- Email: [email protected]
IgG4-Related Disease of the Craniovertebral Junction
Case Report
IgG4-Related Disease of the Craniovertebral Junction Brian J. Park1, Rachel Starks2, Patricia Kirby2, Arnold H. Menezes1, Brian J. Dlouhy1,3,4
Key words Bone - Craniovertebral junction - IgG4-related disease - Spine -
Abbreviations and Acronyms CRP: C-reactive protein CT: Computed tomography CVJ: Craniovertebral junction ESR: Erythrocyte sedimentation rate hpf: High-power field IgG4-RD: Immunoglobulin G4erelated disease MRI: Magnetic resonance imaging PET: Positron emission tomography From the Departments of 1Neurosurgery and 2Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa; and 3 Pappajohn Biomedical Institute and 4Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA To whom correspondence should be addressed: Brian J. Dlouhy, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2020) 134:264-271. https://doi.org/10.1016/j.wneu.2019.10.195 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com
- BACKGROUND:
The majority of the abnormalities and diseases that affect the craniovertebral junction (CVJ) have already been reported, and therefore it is exceedingly rare to identify new pathology that affects the CVJ. Immunoglobulin G4erelated disease (IgG4-RD) is an immune mediated process treated with immunosuppressive medications. To our knowledge, this is the first reported case of IgG4-RD affecting the CVJ.
- CASE
DESCRIPTION: The authors report the case of a woman aged 71 years with IgG4-RD of the CVJ. She presented with intractable left occipital pain and limited flexion, extension, and rotation of the neck. Computed tomography and magnetic resonance imaging revealed a lytic enhancing lesion of the left occipital condyle, left C1 lateral mass, and left C1 anterior arch resulting in cranial settling, basilar invagination, and CVJ instability. An open biopsy, subtotal resection, and occiput to C2 fusion was performed. Pathology revealed IgG4-RD. The patient was subsequently placed on rituximab immunotherapy with complete resolution of enhancement on magnetic resonance imaging and bone growth at the previous site of the lytic IgG4-RD lesion.
- CONCLUSIONS:
To our knowledge, this case describes the first case of IgG4RD affecting the CVJ, which mimicked a tumor-like process. When IgG4-RD affects the CVJ, stability must be accounted for, especially in the cases of osteolytic destruction. The combination of medical therapy to target the underlying inflammatory process and surgery to provide structural stability was successful.
1878-8750/$ - see front matter Published by Elsevier Inc.
INTRODUCTION The majority of the abnormalities and diseases that affect the craniovertebral junction (CVJ) have already been reported, and therefore it is exceedingly rare to identify new pathology that affects the CVJ. Immunoglobulin G4erelated disease (IgG4-RD) is a rare but increasingly recognized immune mediated disorder.1 It is characterized by pathological findings of lymphoplasmacytic lesions rich in IgG4, and a storiform pattern of fibrosis that can lead to pseudotumors of the affected organ.1,2 Multiple organ systems can be affected.1,3,4 Rare cases affecting the central nervous system and spine have been described in the literature.3-19 The CVJ is comprised of the occiput, atlas vertebra, axis vertebra, and accompanying musculature and ligaments. Numerous pathologies affecting the CVJ have been reported that
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can lead to a variety of clinical symptoms as a result of instability.20 Here we present, to our knowledge, the first reported case of IgG4-RD affecting the CVJ resulting in an unusual lytic destruction of the CVJ with subsequent cranial settling, basilar invagination, and instability. We describe the diagnostic workup, and subsequent surgical and medical treatment. We also describe the clinical, pathological, and anatomic characteristics of IgG4-RD of the CVJ. CASE REPORT History and Examination A women aged 71 years presented with 4 months of worsening left occipital pain, which occurred spontaneously on awakening 1 morning. She was evaluated and treated by a pain clinic with an occipital nerve block, epidural steroid injection, gabapentin, and ibuprofen, all without any
significant relief. The pain became intractable. The patient had significant limitation of flexion, extension, and rotation of the neck. A computed tomography (CT) scan done 4 months prior to presentation was unremarkable (Figure 1AeD). A repeat CT scan was performed on presentation, which revealed a lytic lesion involving the left occipital condyle and the left lateral mass and anterior arch of C1 (Figure 2BeD). A magnetic resonance imaging (MRI) study showed a contrastenhancing lesion of the left occipital condyle, left lateral mass, left anterior arch of C1, inferior margin of the clivus, tip of the dens, and adjacent soft tissue (Figure 2FeH). Basilar invagination with a retroodontoid-calcified lesion was also evident (Figure 2A and E). To further identify this pathology, which at this point included tumor or an infectious process, a positron emission tomography
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CASE REPORT BRIAN J. PARK ET AL.
IGG4-RELATED DISEASE OF THE CVJ
Figure 1. Computed tomography (CT) scan at onset of symptoms was normal. Cervical CT scan performed at onset of symptoms 4 months prior to presentation to our hospital
(PET) scan was conducted that showed a hypermetabolic left occipital condyle and left lateral mass lesion (Figure 3A). A nuclear white blood cell scan was also performed with no increased uptake of white blood cells in the left occipital condyle and left lateral mass region (Figure 3B), confirming this was not an infection. The patient was placed in a Miami J cervical collar (American Prosthetics & Orthotics, Iowa City, Iowa, USA) during the diagnostic and surgical workup. She had significant pain relief after being placed in the collar. A percutaneous biopsy was deemed too difficult to obtain. With evidence of a progressive lytic lesion with findings of cranial settling with basilar impression and instability leading to intractable pain with need for a diagnosis, an open biopsy with occiput-C2 posterior fusion was offered. The patient elected to undergo surgical management.
Surgical Treatment The patient was placed under 7 pounds of crown halo stabilization and traction. Midline occipital-cervical incision was used to expose the occiput, C1, and C2. The left
showing unremarkable findings in (A) sagittal, (B) left parasagittal, (C) coronal, and (D) axial views.
C1 lamina was removed to access the more anterior C1 lateral mass. The left C1 lateral mass was found to have a lytic component, as well as a soft tumor-like component, grayish in nature, which was resected and sent for pathology. An occipital plate, occipital screws, and C2 bilateral pars screws were then instrumented. Bilateral hinged rods were used to complete the instrumentation. Calvarial bone graft was harvested and used for osseous fusion. Closure was carried out in multiple layers to reapproximate the muscle, fascia, subcutaneous tissue, and skin.
identified (Figure 4B). Plasma cells were found to equally express kappa or lambda light chains, suggesting this was not multiple myeloma. However, immunohistochemistry for expression of IgG and IgG4 identified 151 IgGpositive cells per high-power field (hpf) and 226 IgG4-positive cells per hpf, with an IgG4/IgG ratio of 1.50 (Figure 4C and D). With >10 IgG4positive plasma cells per hpf and a IgG4/IgG ratio >0.4, these findings met criteria for IgG4-RD.
