Document ZB3wwEYR80rKJ90r6aaD34pNV

Magnetic Resonance Imaging in the Staging of Solitary Plasmacytoma of Bone By Lia A. Moulopoulos, Meletios A. Dimopoulos, Donna Weber, Lillian Fuller, Herman I. Libshitz, and Raymond Alexanian Purpose: To assess prospectively the role of magnetic resonance (MR) imaging in the staging of patients with a solitary bone plasmacytoma (SBP). Patients and Methods: Twelve consecutive patients with an apparent SBP underwent MR imaging of both the primary tumor and the thoracic and lumbosacral spine to seek additional foci of marrow involvement that might have been undetected by standard skeletal survey. All patients received megavoltage irradiation (total dose, 40 Gy) to the primary lesion. Results: MR imaging of the thoracic and lumbosacral spine showed additional foci of marrow replacement in four of 12 patients, with signal characteristics identical to those of the primary tumor. In all four patients, the abnormal protein persisted at greater than 50% of the pretreatment value following radiation treatment. In SOLITARY BONE plasmacytoma (SBP) represents the only disease feature in approximately 5% of patients with plasma cell myeloma.' The diagnosis re- quires histologic evidence of a monoclonal plasma cell infiltrate in one bone lesion, absence of other bone le- sions on skeletal survey, and lack of marrow plasma- cytosis elsewhere. Virtually all patients show preserved levels of uninvolved immunoglobulins (Igs) in contrast to the marked depression in most patients with multiple myeloma.2 4 Although local radiotherapy is usually ef- fective for the primary tumor, most patients develop multiple myeloma within 3 years and less than one third remain stable for more than 10 years.'-5' Early progres- sion most likely results from occult generalized disease that was not recognized at diagnosis. In multiple my- eloma, magnetic resonance (MR) imaging has detected foci of disease not observed on conventional radiographs.6"9 Routine spin echo T I-weighted images of the spine may demonstrate well-defined areas of similar or low signal intensity relative to muscle; on T2-weighted MR images, myeloma lesions are hyperintense relative to muscle.6 9Based on these observations, we conducted MR imaging of the spine in patients with SBP in a search for additional foci of disease that were undetected by standard bone surveys. PATIENTS AND METHODS Between April 1990 and April 1992, 12 patients were referred with presumed SBP. Biopsy of the lesion showed monoclonal plasma cells. Aspiration and biopsy of the primary tumor, electrophoretic studies of serum and urine concentrates, immunofixation and serum Ig quantitation, and skeletal surveys met the diagnostic criteria for a SBP.' - contrast, the myeloma protein disappeared or was reduced by greater than 50% in five of the six patients with secretory disease and without additional marrow abnormalities. One of four patients progressed to multiple myeloma 10 months after diagnosis with new lesions on conventional radiographs in the same areas as detected previously by MR imaging. Conclusion: Four of 12 patients considered to have a SBP by standard criteria may have been understaged, because MR imaging showed additional marrow abnormalities consistent with myeloma. MR imaging of the spine may contribute to the initial staging of SBP, especially since some patients may be cured with radiotherapy. J Clin Oncol 11:131 1-1315. 1993 by American Society of Clinical Oncology. Patient characteristics are listed in Table 1. Ten patients had a monoclonal protein of low level in serum (seven patients) or urine (three patients). Two patients did not show an abnormal protein on immunifixation studies. Uninvolved Igs were preserved in all patients (IgM > 50 mg/dL, IgA > 100 mg/dL, IgG > 700 mg/dL). All patients underwent MR imaging of the primary lesion and of the thoracic and lumbosacral spine before initiation of treatment. All studies were performed on a 1.5T superconducting magnet (Signa, GE Medical Systems, Milwaukee, WI). Routine spin echo Tlweighted and gradient-recalled acquisition in the steady-state (GRASS) images were obtained in sagittal and axial planes. All patients received megavoltage irradiation of the primary lesion. Treatment was administered at 2 Gy daily for 5 days per