- Email: [email protected]
Nerve-Adherent Giant Cell Tumors of Tendon Sheath: A New Presentation
Case Report
Nerve-Adherent Giant Cell Tumors of Tendon Sheath: A New Presentation Mohamed A. Elsherif1, Doris E. Wenger2, Rachael A. Vaubel3, Robert J. Spinner1
Key words Adherent - Extrasynovial - Giant cell tumor of tendon sheath - Implantation - Nerve compression - Peripheral nerves - Tenosynovial giant cell tumors -
Abbreviations and Acronyms GCTTS: Giant cell tumor of tendon sheath MRI: Magnetic resonance imaging PET: Positron emission tomography TSGCT: Tenosynovial giant cell tumors
- BACKGROUND:
Tenosynovial giant cell tumors are a group of slowly growing benign neoplasms of synovial membrane of joints, tendons, and bursae. The localized type or giant cell tumor of tendon sheath (GCTTS) is the extra-articular form of tenosynovial giant cell tumors. We describe two patients with a GCTTS, confirmed histologically at the time of surgical resection, that was adherent to peripheral nerves. Rare GCTTS can cause extrinsic compression of major nerves.
- CASE
Available online: www.sciencedirect.com
DESCRIPTIONS: The first patient was a 36-year-old man with a left wrist mass associated with pain and paresthesia in the radial three digits. On ultrasound and magnetic resonance imaging (MRI), the mass appeared arising from the left median nerve with a picture suggestive of an atypical neurogenic tumor; however, the possibility of GCTTS could not be excluded. Intraoperatively, the tumor was adherent to the median nerve without a connection to nearby intercarpal joints. The second patient was a 25-year-old woman with a history of malignant melanoma and an incidentally discovered mass on routine follow-up. MRI of the pelvis showed an ovoid mass related to the right sciatic nerve. The MRI picture was suggestive of a GCTTS, although a benign neurogenic tumor was favored given the anatomic relation to the sciatic nerve. Intraoperatively, the tumor appeared as a nodule implanted on the nerve, and it was easily peeled off.
1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
- CONCLUSION:
From the Departments of 1Neurologic Surgery, 2Radiology, and 3Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA To whom correspondence should be addressed: Robert J. Spinner, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2016). http://dx.doi.org/10.1016/j.wneu.2016.05.062 Journal homepage: www.WORLDNEUROSURGERY.org
INTRODUCTION Tenosynovial giant cell tumor (TSGCT) is a relatively rare, benign fibro-histiocytic, slowly growing proliferative disorder of the synovial membrane of joints, tendon sheaths, and bursae.1-3 Although histologically similar, these tumors have been classified according to their location and clinical behavior as being extra-articular or intra-articular, or localized or diffuse.4 The World Health Organization had adopted the term giant cell tumor of tendon sheath (GCTTS) for the extra-articular localized form of TSGCTs.5 We present two rare cases of GCTTS that were adherent to major peripheral nerves. We wonder about a possible epineurial origin. Approval from our institutional review board was obtained. CASE REPORTS Patient 1 A 36-year-old man presented with a longstanding left volar wrist mass with
We present a new, rare presentation of GCTTS adherent to peripheral nerves with extrinsic compression. We suggest either an implantation mechanism or an unrecognized extrasynovial origin for such tumors.
occasional pain and paresthesia in the radial three digits. He had no history of macrotrauma, but he reported repetitive use of his left hand as a professional guitarist. Examination revealed a 2-cm mass located just proximal to the wrist crease. The results of a neurologic examination were normal. An ultrasound image of the left wrist demonstrated a 14 11 16-mm eccentric, hypoechoic ovoid mass emanating from the radial aspect of the median nerve proximal to the carpal tunnel inlet with nerve enlargement at the level of the mass, but with normalappearing fascicular echo texture and surrounding musculature. The picture was suggestive of a peripheral nerve sheath tumor. Magnetic resonance imaging (MRI) of the left wrist demonstrated a well-circumscribed nodular mass that was intimately associated with the radial side of the median nerve (Figure 1). The mass
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demonstrated intermediate signal on T1-weighted images and low signal on T2-weighted images with avid contrast enhancement. Although intimately associated with the nerve, the MRI signal characteristics were interpreted as being atypical for a neurogenic tumor, with diagnostic possibilities including GCTTS and fibroma given the diffuse low T2 signal intensity. At operation, the tumor was adherent to the median nerve and was free from the flexor tendons. Total resection was performed (Figure 2). The median nerve was decompressed through the carpal tunnel. Histopathologic examination demonstrated a wellcircumscribed nodule composed of multinucleated giant cells and synoviallike cells in a densely hyalinized background, consistent with a GCTTS (Figure 3). The patient had an uneventful postoperative course and was
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NERVE-ADHERENT GIANT CELL TUMORS
Figure 1. MR Imaging. (A) Axial T1, (B) axial fat-saturated T2, (C) axial post gadolinium spoiled gradient-echo sequence, (D) coronal fat-saturated T2-weighted, and (E) coronal T1-weighted magnetic resonance images of the left wrist (patient 1) show a small, well-circumscribed nodular mass with intermediate signal on T1, low signal on T2, and avid enhancement with
asymptomatic at 1-month follow-up. A follow-up MRI will be conducted at 3 months postoperatively. Patient 2 A 25-year-old woman with a history of surgically resected stage IIIB malignant melanoma of the left chest 2 years prior presented with an incidentally discovered mass on a positron emission tomography (PET) scan done as routine follow-up. MRI of the pelvis revealed a 2.2 1.2 0.9-cm heterogeneously enhancing ovoid mass associated with the peroneal division of the right sciatic nerve in the lower buttock, 1 cm away from the ischial tuberosity (Figure 4). Although the MRI signal characteristics were characteristic of GCTTS with intermediate signal on T1-weighted images, predominantly low signal on T2-weighted images, and avid enhancement, these imaging features could also be seen with a benign neurogenic tumor demonstrating a target sign on T2. Given the anatomic location, this was
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gadolinium (thick arrows). The mass is intimately associated with the median nerve (thin arrows), but it also abuts two adjacent flexor tendons. There is a thin linear layer of low signal intensity surrounding the mass that formed a superficial layer continuous with the nerve proximally and distally that correlated with the intraoperative findings (arrow heads).
