CASE REPORT
Solitary Epibulbar Neurofibroma in Older Adult Patients Thais Shiota Tanaka, MD,* Victor M. Elner, MD, PhD,† and Hakan Demirci, MD*
Purpose: To report a solitary epibulbar neurofibroma in 2 elderly patients without systemic neurofibromatosis.
Methods: Case reports and literature review. Results: A 67-year-old man presented with a 2-month history of left epibulbar mass. On slit-lamp examination, an 8- · 8-mm amelanotic, translucent, gelatinous, circumscribed lesion was present deep to the nasal bulbar conjunctiva. A 60-year-old otherwise healthy man presented with a 6-week history of a subconjunctival growth causing pain and photophobia in his right eye. On slit-lamp examination, an 8- · 8-mm amelanotic, translucent, gelatinous, circumscribed subconjunctival lesion, causing a delle was present near the nasal limbus. In each case, excisional biopsy was performed and histopathologic study revealed the diagnosis of neurofibroma. In both cases, after 12 months of follow-up, there was no evidence of recurrence or systemic disease. Conclusions: Solitary epibulbar neurofibroma in older adult patients without systemic neurofibromatosis is rare but should be considered in the differential diagnosis of epibulbar tumors. Key Words: neurofibroma, conjunctival tumor, neurofibromatosis (Cornea 2015;34:475–478)
N
eurofibroma is a slow growing benign tumor that originates from peripheral nerves and is composed of axons, Schwann cells, perineurial cells, fibroblasts, and mast cells.1,2 It may present as solitary, plexiform, or multiple tumors.1 Multiple neurofibromas are usually associated with neurofibromatosis type 1 (NF1), as the presence of 2 or more neurofibromas is a diagnostic criterion for NF1.2,3 Solitary neurofibroma is not associated with NF1 and seen in the second and third decade without gender preference.1 It shows predilection for dermal tissue of the trunk and head.1,3 Solitary neurofibroma rarely involves the choroid, conjunctiva, eyelid, or orbit.1 In a review of 2455 conjunctival Received for publication October 7, 2014; revision received December 6, 2014; accepted December 11, 2014. Published online ahead of print March 2015. From the *Department of Ophthalmology and Vision Sciences, WK Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI; and †Department of Pathology, University of Michigan Medical School, Ann Arbor, MI. Supported by a generous gift from Mr and Mrs Witham. The authors have no funding or conflicts of interest to disclose. Reprints: Hakan Demirci, MD, Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, WK Kellogg Eye Center, 1000 Wall St, Ann Arbor, MI 48105 (e-mail: hdemirci@med. umich.edu). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Cornea Volume 34, Number 4, April 2015
lesions, Grossniklaus et al4 reported 2 cases of neurofibroma without any information about possible associated systemic disease. Another review of 1643 conjunctival tumors by Shields et al5 revealed only 1 case of epibulbar neurofibroma without any information concerning possible systemic disease. To the best of our knowledge, there are 6 cases with solitary conjunctival neurofibroma in the literature, ranging from the age of 22 to 78 years.1–3,6–8 Only 1 patient was older than 50 years.6 In this report, we present 2 elderly men with epibulbar neurofibromas, which presented as amelanotic epibulbar masses.
CASE REPORTS Case 1 A 67-year-old man with prostate cancer presented with a 2month history of a left epibulbar mass that had doubled in size. His visual acuity was 20/25 OD and 20/20 OS. On slit-lamp examination, an elevated amelanotic, translucent, gelatinous, circumscribed epibulbar mass deep to mobile bulbar conjunctiva measured 8 · 8 mm and was located between 7 and 11 o’clock. Surrounding dilated episcleral vessels, but no feeder vessels or intrinsic vascularization, were present (Fig. 1A). Ultrasound biomicroscopy (UBM) showed the mass to be 2-mm thick and without invasion of the sclera (Fig. 1B). An excision of the lesion with underlying episclera and cryotherapy to the surrounding tissue bed was performed. Systemic evaluation, brain magnetic resonance imaging, and family history were negative for NF1 and neurofibromatosis type 2 (NF2). After 12 months of follow-up, the patient remained healthy without recurrence or evidence of NF1 or NF2.