Pathology The histopathology of the mass showed predominantly small fragments of bone and dense fibrous tissue with mixed acute and chronic inflammatory cells. In some areas, giant cells were present, likely a reaction to bony fragments, as well as inflammatory cells (Figure 4A). The inflammatory cells were confirmed by an immunohistochemical panel of stains to represent a mixed population of lymphocytes, plasma cells, and macrophages. Notably, areas containing mature plasma cells were
Postoperative Course and Treatment The patient did well after surgery with an almost immediate significant reduction in neck pain. Although the IgG4 levels on histology indicated IgG4-RD, the presentation, location, and imaging of this lytic mass was unlike any other previous case of IgG4-RD. Therefore, an extensive malignancy workup was performed to completely rule out myeloma or other tumor with repeat PET scan, MRI of the body, and bone marrow biopsy with cytogenetics and fluorescence in situ hybridization for myeloma panel. A serum protein electrophoresis
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Figure 2. Computed tomography (CT) and magnetic resonance imaging (MRI) showing lytic lesion in left lateral mass of C1, condyle, and anterior arch of C1 causing basilar invagination and instability. CT scan performed 4 months after the onset of symptoms (preoperatively) in the (A) midsagittal, (B) left parasagittal, (C) coronal, and (D) axial plane showing basilar invagination (arrow) and lytic process (asterisk) of the left C1 lateral mass,
with measurement of serum-free kappa and lambda light chains was conducted. A 24hour urine electrophoresis was also done. All of these studies were unremarkable for a
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left condyle, and anterior arch of C1. T1-weighted postcontrast MRI performed at the same time as the CT in the (E) sagittal, (F) left parasagittal, and (G, H) axial views showing retroodontoid mass and basilar invagination (arrow) with enhancement (asterisk) of the dens, left C1 lateral mass, occipital condyle, anterior arch of C1, and adjacent soft tissue.
monoclonal plasma cell disease or neoplastic process. Additional workup with CT scan of chest, abdomen, and pelvis was
unremarkable for additional sites of IgG4RD. IgG4, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were obtained and followed (Table 1). The
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CASE REPORT BRIAN J. PARK ET AL.
IGG4-RELATED DISEASE OF THE CVJ
Figure 3. Positron emission tomography (PET) showing hypermetabolic lesion and single-photon emission computerized tomography (SPECT) showing decreased white blood cell (WBC) activity in left lateral mass of C1 and condyle. PET scan and WBC SPECT scan performed preoperatively during diagnostic workup to further evaluate differential diagnosis including tumor or
patient was started on rituximab infusions in place of prednisone because of her instrumentation and fusion. She received
infectious processes. (A) PET scan shows a hypermetabolic lesion (arrow) at the area of left lateral mass of C1 and occipital condyle. (B) WBC SPECT scan shows decreased activity (arrow) at the area of left lateral mass C1 and occipital condyle suggesting the lesion was a bone marrow replacing lesion and not an infection.
two 1000 mg rituximab infusions spaced 15 days apart approximately 3 months after surgery. This led to a drop in IgG4
Figure 4. Histomorphology of deep lateral craniovertebral mass. (A) Hematoxylin and eosin (H&E) stain at 200x magnification showing tissue fragment with bone, fibrosis, and a mixed acute and chronic inflammation with a foreign body giant cell reaction (arrows),
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levels and inflammatory markers. A 5month postoperative CT scan showed stable alignment with interval bone
and (B) 400x magnification showing an accumulation of plasma cells. (C) Immunohistochemical stains highlight IgG expressing plasma cells and (D) IgG4 expressing plasma cells, both at 400x magnification.
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Table 1. Postoperative Immunoglobulin G4, Erythrocyte Sedimentation Rate, and C-Reactive Protein Measurements Time after Surgery
1 Month
5 Months
8 Months
12 Months
15 Months
IgG4 (1e123 mg/dL)
245
196
168
229
185
ESR (0e20 mm/hr)
30
20
17
12
14
CRP (<0.5 mg/dL)
0.9
<0.5
<0.5
<0.5
<0.5
Values in ( ) indicate the reference range of normal values. The patient was treated with rituximab at 3 months and 9 months after surgery. IgG4, immunoglobulin G4; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.
