Solitary plasmacytoma: is radiation therapy sufficient?

Solitary plasmacytomas are characterized by a localized collection of malignant plasma cells without evidence of a systemic plasma cell proliferative disorder. It accounts for 5–10% of all plasma cell neoplasms and may present with a single bone lesion [solitary bone plasmacytoma (SBP)] or as a single extramedullary or extraosseous lesion [1–3]. In spite of local radiation with curative intent, over half of these patients eventually develop multiple myeloma (MM) [2,4–6]. Patients with SBPs tend to be a decade younger compared with those with myeloma and often present with pain or soft tissue swelling related to extramedullary extension [6]. SBPs can result in pathological fractures, which can occasionally lead to significant neurological symptoms when they affect the vertebral bodies. The axial skeleton is more often involved than appendicular skeleton and the appendicular lesions when present usually involves the proximal bones. As suggested by the terminology, diagnosis of a solitary plasmacytoma requires a complete work up to rule out the presence of a systemic plasma cell disorder [7]. In addition to pathological confirmation of the plasmacytoma, complete skeletal surveys should be done to rule out other bone lesions, and bone marrow should be free of any clonal plasma cells. It is not unusual for the serum or urine to demonstrate presence of monoclonal protein, but these often tend to be small. More recently, additional imaging studies such as MRI of the spine or PET scans are increasingly being utilized in the work up of these patients. Clearly these techniques increase the ability to pick up the presence of additional lesions and exclude the diagnosis of a solitary plasmacytoma, but their role as part of routine evaluation of these patients require further study. Given that over half of patients with SBPs eventually develop MM, there has been significant interest in identifying patients at increased risk of progression. Multiple risk factors have been identified for increased risk and include persistence of monoclonal protein after radiation therapy, large lesions, involvement of axial skeleton, older patients, suppression of uninvolved immunoglobulin levels, abnormal immunoglobulin free light chain ratio, and presence of increased neovascularization in the tumor. In contrast, extramedullary plasmacytomas arising outside of the bone marrow tend to occur most commonly in the head and neck region, especially in the upper airways and upper gastrointestinal tract. However, these lesions can involve nearly any part of the body, and the symptoms typically are related to the pressure effect on the adjacent tissue, or blockage of the respiratory of digestive tract. As with SBPs, diagnosis hinges on exclusion of a systemic plasma cell proliferative disorder and presence of monoclonal protein in the serum or urine does not exclude the diagnosis. It is critical to distinguish these lesions from lymphomas with plasmacytic differentiation of the tumor cells as well as poorly differentiated carcinomas. In contrast to bone plasmacytomas the risk of development of MM is only 10–15%, but risk of local recurrence is higher than with bone lesions. The management of solitary plasmacytomas has traditionally included local radiation therapy (RT) with surgical intervention required only in the event of pathological fractures involving bone lesions or when surgical resection of a soft tissue mass led to the initial diagnosis of a plasmacytoma. In this issue of the journal, Kilciksiz et al. have reviewed the collective experience from Turkish Oncology Group-Sarcoma Working Party and have once again raised questions on the role of surgery in addition to radiation in these patients[8]. The study included 80 patients with solitary plasmacytomas, 57 of who had SBPs, from several centers in Turkey. In contrast to some of the earlier series, this study has the advantage of reasonably long follow-up. The demographic and clinical features of the patients were as expected and as reported in the previous series, the risk of progression was higher among those with bone plasmacytomas. Older patients with bone plasmacytomas are more likely to have progression to myeloma and this study again confirms this observation. In their analysis, the authors raise the question whether the dose of radiation and the use of surgical resection in addition to radiation impact the risk of progression to myeloma. In the univariate analysis of risk factors for progression to myeloma, surgery in addition to RT and presence of macroscopic tumor prior to RT, both influenced the risk. Although the results suggest that surgical intervention and complete resection of the tumor may have added benefit over and above RT, this needs to be interpreted with caution. Clearly patients with extramedullary plasmacytomas are more likely to have undergone surgical resection given that the diagnosis is often made after resection of a suspicious mass, as reflected by the smaller proportion of these patients (43.5% vs. 82.5%) with macroscopic tumors prior to RT. The prognostic value of this finding is likely a reflection of the higher proportion of patients with extramedullary lesion without macroscopic tumor prior to RT, a group with inherently lower risk of progression to myeloma and this is further borne out by the lack of prognostic value in the multivariate analysis. Similarly, the effect of surgery on the risk of recurrence may be a reflection of other disease characteristics rather than a direct beneficial effect of surgery. Patients with bone and extramedullary plasmacytomas often undergo surgical procedures for different reasons, symptomatic bony lesions or fractures that need surgical intervention in the former versus resection of a suspicious mass for diagnosis or palliation in the latter. It is often difficult to determine the rational behind the surgical procedure in a retrospective study. It is