Radiologic Manifestations of Primary Solitary Extramedullary and Multiple Solitary Plasmacytomas
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1 Radiologic Manifestations of Plasmacytomas Oncologic Imaging Clinical Observations C D E M N E U T R Y L I M C I G O F I N G Gaik Cheng Ooi 1 James Chor-Sang Chim 2 Wing-Yeh u 2 Pek-Lan Khong 1 Ooi GC, Chim JC-S, u W-Y, Khong P-L Keywords: CT, MRI, oncologic imaging, plasma cell tumor, plasmacytoma DOI: /JR Received November 18, 2004; accepted after revision February 7, Department of Diagnostic Radiology, The University of Hong Kong and Queen Mary Hospital, K405, Hong Kong SR, Hong Kong. ddress correspondence to G. C. Ooi (cgcooi@hkucc.hku.hk). 2 Department of Medicine, The University of Hong Kong and Queen Mary Hospital, Hong Kong SR, Hong Kong. JR 2006; 186: X/06/ merican Roentgen Ray Society Radiologic Manifestations of Primary Solitary Extramedullary and Multiple Solitary Plasmacytomas OJECTIVE. Primary solitary extramedullary and multiple solitary plasmacytomas are rare manifestations of plasma cell tumors. This study reviews their imaging spectrum in 12 patients. CONCLUSION. Imaging features of primary solitary extramedullary and multiple solitary plasmacytomas are nonspecific but are compatible with solid tumors that are isointense on T1-weighted images and iso- to hyperintense on T2-weighted images relative to muscle and white matter with variable enhancement. Large tumors may show necrosis and destruction, infiltration, or encasement of adjacent structures. Multiplicity of lesions and regional lymphadenopathy were evident on imaging in only five cases each. Imaging alone cannot differentiate these tumors from more common malignant entities such as carcinoma, meningioma in cases of intracranial extramedullary plasmacytomas, or metastasis from other primaries. The role of imaging should be focused on early detection of additional or recurrent lesions and the presence of regional lymphadenopathy, which will influence clinical management. lasmacytoma, a neoplastic proliferation of plasma cells, is one form P of plasma cell dyscrasia that may manifest as multiple myeloma, primary amyloidosis, or monoclonal gammopathy of unknown significance. Plasmacytoma may be primary or secondary to disseminated multiple myeloma and may arise from osseous (medullary) or nonosseous (extramedullary) sites. Primary extramedullary plasmacytoma can be solitary or multiple [1]. The International Myeloma Working Group in 2003 recognized a separate classification of plasmacytomas that occur as multiple sites of disease in soft tissue, bone, or both soft tissue and bone as multiple solitary plasmacytoma [2]. Primary extramedullary plasmacytoma is rare, accounting for only 4% of all plasma cell tumors, the majority (80%) of which occur in the upper aerodigestive tract [2, 3]. Skin and the gastrointestinal tract are less common sites. Primary plasmacytoma, whether osseous or nonosseous, is distinguished from multiple myeloma by the absence of hypercalcemia, renal insufficiency and anemia, normal skeletal survey, absence of bone marrow plasmacytosis, and serum or urinary paraprotein level of less than 2 g/dl [3 5]. The clinical course and prognosis of solitary bone plasmacytoma, extramedullary plasmacytoma, multiple solitary plasmacytoma, and multiple myeloma differ, leading some to consider these as separate disease entities rather than a spectrum of the same disease [2 4]. ecause of its rarity, radiologic descriptions of primary solitary extramedullary plasmacytoma and multiple solitary plasmacytoma have been confined to case reports. The purpose of this review is therefore to study the imaging features and role of imaging in primary solitary extramedullary plasmacytoma and multiple solitary plasmacytoma presenting over a 16-year period to our institution. Materials and Methods ll imaging and clinical and laboratory data of 21 cases of primary plasmacytoma treated at our institution, a tertiary referral center for hematologic malignancies, from 1988 to 2004 were retrieved from the institutional database. Diagnostic criteria included biopsy showing plasma cell infiltration; absence of lytic bone lesions on skeletal survey except at the site of disease; bone marrow plasmacytosis value of less than 5% of all nucleated cells in a random bone marrow sample; serum or urinary paraprotein level of less than 2 g/dl; and absence of anemia, hypercalcemia, or renal impairment, which is suggestive of systemic myeloma [1, 3]. Primary plasmacytoma was characterized as solitary bone plasmacytoma when a single bone plasmacytoma was present [2, 3], solitary extramedullary plasmacytoma when a solitary soft-tissue plasmacytoma JR:186, March