growth within the previous lytic areas seen preoperatively (Figure 5BeD). MRI showed resolution of the abnormal enhancement seen in the same location as the lytic lesion (Figure 5EeG). The basilar invagination seen previously stabilized (Figure 5A). The ESR and CRP levels normalized following rituximab therapy throughout the entire follow-up period. IgG4 levels showed a more variable course. IgG4 levels initially decreased 5 months postoperatively and again 8 months postoperatively. She received another two 1000 mg rituximab infusions 9 months postoperatively. Twelve months postoperatively, her IgG4 levels rose. However, clinically she remained asymptomatic and was observed. At her most recent 15-month immunology testing, IgG4 levels continued to be mildly elevated, but decreased from the 9-month follow-up and inflammatory markers remained low. She is now 2 years since diagnosis and surgery with a continued decline in IgG4 levels, and the patient continues to endorse resolution of clinical symptoms. A maintenance course of rituximab was not pursued, and continued surveillance with inflammatory markers is planned. DISCUSSION IgG4-RD is a relatively new and uncommon disease. To our knowledge, this is the first reported case of IgG4-RD affecting the CVJ. IgG4-RD IgG4-RD is an immune mediated fibroinflammatory disease, characterized by unique pathological features that can affect a multitude of different organs. Classification system of phenotypes based
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on the distribution of organs affected has been previously described.21 The classic histopathological characteristics of IgG4RD have been described as lymphoplasmacytic infiltration, a storiform pattern of fibrosis, and obliterative phlebitis.1,2,22-24 A mix of lymphocytes and plasma cells with predominantly IgG4positive plasma cells are present. The ratio of IgG4/IgG-positive cells is >0.4. The storiform pattern of fibrosis describes radially arranged, interlaced, and often whorled pattern of collagen fibers. Although a specific storiform pattern can sometimes be absent, some sort of fibrosis is always present.2,25 Our patient showed a dense pattern of fibrosis along with a predominance of IgG4-positive plasma cells with an IgG4/IgG ratio of 1.50. The pathophysiology behind IgG4-RD is not fully understood but is generally thought that IgG4 antibodies are not the driving force behind the disease.1,23,24 Rather, CD4 T cells drive the process by activating innate immune cells leading to cytokine release, which is sustained by plasma cells and antigen presenting B cells.1,23,24 Possibly through the same antigen, another T follicular helper cell drives the development of germinal centers and the production of IgG4secreting plasmablasts and plasma cells.1,23,24 Diagnosis is based on tissue biopsy and clinicopathological correlation.1 Imaging can be nonspecific but often show organ infiltration with surrounding inflammation and fibrosis. CT, MRI, single-photon emission CT, and PET scans have all been described for use in the local and systemic workup of IgG4RD.25-28 There can be an elevation of IgG4 serum levels, but this is not always
the case. Increased ratio of IgG4 to IgG serum levels can increase the specificity.1 Measuring IgG4 levels can be a marker for disease activity but is not always reliable. Additional surveillance with inflammatory markers has been used for monitoring disease activity.29 This strategy was implemented in our patient who showed a persistently decreased ESR and CRP after treatment but had varying serum IgG4 levels. The first-line treatment for IgG4-RD are glucocortiocoids.1 In steroid-resistant or contraindicated patients, second-line treatments with steroid-sparing immunosuppressants have been used.1,30 B cell depletion with rituximab is described as well. This method targets CD20-positive cells, interfering with the repletion of IgG4-producing plasma cells.1 Relapses have been reported after initial successful treatment.29 There have been reports describing maintenance regimens aimed to reduce relapse rates.31 Our patient received rituximab therapy as a way to avoid steroids to promote spinal fusion postoperatively. She responded well clinically and radiographically. Maintenance therapy was not pursued after consideration of the potential risks associated with chronic immunosuppression. IgG4-RD of the Spine IgG4-RD of the central nervous system is relatively uncommon, and IgG4-RD of the spine is rare. Only 19 cases affecting the spine have been described in the literature (Table 2).3-19 Most of these cases involve the dura with hypertrophic pachymeningitis with diffuse thickening of the dura or an epidural compressive lesion. Homogenous enhancement in postcontrast MRI scans is usually seen. There are 2 cases that have occurred intradural extramedullary.5,11 Bony spine involvement is rare. There is only 1 other report in which the vertebral bodies were affected. In this case, IgG4-RD of soft tissue origin extended into the bony elements.16 IgG4-RD primarily affecting the bone in general is rare and can mimic the appearance of myeloma.32 Three cases primarily in the temporal bone have also been reported.33 In the case described here, the disease presented as primary lytic lesions of the C1 vertebrae and left occipital condyle. To our knowledge, it is
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CASE REPORT BRIAN J. PARK ET AL.
IGG4-RELATED DISEASE OF THE CVJ
Figure 5. Postoperative imaging, computed tomography (CT) scan performed 5 months postoperatively after occipital-cervical instrumentation and fusion in the (A) sagittal, (B) left parasagittal, (C) coronal, and (D) axial plane showing stabilization of the basilar invagination (arrow), and bone growth (asterisk) within the previous lytic region involving the left condyle, left C1 lateral mass, and left anterior arch of C1. T1-weighted postcontrast
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magnetic resonance imaging performed at the same time as the CT in the (E) left parasagittal, (F) coronal, and (G) axial plane showing resolution of the enhancement (asterisk) seen previously in the left C1 lateral mass, occipital condyle, anterior arch of C1, and adjacent soft tissue. (H) Postoperative radiograph showing occipital-cervical instrumentation and early osseous fusion along the occiput, lateral mass of C1 and C2.
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Table 2. Case Reports of Immunoglobulin G4eRelated Disease of the Spine Author
Spinal Region
Location
T3-T5
Intradural, extramedullary
Chan et al., 2009
T5-T10
Epidural
Choi et al., 20107
T9-T11
Epidural
8
T2-T3
Epidural
9
T10-T12
Epidural
C4-T2
Epidural
Kim et al., 2014
C7-T5
Intradural, extramedullary
Lindstrom et al., 201012
C3-C7
Dural
C2-T9
Dural
Maher et al., 2017
C6-L2
Dural
Milhoushev et al., 20143
C5-T10
Dural
Bridges et al., 20175 6
Ezzeldin et al., 2014 Ferreira et al., 2016 Gu et al., 201610 11
Lu et al., 2016
13 14
15
Radotra et al., 2016
L1-L3
Dural
Rumalla et al., 201716
T4-T6
Epidural extension into vertebral bodies
Sato et al., 20154
T2-T12
Paraspinal
17
L5
Dural
Williams et al., 201718
C4-T1
Epidural and paraspinal
Winkel et al., 201819
L2-L3
Epidural
Wallace et al., 2013
the first reported case involving a lesion originating in the CVJ, and the first case in the spine that appeared to originate in the bone.
CVJ Pathologies The CVJ consists of the occipital bones that surround the foramen magnum, the atlas, the axis, and the associated musculature and ligaments.20,34,35 Flexion and extension of the neck occurs at the occipital-atlas joint, and rotation occurs at the atlantoaxial joint.20 In our case, osteolysis of the occipital condyle and lateral mass of C1 severely limited the patient's neck motion and caused intractable pain. Basilar invagination implies prolapse of the dens through the foramen magnum often leading to impression into the medulla. Softening of the skull with cranial settling is one way basilar impression can form.20 In our patient, the osteolytic lesions led to instability with cranial settling and basilar impression. Subsequent surgical treatment with an occipital-cervical fusion led to resolution of symptoms and radiographic stabilization.
