# Unusual Case of a Proptosed Eye: Isolated Right Maxillary Neurofibroma

Authors: Darren Yap; Hannah Fox; Julia Addams-Williams
Journal: Case Reports in Pathology
 (2016)

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## Abstract

Neurofibroma is a slow growing benign tumour of the peripheral nerve sheath which is frequently associated with neurofibromatosis type 1 (Prakash et al., 2014). Isolated solitary occurrence of neurofibroma in the maxillary sinus is rare with only 29 reported cases in the literature. We present a rare case of a 70-year-old gentleman who was referred to ENT with a right maxillary sinus neurofibroma with extension into the right inferior orbit. He has significant proptosis, ptosis, and limitation in abduction of the right eye. He has a complicated past history of multiple neurofibromas which were completely excised. Craniofacial MRI shows a large mass filling the right maxillary antrum extending anteriorly into subcutaneous tissue towards nasal ala and posterolaterally into inferior temporal fossa and superiorly into orbit and cavernous sinus involvement. Biopsy of the right maxillary mass revealed cellular spindle cell tumour with wavy collagen bundles within myxoid stroma which is consistent with a neurofibroma. Patient’s case was discussed in the skull-base MDT and he has been referred to a specialist center for surgical removal of the neurofibroma with reconstructive surgery. Despite the rarity of this disease, otorhinolaryngologist should consider a possibility of neurofibroma of the paranasal sinuses.


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## Body

## 1. Introduction

Neurofibroma (NF) is a benign slow growing tumour of the peripheral nerve sheath. It may occur as an isolated sporadic lesion or may be associated with neurofibromatosis type 1, which is also known as von Recklinghausen’s disease. Neurofibroma of the maxillary sinus is an exceedingly rare tumour. We report a case of right maxillary sinus neurofibroma and literature review of this rare condition.


## 2. Case

We present a case of 70-year-old gentleman who was referred to the ENT department with a one-year history of right maxillary sinus mass. He presented with significant proptosis, ptosis, and limitation in abduction of the right eye. He also complained of right sided facial pain with no history of epistaxis or nasal congestion.Patient has a past medical history of multiple neurofibromas which had been excised. He is otherwise fit and healthy.Craniofacial MRI scan has shown a large lesion within the maxillary sinus itself which completely fills and extends into the inferior orbit, cavernous sinus, and pterygopalatine fossa as shown in Figures1 and 2.Figure 1
Axial MRI showing lobulated mass in the right maxillary antrum extending anteriorly into the subcutaneous tissue of the cheek and posteriorly into the infratemporal fossa.Figure 2
Postgadolinium MRI coronal sequence showing superior extension into the right orbit.Biopsy of the right maxillary mass revealed cellular spindle cell tumour with wavy collagen bundles within myxoid stroma which is consistent with a neurofibroma. He was treated surgically and currently being followed up annually by the ENT department.