interpreted on MRI as most likely representing a benign neurogenic tumor. The patient remained asymptomatic. Over the next 9 months, there was gradual enlargement of the lesion to 2.7 1.9 1.7 cm. A computed tomographyeguided biopsy result was consistent with metastatic melanoma. A PET scan result was otherwise negative. At operation, we removed a purple nodule implanted on the peroneal division of the sciatic nerve (Figure 5). Intraoperative frozen section demonstrated a highly cellular tumor suggestive of melanoma metastasis. However, permanent histologic sections demonstrated the presence of multinucleated giant cells with numerous synovial-like cells and hemosiderinladen macrophages (Figure 6). Immunohistochemical staining was positive for clusterin, desmin, and CD 68 while negative for Melan-A and S100, thus supporting the diagnosis of GCTTS. The patient did well postoperatively, and she remained asymptomatic. A postoperative
PET scan 6 months after surgery did not demonstrate any evidence of recurrence. DISCUSSION GCTTS is the most common form of tenosynovial giant cell tumor. Adults are more commonly affected than children are, with an incidence of 1:50,000, a peak in the third to fifth decades, and a slight female predominance (1.5e2.1:1).6,7 These tumors comprise 1.6%e3.9% of soft tissue masses and occur most frequently in the wrist and hands or ankle and feet (being second only to a ganglion cyst), and then the knee, elbow, and rarely the hip.8 GCTTSs usually arise as circumscribed nodules related to synovium of a joint or tendon sheath; they tend to have an indolent course. Rare examples of extrinsic nerve compression have been reported at various sites.9-15 In these cases, GCTTSs appeared distinct from the compressed nerves and had a nearby tenosynovial connection. In contrast, in our patients, one of the tumors was found in
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.05.062
CASE REPORT MOHAMED A. ELSHERIF ET AL.
NERVE-ADHERENT GIANT CELL TUMORS
Figure 2. Intraoperative images. (A) A yellowish rounded mass is seen adherent to the long axis of the epineurial surface of the left median nerve (black arrow). (B) The mass is dissected from the fibroconnective tissue surrounding the nerve.
continuity with the median nerve at the level of the wrist. Although the mass was in the vicinity of the flexor tendon sheaths, there was a layer of tissue enveloping the mass that was continuous with the nerve proximally and distally, forming a single unit distinctly separate from the tendon sheaths. In the second case, the mass appeared to be implanted on the sciatic nerve near but separate from the hip and ischial tuberosity (origin of the hamstring tendons). We could not detect synovial connections to nearby joints or tendon sheaths in either patient, despite the relative close proximity. On attempting surgical resection, the tumor masses were contained within a fibroconnective tissue around the epineurial layer of the nerve. They were amenable to being separated from nerve and were entirely extrafascicular and encapsulated. Although the tumor could have arisen from nearby synovium and been implanted into the nerve directly, the possibility of an extrasynovial tissue of origin, most likely the extrafascicular supportive connective tissue layer surrounding the peripheral
nerve trunks, exists. Interestingly, the first case was reminiscent of a recent case of a fibroma of the tendon sheath that arose intraneurally from within the median nerve at the wrist16; both tumor entities (GCTTS and fibroma) classically originate from the synovial membranes of joints or tendons rather than from within nerves. Despite different histopathologic pictures between both GCTTS and fibroma, it appears as though both tumors not only share similar clinical pictures, locations, multinodularity, and recurrence rates; they also may be related histopathologically.17,18 This notion is supported by Satti’s study19 that suggested fibroma of tendon sheath as an end-stage sclerosing phenomenon of GCTTS based on the presence of a transitional histopathological picture—that is, the predominant hyalinization, scanty giant cells, and impaired vascular channels morphology compared with GCTTS. The progressive vascular impairment of GCTTS has been suggested as the underlying cause for such evolutional change to the fibroma picture.19
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Figure 3. Histopathology. (A) Grossly, the tumor was well-circumscribed, firm, and tan-pink with minimal adherent soft tissue. (B, C) Microscopic examination demonstrated a densely collagenous tumor with clusters of multinucleated giant cells and synovial-like cells, consistent with giant cell tumor of tendon sheath. (B, original magnification 40; scale bar, 500 mM; C, original magnification 200; scale bar, 100 mM.)