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CONCLUSIONS To our knowledge, this case describes the first case of IgG4-RD affecting the CVJ, which mimicked a tumor-like process. When IgG4-RD affects the CVJ, stability must be accounted for, especially in the cases of osteolytic destruction. The combination of medical therapy to target the underlying inflammatory process and surgery to provide structural stability was successful. REFERENCES 1. Kamisawa T, Zen Y, Pillai S, Stone J. IgG4-related disease. Lancet. 2015;385:1460-1471. 2. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181-1192. 3. Miloushev V, Cabrera M, Ichise M. A case of immunoglobulin 4-related disease. Clin Nucl Med. 2014;39:537-539. 4. Sato M, Kodaira M, Ishii W, et al. Multifocal fibrosclerosis with hypertrophic pachymeningitis and a soft tissue mass around the thoracic vertebral bodies: a case report with review of the literature. Intern Med. 2015;54:2267-2272. 5. Bridges K, DeDeaux C, Than K. IgG4-related disease presenting as intradural extramedullary
lesion: a case report and review of the literature. Br J Neurosurg. 2017;31:1-7. 6. Chan S, Cheuk W, Chan K, Chan J. IgG4-related sclerosing pachymeningitis: a previously unrecognized form of central nervous system involvement of IgG4-related sclerosing disease. Am J Surg Pathol. 2009;33:1249-1252. 7. Choi S, Lee S, Khang S, Jeon S. IgG4-related sclerosing pachymeningitis causing spinal cord compression. Neurology. 2010;75:1388-1390. 8. Ezzeldin M, Sawagfeh A, Schnadig V, Smith RG, Fang X. Hypertrophic spinal pachymeningitis: idiopathic vs. IgG4-related. J Neurol Sci. 2014;347: 398-400. 9. Ferreira N, Vaz R, Carmona S, et al. IgG4-related disease presenting with an epidural inflammatory pseudotumor: a case report. J Med Case Rep. 2016; 10:61. 10. Gu R, Hao P, Liu J, Wang Z. Cervicothoracic spinal cord compression caused by IgG4-related sclerosing pachymeningitis: a case report and literature review. Eur Spine J. 2016;25:147-151. 11. Kim S, Kang Y, Oh S, Paik S, Kim J. Paraplegia in a patient with IgG4-related sclerosing disease: a case report. Ann Rehabil Med. 2014;38:856-860. 12. Lindstrom K, Cousar J, Lopes M. IgG4-related meningeal disease: clinic-pathological features and proposal for diagnostic criteria. Acta Neuropathol. 2010;120:765-776.
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13. Lu Z, Tongxi L, Jie L, et al. IgG4-related spinal pachymeningitis. Clin Rehumatol. 2016;35: 1549-1553. 14. Maher M, Zanazzi G, Faust P, Nickerson K, Wong T. IgG4-related hypertrophic pachymeningitis of the spine with MPO-ANCA seropositivty. Clin Imaging. 2017;46:108-112. 15. Radotra B, Aggarwal A, Kapoor A, Singla N, Chatterjee D. An orphan disease: IgG4-related spinal pachymeningitis: report of 2 cases. J Neurosurg Spine. 2016;25:790-794. 16. Rumalla K, Smith K, Arnold P. Immunoglobulin G4-related epidural inflammatory pseudotumor presenting with pulmonary complications and spinal cord compression: case report. J Neurosurg Spine. 2017;26:688-693. 17. Wallace Z, Carruthers M, Khosroshahi A, et al. IgG4-related disease and hypertrophic pachymeningitis. Medicine. 2013;92:206-216. 18. Williams M, Mashaly H, Puduvalli V, Jin M, Mendel E. Immunoglobulin G4-related disease mimicking an epidural spinal cord tumor: case report. J Neurosurg Spine. 2017;26:76-80. 19. Winkel M, Lawton C, Sanusi O, Horbinski C, Dahdaleh N, Smith Z. Neuro-surgical considerations for treating IgG4-related disease with rare spinal epidural compression. Surg Neurol Int. 2018; 9:209.
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22. Lu L, Della-Torre E, Stone J, Clark S. IgG4-related hypertrophic pachymeningitis: clinical features, diagnostic criteria, and treatment. JAMA Neurol. 2014;71:785-793. 23. Palazzo E, Palazzo C, Palazzo M. IgG4-related disease. Joint Bone Spine. 2014;81:27-31.
31. Majumder S, Mohapatra S, Lennon R, et al. Rituximab maintenance therapy reduces rate of relapse of pancreaticobiliary immunoglobulin G4related disease. Clin Gastroenterol Hepatol. 2018;16: 1947-1953.
24. Stone J, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366:539-551.
32. Tang S, Lin M, Du J, Liu Y, Hsiao H, Liu T. IgG4related disease with bone marrow involvement mimicking multiple myeloma. Br J Hematol. 2017; 177:673.
25. Horger M, Lamprecht H, Bares R, et al. Systemic IgG4-related sclerosing disease: spectrum of imaging findings and differential diagnosis. AJR Am J Roentgenol. 2012;199:276-282.
33. Li L, Ward B, Cocks M, Kheradmand A, Francis H. IgG4-related disease of bilateral temporal bones. Ann Otol Rhinol Laryngol. 2017;126:236-240.
26. Chuang T, Hsu B, Chi C, Wang Y. Gallium SPECT/CT in evaluation of IgG4-related disease a case report and literature review. Medicine. 2016; 95:37. 27. Lin F, Bentao Y, Junfang X, et al. Computed tomography findings of tissue adjacent to thoracic vertebrae involved by IgG4-related disease. Natl Med J China. 2014;94:3262-3264. 28. Takahashi H, Yamashita H, Morooka M, et al. The utility of FDG-PET/CT and other imaging techniques in the evaluation of IgG4-related disease. Joint Bone Spine. 2014;81:331-336.
20. Menezes A. Craniovertebral junction anomalies: diagnosis and management. Semin Pediatr Neurol. 1997;4:209-223.
29. Wang L, Zhang P, Wang M, et al. Failure of remission induction by glucocorticoids alone or in combination with immunosuppressive agents in IgG4-related disease: a prospective study of 215 patients. Arthritis Res Ther. 2018;20:65.
21. Wallace Z, Zhang Y, Perugino C, Naden R, Choi H, Stone J. Clinical phenotypes of IgG4related disease: an analysis of two international cross-sectional cohorts. Ann Rheum Dis. 2019;78: 406-412.
30. Caso F, Fiocco U, Costa L, Sfriso P, Punzi L, Doria A. Successful use of rituximab in a young patient with immunoglobulin G4-related disease and refractory scleritis. Joint Bone Spine. 2014;81: 190-192.
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34. Dlouhy B, Dahdaleh N, Menezes A. Evolution of transoral approaches, endoscopic endonasal approaches, and reduction strategies for treatment of craniovertebral junction pathology: a treatment algorithm update. Neurosurg Focus. 2015;38:E8. 35. Lopez A, Scheer J, Leibl K, Smith Z, Dlouhy B, Dahdaleh N. Anatomy and biomechanics of the craniovertebral junction. Neurosurg Focus. 2015;38: E2.
