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Case Reports / Journal of Clinical Neuroscience 21 (2014) 1070–1072
but had been held in check by the immune system until the commencement of natalizumab. The incidence and pattern of presentation in MS patients on natalizumab of this otherwise rare tumour in this age group, strongly favours a causal link. Conflicts of interest/disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References
[2] Bozic C, LaGuette J, Panzara M, et al. Natalizumab and central nervous system lymphoma: no clear association. Ann Neurol 2009;66:261–2. [3] Phan-Ba R, Bisg B, Deprez M, et al. Primary central nervous system lymphoma in a patient treated with natalizumab. Ann Neurol 2011;69:1060–1. [4] Matzke M, Schreiber S, Elolf E, et al. Natalizumab-associated central nervous system lymphoma? – Another patient. Mult Scler 2012;18:1653–4. [5] Cote TR, Manns A, Hardy C, et al. Epidemiology of brain lymphoma among people with or without acquired immunodeficiency syndrome. AIDS/cancer study group. J Natl Cancer Inst 1996;88:675–9. [6] Pakpoor J, Disanto G, Gerber JE, et al. The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis. Mult Scler 2013;19:162–6. [7] Volpi A, Pica F. Epstein-Barr virus and CNS infections. In: Singh SK, Ruzek D, editors. Neuroviral infections. Boca Raton, Fl: CRC Press; 2013. p. 245–72. [8] DeAngelis LM. Natalizumab: a double edged sword. Ann Neurol 2009;66:262–3.
[1] Schweikert A, Kremer M, Ringel F, et al. Primary central nervous system lymphoma in a patient treated with natalizumab. Ann Neurol 2009;66:403–6. http://dx.doi.org/10.1016/j.jocn.2013.10.010
Tenosynovial giant cell tumour of brachial plexus Joshua Mingsheng Ye a,b,⇑, Mingwei J. Ye b, Te Whiti Rogers c, Michael Gonzales c, Patrick Lo a,b a
Department of Neurosurgery, Royal Melbourne Hospital, Grattan Street, Parkville, VIC 3050, Australia Department of Surgery (RMH/WH), University of Melbourne, Parkville, VIC, Australia c Department of Pathology, Royal Melbourne Hospital, Parkville, VIC, Australia b
a r t i c l e
i n f o
Article history: Received 10 September 2013 Accepted 12 September 2013
Keywords: Benign neoplasm Brachial plexus Pigmented villonodular synovitis Tenosynovial giant cell tumour
a b s t r a c t Tenosynovial giant cell tumours (TGT) are benign tumours that arise in the synovial lining of joints, tendon sheaths and bursae. Tumours arising from the vertebral column are extremely rare, with few cases reported. In this article, we describe an unusual case of an extra-articular TGT of the brachial plexus, arising from the synovium of the vertebral facet joint. To our knowledge and after a review of the literature, this is the first patient with a TGT involving the brachial plexus. The clinical, radiological and histological features of this tumour are described together with a brief discussion of management options. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Tenosynovial giant cell tumours (TGT) belong to a group of several closely related benign neoplasms that arise in the synovial lining of joints, tendon sheaths and bursae [1]. These lesions can be classified into localised or diffuse forms, depending on their growth characteristics. The localised type typically involves the tendon sheaths along wrists and fingers. In contrast, the diffuse form usually presents in areas adjacent to large weight-bearing joints such as the knee and ankle [2]. TGT rarely arise in the axial skeleton, with very few cases documented in the literature [3]. We describe to our knowledge the first patient with a vertebral TGT presenting as a mass in the brachial plexus. 2. Case report A 79-year-old elderly man initially developed gradual onset left arm pain and weakness. Over the next few months, he reported a rapid deterioration in arm strength despite gradual improvements in pain. There were no symptoms in the right upper limb or lower limbs. He recalled no history of recent trauma, but had a past history of Hodgkin’s lymphoma in the right supraclavicular region
⇑ Corresponding author. Tel.: +61 3 9342 7000; fax: +61 3 9342 7802. E-mail address: [email protected] (J.M. Ye).
