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KOS 2007: Solitary Bone and Extramedullary Plasmacytoma
By Raymond Alexanian, MD
Raymond Alexanian, MD
M. D. Anderson Cancer Center
University of Texas
Houston, TX, USA



Authors: R. Alexanian and D. Weber
M. D. Anderson Cancer Center
University of Texas
Houston, TX, USA


Solitary Bone Plasmacytoma
Among patients with myeloma and bone destruction, approximately 2% show only a solitary lytic lesion, that had usually caused localized bone pain. For rational planning of treatment, selected procedures are required to confirm the diagnosis and to exclude multiple myeloma with as much certainty as possible. These include needle biopsy evidence of monoclonal plasma cells, no other evidence of myeloma on bone survey or random marrow aspirate, and no other complication (anemia, renal impairment) that might be due to myeloma. Despite normal bone survey, magnetic resonance imaging (MRI) of thoracic and lumbar spine has been useful since Moulopoulos et al. detected unexpected bone lesions in 4 of 12 patients considered initially to have SPB.1 Thus, the diagnosis of SPB requires a negative MRI of thoracolumbar spine, with the potential value of MRI of other parts of the skeleton or of PET scans unclear at this time. Electrophoretic studies are also essential. While 75% of patients have a monoclonal protein in serum or urine, the level has been low in most patients so that serum M protein concentrations are usually < 1.0 g/dL (our highest 2.2 g/dL), urine Bence Jones protein < 0.2 g/d (our highest 0.7 g/day).2, 3 For the 25% of patients with apparent nonsecretory disease, free light chain assays have revealed high free kappa or lambda light chain levels in approximately two-thirds of patients.4 Levels of uninvolved serum immunoglobulins are preserved, as only 3 of 76 patients at our center had low values, each of whom considered to have occult systemic disease because of early disease progression. High doses of radiotherapy to the solitary lesion remain the treatment of choice since there is local control in virtually all patients and the prospect of cure for many patients. Too few trials of large numbers of patients have been conducted to define the optimum dose, but Table 1 summarizes the experience of several single institution studies. Following a dose of ³ 40 Gy, local disease progression was nonexistent or rare in all trials so that the practice at our and other centers has been to recommend 45 Gy in 25 fractions over 5 weeks. The United Kingdom Myeloma Forum has recommended 40 Gy in 20 fractions to encompass the tumor mass plus a margin of at least 2 cm beyond disease detectable by MRI; for bulkier disease > 5 cm, 45-50 Gy in 25 fractions was advised.9 Surgery is not indicated for SBP, but some patients require decompressive laminectomy, spine fusion or intramedullary rod fixation of a long bone. Adjuvant chemotherapy has been given without benefit in most studies. The role of intensive therapy supported by autologous stem cells is not clear but is difficult to assess in view of the long disease course and known cure fraction. A major early endpoint associated with prolonged disease stability and long survival has been disappearance of monoclonal protein following radiation therapy, a change that usually occurs within 6 months. Serial assessment of free monoclonal light chain levels in patients with apparent nonsecretory disease allows more patients to be assessed in this manner. Figure 1 depicts the different outcomes at our center among 76 patients with or without resolution of myeloma protein (currently by immunofixation) as an index of effective myeloma control. Myeloma protein persisted in most patients as a reflection of residual disease and was associated with earlier evolution of multiple myeloma. Since none of 11 patients with serum M protein > 1.0 g/dL showed disappearance of abnormal protein after radiotherapy, all patients with such levels probably have multiple myeloma even though asymptomatic, especially since evolution of myeloma occurred after a median 2.0 years. In such patients, control of the local symptomatic lesion should be followed by some form of cytostatic therapy, such as with alpha interferon or thalidomide, until disease progression. The same approach seems reasonable for other patients with lower myeloma protein values that persist after radiotherapy in whom the median time to progression was 2.7 years. Thus, among 76 patients staged by current and older procedures, one-half have developed multiple myeloma within 2 years. Yet, the median survival of all patients was 11.6 years with 30% of deaths due to unrelated diseases; the potential cure fraction based on analyses of cause-specific survival was approximately 35%. Various prognostic factors associated with progression of multiple myeloma have been observed by others, such as spine disease, older age, bulky disease, M protein level, etc., but we could not confirm that any of these factors were harmful. With progressive advances in staging that include MRI and sensitive techniques to detect clonal disease in marrow, the diagnosis of SPB will be made less frequently. When one also requires that uninvolved immunoglobulins be preserved, and that serum M protein be £ 1.0 gm for effective long-term control, a true SBP should be associated with a higher cure fraction after effective radiotherapy.

Extramedullary plasmacytoma
A solitary extramedullary plasmacytoma (EMP) is a rare disorder characterized by a mass of clonal plasma cells unrelated to underlying bone destruction and with no other evidence of multiple myeloma. Careful phenotypic studies are essential to distinguish this process from a reactive plasmacytoma or lymphoma (MALT, marginal zone). Thus, surgical biopsy is useful to affirm plasma cells with CD38 and monoclonal cytoplasmic light chain expression without markers suggestive of lymphoma. As with SBP, there should not be marrow plasmacytosis and bone survey should be normal. Approximately 85% of lesions involve the mucosa of head and neck; the presence of bone destruction with sinus involvement suggests that this subgroup represents a SBP of a sinus bone. Other sites of EMP include GI tract, lung, bladder, thyroid, testis among others. CT or MRI are necessary to define the extent of an EMP but the role of MRI of spine or of PET scan has not been studied carefully. Less than onefourth of 25 patients at our center showed monoclonal globulin in serum or urine by standard studies and levels of uninvolved immunoglobulins have been preserved. Free light chain levels in serum should be assessed even though their value remains unclear. As with SBP, EMP are highly radiosensitive so that local control is usually achieved and approximately one-half of our patients have remained stable for more than 10 years.10 At most centers, radiotherapy doses have ranged from 35-45 Gy, and our practice has been to include prophylactic irradiation of regional lymph nodes when oral cavity, pharynx, larynx or parotid are involved, but not for nasal cavity or maxillary sinus disease. Neither surgery nor adjuvant chemotherapy appear justified.11 Rare patients have shown local recurrence and the disease-free and cause-specific survival after 10 years have been approximately 60% for patients at our center. One-fourth of patients developed multiple myeloma after a median of approximately 1 year presumably from occult disease elsewhere. No prognostic factors have been identified in part because a monoclonal immunoglobulin is present infrequently and modern staging procedures have not been conducted in many patients. Conclusion. SBP and EMP represent uncommon solitary plasmacytomas that are radiosensitive and usually associated with long-term stability. More sensitive techniques for detection and follow up (MRI, PET, free light chain assays) should permit clearer staging so that fewer patients will meet the criteria for diagnosis and the cure fraction will be higher after radiotherapy.

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