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 20 October 2019; accepted 31 October 2019 Citation: World Neurosurg. (2020) 134:264-271. https://doi.org/10.1016/j.wneu.2019.10.195 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter Published by Elsevier Inc.
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IgG4-Related Disease of the Craniovertebral Junction Brian J. Park1, Rachel Starks2, Patricia Kirby2, Arnold H. Menezes1, Brian J. Dlouhy1,3,4
Key words Bone - Craniovertebral junction - IgG4-related disease - Spine -
Abbreviations and Acronyms CRP: C-reactive protein CT: Computed tomography CVJ: Craniovertebral junction ESR: Erythrocyte sedimentation rate hpf: High-power field IgG4-RD: Immunoglobulin G4erelated disease MRI: Magnetic resonance imaging PET: Positron emission tomography From the Departments of 1Neurosurgery and 2Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa; and 3 Pappajohn Biomedical Institute and 4Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA To whom correspondence should be addressed: Brian J. Dlouhy, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2020) 134:264-271. https://doi.org/10.1016/j.wneu.2019.10.195 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com
- BACKGROUND:
The majority of the abnormalities and diseases that affect the craniovertebral junction (CVJ) have already been reported, and therefore it is exceedingly rare to identify new pathology that affects the CVJ. Immunoglobulin G4erelated disease (IgG4-RD) is an immune mediated process treated with immunosuppressive medications. To our knowledge, this is the first reported case of IgG4-RD affecting the CVJ.
- CASE
DESCRIPTION: The authors report the case of a woman aged 71 years with IgG4-RD of the CVJ. She presented with intractable left occipital pain and limited flexion, extension, and rotation of the neck. Computed tomography and magnetic resonance imaging revealed a lytic enhancing lesion of the left occipital condyle, left C1 lateral mass, and left C1 anterior arch resulting in cranial settling, basilar invagination, and CVJ instability. An open biopsy, subtotal resection, and occiput to C2 fusion was performed. Pathology revealed IgG4-RD. The patient was subsequently placed on rituximab immunotherapy with complete resolution of enhancement on magnetic resonance imaging and bone growth at the previous site of the lytic IgG4-RD lesion.
- CONCLUSIONS:
To our knowledge, this case describes the first case of IgG4RD affecting the CVJ, which mimicked a tumor-like process. When IgG4-RD affects the CVJ, stability must be accounted for, especially in the cases of osteolytic destruction. The combination of medical therapy to target the underlying inflammatory process and surgery to provide structural stability was successful.
1878-8750/$ - see front matter Published by Elsevier Inc.
INTRODUCTION The majority of the abnormalities and diseases that affect the craniovertebral junction (CVJ) have already been reported, and therefore it is exceedingly rare to identify new pathology that affects the CVJ. Immunoglobulin G4erelated disease (IgG4-RD) is a rare but increasingly recognized immune mediated disorder.1 It is characterized by pathological findings of lymphoplasmacytic lesions rich in IgG4, and a storiform pattern of fibrosis that can lead to pseudotumors of the affected organ.1,2 Multiple organ systems can be affected.1,3,4 Rare cases affecting the central nervous system and spine have been described in the literature.3-19 The CVJ is comprised of the occiput, atlas vertebra, axis vertebra, and accompanying musculature and ligaments. Numerous pathologies affecting the CVJ have been reported that
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can lead to a variety of clinical symptoms as a result of instability.20 Here we present, to our knowledge, the first reported case of IgG4-RD affecting the CVJ resulting in an unusual lytic destruction of the CVJ with subsequent cranial settling, basilar invagination, and instability. We describe the diagnostic workup, and subsequent surgical and medical treatment. We also describe the clinical, pathological, and anatomic characteristics of IgG4-RD of the CVJ. CASE REPORT History and Examination A women aged 71 years presented with 4 months of worsening left occipital pain, which occurred spontaneously on awakening 1 morning. She was evaluated and treated by a pain clinic with an occipital nerve block, epidural steroid injection, gabapentin, and ibuprofen, all without any
significant relief. The pain became intractable. The patient had significant limitation of flexion, extension, and rotation of the neck. A computed tomography (CT) scan done 4 months prior to presentation was unremarkable (Figure 1AeD). A repeat CT scan was performed on presentation, which revealed a lytic lesion involving the left occipital condyle and the left lateral mass and anterior arch of C1 (Figure 2BeD). A magnetic resonance imaging (MRI) study showed a contrastenhancing lesion of the left occipital condyle, left lateral mass, left anterior arch of C1, inferior margin of the clivus, tip of the dens, and adjacent soft tissue (Figure 2FeH). Basilar invagination with a retroodontoid-calcified lesion was also evident (Figure 2A and E). To further identify this pathology, which at this point included tumor or an infectious process, a positron emission tomography
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Figure 1. Computed tomography (CT) scan at onset of symptoms was normal. Cervical CT scan performed at onset of symptoms 4 months prior to presentation to our hospital
(PET) scan was conducted that showed a hypermetabolic left occipital condyle and left lateral mass lesion (Figure 3A). A nuclear white blood cell scan was also performed with no increased uptake of white blood cells in the left occipital condyle and left lateral mass region (Figure 3B), confirming this was not an infection. The patient was placed in a Miami J cervical collar (American Prosthetics & Orthotics, Iowa City, Iowa, USA) during the diagnostic and surgical workup. She had significant pain relief after being placed in the collar. A percutaneous biopsy was deemed too difficult to obtain. With evidence of a progressive lytic lesion with findings of cranial settling with basilar impression and instability leading to intractable pain with need for a diagnosis, an open biopsy with occiput-C2 posterior fusion was offered. The patient elected to undergo surgical management.
Surgical Treatment The patient was placed under 7 pounds of crown halo stabilization and traction. Midline occipital-cervical incision was used to expose the occiput, C1, and C2. The left
showing unremarkable findings in (A) sagittal, (B) left parasagittal, (C) coronal, and (D) axial views.
C1 lamina was removed to access the more anterior C1 lateral mass. The left C1 lateral mass was found to have a lytic component, as well as a soft tumor-like component, grayish in nature, which was resected and sent for pathology. An occipital plate, occipital screws, and C2 bilateral pars screws were then instrumented. Bilateral hinged rods were used to complete the instrumentation. Calvarial bone graft was harvested and used for osseous fusion. Closure was carried out in multiple layers to reapproximate the muscle, fascia, subcutaneous tissue, and skin.
identified (Figure 4B). Plasma cells were found to equally express kappa or lambda light chains, suggesting this was not multiple myeloma. However, immunohistochemistry for expression of IgG and IgG4 identified 151 IgGpositive cells per high-power field (hpf) and 226 IgG4-positive cells per hpf, with an IgG4/IgG ratio of 1.50 (Figure 4C and D). With >10 IgG4positive plasma cells per hpf and a IgG4/IgG ratio >0.4, these findings met criteria for IgG4-RD.