treated by surgery and radiotherapy 30 years ago. Radiation targeting that area may not have been precise at the time of treatment and electromyography suggested radiation injury to that area, as myokymia could be detected in his left upper limb. His other significant medical history included prostate cancer diagnosed 8 years previously, which was treated with radiation therapy. Physical examination of his upper limb revealed wasting of his left triceps. Power was reduced in the left radial nerve innervated muscles to Medical Research Council grade 1. There was sensory loss over the anatomical snuff box and also sensory disturbance in the distribution of the left median nerve. Examination of right arm and lower limbs were otherwise unremarkable. Initial investigations were inconclusive. No lesions were detected on cervical spine radiographs and chest CT scan demonstrated no lesions in the left axilla. Nerve conduction studies identified a left radial mononeuropathy and myokymia in the left first dorsal interossei. Myokymia is an expected late complication of radiotherapy to the brachial plexus region but did not explain the disproportionate denervation changes of radial nerve muscles. MRI of the neck and brachial plexus was subsequently performed 1 month later which showed a complex cystic mass measuring 6.8 cm in length involving the left inferior brachial plexus as it passed across the first rib and second rib towards the axilla along the line of the neurovascular bundle, and appeared to be separate from the major veins and arteries. There was a mixture of signal intensity within the mass, but minimal surrounding oedema
Case Reports / Journal of Clinical Neuroscience 21 (2014) 1070–1072
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Fig. 2. Haematoxylin and eosin staining of left brachial plexus lesion showing (a) mononuclear and multinucleated (giant cell) histiocytes (low power view), and (b) better cell morphology with histiocytes having abundant amphophilic cytoplasm, oval nuclei with smooth chromatin and small nucleoli (high power view).
Fig. 1. (a) Coronal short inversion time inversion recovery MRI showing high signal intensity in left brachial plexus and (b) axial T2-weighted MRI showing a mixture of signal intensity in left brachial plexus.
(Fig. 1). On the basis of imaging findings, a nerve sheath tumour or perineural metastatic deposit seemed the most likely diagnosis. In view of the patient’s previous exposure to radiation and the rapidity of symptom progression, surgical excision and diagnostic biopsy was performed. Ultrasonic localisation of the tumour allowed for stereotactic guidance during surgery. A slight oblique left neck supraclavicular incision was made and a very large, ill defined, adherent and highly vascular tumour was found to encase the entire brachial plexus. The tumour mass was subtotally removed and biopsies were taken for pathology. Histological sections of the left brachial plexus lesion showed a moderately hypercellular tumour composed predominantly of osteoclast-like multinucleated giant cells (Fig. 2). These were admixed with moderately pleomorphic uninucleated cells arranged in diffuse sheets. Moderate numbers of small lymphocytes were also present. The large multinucleated and small uninucleated cells showed strong cytoplasmic immunostaining for CD68 (Fig. 3). Scattered small cells showed moderately strong cytoplasmic staining for CD1a. The topoisomerase proliferation index was approximately 2%. The features were of TGT and the most likely
Fig. 3. Positive CD68 immunostaining confirming that the cells are of histiocytic origin (high power view).
site of origin of this tumour was the synovium of a vertebral facet joint. Postoperatively, the patient reported significant improvement in symptoms and increased mobility within the intrinsic hand
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Case Reports / Journal of Clinical Neuroscience 21 (2014) 1070–1072
muscles. MRI and follow-up will be required to monitor his condition.
