Photo Essay Section Editor: Timothy J. McCulley, MD
Optic Neuropathy Secondary to Eosinophilic Angiocentric Fibrosis Adam P. Lloyd, MSc (Hons), MBChB, James D. Benzimra, MBBS, FRCOphth, Adrian T. Warfield, MBChB, FRCPath, Balaji T. S. Prasad, MS, DNB, FRCSEd, Timothy D. Matthews, BSc, MBBS, DO, FRCS, FRCOphth, Shahzada K. Ahmed, BSc (Hons) DLO, MBChB, FRCS (ORL-HNS), PhD
FIG. 1. A. Axial computed tomography demonstrates sclerosis and thickening of the lateral wall of the opacified left sphenoid sinus (arrow). B. Postcontrast T1 fat-suppressed axial magnetic resonance imaging shows moderately enhancing soft tissue mass surrounding prechiasmal left optic nerve (arrows). There is flattening of the left globe. C. Postcontrast T1 image confirms opacificity of the left sphenoid sinus with involvement of the left cavernous sinus (arrow). Abstract: Eosinophilic angiocentric fibrosis (EAF) is a rare fibroinflammatory disorder with a predilection for upper respiratory tract submucosa. We report a 45-year-old man with progressive unilateral visual loss secondary to a retroorbital soft tissue mass with histological features consistent with EAF. The patient experienced marked improvement in vision after endoscopic optic nerve decompression through sphenoethmoidectomy. Journal of Neuro-Ophthalmology 2015;35:45–47 doi: 10.1097/WNO.0000000000000175 © 2014 by North American Neuro-Ophthalmology Society
Department of Otolaryngology (APL, SKA), University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom; Birmingham Neuro-Ophthalmology Unit (JDB, TDM), Department of Ophthalmology, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom; Department of Pathology (AW), University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom; Department of Ophthalmology (BTSP), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom. The authors report no conflicts of interest. Address correspondence to Adam Lloyd, MSc (Hons), MBChB, Office 30, Education Centre, New Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB, United Kingdom; E-mail: [email protected] Lloyd et al: J Neuro-Ophthalmol 2015; 35: 45-47
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45-year-old man was referred for progressive visual loss in his left eye. Three years previously, he developed epistaxis and headaches and was found to have a positive antineutrophil cytoplasmic antibody and elevated protein 3 (PR3). His renal function was normal, and although a tissue diagnosis was not obtained, the patient was diagnosed with presumed granulomatosis with polyangitis (GPA) (formerly Wegener granulomatosis). His symptoms resolved with steroid therapy, and he was maintained on steroids, azathioprine, and co-trimoxazole. Twelve months before referral to our hospital, he became aware of a gradual reduction in vision in his left eye accompanied by mild retroorbital pain. On presentation to his local ophthalmology department, vision was 20/ 25 bilaterally, and choroidal folds were noted in the left eye. Inflammatory markers and PR3 were within normal limits. On neuroimaging, there was enhancing soft tissue at the left orbital apex, encompassing the intracranial optic nerve and involving the left cavernous sinus and pterygopalatine fossa (Fig. 1). The bony anatomy showed evidence of sclerosis and thickening of the lateral wall of the opacified left sphenoid sinus. The patient was prescribed 80 mg of prednisone, but, on tapering, the vision 45
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
Photo Essay in the left eye continued to deteriorate over the next 4 months to 20/100. On referral to our institution, visual acuity was 20/15 in the right eye and 20/100 in the left eye. Color vision was reduced in the left eye, and there was a left relative afferent pupillary defect and a centrocecal scotoma in the left visual field. External ocular examination and ocular motility were normal. Although the right fundus appeared normal, there was left temporal disc pallor and choroidal folds. The patient underwent endoscopic decompression of the left optic nerve through sphenoethmoidectomy. Biopsy specimens showed marked fibrosis with a perivascular onion-skin pattern and a lymphoplasmacytic infiltrate along with some eosinophils (Fig. 2). No granulomatous