Case 2 A 60-year-old man presented with a 6-week history of a right eye epibulbar mass. He complained of pain and photophobia in his right eye. His visual acuity was 20/20 OU. On slit-lamp examination, conjunctival chemosis was present inferiorly and an 8- · 8-mm elevated amelanotic, translucent, gelatinous, circumscribed epibulbar mass was present deep to mobile conjunctiva near the nasal limbus. The lesion had surrounding dilated episcleral vessels, but no feeder vessels or intrinsic vascularization. Because of the elevation, a delle measuring 1.2 · 1.0 mm was noted in the nasal cornea (Fig. 2A). UBM showed no invasion of the sclera (Fig. 2B). An excisional biopsy of the lesion with underlying episclera was performed. Systemic evaluation, brain magnetic resonance imaging, and family history were negative for NF1 and NF2. After 12 months of follow-up, the patient remained without recurrence or evidence of NF1 or NF2. www.corneajrnl.com |
475
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Cornea Volume 34, Number 4, April 2015
Tanaka et al
FIGURE 1. A, Slit-lamp photograph showing an amelanotic, translucent lesion deep to the nasal conjunctiva (arrow). B, UBM showing a lesion without invasion of sclera. C–H, Photomicrograph of neurofibroma showing Schwann cells, fibroblasts, and mast cells (C); immunohistochemical positivity for S100 antigen (D), neurofilament antigen (E), CD34 antigen (F), immunonegativity for calretinin, which stains only mast cells in the tumor (G); and alcian blue positivity for mucopolysaccharides (H). (Hematoxylin– eosin staining, S100 immunostaining, neurofilament immunostaining, CD34 immunostaining, calretinin immunostaining, and alcian blue staining, respectively; all with original magnification ·200, except neurofilament, original magnification ·600).
Histopathological Analysis
The 6 solitary conjunctival neurofibroma cases reported in the literature had no sex predilection (Table 1). Four cases were between the ages of 22 and 38 years, similar to solitary
neurofibromas in the rest of the body.1–3,8 There was only 1 case of a patient older than 60 years.6 Both of our patients were older than 60 years. Although solitary conjunctival neurofibroma has been reported to be a nodular, amelanotic epibulbar mass with color varying from gray, tan, yellow, salmon, or pink, we observed the tumors to be colorless and translucent.1–3,6–8 In our cases, the lesions were gelatinous, likely because of abundant alcian blue-positive mucopolysaccharides in the extracellular matrix of the neurofibromas. Solitary epibulbar neurofibroma has been reported to be located in the temporal limbus (67%), superior limbus (12%), and inferior limbus (12%), suggestive of a ciliary nerve origin in these locations.1–3,6–8 However, in both our cases, the tumors were located near the nasal limbus. On UBM, both tumors appeared solid, consistent with the organized histopathological structure of neurofibroma and the presence of
476
Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.
Microscopically, both tumors were composed of benign spindle cells, neurites, and numerous mast cells, all consistent with neurofibroma. Immunohistochemistry of both lesions showed immunopositivity for S100 protein, CD34, and neurofilament antigens because of the presence of Schwann cells, fibroblasts, and axons, respectively. Immunohistochemistry for factor XIIIa was also positive, consistent with the presence of perineurial cells within both neurofibromas. Both tumors did not stain for calretinin or CD56 antigens. Alcian blue stain was diffusely positive, indicating the presence of abundant mucinous matrix, correlating with the gelatinous and translucent clinical appearances of the lesions (Figs, 1C–H and Figs. 2C–H).