week to a total dose of at least 40 Gy. Serial electrophoretic studies were conducted every 2 months to monitor changes in abnormal protein level. RESULTS The SBP was located in the axial skeleton in 11 of 12 patients (Table 1). With conventional radiographs, 10 pa- tients showed purely lytic bone destruction, one patient had a collapsed vertebra with coarsened trabeculae, and one showed sclerotic involvement ofthe first lumbar vertebra. On MR imaging, the signal intensity of the SBP was similar to muscle on T 1-weighted images and hyperintense to muscle on T2-weighted images in 11 of 12 pa- From the Departments of Diagnostic Imaging, Hematology, and Radiotherapy,The University of Texas M.D. Anderson CancerCenter, Houston, TX. Submitted October 14, 1992; accepted March 8, 1993. Address reprint requests to Lia A. Moulopoulos, MD, Department of DiagnosticImaging, Box 57, The University of Texas, M.D. Anderson CancerCenter, 1515 Holcombe Blvd, Houston, TX 77030. 1993 by American Society of ClinicalOncology. 0732-183X/93/1107-0017$3.00/0 Journal of Clinical Oncology, Vol 11, No 7 (July), 1993: pp 131 1-1315 1311 Downloaded from jco.ascopubs.org on September 7, 2010. For personal use only. No other uses without permission. Copyright 1993 American Society of Clinical Oncology. All rights reserved. 1312 MOULOPOULOS ET AL Table 1. Characteristics of Patients With SBP No. of Patients Lesions on MR imaging 1 2 3 4 No lesions on MR imaging 1 2 3 4 5 6 7 8 Age (years) 44 31 47 39 53 44 70 30 47 45 38 44 Site Sacrum L-1 C-3 T-12 Pelvis Pelvis Sacrum L-5 Radius T-6 L-5 L-1 Myeloma Protein Type Kappa only IgGK IgGk IgGk IgGL None IgAK Kappa only IgGk None Lambda only IgAL Protein Levels (g/dL) Pretreatment Posttreatment 0.3* 2.3 1.5 1.1 0.8 0 1.3 0.3* 1.2 0 0.25* 0.3 0.25* 1.7 2.8 0.6 0 0 0.3 0* 0.6 0 0.01 0.2 *Bence-Jones protein excretion in urine (g/d). Months of Stability 31+ 28+ 10 10+ 33+ 24+ 16+ 12+ 10+ 9+ 6+ 6+ tients (Fig 1); in the patient with a sclerotic lesion on conventional radiographs, the involved vertebra was predominantly hypointense to muscle on both Tl- and T2weighted images. An extraosseous soft tissue component was identified in all patients, with extension into the spinal canal in six of nine patients with vertebral involvement. MR imaging ofthe lumbosacral and thoracic spine showed additional foci of marrow-replacing signal abnormalities in four of 12 patients (Figs 2 through 4). Multiple additional sites of involvement were found in three patients and one additional focus of disease was detected in one patient. The lesions varied in size from 0.3 to 2 cm and the MR signal characteristics were identical to those ofthe primary tumor. In three patients, the lesions were of low signal intensity on T I-weighted images and high signal intensity on T2-weighted images. In the fourth patient with a sclerotic lesion, the additional foci depicted with MR imaging were hypointense to muscle on both T1- and T2-weighted sequences; computed tomographic (CT) examination of the spine in this patient confirmed the sclerotic nature of the abnormal foci. Biopsies of the additional foci were not performed due to the hazards ofthis procedure in patients with small vertebral lesions. Follow-up MR imaging in one patient (patient no. 1, Table 1) with unexpected lesions showed progression of the marrow involvement (Fig 3). This patient remains asymptomatic. Fig 1. (A) GRASS sagittal MR image (250/20; 20-degree flip angle) shows hyperintense signal intensity in the L-5 vertebra, which is compressed. Note extension of tumor into the spinal canal (arrows). (B) Axial Ti -weighted MR image (600/20) at the level of L-5 shows tumor in the spinal canal (white arrows) and in the right paraspinal region (black arrows). Downloaded from jco.ascopubs.org on September 7, 2010. For personal use only. No other uses without permission. Copyright 1993 American Society of Clinical Oncology. All rights reserved. SOLITARY BONE PLASMACYTOMA, MR IMAGING 1313 With a median follow-up of 13 months (range, 6 to 33), no patient has developed a recurrence within the field of radiotherapy. All eight patients without other lesions have been monitored without additional treatment and have remained stable without evidence of myeloma. Among six patients with a myeloma protein, there