3. Discussion TGT is a benign lesion of the synovial lining that frequently occurs between the third and fifth decade of life, with females more commonly affected than males [2]. They tend to predominantly affect hand tendon sheaths [4]. TGT of the vertebral column are exceptionally rare, with the cervical spine the most commonly affected site. These tumours can be classified into intra-articular, extra-articular or extra-articular extensions of primary intra-articular lesion. Extra-articular tumours are extremely rare in the literature, with few cases reported to date. Affected patients typically complain of pain localised to the spinal region. Other common presenting symptoms include radicular pain or numbness [3]. Obtaining a histological diagnosis of TGT is not difficult [2]. Prior to biopsy, differential diagnosis for TGT of the vertebral column includes giant cell tumour of the bone, osteoblastoma, peripheral nerve sheath tumour and hypertrophic synovitis [3]. Histologically, TGT is characterised by a discrete proliferation of mononuclear epitheloid cells accompanied by a variable number of multinucleated giant cells, lymphocytes, siderophages, and xanthoma cells. These lesions can be further divided into localised and diffuse forms, with slight histological variations between the two forms [2]. Localised TGT are generally well demarcated from the surrounding structures by a dense collagenous capsule. In contrast, diffuse forms grow in expansive sheets with less numerous giant cells and diminished collagen. Despite attempts to differentiate these tumours into different histological forms, tumours arising from the axial skeleton can be difficult to classify into localised or diffuse forms [3]. The pathogenesis of TGT remains unclear. They were initially considered by Jaffe et al. to be reactive synovial proliferations [5]. However, recent cytogenic studies have demonstrated chromosomal abnormalities in these lesions, indicating a neoplastic aetiology [6]. Another important observation favouring a neoplastic origin is that these lesions are capable of a certain degree of autonomous growth. Apart from the uncertain aetiology, the exact site of origin of these tumours is also difficult to define [2,7]. For instance, in our patient, the lesion most probably arose from synovium of the vertebral facet joint and extended extra-articularly before encasing the entire left brachial plexus. http://dx.doi.org/10.1016/j.jocn.2013.09.012
There is a well documented tendency for TGT of the vertebral column to recur locally [1–3]. Gross total removal is not only the treatment of choice but is also curative. Furlong et al. [3]. reported no evidence of recurrent disease in patients who had undergone gross total removal of tumour. However, complete tumour removal may not be possible in some patients due to surgical inaccessibility and risk of damage to vital surrounding structures. For these patients, partial resection is carried out with repeat surgical excision for persistent or recurrent disease [3]. Some authors have advocated the use of radiation therapy in patients with residual tumour, although it is still unclear whether this has any beneficial effect [7,8]. 4. Conclusion TGT arising from the vertebral column are rare. Complete surgical resection of tumour is the treatment of choice and appears to be curative. Local recurrences are common in patients with residual tumour. For these patients, repeat surgical excision or adjuvant radiotherapy may be considered. In the meantime, follow-up and monitoring is warranted. References [1] Rosenberg A. Giant cell tumor of tendon sheath and pigmented villonodular synovitis. In: Cotran RS, Kumar V, Collins T, editors. Robbins pathologic basis of disease. Philadelphia: Saunders; 1999. p. 1258–9. [2] Enzinger FM, Weiss SW. Benign tumors and tumorlike lesions of synovial tissue. In: Enzinger FM, Weiss SW, editors. Soft tissue tumors. St. Louis: CV Mosby; 1995. p. 736–49. [3] Furlong MA, Motamedi K, Laskin WB, et al. Synovial-type giant cell tumors of the vertebral column: a clinicopathologic study of 15 cases, with a review of the literature and discussion of the differential diagnosis. Hum Pathol 2003;34:670–9. [4] Monaghan H, Salter DM, Al-Hafussi A. Giant cell tumour of tendon sheath (localised nodular tenosynovitis): clinicopathological features of 71 cases. J Clin Pathol 2001;54:404–7. [5] Jaffe HL, Lichtenstein L, Sutro CJ. Pigemented villonodular synovitis, bursitis and tenosynovitis: a discussion of the synovial and bursal equivalents of the tenosynovial lesions commonly denoted as xanthoma, xanthogranuloma, giant cell tumor or myeloplaxoma of the tendon sheath, with some considerations of this tendon sheath itself. Arch Pathol 1941;31:731–65. [6] Dal Cin P, Scoit R, Samson I, et al. Cytogenetic characterization of tenosynovial giant cell tumors (nodular tenosynovitis). Cancer Res 1994;54:3986–7. [7] Mahmood A, Caccamo DV, Morgan JK. Tenosynovial giant-cell tumor of the cervical spine. J Neurosurg 1992;77:952–5. [8] Weidner N, Challa VR, Bonsib SM, et al. Giant cell tumors of synovium (pigmented villonodular synovitis) involving the vertebral column. Cancer 1986;57:2030–6.