DISCUSSION
| www.corneajrnl.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Cornea Volume 34, Number 4, April 2015
Conjunctival Neurofibroma
FIGURE 2. A, Slit-lamp photograph showing an elevated amelanotic, translucent epibulbar lesion deep to the nasal conjunctiva (black arrow) with corneal delle (white arrow). B, UBM showing a lesion without invasion of sclera. C–H, Photomicrograph showing the presence of Schwann cells, fibroblasts, and mast cells (C), with positivity for S100 antigen staining Schwann cells with axons remained unstained (D), neurofilament antigen staining of axons (E), CD34 antigen (F), immunonegativity for calretinin, which stains only mast cells in the tumor (G); and alcian blue showing positivity for mucopolysaccharides (H). (Hematoxylin–eosin staining, S100 immunostaining, neurofilament immunostaining, CD34 immunostaining, calretinin immunostaining, and alcian blue staining, respectively, original magnification ·100, except neurofilament and alcian blue, original magnification ·200).
mucopolysaccharides in the tumor matrix. There was no scleral invasion in either case. The differential diagnosis of conjunctival neurofibroma includes schwannoma, epibulbar dermoid, leiomyoma, fibrous histiocytoma, lymphoma, myxoma, nodular scleritis, mucosal neuroma, and solitary circumscribed neuroma. It is diagnosed by histopathological examination.1–3,6–8 Mucosal neuroma is a benign peripheral tumor, usually present in patients with multiple endocrine neoplasia type 2B. Solitary circumscribed neuroma is a benign, well-circumscribed, partially encapsulated spindle-cell tumor.4 It is important to differentiate a neurofibroma from a schwannoma. They are both peripheral nerve sheath tumors, Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.
but malignant degeneration is more likely to develop in large, deep-seated neurofibromas associated with neurofibromatosis.1,6 Histopathologically, solitary neurofibromas may be circumscribed, but are not encapsulated.1,3,6 In contrast, schwannomas are often encapsulated, and the capsule can be delineated with the aid of immunohistochemical stains, epithelial membrane antigen, and Glut-1.9 Immunohistochemical stains for S100 protein, neurofilament, factor XIIIa, CD34, calretinin, and CD56 assist in confirming the diagnosis.9,10 S100 protein is a preferred marker for identifying cells of neural origin, and neurofilament is a marker for axonal filaments, but they do not distinguish neurofibroma from schwannoma.9,10 Factor XIIIa stains perineurial cells within www.corneajrnl.com |
477
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Cornea Volume 34, Number 4, April 2015
Tanaka et al
TABLE 1. Cases of Neurofibroma With No History of Neurofibromatosis Reference
Age, Gender Appearance
Dabezies et al7
50, F
Perry2
22, F
Kalina et al3
34, M
Ang et al1
36, M
Kumar et al6
78, M
Mohyudin et al8
37, F
Firm, gray, nodular mass Lobulated, oval yellowwhite Solid, nodular, tan Firm, oval, grayish blue Pink, smooth, vascular Firm, smooth, salmonpink
Location
Management
Diagnosis Approach
Histopathology
Upper temporal Excision, 3· Histopathology, quadrant, OS systemic, and family history evaluation Inferior Excision Histopathology, perilimbal, systemic evaluation OD
Neurofibroma
Temporal corneoscleral limbus, OS Temporal perilimbal, OS Temporal perilimbal, OS Superior perilimbal, OS
Solitary neurofibroma
Excision
NA
Excisional biopsy
Histopathology, systemic, and family history evaluation Histopathology, systemic evaluation Histopathology, systemic, and family history evaluation
Excision
Biopsy
Immunohistochemistry Stain
Systemic Disease
Wilder, Bodian
NA
Isolated Bodian, Giemsa, reticulin 4 yrs later NF2 neurofibroma
NA
NA
Neurofibroma
S100
NA
Neurofibroma
S100, neurofilament
Bladder carcinoma
Diffuse neurofibroma
S-100, neurofilament
Hypothyroid
NA, not available; NF2, neurofibromatosis type 2.
neurofibromas, and CD34 marks perineurial fibroblasts, assisting in confirming the diagnosis of neurofibroma.10 However, calretinin, which stains plasma cells in neurofibromas, fails to stain tumor cells as it does in schwannoma.10 CD56, a sensitive marker for Schwann cells, did not stain the neurofibroma.10 Of the 6 solitary conjunctival neurofibromas published in the medical literature, only 1 case used S100 protein to confirm the diagnosis of neurofibroma; 2 used S100 and neurofilament; 2 used Bodian stain with or without Wilder, Giemsa, or reticulin histochemical stains; and 1 did not specify the stain used.1–3,6–8 The management of conjunctival neurofibroma involves excisional biopsy. Of the 6 published cases, only 1 developed multiple recurrences after the excision, none developed malignant transformations, and only 1 was diagnosed with systemic disease, NF2 after 4 years of follow-up.2,7 REFERENCES 1. Ang LP, Heng WJ, Chan WK. A case of episcleral neurofibroma. Int Ophthalmol. 1999;22:201–210.
