- Email: [email protected]
Clivus Inflammatory Pseudotumor Associated with Immunoglobulin G4-Related Disease
Accepted Manuscript Clivus lesion revealed inflammatory pseudotumor associated with IgG4-related disease: a case report Hailiang Tang, MD, Guanfu Ding, MD, Ji Xiong, MD, Hongda Zhu, MD, Lingyang Hua, MD, Qing Xie, MD, Ye Gong, MD PII:
S1878-8750(18)31390-1
DOI:
10.1016/j.wneu.2018.06.174
Reference:
WNEU 8487
To appear in:
World Neurosurgery
Received Date: 8 February 2018 Revised Date:
19 June 2018
Accepted Date: 20 June 2018
Please cite this article as: Tang H, Ding G, Xiong J, Zhu H, Hua L, Xie Q, Gong Y, Clivus lesion revealed inflammatory pseudotumor associated with IgG4-related disease: a case report, World Neurosurgery (2018), doi: 10.1016/j.wneu.2018.06.174. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Clivus lesion revealed inflammatory pseudotumor associated with
2
IgG4-related disease: a case report
3
Hailiang Tang, MD1,#, Guanfu Ding, MD2,#, Ji Xiong, MD3, Hongda Zhu, MD1,
5
Lingyang Hua, MD1, Qing Xie, MD1,*, Ye Gong, MD1,*
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1
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China;
8
2
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Jiangxi Province, China;
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Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai200040,
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Department of Neurosurgery, 1st Hospital Affiliated to Gannan Medical College,
10
3
11
China.
12
#These authors contribute equally to this paper.
13
*Corresponding to: Ye Gong (No.12 Middle Wulumuqi Road, Shanghai200040,
14
China. Email: [email protected]), and Qing Xie (No.12 Middle Wulumuqi Road,
15
Shanghai200040, China. Email: [email protected]).
16 17
Acknowledgement:
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Department of Pathology, Huashan Hospital, Fudan University, Shanghai200040,
This study was supported by grants from the National Natural Science
19
Foundation of China (81372707, 81072070), and Shanghai Committee of Science and
20
Technology (15140902200, 16140903000).
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Abstract:
31
Background: Immunoglobulin G4 (IgG4)-related disease is a syndrome which had
32
just been gradually recognized recently. It features with increasing IgG4-positive
33
plasma cells and lymphocytes infiltration. However, reports of intracranial
34
pseudotumors associated with IgG4-related disease are very rare. Here, we reported a
35
rare case of clivus pseudotumor associated with IgG4-related disease mimicking
36
meningioma.
37
Case Description: The patient was a 50-year-old male who presented with abducent
38
paralysis of his right eye. Brain magnetic resonance imaging (MRI) revealed
39
uniformly enhanced mass located at rightside upper clivus area and meningioma was
40
highly suspected. The tumor was totally resected using retrosigmoid approach
41
craniotomy, which achieved sufficient decompression of the right abducent nerve.
42
Post-operation pathology revealed IgG4-related disease with IgG4 was strongly
43
positive on immunohistochemical staining. The patient in our report had no history of
44
autoimmune disease. Post-operation laboratory data revealed no elevation of IgG
45
(6.94g/L) and IgG4 (0.131g/L) either. Follow-up contrast MRI showed the lesion was
46
disappeared.
47
Conclusion: Although several cases of intrasellar hypophysitis have been reported,
48
there are seldom reports of intracranial pseudotumors associated with IgG4-related
49
disease. In differential diagnosis, it requires special attention when meningioma is
50
considered. Preoperative diagnosis is very important because inflammatory
51
pseudotumors associated with IgG4-related disease could be subject to steroid
52
therapy.
