Solitary plasmacytoma of bone

INTRODUCTION — Plasma cell neoplasms (plasma cell dyscrasias) are a group of entities characterized by the neoplastic proliferation of clonal plasma cells, typically producing a monoclonal immunoglobulin. Plasma cell neoplasms can present as a single lesion (solitary plasmacytoma) or as multiple lesions (multiple myeloma [MM]). 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 MM 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 MM (ie, anemia, hypercalcemia, kidney impairment, or multiple lytic bone lesions).

The diagnosis and management of SPB will be reviewed here. The diagnosis and treatment of other plasma cell disorders (eg, solitary extramedullary plasmacytoma, MM, immunoglobulin light chain [AL] amyloidosis, monoclonal gammopathy of undetermined significance) are discussed separately.

●(See "Solitary extramedullary plasmacytoma".)

●(See "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis".)

●(See "Multiple myeloma: Overview of management".)

●(See "Clinical presentation, laboratory manifestations, and diagnosis of immunoglobulin light chain (AL) amyloidosis".)

●(See "Diagnosis of monoclonal gammopathy of undetermined significance".)

EPIDEMIOLOGY — SPB accounts for approximately 5 percent of all plasma cell disorders [1].

●Annual incidence – In the United States (SEER database), the incidence is approximately 0.15 cases/100,000 person-years accounting for approximately 450 new cases per year. The incidence is highest in Black Americans and lowest in Asian/Pacific Islanders (as reported in the SEER database) [1].

●Age and sex distribution – 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 (MM) [1-3]. SPB has been reported in patients as young as 15 years [4,5]. The diagnosis is twice as common in males.

●Familial risk – Although an increased risk of plasma cell dyscrasia has been reported in first-degree relatives of patients with monoclonal gammopathy of undetermined significance and patients with MM [6], there are no data on familial predisposition in solitary plasmacytoma.

CLINICAL FEATURES — Most patients with SPB 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 [3,7]. The following bone sites are listed in order of decreasing frequency of involvement: the vertebrae, pelvis, ribs, upper extremities, face, skull, femur, and sternum [8]. The thoracic vertebrae are more commonly involved than the lumbar, sacral, or cervical spine [9].

By definition, patients with SPB do not have anemia, hypercalcemia, or kidney impairment 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:

●A biopsy of the suspected lesion, usually obtained using computed tomography (CT) or magnetic resonance imaging (MRI) guidance.

●A complete blood count and differential with examination of the peripheral blood smear.

●A chemistry screen that includes measurements of serum calcium, creatinine, albumin, lactate dehydrogenase, beta-2 microglobulin, and C-reactive protein. (See "Multiple myeloma: Staging and prognostic studies".)

●A serum protein electrophoresis (SPEP) with immunofixation and quantitation of immunoglobulins, and a serum free light chain (FLC) assay. (See "Laboratory methods for analyzing monoclonal proteins".)

●A routine urinalysis and a 24-hour urine collection for urine protein electrophoresis (UPEP) and immunofixation. The FLC assay cannot replace the 24-hour urine collection with UPEP and immunofixation in patients with a confirmed plasma cell proliferative disorder. (See "Laboratory methods for analyzing monoclonal proteins".)

●A unilateral bone marrow aspiration and/or biopsy with cytogenetic/fluorescence in situ hybridization (FISH) analysis [10].

●Whole-body MRI and/or combined ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/CT are needed to exclude the presence of additional lesions, and the use of at least one of these examinations is mandatory [11,12]. Small prospective studies support their use in staging, and PET/CT provides additional prognostic information [13-16]. Using both PET/CT and MRI may offer complementary information. If neither PET/CT nor MRI is available, whole-body CT can be used to exclude other lesions. (See 'Imaging' below.)

DIAGNOSIS

SPB — The diagnosis of solitary plasmacytoma of bone (SPB) requires the following (table 1) [17]:

●Biopsy-proven solitary tumor of bone with evidence of clonal plasma cells (picture 1). (See "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis", section on 'Morphology and immunophenotype'.)

●Cross-sectional imaging demonstrates no other lytic lesions and no extramedullary lesions.

●Bone marrow aspirate and/or biopsy contains no clonal plasma cells.

●No anemia, hypercalcemia, or kidney impairment that could be attributed to a clonal plasma cell proliferative disorder. (See 'Clinical features' above.)