The exact etiology of GCTTS has been a matter of debate. Inflammatory, metabolic, and traumatic theories have been suggested. Recent cytogenetic studies have proved GCTTS as a neoplastic process; a small population of mononuclear cells exhibits various chromosomal aberrations and translocations resulting in overexpression of a cytokine factor— namely, macrophage colony stimulating factor.20 The resultant attraction and proliferation of monocytes and macrophages eventually form a mass lesion, a phenomenon described as
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NERVE-ADHERENT GIANT CELL TUMORS
Figure 4. Imaging. (A) Axial T1, (B) coronal fat saturated T2, (C) axial T2, and (D) axial post gadolinium spoiled gradient-echo sequence magnetic resonance images of the right hip (patient 2) show a well-circumscribed heterogeneous solid nodular mass (thick arrows) that is intimately associated with the peroneal division of the right sciatic nerve (thin arrows). There is obliteration of the fat plane between the mass and the sciatic nerve forming a claw-like configuration about the nerve (arrowheads). Of note, there is no contact between the mass and the hamstring tendon sheath (asterisk). The mass demonstrates intermediate signal on T1, heterogeneous, but predominantly low signal on T2 and enhances heterogeneously with gadolinium.
tumor-landscaping.7,21 The propensity for recurrence, rare malignant transformation, and metastasis also supports the notion of the neoplastic theory.22-25 MRI is helpful for the diagnosis of GCTTS because of its unique signal characteristics that can often distinguish it from other entities. GCTTS typically
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appears as a well-circumscribed mass in the vicinity of a joint or tendon sheath and shows low to intermediate signal intensity on T1- and characteristically low signal intensity on T2-weighted images. The low signal intensity on T2-weighted images reflects the paramagnetic effect of hemosiderin that is laden within the tissues, and can result in a characteristic
blooming effect on gradient echo sequences. Although the signal characteristics were typical of GCTTS in both of these cases, the diagnosis was unexpected given the atypical location involving the nerve. The presence of capillary networks within the tumor stroma accounts for their postgadolinium enhancement.26 The absence of a synovial connection to the adjacent joint space differentiates it from its intra-articular counterpart that poses different treatment strategies. The T2 signal intensity of GCTTS can be variable, ranging from low to high signal intensity, with varying degrees of heterogeneity.27 If the mass shows predominantly low T2 signal, the differential diagnosis may also include a fibroma of tendon sheath. If there is heterogeneous or predominantly high signal on T2-weighted images, the differential diagnosis may also include a variety of other neoplasms, including sarcomas such as synovial sarcoma or epithelioid sarcoma.28 In one of our patients, the diagnosis of a benign peripheral nerve sheath tumor was favored, while in the other, GCTTS or fibroma was considered on the differential diagnosis. Reinterpretation of the MRI examinations in both cases revealed imaging features consistent with the diagnosis of GCTTS. Surgical removal is the mainstay of treatment, and histologic analysis is necessary to confirm the diagnosis.29 The occasional presence of a high population of hemosiderin pigment laden histiocytes accounts for histopathologic confusion with other morphologically similar histiocytic tumors, such as malignant melanoma, which explains the preliminary microscopic interpretation in patient 2.30 This finding was also similar to a recent report of similar confusion with what was thought to be a metastatic choroidal melanoma.31 Recurrence rate ranges from 10% to 20% for the classically recognized GCTTS.32 It is unclear whether it is the same for our cases given the unusual origin. However, incomplete resection, relation to the joint, satellite lesions, bony erosion, tumor cellularity, and increased mitotic activity have been described as main predictors of recurrence.33,34
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NERVE-ADHERENT GIANT CELL TUMORS
CONCLUSION Adherence to peripheral nerves with compression is a new, unrecognized picture of GCTTS. Absence of a connection to a nearby joint or tendon is also rare. We propose either an implantation mechanism or an extrasynovial epineurial origin as an explanation. REFERENCES 1. Jo VY, Fletcher CDM. WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition. Pathology. 2014;46:95-104. 2. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, eds. World Health Organization classification of tumours of soft tissue and bone. 4th ed. Lyon: IARC Press; 2013. 3. de St Aubain Somerhausen DCP. Giant Cell Tumour of Tendon Sheath. Lyon, France: IARC Press; 2002. 4. Byers P, Cotton RE, Deacon O, Lowy M, Newman P, Sissons H, et al. The diagnosis and treatment of pigmented villonodular synovitis. J Bone Joint Surg Br. 1968;50:290-305.
Figure 5. Intraoperative images. (A) A dark brownish ovoid mass implanted on and abutting the surface of the peroneal division of the right sciatic nerve. (B) The mass is peeled off the nerve with the surrounding fibrofatty tissue.
5. Fletcher CDM, Unni KK, Mertens F, eds. World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone. Lyon: IARC Press; 2002. 6. Rukavina I, Caleta D. Giant-cell tumour of the tendon sheath: a review. OA Orthopaedics. 2014;2: 11. 7. Lucas DR. Tenosynovial giant cell tumor: case report and review. Arch Pathol Lab Med. 2012;136: 901-906. 8. Murphey MD, Rhee JH, Lewis RB, FanburgSmith JC, Flemming DJ, Walker EA. Pigmented villonodular synovitis: radiologic-pathologic correlation 1. Radiographics. 2008;28:1493-1518. 9. Nucci F, Artico M, Antonini G, Millefiorini M, Bastianello S, Bozzao L. Compression of the ulnar nerve in Guyon’s canal by a giant cell tumor. Zentralbl Neurochir. 1989;50:196-198. 10. Budny PG, Regan PJ, Roberts AH. Localized nodular synovitis: a rare cause of ulnar nerve compression in Guyon’s canal. J Hand Surg Am. 1992;17:663-664. 11. Martin RC 2nd, Osborne DL, Edwards MJ, Wrightson W, McMasters KM. Giant cell tumor of tendon sheath, tenosynovial giant cell tumor, and pigmented villonodular synovitis: defining the presentation, surgical therapy and recurrence. Oncol Rep. 2000;7:413-419.