Pathology The histopathology of the mass showed predominantly small fragments of bone and dense fibrous tissue with mixed acute and chronic inflammatory cells. In some areas, giant cells were present, likely a reaction to bony fragments, as well as inflammatory cells (Figure 4A). The inflammatory cells were confirmed by an immunohistochemical panel of stains to represent a mixed population of lymphocytes, plasma cells, and macrophages. Notably, areas containing mature plasma cells were
Postoperative Course and Treatment The patient did well after surgery with an almost immediate significant reduction in neck pain. Although the IgG4 levels on histology indicated IgG4-RD, the presentation, location, and imaging of this lytic mass was unlike any other previous case of IgG4-RD. Therefore, an extensive malignancy workup was performed to completely rule out myeloma or other tumor with repeat PET scan, MRI of the body, and bone marrow biopsy with cytogenetics and fluorescence in situ hybridization for myeloma panel. A serum protein electrophoresis
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Figure 2. Computed tomography (CT) and magnetic resonance imaging (MRI) showing lytic lesion in left lateral mass of C1, condyle, and anterior arch of C1 causing basilar invagination and instability. CT scan performed 4 months after the onset of symptoms (preoperatively) in the (A) midsagittal, (B) left parasagittal, (C) coronal, and (D) axial plane showing basilar invagination (arrow) and lytic process (asterisk) of the left C1 lateral mass,
with measurement of serum-free kappa and lambda light chains was conducted. A 24hour urine electrophoresis was also done. All of these studies were unremarkable for a
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left condyle, and anterior arch of C1. T1-weighted postcontrast MRI performed at the same time as the CT in the (E) sagittal, (F) left parasagittal, and (G, H) axial views showing retroodontoid mass and basilar invagination (arrow) with enhancement (asterisk) of the dens, left C1 lateral mass, occipital condyle, anterior arch of C1, and adjacent soft tissue.
monoclonal plasma cell disease or neoplastic process. Additional workup with CT scan of chest, abdomen, and pelvis was
unremarkable for additional sites of IgG4RD. IgG4, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were obtained and followed (Table 1). The
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Figure 3. Positron emission tomography (PET) showing hypermetabolic lesion and single-photon emission computerized tomography (SPECT) showing decreased white blood cell (WBC) activity in left lateral mass of C1 and condyle. PET scan and WBC SPECT scan performed preoperatively during diagnostic workup to further evaluate differential diagnosis including tumor or
patient was started on rituximab infusions in place of prednisone because of her instrumentation and fusion. She received
infectious processes. (A) PET scan shows a hypermetabolic lesion (arrow) at the area of left lateral mass of C1 and occipital condyle. (B) WBC SPECT scan shows decreased activity (arrow) at the area of left lateral mass C1 and occipital condyle suggesting the lesion was a bone marrow replacing lesion and not an infection.
two 1000 mg rituximab infusions spaced 15 days apart approximately 3 months after surgery. This led to a drop in IgG4
Figure 4. Histomorphology of deep lateral craniovertebral mass. (A) Hematoxylin and eosin (H&E) stain at 200x magnification showing tissue fragment with bone, fibrosis, and a mixed acute and chronic inflammation with a foreign body giant cell reaction (arrows),
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levels and inflammatory markers. A 5month postoperative CT scan showed stable alignment with interval bone
and (B) 400x magnification showing an accumulation of plasma cells. (C) Immunohistochemical stains highlight IgG expressing plasma cells and (D) IgG4 expressing plasma cells, both at 400x magnification.
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Table 1. Postoperative Immunoglobulin G4, Erythrocyte Sedimentation Rate, and C-Reactive Protein Measurements Time after Surgery
1 Month
5 Months
8 Months
12 Months
15 Months
IgG4 (1e123 mg/dL)
245
196
168
229
185
ESR (0e20 mm/hr)
30
20
17
12
14
CRP (<0.5 mg/dL)
0.9
<0.5
<0.5
<0.5
<0.5
Values in ( ) indicate the reference range of normal values. The patient was treated with rituximab at 3 months and 9 months after surgery. IgG4, immunoglobulin G4; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.
