a pictorial review on extraosseous manifestations of ... · imaging studies show diffuse...

Extraosseous multiple myeloma is defined as a local-ized plasma cell neoplasm in soft tissue with the pres-ence of systemic multiple myeloma. By definition, ex-traosseous myeloma cannot arise within bones (1).Extraosseous involvement of multiple myeloma, whichcan arise in any tissues, can be seen clinically or radio-logically in approximately 10-20% of patients at thetime of initial diagnosis and may develop in an addition-

al 15% of patients during the course of the disease (2, 3).Extraosseous myeloma is more common in youngermyeloma patients, and is more frequent than nonsecre-tory myeloma and IgD myeloma (the more aggressivesubtypes of myeloma) (1).

In addition to a skeletal survey, magnetic resonance(MR) imaging or 18F-fluorine deoxyglucose (FDG)PET/CT may be performed to identify occult skeletal in-volvement of multiple myelomas (4). Because a sizablenumber of patients with multiple myelomas have ex-traosseous involvement of the disease at initial presenta-tion or during the follow-up imaging evaluation (withtreatment including stem cell transplantation), we mayencounter cases of extraosseous involvement of multi-ple myeloma more frequently. Thus, it is important tobe familiar with the imaging findings of extraosseousmyeloma involvement. The purpose of this pictorial re-

J Korean Soc Radiol 2011;64:567-575

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A Pictorial Review on Extraosseous Manifestations ofMultiple Myelomas1

Jung Min Seo, M.D., Kyung Soo Lee, M.D., Chin A Yi, M.D., Seong Hyun Kim, M.D., Byung Kwan Park, M.D., Boo-Kyung Han, M.D., Hyung-Jin Kim, M.D.

1Department of Radiology and Center for Imaging Science, SamsungMedical Center, Sungkyunkwan University School of Medicine, Seoul,KoreaThis pictorial essay was presented as an educational exhibit at the 2010RSNA scientific assembly (LL-MSE2639).Received April 11, 2011 ; Accepted April 13, 2011Address reprint requests to : Kyung Soo Lee, M.D., Department ofRadiology, Samsung Medical Center, Sungkyunkwan University Schoolof Medicine, 50 Ilwon-dong, Gangnam-gu, Seoul 135-710, Korea.Tel. 82-2-3410-2511 Fax. 82-2-3410-2559E-mail: [email protected]

Extraosseous involvement of multiple myelomas can be seen clinically or radiologi-cally in approximately 10-20% of patients at the time of initial diagnosis and may de-velop in an additional 15% of patients over the course of the disease. The conditioncan arise in any tissue of the body and its presence has been associated with more ag-gressive disease, a guarded prognosis, or high-dose chemotherapy. Imaging findings ofextraosseous multiple myelomas are diverse. They usually show high enhancement oncontrast-medium enhanced CT scans, exhibit iso-signal intensity on both T1- and T2-weighted images, and variable 18F-fluorine deoxyglucose (FDG) uptake at PET. Thedisease may simulate an infectious condition since it may be concurrent with underly-ing multiple myelomas per se or it may occur during myeloma treatment includingstem cell transplantation.

Index words : Multiple MyelomaTomograhy, X-Ray ComputedMagnetic Resonance ImagingPositron-Emission Tomography

view was to illustrate the imaging findings of the ex-traosseous manifestation of multiple myelomas. Image Sources

A review of the medical records performed to docu-ment multiple myeloma cases with extraosseous in-volvement from a single tertiary hospital for 16 yearsfrom 1995 to 2010 found 11 cases from 11 consecutivepatients. Of the 11 patients, six were six men and fivewere women (age range, 45-76 years; mean age ± stan-dard deviation, 60 ± 8). The summary of the involvedextraosseous tissues from all 11 patients included 15 or-gans: oropharynx, orbit, brain, lung, pleura, medi-astinum (in two patients), liver (in two patients), spleen,kidney, retroperitoneum, lymph node, muscle, andbreast. Extraosseous plasma-cell myelomatous involve-ment was confirmed histopathologically in eight of the15 lesion sites. The involvement of the brain and lungswas confirmed by observing the presence of plasmacells in the CSF and pleural effusion, respectively.Under these conditions, abnormal lesions could be ob-served in the brain and lungs. The lesions in the orbit,