Figure 6. Histopathology. (A, B) Microscopic examination demonstrated a circumscribed, highly cellular tumor composed predominantly of synovial-like cells with scattered multinucleated giant cells. The presence of hemosiderin-laden macrophages gave the impression of a pigmented lesion. By immunohistochemistry, the synovial-like cells were positive for clusterin (C), CD68 (D), and desmin (not shown). (A, original magnification 40, scale bar 500 mM; BeD, original magnification 200, scale bar 100 mM.)
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12. Francisco BS, Agarwal JP. Giant cell tumor of tendon sheath in Guyon’s canal causing ulnar tunnel syndrome. A case report and review of the literature. Eplasty. 2009;9:e8. 13. McClain EJ, Wissinger HA. The acute carpal tunnel syndrome: nine case reports. J Trauma. 1976;16: 75-78.
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14. Aboulafia AJ, Kaplan L, Jelinek J, Benevenia J, Monson DK. Neuropathy secondary to pigmented villonodular synovitis of the hip. Clin Orthop Relat Res. 1996;325:174-180. 15. Rengachary SS, Arjunan K. Compression of the ulnar nerve in Guyon’s Canal by a soft tissue giant cell tumor. Neurosurgery. 1981;8:400-405. 16. Burrows AM, Folpe AL, Wenger DE, Spinner RJ. Intraneural fibroma of the median nerve at the wrist. J Clin Neurosci. 2014;21:1054-1056. 17. Chung E, Enzinger FM. Fibroma of tendon sheath. Cancer. 1979;44:1945-1954. 18. Humphreys S, McKee P, Fletcher C. Fibroma of tendon sheath: a clinicopathologic study. J Cutan Pathol. 1986;13:331-338. 19. Satti MB. Tendon sheath tumours: a pathological study of the relationship between giant cell tumour and fibroma of tendon sheath. Histopathology. 1992;20:213-220. 20. Brandal P, Bjerkehagen B, Heim S. Molecular cytogenetic characterization of tenosynovial giant cell tumors. Neoplasia. 2004;6:578-583. 21. West RB, Rubin BP, Miller MA, Subramanian S, Kaygusuz G, Montgomery K, et al. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci U S A. 2006;103:690-695. 22. Abdul-Karim FW, El-Naggar AK, Joyce MJ, Makley JT, Carter JR. Diffuse and localized tenosynovial giant cell tumor and pigmented villonodular synovitis: a clinicopathologic and flow
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cytometric DNA analysis. Hum Pathol. 1992;23: 729-735. 23. Shinjo K, Miyake N, Takahashi Y. Malignant giant cell tumor of the tendon sheath: an autopsy report and review of the literature. Jpn J Clin Oncol. 1993; 23:317-324. 24. Kahn LB. Malignant giant cell tumor of the tendon sheath. Ultrastructural study and review of the literature. Arch Pathol. 1973;95:203-208. 25. Nielsen AL, Kiær T. Malignant giant cell tumor of synovium and locally destructive pigmented villonodular synovitis: ultrastructural and immunohistochemical study and review of the literature. Hum Pathol. 1989;20:765-771. 26. De Beuckeleer L, De Schepper A, De Belder F, Van Goethem J, Marques MC, Broeckx J, et al. Magnetic resonance imaging of localized giant cell tumour of the tendon sheath (MRI of localized GCTTS). Eur Radiol. 1997;7:198-201. 27. Jelinek JS, Kransdorf MJ, Shmookler BM, Aboulafia AA, Malawer MM. Giant cell tumor of the tendon sheath: MR findings in nine cases. AJR Am J Roentgenol. 1994;162:919-922. 28. Narváez JA, Narváez J, Aguilera C, De Lama E, Portabella F. MR imaging of synovial tumors and tumor-like lesions. Eur Radiol. 2001;11:2549-2560. 29. Ushijima M, Hashimoto H, Tsuneyoshi M, Enjoji M. Giant cell tumor of the tendon sheath (nodular tenosynovitis). A study of 207 cases to compare the large joint group with the common digit group. Cancer. 1986;57:875-884.