●Involved:uninvolved serum free light chain (FLC) ratio <100.

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.

Patients with true SPB who meet the strict criteria listed above have a recurrence/progression rate of approximately 10 percent within three years [18,19].

SPB with minimal marrow involvement — The bone marrow of patients with solitary plasmacytoma of bone (SPB) should have no clonal plasma cells. Patients who otherwise meet the criteria for SPB and have up to 10 percent clonal plasma cells have "SPB with minimal marrow involvement" [17].

SPB with minimal marrow involvement is treated in a similar fashion to SPB with no clonal plasma cells but has a much higher risk of developing a recurrent or new SPB or progression to symptomatic myeloma.

In two independent studies, low levels of clonal plasma cells were detected by flow cytometry in 49 to 68 percent of patients with SPB [18,19]. In both studies, 71 to 72 percent of these patients with minimal marrow involvement progressed to multiple myeloma (MM) or developed a recurrent or new plasmacytoma. This compares with a reported recurrence/progression rate of approximately 10 percent in patients with SPB with no clonal plasma cells [18,19].

SPB meeting criteria for multiple myeloma — Patients initially suspected to have solitary plasmacytoma of bone (SPB) may meet diagnostic criteria for MM (table 2) [17]. (See 'Multiple myeloma' below.)

Two scenarios are of particular note:

●Patients with a single plasmacytoma and ≥10 percent clonal plasma cells in the bone marrow and no other myeloma-defining events (ie, no evidence of end-organ damage or biomarkers of malignancy). While these patients meet the criteria for MM, they are not well represented in myeloma trials, and there are limited data to guide therapy. We agree with the International Myeloma Working Group (IMWG) guidelines that such patients do not have a clear indication for systemic therapy [17]. They may be treated in a similar fashion to SPB if the bone marrow plasmacytosis is modest. Most of these patients will be staged as Durie-Salmon stage I myeloma. If patients have more extensive plasmacytosis, systemic therapy can be considered in addition. (See "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis", section on 'Diagnosis'.)

●Patients with multiple lytic bone lesions and <10 percent clonal plasma cells in the intervening bone marrow. Such patients have a small but recognized clinical subtype of MM called "macrofocal multiple myeloma" and previously referred to as "multiple solitary plasmacytoma of bone." The management of these patients depends on the number and location of lesions. (See 'Patients with multiple plasmacytomas (macrofocal myeloma)' below.)

The use of palliative radiation therapy (RT) to control local lesions in patients with overt MM is discussed separately. (See "Multiple myeloma: Overview of management", section on 'Skeletal lesions and bone health'.)

DIFFERENTIAL DIAGNOSIS — It is important to distinguish SPB both from benign causes, which can present with similar manifestations, and from other plasma cell dyscrasias for the purposes of prognosis and treatment. Among benign causes, patients with fibrous dysplasia can present with lytic bone lesions that can be confused with myeloma [20]. (See "Nonmalignant bone lesions in children and adolescents", section on 'Fibrous dysplasia'.)

The main conditions to consider in the differential diagnosis are multiple myeloma (MM), POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) syndrome, and metastatic carcinoma. This differential diagnosis is discussed in more detail separately. (See "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis", section on 'Differential diagnosis'.)

Multiple myeloma — The plasma cells of SPB are histologically identical to those seen in MM; however, the treatment of these two entities differs dramatically, necessitating a careful review of the diagnosis. (See "Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis".)

SPB and SPB with minimal marrow involvement are distinguished from MM by the following:

●Bone marrow demonstrates <10 percent clonal plasma cells. As noted above, patients with an apparent SPB and <10 percent clonal plasma cells in the marrow are considered to have SPB with minimal bone marrow involvement. (See 'SPB with minimal marrow involvement' above.)

●MRI and/or positron emission tomography (PET)/CT show no other lytic or marrow lesions (except for the primary solitary lesion).

●No other end-organ damage attributable to the underlying plasma cell disorder (eg, anemia, hypercalcemia, and kidney impairment).

●Involved:uninvolved serum free light chain (FLC) ratio <100.