2 was present [1 3], or multiple solitary plasmacytoma when there was more than one localized bone or extramedullary tumor of clonal plasma cells [1, 2]. Of the 21 cases of primary plasmacytoma, seven cases of solitary bone plasmacytoma were excluded. Imaging was available in 12 (eight men; mean age ± SD, 59.7 ± 13.6 years) of the remaining 14 cases of primary plasmacytomas. ll imaging examinations performed at presentation of illness and subsequent follow-up were reviewed together by two experienced radiologists. These comprised conventional radiographs, CT scans, MR images, and radionuclide bone scans. The site of the plasmacytoma and its enhancement features and the presence of invasion of adjacent structures, bone destruction or erosion, and enlarged regional lymph nodes were noted. CT scans were obtained on one of two scanners (LightSpeed or HiSpeed, GE Healthcare), and MRI was performed on a 1.5-T scanner (Signa, GE Healthcare). One unenhanced CT, 15 contrast-enhanced CT, and three gadolinium-enhanced MR scans were reviewed. Two radionuclide bone scans were also available for review. Results There were six patients with solitary extramedullary plasmacytoma (three men; mean age ± SD, 60.3 ± 18.6 years) and six with multiple solitary plasmacytoma (five men; mean age ± SD, 59 ± 7.8 years). multiplicity of multiple solitary plasmacytoma lesions was noted only after radiologic evaluation in five of the six cases. Plasmacytomas in four cases of multiple solitary plasmacytoma comprised multiple extramedullary plasmacytomas, whereas in two cases a bone plasmacytoma and an extramedullary plasmacytoma coexisted. Two cases of solitary extramedullary plasmacytoma and one case of multiple solitary plasmacytomas relapsed within a year of treatment without evidence of disseminated bone marrow involvement or serum or urinary paraprotein level of more than 2 g/dl. The solitary extramedullary plasmacytoma cases relapsed as multiple solitary plasmacytomas in the lymph nodes, pancreas, and skin in one case and in the adrenal gland and mediastinum in the second case. The multiple solitary plasmacytoma case relapsed with a solitary pelvic extramedullary plasmacytoma. In total, 23 plasmacytoma lesions including the recurrent lesions were reviewed (Table 1), 21 of which were extramedullary plasmacytomas in the axillary lymph nodes (n = 1), head and neck (n = 7), thorax (n = 6), and abdomen (n =7). one involvement (humerus and rib) in two multiple solitary plasmacytoma cases was TLE 1: Site of Primary Extramedullary Plasmacytoma and Multiple Solitary Plasmacytomas Site of Lesion No. of Cases Head and Neck Nasopharynx 1 Orbit 1 Posterior to the clivus 1 Nasal ala 2 Neck soft tissue 1 Submandibular gland 1 Thorax Pleura 1 Mediastinum 2 a Heart 1 Lung 1 Skin bdomen Kidney 2 Liver 1 Spleen 1 drenal gland Pelvis Pancreas one Humerus 1 b Rib 1 c Lymph node xilla 1 d a Recurrent plasmacytoma after local treatment of presenting lesion. b Presenting lesion was a neck mass. c Presenting lesion with concomitant pleural plasmacytoma. d Primary lymph node plasmacytoma. lytic and ill-defined; an enhancing soft-tissue component was associated with the rib lesion. ll extramedullary plasmacytoma lesions were generally well-defined soft-tissue masses on CT, isointense to muscle and white matter on T1-weighted images, and iso- to hyperintense to muscle and white matter on T2- weighted images, with heterogeneous enhancement especially on MRI. Infiltration of adjacent fat was noted in three relatively small (1 2 cm) extramedullary plasmacytomas (renal, nasal, and skin) (Fig. 1), whereas bone erosion was present in three larger (4.5 7 cm) extramedullary plasmacytomas arising in the mediastinum, nose, and neck and destroying the adjacent sternum, medial maxillary wall and nasal septum (Fig. 2), and transverse process of thoracic vertebra, respectively. Vascular encasement was found in three large extramedullary plasmacytoma lesions, which ranged in size from 7 to 15 cm, arising