Extra-articular knee lesion with high fluorodeoxyglucose-uptake on positron emission tomography.
She was referred to our clinic with an atypical distribution of pain over the temporomandibular joints, biceps, lower back, palms, and bilateral lower legs. She denied fever, rash, or mucosal lesions to suggest a systemic connective-tissue disease. Rheumatologic workup was negative for polymyalgia rheumatica, rheumatoid arthritis, and polymyositis. Physical examination revealed palpable swelling of the affected knee without warmth, tenderness, or erythema, although she denied recent trauma or knee pain proportionally greater than her other complaints.
Given the significant personal and family history of cancer, a whole body PET was performed demonstrating a hypermetabolic area in the left knee. A 3.8 x 1.4 cm homogeneous well-circumscribed soft tissue radio-dense structure (37 Hounsfield Units) just deep to the distal left vastus medialis tendon, medial to the inferior patella was noted to be hypermetabolic with an SUV of 15.1 (Fig. 1).
MRI of the left knee showed a diffusely contrastenhancing solid lesion measuring 5.4 x 4.3 x 1.2 cm in the anteromedial joint capsule adjacent to and contacting the medial pole of the patella and the anteromedial surface of the medial femoral condyle. It was heterogeneous with amorphous low-signal foci (Fig. 2).
These findings suggest several possible differential diagnoses: soft tissue sarcoma, metastatic lesion, pigmented villonodular synovitis, infection, and myositis.
Because of the high SUV, malignant lesion could not be excluded. An excisional biopsy was therefore performed to obtain tissue diagnosis. Intraoperatively, a dark, brown-colored tumor was observed outside the joint capsule fixed and adherent to the vastus medialis tendon. The tumor was excised, and a soft tissue specimen measuring 1.3 x 1.0 x 0.4 cm was sent for final diagnosis. The histologic examination revealed sheets of proliferating cells creating fronds protruding the synovial lining, which is compatible with pigmented villonodular synovitis (PVNS) (Fig. 3). There was no evidence of infection or sarcoma.
Discussion and Treatment
PVNS is a benign, slow growing, but locally aggressive intraarticular lesion known to arise from a polyclonal population of cells in synovial joints, tendon sheaths, and bursae. (1,2) The increased synovial proliferation typically results in monoarticular disease most commonly affecting the knee. (3,4)
PVNS is typically diagnosed by history, physical examination, and MRI. Pathologic examination of tissue biopsy is required for definitive diagnosis, and histologic appearance is characterized by hemosiderin deposition, histiocytic infiltrate, and giant cells. Hemosiderin causes the distinctive brownish color and manifests as either patchy or continuous low foci signal by MRI on T1- and T2-weighted sequences. (5-7) However, early inflammatory lesions with less hemosiderin can produce large amounts of bright signal on T2 sequences.
The tumor's growth pattern can result in either a localized nodular mass or a diffuse process affecting the entire synovium. The former is managed effectively with synovectomy and has a low recurrence rate, while the latter is more common and has a high recurrence rate of up to 46%. (8) The lesion can be aggressive and extend outside the articular space, and the condition can raise the risk of secondary osteoarthritis. (9)
There are reported cases of malignant synovial tumors, (10) but generally PVNS has low potential for metastasis. While radiotracer scintigraphy has previously been useful in initial detection of PVNS and other tumors, (11,12) fluorodeoxyglucose-positron imaging tomography (FDG-PET) can serve as a clinically useful noninvasive assessment of the degree of malignancy, although it is primarily used to monitor tumors with an established diagnosis.