Patients suspected of having SPB with ≥10 percent clonal plasma cells in the bone marrow may be treated in a similar fashion to SPB if the bone marrow plasmacytosis is modest and there are no other myeloma-defining events. Most of these patients will be staged as Durie-Salmon stage I MM (table 2). If patients have more extensive plasmacytosis, systemic therapy can be considered in addition, although there are limited data available to guide therapy.

The term "macrofocal multiple myeloma" (previously referred to as "multiple solitary plasmacytoma of bone") is used to describe an uncommon but recognized clinical subtype of MM that presents with multiple lytic bone lesions and <10 percent clonal plasma cells in the intervening bone marrow.

Patients with macrofocal myeloma are generally younger than the overall myeloma population and have a better prognosis, responding well to proteasome inhibitors [21,22]. (See 'Patients with multiple plasmacytomas (macrofocal myeloma)' below.)

POEMS syndrome — POEMS syndrome (osteosclerotic myeloma; polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) is a monoclonal plasma cell disorder accompanied by symptoms and/or signs of peripheral neuropathy, osteosclerotic lesions, Castleman disease, organomegaly, endocrinopathy (excluding diabetes mellitus or hypothyroidism), edema, typical skin changes, and/or papilledema. These patients typically have elevated serum vascular endothelial growth factor (VEGF) levels. (See "POEMS syndrome".)

Patients with either SPB or POEMS syndrome may present with a single osteolytic bone lesion with a sclerotic rim or a single osteosclerotic bone lesion and a small amount of a monoclonal protein in the serum or urine. Although not diagnostic, the presence of an osteosclerotic component to the bone lesion and/or other minor criteria for POEMS should distinguish patients with POEMS from those with SPB (table 3).

Metastatic carcinoma — The presence of a lytic bone lesion in a patient with a monoclonal gammopathy suggests the possibility of SPB or MM. However, metastatic carcinoma (eg, kidney, breast, non-small cell lung cancer) can produce lytic lesions, and a subset of patients presenting in this way will have metastatic cancer with an associated, unrelated monoclonal gammopathy (eg, monoclonal gammopathy of undetermined significance [MGUS]). Typically, however, patients with metastatic carcinoma have multiple lytic or mixed lytic sclerotic bone lesions rather than a single lesion such as that seen with SPB.

Persons presenting with lytic bone lesions, constitutional symptoms, a small monoclonal (M) component, and <10 percent clonal plasma cells in the bone marrow are more likely to have metastatic carcinoma with an unrelated MGUS rather than SPB. This can be confirmed with a biopsy of the bone lesion.

TREATMENT — The primary treatment for patients with SPB is localized radiation therapy (RT). Surgery may occasionally be required for patients with structural instability of the bone, retropulsed bone, or rapidly progressive symptoms from cord compression. (See "Multiple myeloma: Overview of management", section on 'Skeletal lesions and bone health' and "Treatment and prognosis of neoplastic epidural spinal cord compression".)

The use of concurrent, adjuvant, or prophylactic systemic therapy in this population is controversial. Osteoclast inhibitors (eg, bisphosphonates) are not routinely used for patients with SPB, except in the setting of underlying osteopenia. (See "Multiple myeloma: The use of osteoclast inhibitors", section on 'Indications'.)

Radiation — For patients with SPB, we recommend localized RT rather than chemotherapy or observation. RT 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 [23-27] and appears to be highest in tumors <5 cm in maximum diameter [8,25,28].

●Radiation dose – The ideal radiation dose for SPB is unknown, and guidelines differ in their suggested dose range [29-31]. Published papers have reported doses ranging from 30 to 60 Gy, with most radiation oncologists advocating the use of 35 to 50 Gy [3,8]. Doses in the lower range (eg, 35 to 40 Gy) may be used for tumors <5 cm, while doses in the higher range (eg, 40 to 50 Gy) are preferred for larger tumors.

●Treatment field – RT is directed at the tumor or site of tumor resection (if completely excised). The radiation field should contain all the involved tissue on imaging plus an at least 2 cm margin of healthy tissue. If there is vertebral involvement, the radiation field should include at least one uninvolved vertebra on either side.

