Experimental Oncology 27, 7-12, 2005 (March) 7 Exp Oncol 2005 27, 1, 7-12 UP-DATE ON SOLITARY PLASMACYTOMA AND ITS MAIN DIFFERENCES WITH MULTIPLE MYELOMA P. Di Micco1,*, B. Di Micco2 1Thrombosis center, Instituto Clinico Humanitas, Milan, Italy 2Clinical Chemistry, University of Sannio, Benevento, Italy Solitary plasmacytoma is plasma cell neoplasm. 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. kidney failure, 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 cryoglobulinemia [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 infection [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, hepatitis C virus proliferation is localized in bone marrow, bone pain, bone has been often suggested to play a role in pathophysiol- destruction and pathological fractures represent the most ogy of lymphoproliferative malignancies [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 lymphoma [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 immunodeficiency (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 signs and symptoms associated to plasma cells if vertebrae are involved (e.g. spinal cord compression). malignancy; 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