30. Ding Y, Griffin JE, Raghavan M, Xu H, Henderson-Jackson E, Bui MM. Tenosynovial giant cell tumors lacking giant cells: report of diagnostic pitfalls. Ann Clin Lab Sci. 2014;44:222-227. 31. Takeuchi A, Yamamoto N, Hayashi K, Miwa S, Takahira M, Fukui K, et al. Tenosynovial giant cell tumors in unusual locations detected by positron emission tomography imaging confused with malignant tumors: report of two cases. BMC Musculoskelet Disord. 2016;17:180. 32. O’Connell JX. Pathology of the synovium. Am J Clin Pathol. 2000;114:773-784. 33. Lanzinger WD, Bindra R. Giant cell tumor of the tendon sheath. J Hand Surg Br. 2013;38:154-157. 34. Gholve PA, Hosalkar HS, Kreiger PA, Dormans JP. Giant cell tumor of tendon sheath: largest single series in children. J Pediatr Orthop. 2007;27:67-74.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 21 April 2016; accepted 20 May 2016 Citation: World Neurosurg. (2016). http://dx.doi.org/10.1016/j.wneu.2016.05.062 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.05.062
Nerve-Adherent Giant Cell Tumors of Tendon Sheath: A New Presentation Mohamed A. Elsherif1, Doris E. Wenger2, Rachael A. Vaubel3, Robert J. Spinner1
Key words Adherent - Extrasynovial - Giant cell tumor of tendon sheath - Implantation - Nerve compression - Peripheral nerves - Tenosynovial giant cell tumors -
Abbreviations and Acronyms GCTTS: Giant cell tumor of tendon sheath MRI: Magnetic resonance imaging PET: Positron emission tomography TSGCT: Tenosynovial giant cell tumors
- BACKGROUND:
Tenosynovial giant cell tumors are a group of slowly growing benign neoplasms of synovial membrane of joints, tendons, and bursae. The localized type or giant cell tumor of tendon sheath (GCTTS) is the extra-articular form of tenosynovial giant cell tumors. We describe two patients with a GCTTS, confirmed histologically at the time of surgical resection, that was adherent to peripheral nerves. Rare GCTTS can cause extrinsic compression of major nerves.
- CASE
Available online: www.sciencedirect.com
DESCRIPTIONS: The first patient was a 36-year-old man with a left wrist mass associated with pain and paresthesia in the radial three digits. On ultrasound and magnetic resonance imaging (MRI), the mass appeared arising from the left median nerve with a picture suggestive of an atypical neurogenic tumor; however, the possibility of GCTTS could not be excluded. Intraoperatively, the tumor was adherent to the median nerve without a connection to nearby intercarpal joints. The second patient was a 25-year-old woman with a history of malignant melanoma and an incidentally discovered mass on routine follow-up. MRI of the pelvis showed an ovoid mass related to the right sciatic nerve. The MRI picture was suggestive of a GCTTS, although a benign neurogenic tumor was favored given the anatomic relation to the sciatic nerve. Intraoperatively, the tumor appeared as a nodule implanted on the nerve, and it was easily peeled off.
1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
- CONCLUSION:
From the Departments of 1Neurologic Surgery, 2Radiology, and 3Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA To whom correspondence should be addressed: Robert J. Spinner, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2016). http://dx.doi.org/10.1016/j.wneu.2016.05.062 Journal homepage: www.WORLDNEUROSURGERY.org
INTRODUCTION Tenosynovial giant cell tumor (TSGCT) is a relatively rare, benign fibro-histiocytic, slowly growing proliferative disorder of the synovial membrane of joints, tendon sheaths, and bursae.1-3 Although histologically similar, these tumors have been classified according to their location and clinical behavior as being extra-articular or intra-articular, or localized or diffuse.4 The World Health Organization had adopted the term giant cell tumor of tendon sheath (GCTTS) for the extra-articular localized form of TSGCTs.5 We present two rare cases of GCTTS that were adherent to major peripheral nerves. We wonder about a possible epineurial origin. Approval from our institutional review board was obtained. CASE REPORTS Patient 1 A 36-year-old man presented with a longstanding left volar wrist mass with
We present a new, rare presentation of GCTTS adherent to peripheral nerves with extrinsic compression. We suggest either an implantation mechanism or an unrecognized extrasynovial origin for such tumors.
occasional pain and paresthesia in the radial three digits. He had no history of macrotrauma, but he reported repetitive use of his left hand as a professional guitarist. Examination revealed a 2-cm mass located just proximal to the wrist crease. The results of a neurologic examination were normal. An ultrasound image of the left wrist demonstrated a 14 11 16-mm eccentric, hypoechoic ovoid mass emanating from the radial aspect of the median nerve proximal to the carpal tunnel inlet with nerve enlargement at the level of the mass, but with normalappearing fascicular echo texture and surrounding musculature. The picture was suggestive of a peripheral nerve sheath tumor. Magnetic resonance imaging (MRI) of the left wrist demonstrated a well-circumscribed nodular mass that was intimately associated with the radial side of the median nerve (Figure 1). The mass
WORLD NEUROSURGERY -: ---, MONTH 2016
demonstrated intermediate signal on T1-weighted images and low signal on T2-weighted images with avid contrast enhancement. Although intimately associated with the nerve, the MRI signal characteristics were interpreted as being atypical for a neurogenic tumor, with diagnostic possibilities including GCTTS and fibroma given the diffuse low T2 signal intensity. At operation, the tumor was adherent to the median nerve and was free from the flexor tendons. Total resection was performed (Figure 2). The median nerve was decompressed through the carpal tunnel. Histopathologic examination demonstrated a wellcircumscribed nodule composed of multinucleated giant cells and synoviallike cells in a densely hyalinized background, consistent with a GCTTS (Figure 3). The patient had an uneventful postoperative course and was
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CASE REPORT MOHAMED A. ELSHERIF ET AL.