478
| www.corneajrnl.com
2. Perry HD. Isolated episcleral neurofibroma. Ophthalmology. 1982;89: 1095–1098. 3. Kalina PH, Bartley GB, Campbell RJ, et al. Isolated neurofibromas of the conjunctiva. Am J Ophthalmol. 1991;111:694–698. 4. Grossniklaus HE, Green WR, Luckenbach M, et al. Conjunctival lesions in adults. A clinical and histopathologic review. Cornea. 1987; 6:78–116. 5. Shields CL, Demirci H, Karatza E, et al. Clinical survey of 1643 melanocytic and nonmelanocytic conjunctival tumors. Ophthalmology. 2004;111:1747–1754. 6. Kumar BV, Rennie IG, Mudhar HS. A case of episcleral cellular neurofibroma. Int Ophthalmol. 2005;26:239–241. 7. Dabezies OH Jr, Penner R. Neurofibroma or neurilemmoma of the bulbar conjunctiva. Arch Ophthalmol. 1961;66:99–101. 8. Mohyudin MN, Darrad M, Murray A, et al. Isolated diffuse episcleral neurofibroma. Orbit. 2013;32:130–131. 9. Nascimento AF, Fletcher CDM. The controversial nosology of benign nerve sheath tumors: neurofilament protein staining demonstrates intramural axons in many sporadic schwannomas. Am J Surg Pathol. 2007;31:1363–1370. 10. Park JY, Park H, Park NJ, et al. Use of calretinin, CD56, and CD34 for differential diagnosis of Schwannoma and neurofibroma. Korean J Pathol. 2011;45:30–35.
Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Solitary Epibulbar Neurofibroma in Older Adult Patients Thais Shiota Tanaka, MD,* Victor M. Elner, MD, PhD,† and Hakan Demirci, MD*
Purpose: To report a solitary epibulbar neurofibroma in 2 elderly patients without systemic neurofibromatosis.
Methods: Case reports and literature review. Results: A 67-year-old man presented with a 2-month history of left epibulbar mass. On slit-lamp examination, an 8- · 8-mm amelanotic, translucent, gelatinous, circumscribed lesion was present deep to the nasal bulbar conjunctiva. A 60-year-old otherwise healthy man presented with a 6-week history of a subconjunctival growth causing pain and photophobia in his right eye. On slit-lamp examination, an 8- · 8-mm amelanotic, translucent, gelatinous, circumscribed subconjunctival lesion, causing a delle was present near the nasal limbus. In each case, excisional biopsy was performed and histopathologic study revealed the diagnosis of neurofibroma. In both cases, after 12 months of follow-up, there was no evidence of recurrence or systemic disease. Conclusions: Solitary epibulbar neurofibroma in older adult patients without systemic neurofibromatosis is rare but should be considered in the differential diagnosis of epibulbar tumors. Key Words: neurofibroma, conjunctival tumor, neurofibromatosis (Cornea 2015;34:475–478)
N
eurofibroma is a slow growing benign tumor that originates from peripheral nerves and is composed of axons, Schwann cells, perineurial cells, fibroblasts, and mast cells.1,2 It may present as solitary, plexiform, or multiple tumors.1 Multiple neurofibromas are usually associated with neurofibromatosis type 1 (NF1), as the presence of 2 or more neurofibromas is a diagnostic criterion for NF1.2,3 Solitary neurofibroma is not associated with NF1 and seen in the second and third decade without gender preference.1 It shows predilection for dermal tissue of the trunk and head.1,3 Solitary neurofibroma rarely involves the choroid, conjunctiva, eyelid, or orbit.1 In a review of 2455 conjunctival Received for publication October 7, 2014; revision received December 6, 2014; accepted December 11, 2014. Published online ahead of print March 2015. From the *Department of Ophthalmology and Vision Sciences, WK Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, MI; and †Department of Pathology, University of Michigan Medical School, Ann Arbor, MI. Supported by a generous gift from Mr and Mrs Witham. The authors have no funding or conflicts of interest to disclose. Reprints: Hakan Demirci, MD, Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, WK Kellogg Eye Center, 1000 Wall St, Ann Arbor, MI 48105 (e-mail: hdemirci@med. umich.edu). Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Cornea Volume 34, Number 4, April 2015
lesions, Grossniklaus et al4 reported 2 cases of neurofibroma without any information about possible associated systemic disease. Another review of 1643 conjunctival tumors by Shields et al5 revealed only 1 case of epibulbar neurofibroma without any information concerning possible systemic disease. To the best of our knowledge, there are 6 cases with solitary conjunctival neurofibroma in the literature, ranging from the age of 22 to 78 years.1–3,6–8 Only 1 patient was older than 50 years.6 In this report, we present 2 elderly men with epibulbar neurofibromas, which presented as amelanotic epibulbar masses.
