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

4. Solitary Extramedullary Plasmacytoma (SEP)

4.1. Context

Solitary extramedullary (soft tissue) plasmacytomas (SEP) are less common than SBP but carry a better prognosis as the majority can be cured by local radiotherapy (Dimopoulos et al, 1999). Although SEP can arise throughout the body almost 90% arise in the head and neck, especially in the upper respiratory tract including the nasal cavity, sinuses, oropharynx, salivary glands and larynx (Brinch et al, 1990; Wax et al, 1993; Susnerwala et al, 1997; Liebross et al, 1999; Galieni et al, 2000).

The next most frequent site is the gastro-intestinal tract. A variety of other sites can rarely be involved, including testis, bladder, urethra, breast, ovary, lung, pleura, thyroid, orbit, brain and skin ( Fischer et al, 1996; Matsumiyama et al, 1992; di Chiara et al, 2001; Emery et al, 1999; Cavanna et al, 1990; Nonamura et al, 1992; Rubin et al, 1990; Adkins et al, 1996; Tuting and Bork 1996; Wong et al, 1994; Muscardin et al, 2000).

A monoclonal paraprotein is detected in the serum and/or urine in fewer than 25% of patients (Table II). After radiotherapy local recurrence rates of <5% are quoted (Liebross et al, 1999). The risk of distant relapse appears to be <30% i.e. significantly less than with SBP (Mayr et al, 1990). Progressive disease may present as multiple myeloma, SBP or soft tissue involvement of lymph nodes, skin or subcutaneous tissues. When distant relapse occurs this tends to be within 2-3 years of initial diagnosis. At least two thirds of patients survive for more than 10 years (Brinch et al, 1990; Galieni et al, 2000).

 

4.2. Diagnosis and investigation of SEP

4.2.1. Diagnostic criteria

CT or MR scanning is required to delineate the extent of the lesion but the role of MRI imaging of other areas in the staging of SEP has not been evaluated. As there is a low risk of progression to MM in these patients and the role of MR imaging in the staging of SEP has not been studied, we do not consider MRI of the spine to be necessary for the diagnosis of SEP. Recommended diagnostic criteria are shown in Table III.

4.2.2. Pathology review

For most patients the diagnosis can be established by fine needle aspiration or biopsy (Kumar et al, 1997). As these tumours are rare, and can be confused with non - Hodgkin's lymphoma, pathology review by a histopathologist with a special interest in lymphoproliferative disorders is strongly recommended.

4.2.3. Investigations

As noted above, CT or MR scanning is required to delineate the extent of the lesion but we do not consider MRI to be necessary part of the diagnostic criteria. Other investigations should be as for SBP.

 

4.3. Treatment of SEP

4.3.1. Radiotherapy

SEP are highly radiosensitive tumours. Local control rates of 80-100% are consistently reported with moderate doses of radiotherapy (Mayr et al, 1990; Bolek et al, 1996; Jyothirmayi et al, 1997; Liebross et al, 1998). Radiotherapy dose and anatomical volume should be chosen to minimise early and late side effects and maximise local control. There is no firmly established dose response relationship, due to small patient series and low local failure rates. Tsang et al (2001) achieved local control in 13/14 (93%) of patients with 35Gy. The only failure was in a patient with a large primary tumour greater than 5cm. Similarly, Jyothirmayi et al (1997) achieved local control in 6/7 patients with 35-45Gy (median dose 40 Gy in 20 fractions). The only failure was in a patient with an extensive nasopharyngeal tumour. No dose response relationship was observed. Holland et al (1992) also reported poorer local control in tumours greater than 5cm and similarly observed no evidence of a radiation dose response effect over the dose range 16.11 Gy to 62 Gy (median dose 46.1 Gy).

Several series report 100% local control rates. Bolek et al (1996) reported 100% local control in 10 patients with doses ranging from 9 to 50 Gy (median dose 45 Gy) and concluded by recommending a dose of 40 Gy in 20 fractions. Shih et al (1995) reported on 10 patients with SEP, seven of whom were treated by radiotherapy, using doses of 47 - 65 Gy. Local control was achieved in all the irradiated patients, raising the possibility that local control could have been achieved with lower radiation doses.

The optimal radiation dose therefore appears to be in the range of 40-50Gy. SEP <5cm have an excellent chance of local control with radiation doses in the region of 40 Gy in 20 fractions, whereas there is a higher risk of local failure in tumours greater than 5cm, which require a higher dose in the region of 50 Gy in 25 fractions.