inflammation, necrotizing vasculitis, or obliterative thrombophlebitis were found. IgG4-positive cells were identified at a low ratio to IgG-positive cells, and serum IgG4 was normal. Fungal stains were negative. Histopathological features were consistent with a diagnosis of eosinophilic angiocentric fibrosis (EAF). The patient’s visual acuity improved to 20/30 two weeks after surgery. EAF is a progressive fibroinflammatory disorder of upper respiratory tract submucosa of uncertain etiology. Since its original description as a variant of granuloma faciale in 1983 (1) and subsequent histological classification 2 years later (2), approximately 50 reported cases have been published (3). The pathognomonic histological features of EAF progress from an
early submucosal vasculitis with predominant eosinophilic infiltrate to late stage whorled fibrosis of the microvasculature giving a characteristic “onion-skin” appearance (2,4). Typically, EAF has a predilection for the nasal cavity with patients presenting with nonspecific symptoms such as nasal obstruction or epistasix because of an enlarging sinonasal soft tissue mass (5). Ophthalmic manifestations have been reported infrequently, often with orbital involvement causing epiphora, proptosis, and diplopia (3,6–8). Our patient with EAF had a unique presentation with visual loss from compression of the retroorbital optic nerve. The pathophysiology of EAF remains uncertain. Some have suggested an association with allergic and atopic disorders (4), whereas there is recent evidence that EAF may be an IgG4 related systemic disease (9). EAF has been reported in association with granuloma faciale and atopy but has only once been documented in a patient with a confirmed diagnosis of GPA (10). It has been proposed that EAF may represent an exaggerated fibrotic reaction pattern rather than a distinct disease entity. Onion-skin fibrosis also has been reported in a sclerosing form of GPA of the orbit (11), in association with other expected features including necrotizing vasculitis and granulomatous inflammation. It is the absence of necrotizing vasculitis or granulomatous inflammation that distinguishes EAF histologically from other lesions with prominent eosinophilic infiltrates or onion-skin fibrosis (5,12).
FIG. 2. Eosinophilic angiocentric fibrosis. A. There is paucicellular dense fibro-hyaline tissue with fields of concentrically lamellated pattern (“onion skin”) consistent with an angiocentric distribution (hematoxylin & eosin, ·4). B. “Onion-skin” fibrosis is seen mantling small blood vessels and vascular remnants (hematoxylin & eosin, ·10). C. Moderately cellular fibromyxoid connective tissue is present with numerous eosinophil polymorphs, scattered small lymphocytes and a few mature plasma cells (hematoxylin & eosin, ·40). D. A mixed inflammatory cell population includes scattered mature plasma cells, a proportion of which show avid cytoplasmic IgG4 immunopositivity. There is some background reactivity, possibly representing serum IgG4 (IgG4 immunoperioxidase stain, ·40).
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Lloyd et al: J Neuro-Ophthalmol 2015; 35: 45-47
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
Photo Essay The management of EAF is challenging. Response has been poor to a variety of agents including azathioprine, dapsone, hydroxychloroquine, and tamoxifen (12). Surgical resection or debulking is commonly required with a high recurrence rate (5).
6.
7.
REFERENCES 1. Holmes DK, Panje WR. Intranasal granuloma faciale. Am J Otolaryngol. 1983;4:184–186. 2. Roberts PF, McCann BG. Eosinophilic angiocentric fibrosis of the upper respiratory tract: a mucosal variant of granuloma faciale? A report of three cases. Histopathology. 1985;9:1217–1225. 3. Karligkiotis A, Volpi L, Ferreli F, Cerati M, Kagkelari E, Meloni F, Casteinuovo P. Primary orbital eosinophilic angiocentric fibrosis with intranasal extension. Head Neck. 2014;36:E8–E11. 4. Holsinger JM, Magro C, Allen C, Powell D, Agrawal A. Eosinophilic angiocentric fibrosis. J Otolaryngol Head Neck Surg. 2008;37:E155–E158. 5. Jain R, Robblee JV, O’Sullivan-Mejia E, Lea J, Heller A, Faquin WC, Powers CN: Sinonasal eosinophilic angiocentric
Lloyd et al: J Neuro-Ophthalmol 2015; 35: 45-47
8. 9.