CASE REPORTS Case 1 A 67-year-old man with prostate cancer presented with a 2month history of a left epibulbar mass that had doubled in size. His visual acuity was 20/25 OD and 20/20 OS. On slit-lamp examination, an elevated amelanotic, translucent, gelatinous, circumscribed epibulbar mass deep to mobile bulbar conjunctiva measured 8 · 8 mm and was located between 7 and 11 o’clock. Surrounding dilated episcleral vessels, but no feeder vessels or intrinsic vascularization, were present (Fig. 1A). Ultrasound biomicroscopy (UBM) showed the mass to be 2-mm thick and without invasion of the sclera (Fig. 1B). An excision of the lesion with underlying episclera and cryotherapy to the surrounding tissue bed was performed. Systemic evaluation, brain magnetic resonance imaging, and family history were negative for NF1 and neurofibromatosis type 2 (NF2). After 12 months of follow-up, the patient remained healthy without recurrence or evidence of NF1 or NF2.
Case 2 A 60-year-old man presented with a 6-week history of a right eye epibulbar mass. He complained of pain and photophobia in his right eye. His visual acuity was 20/20 OU. On slit-lamp examination, conjunctival chemosis was present inferiorly and an 8- · 8-mm elevated amelanotic, translucent, gelatinous, circumscribed epibulbar mass was present deep to mobile conjunctiva near the nasal limbus. The lesion had surrounding dilated episcleral vessels, but no feeder vessels or intrinsic vascularization. Because of the elevation, a delle measuring 1.2 · 1.0 mm was noted in the nasal cornea (Fig. 2A). UBM showed no invasion of the sclera (Fig. 2B). An excisional biopsy of the lesion with underlying episclera was performed. Systemic evaluation, brain magnetic resonance imaging, and family history were negative for NF1 and NF2. After 12 months of follow-up, the patient remained without recurrence or evidence of NF1 or NF2. www.corneajrnl.com |
475
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Cornea Volume 34, Number 4, April 2015
Tanaka et al
FIGURE 1. A, Slit-lamp photograph showing an amelanotic, translucent lesion deep to the nasal conjunctiva (arrow). B, UBM showing a lesion without invasion of sclera. C–H, Photomicrograph of neurofibroma showing Schwann cells, fibroblasts, and mast cells (C); immunohistochemical positivity for S100 antigen (D), neurofilament antigen (E), CD34 antigen (F), immunonegativity for calretinin, which stains only mast cells in the tumor (G); and alcian blue positivity for mucopolysaccharides (H). (Hematoxylin– eosin staining, S100 immunostaining, neurofilament immunostaining, CD34 immunostaining, calretinin immunostaining, and alcian blue staining, respectively; all with original magnification ·200, except neurofilament, original magnification ·600).