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Key words: IgG4-related disease, meningioma, inflammatory pseudotumor
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INTRODUCTION
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Immunoglobulin G4 (IgG4)-related disease was firstly described in patients with
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sclerosing pancreatitis in 2001 (1), and thereafter, with the increasing awareness of
65
the disease, it was found to be responsible for many previously unexplained
66
inflammations in other organs like lung, kidney and so on (2). In 2010, the disease
67
was named IgG4-related disease (3). IgG4-related disease is characterized by
68
increased serum IgG4-positive plasma cells, abundant infiltration of IgG4-positive
69
plasma cells, and high-grade sclerosis of the affected tissue (1-3). Although several
70
cases of intrasellar hypophysitis have been reported, there are seldom reports of
71
intracranial pseudotumors associated with IgG4-related disease (4-6). The
72
preoperative recognition of the disease is very important because IgG4-related disease
73
is likely subject to steroid therapy (7). Here, we reported a rare case of IgG4-related
74
pseudotumors at upper clivus area mimicking meningioma, and reviewed the
75
literature on such cases.
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CASE REPORT
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History and Imaging findings
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The patient in our report is a 50-year-old male, presented with two weeks’
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history of movement disability for his right eye. On physical examination, he was
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alert with right abducent paralysis and no other cranial nerves deficits. He had no past
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history of autoimmune disease or other illness. Magnetic resonance imaging (MRI) of
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the brain showed a mass located at rightside upper clivus area. The lesion showed
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isointensity signal in T1-weighted MRI, hypointensity signal in T2-weighted MRI,
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and it’s homogenous enhanced after contrast MRI (Figure 1). Thus, our initial 3
ACCEPTED MANUSCRIPT diagnosis was meningioma. Routine laboratory test showed no abnormal data. Blood
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tests for complete blood count, liver and renal function were normal. The total white
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blood cell (WBC) count was 9.13×109/L (reference range was 3.5-9.5×109/L), among
89
which neutrophils accounted for 58.7% (reference range was 40.0-75.0%), monocyte
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was 7.1% (reference range was 3.0-10.0%), lymphocyte was 29.9% (reference range
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was 20.0-50.0%), eosinophil was 3.8% (reference range was 0.4-8.0%), and basophil
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was 0.5% (reference range was 0.0-1.0%).
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Surgical intervention
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After thorough evaluation of the whole body condition, the patient underwent
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retrosigmoid craniotomy surgery with microscopy. During the operation, we found
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that the base of the tumor was located at rightside upper clivus area, and the tumor
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was yellowish, soft, mimicking meningioma in texture. We carefully exposed the
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tumor from the space between the facial nerve and trigeminal nerve, and found that
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the tumor was adhered to the facial nerve and the abducent nerve was pushed away by
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the tumor (Figure 2). We performed total removal of the tumor, which provided
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sufficient decompression of the right abducent nerve, and all the cranial nerves were
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protected well (Figure 2). Postoperatively, disturbance of right eye movement was
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improved a little, and the patient did not suffer from additional neurological deficits.
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Post-operational treatment
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One week after surgery, the histopathologic findings revealed it’s a
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fibroinflammatory lesion, with strands of sclerosing fibrosis mixed with lymphocytes
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and plasma cells (Figure 3). Immunohistochemistry revealed numerous IgG4-positive
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plasma cells that had infiltrated into the lesion (Figure 3). Thus, the pathologic
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diagnosis was IgG4-related disease. Then, we re-drawn the blood sample from the
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patient for further blood investigations, and found no elevation levels of IgG 6.94g/L
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(reference range was 7-16g/L) and IgG4 0.131g/L (reference range was 0.03-2.01g/L)
114
in the serum. Subsequent ultrasonography did not reveal any abnormalities in the 4
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pancreaticobiliary system and salivary gland. The patient in our report did not receive
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further courses of steroids therapy. Follow-up brain MRI was performed one month
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after surgery and showed the disappear of the lesion.