10.
11.
12.
fibrosis: a report of four cases and review of literature. Head Neck Pathol. 2008;2:309–315. Leibovitch I, James CL, Wormaid PJ, Selva D. Orbital eosinophilic angiocentric fibrosis cases report and review of the literature. Ophthalmology. 2006;113:148–152. Valenzuela AA, Whitehead KJ, Brown I, Sullivan TJ. Eosinophilic angiocentric fibrosis: an unusual entity producing complete lacrimal duct obstruction. Orbit. 2006;25:159–161. Kiratli H, Özseker H. Eosinophilic angiocentric fibrosis of the orbit. Clin Experiment Ophthalmol. 2008;36:274–276. Deshpande V, Khosroshahi A, Nielsen GP, Hamilos DL, Stone JH. Eosinophilic angiocentric fibrosis is a form of IgG4related systemic disease. Am J Surg Pathol. 2011;35:701–706. Loane J, Jaramillo M, Young HA, Kerr KM. Eosinophilic angiocentric fibrosis and Wegener’s granulomatosis: a case report and literature review. J Clin Pathol. 2001;54:640–641. Ostri C, Heegaard S, Prause JU. Sclerosis Wegener’s granulomatosis in the orbit. Acta Ophthalmol. 2008;86:917–920. Sunde J, Alexander KA, Reddy VVB, Woodworth BA. Intranasal eosinophilic angiocentric fibrosis: a case report and review. Head Neck Pathol. 2010;4:246–248.
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Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
Optic Neuropathy Secondary to Eosinophilic Angiocentric Fibrosis Adam P. Lloyd, MSc (Hons), MBChB, James D. Benzimra, MBBS, FRCOphth, Adrian T. Warfield, MBChB, FRCPath, Balaji T. S. Prasad, MS, DNB, FRCSEd, Timothy D. Matthews, BSc, MBBS, DO, FRCS, FRCOphth, Shahzada K. Ahmed, BSc (Hons) DLO, MBChB, FRCS (ORL-HNS), PhD
FIG. 1. A. Axial computed tomography demonstrates sclerosis and thickening of the lateral wall of the opacified left sphenoid sinus (arrow). B. Postcontrast T1 fat-suppressed axial magnetic resonance imaging shows moderately enhancing soft tissue mass surrounding prechiasmal left optic nerve (arrows). There is flattening of the left globe. C. Postcontrast T1 image confirms opacificity of the left sphenoid sinus with involvement of the left cavernous sinus (arrow). Abstract: Eosinophilic angiocentric fibrosis (EAF) is a rare fibroinflammatory disorder with a predilection for upper respiratory tract submucosa. We report a 45-year-old man with progressive unilateral visual loss secondary to a retroorbital soft tissue mass with histological features consistent with EAF. The patient experienced marked improvement in vision after endoscopic optic nerve decompression through sphenoethmoidectomy. Journal of Neuro-Ophthalmology 2015;35:45–47 doi: 10.1097/WNO.0000000000000175 © 2014 by North American Neuro-Ophthalmology Society
Department of Otolaryngology (APL, SKA), University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom; Birmingham Neuro-Ophthalmology Unit (JDB, TDM), Department of Ophthalmology, University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom; Department of Pathology (AW), University Hospitals Birmingham NHS Trust, Queen Elizabeth Hospital, Birmingham, United Kingdom; Department of Ophthalmology (BTSP), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom. The authors report no conflicts of interest. Address correspondence to Adam Lloyd, MSc (Hons), MBChB, Office 30, Education Centre, New Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB, United Kingdom; E-mail: [email protected] Lloyd et al: J Neuro-Ophthalmol 2015; 35: 45-47
A
