Oral Schwannoma: A Systematic Review of the Case Reports

Document Type: Review Article

Authors

1 Professor, Department of Oral and Maxillofacial Pathology, Dental Research Center, School of Dentistry, Mashhad University Of Medical Science, Mashhad, Iran.

2 Assistant Professor, Department of Oral and Maxillofacial Radiology, School of Dentistry, Zahedan University of Medical Sciences, Zahedan, Iran

3 Associated Professor, Department of Oral and Maxillofacial Pathology, Mashhad University of Medical Science, Mashhad, Iran

4 Postgraduate Student, Department of Oral and Maxillofacial Radiology, Mashhad University of Medical Science, Mashhad, Iran.

5 Postgraduate Student, Department of Oral and Maxillofacial Pathology, Mashhad University of Medical Science, Mashhad, Iran.

Abstract

 Schwannomas are benign neoplasms with unknown etiology, which apparently arise from neural sheath Schwann cells. Intraoral schwannomas are solitary, slow-growing lesions occurring at different ages; these lesions are normally asymptomatic and in some cases, they are accompanied by pain and paresthesia if spotted in the intraosseous regions of the mandibles. Definitive diagnosis of schwannoma is established through histopathological examination and immunohistochemical evaluation, and the first-line treatment involves the surgical excision of the tumor with preservation of neighboring structures. Anti-S100 protein is the most significant antibody used to identify schwannomas. Schwannomas are known to have good prognosis, and if the lesion is completely removed, there is a low risk of recurrence. This systematic review aimed to determine the most significant variables influencing intraoral schwannoma and evaluate effective methods for the diagnosis and treatment of these tumors.

Keywords

Main Subjects


Introduction

Schwannomas, also known as neurilemmoma, neurinoma, or perineural fibroblastoma, are benign neoplasms that commonly appear in the soft tissues of head and neck (25-45%) (1). According to a study by Leu and Chang, intraoral schwannomas were identified in only seven cases among 52 patients presented with schwannoma in the head and neck (2). Oral schwannomas are rare, slow-growing tumors with unknown etiology, which apparently arise from neural sheath Schwann cells. These solitary lesions may occur at different ages (usually within the second and third decades of life), and the prevalence is not significantly different between men and women. Oral schwannomas are normally asymptomatic, while in some cases, they might be accompanied by pain and paresthesia if spotted in the intraosseous regions of the mandibles. In such cases, these tumors may cause bone expansion, pain and paresthesia (3).

In general, schwannomas are solitary lesions; however, they are capable of multiplying when associated with neurofibromatosis. The most frequent sites of intraoral schwannomas are the tongue, palate, mouth floor, buccal mucosa, lips and jaws (4).

Schwannomas could be confused with other benign tumoral lesions, such as fibroma, mucocele, lipoma, neurofibroma and other salivary gland tumors. Immunohistochemical and radiological examinations are usually performed to determine the extension of these tumors, and immunohistochemical features of these tumors are evaluated in order to verify the neural differentiation of schwannomas.

Anti-S100 protein is the most significant antibody used to identify schwannomas. These lesions have good prognosis, and the first-line treatment involves the surgical excision of the tumor. If completely removed, schwannomas have a low risk of recurrence (4). This systematic review aimed to address the following questions:

  1. What are the most influential factors in the occurrence of intraoral schwannoma?
  2. What are the most common symptoms and complications associated with intraoral schwannoma?
  3. What are the most effective methods used for the differential diagnosis of schwannoma from other lesions?
  4. What are the most effective methods for the diagnosis and treatment of intraoral schwannoma?

 

.Materials and Methods

This systematic review aimed to evaluate articles focusing on oral schwannoma via searching in databases such as PubMed and Google Scholar during 2005-2015. Initially, all the articles with related abstracts were assessed by one researcher. Search for related studies was conducted using two key words of intraoral and schwannoma. Selected articles were published in English and Persian, and duplicate reports were excluded from the study.

In this review, we only included case reports and case series studies about oral schwannoma, and other studies were excluded. Additionally, different variables such as age, gender, location and size of schwannoma, duration of disease, associated complications, and type of treatment and diagnosis were evaluated in the present study. Previous reviews, meta-analyses, expert opinions, consensus statements, original articles, editorials, letters and qualitative studies were excluded from this review.

In total, 132 articles were selected out of 945 related studies, and other excluded articles were as follows: 6 reviews and narrative articles, 17 qualitative articles, 32 unrelated studies, 24 studies with missing data, 12 studies with unavailable data, and 4 republished articles. Eventually, 37 case reports were systematically reviewed by the researchers.

Required data were extracted by one researcher, and all the selected articles were reviewed in full text after screening. Moreover, the results obtained by each case report were studied in detail and evaluated based on the objectives of the study. The screening process is depicted in the PRISMA Flow Diagram.

PRISMA Flow Diagram:

Screening Process of Articles in the Current Review 945.

 

 

 

 

945 Articles Found

 

23 Reviews and Qualitative Studies

4 Republished Articles

132 Articles Extracted

24 Studies with Missing Data

 

32 Unrelated Studies

12 Studies with Unavailable Data

37 Case Reports Reviewed

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


Results

 In the present review, different variables such as age, gender, location and size of schwannoma, duration of disease, complications caused by the tumor, type of treatment and diagnosis, and follow-up of the patients were evaluated. The results are shown in (Table 1).

In total, 37 case reports were reviewed in this study, 18 of which were case report reviews, and other articles were case reports only. The majority of these studies focused on one reported case of schwannoma, while a few studies evaluated two cases of these tumors. In almost all these cases, patients underwent surgical procedures for the tumor resection.