in the lung (Fig. 3), mediastinum, and kidney (Fig. 4). On CT, the lung extramedullary plasmacytoma was shown to infiltrate the pleura and pericardium with a second separate lesion arising from the right atrium and superior vena cava (Fig. 3), causing this solitary extramedullary plasmacytoma to be reclassified as a case of multiple solitary plasmacytoma. Central necrosis was present in a cm renal and a 7 4 cm adrenal extramedullary plasmacytoma (Fig. 4). The smaller of the two renal extramedullary plasmacytomas showed marked heterogeneous arterial enhancement akin to renal cell carcinoma. Imaging findings led to another case of presumed solitary extramedullary plasmacytoma, an intraorbital superior extraconal mass that had permeated the adjacent orbital roof (Fig. 5), to be reclassified as multiple solitary plasmacytomas when a second asymptomatic lesion was found posterior to the clivus and dorsum sella. oth lesions were mildly hyperdense to brain tissue on CT and were isointense to white matter on both T1- and T2- weighted imaging, with marked enhancement (Fig. 5). dural tail was noted in the posterior clival lesion. The intraorbital mass was hypermetabolic on radionuclide bone scans. The only other patient who underwent radionuclide bone scanning was a patient with a neck extramedullary plasmacytoma, which showed no uptake on the bone scans. Plasmacytomas in the liver and spleen were multiple nodular lesions that showed mild peripheral enhancement with central hypodense areas. Involvement of regional lymph nodes was evident on imaging in only five of six cases with nodal involvement (five cases of multiple solitary plasmacytomas and one of solitary extramedullary plasmacytoma) (Fig. 4). The plasmacytoma lesions arose in the kidney, pleura, neck, liver and spleen, and nasopharynx and nose. Plasmacytosis of less than 5% of all nucleated cells was noted in the bone marrow of 10 patients, whereas the remaining two patients had normal bone marrow biopsy results. No urinary or serum paraprotein was found in six patients, while in the remaining patients, negligible urinary paraprotein (< 2 g/dl) was present. t the time of writing this article, three patients had been lost to follow-up, three had died from refractory or 822 JR:186, March 2006
3 Radiologic Manifestations of Plasmacytomas progressive disease, two had died from unrelated causes, three had progressed to multiple myeloma (one case of extramedullary plasmacytoma and two cases of multiple solitary plasmacytomas), and one remained in remission. Fig year-old woman with treated primary extramedullary plasmacytoma of mediastinum who relapsed with multiple solitary plasmacytoma 9 months later. and, xial enhanced CT scans show multiple enhancing cutaneous (arrowheads, ) and subcutaneous (arrows, ) lesions and heterogeneously enhancing pancreatic extramedullary plasmacytoma (arrows, ). Discussion Primary extramedullary plasmacytomas in this study irrespective of solitary (extramedullary plasmacytoma) or multiple (multiple solitary plasmacytomas) lesions manifested as soft-tissue tumors with variable mass effect. Large lesions Fig year-old man with nasal extramedullary plasmacytoma. Unenhanced axial CT scan through head shows large soft-tissue mass arises from right nasal passage and extends anteriorly (black arrow) through nasal ala resulting in deviation and erosion of nasal septum and erosion of medial wall of right maxillary sinus (white arrows). showed aggressive traits such as infiltration and destruction of adjacent bone, muscle, and fat and vascular encasement. Extramedullary plasmacytoma lesions classically arise in the upper aerodigestive tract, with a predilection for the head and neck [1, 4]. In a JR:186, March