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DISCUSSION
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IgG4-related disease is a syndrome that forms inflammatory pseudotumor with
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increasing IgG4-positive plasma cells and lymphocytes infiltrating into the tissues,
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such as lacrimal gland, salivary gland, pancreas, bile duct, liver, kidney, and
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retroperitoneum (1, 8-10). Definitive diagnosis of IgG4-related disease should include
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the following 3 histologic criteria, proposed by a consensus group in 2012: 1) dense
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lymphoplasmocytic infiltrate; 2) fibrosis, arranged at least focally in a storiform
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pattern; and 3) obliterative phlebitis (11). In addition, patients with IgG4-related
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disease usually show increased serum IgG4 level. However, in some cases, there is no
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IgG4 level elevation. And serum IgG4 level elevation is nonspecific index for
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IgG4-related disease.
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Intracranial pseudotumor associated with IgG4-related disease is very rare, but
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there have been a few reports of these cases (12-15). In our case, the inflammatory
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pseudotumor was located at rightside upper clivus area. It was difficult for us to
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differentiate the inflammatory pseudotumor from meningioma by MRI images before
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operation. We performed craniotomy surgery, totally removed the mass and
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decompressed the right abducent nerve (Figure 2). The pathological findings revealed
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the diagnosis of IgG4-related disease (Figure 3).
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With respect of therapy, glucocorticoids are usually the first-line therapy when
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diagnosis was confirmed (2). In the cases of intracranial pseudotumor associated with
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IgG4-related disease, several cases were reported and effectively treated with
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glucocorticoids (16-21). However, in our case, we didn’t use glucocorticoid for the
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patient after surgery, and there was no lesion was found after one month’s MRI
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follow-up (Figure 1).
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The pathogenesis of IgG4-related disease is unknown, but it is believed to be an 5
ACCEPTED MANUSCRIPT antigen-driven activation of T and B cells with an overexpression of IgG4 for
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unknown reason (22-24). Multiple immune-mediated mechanisms contribute to the
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fibroinflammatory process of IgG4-related disease (1, 2). The cerebral convexity,
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parasagittal-falx, and skull base (such as sphenoid ridge regions) are common sites of
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occurrence of meningioma (25, 26), but these sites are different from the location of
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the mass in our case (clivus area).
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As mentioned above, several reports of such pseudotumors associated with
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IgG4-related disease had been shared (12-15), we think special attention should be
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paid when skull base meningioma is considered. If pre-operative diagnosis was
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suspected as IgG4-related disease, the intra-operative biopsy would be preferred and
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followed by steroids therapy. This would be a safer therapeutic plan for patients,
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because skull base mass (clivus area) was deep inside the brain, and surrounded by
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many important structures. Thus, it’s very difficult for surgery and had potential risk
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of neurological damage. Further cases need to be investigated to know more about
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this disease and long-term prognosis should be evaluated.
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CONCLUSION
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We reported a rare case of clivus inflammatory pseudotumor associated with
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IgG4-related disease confirmed by postoperative pathologic diagnosis. The male
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patient had no history of autoimmune disease, and it is difficult to differentiate from
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meningioma by MRI imaging. The patient underwent craniotomy surgery in the merit
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of sufficient decompression of his right abducent nerve compressed by the mass. Or
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he could be subject to steroid therapy if IgG4-related disease was confirmed before
167
operation. IgG4-related disease is an uncommon condition, resembling meningioma
168
in our case. Currently, more understandings on the natural history of the disease is
169
necessary, and the long-term prognosis of this disease needs to be determined.
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REFERENCES
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1. Hamano H, Kawa S, Horiuchi A, Unno H, Furuya N, Akamatsu T, et al. High serum IgG4 6
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2. Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med;366(6):539-51, 2012.
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3. Takahashi H, Yamamoto M, Suzuki C, Naishiro Y, Shinomura Y, Imai K. The birthday of a
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2010. 4. Hadjigeorgiou GF, Lund EL, Poulsgaard L, Feldt-Rasmussen U, Rasmussen ÅK, Wegener M,
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6. Yuen KCJ, Moloney KJ, Mercado JU, Rostad S, McCullough BJ, Litvack ZN, et al. A case
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7. Marlin ES, Dornbos D 3rd, Ikeda DS, Lehman NL, Powers CJ. IgG4-Related Disease: A New
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pathology of IgG4-related disease. Mod Pathol;25(9):1181-92, 2012.