Case Reports / Journal of Clinical Neuroscience 21 (2014) 1070–1072
but had been held in check by the immune system until the commencement of natalizumab. The incidence and pattern of presentation in MS patients on natalizumab of this otherwise rare tumour in this age group, strongly favours a causal link. Conflicts of interest/disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. References
[2] Bozic C, LaGuette J, Panzara M, et al. Natalizumab and central nervous system lymphoma: no clear association. Ann Neurol 2009;66:261–2. [3] Phan-Ba R, Bisg B, Deprez M, et al. Primary central nervous system lymphoma in a patient treated with natalizumab. Ann Neurol 2011;69:1060–1. [4] Matzke M, Schreiber S, Elolf E, et al. Natalizumab-associated central nervous system lymphoma? – Another patient. Mult Scler 2012;18:1653–4. [5] Cote TR, Manns A, Hardy C, et al. Epidemiology of brain lymphoma among people with or without acquired immunodeficiency syndrome. AIDS/cancer study group. J Natl Cancer Inst 1996;88:675–9. [6] Pakpoor J, Disanto G, Gerber JE, et al. The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis. Mult Scler 2013;19:162–6. [7] Volpi A, Pica F. Epstein-Barr virus and CNS infections. In: Singh SK, Ruzek D, editors. Neuroviral infections. Boca Raton, Fl: CRC Press; 2013. p. 245–72. [8] DeAngelis LM. Natalizumab: a double edged sword. Ann Neurol 2009;66:262–3.
[1] Schweikert A, Kremer M, Ringel F, et al. Primary central nervous system lymphoma in a patient treated with natalizumab. Ann Neurol 2009;66:403–6. http://dx.doi.org/10.1016/j.jocn.2013.10.010
Tenosynovial giant cell tumour of brachial plexus Joshua Mingsheng Ye a,b,⇑, Mingwei J. Ye b, Te Whiti Rogers c, Michael Gonzales c, Patrick Lo a,b a
Department of Neurosurgery, Royal Melbourne Hospital, Grattan Street, Parkville, VIC 3050, Australia Department of Surgery (RMH/WH), University of Melbourne, Parkville, VIC, Australia c Department of Pathology, Royal Melbourne Hospital, Parkville, VIC, Australia b
a r t i c l e
i n f o
Article history: Received 10 September 2013 Accepted 12 September 2013
Keywords: Benign neoplasm Brachial plexus Pigmented villonodular synovitis Tenosynovial giant cell tumour
a b s t r a c t Tenosynovial giant cell tumours (TGT) are benign tumours that arise in the synovial lining of joints, tendon sheaths and bursae. Tumours arising from the vertebral column are extremely rare, with few cases reported. In this article, we describe an unusual case of an extra-articular TGT of the brachial plexus, arising from the synovium of the vertebral facet joint. To our knowledge and after a review of the literature, this is the first patient with a TGT involving the brachial plexus. The clinical, radiological and histological features of this tumour are described together with a brief discussion of management options. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Tenosynovial giant cell tumours (TGT) belong to a group of several closely related benign neoplasms that arise in the synovial lining of joints, tendon sheaths and bursae [1]. These lesions can be classified into localised or diffuse forms, depending on their growth characteristics. The localised type typically involves the tendon sheaths along wrists and fingers. In contrast, the diffuse form usually presents in areas adjacent to large weight-bearing joints such as the knee and ankle [2]. TGT rarely arise in the axial skeleton, with very few cases documented in the literature [3]. We describe to our knowledge the first patient with a vertebral TGT presenting as a mass in the brachial plexus. 2. Case report A 79-year-old elderly man initially developed gradual onset left arm pain and weakness. Over the next few months, he reported a rapid deterioration in arm strength despite gradual improvements in pain. There were no symptoms in the right upper limb or lower limbs. He recalled no history of recent trauma, but had a past history of Hodgkin’s lymphoma in the right supraclavicular region
⇑ Corresponding author. Tel.: +61 3 9342 7000; fax: +61 3 9342 7802. E-mail address: [email protected] (J.M. Ye).