## 3. Discussion

### 3.1. Discussion

Neurofibromas are benign, slow growing, and relatively circumscribed but nonencapsulated peripheral nerve sheath tumours arising from nonmyelinating Schwann cells [1–5]. They can arise as solitary tumours or multiple tumours as a component of neurofibromatosis [2, 4–6]. Neurofibromatosis is not a single entity, but a group of heterogeneous multisystemic neurocutaneous disorders involving both neuroectodermal and mesenchymal derivatives [7]. It is one of the most common hereditary diseases occurring in 1 of every 3000 births [8].The National Institute of Health (NIH) has defined neurofibromatosis to two distinct types [9, 10]:(1)
Peripheral type (NF-I; von Recklinghausen’s disease) is associated with changes in the long arm of chromosome number 17 and accounts for over 90% of cases. Major defining features include neurofibromas, cutaneous café au lait macules, and Lisch nodules (pigmented iris hamartomas).
(2)
Central type (NF-II) is associated with a defect near the center of long arm of chromosome number 22 and is characterized by bilateral acoustic neuromas.The World Health Organization (WHO) further classifies neurofibromas into dermal and plexiform. Dermal neurofibromas are located mainly in skin areas and composed of single peripheral nerve with soft pedunculated masses of skin in a form of bump. On the other hand, plexiform neurofibromas are composed of many nerve bundles and located mainly within subcutaneous area [3].Neurofibromas of the nose and paranasal sinuses arise from the ophthalmic and maxillary division of the trigeminal nerve and autonomic plexuses [4, 11, 12]. At present there are only 29 reported cases in literature as shown in Table 1, with only two reported bilateral solitary maxillary sinus neurofibromas and the youngest case being 5 months old [13, 14].Table 1
Case reports on maxillary neurofibroma.
Number
Year
Author
Age (year)
Gender
Site (maxilla)
Journal
1
2016
Toms et al. [15]
n/a
n/a
Bilateral
Journal of Neurosurgery
2
2015
Warhekar [10]
22
Male
Left
Journal of Clinical and Diagnostic Research
3
2014
Jain et al. [16]
65
Female
Right
Contemporary Clinical Dentistry
4
2014
Azani et al. [17]
52333466
FemaleFemaleMaleFemale
RightRightLeftLeft
Head and Neck Pathology(case series)
5
2014
Adnane et al. [6]
14
Male
Left
Journal of Head and Neck Physicians and Surgeons
6
2014
Prakash et al. [1]
60
Female
Right
Research in Otolaryngology
7
2014
Komorski et al. [3]
79
Female
Left
Otolaryngologia Polska
8
2013
Solomon et al. [2]
12
Female
Right
Innovative Journal of Medical and Health Science
9
2012
Rokutanda et al. [12]
41
Male
Right
Journal of Oral and Maxillofacial Surgery, Medicine and Pathology
10
2012
Dalili and Adham [18]
16
Male
Right
Iranian Journal of Radiology
11
2011
Cegarra-Navarro et al. [11]
70
Female
Left
Acta Otorrinolaringol Esp
12
2011
Biswas and Mal [19]
n/a
n/a
Bilateral
Ear, Nose and Throat Journal
13
2011
Thammaiah et al. [7]
2.5
Female
Right
Journal of Paediatric Neurosciences
14
2010
Dass et al. [20]
25
Male
Right
Clinical Rhinology: An International Journal
15
2010
Hachem et al. [5]
10
Female
Right
International Journal of Pediatric Otorhinolaryngology
16
2009
Sharma et al. [14]
5 months
Male
Right
Journal of Indian Society of Pedodontics and Preventive Dentistry
17
2009
Nao et al. [21]
35
Female
Left
Annales d’Otolaryngologie et de Chirurgie Cervico-Faciale
18
2005
Boedeker et al. [4]
25
Male
Left
American Academy of Otolaryngology–Head and Neck Surgery Foundation
19
1997
Poupard and Mintz [22]
n/a
n/a
Solitary neurofibroma of the maxilla
Journal of Oral Maxillofacial Surgery
20
1993
Mori et al. [23]
n/a
n/a
Solitary intraosseous neurofibroma of maxilla
Journal of Oral and Maxillofacial Surgery
21
1988
Tandon and Deka et al. [24]
n/a
n/a
Maxillary neurofibromas
Indian Journal of Otolaryngology
22
1988
Skouteris and Sotereanos [25]
n/a
n/a
n/a
Journal of Oral and Maxillofacial Surgery
23
1982
Brady et al. [26]
n/a
n/a
n/a
Journal of Oral and Maxillofacial Surgery
24
1980
Badger [27]
n/a
n/a
n/a
Journal of the American Dental Association
25
1979
Agarwal et al. [28]
n/a
n/a
n/a
Oral Surgery, Oral Medicine, Oral Pathology
26
1975
Robitaille et al. [29]
45
Male
Right
American Society of Clinical Oncology
27
1975
Toth et al. [30]
n/a
n/a
n/a
Oral Surgery, Oral Medicine, Oral Pathology
28
1970
De Costa et al. [31]
n/a
n/a
n/a
Hospital (Rio de Janeiro, Brazil)
29
1965
Yamazaki et al. [32]
n/a
n/a
n/a
Jibi Inkoka Otolaryngology


### 3.2. Sign and Symptoms

Symptoms described by patients are nonspecific and depend heavily on the exact location and extension of the lesion [4, 6]. They are thus often clinically silent reaching considerable size in this location before diagnosis [6, 11, 12]. Advanced neurofibromas arising in the maxillary sinus cause pain, epistaxis, nasal obstruction, proptosis, and swelling of the face as described in this case [12, 29].


### 3.3. Imaging

Imaging may not provide a definitive diagnosis; however it plays an important part in assessing, staging, operative planning, and monitoring of the progression of the disease [5].CT scan may show heterogeneous soft tissue density and destruction of paranasal sinuses dependent on the stage of the disease [6]. Whereas MRI scan usually shows an isotense (lower intensity signal than gray matter) on T1-weighted images and hypertense (higher intensity signal than gray matter) on T2-weighted images [4, 5, 11, 12].