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12. Li LF, Tse PY, Tsang FC, Lo RC, Lui WM, Leung GK. IgG4-Related Hypertrophic
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Pachymeningitis at the Falx Cerebrii with Brain Parenchymal Invasion: A Case Report. World
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13. Okano A, Nakatomi H, Shibahara J, Tsuchiya T, Saito N. Intracranial Inflammatory
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Pseudotumors Associated with Immunoglobulin G4-Related Disease Mimicking Multiple
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Meningiomas: A Case Report and Review of the Literature. World Neurosurg;83(6):1181.e1-4,
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2015. 14. Bakhit MS, Fujii M, Jinguji S, Sato T, Sakuma J, Saito K. Jugular Foramen Collision Tumor
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15. Seol JG, Loevner LA, O'Malley BW Jr, Grady MS. Inflammatory pseudotumor of the
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AJNR Am J Neuroradiol;32(8):E150-2, 2011.
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18. Kosakai A, Ito D, Yamada S, Ideta S, Ota Y, Suzuki N. A case of definite IgG4-related
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pachymeningitis involving cerebral parenchyma. J Neurosurg;115(6):1242-7, 2011.
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pachymeningitis. Neurology;75(15):1390-2, 2010. 19. Lindstrom KM, Cousar JB, Lopes MB. IgG4-related meningeal disease: clinico-pathological
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features and proposal for diagnostic criteria. Acta Neuropathol;120(6):765-76, 2010. 20. Mehta SH, Switzer JA, Biddinger P, Rojiani AM. IgG4-related leptomeningitis: a reversible
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cause of rapidly progressive cognitive decline. Neurology;82(6):540-2, 2014. 21. Noshiro S, Wanibuchi M, Akiyama Y, Okawa S, Ohtaki S, Sugino T, et al. IgG4-related
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disease initially presented as an orbital mass lesion mimicking optic nerve sheath meningioma.
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Brain Tumor Pathol;32(4):286-90, 2015.
22. Lee S, Choi JH, Kim CJ, Kim JH. Clinical Interrogation for Unveiling an Isolated
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Hypophysitis Mimicking Pituitary Adenoma. World Neurosurg;99:735-744, 2017.
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23. Bernreuther C, Illies C, Flitsch J, Buchfelder M, Buslei R, Glatzel M, et al. IgG4-related
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hypophysitis is highly prevalent among cases of histologically confirmed hypophysitis. Brain
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Pathol;27(6):839-845, 2017. 8
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24. Varrassi M, Gianneramo C, Arrigoni F, Cerrone P, Sucapane P, Marini C, et al. Neurological
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involvement of IgG4-related disease: description of a case and review of the literature.
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Neuroradiol J:1971400917698173, 2017. 25. Zhu HD, Xie Q, Gong Y, Mao Y, Zhong P, Hang FP, et al. Lymphoplasmacyte-rich
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meningioma: our experience with 19 cases and a systematic literature review. Int J Clin Exp
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26. Tang H, Zhu H, Wang X, Hua L, Li J, Xie Q, et al. KLF4 is a tumor suppressor in anaplastic
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meningioma stem-like cells and human meningiomas. J Mol Cell Biol;9(4):315-324, 2017.
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Figure legends:
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Figure 1: Brain CT&MRI images showed intracranial mass located at rightside
243
clivus region
A: Brain CT scan showed slightly high density lesion located at right clivus region
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without bone invasion.