treated by surgery and radiotherapy 30 years ago. Radiation targeting that area may not have been precise at the time of treatment and electromyography suggested radiation injury to that area, as myokymia could be detected in his left upper limb. His other significant medical history included prostate cancer diagnosed 8 years previously, which was treated with radiation therapy. Physical examination of his upper limb revealed wasting of his left triceps. Power was reduced in the left radial nerve innervated muscles to Medical Research Council grade 1. There was sensory loss over the anatomical snuff box and also sensory disturbance in the distribution of the left median nerve. Examination of right arm and lower limbs were otherwise unremarkable. Initial investigations were inconclusive. No lesions were detected on cervical spine radiographs and chest CT scan demonstrated no lesions in the left axilla. Nerve conduction studies identified a left radial mononeuropathy and myokymia in the left first dorsal interossei. Myokymia is an expected late complication of radiotherapy to the brachial plexus region but did not explain the disproportionate denervation changes of radial nerve muscles. MRI of the neck and brachial plexus was subsequently performed 1 month later which showed a complex cystic mass measuring 6.8 cm in length involving the left inferior brachial plexus as it passed across the first rib and second rib towards the axilla along the line of the neurovascular bundle, and appeared to be separate from the major veins and arteries. There was a mixture of signal intensity within the mass, but minimal surrounding oedema
Case Reports / Journal of Clinical Neuroscience 21 (2014) 1070–1072
1071
Fig. 2. Haematoxylin and eosin staining of left brachial plexus lesion showing (a) mononuclear and multinucleated (giant cell) histiocytes (low power view), and (b) better cell morphology with histiocytes having abundant amphophilic cytoplasm, oval nuclei with smooth chromatin and small nucleoli (high power view).
Fig. 1. (a) Coronal short inversion time inversion recovery MRI showing high signal intensity in left brachial plexus and (b) axial T2-weighted MRI showing a mixture of signal intensity in left brachial plexus.
(Fig. 1). On the basis of imaging findings, a nerve sheath tumour or perineural metastatic deposit seemed the most likely diagnosis. In view of the patient’s previous exposure to radiation and the rapidity of symptom progression, surgical excision and diagnostic biopsy was performed. Ultrasonic localisation of the tumour allowed for stereotactic guidance during surgery. A slight oblique left neck supraclavicular incision was made and a very large, ill defined, adherent and highly vascular tumour was found to encase the entire brachial plexus. The tumour mass was subtotally removed and biopsies were taken for pathology. Histological sections of the left brachial plexus lesion showed a moderately hypercellular tumour composed predominantly of osteoclast-like multinucleated giant cells (Fig. 2). These were admixed with moderately pleomorphic uninucleated cells arranged in diffuse sheets. Moderate numbers of small lymphocytes were also present. The large multinucleated and small uninucleated cells showed strong cytoplasmic immunostaining for CD68 (Fig. 3). Scattered small cells showed moderately strong cytoplasmic staining for CD1a. The topoisomerase proliferation index was approximately 2%. The features were of TGT and the most likely
Fig. 3. Positive CD68 immunostaining confirming that the cells are of histiocytic origin (high power view).
site of origin of this tumour was the synovium of a vertebral facet joint. Postoperatively, the patient reported significant improvement in symptoms and increased mobility within the intrinsic hand
1072
Case Reports / Journal of Clinical Neuroscience 21 (2014) 1070–1072
muscles. MRI and follow-up will be required to monitor his condition.