45-year-old man was referred for progressive visual loss in his left eye. Three years previously, he developed epistaxis and headaches and was found to have a positive antineutrophil cytoplasmic antibody and elevated protein 3 (PR3). His renal function was normal, and although a tissue diagnosis was not obtained, the patient was diagnosed with presumed granulomatosis with polyangitis (GPA) (formerly Wegener granulomatosis). His symptoms resolved with steroid therapy, and he was maintained on steroids, azathioprine, and co-trimoxazole. Twelve months before referral to our hospital, he became aware of a gradual reduction in vision in his left eye accompanied by mild retroorbital pain. On presentation to his local ophthalmology department, vision was 20/ 25 bilaterally, and choroidal folds were noted in the left eye. Inflammatory markers and PR3 were within normal limits. On neuroimaging, there was enhancing soft tissue at the left orbital apex, encompassing the intracranial optic nerve and involving the left cavernous sinus and pterygopalatine fossa (Fig. 1). The bony anatomy showed evidence of sclerosis and thickening of the lateral wall of the opacified left sphenoid sinus. The patient was prescribed 80 mg of prednisone, but, on tapering, the vision 45
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
Photo Essay in the left eye continued to deteriorate over the next 4 months to 20/100. On referral to our institution, visual acuity was 20/15 in the right eye and 20/100 in the left eye. Color vision was reduced in the left eye, and there was a left relative afferent pupillary defect and a centrocecal scotoma in the left visual field. External ocular examination and ocular motility were normal. Although the right fundus appeared normal, there was left temporal disc pallor and choroidal folds. The patient underwent endoscopic decompression of the left optic nerve through sphenoethmoidectomy. Biopsy specimens showed marked fibrosis with a perivascular onion-skin pattern and a lymphoplasmacytic infiltrate along with some eosinophils (Fig. 2). No granulomatous inflammation, necrotizing vasculitis, or obliterative thrombophlebitis were found. IgG4-positive cells were identified at a low ratio to IgG-positive cells, and serum IgG4 was normal. Fungal stains were negative. Histopathological features were consistent with a diagnosis of eosinophilic angiocentric fibrosis (EAF). The patient’s visual acuity improved to 20/30 two weeks after surgery. EAF is a progressive fibroinflammatory disorder of upper respiratory tract submucosa of uncertain etiology. Since its original description as a variant of granuloma faciale in 1983 (1) and subsequent histological classification 2 years later (2), approximately 50 reported cases have been published (3). The pathognomonic histological features of EAF progress from an
early submucosal vasculitis with predominant eosinophilic infiltrate to late stage whorled fibrosis of the microvasculature giving a characteristic “onion-skin” appearance (2,4). Typically, EAF has a predilection for the nasal cavity with patients presenting with nonspecific symptoms such as nasal obstruction or epistasix because of an enlarging sinonasal soft tissue mass (5). Ophthalmic manifestations have been reported infrequently, often with orbital involvement causing epiphora, proptosis, and diplopia (3,6–8). Our patient with EAF had a unique presentation with visual loss from compression of the retroorbital optic nerve. The pathophysiology of EAF remains uncertain. Some have suggested an association with allergic and atopic disorders (4), whereas there is recent evidence that EAF may be an IgG4 related systemic disease (9). EAF has been reported in association with granuloma faciale and atopy but has only once been documented in a patient with a confirmed diagnosis of GPA (10). It has been proposed that EAF may represent an exaggerated fibrotic reaction pattern rather than a distinct disease entity. Onion-skin fibrosis also has been reported in a sclerosing form of GPA of the orbit (11), in association with other expected features including necrotizing vasculitis and granulomatous inflammation. It is the absence of necrotizing vasculitis or granulomatous inflammation that distinguishes EAF histologically from other lesions with prominent eosinophilic infiltrates or onion-skin fibrosis (5,12).