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B-C: The lesion presented with isointense signal in T1-weighted MRI image (B), and
247
isointense/hypointense signal in T2-weighted MRI image (C);
248
D: The lesion showed hypointense signal in diffusion-weighted imaging (as the arrow
249
showed);
250
E-G: The mass was uniformly enhanced after contrast MRI scan, and the base of the
251
tumor was extensively stick to the adjacent dura, showing meningeal tail sign (the
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white arrow in E&G indicated), thus meningioma was highly suspected.
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H: The follow-up brain MRI showed the mass was disappeared.
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Figure 2: Intra-operative situation of the mass located at clivus area
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A: During the operation, it’s found the tumor was sticky to facial nerve, and pushed
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the abducent nerve away (1: facial nerve; 4: tumor);
258
B: After tumor resection, all the cranial nerves were protected well (1: facial nerve; 2:
259
abducent nerve; 3: trigeminal nerve). 9
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Figure 3: Histological features of the lesion revealed inflammatory pseudotumor
262
associated with IgG4-related disease
263
A: Hematoxylin and eosin (H&E) section showed the lesion is composed of
264
sclerosing fibrosis associated with dense lymphoplasmacytic infiltration (×200);
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B-D: Immunohistochemical analysis revealed an increased number of IgG4-positive
266
staining plasma cells (B, IgG, ×200; C, IgG4, ×200; D, lithocholic acid, ×200).
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Figure 4: Histological results showed no infectious organisms in the specimen.
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A: Acid-fast staining showed no tubercle bacillus was detected (×200);
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B: Periodic Acid-Schiff staining found no bacteria or fungus (×200);
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C: Silver staining showed no pathogen was identified in the specimen (×200).
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ACCEPTED MANUSCRIPT We reported a rare case of clivus inflammatory pseudotumor associated with IgG4-related disease confirmed by postoperative pathologic diagnosis. The male patient had no history of autoimmune disease, and it is difficult to differentiate from meningioma by MRI imaging. The patient underwent craniotomy surgery in the merit
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of sufficient decompression of his right abducent nerve compressed by the mass. Or he could be subject to steroid therapy if IgG4-related disease was confirmed before operation. IgG4-related disease is an uncommon condition, resembling meningioma in our case. Currently, more understandings on the natural history of the disease is
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necessary, and the long-term prognosis of this disease needs to be determined.
ACCEPTED MANUSCRIPT immunoglobulin G4: IgG4 magnetic resonance imaging: MRI
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lithocholic acid: LCA
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Conflict of Interest Statement: None
S1878-8750(18)31390-1
DOI:
10.1016/j.wneu.2018.06.174
Reference:
WNEU 8487
To appear in:
World Neurosurgery
Received Date: 8 February 2018 Revised Date:
19 June 2018
Accepted Date: 20 June 2018
Please cite this article as: Tang H, Ding G, Xiong J, Zhu H, Hua L, Xie Q, Gong Y, Clivus lesion revealed inflammatory pseudotumor associated with IgG4-related disease: a case report, World Neurosurgery (2018), doi: 10.1016/j.wneu.2018.06.174. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Clivus lesion revealed inflammatory pseudotumor associated with
2
IgG4-related disease: a case report
3
Hailiang Tang, MD1,#, Guanfu Ding, MD2,#, Ji Xiong, MD3, Hongda Zhu, MD1,
5
Lingyang Hua, MD1, Qing Xie, MD1,*, Ye Gong, MD1,*
6
1
7
China;
8
2
9
Jiangxi Province, China;
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4
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai200040,
SC
Department of Neurosurgery, 1st Hospital Affiliated to Gannan Medical College,
10
3
11
China.
12
#These authors contribute equally to this paper.
13
*Corresponding to: Ye Gong (No.12 Middle Wulumuqi Road, Shanghai200040,
14
China. Email: [email protected]), and Qing Xie (No.12 Middle Wulumuqi Road,
15
Shanghai200040, China. Email: [email protected]).