was disappearance in two patients and a reduction of protein levels by at least 50% in three additional patients; in none of the four patients with abnormal foci on MR imaging was the myeloma protein reduced by 50% (P < .01) (Table 1). All four patients with marrow abnormalities on MR imaging were treated with interferon alfa-2b at a dose of 2 MU/m 2 subcutaneously three times a week after completion of radiotherapy. Three patients have remained clinically stable for 10, 28, and 31 months. One patient (patient no. 3, Table 1)developed multiple symptomatic bone lesions at the site of the initial MR abnormalities with increasing levels of myeloma protein 10 months after radiotherapy; she has responded to combination chemotherapy for multiple myeloma and is currently in remission. DISCUSSION The diagnosis of SBP is based on specific criteria that require a solitary plasma cell tumor without evidence of other disease. Some investigators have postulated that multiple myeloma begins as a SBP that then becomes generalized after several years.4 Because SBP is radiosensitive, there is a potential for cure with early diagnosis. Nevertheless, fewer than one third of patients with SBP have remained stable for more than 10 years, presumably because occult generalized disease is present in most patients at diagnosis. 3' 4 This report indicates that additional foci of marrow disease are present by MR imaging in approximately one third of patients considered to have a SBP on standard studies. Most patients with SBP have a lytic destructive lesion on conventional radiographs, but rare occurrences of a cystic, trabeculated lesion resembling a giant-cell tumor or an aneurysmal bone cyst have been described.'l Among our patients, a lytic feature was dominant in 10, but one patient showed a compressed vertebra with coarsened trabeculae. Sclerotic lesions, as seen in another patient, occur in less than 3% of patients with multiple myeloma, some of whom have other clinical features such as polyneuropathy, organomegaly, endocrinopathy, and skin changes (POEMS syndrome)." Our patient with sclerotic SBP did not have any other clinical features of POEMS syndrome. There is virtually no information regarding the MR Fig 2. (A) Conventional radiograph of the lumbar spine shows pathologic compression fracture of the T-12 vertebra. (B) GRASS sagittal MR image (250/20; 20-degree flip angle) shows the involvement of the T-1 2 vertebra and an additional focus of disease at L-4 (arrow). appearance of SBP. In 11 of 12 patients, the MR appearance resembled that of other primary or secondary malignancies that produce lytic destruction of bone. In the sclerotic SBP, the lack of bright signal on T2-weighted images reflected the dense bone and was indistinguishable from blastic involvement of any etiology. In all patients, an extraosseous soft tissue component was present. MR imaging is of value and superior to CT scanning in depicting the extent of both the intraspinal tumor and the paraspinal soft tissue component so that portals of radiation treatment can be defined with maximum precision. MR imaging showed unanticipated foci in the marrow of four of 12 patients with SBP. The MR imaging features of these abnormalities were identical to those of each patient's histologically confirmed primary SBP and to the appearance of marrow involvement by multiple myeloma in other patients.6" The small size of the lesions and the known hazards of spinal biopsies prevented us from confirming unequivocally the histologic nature of these foci. None of these patients had or developed signs of any other disease that could account for the MR imaging findings. The later development of overt disease in the same area Downloaded from jco.ascopubs.org on September 7, 2010. For personal use only. No other uses without permission. Copyright 1993 American Society of Clinical Oncology. All rights reserved. 