NERVE-ADHERENT GIANT CELL TUMORS
Figure 1. MR Imaging. (A) Axial T1, (B) axial fat-saturated T2, (C) axial post gadolinium spoiled gradient-echo sequence, (D) coronal fat-saturated T2-weighted, and (E) coronal T1-weighted magnetic resonance images of the left wrist (patient 1) show a small, well-circumscribed nodular mass with intermediate signal on T1, low signal on T2, and avid enhancement with
asymptomatic at 1-month follow-up. A follow-up MRI will be conducted at 3 months postoperatively. Patient 2 A 25-year-old woman with a history of surgically resected stage IIIB malignant melanoma of the left chest 2 years prior presented with an incidentally discovered mass on a positron emission tomography (PET) scan done as routine follow-up. MRI of the pelvis revealed a 2.2 1.2 0.9-cm heterogeneously enhancing ovoid mass associated with the peroneal division of the right sciatic nerve in the lower buttock, 1 cm away from the ischial tuberosity (Figure 4). Although the MRI signal characteristics were characteristic of GCTTS with intermediate signal on T1-weighted images, predominantly low signal on T2-weighted images, and avid enhancement, these imaging features could also be seen with a benign neurogenic tumor demonstrating a target sign on T2. Given the anatomic location, this was
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gadolinium (thick arrows). The mass is intimately associated with the median nerve (thin arrows), but it also abuts two adjacent flexor tendons. There is a thin linear layer of low signal intensity surrounding the mass that formed a superficial layer continuous with the nerve proximally and distally that correlated with the intraoperative findings (arrow heads).
interpreted on MRI as most likely representing a benign neurogenic tumor. The patient remained asymptomatic. Over the next 9 months, there was gradual enlargement of the lesion to 2.7 1.9 1.7 cm. A computed tomographyeguided biopsy result was consistent with metastatic melanoma. A PET scan result was otherwise negative. At operation, we removed a purple nodule implanted on the peroneal division of the sciatic nerve (Figure 5). Intraoperative frozen section demonstrated a highly cellular tumor suggestive of melanoma metastasis. However, permanent histologic sections demonstrated the presence of multinucleated giant cells with numerous synovial-like cells and hemosiderinladen macrophages (Figure 6). Immunohistochemical staining was positive for clusterin, desmin, and CD 68 while negative for Melan-A and S100, thus supporting the diagnosis of GCTTS. The patient did well postoperatively, and she remained asymptomatic. A postoperative
PET scan 6 months after surgery did not demonstrate any evidence of recurrence. DISCUSSION GCTTS is the most common form of tenosynovial giant cell tumor. Adults are more commonly affected than children are, with an incidence of 1:50,000, a peak in the third to fifth decades, and a slight female predominance (1.5e2.1:1).6,7 These tumors comprise 1.6%e3.9% of soft tissue masses and occur most frequently in the wrist and hands or ankle and feet (being second only to a ganglion cyst), and then the knee, elbow, and rarely the hip.8 GCTTSs usually arise as circumscribed nodules related to synovium of a joint or tendon sheath; they tend to have an indolent course. Rare examples of extrinsic nerve compression have been reported at various sites.9-15 In these cases, GCTTSs appeared distinct from the compressed nerves and had a nearby tenosynovial connection. In contrast, in our patients, one of the tumors was found in
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.05.062
CASE REPORT MOHAMED A. ELSHERIF ET AL.
NERVE-ADHERENT GIANT CELL TUMORS
Figure 2. Intraoperative images. (A) A yellowish rounded mass is seen adherent to the long axis of the epineurial surface of the left median nerve (black arrow). (B) The mass is dissected from the fibroconnective tissue surrounding the nerve.
continuity with the median nerve at the level of the wrist. Although the mass was in the vicinity of the flexor tendon sheaths, there was a layer of tissue enveloping the mass that was continuous with the nerve proximally and distally, forming a single unit distinctly separate from the tendon sheaths. In the second case, the mass appeared to be implanted on the sciatic nerve near but separate from the hip and ischial tuberosity (origin of the hamstring tendons). We could not detect synovial connections to nearby joints or tendon sheaths in either patient, despite the relative close proximity. On attempting surgical resection, the tumor masses were contained within a fibroconnective tissue around the epineurial layer of the nerve. They were amenable to being separated from nerve and were entirely extrafascicular and encapsulated. Although the tumor could have arisen from nearby synovium and been implanted into the nerve directly, the possibility of an extrasynovial tissue of origin, most likely the extrafascicular supportive connective tissue layer surrounding the peripheral
nerve trunks, exists. Interestingly, the first case was reminiscent of a recent case of a fibroma of the tendon sheath that arose intraneurally from within the median nerve at the wrist16; both tumor entities (GCTTS and fibroma) classically originate from the synovial membranes of joints or tendons rather than from within nerves. Despite different histopathologic pictures between both GCTTS and fibroma, it appears as though both tumors not only share similar clinical pictures, locations, multinodularity, and recurrence rates; they also may be related histopathologically.17,18 This notion is supported by Satti’s study19 that suggested fibroma of tendon sheath as an end-stage sclerosing phenomenon of GCTTS based on the presence of a transitional histopathological picture—that is, the predominant hyalinization, scanty giant cells, and impaired vascular channels morphology compared with GCTTS. The progressive vascular impairment of GCTTS has been suggested as the underlying cause for such evolutional change to the fibroma picture.19
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Figure 3. Histopathology. (A) Grossly, the tumor was well-circumscribed, firm, and tan-pink with minimal adherent soft tissue. (B, C) Microscopic examination demonstrated a densely collagenous tumor with clusters of multinucleated giant cells and synovial-like cells, consistent with giant cell tumor of tendon sheath. (B, original magnification 40; scale bar, 500 mM; C, original magnification 200; scale bar, 100 mM.)