16 17
Acknowledgement:
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Department of Pathology, Huashan Hospital, Fudan University, Shanghai200040,
This study was supported by grants from the National Natural Science
19
Foundation of China (81372707, 81072070), and Shanghai Committee of Science and
20
Technology (15140902200, 16140903000).
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Abstract:
31
Background: Immunoglobulin G4 (IgG4)-related disease is a syndrome which had
32
just been gradually recognized recently. It features with increasing IgG4-positive
33
plasma cells and lymphocytes infiltration. However, reports of intracranial
34
pseudotumors associated with IgG4-related disease are very rare. Here, we reported a
35
rare case of clivus pseudotumor associated with IgG4-related disease mimicking
36
meningioma.
37
Case Description: The patient was a 50-year-old male who presented with abducent
38
paralysis of his right eye. Brain magnetic resonance imaging (MRI) revealed
39
uniformly enhanced mass located at rightside upper clivus area and meningioma was
40
highly suspected. The tumor was totally resected using retrosigmoid approach
41
craniotomy, which achieved sufficient decompression of the right abducent nerve.
42
Post-operation pathology revealed IgG4-related disease with IgG4 was strongly
43
positive on immunohistochemical staining. The patient in our report had no history of
44
autoimmune disease. Post-operation laboratory data revealed no elevation of IgG
45
(6.94g/L) and IgG4 (0.131g/L) either. Follow-up contrast MRI showed the lesion was
46
disappeared.
47
Conclusion: Although several cases of intrasellar hypophysitis have been reported,
48
there are seldom reports of intracranial pseudotumors associated with IgG4-related
49
disease. In differential diagnosis, it requires special attention when meningioma is
50
considered. Preoperative diagnosis is very important because inflammatory
51
pseudotumors associated with IgG4-related disease could be subject to steroid
52
therapy.
53
Key words: IgG4-related disease, meningioma, inflammatory pseudotumor
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54 55 56 57 2
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INTRODUCTION
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Immunoglobulin G4 (IgG4)-related disease was firstly described in patients with
64
sclerosing pancreatitis in 2001 (1), and thereafter, with the increasing awareness of
65
the disease, it was found to be responsible for many previously unexplained
66
inflammations in other organs like lung, kidney and so on (2). In 2010, the disease
67
was named IgG4-related disease (3). IgG4-related disease is characterized by
68
increased serum IgG4-positive plasma cells, abundant infiltration of IgG4-positive
69
plasma cells, and high-grade sclerosis of the affected tissue (1-3). Although several
70
cases of intrasellar hypophysitis have been reported, there are seldom reports of
71
intracranial pseudotumors associated with IgG4-related disease (4-6). The
72
preoperative recognition of the disease is very important because IgG4-related disease
73
is likely subject to steroid therapy (7). Here, we reported a rare case of IgG4-related
74
pseudotumors at upper clivus area mimicking meningioma, and reviewed the
75
literature on such cases.
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CASE REPORT
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History and Imaging findings
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The patient in our report is a 50-year-old male, presented with two weeks’
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history of movement disability for his right eye. On physical examination, he was
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alert with right abducent paralysis and no other cranial nerves deficits. He had no past
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history of autoimmune disease or other illness. Magnetic resonance imaging (MRI) of
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the brain showed a mass located at rightside upper clivus area. The lesion showed
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isointensity signal in T1-weighted MRI, hypointensity signal in T2-weighted MRI,
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and it’s homogenous enhanced after contrast MRI (Figure 1). Thus, our initial 3
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tests for complete blood count, liver and renal function were normal. The total white
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blood cell (WBC) count was 9.13×109/L (reference range was 3.5-9.5×109/L), among
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which neutrophils accounted for 58.7% (reference range was 40.0-75.0%), monocyte
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was 7.1% (reference range was 3.0-10.0%), lymphocyte was 29.9% (reference range
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was 20.0-50.0%), eosinophil was 3.8% (reference range was 0.4-8.0%), and basophil
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was 0.5% (reference range was 0.0-1.0%).