Fluorodeoxyglucose (FDG) is a glucose analog used as a tracer to detect the hypermetabolic activity of tumors. FDG-PET uses a standardized uptake value (SUV), an estimate used to quantify the uptake of the tracer in the region of interest. This approximates the local metabolic activity in order to monitor tumor size during cancer therapy. Studies have shown that PET is also effective in detection of malignancy in the extremities, identifying sarcoma with a sensitivity of 0.91 and specificity of 0.85.13
We present a case of PVNS of the knee with an SUV of 15.1 detected by FDG-PET, in order to demonstrate to clinicians that even a remarkable elevation of FDG-uptake by PET can still represent a benign lesion. In addition, the high SUV suggests a high level of metabolic activity in PVNS. In this case, whole-body FDG-PET imaging was performed because of the patient's constitutional symptoms in the setting of leukemia. The high metabolic activity enhanced suspicion for malignancy.
High metabolic activity has been demonstrated to correlate with aggressive activity and high tumor grade in lung cancer, colorectal cancer, breast cancer, melanoma, and malignant lymphoma. (14) Specifically in non-small cell lung cancer, SUVs ranging from 2.5 to 20 have been used as a prognostic cutoff, (15) and one study showed overall survival was significantly longer in patients with SUV < 15. (16)
To date, four case reports of PVNS with a high-SUV provide insight into the use of FDG-PET for this disease (Table 1). Kitapci and coworkers reported detection of PVNS lesion at the acetabulum with an SUV of 11.3, which was thought to be metastasis. (17) The other case reports do not specify the SUV but reported a similar diagnostic dilemma and concern for a malignant lesion. (18-20) All four cases indicated suspicion for sarcoma or metastasis based on a personal or family history of malignancy.
As imaging is critical to the management of musculoskeletal tumors, studies have reported the potential and promise for FDG-PET to distinguish a malignant lesion from a benign soft tissue mass or bone tumor. (21) In one series, 10 malignant soft tissue tumors were distinguished from 10 benign lesions using a cutoff SUV of 1.90.22 Similar cutoff values were used to differentiate benign and malignant primary intraosseous lesions. (23,24) However, initial reports supporting the use of FDG-PET as a diagnostic tool (25-30) were challenged by a number of studies which were not able to distinguish benign from malignant bone tumors. (31-33) Results were often complicated by high-uptake aggressive-benign tumors or inflammatory lesions, which often are highly vascular, with elevated cell turnover.
False-positive detection of locally aggressive-benign lesions that do not metastasize, therefore, limits the use of FDG-PET as a tool for differential diagnosis. Given the considerable frequency of high-uptake benign lesions, it has been suggested that FDG-PET use be confined to grading and monitoring of soft-tissue sarcoma. (34)
Interestingly, our patient had constitutional symptoms including complex myalgias and arthralgias (with notable exception of the knee). Though the symptoms are more likely coincidental with the lesion, there has been a report of diffuse back pain and paresthesias in the extremities in the setting of PVNS of the zygapophyseal joint. (35)
After tumor excision at the knee, the generalized pain was improved, but she continued complaining of residual pain in the jaw and hip joints. A paraneoplastic panel was sent, which was negative for all autoantibodies with the exception of striational paraneoplastic autoantibody, which is compatible with neurologic dysfunction. But, further neurologic workup revealed mild sensory neuropathy of no apparent cause.
At 6 months postoperative follow-up, the patient's status was substantially improved, and she reported resolution of her musculoskeletal pain and was progressing well with physical therapy. Although the constitutional symptoms improved with excision of the mass, the exact mechanism by which PVNS relates to these phenomena cannot be determined.
In summary, while a high SUV on PET is most consistent with a malignancy, some benign-aggressive lesions, such as the one presented in this case, can also show high signal. The biology and prognosis of this subset of tumor are not well elucidated, and this high metabolic activity may have implications for the risk of recurrence. A prospective study on SUV and rate of recurrence of PVNS might help answer this question. Nevertheless, it is important to manage a high-SUV lesion as malignant until proven otherwise.
The authors wish to thank Dr. Keith Tobin, MD, of Lenox Hill Radiology for the MR images, and Drs. Molly Dyrsen and Adam Gersten of the New York Hospital Department of Pathology for the pathology images and Dr. Quang Ton of Hospital for Special Surgery for administrative assistance, thoughtful discussions, and helpful suggestions.