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 5056 patients with SPB (3528 patients) or extramedullary plasmacytoma (1528 patients). Details on treatment were available for 3967 patients; treatment consisted of RT alone (1803 patients), RT plus surgery (1013 patients), surgery alone (643 patients), and neither modality (508 patients) [32]. The median radiation dose used was 45 Gy. RT doses over 40 Gy improved survival over that seen with lower doses (hazard ratio [HR] 0.62, 95% CI 0.54-0.72). Although treatment with both RT and surgery improved survival over that seen with either modality alone, since treatment differed significantly by site of involvement, it is not known whether these survival differences are due to treatment given, site involved, or a combination of the two.

Another retrospective study included 258 patients with SPB (206 patients) or extramedullary plasmacytoma (52 patients) [8]. 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).

Limited role for systemic therapy — For patients with SPB, we suggest observation after initial RT rather than the use of concurrent or adjuvant systemic therapy. The use of concurrent, adjuvant, or prophylactic systemic therapy for SPB is controversial. Some studies have suggested no benefit with systemic therapy [2,33,34], while others suggest that systemic therapy prevents or delays the median time to progression to multiple myeloma (MM) [23,24,35].

Most of the studies evaluating systemic therapy in SPB used outdated treatment regimens (eg, melphalan plus prednisone) and outdated radiation techniques. There are few studies using modern systemic therapy.

As an example, the use of concurrent lenalidomide plus dexamethasone (Rd) was evaluated in a retrospective study of 46 patients with SPB (40 patients) or extramedullary plasmacytoma treated with intensity-modulated radiation therapy (IMRT) to a total dose of 40 to 46 Gy [36]. Administration of Rd was left at the discretion of the treating hematologist. The entire study population experienced good five-year rates of local control (96 percent), multiple myeloma-free survival (MMFS; 85 percent), and progression-free survival (PFS; 60 percent). When compared with those who received IMRT alone, the 19 patients receiving concurrent Rd had better rates of MMFS (100 versus 77 percent) and PFS (82 versus 48 percent). Rd did not impact local control, plasmacytoma recurrence, or overall survival.

Studies evaluating systemic therapy are small, and overall we believe that the available literature does not support the use of systemic therapy in patients with SPB outside of a clinical trial [37].

Patients with multiple plasmacytomas (macrofocal myeloma) — The term "macrofocal multiple myeloma" (previously "multiple solitary plasmacytoma of bone") is used to describe an uncommon but well-recognized clinical subtype of MM that presents with multiple lytic bone lesions and <10 percent clonal plasma cells in the intervening bone marrow. Approximately 30 to 50 percent of patients with suspected SPB will have multiple asymptomatic lesions detected by imaging and meet these criteria.

The management of these patients is challenging. Many clinicians advocate the use of local radiation directed at the symptomatic site with further treatment postponed until the development of symptoms. In contrast, our approach depends on the number and location of involved sites:

●If a patient has two concurrent distinct plasmacytomas with no bone marrow involvement, we would proceed with radiation to both sites followed by observation provided the radiation fields are limited. If the radiation fields will be large and may interfere with stem cell collection or bone marrow reserve, we administer systemic therapy identical to that used for MM instead of radiation. (See "Multiple myeloma: Initial treatment".)

●If a patient has >2 concurrent lesions, we administer systemic therapy identical to that used for MM, even if the bone marrow is normal.

●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.

These patients are generally younger than the overall myeloma population and have a better prognosis, responding well to proteasome inhibitors [21,22]. (See 'Prognosis' below.)

RESPONSE ASSESSMENT AND FOLLOW-UP — After completion of radiotherapy, patients are seen at periodic intervals to monitor for treatment complications and assess for possible relapse. The frequency and extent of these visits depend on the comfort of both the patient and clinician. In general, we see patients every four to six months for one year, and annually thereafter.

At these timepoints, we measure:

●Urine and serum protein electrophoresis with immunofixation and serum free light chain (FLC) assay

●Complete blood count, serum creatinine, and serum calcium

We repeat imaging three to four months after completing therapy and then yearly for at least five years [12]. It is preferable to use the same imaging technique for diagnosis and evaluation of treatment response. ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/CT is more sensitive than MRI for treatment response assessment. Irradiated sites may demonstrate low tracer uptake due to bone remodeling. In contrast, persistently high uptake on ¹⁸F-FDG PET/CT may signify residual disease, which might be confirmed by biopsy.

