushima M, Kimura S, Nakamaki T, Sato I, Takaba T. A surgical case of solitary plasmacytoma of rib trol. Furthermore, amenorrhea could be presented in origin with biclonal gammopathy. Jpn J Clin Oncol 2000; males such as impotence and gynecomastia in females. 30: 191–5. It seems that plasmacytoma treatment could improve 11. Persico M, De Marino FA, Di Giacomo Russo G, POEMS syndrome manifestations [51]. Persico E, Morante A, Palmentieri B, Torella R. Preva- lence and incidence of cryoglobulins in hepatitis C virus- Natural history related chronic hepatitis patients: a prospective study. Am We previously underlined that the majority of pa- J Gastroenterol 2003; 98: 884–8. tients affected by solitary plasmacytoma have an indo- 12. De Vita S, Sansonno D, Dolcetti R, Ferraccioli G, lent course, so showing a really slow progression of Carbone A, Cornacchiulo V, Santini G, Crovatto M, the disease over many years. Usually, in fact, patients Giorgini A, Dammacco F, Bolocchi M. Hepatitis C virus Experimental Oncology 27, 7-12, 2005 (March) 11 within a malignant lymphoma lesion in the corse of type II Clinical outcome of extramedullary plasmacytoma. Hae- mixed cryoglobulinaemia. Blood 1995; 86: 1887–992. matologica 2000; 85: 47–51. 13. Ing EB, Woolf IZ, Younge BR, Bjornsson J, Lea- 30. Brame LA, Dwivedi R, Rice TW, Skierczynski PA. vitt JA. Systemic amyloidosis with temporal artery in- Atrial plasmacytoma and hypercalcemia. Endocr Pract 2003; volvement mimicking temporal arteritis. Ophtalmic Surg 9: 225–8. Lasers 1997; 28: 328–31. 31. Mandagere KA, Schimke RN, Kyner JL, Bateia PS. 14. River GL, Tewksbury DA, Fudenberg HH. “Non- An unusual cellar mass: solitary plasmacytoma. Endocr Pract secretory” multiple myeloma. Blood 1972: 40: 204–6. 1998; 4: 382–6. 15. Hurez D, Preud’ Homme JL, Seligmann M. In- 32. Urbanska-Rys H, Wierzbowska A, Robak T. Cir- tracellular “monoclonal” immunoglobulin in non-secretory culating angiogenic cytokines in multiple myeloma and human myeloma. J Immunol 1970; 104: 263–4. related disorders. Eur Cytokine Network 2003; 14: 40–51. 16. Fonseca R, Blood E, Rue M, Harrington D, 33. Lauta VM. A review of the cytokine network in Oken MM, Kyle RA, Dewald GW, Van Ness B, Van multiple myeloma: diagnostic, prognostic, and therapeuti- Wier SA, Henderson KJ, Bailey RJ, Greipp PR. Clini- cal implications. Cancer 2003; 97: 2440–52. cal and biologic implications of recurrent genomic aberra- 34. Urbanska-Rys H, Robak T. High serum level of tions in myeloma. Blood 2003; 101: 4569–75. endostatin in multiple myeloma at diagnosis but not in the 17. Luppi M, Ferrari MG, Bonaccorsi G, Longo G, plateau phase after treatment. Mediators Inflamm 2003; Numi F, Birozzi P, Marasca R, Mussini C, Torelli G. 12: 229–35. Hepatitits C virus infection in subsets of neoplastic lym- 35. Standal T, Borset M, Sundan A. The role of os- phoproliferation not associated with cryoglobulinaemia. teopontin in adhesion, migration, cell survival and bone Leukemia 1996; 10: 351–5. remodelling. Exp Oncol 2004; 26: 179–84. 