Jung Min Seo, et al : A Pictorial Review on Extraosseous Manifestations of Multiple Myelomas

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A B

C

Fig. 2. An ocular myeloma in a 60-year-old man with extensivesystemic manifestation of IgM multiple myeloma. A, B. T1-weighted (A) and T2-weighted (B) MR images show aniso-signal intensity lesion (arrows) in the right eye orbit. C. A contrast-enhanced T1-weighted MR image demonstrateshomogenous enhancement (arrow) of the lesion.

Fig. 1. Biopsy-proven plasmacytoma in the oropharynx of a 76-year-old man with IgG multiple myeloma. A contrast en-hanced CT scan at the level of the tongue base shows a ho-mogenous, well-enhancing, soft-tissue mass (arrows) in the an-terior wall of oropharynx.

kidney, lymph node, spleen, and muscle from three pa-tients were not confirmed histopathologically.However, the lesions sufficiently qualified as being diag-nosed as myeloma with extraosseous involvement, be-cause the lesions manifested as newly-appearing lesionsin patients with aggressive extra- and intra-osseousmyeloma during the disease progress, without clinicalevidence of infection, or showed a decrease in disease

extent on follow-up images after chemotherapy.

Head and Neck Involvement

Oropharynx

The oropharynx is the most common site (80%) of ex-tramedullary plasmacytoma. The organ can be involvedeven in patients who had no systemic involvement inthe disease. Involvement is associated with the bestlong-term prognosis (5), and can be seen as a soft-tissuemass (Fig. 1) on CT scans. However, the oral cavity isoccasionally involved with myeloma; plasma cell infil-tration is seen in 5% of patients with multiple myeloma.


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A BFig. 4. Pulmonary light-chain myelomas in a 58-year-old woman. A, B. Conventional CT images (5.0-mm-section thickness) obtained at the levels of thoracic inlet (A) and bronchus intermedius (B),respectively, show multiple variable sized lung nodules (arrows) scattered in both lungs. Lung lesions were considered to inferlung involvement of multiple myeloma due to the absence of signs of infection and regression after chemotherapy (not shownhere). Small amounts of bilateral pleural effusions were also seen. Plasma cells were identified in a pleural fluid analysis.

Fig. 3. Cavernous sinus light-chain myeloma in a 58-year-oldwoman. A contrast enhanced T1-weighted MR image shows anewly developed soft-tissue nodule (arrow) in the left cav-ernous sinus. The lesion was absent on MR images obtainedone year ago. CSF analysis revealed atypical plasmacytoidcells.

Fig. 5. Pleural IgM myeloma in a 60-year-old man. EnhancedCT scan (2.5-mm-section thickness) obtained at the atrial levelshows bilateral pleural effusions. Also note the multifocal ar-eas of pleural thickening and mass-like lesions (arrows).

Orbit

Orbital involvement by multiple myeloma is relativelyrare, and approximately 60 cases of orbital involvementhave been reported to date. Almost any structures in theorbit can be involved with multiple myeloma. Patientswith this disease complain of proptosis, chemosis, visualacuity changes, epiphora, and diplopia. The lesion maymanifest as having iso-signal intensity on both T1- andT2-weighted images and showing noticeable enhance-ment on contrast enhanced CT scans (Fig. 2).

Intracranial Myeloma

The incidence of intracranial myeloma is rare, and theprognosis of meningeal and cerebral myeloma is poor(6). The leptomeninges is the most common site of in-tracranial mylomatous involvement. In this condition,imaging studies show diffuse enhancement or a focalenhancing nodule or mass (Fig. 3). Therefore, imagingfindings may mimic meningitis or a meningioma.

Cerebral plasmacytomas manifest as an intensely andhomogeneously enhancing lesion with perilesional ede-ma.


