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Diagnosis and management of solitary
plasmacytoma of bone
INTRODUCTION — Plasma cell neoplasms (plasma cell dyscrasias) are a group of entities characterized by the neoplastic proliferation of a single clone of plasma cells, typically producing a monoclonal immunoglobulin. Plasma cell neoplasms can present as a single lesion (solitary plasmacytoma) or as multiple lesions (multiple myeloma). Solitary plasmacytomas most frequently occur in bone (plasmacytoma of bone), but can also be found outside bone in soft tissues (extramedullary plasmacytoma). Why some patients develop multiple myeloma and others plasmacytoma is not understood, but might be related to differences in cellular adhesion molecules or chemokine receptor expression profiles of the malignant plasma cells. Solitary plasmacytoma of bone (SPB, also called osseous plasmacytoma) is a localized tumor in the bone comprised of a single clone of plasma cells in the absence of other features of multiple myeloma (ie, anemia, hypercalcemia, renal insufficiency, or multiple lytic bone lesions) EPIDEMIOLOGY — About 5 percent of all cases of plasma cell disorders are SPB. In the United States, the incidence is approximately 0.15 cases/100,000 person-years accounting for approximately 450 new cases per year. The incidence is highest in Blacks and lowest in Asians and Pacific Islanders. Men are diagnosed twice as frequently as women. The median age at diagnosis is 55 to 65 years, which compares with a median age at diagnosis of 71 years for patients with multiple myeloma. SPB has been reported in patients as young as 15 years CLINICAL FEATURES — Most patients present with skeletal pain or a pathologic fracture of the affected bone. Patients with vertebral involvement may have severe back pain or neurologic compromise (eg, cord compression). Less commonly, SPB can extend into the surrounding soft-tissue, resulting in a palpable mass. The most common bones involved are those with active hematopoiesis; the axial skeleton is more commonly involved than is the appendicular skeleton, while disease in the distal appendicular skeleton below the knees or elbow is extremely rare The following bone sites are listed in order of decreasing frequency of involvement: the vertebrae, pelvis, ribs, upper extremities, face, skull, femur, and sternum. The thoracic vertebrae are more commonly involved than the lumbar, sacral, or cervical spine By definition, patients with SPB do not have anemia (ie, hemoglobin <10 g/dL or 2 g/dL below normal), hypercalcemia (ie, serum calcium >11.5 mg/dL [2.875 mmol/liter]), or renal insufficiency (ie, serum creatinine >2 mg/dL [176.8 µmol/liter]) attributable to the underlying plasma cell disorder. EVALUATION — The evaluation of a patient with a suspected SPB should include the following studies in addition to a complete history and physical examination:
DIAGNOSIS — The diagnosis of SPB requires the following
The presence of a monoclonal (M) protein does not exclude the diagnosis of SPB, and a small M-protein may be present in 30 to 75 percent of cases. This M-protein may or may not disappear with treatment. The bone marrow of patients with SPB should have no clonal plasma cells. Some patients may demonstrate up to 10 percent clonal plasma cells, and are considered as having both SPB and monoclonal gammopathy of undetermined significance (MGUS). These patients are treated in a similar fashion to SPB, but may have a higher risk of progression to symptomatic myeloma. If patients suspected to have SPB have 10 percent or more clonal plasma cells in the bone marrow, they should be considered to have Durie-Salmon stage I myeloma rather than SPB. These patients should be treated in a similar fashion to SPB. TREATMENT — The primary treatment for patients with SPB is localized radiation therapy. Surgery may be required for patients with structural instability of the bone, retropulsed bone, or rapidly progressive symptoms from cord compression. The use of adjuvant of prophylactic chemotherapy in this population is controversial. Bisphosphonates are not recommended for patients with SPB, except in the setting of underlying osteopenia. The median overall survival of patients with SPB is approximately 10 years. Overall survival rates at 5 and 10 years are approximately 75 and 45 percent, respectively with corresponding disease-free survival rates of 45 and 25 percent. A little more than half of patients with SPB will eventually develop overt multiple myeloma. Radiation — Localized radiation therapy (RT), given at a dose of 40 to 50 Gy over approximately four weeks, is the treatment of choice for SPB. Localized RT directed at the tumor site should be given even if the plasmacytoma appears to have been completely excised for diagnostic purposes. The local response rate to RT exceeds 80 to 90 percent, and appears to be highest in tumors <5 cm in maximum diameter The use of RT for the treatment of SPB is largely based upon data from retrospective studies. There have been no randomized trials of RT for patients with SPB. The largest retrospective study included 258 patients with SPB (206 patients) or extramedullary plasmacytoma (52 patients). Treatments included RT alone (214 patients), RT plus chemotherapy (34 patients), and surgery alone (8 patients). Five-year rates of overall survival, disease-free survival, and