18. Persico M, De Renzo A, Persico E, Torella D, 36. Standal T, Hjorth-Hansen H, Rasmussen T, Rotoli B, Torella R. Chronic liver disease and lymphop- Dahl IMS, Lenhoff S, Brenne AT, Seidel C, Baykov V, roliferative disorders in HCV-positive patients: a working Waage A, Borset M, Sundan A, Hjertner O. Osteopon- hypothesis. J Hepatol 1998; 29: 857–9. tin is an adesive factor for myeloma cells and is found in 19. Mazzaro C, Zagonel V, Monfardini S, Tulissi P, increased levels in plasma from patients with multiple Passini E, Fanni M, Sorio R, Bortolus R, Crovatto M, myeloma. Haematologica 2004; 89: 174–82. Santini G, Tiribelli C, Sasso F, Masutti R, Pozzato G. 37. Hotte SJ, Winqvist EW, Stitt L, Wilson SM, Hepatitis C virus and non-Hodgkin’s lymphomas. Br J Chambers AF. Plasma osteopontin: associations with sur- Haematol 1996; 94: 544–50. vival and metastasis to bone in men with hormone-refrac- 20. Hausfater P, Rosenthal E, Cacoub P. Lympho- tory prostate carcinoma. Cancer 2002; 95: 506–12. proliferative disease and hepatitis C virus infection. Ann 38. Di Micco B, Metafora S, Colonna G, Carteni` M, Med Interne 2000; 151: 53–7. Ragone R, Macalello MA, Di Micco P, Baroni A, Cata- 21. Zuckerman E, Zuckerman T, Levine Am, Douer D, lanotti P, Tufano MA. Porins from Salmonella typhimuri- Gutenkust K, Mizokami M, Qian DG, Velankar M, Nath- um accelerate human blood coagulation in vitro by selec- wani BN, Fong TL. Hepatitis C virus infection in pa- tive stimulation of thrombin activity: implication in septic tients with B-cell non-. Ann Intern shock DIC pathogenesis. J Endotoxin Res 2001; 7: 211–7. Med 1997; 127: 423–8. 39. Levi M. Pathogenesis and treatment of disseminat- 22. Radkowsky M, Kubicka J, Kisiel E, Cianciara J, ed intravascular coagulation in the septic patient. J Crit Novicki M, Rasela J, Laskus T. Detection of active he- Care 2001; 16: 167–77. patitis C virus and hepatitis G virus/GB virus C replication 40. Fornasieri A, Bernasconi P, Ribero ML, Sinico RA, in bone marrow in human subjects. Blood 2000; 95: 3986–9. Fasola M, Zhou J, Portera G, Tagger A, Gibelli S, 23. Montella M, Crispo A, Russo F, Ronga D, Tri- D’Amico G. Hepatitis C virus (HCV) in lymphocytes sub- dente V, Tamburini M. Hepatitis C virus infection and sets and in B lymphocytes expressing rheumatoid factor new association with extrahepatic disease: multiple myelo- cross-reacting idiotype in type II mixed cryoglobulinaemia. ma. Haematologica 2000; 85: 833–4. Clin Exp Immunol 2000; 122: 400–3. 24. Wack A, Soldaini E, Tseng C, Nuti S, Klimpel G, 41. Falanga A. Mechanism of hypercoagulation in ma- Abrignani S. Binding of the hepatitis C virus envelope lignancy and during chemotherapy. Haemostasis 1998; protein E2 to CD 81 provides a co-stimulatory signal for 28: 50–60. human T-cells. Eur J Immunol 2001; 31: 166–75. 42. Di Micco P, D’Uva M. Editorial comment. To 25. Mayo MJ. Extrahepatic manifestations of hepatitis C understand the two way clinical association between can- infection. Am J Med Sci 2003; 325: 135–48. cer and thrombophilia. Exp Oncol 2003; 25: 243–4. 26. Singh D, Wadhwa J, Kumar L, Raina V, Agarwal A, 43. Sipe JD. Amyloidosis. Crit Rec Clin Lab Sci 1994; Kochupillai V. POEMS syndrome: experience with four- 31: 325–54. teen cases. Leuk Lymphoma 2003; 44: 1749–52. 44. Jones LA. Advances in amyloidosis. Curr Opin 27. Scutellari PN, Orzincolo C. Bone disease in mul- Rheumatol 1993; 5: 62–76. tiple myeloma. Analysis of 253 controlled cases, with reap- 45. Sipe JD, Cohen AS. Amyloidosis. In: Principles of praisal of diagnostic criteria and current imaging tecqniques. Internal Medicine. Harrison 15th Ed. New York: McGraw Radiol Med 1993; 85: 235–46. Hill Inc, 2001; 1974–9. 