Guidelines on the Diagnosis and Management of Solitary Plasmacytoma of Bone (SBP) and Solitary Extramedullary Plasmacytoma (SEP)

3. Solitary Bone Plasmacytoma (SBP)

3.1. Context

3.1.1. Epidemiology and Clinical Features

SBP has a male to female ratio of 2:1, median age of 55 years and primarily affects the axial skeleton especially the vertebrae, see Table II (Dimopoulos et al, 2000). Malignant bone tumours of the spine are extremely rare (less than 0.05% of primary neoplasms). Solitary plasmacytoma is the commonest separate entity within this group accounting for approximately 30% of the total (McLain and Weinstein, 1989). These tumours occur in the spine twice as often as other bony sites (Chang et al, 1994). The commonest symptom is pain but it can also present with cord or root compression. Involvement of the base of the skull can present with cranial nerve palsies (Vijaya-Sekaran et al, 1999; Vaicys et al, 1999).

Localised amyloidosis can be a feature of both SBP and SEP (Pambuccian et al, 1997; Nagasaka et al, 2001). As well as the appropriate blood and urine tests, specific imaging of the spine is required and best achieved by MRI +/- CT. Bone scans are unreliable. Biopsy is usually possible percutaneously, guided either by fluoroscopy or CT.

The presence of a monoclonal paraprotein (M protein) has been reported in 24% - 72% of patients in different series (Dimopoulos et al, 2000). The frequency probably depends on the level of sensitivity of the tests used. In a recently reported series of 60 patients from the MD Anderson Hospital presenting between 1995 and 2000 (Wilder et al, 2002), a serum or urinary paraprotein was detectable in 43 patients (62%) by routine electrophoresis or immunofixation / immuno-electrophoresis. However the levels of paraprotein were generally low. Of the 37 patients who had a serum paraprotein, only 11 had levels over 10 g/l and the highest level was 22 g/l. In the 6 patients who only had Bence-Jones protein in the urine, total daily excretion of urinary free light chain was below 100 mg/day in all patients.

3.1.2. Natural History and Prognosis

The majority of patients with apparent SBP develop myeloma, with a median time of 2-4 years (Table II). The median overall survival in different series varies from 7.5 to 12 years (Dimopoulos et al, 2000). Most reported series extend over a long time period and the majority of included patients have not had MRI scans. These patients will therefore include a proportion of patients with asymptomatic myeloma. The progression-free and overall survival in patients with SBP may improve as MRI examination becomes an established part of the staging criteria for the diagnosis and patients with early MM are excluded.

Quoted adverse prognostic features for progression to MM include low levels of uninvolved immunoglobulins, axial disease, older age, lesion size >5cm, and persistence of the M protein after treatment (Bataille et al, 1981; Holland et al, 1992; Tsang et al, 2001). However, these adverse prognostic features have not been consistent between series (Bolek et al, 1996; Chak et al, 1987; Liebross et al, 1998; Frassica et al, 1989).

A recent multivariate analysis of prognostic factors in a series of 60 patients from the MD Anderson Hospital (most of whom were not staged by MRI) concluded that persistence of M protein for more than 1 year after radiotherapy was the only independent adverse prognostic factor (Wilder et al, 2002). The paraprotein disappeared in 13 patients and persisted in 32, while 15 patients had non-secretory disease. At a median follow-up of 7.8 years, only 1/13 patients with resolution of the paraprotein progressed to MM while over 90% of patients with persistent paraprotein had progressed. Most patients with persistent M protein progressed to MM within 2 years of treatment. Age, tumour size and level of paraprotein at diagnosis had no independent prognostic value. In this series, patients with non-secretory disease appeared to do less well than those with a paraprotein that disappeared after radiotherapy.

As already indicated, it is likely that many of the patients with apparent SBP who progress actually have disseminated disease at presentation. MRI examination of the spine can detect occult disease in approximately 26% of patients with apparent SBP (Moulopoulos et al, 1993, Wilder et al, 2002). Conversely a negative MRI of the spine is a good prognostic feature. Liebross et al, (1998) showed that in a series of 15 patients with a spinal plasmacytoma who did not have a positive MRI examination, progression to MM occurred in 7/8 patients where MRI had not been performed as opposed to 1/7 with a negative MRI of spine (patients with other lesions on MRI were considered to have MM).

Those patients with SBP who do subsequently develop multiple myeloma have a relatively good prognosis. Liebross et al (1998) reported that their patients with SBP who progressed to MM were characterised by low tumour mass, 77% response rate to chemotherapy and a median survival from progression of over 5 years. Patients progressing to MM should be treated according to the BCSH guideline on the management of multiple myeloma (UK Myeloma Forum, 2001). Also, patients presenting as SBP but found on MRI scan to have more extensive disease should be considered as having MM and treated accordingly.

3.2. Diagnosis and investigation of SBP

3.2.1. Diagnostic criteria

Recommended diagnostic criteria are summarised in Table III. Based on the data discussed above, the following criteria are recommended:

• Single area of bone destruction due to clonal plasma cells
• Histologically normal marrow aspirate and trephine
• Normal results on skeletal survey, including radiology of long bones
• No anaemia, hypercalcaemia or renal impairment due to plasma cell dyscrasia
• Absent or low serum or urinary level of monoclonal immunoglobulin (level of >20 g/l suspicious of MM, see above)
• No additional lesions on MRI scan of the spine (see below for criteria of involvement)

3.2.2. Pathology review

SBP is generally diagnosed by biopsy or FNA. Percutaneously guided biopsy of the spine is usually possible either by fluoroscopy or CT. As these tumours are rare, pathology review by a histopathologist with a special interest in either bone tumours or lymphoproliferative disorders is strongly recommended.

3.2.3. Further investigations

The following investigations should be performed in all patients:

• Full blood count
• Biochemical screen including electrolytes and corrected calcium
• Serum immunoglobulin levels
• Serum and urine protein electrophoresis and immunofixation
• Full skeletal survey, including standard X-rays of the skeleton including lateral and AP cervical, thoracic and lumbar spine, skull, chest, pelvis, humeri and femora (UK Myeloma Forum, 2001)
• MRI of thoracic and lumbar spine
• Bone marrow aspirate and trephine

Additional investigations may be useful in selected patients, including:

• MR imaging of pelvis, proximal femora and humeri
• immunophenotyping and molecular assessment of bone marrow plasma cells
• PET scanning (Orchard et al, 2002)

The role of β₂-microglobulin in the diagnosis and management of SBP has not been established. There are at present no data on the use of the serum free light chain assay in SBP.

3.2.4. MRI Examination

There are no reported guidelines to define involvement on an MRI scan. However the presence of one or more foci of abnormal signal intensity (low on T1 weighted imaging and high on T2 weighted or STIR images), which enhance after the administration of paramagnetic contrast in the absence of known recent compression fractures, other primary malignancy or typical characteristics of benign or malignant primary bone tumours, is considered evidence of distant involvement in patients with apparent SBP (M Dimopoulos, personal communication).