growth within the previous lytic areas seen preoperatively (Figure 5BeD). MRI showed resolution of the abnormal enhancement seen in the same location as the lytic lesion (Figure 5EeG). The basilar invagination seen previously stabilized (Figure 5A). The ESR and CRP levels normalized following rituximab therapy throughout the entire follow-up period. IgG4 levels showed a more variable course. IgG4 levels initially decreased 5 months postoperatively and again 8 months postoperatively. She received another two 1000 mg rituximab infusions 9 months postoperatively. Twelve months postoperatively, her IgG4 levels rose. However, clinically she remained asymptomatic and was observed. At her most recent 15-month immunology testing, IgG4 levels continued to be mildly elevated, but decreased from the 9-month follow-up and inflammatory markers remained low. She is now 2 years since diagnosis and surgery with a continued decline in IgG4 levels, and the patient continues to endorse resolution of clinical symptoms. A maintenance course of rituximab was not pursued, and continued surveillance with inflammatory markers is planned. DISCUSSION IgG4-RD is a relatively new and uncommon disease. To our knowledge, this is the first reported case of IgG4-RD affecting the CVJ. IgG4-RD IgG4-RD is an immune mediated fibroinflammatory disease, characterized by unique pathological features that can affect a multitude of different organs. Classification system of phenotypes based
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on the distribution of organs affected has been previously described.21 The classic histopathological characteristics of IgG4RD have been described as lymphoplasmacytic infiltration, a storiform pattern of fibrosis, and obliterative phlebitis.1,2,22-24 A mix of lymphocytes and plasma cells with predominantly IgG4positive plasma cells are present. The ratio of IgG4/IgG-positive cells is >0.4. The storiform pattern of fibrosis describes radially arranged, interlaced, and often whorled pattern of collagen fibers. Although a specific storiform pattern can sometimes be absent, some sort of fibrosis is always present.2,25 Our patient showed a dense pattern of fibrosis along with a predominance of IgG4-positive plasma cells with an IgG4/IgG ratio of 1.50. The pathophysiology behind IgG4-RD is not fully understood but is generally thought that IgG4 antibodies are not the driving force behind the disease.1,23,24 Rather, CD4 T cells drive the process by activating innate immune cells leading to cytokine release, which is sustained by plasma cells and antigen presenting B cells.1,23,24 Possibly through the same antigen, another T follicular helper cell drives the development of germinal centers and the production of IgG4secreting plasmablasts and plasma cells.1,23,24 Diagnosis is based on tissue biopsy and clinicopathological correlation.1 Imaging can be nonspecific but often show organ infiltration with surrounding inflammation and fibrosis. CT, MRI, single-photon emission CT, and PET scans have all been described for use in the local and systemic workup of IgG4RD.25-28 There can be an elevation of IgG4 serum levels, but this is not always
the case. Increased ratio of IgG4 to IgG serum levels can increase the specificity.1 Measuring IgG4 levels can be a marker for disease activity but is not always reliable. Additional surveillance with inflammatory markers has been used for monitoring disease activity.29 This strategy was implemented in our patient who showed a persistently decreased ESR and CRP after treatment but had varying serum IgG4 levels. The first-line treatment for IgG4-RD are glucocortiocoids.1 In steroid-resistant or contraindicated patients, second-line treatments with steroid-sparing immunosuppressants have been used.1,30 B cell depletion with rituximab is described as well. This method targets CD20-positive cells, interfering with the repletion of IgG4-producing plasma cells.1 Relapses have been reported after initial successful treatment.29 There have been reports describing maintenance regimens aimed to reduce relapse rates.31 Our patient received rituximab therapy as a way to avoid steroids to promote spinal fusion postoperatively. She responded well clinically and radiographically. Maintenance therapy was not pursued after consideration of the potential risks associated with chronic immunosuppression. IgG4-RD of the Spine IgG4-RD of the central nervous system is relatively uncommon, and IgG4-RD of the spine is rare. Only 19 cases affecting the spine have been described in the literature (Table 2).3-19 Most of these cases involve the dura with hypertrophic pachymeningitis with diffuse thickening of the dura or an epidural compressive lesion. Homogenous enhancement in postcontrast MRI scans is usually seen. There are 2 cases that have occurred intradural extramedullary.5,11 Bony spine involvement is rare. There is only 1 other report in which the vertebral bodies were affected. In this case, IgG4-RD of soft tissue origin extended into the bony elements.16 IgG4-RD primarily affecting the bone in general is rare and can mimic the appearance of myeloma.32 Three cases primarily in the temporal bone have also been reported.33 In the case described here, the disease presented as primary lytic lesions of the C1 vertebrae and left occipital condyle. To our knowledge, it is
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Figure 5. Postoperative imaging, computed tomography (CT) scan performed 5 months postoperatively after occipital-cervical instrumentation and fusion in the (A) sagittal, (B) left parasagittal, (C) coronal, and (D) axial plane showing stabilization of the basilar invagination (arrow), and bone growth (asterisk) within the previous lytic region involving the left condyle, left C1 lateral mass, and left anterior arch of C1. T1-weighted postcontrast
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magnetic resonance imaging performed at the same time as the CT in the (E) left parasagittal, (F) coronal, and (G) axial plane showing resolution of the enhancement (asterisk) seen previously in the left C1 lateral mass, occipital condyle, anterior arch of C1, and adjacent soft tissue. (H) Postoperative radiograph showing occipital-cervical instrumentation and early osseous fusion along the occiput, lateral mass of C1 and C2.
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Table 2. Case Reports of Immunoglobulin G4eRelated Disease of the Spine Author
Spinal Region
Location
T3-T5
Intradural, extramedullary
Chan et al., 2009
T5-T10
Epidural
Choi et al., 20107
T9-T11
Epidural
8
T2-T3
Epidural
9
T10-T12
Epidural
C4-T2
Epidural
Kim et al., 2014
C7-T5
Intradural, extramedullary
Lindstrom et al., 201012
C3-C7
Dural
C2-T9
Dural
Maher et al., 2017
C6-L2
Dural
Milhoushev et al., 20143
C5-T10
Dural
Bridges et al., 20175 6
Ezzeldin et al., 2014 Ferreira et al., 2016 Gu et al., 201610 11
Lu et al., 2016
13 14
15
Radotra et al., 2016
L1-L3
Dural
Rumalla et al., 201716
T4-T6
Epidural extension into vertebral bodies
Sato et al., 20154
T2-T12
Paraspinal
17
L5
Dural
Williams et al., 201718
C4-T1
Epidural and paraspinal
Winkel et al., 201819
L2-L3
Epidural
Wallace et al., 2013
the first reported case involving a lesion originating in the CVJ, and the first case in the spine that appeared to originate in the bone.
CVJ Pathologies The CVJ consists of the occipital bones that surround the foramen magnum, the atlas, the axis, and the associated musculature and ligaments.20,34,35 Flexion and extension of the neck occurs at the occipital-atlas joint, and rotation occurs at the atlantoaxial joint.20 In our case, osteolysis of the occipital condyle and lateral mass of C1 severely limited the patient's neck motion and caused intractable pain. Basilar invagination implies prolapse of the dens through the foramen magnum often leading to impression into the medulla. Softening of the skull with cranial settling is one way basilar impression can form.20 In our patient, the osteolytic lesions led to instability with cranial settling and basilar impression. Subsequent surgical treatment with an occipital-cervical fusion led to resolution of symptoms and radiographic stabilization.