The exact etiology of GCTTS has been a matter of debate. Inflammatory, metabolic, and traumatic theories have been suggested. Recent cytogenetic studies have proved GCTTS as a neoplastic process; a small population of mononuclear cells exhibits various chromosomal aberrations and translocations resulting in overexpression of a cytokine factor— namely, macrophage colony stimulating factor.20 The resultant attraction and proliferation of monocytes and macrophages eventually form a mass lesion, a phenomenon described as
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Figure 4. Imaging. (A) Axial T1, (B) coronal fat saturated T2, (C) axial T2, and (D) axial post gadolinium spoiled gradient-echo sequence magnetic resonance images of the right hip (patient 2) show a well-circumscribed heterogeneous solid nodular mass (thick arrows) that is intimately associated with the peroneal division of the right sciatic nerve (thin arrows). There is obliteration of the fat plane between the mass and the sciatic nerve forming a claw-like configuration about the nerve (arrowheads). Of note, there is no contact between the mass and the hamstring tendon sheath (asterisk). The mass demonstrates intermediate signal on T1, heterogeneous, but predominantly low signal on T2 and enhances heterogeneously with gadolinium.
tumor-landscaping.7,21 The propensity for recurrence, rare malignant transformation, and metastasis also supports the notion of the neoplastic theory.22-25 MRI is helpful for the diagnosis of GCTTS because of its unique signal characteristics that can often distinguish it from other entities. GCTTS typically
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appears as a well-circumscribed mass in the vicinity of a joint or tendon sheath and shows low to intermediate signal intensity on T1- and characteristically low signal intensity on T2-weighted images. The low signal intensity on T2-weighted images reflects the paramagnetic effect of hemosiderin that is laden within the tissues, and can result in a characteristic
blooming effect on gradient echo sequences. Although the signal characteristics were typical of GCTTS in both of these cases, the diagnosis was unexpected given the atypical location involving the nerve. The presence of capillary networks within the tumor stroma accounts for their postgadolinium enhancement.26 The absence of a synovial connection to the adjacent joint space differentiates it from its intra-articular counterpart that poses different treatment strategies. The T2 signal intensity of GCTTS can be variable, ranging from low to high signal intensity, with varying degrees of heterogeneity.27 If the mass shows predominantly low T2 signal, the differential diagnosis may also include a fibroma of tendon sheath. If there is heterogeneous or predominantly high signal on T2-weighted images, the differential diagnosis may also include a variety of other neoplasms, including sarcomas such as synovial sarcoma or epithelioid sarcoma.28 In one of our patients, the diagnosis of a benign peripheral nerve sheath tumor was favored, while in the other, GCTTS or fibroma was considered on the differential diagnosis. Reinterpretation of the MRI examinations in both cases revealed imaging features consistent with the diagnosis of GCTTS. Surgical removal is the mainstay of treatment, and histologic analysis is necessary to confirm the diagnosis.29 The occasional presence of a high population of hemosiderin pigment laden histiocytes accounts for histopathologic confusion with other morphologically similar histiocytic tumors, such as malignant melanoma, which explains the preliminary microscopic interpretation in patient 2.30 This finding was also similar to a recent report of similar confusion with what was thought to be a metastatic choroidal melanoma.31 Recurrence rate ranges from 10% to 20% for the classically recognized GCTTS.32 It is unclear whether it is the same for our cases given the unusual origin. However, incomplete resection, relation to the joint, satellite lesions, bony erosion, tumor cellularity, and increased mitotic activity have been described as main predictors of recurrence.33,34
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CONCLUSION Adherence to peripheral nerves with compression is a new, unrecognized picture of GCTTS. Absence of a connection to a nearby joint or tendon is also rare. We propose either an implantation mechanism or an extrasynovial epineurial origin as an explanation. REFERENCES 1. Jo VY, Fletcher CDM. WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition. Pathology. 2014;46:95-104. 2. Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, eds. World Health Organization classification of tumours of soft tissue and bone. 4th ed. Lyon: IARC Press; 2013. 3. de St Aubain Somerhausen DCP. Giant Cell Tumour of Tendon Sheath. Lyon, France: IARC Press; 2002. 4. Byers P, Cotton RE, Deacon O, Lowy M, Newman P, Sissons H, et al. The diagnosis and treatment of pigmented villonodular synovitis. J Bone Joint Surg Br. 1968;50:290-305.
Figure 5. Intraoperative images. (A) A dark brownish ovoid mass implanted on and abutting the surface of the peroneal division of the right sciatic nerve. (B) The mass is peeled off the nerve with the surrounding fibrofatty tissue.
5. Fletcher CDM, Unni KK, Mertens F, eds. World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone. Lyon: IARC Press; 2002. 6. Rukavina I, Caleta D. Giant-cell tumour of the tendon sheath: a review. OA Orthopaedics. 2014;2: 11. 7. Lucas DR. Tenosynovial giant cell tumor: case report and review. Arch Pathol Lab Med. 2012;136: 901-906. 8. Murphey MD, Rhee JH, Lewis RB, FanburgSmith JC, Flemming DJ, Walker EA. Pigmented villonodular synovitis: radiologic-pathologic correlation 1. Radiographics. 2008;28:1493-1518. 9. Nucci F, Artico M, Antonini G, Millefiorini M, Bastianello S, Bozzao L. Compression of the ulnar nerve in Guyon’s canal by a giant cell tumor. Zentralbl Neurochir. 1989;50:196-198. 10. Budny PG, Regan PJ, Roberts AH. Localized nodular synovitis: a rare cause of ulnar nerve compression in Guyon’s canal. J Hand Surg Am. 1992;17:663-664. 11. Martin RC 2nd, Osborne DL, Edwards MJ, Wrightson W, McMasters KM. Giant cell tumor of tendon sheath, tenosynovial giant cell tumor, and pigmented villonodular synovitis: defining the presentation, surgical therapy and recurrence. Oncol Rep. 2000;7:413-419.