There are no guidelines for the assessment of treatment response in SPB, and practice varies. We agree with an approach proposed by a European expert panel that combines response evaluation criteria in solid tumors (RECIST) with the International Myeloma Working Group (IMWG) response criteria for multiple myeloma (MM) (table 4) [38-40]. RECIST is used to evaluate the extramedullary tumor while the IMWG response criteria are used to evaluate the monoclonal protein.

When present, the serum monoclonal protein can remain stable for several months before declining. If serum monoclonal protein levels increase, FLC ratio worsens, and/or if the patient develops signs of myeloma-associated, end-organ damage, a new bone marrow sample should be obtained to quantify and analyze the plasma cell infiltration, and imaging should be repeated.

RELAPSED OR REFRACTORY DISEASE — There is no consensus about the treatment of relapsed or refractory SPB because of the high cure rates following surgery or radiation therapy (RT) and limited data to guide management. At the time of relapse, a full repeat diagnostic evaluation (with a new biopsy) is required to confirm the clonal plasma cell infiltration and exclude other plasma cell disorders (table 1). (See 'Evaluation' above.)

If the evaluation at relapse reveals a myeloma-defining event (eg, end-organ damage or a biomarker for myeloma), SPB has evolved to multiple myeloma (MM), and systemic therapy for MM is appropriate. (See "Multiple myeloma: Initial treatment".)

If there are no myeloma-defining events and the SPB occurs in a new location that is distinct from the original location at diagnosis, the new lesion can be treated with RT. (See 'Radiation' above.)

If there are no myeloma-defining events and >2 concurrent lesions are detected at relapse, systemic antimyeloma therapy is usually preferred, especially if the new plasmacytomas occurred within a period of one to two years after the end of radiotherapy for the original SPB.

PROGNOSIS

Risk of progression and overall survival — The median overall survival of patients with SPB is approximately 10 years [3,7,23,33,41-43]. 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 [3].

Overt multiple myeloma (MM) ultimately develops in 50 to 60 percent of patients with SPB after initial radiation therapy (RT) [23,25,26,29,41,44-46]. This disease progression is thought to arise from previously undetectable myeloma cells in areas outside the radiation field or from myeloma within the radiation field in the setting of sublethal radiation doses.

The prognosis of SPB varies depending on the adequacy of initial staging. In one study, among 91 patients seen at the Mayo Clinic with newly diagnosed SPB and no clonal bone marrow plasma cells by immunofluorescence, approximately 40 percent were free of recurrence at eight years [47]. The risk of recurrence decreases further among patients with no evidence of disease elsewhere on combined positron emission tomography (PET)/CT. In contrast, there is almost always recurrence if there are detectable clonal bone marrow plasma cells at the time of initial diagnosis (eg, SPB with minimal marrow involvement). In two retrospective studies, detection of phenotypically aberrant clonal plasma cells by flow cytometry of the bone marrow was associated with a higher likelihood of progression to MM at 26 months (approximately 70 versus 6 to 12 percent) [18,19].

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 [3,41], although progression can occur as late as 13 years [3]. Three patterns of failure were seen:

●Development of MM – 54 percent

●Local recurrence – 11 percent

●Development of new lesions (multiple plasmacytomas) in the absence of MM – 2 percent

Relapse rates appear to be higher and time to progression shorter in patients with high-risk cytogenetic findings on FISH defined as del(17p), gain/amp 1q, t(4;14), t(14;16), and t(14;20) [10]. Relapse rates are also higher in older patients and in those with axial skeletal lesions [7,25,26], while patients younger than 60 years and with tumors <5 cm have a better overall survival rate [26]. Other reported predictors for conversion to MM include a large solitary lesion [23], the presence of osteopenia, reduction in uninvolved immunoglobulin levels (eg, low levels of immunoglobulin A [IgA] and/or immunoglobulin M [IgM] in a patient with an immunoglobulin G [IgG] plasmacytoma) [48], and the presence of high-grade angiogenesis in the tumor sample [49].

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 [3], although persistence of a serum M protein after RT appears to be a predictor of subsequent progression to MM [7,13,23,33,41]. In one series, for example, the 10-year myeloma-free survival was superior for those whose M protein resolved at one year following RT (91 versus 29 percent) [13].

In another study of 116 patients with SPB, two factors were predictive of disease progression to myeloma at five years [50]:

●A persistent serum M protein level ≥0.5 g/dL one to two years after diagnosis

●An abnormal free light chain (FLC) ratio at the time of diagnosis

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.