Caption: Figure 1 FDG-PET demonstrated a region of increased uptake at the medial aspect of the left knee. Coronal (A) and transaxial (B) three-dimensionally reconstructed FDG-PET imaging of both knees demonstrates a hypermetabolic mass (SUVmax = 15.1 g/mL) in the left knee. Coronal (A) and transaxial CT (C) shows the mass is a homogeneous well-circumscribed soft tissue density (arrows). Coronal (E) and transaxial (F) views of merged CT and PET imaging localizes the structure as deep to the distal left vastus medialis tendon and medial to the inferior patella.
Caption: Figure 2 MR imaging of the left knee demonstrates a mass compatible with PVNS. Coronal sections of (A) proton density-weighted, (B) T1-weighted fat-suppressed, and (C) T2-weighted fat-suppressed sequences show a heterogeneous gadolinium-enhancing solid mass in the joint capsule along the anteromedial surface of medial femoral condyle with amorphous low-signal foci (arrows in A), consistent with PVNS.
Caption: Figure 3 Excised mass from left vastus medialis fixed, sectioned, and stained with hematoxylin and eosin and viewed at (A) low, (B) medium, and (C) high magnification. There is marked synovial proliferation with a mixed population of mononuclear cells and multinucleated giant cells (arrow in C).
JML serves as consultant as part of the following healthcare industry relationships as of March 2, 2010: Amgen; BioMimetic Therapeutics, Inc.; Bone Therapeutics; D'Fine, Inc.; Eli Lilly; Fate Therapeutics, Inc.; Graftys Sari; Innovative Clinical Solutions, Inc.; Novartis; Sanofi Aventis; Warner Chilcott; Zelos Therapeutics; and Zimmer (Scientific Advisory Board). Each author certifies that he has not and will not receive payments or benefits from any commercial entity related to this work. No author has directly received research funding. The authors declare that they have no conflict of interest. The institution and each of the authors certify to the absence of any commercial associations (with exception to the consultancies noted above) that might pose a conflict of interest in connection with the submitted article.
(1.) Frassica FJ, Bhimani MA, McCarthy EF, Wenz J. Pigmented villonodular synovitis of the hip and knee. Am Fam Physician. 1999 Oct 1;60(5):1404-10; discussion 1415.
(2.) Fletcher JA, Henkle C, Atkins L, et al. Trisomy 5 and trisomy 7 are nonrandom aberrations in pigmented villonodular synovitis: confirmation of trisomy 7 in uncultured cells. Genes Chromosomes Cancer. 1992 Apr;4(3):264-6.
(3.) Flandry F, Hughston JC, McCann SB, Kurtz DM. Diagnostic features of diffuse pigmented villonodular synovitis of the knee. Clin Orthop Relat Res. 1994 Jan;(298):212-20.
(4.) Myers BW, Masi AT. Pigmented villonodular synovitis and tenosynovitis: a clinical epidemiologic study of 166 cases and literature review. Medicine (Baltimore). 1980 May;59(3):22338.
(5.) Bravo SM, Winalski CS, BN Weissman BN. Pigmented villonodular synovitis. Radiol Clin NorthAm. 1996 Mar;34(2):31126, x-xi.
(6.) Cheng XG, You YH, Liu W, et al. MRI features of pigmented villonodular synovitis (PVNS). Clin Rheumatol. 2004 Feb;23(1):31-4.
(7.) Mandelbaum BR, Grant TT, Hartzman S, et al. The use of MRI to assist in diagnosis of pigmented villonodular synovitis of the knee joint. Clin Orthop Relat Res. 1988 Jun;(231):135-9.
(8.) Byers PD, Cotton RE, Deacon OW, et al. The diagnosis and treatment of pigmented villonodular synovitis. J Bone Joint Surg Br. 1968 May;50(2):290-305.
(9.) Gonzalez Della Valle A, Piccaluga F, Potter HG, et al. Pigmented villonodular synovitis of the hip: 2- to 23-year followup study. Clin Orthop Relat Res. 2001 Jul;(388):187-99.