local control were 74, 50, and 86 percent, respectively. Patients who received localized RT had a lower rate of local relapse than those who did not receive radiation (12 versus 60 percent). The ideal radiation dose for SPB is unknown. Published papers have reported doses ranging from 30 to 60 Gy, with most radiation oncologists advocating the use 40 to 50 Gy. For patients with SPB, we recommend initial localized RT rather than chemotherapy or observation. RT should be delivered at a dose of 40 to 50 Gy over four weeks directed at the tumor or site of tumor resection (in the case of complete diagnostic excision). Chemotherapy — The use of adjuvant or prophylactic chemotherapy for SPB is controversial. Some studies have suggested no benefit with adjuvant therapy while others have concluded that adjuvant chemotherapy prevents or delays the median time to progression to multiple myeloma (MM) However, the above studies are small, and overall we believe that the available literature does not support the use of adjuvant chemotherapy in patients with SPB. This approach treats patients with locally treated SPB in a similar fashion to those with asymptomatic MM. For this group of patients there is an absence of clear benefit from chemotherapy with currently available therapies and reports that some patients remain stable without treatment over extended periods of time. For patients with SPB, we suggest observation after initial radiation therapy rather than the use of adjuvant chemotherapy. Patients with multiple plasmacytoma — Approximately 30 to 50 percent of patients with suspected SPB will have multiple asymptomatic lesions detected by PET/CT or MRI of the spine. The management of patients with "multiple solitary plasmacytomas," defined as the presence of more than one plasmacytoma (occurring concurrently or sequentially) in the absence of bone marrow evidence of multiple myeloma (MM), is challenging. Many clinicians advocate the use of local radiation directed at the symptomatic site with further treatment postponed until the development of symptoms. It is our opinion that if the patient develops two or three apparently solitary lesions within a period of one to two years, subsequent therapy should be as if the patient has MM. PROGNOSIS General — The median overall survival of patients with SPB is approximately 10 years. Overt multiple myeloma (MM) ultimately develops in 50 to 60 percent of patients with SPB after initial radiation therapy. This disease progression is thought to arise from previously undetectable myeloma cells in areas outside of the radiation field or from myeloma within the radiation field in the setting of sublethal radiation doses. It is unknown whether this rate of progression will decrease with the incorporation of more sensitive imaging modalities (eg, MRI) at the time of diagnosis. While most patients will progress to MM within the first four years, others may demonstrate progression more than a decade after completion of therapy. As an example, two retrospective analyses found that approximately two-thirds of the patients who progress do so within four years, although progression can occur as late as 13 years. Three patterns of failure were seen:
Relapse rates are higher in older patients and in those with axial skeletal lesions, while patients younger than 60 years and with tumors <5 cm have a better overall survival rate Other reported predictors for conversion to MM include a large solitary lesion, the presence of osteopenia, reduction in uninvolved immunoglobulin levels (eg, low levels of IgA and/or IgM in a patient with an IgG plasmacytoma), and the presence of high-grade angiogenesis in the tumor sample. Monoclonal protein and abnormal free light chain ratio — The presence or absence of a monoclonal (M) protein at the time of diagnosis of SPB does not appear to have a major effect on long-term outcome, although persistence of a serum M-protein after radiation therapy appears to be a significant predictor of subsequent progression to MM. In one series, for example, the 10-year myeloma-free survival was superior for those whose M-protein resolved at one year following radiation therapy (91 versus 29 percent) In another study of 116 patients with SPB, two factors were predictive of disease progression to myeloma at five years
A risk stratification model consisting of these two variables yielded five-year progression rates of 13, 26, and 62 percent for those with zero (low risk), one (intermediate risk), or two (high risk) of these risk factors, respectively. SUMMARY AND RECOMMENDATIONS — Solitary plasmacytoma of bone (SPB) is a localized tumor in the bone comprised of a single clone of plasma cells in the absence of other features of multiple myeloma (ie, anemia, hypercalcemia, renal insufficiency, or multiple lytic bone lesions). Most patients present with skeletal pain or a pathologic fracture of the affected bone. The evaluation of a patient with a suspected SPB should include a biopsy of the suspected lesion, a unilateral bone marrow aspirate and biopsy, and laboratory studies. Imaging should include a metastatic bone survey and either a positron emission tomography/computed tomography (PET/CT) scan or magnetic resonance imaging (MRI) of the entire spine and pelvis.
Bisphosphonates are not recommended for patients with SPB, except in the setting of underlying osteopenia. |