The optimal radiotherapy target volume is similarly controversial. SEP arising in the upper gastro-intestinal or respiratory tract (greater than 80% cases) metastasise to cervical lymph nodes in 10-40% of cases (Susnerwala et al, 1997, Hu and Yahalom, 2000). The inclusion of draining cervical nodes in the radiation fields significantly adds to acute and late morbidity, especially xerostomia, which may not fully recover. Excellent local control rates are reported when the cervical nodes are electively included (Bolek et al, 1996).

However, similarly good results are also reported from series in which the cervical nodes are only included if clinically involved. Tsang et al (2001) irradiated the primary site alone, except in patients whose primary was in the lymphatic tissue of Waldeyer's ring, when the first echelon (level) cervical nodes were included. There were no cervical node failures in 14 patients. Jyothirmayi et al (1997) irradiated the primary site only in 7 patients and reported no cervical node relapses. Susnerwala et al (1997) treated the primary site only in 23 patients and only included the cervical nodes in 2 patients with clinical cervical node involvement. Again, no lymph node failures occurred. In contrast, Mayr et al (1990) reported cervical node failures in 2/11 patients treated to the primary site only and recommended elective cervical node irradiation.

In view of the morbidity of cervical nodal irradiation and the high local control rates reported without it, the balance of evidence favours a policy of treating the primary site with a margin and including the cervical nodes only if clinically involved, or regarded at high risk, as in primary sites involving Waldeyer's ring.

Recommendations:

4.3.2. Surgery

The majority of SEP occur in the head and neck. Surgery is generally not required for diagnosis. Radical surgery with curative intent is a generally mutilating procedure that is not indicated as the tumours are generally highly radiosensitive and the majority of patients are cured with radiotherapy. For patients with SEP in other areas complete surgical removal should be considered.

A detailed review of the literature by Alexiou et al (1999) compared the outcome of patients treated with surgery alone, radiotherapy alone, or combined surgery and radiotherapy. They found reports of 714 cases involving the upper aerodigestive tract (UAD) and 155 cases in other body regions (non-UAD). Most of the latter patients were treated with surgery alone (55.6%) or combined modality treatment (19.8%) and only 11% were treated with radiotherapy alone. The risk of recurrence was the same for the 3 treatment approaches. It is not clear whether patients receiving a combined approach did so because of incomplete surgical removal.

On the other hand, most of the patients with SEP in the UAD were treated with radiotherapy alone (44.3%) or combined radiotherapy and surgery (26.9%); surgery alone was used in 21.9%. Overall and recurrence-free survival were better in those treated with combined therapy (p=0.0027). They concluded that patients with UAD plasmacytoma might benefit from a combined approach. However, this review is somewhat difficult to interpret, as it spans almost a century - 1905 to 1997 and radiotherapy was not available in any meaningful form for at least half this period. Furthermore there are likely to have been significant differences between the patients treated by the different modalities.

It is therefore unclear as to whether surgery offers any additional benefit over radiotherapy alone in patients with SEP of the head and neck. Radiotherapy alone is curative in the vast majority of patients. Conversely, where patients have been treated by primary surgery, radiotherapy would only be required in patients with inadequate surgical margins. In contrast to SPB, radiotherapy can be used following surgery without compromise as metal supports are not used in this context.

Recommendations:

4.3.3. Adjuvant Chemotherapy

There is no published evidence on the role of adjuvant chemotherapy in the treatment of SEP. It may have a role in selected high-risk patients. Susnerwala et al, (1997) suggested a higher failure rate in 'high grade' tumours using the multiple myeloma grading criteria of Bartl et al (1987). Tsang et al (2000) and Holland et al (1992) suggest that tumours greater than 5cm are at higher risk of failure.

Recommendations:

4.3.4. Other treatment approaches

There is no theoretical indication for, and no available data on, the use of bisphosphonates in SEP. Thalidomide has been used to treat extramedullary plasmacytoma in the context of relapsed MM with variable results (Blade et al, 2001; Myers et al, 2001; Biagi et al, 2001) but there is no published data on its use in SEP.

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5. Patient Information and Support

Provision of appropriate patient information and support forms an important part of the care of patients with SPB and SEP. General principles are the same as those for patients with myeloma (UK Myeloma Forum, 2001). The International Myeloma Foundation (UK) produces a booklet for patients with solitary plasmacytoma.