Histopathological Analysis
The 6 solitary conjunctival neurofibroma cases reported in the literature had no sex predilection (Table 1). Four cases were between the ages of 22 and 38 years, similar to solitary
neurofibromas in the rest of the body.1–3,8 There was only 1 case of a patient older than 60 years.6 Both of our patients were older than 60 years. Although solitary conjunctival neurofibroma has been reported to be a nodular, amelanotic epibulbar mass with color varying from gray, tan, yellow, salmon, or pink, we observed the tumors to be colorless and translucent.1–3,6–8 In our cases, the lesions were gelatinous, likely because of abundant alcian blue-positive mucopolysaccharides in the extracellular matrix of the neurofibromas. Solitary epibulbar neurofibroma has been reported to be located in the temporal limbus (67%), superior limbus (12%), and inferior limbus (12%), suggestive of a ciliary nerve origin in these locations.1–3,6–8 However, in both our cases, the tumors were located near the nasal limbus. On UBM, both tumors appeared solid, consistent with the organized histopathological structure of neurofibroma and the presence of
476
Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.
Microscopically, both tumors were composed of benign spindle cells, neurites, and numerous mast cells, all consistent with neurofibroma. Immunohistochemistry of both lesions showed immunopositivity for S100 protein, CD34, and neurofilament antigens because of the presence of Schwann cells, fibroblasts, and axons, respectively. Immunohistochemistry for factor XIIIa was also positive, consistent with the presence of perineurial cells within both neurofibromas. Both tumors did not stain for calretinin or CD56 antigens. Alcian blue stain was diffusely positive, indicating the presence of abundant mucinous matrix, correlating with the gelatinous and translucent clinical appearances of the lesions (Figs, 1C–H and Figs. 2C–H).
DISCUSSION
| www.corneajrnl.com
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Cornea Volume 34, Number 4, April 2015
Conjunctival Neurofibroma
FIGURE 2. A, Slit-lamp photograph showing an elevated amelanotic, translucent epibulbar lesion deep to the nasal conjunctiva (black arrow) with corneal delle (white arrow). B, UBM showing a lesion without invasion of sclera. C–H, Photomicrograph showing the presence of Schwann cells, fibroblasts, and mast cells (C), with positivity for S100 antigen staining Schwann cells with axons remained unstained (D), neurofilament antigen staining of axons (E), CD34 antigen (F), immunonegativity for calretinin, which stains only mast cells in the tumor (G); and alcian blue showing positivity for mucopolysaccharides (H). (Hematoxylin–eosin staining, S100 immunostaining, neurofilament immunostaining, CD34 immunostaining, calretinin immunostaining, and alcian blue staining, respectively, original magnification ·100, except neurofilament and alcian blue, original magnification ·200).
mucopolysaccharides in the tumor matrix. There was no scleral invasion in either case. The differential diagnosis of conjunctival neurofibroma includes schwannoma, epibulbar dermoid, leiomyoma, fibrous histiocytoma, lymphoma, myxoma, nodular scleritis, mucosal neuroma, and solitary circumscribed neuroma. It is diagnosed by histopathological examination.1–3,6–8 Mucosal neuroma is a benign peripheral tumor, usually present in patients with multiple endocrine neoplasia type 2B. Solitary circumscribed neuroma is a benign, well-circumscribed, partially encapsulated spindle-cell tumor.4 It is important to differentiate a neurofibroma from a schwannoma. They are both peripheral nerve sheath tumors, Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.