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A BFig. 6. Biopsy-proven mediastinal light-chain myeloma in a 45-year-old man.A. Chest radiograph shows bilateral mediastinal widening (arrows). B. A contrast-enhanced CT scan (2.5-mm-section thickness) obtained at the level of the main bronchi demonstrates a large bilateralanterior mediastinal mass that shows mild enhancement. Small amounts of bilateral pleural effusions, small in amount are also as-sociated. A surgical biopsy specimen revealed a myelomatous lesion. (Min JH, et al. J Korean Soc Radiol 2010;62:365-368, with per-mission)

A BFig. 7. Biopsy-proven mediastinal IgD myeloma in a 60-year-old man.A. A contrast-enhanced CT scan (5.0-mm-section thickness) obtained at the level of the azygos arch shows an enhancing left anteri-or mediastinal mass (arrow). B. PET scan obtained at a similar level to a demonstrates little FDG uptake within the lesion. After chemotherapy, the left anteriormediastinal mass disappeared (not shown here).

Thorax

Lungs

Myeloma cases with lung involvement are rare and

have a poor prognosis. The involvement is reported todemonstrate a mass or an infiltrative lesion which is in-distinguishable from a lung metastatic lesion from an ex-


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A B

C D

EFig. 8. Biopsy-proven hepatic light-chain myelomas in a 49-year-old woman who is a hepatitis-B virus carrier.A. Ultrasonography of the liver shows multiple hypoechoic nodules (arrows) in both lobes of the liver.B, C. Enhanced liver CT scans obtained at the levels of the liver dome (B) and hepatic veins (C), respectively, and in the portalphase, show enhancing small hepatic nodules (arrows) in both lobes of the liver.D. T2-weighted MR image shows multiple hyperintense nodular lesions (arrows) in the liver.E. Dynamic MR images obtained after the injection of gadoxetic acid show multiple nodules in the liver. The nodules show en-hancement at the arterial phase (A) and washout in both the equilibrium (E) and hepatobiliary (H) phases.

tra-thoracic malignancy (2) . They may appear as multi-ple lung nodules scattered in both lungs (Fig. 4).

Pleura

Pleural myeloma may exhibit pleural effusions withpleural thickening and nodular lesions, independentfrom the osseous involvement of multiple myeloma.The pleural lesions may be indistinguishable from ma-lignant pleural mesothelioma (Fig. 5) (2).

Mediastinum

There have been few cases of myeloma that involved

the mediastinum (7). These lesions show relatively ho-mogeneous enhancement following intravenous con-trast-medium administration. The differential diagnosesinclude non-Hodgkin lymphoma, malignant thymic ep-ithelial tumor, and small cell lung cancer. In our cases,the lesions showed mild homogenous enhancement onCT scans and little FDG uptake on PET scans (Figs. 6, 7).

Abdomen

Liver

Liver is most commonly involved with extraosseousmyeloma in the abdomen. The involvement demon-


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A B

Fig. 9. Biopsy-proven hepatic IgDmyelomas in 69-year-old man.A. An enhanced whole-body MR im-age shows iso- to slightly high-signalintensity lesions (arrows, osseous in-volvement of myeloma) in the rightproximal and distal tibia. Also noted isa round lesion (arrowhead) in the liverwith slightly lower-signal intensitythan normal liver. The hepatic lesionshowed early arterial enhancementand delayed washout on dynamic MRimages as in Figure 8 (not shownhere).B. A PET scan does not show any evi-dence of FDG uptake either in bone le-sions in the right tibia or in the liver le-sion.

strates two different features; hepatomegaly without fo-cal lesion is one of its manifestations when the plasmacell infiltrates into the sinusoids. The other manifesta-tion is a nodular form which is indistinguishable from ahepatic metastatic lesion (2). The attenuation of the nod-ule has been known to be lower than that of normal liv-er parenchyma in all phases on dynamic CT scans (8),but it is not always the case. The lesion may be hyper-vascular and may manifest an enhancing lesion in thearterial phase, and delayed washout on dynamic CT andMRI (Fig. 8). The hepatic lesion may show little FDGuptake at PET (Fig. 9).

Spleen

The involvement of the spleen is rare in patients withmultiple myeloma. Less than 1% of patients with multi-ple myeloma show splenomegaly (2).