FIG. 2. Eosinophilic angiocentric fibrosis. A. There is paucicellular dense fibro-hyaline tissue with fields of concentrically lamellated pattern (“onion skin”) consistent with an angiocentric distribution (hematoxylin & eosin, ·4). B. “Onion-skin” fibrosis is seen mantling small blood vessels and vascular remnants (hematoxylin & eosin, ·10). C. Moderately cellular fibromyxoid connective tissue is present with numerous eosinophil polymorphs, scattered small lymphocytes and a few mature plasma cells (hematoxylin & eosin, ·40). D. A mixed inflammatory cell population includes scattered mature plasma cells, a proportion of which show avid cytoplasmic IgG4 immunopositivity. There is some background reactivity, possibly representing serum IgG4 (IgG4 immunoperioxidase stain, ·40).
46
Lloyd et al: J Neuro-Ophthalmol 2015; 35: 45-47
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
Photo Essay The management of EAF is challenging. Response has been poor to a variety of agents including azathioprine, dapsone, hydroxychloroquine, and tamoxifen (12). Surgical resection or debulking is commonly required with a high recurrence rate (5).
6.
7.
REFERENCES 1. Holmes DK, Panje WR. Intranasal granuloma faciale. Am J Otolaryngol. 1983;4:184–186. 2. Roberts PF, McCann BG. Eosinophilic angiocentric fibrosis of the upper respiratory tract: a mucosal variant of granuloma faciale? A report of three cases. Histopathology. 1985;9:1217–1225. 3. Karligkiotis A, Volpi L, Ferreli F, Cerati M, Kagkelari E, Meloni F, Casteinuovo P. Primary orbital eosinophilic angiocentric fibrosis with intranasal extension. Head Neck. 2014;36:E8–E11. 4. Holsinger JM, Magro C, Allen C, Powell D, Agrawal A. Eosinophilic angiocentric fibrosis. J Otolaryngol Head Neck Surg. 2008;37:E155–E158. 5. Jain R, Robblee JV, O’Sullivan-Mejia E, Lea J, Heller A, Faquin WC, Powers CN: Sinonasal eosinophilic angiocentric
Lloyd et al: J Neuro-Ophthalmol 2015; 35: 45-47
8. 9.
10.
11.
12.
fibrosis: a report of four cases and review of literature. Head Neck Pathol. 2008;2:309–315. Leibovitch I, James CL, Wormaid PJ, Selva D. Orbital eosinophilic angiocentric fibrosis cases report and review of the literature. Ophthalmology. 2006;113:148–152. Valenzuela AA, Whitehead KJ, Brown I, Sullivan TJ. Eosinophilic angiocentric fibrosis: an unusual entity producing complete lacrimal duct obstruction. Orbit. 2006;25:159–161. Kiratli H, Özseker H. Eosinophilic angiocentric fibrosis of the orbit. Clin Experiment Ophthalmol. 2008;36:274–276. Deshpande V, Khosroshahi A, Nielsen GP, Hamilos DL, Stone JH. Eosinophilic angiocentric fibrosis is a form of IgG4related systemic disease. Am J Surg Pathol. 2011;35:701–706. Loane J, Jaramillo M, Young HA, Kerr KM. Eosinophilic angiocentric fibrosis and Wegener’s granulomatosis: a case report and literature review. J Clin Pathol. 2001;54:640–641. Ostri C, Heegaard S, Prause JU. Sclerosis Wegener’s granulomatosis in the orbit. Acta Ophthalmol. 2008;86:917–920. Sunde J, Alexander KA, Reddy VVB, Woodworth BA. Intranasal eosinophilic angiocentric fibrosis: a case report and review. Head Neck Pathol. 2010;4:246–248.
47
Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