1314 as the MR lesions in one patient and the progression of the lesions on follow-up MR study in another patient support our view that the additional foci represented occult myeloma. In contrast to multiple myeloma, where approximately 97% of patients have an abnormal protein in the serum or urine, an abnormal protein has been found in approx- MOULOPOULOS ET AL Fig 4. (A) Conventional radiograph of the lumbar spine shows sclerotic changes in the L-1 vertebra (arrow). (B) MR image (600/20) shows fatty marrow replacement in L-1, as well as multiple welldefined areas of disease throughout the spine (arrows). imately one half of patients with SBP.1-4 In those with a protein marker, serial electrophoreses help to define a response to treatment and to identify a residual clonal population after radiation treatment. Among our patients, there was a significant correlation between the persistence of myeloma protein and the presence of additional lesions on MR imaging. The evolution of SBP to myeloma is not prevented, but may be slowed with adjuvant chemotherapy. 5 Because prolonged administration of alkylating agents may cause a treatment-related leukemia or the earlier evolution of resistant subclones, we administered in- Fig 3. (A) T1 -weighted sagittal MR image (600/20)of the thoracic spine shows small hypointense lesion in the T-8 vertebra (arrows). (B)On corresponding T2-weighted MR image (2,000/80), the lesion is hyperintense to muscle and marrow (arrows). (C) Twenty-fourmonth follow-up T 1-weighted sagittal MR image of the thoracic spine shows almost complete involvement of the vertebral body of T-8 with sparing of the pedicle (arrows) and a new lesion in T-9 (long arrow). (D) On the corresponding T2-weighted image, mild increase in signal intensity can be seen in the involved vertebral body of T-8 (arrows). The lesion in T-7 is seen (long arrow). Downloaded from jco.ascopubs.org on September 7, 2010. For personal use only. No other uses without permission. Copyright 1993 American Society of Clinical Oncology. All rights reserved. SOLITARY BONE PLASMACYTOMA, MR IMAGING terferon alfa to our four patients with additional MR signal abnormalities as part of a prospective study.12 Interferon alfa has an established cytostatic effect against myeloma when given during remission mainte- 1315 nance and has not been associated with secondary leukemias.'3 Our study constitutes a preliminary report on the potential value of MR imaging in the initial assessment of patients with SBP. REFERENCES 1. Knowling MA, Harwood AR, Bergsagel DE: Comparison of extramedullary plasmacytomas with solitary and multiple plasma cell tumors of bone. J Clin Oncol 1:255-262, 1983 2. Chak LY, Cox RS, Bostwick DG, et al: Solitary plasmacytoma of bone: Treatment, progression and survival. J Clin Oncol 5:18111815, 1987 3. Frassica DA, Frassica FJ, Schray MF, et al: Solitary plasmacytoma of bone: Mayo Clinic experience. Int J Radiat Oncol Biol Phys 16:43-48, 1989 4. Dimopoulos MA, Goldstein J, Fuller L, et al: Curability of solitary bone plasmacytoma. 3 Clin Oncol 10:587-590, 1992 5. Holland J, Trenkner DA, Wasserman TH, et al: Plasmcytoma. Treatment results and conversion to myeloma. Cancer 69:1513-1517, 1992 6. Fruehwald FXJ, Tscholakoff D, Schwaighofer B, et al: Magnetic resonance imaging of the lower vertebral column in patients with multiple myeloma. Invest Radiol 23:193-199, 1988 7. Daffner RH, Lupetin AR, Dash N, et al: MRI in the detection of malignant infiltration of bone marrow. Am J Roentgenol 146:353358, 1986 8. Libshitz HI, Malthouse SR, Cunningham D, et al: Magnetic resonance appearance of multiple myeloma. Radiology 182:833-837, 1992 9. Moulopoulos LA, Varma DGK, Dimopoulos MA, et al: MR imaging of the spine in untreated newly diagnosed multiple myeloma. Radiology 185:833-840, 1992 10. Huvos AG: Multiple myeloma including solitary osseous myeloma, in (eds): Bone Tumors: Diagnosis, Treatment and Prognosis. Philadelphia, PA, Saunders, 1992, pp 653-676 II1. Miralles GD, O'Fallon JR, Talley NJ: Plasma cell dyscrasia with polyneuropathy-The spectrum of POEMS syndrome. N Engl J Med 327:1919-1923, 1992 12. Delauche-Cavallier MC, Laredo JD, Wybier M, et al: Solitary plasmacytoma of the spine; Long term clinical course. Cancer 61: 1707-1714, 1988 13. Mandelli F, Avisati G, Amadori S, et al: Maintenance treatment with recombinant interferon alpha-2b in patients with multiple myeloma responding to conventional induction chemotherapy. N Engl J Med 322:1430-1434, 1990 Downloaded from jco.ascopubs.org on September 7, 2010. For personal use only. No other uses without permission. Copyright 1993 American Society of Clinical Oncology. All rights reserved.