4 Fig year-old woman with multiple solitary plasmacytoma., Contrast-enhanced axial CT scan of thorax shows mass arising from left upper lobe with left pleural effusion., Coronal reformatted CT image shows second lesion arising from superior aspects of right atrium (arrowheads) with extension of intraatrial extramedullary plasmacytoma (arrows) into superior vena cava. review of more than 400 published articles, 82.2% of extramedullary plasmacytomas were found in the upper aerodigestive tract with 17.8% arising in the gastrointestinal tract, urogenital tract, skin, lung, and breast in that order [1]. In the present study, extramedullary plasmacytomas, both solitary and multiple, were found in the head and neck (30.4%), abdomen (30.4%), and thorax (39.2%), with pure upper aerodigestive involvement comprising only 13% (n = 3) of the total. The tumors were softtissue masses that appeared isointense on T1- weighted images and iso- to hyperintense on T2-weighted images relative to muscle and white matter, with mild to marked heterogeneous enhancement on both CT and MRI. Nasal extramedullary plasmacytomas in this series were indistinguishable from other malignant lesions of the paranasal sinuses, primarily natural killer cell lymphoma, a tumor peculiar to East sia [6]; squamous cell carcinoma; adenocystic carcinoma; and rhabdomyosarcoma, among others. one destruction is not seen in all cases, although it is common in large paranasal or nasopharyngeal extramedullary plasmacytomas; CT is superior to MRI in delineating subtle bone erosions. Intracranial manifestations of extramedullary plasmacytoma include a solitary extraaxial mass similar to a meningioma as in our case, diffuse leptomeningeal disease mimicking leptomeningeal carcinomatosis or lymphoma [5], and very rarely intracerebral lesions with vasogenic edema. Other conditions that share similar imaging features include plasma cell granuloma, lymphoma, metastasis, dural sarcoma, and infectious meningitis. On a similar note, imaging alone could not differentiate lung and mediastinal plasmacytomas in this study from primary bronchogenic carcinomas or lymphomas, although the latter are usually hypodense without significant enhancement. Of seven published cases of cardiac plasmacytomas with microscopic description, four were an extramedullary manifestation of multiple myeloma, one was a solitary intracardiac extramedullary plasmacytoma, and two were multiple solitary plasmacytomas [7]. oth atria, particularly the right, were involved in nearly all cases including our own. It has been postulated that in disseminated multiple myeloma, circulating plasma cells implant in at least the right atrium via the venous system [7]. Differential diagnoses include the more common atrial myxoma, other intracardiac metastases, and sarcomas. Nearly 10% of primary extramedullary plasmacytomas occur in the gastrointestinal tract, with the stomach and colon as the most common sites followed by the small bowel and esophagus [1]. lthough liver, spleen, and lymph nodes are common extramedullary manifestations of multiple myeloma, primary extramedullary plasmacytomas of these organs including the pancreas and adrenal gland are extremely rare. The liver and spleen extramedullary plasmacytomas in this study resembled metastases. The few published cases of adrenal extramedullary plasmacytoma, including ours, ranged from 3.5 to 10 mm; were heterogeneously enhancing solid tumors; and did not show signal reduction on opposed phase MRI, a finding that typifies adenoma. Renal extramedullary plasmacytoma can manifest as a very large mass with enlarged retroperitoneal lymph nodes, a perinephric mass akin to metastatic melanoma, or a vascular mass that mimics renal cell or transitional cell carcinoma [8]. Regional lymphadenopathy was noted on imaging in half of our patients. This underscores the importance of local treatment to re- 824 JR:186, March 2006
5 Radiologic Manifestations of Plasmacytomas C Fig year-old man with multiple solitary plasmacytomas arising from right kidney and mediastinum. and, xial contrast-enhanced CT scans through abdomen show large right renal mass (arrows, ) with areas of necrosis encasing aorta, inferior vena cava, and superior mesenteric vessels; in, large retroperitoneal and mesenteric lymph nodes are visible. Six months after radiation therapy and chemotherapy, recurrent solitary plasmacytomas were found in mediastinum and right adrenal. C, xial fast spin-echo T2-weighted scan of thorax shows hyperintense bilobed soft-tissue mass (arrows) in mediastinum encasing descending aorta and closely associated with left atrium. D, xial postcontrast CT scan shows another extramedullary plasmacytoma (asterisks) with central necrosis and heterogeneous enhancement arising from right adrenal gland. gional lymph nodes and the usefulness of imaging in staging primary plasmacytoma [2, 3], particularly in the head and neck region where regional lymph node recurrence occurs after radiation