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Surgical intervention
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After thorough evaluation of the whole body condition, the patient underwent
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retrosigmoid craniotomy surgery with microscopy. During the operation, we found
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that the base of the tumor was located at rightside upper clivus area, and the tumor
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was yellowish, soft, mimicking meningioma in texture. We carefully exposed the
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tumor from the space between the facial nerve and trigeminal nerve, and found that
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the tumor was adhered to the facial nerve and the abducent nerve was pushed away by
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the tumor (Figure 2). We performed total removal of the tumor, which provided
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sufficient decompression of the right abducent nerve, and all the cranial nerves were
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protected well (Figure 2). Postoperatively, disturbance of right eye movement was
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improved a little, and the patient did not suffer from additional neurological deficits.
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Post-operational treatment
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fibroinflammatory lesion, with strands of sclerosing fibrosis mixed with lymphocytes
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and plasma cells (Figure 3). Immunohistochemistry revealed numerous IgG4-positive
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plasma cells that had infiltrated into the lesion (Figure 3). Thus, the pathologic
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diagnosis was IgG4-related disease. Then, we re-drawn the blood sample from the
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patient for further blood investigations, and found no elevation levels of IgG 6.94g/L
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(reference range was 7-16g/L) and IgG4 0.131g/L (reference range was 0.03-2.01g/L)
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in the serum. Subsequent ultrasonography did not reveal any abnormalities in the 4
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pancreaticobiliary system and salivary gland. The patient in our report did not receive
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further courses of steroids therapy. Follow-up brain MRI was performed one month
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after surgery and showed the disappear of the lesion.
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DISCUSSION
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IgG4-related disease is a syndrome that forms inflammatory pseudotumor with
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increasing IgG4-positive plasma cells and lymphocytes infiltrating into the tissues,
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such as lacrimal gland, salivary gland, pancreas, bile duct, liver, kidney, and
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retroperitoneum (1, 8-10). Definitive diagnosis of IgG4-related disease should include
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the following 3 histologic criteria, proposed by a consensus group in 2012: 1) dense
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lymphoplasmocytic infiltrate; 2) fibrosis, arranged at least focally in a storiform
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pattern; and 3) obliterative phlebitis (11). In addition, patients with IgG4-related
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disease usually show increased serum IgG4 level. However, in some cases, there is no
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IgG4 level elevation. And serum IgG4 level elevation is nonspecific index for
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IgG4-related disease.
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Intracranial pseudotumor associated with IgG4-related disease is very rare, but
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there have been a few reports of these cases (12-15). In our case, the inflammatory
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pseudotumor was located at rightside upper clivus area. It was difficult for us to
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differentiate the inflammatory pseudotumor from meningioma by MRI images before
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operation. We performed craniotomy surgery, totally removed the mass and
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decompressed the right abducent nerve (Figure 2). The pathological findings revealed
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the diagnosis of IgG4-related disease (Figure 3).
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With respect of therapy, glucocorticoids are usually the first-line therapy when
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diagnosis was confirmed (2). In the cases of intracranial pseudotumor associated with
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IgG4-related disease, several cases were reported and effectively treated with
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glucocorticoids (16-21). However, in our case, we didn’t use glucocorticoid for the
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patient after surgery, and there was no lesion was found after one month’s MRI
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follow-up (Figure 1).
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The pathogenesis of IgG4-related disease is unknown, but it is believed to be an 5
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unknown reason (22-24). Multiple immune-mediated mechanisms contribute to the
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fibroinflammatory process of IgG4-related disease (1, 2). The cerebral convexity,
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parasagittal-falx, and skull base (such as sphenoid ridge regions) are common sites of
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occurrence of meningioma (25, 26), but these sites are different from the location of
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the mass in our case (clivus area).