### 3.4. Immunohistochemistry

These lesions may be difficult to distinguish initially as their histology may be similar to other fibrous lesions such as juvenile fibromatosis or fibromyxoma in small biopsy or curettage specimens [12, 14]. Therefore biopsy should include an area of the lesion from deeper portions of the soft tissue swelling, sufficient for macroscopic and microscopic examination and immunohistochemical study [12, 14].Histopathological examination of neurofibroma typically shows curve indent and ovoid Schwann cell nuclei with spindle cells, wavy nuclei, wavy collagen fibrils, and scatter mast cells embedded in an extended extracellular matrix [1, 4, 12, 17].Whereas schwannomas show distinctive areas identified as Antoni types A and B, typical palisade pattern of nuclei, encapsulated, solitary, and tumour density is higher compared to neurofibromas, which usually show a mucoid extracellular matrix with only scatter tumour cells [5, 20].In contrast, malignant peripheral nerve sheath tumours (PNST) are characterized by hypercellularity, “herringbone” fascicular growth pattern, atypical mitotic figures, and pleomorphic tumour cells and nuclei [17, 20].Immunochemistry can further help to differentiate neurofibromas from schwannomas and malignant peripheral nerve sheath tumours. Neurofibromas show characteristic immunoreactivity with S-100, neurospecific enolase (NSE), and Vimentin [1, 2, 4, 6, 20].However it is weak and shows focal to patchy reactivity to GFAP, SOX10, and bcl-2 [17].Malignant PNST tend to show higher percentage of cells positivity and stronger intensity of staining [33].Calretinin is a calcium-binding protein which is present in a diffuse and strong fashion in schwannoma; aiding the differentiation between neurofibroma and schwannoma as S-100 protein is positive in both tumours.


### 3.5. Differential Diagnosis

NF of the sinonasal tract is difficult and often misdiagnosed. Differential diagnoses in the order of frequency are shown as follows [18, 33].Differential diagnosis of sinonasal tract neurofibroma (in order of frequency):(1)
Schwannoma
(2)
Dermatofibrosarcoma protuberans
(3)
Fibrosarcoma
(4)
Meningioma
(5)
Leiomyoma
(6)
Solitary fibrous tumour
(7)
Leiomyosarcoma
(8)
Malignant fibrous histiocytoma
(9)
Low-grade sinonasal sarcoma with neural and myogenic features
(10)
Proliferative fasciitis
(11)
Inflammatory pseudotumour
(12)
Fibromatosis
(13)
Fibrous histiocytoma


### 3.6. Treatment

Peripheral nerve tumours are insensitive to radiotherapy and respond poorly to chemotherapy [5, 29]. Hence, early diagnosis and complete surgical excision are the gold standard treatment in symptomatic masses [1, 2, 4, 5, 20].At present there is no consensus regarding the indication and optimal timing for resection. In general the tumour can be resected if surgery could be performed without risk of damaging vital structures and disfiguring the patient [5].If surgical resection is not possible, patients are generally managed conservatively with close observation [5]. Although recurrence rate is low, there have been case reports of malignant transformation of these tumours. The transformation of neurofibroma into malignant peripheral nerve sheath tumour has been observed in 2–14% of cases of neurofibromatosis type 1, with a latency period of about 10–20 years. Thus a close followup is warranted [4, 5, 11, 14, 20, 34]. Pain, change in texture, rapid increase in size, and neurological deficits are indications of a malignant transformation within a preexisting neurofibroma [4, 5].