therapy in 7% of the patients [9]. Treatment of primary plasmacytoma is aimed at local control with local radiation therapy, surgical resection, or both depending on the site. Systemic therapy, such as chemotherapy or autologous stem cell transplantation, is recommended for refractory, recurrent, and multiple plasmacytomas [1, 2, 4]. The increasing use of MRI, CT, and PET in the staging and evaluation of apparently solitary plasmacytomas may reveal multiple softtissue lesions or additional bone lesions [10, 11]. MRI of the spine has been reported to be a useful prognostic tool in monoclonal gammopathy of unknown significance, asymptomatic multiple myeloma, and established multiple myeloma, revealing additional bone lesions in 40% of patients with stage I multiple myeloma and 50% with asymptomatic multiple myeloma [12]. Whole-body MRI may be another technique to consider in the staging of apparent solitary extramedullary plasmacytoma because the detection of multiple, recurrent, or new lesions will influence the course of management that is, when systemic chemotherapy or autologous stem cell transplantation may be instituted. Despite the retrospective nature of this study and the small number of cases involved, D JR:186, March
6 C Fig year-old woman with multiple solitary plasmacytomas., Coronal CT scan through orbits shows slightly hyperdense intraorbital superior extraconal mass compressing left globe with erosion through roof of orbit (arrows) into anterior cranial fossa., On T1-weighted sagittal scan of brain, a second lesion (M) is revealed to arise behind dorsum sella and clivus. It appears isointense to white matter. C, Second lesion (M) is markedly enhancing with dural tail (arrowheads) on gadolinium-enhanced T1-weighted sagittal scan. we conclude that the imaging features of primary solitary extramedullary plasmacytoma and multiple solitary plasmacytomas are nonspecific but are compatible with solid tumors with invariable enhancement. Large tumors may show areas of necrosis and are usually associated with destruction, infiltration, or encasement of adjacent structures. Imaging alone cannot differentiate these tumors from more common malignant entities such as carcinoma, meningioma in cases of intracranial extramedullary plasmacytoma, or metastasis 826 JR:186, March 2006
7 Radiologic Manifestations of Plasmacytomas from other primaries. The role of imaging should be focused on the early detection of additional or recurrent lesions and the presence of regional lymphadenopathy, which will influence clinical management. References 1. lexiou C, Kau RJ, Dietzfelbinger H, et al. Extramedullary plasmacytoma: tumor occurrence and therapeutic concepts. Cancer 1999; 85: International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. r J Haematol 2003; 121: Galieni P, Cavo M, vvisati G, et al. Solitary plasmacytoma of bone and extramedullary plasmacytoma: two different entities? nn Oncol 1995; 6: Soesan M, Paccagnella, Chiarion-Sileni V, et al. Extramedullary plasmacytoma: clinical behaviour and response to treatment. nn Oncol 1992; 3: Moran CC, nderson CC, Caldemeyer KS, Smith RR. Meningeal myelomatosis: CT and MR appearances. m J Neuroradiol 1995; 16: Ooi GC, Chim CS, Liang R, Tsang KWT, Kwong YL. Nasal T-cell/natural killer cell lymphoma: CT and MR imaging features of a new clinicopathological entity. JR 2000; 174: Keung YK, Lau S, Gill P. Extramedullary plasmacytoma of the heart presenting as cardiac emergency: review of the literature. m J Clin Oncol 1994; 17: Sered S, Nikolaidis P. CT findings of perirenal plasmacytoma. JR 2003; 181: Knowling M, Harwood R, ergsagel DE. Comparison of extramedullary plasmacytoma with solitary and multiple plasma cell tumours of bone. J Clin Oncol 1983; 1: Moulopoulos L, Dimopoulos M, Weber D, Fuller L, Linshitz H, lexanian R. Magnetic resonance imaging in the staging of solitary plasmacytoma of bone. J Clin Oncol 1993; 11: Orchard K, arrington S, uscumbe J, Hilson, Prentice HG, Mehta. Fluoro-deoxyglucose positron emission tomography imaging for the detection of occult disease in multiple myeloma. r J Haematol 2002; 117: Moulopoulos L, Dimopoulos M, Smith TL, et al. Prognostic significance of magnetic resonance imaging in patients with asymptomatic multiple myeloma. J Clin Oncol 1995; 13: JR:186, March
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