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As mentioned above, several reports of such pseudotumors associated with
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IgG4-related disease had been shared (12-15), we think special attention should be
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paid when skull base meningioma is considered. If pre-operative diagnosis was
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suspected as IgG4-related disease, the intra-operative biopsy would be preferred and
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followed by steroids therapy. This would be a safer therapeutic plan for patients,
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because skull base mass (clivus area) was deep inside the brain, and surrounded by
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many important structures. Thus, it’s very difficult for surgery and had potential risk
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of neurological damage. Further cases need to be investigated to know more about
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this disease and long-term prognosis should be evaluated.
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CONCLUSION
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We reported a rare case of clivus inflammatory pseudotumor associated with
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IgG4-related disease confirmed by postoperative pathologic diagnosis. The male
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patient had no history of autoimmune disease, and it is difficult to differentiate from
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meningioma by MRI imaging. The patient underwent craniotomy surgery in the merit
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of sufficient decompression of his right abducent nerve compressed by the mass. Or
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he could be subject to steroid therapy if IgG4-related disease was confirmed before
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operation. IgG4-related disease is an uncommon condition, resembling meningioma
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in our case. Currently, more understandings on the natural history of the disease is
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necessary, and the long-term prognosis of this disease needs to be determined.
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24. Varrassi M, Gianneramo C, Arrigoni F, Cerrone P, Sucapane P, Marini C, et al. Neurological
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Figure legends:
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Figure 1: Brain CT&MRI images showed intracranial mass located at rightside
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clivus region
A: Brain CT scan showed slightly high density lesion located at right clivus region
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without bone invasion.
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B-C: The lesion presented with isointense signal in T1-weighted MRI image (B), and
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isointense/hypointense signal in T2-weighted MRI image (C);
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D: The lesion showed hypointense signal in diffusion-weighted imaging (as the arrow
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showed);
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E-G: The mass was uniformly enhanced after contrast MRI scan, and the base of the
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tumor was extensively stick to the adjacent dura, showing meningeal tail sign (the
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white arrow in E&G indicated), thus meningioma was highly suspected.
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H: The follow-up brain MRI showed the mass was disappeared.
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Figure 2: Intra-operative situation of the mass located at clivus area
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A: During the operation, it’s found the tumor was sticky to facial nerve, and pushed
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the abducent nerve away (1: facial nerve; 4: tumor);
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B: After tumor resection, all the cranial nerves were protected well (1: facial nerve; 2:
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abducent nerve; 3: trigeminal nerve). 9
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Figure 3: Histological features of the lesion revealed inflammatory pseudotumor
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associated with IgG4-related disease
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A: Hematoxylin and eosin (H&E) section showed the lesion is composed of
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sclerosing fibrosis associated with dense lymphoplasmacytic infiltration (×200);
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B-D: Immunohistochemical analysis revealed an increased number of IgG4-positive
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staining plasma cells (B, IgG, ×200; C, IgG4, ×200; D, lithocholic acid, ×200).
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Figure 4: Histological results showed no infectious organisms in the specimen.
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A: Acid-fast staining showed no tubercle bacillus was detected (×200);
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B: Periodic Acid-Schiff staining found no bacteria or fungus (×200);
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C: Silver staining showed no pathogen was identified in the specimen (×200).
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ACCEPTED MANUSCRIPT We reported a rare case of clivus inflammatory pseudotumor associated with IgG4-related disease confirmed by postoperative pathologic diagnosis. The male patient had no history of autoimmune disease, and it is difficult to differentiate from meningioma by MRI imaging. The patient underwent craniotomy surgery in the merit
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of sufficient decompression of his right abducent nerve compressed by the mass. Or he could be subject to steroid therapy if IgG4-related disease was confirmed before operation. IgG4-related disease is an uncommon condition, resembling meningioma in our case. Currently, more understandings on the natural history of the disease is
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necessary, and the long-term prognosis of this disease needs to be determined.
ACCEPTED MANUSCRIPT immunoglobulin G4: IgG4 magnetic resonance imaging: MRI
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lithocholic acid: LCA
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Conflict of Interest Statement: None