(10.) Bhadra AK, Pollock R, Tirabosco RP, et al. Primary tumours of the synovium. A report of four cases of malignant tumour. J Bone Joint Surg Br. 2007 Nov;89(11):1504-8.
(11.) Mackie GC. Pigmented villonodular synovitis and giant cell tumor of the tendon sheath: scintigraphic findings in 10 cases. Clin Nucl Med. 2003 Nov;28(11):881-5.
(12.) Kobayashi H, Sakahara H, Hosono M, et al. Scintigraphic evaluation of tenosynovial giant-cell tumor using technetium-99m(V)-dimercaptosuccinic acid. J Nucl Med. 1993 Oct;34(10):1745-7.
(13.) Bastiaannet E, Groen H, Jager PL, et al. The value of FDGPET in the detection, grading and response to therapy of soft tissue and bone sarcomas; a systematic review and metaanalysis. Cancer Treat Rev. 2004 Feb;30(1):83-101.
(14.) Bar-Shalom R, Valdivia AY, Blaufox MD. PET imaging in oncology. Semin Nucl Med. 2000 Jul;30(3):150-85.
(15.) Berghmans T, Dusart M, Paesmans M, et al. Primary tumor standardized uptake value (SUVmax) measured on fluorodeoxyglucose positron emission tomography (FDG-PET) is of prognostic value for survival in non-small cell lung cancer (NSCLC): a systematic review and meta-analysis (MA) by the European Lung Cancer Working Party for the IASLC Lung Cancer Staging Project. J Thorac Oncol. 2008 Jan;3(1):6-12.
(16.) Al-Sarraf N, Gately K, Lucey J, et al. Clinical implication and prognostic significance of standardised uptake value of primary non-small cell lung cancer on positron emission tomography: analysis of 176 cases. Eur J Cardiothorac Surg. 2008 Oct;34(4):892-7.
(17.) Kitapci MT, RE Coleman. Incidental detection of pigmented villonodular synovitis on FDG PET. Clin Nucl Med. 2003 Aug;28(8):668-9.
(18.) Lee MK, Choong PF, Smith PJ, et al. Pigmented villonodular synovitis of the hip mimicking soft-tissue sarcoma: a case report. J Orthop Surg (Hong Kong). 2006 Apr;14(1):76-80.
(19.) Nguyen BD. PET, CT, and MR imaging of extra-articular pigmented villonodular synovitis. Clin Nucl Med. 2007 Jun;32(6):493-5.
(20.) Yoshida T, Sakamoto A, Tanaka K, et al. Intramuscular diffuse-type giant cell tumor within the hamstring muscle. Skeletal Radiol. 2007 Apr;36(4):331-3.
(21.) el-Zeftawy H, Heiba SI, Jana S, et al. Role of repeated F-18 fluorodeoxyglucose imaging in management of patients with bone and soft tissue sarcoma. Cancer Biother Radiopharm. 2001 Feb;16(1):37-46.
(22.) Griffeth LK, Dehdashti F, McGuire AH, et al. PET evaluation of soft-tissue masses with fluorine-18 fluoro-2-deoxy-Dglucose. Radiology. 1992 Jan;182(1):185-94.
(23.) Aoki J, Watanabe H, Shinozaki T, et al. FDG PET of primary benign and malignant bone tumors: standardized uptake value in 52 lesions. Radiology. 2001 Jun;219(3):774-7.
(24.) Dehdashti F, Siegel BA, Griffeth LK, et al. Benign versus malignant intraosseous lesions: discrimination by means of PET with 2-[F-18]fluoro-2-deoxy-D-glucose. Radiology. 1996 Jul;200(1):243-7.
(25.) Adler LP, Blair HF, Makley JT, et al. Noninvasive grading of musculoskeletal tumors using PET. J Nucl Med. 1991 Aug;32(8):1508-12.
(26.) Eary JF, Conrad EU, Bruckner JD, et al. Quantitative [F-18] fluorodeoxyglucose positron emission tomography in pretreatment and grading of sarcoma. Clin Cancer Res. 1998 May;4(5):1215-20.