## 3.1. Discussion

Neurofibromas are benign, slow growing, and relatively circumscribed but nonencapsulated peripheral nerve sheath tumours arising from nonmyelinating Schwann cells [1–5]. They can arise as solitary tumours or multiple tumours as a component of neurofibromatosis [2, 4–6]. Neurofibromatosis is not a single entity, but a group of heterogeneous multisystemic neurocutaneous disorders involving both neuroectodermal and mesenchymal derivatives [7]. It is one of the most common hereditary diseases occurring in 1 of every 3000 births [8].The National Institute of Health (NIH) has defined neurofibromatosis to two distinct types [9, 10]:(1)
Peripheral type (NF-I; von Recklinghausen’s disease) is associated with changes in the long arm of chromosome number 17 and accounts for over 90% of cases. Major defining features include neurofibromas, cutaneous café au lait macules, and Lisch nodules (pigmented iris hamartomas).
(2)
Central type (NF-II) is associated with a defect near the center of long arm of chromosome number 22 and is characterized by bilateral acoustic neuromas.The World Health Organization (WHO) further classifies neurofibromas into dermal and plexiform. Dermal neurofibromas are located mainly in skin areas and composed of single peripheral nerve with soft pedunculated masses of skin in a form of bump. On the other hand, plexiform neurofibromas are composed of many nerve bundles and located mainly within subcutaneous area [3].Neurofibromas of the nose and paranasal sinuses arise from the ophthalmic and maxillary division of the trigeminal nerve and autonomic plexuses [4, 11, 12]. At present there are only 29 reported cases in literature as shown in Table 1, with only two reported bilateral solitary maxillary sinus neurofibromas and the youngest case being 5 months old [13, 14].Table 1
Case reports on maxillary neurofibroma.
Number
Year
Author
Age (year)
Gender
Site (maxilla)
Journal
1
2016
Toms et al. [15]
n/a
n/a
Bilateral
Journal of Neurosurgery
2
2015
Warhekar [10]
22
Male
Left
Journal of Clinical and Diagnostic Research
3
2014
Jain et al. [16]
65
Female
Right
Contemporary Clinical Dentistry
4
2014
Azani et al. [17]
52333466
FemaleFemaleMaleFemale
RightRightLeftLeft
Head and Neck Pathology(case series)
5
2014
Adnane et al. [6]
14
Male
Left
Journal of Head and Neck Physicians and Surgeons
6
2014
Prakash et al. [1]
60
Female
Right
Research in Otolaryngology
7
2014
Komorski et al. [3]
79
Female
Left
Otolaryngologia Polska
8
2013
Solomon et al. [2]
12
Female
Right
Innovative Journal of Medical and Health Science
9
2012
Rokutanda et al. [12]
41
Male
Right
Journal of Oral and Maxillofacial Surgery, Medicine and Pathology
10
2012
Dalili and Adham [18]
16
Male
Right
Iranian Journal of Radiology
11
2011
Cegarra-Navarro et al. [11]
70
Female
Left
Acta Otorrinolaringol Esp
12
2011
Biswas and Mal [19]
n/a
n/a
Bilateral
Ear, Nose and Throat Journal
13
2011
Thammaiah et al. [7]
2.5
Female
Right
Journal of Paediatric Neurosciences
14
2010
Dass et al. [20]
25
Male
Right
Clinical Rhinology: An International Journal
15
2010
Hachem et al. [5]
10
Female
Right
International Journal of Pediatric Otorhinolaryngology
16
2009
Sharma et al. [14]
5 months
Male
Right
Journal of Indian Society of Pedodontics and Preventive Dentistry
17
2009
Nao et al. [21]
35
Female
Left
Annales d’Otolaryngologie et de Chirurgie Cervico-Faciale
18
2005
Boedeker et al. [4]
25
Male
Left
American Academy of Otolaryngology–Head and Neck Surgery Foundation
19
1997
Poupard and Mintz [22]
n/a
n/a
Solitary neurofibroma of the maxilla
Journal of Oral Maxillofacial Surgery
20
1993
Mori et al. [23]
n/a
n/a
Solitary intraosseous neurofibroma of maxilla
Journal of Oral and Maxillofacial Surgery
21
1988
Tandon and Deka et al. [24]
n/a
n/a
Maxillary neurofibromas
Indian Journal of Otolaryngology
22
1988
Skouteris and Sotereanos [25]
n/a
n/a
n/a
Journal of Oral and Maxillofacial Surgery
23
1982
Brady et al. [26]
n/a
n/a
n/a
Journal of Oral and Maxillofacial Surgery
24
1980
Badger [27]
n/a
n/a
n/a
Journal of the American Dental Association
25
1979
Agarwal et al. [28]
n/a
n/a
n/a
Oral Surgery, Oral Medicine, Oral Pathology
26
1975
Robitaille et al. [29]
45
Male
Right
American Society of Clinical Oncology
27
1975
Toth et al. [30]
n/a
n/a
n/a
Oral Surgery, Oral Medicine, Oral Pathology
28
1970
De Costa et al. [31]
n/a
n/a
n/a
Hospital (Rio de Janeiro, Brazil)
29
1965
Yamazaki et al. [32]
n/a
n/a
n/a
Jibi Inkoka Otolaryngology


## 3.2. Sign and Symptoms

Symptoms described by patients are nonspecific and depend heavily on the exact location and extension of the lesion [4, 6]. They are thus often clinically silent reaching considerable size in this location before diagnosis [6, 11, 12]. Advanced neurofibromas arising in the maxillary sinus cause pain, epistaxis, nasal obstruction, proptosis, and swelling of the face as described in this case [12, 29].