Figure 6. Histopathology. (A, B) Microscopic examination demonstrated a circumscribed, highly cellular tumor composed predominantly of synovial-like cells with scattered multinucleated giant cells. The presence of hemosiderin-laden macrophages gave the impression of a pigmented lesion. By immunohistochemistry, the synovial-like cells were positive for clusterin (C), CD68 (D), and desmin (not shown). (A, original magnification 40, scale bar 500 mM; BeD, original magnification 200, scale bar 100 mM.)
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14. Aboulafia AJ, Kaplan L, Jelinek J, Benevenia J, Monson DK. Neuropathy secondary to pigmented villonodular synovitis of the hip. Clin Orthop Relat Res. 1996;325:174-180. 15. Rengachary SS, Arjunan K. Compression of the ulnar nerve in Guyon’s Canal by a soft tissue giant cell tumor. Neurosurgery. 1981;8:400-405. 16. Burrows AM, Folpe AL, Wenger DE, Spinner RJ. Intraneural fibroma of the median nerve at the wrist. J Clin Neurosci. 2014;21:1054-1056. 17. Chung E, Enzinger FM. Fibroma of tendon sheath. Cancer. 1979;44:1945-1954. 18. Humphreys S, McKee P, Fletcher C. Fibroma of tendon sheath: a clinicopathologic study. J Cutan Pathol. 1986;13:331-338. 19. Satti MB. Tendon sheath tumours: a pathological study of the relationship between giant cell tumour and fibroma of tendon sheath. Histopathology. 1992;20:213-220. 20. Brandal P, Bjerkehagen B, Heim S. Molecular cytogenetic characterization of tenosynovial giant cell tumors. Neoplasia. 2004;6:578-583. 21. West RB, Rubin BP, Miller MA, Subramanian S, Kaygusuz G, Montgomery K, et al. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci U S A. 2006;103:690-695. 22. Abdul-Karim FW, El-Naggar AK, Joyce MJ, Makley JT, Carter JR. Diffuse and localized tenosynovial giant cell tumor and pigmented villonodular synovitis: a clinicopathologic and flow
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cytometric DNA analysis. Hum Pathol. 1992;23: 729-735. 23. Shinjo K, Miyake N, Takahashi Y. Malignant giant cell tumor of the tendon sheath: an autopsy report and review of the literature. Jpn J Clin Oncol. 1993; 23:317-324. 24. Kahn LB. Malignant giant cell tumor of the tendon sheath. Ultrastructural study and review of the literature. Arch Pathol. 1973;95:203-208. 25. Nielsen AL, Kiær T. Malignant giant cell tumor of synovium and locally destructive pigmented villonodular synovitis: ultrastructural and immunohistochemical study and review of the literature. Hum Pathol. 1989;20:765-771. 26. De Beuckeleer L, De Schepper A, De Belder F, Van Goethem J, Marques MC, Broeckx J, et al. Magnetic resonance imaging of localized giant cell tumour of the tendon sheath (MRI of localized GCTTS). Eur Radiol. 1997;7:198-201. 27. Jelinek JS, Kransdorf MJ, Shmookler BM, Aboulafia AA, Malawer MM. Giant cell tumor of the tendon sheath: MR findings in nine cases. AJR Am J Roentgenol. 1994;162:919-922. 28. Narváez JA, Narváez J, Aguilera C, De Lama E, Portabella F. MR imaging of synovial tumors and tumor-like lesions. Eur Radiol. 2001;11:2549-2560. 29. Ushijima M, Hashimoto H, Tsuneyoshi M, Enjoji M. Giant cell tumor of the tendon sheath (nodular tenosynovitis). A study of 207 cases to compare the large joint group with the common digit group. Cancer. 1986;57:875-884.
30. Ding Y, Griffin JE, Raghavan M, Xu H, Henderson-Jackson E, Bui MM. Tenosynovial giant cell tumors lacking giant cells: report of diagnostic pitfalls. Ann Clin Lab Sci. 2014;44:222-227. 31. Takeuchi A, Yamamoto N, Hayashi K, Miwa S, Takahira M, Fukui K, et al. Tenosynovial giant cell tumors in unusual locations detected by positron emission tomography imaging confused with malignant tumors: report of two cases. BMC Musculoskelet Disord. 2016;17:180. 32. O’Connell JX. Pathology of the synovium. Am J Clin Pathol. 2000;114:773-784. 33. Lanzinger WD, Bindra R. Giant cell tumor of the tendon sheath. J Hand Surg Br. 2013;38:154-157. 34. Gholve PA, Hosalkar HS, Kreiger PA, Dormans JP. Giant cell tumor of tendon sheath: largest single series in children. J Pediatr Orthop. 2007;27:67-74.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 21 April 2016; accepted 20 May 2016 Citation: World Neurosurg. (2016). http://dx.doi.org/10.1016/j.wneu.2016.05.062 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
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