(27.) Kern KA, Brunetti A, Norton JA, et al. Metabolic imaging of human extremity musculoskeletal tumors by PET. J Nucl Med. 1988 Feb;29(2):181-6.
(28.) Schwarzbach MH, Dimitrakopoulou-Strauss A, Willeke F, et al. Clinical value of [18-F]] fluorodeoxyglucose positron emission tomography imaging in soft tissue sarcomas. Ann Surg. 2000 Mar;231(3):380-6.
(29.) Lucas JD, O'Doherty MJ, Cronin BF, et al. Prospective evaluation of soft tissue masses and sarcomas using fluorodeoxyglucose positron emission tomography. Br J Surg. 1999 Apr;86(4):550-6.
(30.) Nieweg OE, Pruim J, van Ginkel RJ, et al. Fluorine-18-fluorodeoxyglucose PET imaging of soft-tissue sarcoma. J Nucl Med. 1996 Feb;37(2):257-61.
(31.) Kole AC, Nieweg OE, Hoekstra HJ, et al. Fluorine-18-fluorodeoxyglucose assessment of glucose metabolism in bone tumors. J Nucl Med. 1998 May;39(5):810-5.
(32.) Feldman F, van Heertum R, Manos C. 18FDG PET scanning of benign and malignant musculoskeletal lesions. Skeletal Radiol. 2003 Apr;32(4):201-8.
(33.) Aoki J, Watanabe H, Shinozaki T, et al. FDG-PET for preoperative differential diagnosis between benign and malignant soft tissue masses. Skeletal Radiol. 2003 Mar;32(3):133-8.
(34.) Aoki J, Endo K, Watanabe H, et al. FDG-PET for evaluating musculoskeletal tumors: a review. J Orthop Sci. 2003;8(3):435-41.
(35.) Rovner J, Yaghoobian A, Gott M, et al. Pigmented villonodular synovitis of the zygoapophyseal joint: a case report. Spine (Phila Pa 1976). 2008 Aug 15;33(18):E656-8.
Justin C. Paul, M.D., Ph.D., is in the Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, New York, New York. Aasis Unnanuntana, M.D., and Joseph M. Lane, M.D., are in the Department of Orthopaedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, New York. Stanley J. Goldsmith, M.D., is in the Department of Nuclear Medicine, NY Presbyterian Hospital and Weill Cornell Medical College, New York, New York. Correspondence: Justin C. Paul, M.D., Ph.D., NYU Hospital for Joint Diseases, 301 East 17th Street, New York, New York 10003; Justin.Paul@nyumc.org.
Table 1 Case Reports of PVNS Detected by FDG-PET Reference Gender Lesion (Age) characteristics Lee (18) F (30) Hip PVNS Nguyen (19) F (76) Distal thigh PVNS Yoshida (20) M (62) Hamstring PVNS Kitapci (17) F (49) Acetabular PVNS Reference FDG uptake (SUV) on PET scan Suspected tumor/Outcome Lee (18) Not reported * Suspected soft-tissue sarcoma versus tuberculosis of the hip * PET useful in guiding biopsy of the metabolically active parts of the lesion. Nguyen (19) Not reported * Suspected breast cancer metastasis * Open biopsy showed PVNS * Increase in size and high FDG uptake prompted repeat biopsy to exclude malignancy Yoshida (20) Not reported * Detected incidentally on PET scan staging for gastric cancer * Lesion resected, no metastasis Kitapci (17) 11.3 * Suspected metastatic melanoma * Final pathology revealed PVNS, no malignancy
Please note: Illustration(s) are not available due to copyright restrictions.
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|Author:||Paul, Justin C.; Unnanuntana, Aasis; Goldsmith, Stanley J.; Lane, Joseph M.|
|Publication:||Bulletin of the NYU Hospital for Joint Diseases|
|Article Type:||Clinical report|
|Date:||Apr 1, 2013|
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