Imaging — Cross-sectional imaging with combined ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET/CT and/or a whole-body MRI is included in the initial evaluation of a patient with suspected SPB because patients with multiple bone lesions have a worse prognosis and should be considered as having early MM rather than SPB.

Pretreatment cross-sectional imaging impacts management. In three separate studies, MRI of the spine showed unsuspected bone lesions in one-quarter to one-third of patients with presumed SPB [13-15]. Patients with bone lesions on MRI were at greater risk for progression to symptomatic MM. Similarly, in a retrospective study of 21 patients with apparently solitary plasmacytoma, pretreatment PET scans influenced management 35 percent of the time, either by demonstrating multiple lesions or by demonstrating normal activity in a previously suspected lesion [16].

PET/CT appears to offer additional prognostic information over that seen with MRI. One study evaluated imaging in 43 patients with SPB (33 patients) or extramedullary plasmacytoma who underwent whole-body PET/CT and MRI of the spine and pelvis prior to local RT and were followed for a median of 50 months [51]. PET/CT identified ≥2 hypermetabolic lesions in 10 patients, six of whom progressed to MM. Time to MM progression was shorter in those with ≥2 lesions on PET/CT (median 23 months versus not reached). MRI identified ≥2 focal lesions in seven patients, four of whom progressed to MM. Those with ≥2 lesions on MRI had numerically shorter time to MM progression, although this did not reach statistical significance.

Fluorodeoxyglucose (FDG) uptake correlates with tumor size. In one study of 62 patients with solitary plasmacytoma, FDG-avid lesions were larger than FDG-negative lesions (41.4 versus 23.5 mm) and more likely to progress to MM [52].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Solitary plasmacytoma".)

SUMMARY AND RECOMMENDATIONS

●Clinical presentation – Solitary plasmacytoma of bone (SPB) is a localized tumor in the bone comprised of clonal plasma cells in the absence of other features of multiple myeloma (MM; ie, anemia, hypercalcemia, kidney impairment, or multiple lytic bone lesions). Most patients present with skeletal pain or a pathologic fracture of the affected bone. (See 'Clinical features' above and 'Diagnosis' above.)

●Diagnostic evaluation – The evaluation of a patient with a suspected SPB should include a biopsy of the suspected lesion, a unilateral bone marrow aspirate and/or biopsy, and laboratory studies. Cross-sectional imaging with a whole-body MRI scan and/or combined ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/CT should be performed. (See 'Evaluation' above.)

The diagnosis of SPB requires the following (table 1):

•Biopsy-proven solitary tumor of bone with evidence of clonal plasma cells.

•Cross-sectional imaging must show no other lytic lesions or extramedullary lesions.

•Bone marrow aspirate and biopsy contains no clonal plasma cells.

•There is no anemia, hypercalcemia, or kidney impairment that could be attributed to a clonal plasma cell proliferative disorder.

The presence of clonal plasma cells (<10 percent) in the bone marrow is considered SPB with minimal marrow involvement. Presence of 10 percent or more clonal bone marrow plasma cells in a patient with SPB will automatically meet required criteria for MM. However, patients with a single plasmacytoma and ≥10 percent clonal plasma cells in the bone marrow and no other myeloma-defining events (ie, no evidence of end-organ damage or biomarkers of malignancy) are not well represented in myeloma trials, and there are limited data to guide therapy. They may be treated in a similar fashion to SPB if the bone marrow plasmacytosis is modest.

●Management – For patients with SPB, we recommend initial therapy with localized radiation rather than chemotherapy or observation (Grade 1C). Radiation should be delivered at a dose of 35 to 50 Gy over four weeks directed at the tumor or site of tumor resection (in the case of complete diagnostic excision). (See 'Radiation' above.)

After initial radiation therapy (RT) for patients with SPB, we suggest observation rather than the use of concurrent or adjuvant systemic therapy (Grade 2C). (See 'Limited role for systemic therapy' above.)

●Limited role for bisphosphonates – Osteoclast inhibitors (eg, bisphosphonates) are not routinely used for patients with SPB, except in the setting of underlying osteopenia. (See "Multiple myeloma: The use of osteoclast inhibitors", section on 'Indications'.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Robert A Kyle, MD, who made extensive contributions to earlier versions of this topic review.