Kidneys

Renal disease is rarely caused by plasma cell infiltra-tion in patients with multiple myeloma, which can in-volve the renal parenchyma as well as perirenal spacesas soft tissue masses (Fig. 10) (3).

Mesentery and Peritoneum

The mesentery or the peritoneum is a rare site of ex-


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Fig. 10. Renal involvement of light-chain myeloma in a 49-year-old woman. Newly developed multifocal low-attenuationlesions (arrows) are observed in both kidneys on delayed-phase CT images. Patients had such renal lesions on regularfollow-up CT studies after the complete remission of multiplemyeloma.

Fig. 12. Retroperitoneal IgG and light-chain myeloma in a 68-year-old woman. A contrast-enhanced CT scan (5.0-mm-sec-tion thickness) shows a highly enhancing infiltrative mass (ar-rows) in the presacral and right parapelvic areas. A double-Jcatheter (arrowhead) was inserted into the right ureter, owingto its invasion by the mass.

Fig. 13. Lymph node involvement of light-chain myeloma ina 49-year-old woman. A contrast-enhanced CT scan (5.0-mm-section thickness) obtained at the level of porta hepatis showsenlarged lymph nodes (arrows) around the caudate lobe of theliver and splenic artery, respectively. The lesions were absenton CT scans (not shown here) taken two years ago.

Fig. 11. Mesenteric IgG and light-chain myeloma in a 51-year-old woman. Contrast enhanced CT scan (5.0-mm-sectionthickness) shows a large mass lesion (arrows) within themesenteries. The lesion harbors a central necrotic portion, andentraps the superior mesenteric vessels. Plasmacytoma washistopathologically confirmed.

tramedullary involvement by plasmacytoma. With thisinvolvement, CT may exhibit discrete mass lesions (Fig.11) or permeative and infiltrative tumor growth. The ex-traosseous myeloma present as mesenteric panniculitis(9). Under these conditions, abdominal CT scansshowed mesenteric thickening and inhomogeneous ar-eas of fat interspersed with soft-tissue attenuation.

Retroperitoneum

Extraosseous multiple myeloma in the retroperi-toneum manifests as a retroperitoneal soft-tissue mass.

Also, obstructive uropathy due to encasement of theureter may be associated (Fig. 12).

Miscellaneous Organs

Lymph Nodes

Lymph nodes are one of the most frequently involvedextraosseous tissues in multiple myeloma. In one autop-sy series, lymph nodes were enlarged in 12 (23%) of 52patients with multiple myeloma (10). Imaging findingson CT scans are similar to those of lymphoma, withmultiple nodal groups involved (Fig. 13).

Muscles

Plasma cell tumor in the muscle independent frombone involvement is rare. In our case series, a patienthad the psoas muscle was involved with extensive mul-tiple myeloma was. In this particular case, biopsy con-firmation was not performed, but the lesion showed re-gression after chemotherapy (Fig. 14).

Breasts

Breast plasmacytomas are solid, non-tender, and well-defined masses of variable sizes. Imaging findings ofbreast plasma are round and well-defined masses onmammography, and solid well-demarcated masses witha homogenous echo-texture on ultrasonography (Fig. 15).

Conclusion

Imaging may play an important role in the manage-ment of extraosseous myelomas, because it facilitates


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Fig. 14. Psoas muscle light-chain myeloma in a 48-year-oldwoman. A contrast enhanced CT scan (5.0-mm-section thick-ness obtained at the level of pelvic inlet shows a heteroge-neously enhancing mass lesion (arrows) in the right psoasmuscle. Also note a smaller enhancing lesion (arrowhead) inthe right iliacus muscle area.