3. Discussion TGT is a benign lesion of the synovial lining that frequently occurs between the third and fifth decade of life, with females more commonly affected than males [2]. They tend to predominantly affect hand tendon sheaths [4]. TGT of the vertebral column are exceptionally rare, with the cervical spine the most commonly affected site. These tumours can be classified into intra-articular, extra-articular or extra-articular extensions of primary intra-articular lesion. Extra-articular tumours are extremely rare in the literature, with few cases reported to date. Affected patients typically complain of pain localised to the spinal region. Other common presenting symptoms include radicular pain or numbness [3]. Obtaining a histological diagnosis of TGT is not difficult [2]. Prior to biopsy, differential diagnosis for TGT of the vertebral column includes giant cell tumour of the bone, osteoblastoma, peripheral nerve sheath tumour and hypertrophic synovitis [3]. Histologically, TGT is characterised by a discrete proliferation of mononuclear epitheloid cells accompanied by a variable number of multinucleated giant cells, lymphocytes, siderophages, and xanthoma cells. These lesions can be further divided into localised and diffuse forms, with slight histological variations between the two forms [2]. Localised TGT are generally well demarcated from the surrounding structures by a dense collagenous capsule. In contrast, diffuse forms grow in expansive sheets with less numerous giant cells and diminished collagen. Despite attempts to differentiate these tumours into different histological forms, tumours arising from the axial skeleton can be difficult to classify into localised or diffuse forms [3]. The pathogenesis of TGT remains unclear. They were initially considered by Jaffe et al. to be reactive synovial proliferations [5]. However, recent cytogenic studies have demonstrated chromosomal abnormalities in these lesions, indicating a neoplastic aetiology [6]. Another important observation favouring a neoplastic origin is that these lesions are capable of a certain degree of autonomous growth. Apart from the uncertain aetiology, the exact site of origin of these tumours is also difficult to define [2,7]. For instance, in our patient, the lesion most probably arose from synovium of the vertebral facet joint and extended extra-articularly before encasing the entire left brachial plexus. http://dx.doi.org/10.1016/j.jocn.2013.09.012
There is a well documented tendency for TGT of the vertebral column to recur locally [1–3]. Gross total removal is not only the treatment of choice but is also curative. Furlong et al. [3]. reported no evidence of recurrent disease in patients who had undergone gross total removal of tumour. However, complete tumour removal may not be possible in some patients due to surgical inaccessibility and risk of damage to vital surrounding structures. For these patients, partial resection is carried out with repeat surgical excision for persistent or recurrent disease [3]. Some authors have advocated the use of radiation therapy in patients with residual tumour, although it is still unclear whether this has any beneficial effect [7,8]. 4. Conclusion TGT arising from the vertebral column are rare. Complete surgical resection of tumour is the treatment of choice and appears to be curative. Local recurrences are common in patients with residual tumour. For these patients, repeat surgical excision or adjuvant radiotherapy may be considered. In the meantime, follow-up and monitoring is warranted. References [1] Rosenberg A. Giant cell tumor of tendon sheath and pigmented villonodular synovitis. In: Cotran RS, Kumar V, Collins T, editors. Robbins pathologic basis of disease. Philadelphia: Saunders; 1999. p. 1258–9. [2] Enzinger FM, Weiss SW. Benign tumors and tumorlike lesions of synovial tissue. In: Enzinger FM, Weiss SW, editors. Soft tissue tumors. St. Louis: CV Mosby; 1995. p. 736–49. [3] Furlong MA, Motamedi K, Laskin WB, et al. Synovial-type giant cell tumors of the vertebral column: a clinicopathologic study of 15 cases, with a review of the literature and discussion of the differential diagnosis. Hum Pathol 2003;34:670–9. [4] Monaghan H, Salter DM, Al-Hafussi A. Giant cell tumour of tendon sheath (localised nodular tenosynovitis): clinicopathological features of 71 cases. J Clin Pathol 2001;54:404–7. [5] Jaffe HL, Lichtenstein L, Sutro CJ. Pigemented villonodular synovitis, bursitis and tenosynovitis: a discussion of the synovial and bursal equivalents of the tenosynovial lesions commonly denoted as xanthoma, xanthogranuloma, giant cell tumor or myeloplaxoma of the tendon sheath, with some considerations of this tendon sheath itself. Arch Pathol 1941;31:731–65. [6] Dal Cin P, Scoit R, Samson I, et al. Cytogenetic characterization of tenosynovial giant cell tumors (nodular tenosynovitis). Cancer Res 1994;54:3986–7. [7] Mahmood A, Caccamo DV, Morgan JK. Tenosynovial giant-cell tumor of the cervical spine. J Neurosurg 1992;77:952–5. [8] Weidner N, Challa VR, Bonsib SM, et al. Giant cell tumors of synovium (pigmented villonodular synovitis) involving the vertebral column. Cancer 1986;57:2030–6.