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CONCLUSIONS To our knowledge, this case describes the first case of IgG4-RD affecting the CVJ, which mimicked a tumor-like process. When IgG4-RD affects the CVJ, stability must be accounted for, especially in the cases of osteolytic destruction. The combination of medical therapy to target the underlying inflammatory process and surgery to provide structural stability was successful. REFERENCES 1. Kamisawa T, Zen Y, Pillai S, Stone J. IgG4-related disease. Lancet. 2015;385:1460-1471. 2. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181-1192. 3. Miloushev V, Cabrera M, Ichise M. A case of immunoglobulin 4-related disease. Clin Nucl Med. 2014;39:537-539. 4. Sato M, Kodaira M, Ishii W, et al. Multifocal fibrosclerosis with hypertrophic pachymeningitis and a soft tissue mass around the thoracic vertebral bodies: a case report with review of the literature. Intern Med. 2015;54:2267-2272. 5. Bridges K, DeDeaux C, Than K. IgG4-related disease presenting as intradural extramedullary
lesion: a case report and review of the literature. Br J Neurosurg. 2017;31:1-7. 6. Chan S, Cheuk W, Chan K, Chan J. IgG4-related sclerosing pachymeningitis: a previously unrecognized form of central nervous system involvement of IgG4-related sclerosing disease. Am J Surg Pathol. 2009;33:1249-1252. 7. Choi S, Lee S, Khang S, Jeon S. IgG4-related sclerosing pachymeningitis causing spinal cord compression. Neurology. 2010;75:1388-1390. 8. Ezzeldin M, Sawagfeh A, Schnadig V, Smith RG, Fang X. Hypertrophic spinal pachymeningitis: idiopathic vs. IgG4-related. J Neurol Sci. 2014;347: 398-400. 9. Ferreira N, Vaz R, Carmona S, et al. IgG4-related disease presenting with an epidural inflammatory pseudotumor: a case report. J Med Case Rep. 2016; 10:61. 10. Gu R, Hao P, Liu J, Wang Z. Cervicothoracic spinal cord compression caused by IgG4-related sclerosing pachymeningitis: a case report and literature review. Eur Spine J. 2016;25:147-151. 11. Kim S, Kang Y, Oh S, Paik S, Kim J. Paraplegia in a patient with IgG4-related sclerosing disease: a case report. Ann Rehabil Med. 2014;38:856-860. 12. Lindstrom K, Cousar J, Lopes M. IgG4-related meningeal disease: clinic-pathological features and proposal for diagnostic criteria. Acta Neuropathol. 2010;120:765-776.
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13. Lu Z, Tongxi L, Jie L, et al. IgG4-related spinal pachymeningitis. Clin Rehumatol. 2016;35: 1549-1553. 14. Maher M, Zanazzi G, Faust P, Nickerson K, Wong T. IgG4-related hypertrophic pachymeningitis of the spine with MPO-ANCA seropositivty. Clin Imaging. 2017;46:108-112. 15. Radotra B, Aggarwal A, Kapoor A, Singla N, Chatterjee D. An orphan disease: IgG4-related spinal pachymeningitis: report of 2 cases. J Neurosurg Spine. 2016;25:790-794. 16. Rumalla K, Smith K, Arnold P. Immunoglobulin G4-related epidural inflammatory pseudotumor presenting with pulmonary complications and spinal cord compression: case report. J Neurosurg Spine. 2017;26:688-693. 17. Wallace Z, Carruthers M, Khosroshahi A, et al. IgG4-related disease and hypertrophic pachymeningitis. Medicine. 2013;92:206-216. 18. Williams M, Mashaly H, Puduvalli V, Jin M, Mendel E. Immunoglobulin G4-related disease mimicking an epidural spinal cord tumor: case report. J Neurosurg Spine. 2017;26:76-80. 19. Winkel M, Lawton C, Sanusi O, Horbinski C, Dahdaleh N, Smith Z. Neuro-surgical considerations for treating IgG4-related disease with rare spinal epidural compression. Surg Neurol Int. 2018; 9:209.
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22. Lu L, Della-Torre E, Stone J, Clark S. IgG4-related hypertrophic pachymeningitis: clinical features, diagnostic criteria, and treatment. JAMA Neurol. 2014;71:785-793. 23. Palazzo E, Palazzo C, Palazzo M. IgG4-related disease. Joint Bone Spine. 2014;81:27-31.
31. Majumder S, Mohapatra S, Lennon R, et al. Rituximab maintenance therapy reduces rate of relapse of pancreaticobiliary immunoglobulin G4related disease. Clin Gastroenterol Hepatol. 2018;16: 1947-1953.
24. Stone J, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366:539-551.
32. Tang S, Lin M, Du J, Liu Y, Hsiao H, Liu T. IgG4related disease with bone marrow involvement mimicking multiple myeloma. Br J Hematol. 2017; 177:673.
25. Horger M, Lamprecht H, Bares R, et al. Systemic IgG4-related sclerosing disease: spectrum of imaging findings and differential diagnosis. AJR Am J Roentgenol. 2012;199:276-282.
33. Li L, Ward B, Cocks M, Kheradmand A, Francis H. IgG4-related disease of bilateral temporal bones. Ann Otol Rhinol Laryngol. 2017;126:236-240.
26. Chuang T, Hsu B, Chi C, Wang Y. Gallium SPECT/CT in evaluation of IgG4-related disease a case report and literature review. Medicine. 2016; 95:37. 27. Lin F, Bentao Y, Junfang X, et al. Computed tomography findings of tissue adjacent to thoracic vertebrae involved by IgG4-related disease. Natl Med J China. 2014;94:3262-3264. 28. Takahashi H, Yamashita H, Morooka M, et al. The utility of FDG-PET/CT and other imaging techniques in the evaluation of IgG4-related disease. Joint Bone Spine. 2014;81:331-336.
20. Menezes A. Craniovertebral junction anomalies: diagnosis and management. Semin Pediatr Neurol. 1997;4:209-223.
29. Wang L, Zhang P, Wang M, et al. Failure of remission induction by glucocorticoids alone or in combination with immunosuppressive agents in IgG4-related disease: a prospective study of 215 patients. Arthritis Res Ther. 2018;20:65.
21. Wallace Z, Zhang Y, Perugino C, Naden R, Choi H, Stone J. Clinical phenotypes of IgG4related disease: an analysis of two international cross-sectional cohorts. Ann Rheum Dis. 2019;78: 406-412.
30. Caso F, Fiocco U, Costa L, Sfriso P, Punzi L, Doria A. Successful use of rituximab in a young patient with immunoglobulin G4-related disease and refractory scleritis. Joint Bone Spine. 2014;81: 190-192.
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34. Dlouhy B, Dahdaleh N, Menezes A. Evolution of transoral approaches, endoscopic endonasal approaches, and reduction strategies for treatment of craniovertebral junction pathology: a treatment algorithm update. Neurosurg Focus. 2015;38:E8. 35. Lopez A, Scheer J, Leibl K, Smith Z, Dlouhy B, Dahdaleh N. Anatomy and biomechanics of the craniovertebral junction. Neurosurg Focus. 2015;38: E2.
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 20 October 2019; accepted 31 October 2019 Citation: World Neurosurg. (2020) 134:264-271. https://doi.org/10.1016/j.wneu.2019.10.195 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter Published by Elsevier Inc.
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