A BFig. 15. Breast IgG and light-chain myeloma in a 65-year-old woman.A. Mediolateral oblique view of mammography shows a well-circumscribed hyperdense mass (arrow) in the upper central portionof the right breast. B. Ultrasonography of right breast shows a heterogeneous low-echoic mass (arrows) in the corresponding mammographic area.

the early diagnosis of this condition, differentiates thiscondition from other diseases such as infectious dis-eases, and evaluates the response to a certain kind oftherapy. Although imaging findings of extraosseousmultiple myelomas are frequently nonspecific and di-verse, they can be categorized into an infiltrative soft-tis-sue pattern and a nodular or mass-forming pattern. Inthe pleura, mesentery, and peritoneum or the liver, ex-traosseous multiple myelomas may manifest as infiltra-tive soft tissue lesions. The lesions frequently appear asenhancing soft-tissue lesions or masses with early en-hancement and delayed washout on dynamic CT scansor dynamic MR images. The lesions show an isointensesignal on T1-weighted MR images and a hyperintensesignal on T2-weighted images. FDG PET plays a limitedrole in the evaluation of extraosseous involvement ofmyeloma because the lesions show variable FDG up-take.

References

1. Varettoni M, Corso A, Pica G, Mangiacavalli S, Pascutto C,Lazzarino M. Incidence, presenting features and outcome of ex-tramedullary disease in multiple myeloma: a longitudinal study on

1003 consecutive patients. Ann Oncol 2010;21:325-3302. Moulopoulos LA, Granfield CA, Dimopoulos MA, Kim EE,

Alexanian R, Libshitz HI. Extraosseous multiple myeloma: imag-ing features. AJR Am J Roentgenol 1993;161:1083-1087

3. Patlas M, Hadas-Halpern I, Libson E. Imaging findings of ex-traosseous multiple myeloma. Cancer Imaging 2002;2:120-122

4. Hall MN, Jagannathan JP, Ramaiya NH, Shinagare AB, Van denAbbeele AD. Imaging of extraosseous myeloma: CT, PET/CT, andMRI features. AJR Am J Roentgenol 2010;195:1057-1065

5. Damaj G, Mohty M, Vey N, Dincan E, Bouabdallah R, Faucher C,et al. Features of extramedullary and extraosseous multiple myelo-ma: a report of 19 patients from a single center. Eur J Haematol2004;73:402-406

6. Patriarca F, Zaja F, Silvestri F, Sperotto A, Scalise A, Gigli G, et al.Meningeal and cerebral involvement in multiple myeloma pa-tients. Ann Hematol 2001;80:758-762

7. Masood A, Hudhud KH, Hegazi A, Syed G. Mediastinal plasmacy-toma with multiple myeloma presenting as a diagnostic dilemma.Cases J 2008;1:116

8. Patlas M, Khalili K, Dill-Macky MJ, Wilson SR. Spectrum of imag-ing findings in abdominal extraosseous myeloma. AJR Am JRoentgenol 2004;183:929-932

9. Goh J, Otridge B, Brady H, Breatnach E, Dervan P, MacMathunaP. Aggressive multiple myeloma presenting as mesenteric panni-culitis. Am J Gastroenterol 2001;96:238-241

10. Oshima K, Kanda Y, Nannya Y, Kaneko M, Hamaki T, Suguro M,et al. Clinical and pathologic findings in 52 consecutively autop-sied cases with multiple myeloma. Am J Hematol 2001;67:1-5


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한 상의학회지 2011;64:567-575

다발성골수종의골외발현1

1성균관의 삼성서울병원 상의학과

서정민∙이경수∙이진아∙김성현∙박병관∙한부경∙김형진

약 10-20%의 다발성골수종 환자에서 처음 진단 시에 골외 침범이 발견되며 질병의 경과 중 15%의 환자에서 골

외 침범이 더 발견된다. 골외 다발성골수종은 신체의 어느 부위에서도 발병할 수 있고 더 침습적이고 예후가 좋지 않

은 것으로 알려져 있다. 골외 다발성골수종의 상의학적 소견은 다양한데, CT에서는 조 증강이 잘 되고 T1과

T2 강조 상에서는 동신호강도를 보이며, PET에서는 다양한 정도의 (18F-fluorine deoxyglucose (FDG))흡

수를 보인다. 이 질환은 다발성골수종 자체에 의한 혹은 조혈모세포 이식 후에 발생할 수 있는 감염 질환으로 오인될

수 있어 이와의 감별을 요한다.

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