28. Ruiz Montes F, Rene Espinet JM, Buenestado 46. Benson MD. Inherited amyloidosis. J Med Genet Garcia J, Panades Siurana MJ, Egido Garcia R, Ramos 1991; 28: 73–8. Yanes J. Primary gastric plasmacytoma of rapid growth 47. Tabachnik TT, Levine B. Multiple myeloma involving presenting with upper gatrointestinal bleeding. Am J Gas- the jaw and oral soft tissues. J Oral Surg 1976; 34: 931–3. troenterol 1995; 90: 1349–50. 48. Hutson TE, Hoffman GS. Temporal concurrence 29. Galieni P, Cavo M, Pulsioni A, Avvisati G, Bigaz- of and cancer: a report of 12 cases. Arthritis zi C, Neri S, Caliceti U, Benni M, Ronconi S, Lauria F. Care Res 2000; 13: 417–23. 12 Experimental Oncology 27, 7-12, 2005 (March)

49. Rodon P, Friocourt P, Blanchet S, Levallois D. Tem- Tura S. Melphalan-prednisone (MP) versus alternating poral artery involvement revealing AL amyloidosis and Ig D combination VAD/MP or VDN/MP as primary therapy . J Rheumatol 1996; 23: 189–90. for multiple myeloma: final analysis of a randomized clin- 50. Myers B, Lachmann H, Russel NH. Novel combi- ical study. Haematologica 2002; 87: 934–42. nation chemotherapy for primary (AL) amyloidosis my- 53. Bolek M, Sztuk S. Ten years survival of solitary eloma: clinical, laboratory and serum amyloid-P protein plasmacytoma. Pol Merkuriusz Lek 2001; 11: 160–1. scan improvement. Br J Haematol 2003; 121: 816–7. 54. Piccinini L, Artusi T, Bonacorsi G, Arigliano V. 51. Singh D, Wadhwa J, Kumar L, Raina V, Agarwal A, Acute leukemia of plasmablastic type as terminal phase of Kochupillai V. POEMS syndrome: experience with four- multiple myeloma. Haematologica 2002; 87: EIM04. teen cases. Leuk Lymphoma 2003; 44: 1749–52. 55. Crawford J, Dale DC, Lyman GH. Chemothera- 52. Cavo M, Benni M, Ronconi S, Fiacchini M, py-induced neutropenia: risks, consequences, and new di- Gozzetti A, Zamagni E, Cellini C, Tosi P, Baccarani M, rections for its management. Cancer 2004; 100: 228–37.

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Ñîëèòàðíàÿ ïëàçìîöèòîìà — îïóõîëü, ñîñòîÿùàÿ èç ïëàçìàòè÷åñêèõ êëåòîê, — ÿâëÿåòñÿ ëîêàëüíûì çàáîëåâàíè- åì êîñòíîé òêàíè è ýòèì îòëè÷àåòñÿ îò ìíîæåñòâåííîé ìèåëîìû (ñèñòåìíîãî íåîïëàñòè÷åñêîãî ïðîöåññà èç ïëàçìàòè÷åñêèõ êëåòîê). Èíîãäà ñîëèòàðíàÿ ïëàçìîöèòîìà ïðåäøåñòâóåò ðàçâèòèþ ìíîæåñòâåííîé ìèåëîìû. Êëèíè÷åñêèå ïðîÿâëåíèÿ ñîëèòàðíîé ïëàçìîöèòîìû îòíîñÿòñÿ ê îäèíî÷íîé ëîêàëèçàöèè íà ïîâðåæäåííîé êîñ- òè, â òî âðåìÿ êàê ëàáîðàòîðíûå ïîêàçàòåëè ìîãóò áûòü ñõîäíûìè ñ òàêîâûìè ïðè ìíîæåñòâåííîé ìèåëîìå (íàëè÷èå M-ãðàäèåíòà, äèñôóíêöèè ïî÷åê, èçìåíåíèé ñîäåðæàíèÿ êàëüöèÿ â êðîâè, ïîâûøåííûé óðîâåíü β-2-ìèêðîãëîáóëèíà). Îäíàêî ðàçâèòèå ñîëèòàðíîé ïëàçìîöèòîìû ìîæåò íå ñîïðîâîæäàòüñÿ èçìåíåíèÿìè ëàáî- ðàòîðíûõ ïîêàçàòåëåé è îäíîâðåìåííûì âîçíèêíîâåíèåì òàêèõ êëèíè÷åñêèõ îñëîæíåíèé, êàê ïî÷å÷íàÿ íåäîñòà- òî÷íîñòü, èììóíîëîãè÷åñêèå íàðóøåíèÿ ñ òåíäåíöèåé ê ðàçâèòèþ èíôåêöèîííûõ çàáîëåâàíèé è/èëè àóòîèììóí- íûõ çàáîëåâàíèé, íåâðîëîãè÷åñêèå è ãåìàòîëîãè÷åñêèå ðàññòðîéñòâà, àìèëîèäîç, POEMS). Ýòèì îáúÿñíÿåòñÿ òîò ôàêò, ÷òî ïðîãíîç ïðè ñîëèòàðíîé ïëàçìîöèòîìå áëàãîïðèÿòíåé, ÷åì òàêîâîé ïðè ìíîæåñòâåííîé ìèåëîìå. Êëþ÷åâûå ñëîâà: ñîëèòàðíàÿ ïëàçìàöèòîìà, ìíîæåñòâåííàÿ ìèåëîìà.

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