but malignant degeneration is more likely to develop in large, deep-seated neurofibromas associated with neurofibromatosis.1,6 Histopathologically, solitary neurofibromas may be circumscribed, but are not encapsulated.1,3,6 In contrast, schwannomas are often encapsulated, and the capsule can be delineated with the aid of immunohistochemical stains, epithelial membrane antigen, and Glut-1.9 Immunohistochemical stains for S100 protein, neurofilament, factor XIIIa, CD34, calretinin, and CD56 assist in confirming the diagnosis.9,10 S100 protein is a preferred marker for identifying cells of neural origin, and neurofilament is a marker for axonal filaments, but they do not distinguish neurofibroma from schwannoma.9,10 Factor XIIIa stains perineurial cells within www.corneajrnl.com |
477
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Cornea Volume 34, Number 4, April 2015
Tanaka et al
TABLE 1. Cases of Neurofibroma With No History of Neurofibromatosis Reference
Age, Gender Appearance
Dabezies et al7
50, F
Perry2
22, F
Kalina et al3
34, M
Ang et al1
36, M
Kumar et al6
78, M
Mohyudin et al8
37, F
Firm, gray, nodular mass Lobulated, oval yellowwhite Solid, nodular, tan Firm, oval, grayish blue Pink, smooth, vascular Firm, smooth, salmonpink
Location
Management
Diagnosis Approach
Histopathology
Upper temporal Excision, 3· Histopathology, quadrant, OS systemic, and family history evaluation Inferior Excision Histopathology, perilimbal, systemic evaluation OD
Neurofibroma
Temporal corneoscleral limbus, OS Temporal perilimbal, OS Temporal perilimbal, OS Superior perilimbal, OS
Solitary neurofibroma
Excision
NA
Excisional biopsy
Histopathology, systemic, and family history evaluation Histopathology, systemic evaluation Histopathology, systemic, and family history evaluation
Excision
Biopsy
Immunohistochemistry Stain
Systemic Disease
Wilder, Bodian
NA
Isolated Bodian, Giemsa, reticulin 4 yrs later NF2 neurofibroma
NA
NA
Neurofibroma
S100
NA
Neurofibroma
S100, neurofilament
Bladder carcinoma
Diffuse neurofibroma
S-100, neurofilament
Hypothyroid
NA, not available; NF2, neurofibromatosis type 2.
neurofibromas, and CD34 marks perineurial fibroblasts, assisting in confirming the diagnosis of neurofibroma.10 However, calretinin, which stains plasma cells in neurofibromas, fails to stain tumor cells as it does in schwannoma.10 CD56, a sensitive marker for Schwann cells, did not stain the neurofibroma.10 Of the 6 solitary conjunctival neurofibromas published in the medical literature, only 1 case used S100 protein to confirm the diagnosis of neurofibroma; 2 used S100 and neurofilament; 2 used Bodian stain with or without Wilder, Giemsa, or reticulin histochemical stains; and 1 did not specify the stain used.1–3,6–8 The management of conjunctival neurofibroma involves excisional biopsy. Of the 6 published cases, only 1 developed multiple recurrences after the excision, none developed malignant transformations, and only 1 was diagnosed with systemic disease, NF2 after 4 years of follow-up.2,7 REFERENCES 1. Ang LP, Heng WJ, Chan WK. A case of episcleral neurofibroma. Int Ophthalmol. 1999;22:201–210.
478
| www.corneajrnl.com
2. Perry HD. Isolated episcleral neurofibroma. Ophthalmology. 1982;89: 1095–1098. 3. Kalina PH, Bartley GB, Campbell RJ, et al. Isolated neurofibromas of the conjunctiva. Am J Ophthalmol. 1991;111:694–698. 4. Grossniklaus HE, Green WR, Luckenbach M, et al. Conjunctival lesions in adults. A clinical and histopathologic review. Cornea. 1987; 6:78–116. 5. Shields CL, Demirci H, Karatza E, et al. Clinical survey of 1643 melanocytic and nonmelanocytic conjunctival tumors. Ophthalmology. 2004;111:1747–1754. 6. Kumar BV, Rennie IG, Mudhar HS. A case of episcleral cellular neurofibroma. Int Ophthalmol. 2005;26:239–241. 7. Dabezies OH Jr, Penner R. Neurofibroma or neurilemmoma of the bulbar conjunctiva. Arch Ophthalmol. 1961;66:99–101. 8. Mohyudin MN, Darrad M, Murray A, et al. Isolated diffuse episcleral neurofibroma. Orbit. 2013;32:130–131. 9. Nascimento AF, Fletcher CDM. The controversial nosology of benign nerve sheath tumors: neurofilament protein staining demonstrates intramural axons in many sporadic schwannomas. Am J Surg Pathol. 2007;31:1363–1370. 10. Park JY, Park H, Park NJ, et al. Use of calretinin, CD56, and CD34 for differential diagnosis of Schwannoma and neurofibroma. Korean J Pathol. 2011;45:30–35.
Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