## 3.3. Imaging

Imaging may not provide a definitive diagnosis; however it plays an important part in assessing, staging, operative planning, and monitoring of the progression of the disease [5].CT scan may show heterogeneous soft tissue density and destruction of paranasal sinuses dependent on the stage of the disease [6]. Whereas MRI scan usually shows an isotense (lower intensity signal than gray matter) on T1-weighted images and hypertense (higher intensity signal than gray matter) on T2-weighted images [4, 5, 11, 12].


## 3.4. Immunohistochemistry

These lesions may be difficult to distinguish initially as their histology may be similar to other fibrous lesions such as juvenile fibromatosis or fibromyxoma in small biopsy or curettage specimens [12, 14]. Therefore biopsy should include an area of the lesion from deeper portions of the soft tissue swelling, sufficient for macroscopic and microscopic examination and immunohistochemical study [12, 14].Histopathological examination of neurofibroma typically shows curve indent and ovoid Schwann cell nuclei with spindle cells, wavy nuclei, wavy collagen fibrils, and scatter mast cells embedded in an extended extracellular matrix [1, 4, 12, 17].Whereas schwannomas show distinctive areas identified as Antoni types A and B, typical palisade pattern of nuclei, encapsulated, solitary, and tumour density is higher compared to neurofibromas, which usually show a mucoid extracellular matrix with only scatter tumour cells [5, 20].In contrast, malignant peripheral nerve sheath tumours (PNST) are characterized by hypercellularity, “herringbone” fascicular growth pattern, atypical mitotic figures, and pleomorphic tumour cells and nuclei [17, 20].Immunochemistry can further help to differentiate neurofibromas from schwannomas and malignant peripheral nerve sheath tumours. Neurofibromas show characteristic immunoreactivity with S-100, neurospecific enolase (NSE), and Vimentin [1, 2, 4, 6, 20].However it is weak and shows focal to patchy reactivity to GFAP, SOX10, and bcl-2 [17].Malignant PNST tend to show higher percentage of cells positivity and stronger intensity of staining [33].Calretinin is a calcium-binding protein which is present in a diffuse and strong fashion in schwannoma; aiding the differentiation between neurofibroma and schwannoma as S-100 protein is positive in both tumours.


## 3.5. Differential Diagnosis

NF of the sinonasal tract is difficult and often misdiagnosed. Differential diagnoses in the order of frequency are shown as follows [18, 33].Differential diagnosis of sinonasal tract neurofibroma (in order of frequency):(1)
Schwannoma
(2)
Dermatofibrosarcoma protuberans
(3)
Fibrosarcoma
(4)
Meningioma
(5)
Leiomyoma
(6)
Solitary fibrous tumour
(7)
Leiomyosarcoma
(8)
Malignant fibrous histiocytoma
(9)
Low-grade sinonasal sarcoma with neural and myogenic features
(10)
Proliferative fasciitis
(11)
Inflammatory pseudotumour
(12)
Fibromatosis
(13)
Fibrous histiocytoma


## 3.6. Treatment

Peripheral nerve tumours are insensitive to radiotherapy and respond poorly to chemotherapy [5, 29]. Hence, early diagnosis and complete surgical excision are the gold standard treatment in symptomatic masses [1, 2, 4, 5, 20].At present there is no consensus regarding the indication and optimal timing for resection. In general the tumour can be resected if surgery could be performed without risk of damaging vital structures and disfiguring the patient [5].If surgical resection is not possible, patients are generally managed conservatively with close observation [5]. Although recurrence rate is low, there have been case reports of malignant transformation of these tumours. The transformation of neurofibroma into malignant peripheral nerve sheath tumour has been observed in 2–14% of cases of neurofibromatosis type 1, with a latency period of about 10–20 years. Thus a close followup is warranted [4, 5, 11, 14, 20, 34]. Pain, change in texture, rapid increase in size, and neurological deficits are indications of a malignant transformation within a preexisting neurofibroma [4, 5].


## 4. Conclusion

Despite the rarity of this disease, otorhinolaryngologist should consider a possibility of neurofibroma of the paranasal sinuses.



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*Source: 4294729-2016-09-28.xml*