Among the reviewed cases presented with schwannoma, 18 patients were male and 19 were female within different age ranges. These cases were reported in different countries, and among 37 articles, 8 cases were reported in India. In general, several of schwannoma cases were reported in regions of Southeast Asia. In addition, duration of disease ranged between three months and 20 years, and recurrence was observed in none of the studied cases.

 

 

 

 

 

Table 1.  Evaluation of Variables Associated with Schwannoma based on Literature Review

 

Authors/

Publication Year

(Reference)

Country

 

Age

Gender

Location of Schwannoma

Size

Duration  of Disease

 

Reported Complications

 

Type of Treatment

Follow-up

Diagnostic modalities(histopathological findings)

Amirchaghm et al.

(2010)

(5)

Iran

14

Male

Gingival, Right Mandibular Canine Tooth

1.5 cm

1 year

Asymptomatic, No tender mass

enlargement or mobility

Surgical Excision

Unknown

Loss of crest bone and lamina dura in some teeth/

Immunostaining with Anti-S100 Protein:

Positive in cellular areas

Subhashraj et al.

(2009)

(6)

 

19

Male

Periapical Region of Left

Lower First Premolar

31×24×12

Mm

8 Months

Asymptomatic, Enlarging Mass

Surgical Excision using high labial incisions in left mandibular

Region

18 Months

Proliferation of spindle cells without atypia arranged in nuclear palisades

Degenerative Changes and Hyalinization Detected

Enzo et al.

(2006)

(7)

Turkey

7

Male

Anterior Mobile Region of Tongue

25 mm

8 Months

Easily visible and palpable,  Swelling associated with pain and tenderness

Excision of tumor, capsule  and a small border of uninvolved surrounding tissue

5 Years

Immunohistochemical Evaluation:

Positive staining for S-100 protein, Leu-7 antigen, vimentin and glial fibrillary acidic protein

Lollar et al.

(2009)

(3)

USA

33

Male

Midline of Hard Palate

2×2 cm

3

Months

Asymptomatic

Wide Local Excision of Mass

Unknown

Variable cellular proliferation of spindled cells with foci of nuclear palisades

 

Immunohistochemical Evaluation:

Positive for S-100 protein and vimentin

Chen et al.

(2006)

(8)

Taiwan

34

Male

Left Anterior Mouth Floor

3×3×2.5 cm

18

Years

Asymptomatic

Encapsulated tumor removed by blunt dissection

2  Years

-------------

Salehinejad et al.

(2011)

(9)

Iran

27

Female

Ramus and Angle Region of Left Mandible

 

2 Years

Asymptomatic

Surgery by retromolar incision and blunt dissection  under general anesthesia

9 Months

Schwann cells in fibrous  with stromal myxoid changes

Clinical Diagnosis: Ameloblastoma and Myxoma

 

Immunohistochemical Evaluation:

S-100 protein positive

Bansal et al.

(2005)

(1)

India

26

Male

Ventral Surface of Right Side of Tongue

3-4 cm

4-5 Years

Gradual growth,

paresthesia of tongue, and difficulty in phonation

Excision with adequate surgical margins of resection

2 Years

Spindle shaped cells with long, twisted, curled nuclei, plentiful pale eosinophilic cytoplasm and uncertain cytoplasmic borders

 

Immunohistochemical Evaluation:

S-100 protein positive

De Bree et al.

(2000)

(10)

Netherlands

24

Female

Right Base of Tongue

5×5×3 cm

6 Months

Asymptomatic

Lesion removed using a submandibular approach

Unknown

MRI:

Enlarged, Well-circumscribed Solid Mass

Histopathological Examination:

Schwannoma

Parikh & Desai

(2010)

(11)

India

64

Female

Anterior Hard Palate

2×2 cm

3  Years

Asymptomatic

Tumor removed with incision of tongue in the midline

Unknown

 

Well-defined radiolucency with sclerotic lining in palate

Karaca et al.

(2010)

(12)

Turkey

13

---

Anterior Corpus of Tongue

---

1 Year

Disturbance in mastication and phonation

Surgical Excision

Unknown

Schwannoma/

Histopathological identification of Antoni A and B areas

Staining S-100 Protein:

Positive

Baranović et al.

(2005)

(13)

Croatia

53

Female

Lingual Mucosa of Mandible

11 mm

10 Months

Asymptomatic

Surgical Excision

Unknown

Mass with interlacing fascicles of compact spindle cells and twisted nuclei

Kim et al.

(2011)

(14)

Korea

66

Female

Buccal Region of Left Lower First Premolar

Area

2.0×1.3×1.0 cm

13 Years

Asymptomatic

Complete Excision using Intraoral Approach

9 Months

Well-demarcated, unencapsulated lesion, curled form, poorly defined cytoplasm and oval nuclei

S-100 Protein:

Positive

 

 

35

Female

Left Mandible Body

3.0×1.5×2.0 cm

---

Paresthesia

Incomplete

Surgery

Died

Spindle cells in fascicles

Immunohistochemical Evaluation:

Positive and Negative for Pancytokeratin

Murthy et al.

(2009)

(15)

Turkey

28

Female

Anterior Hard Palate

1.5×1.5 cm

4 Months

Occasionally bleeding due to pressure with tip of the tongue

Surgical Excision

Unknown

Histopathological Evaluation: Schwannoma

Cohen et al.

(2009)

(16)

USA

19

Female

Right Posterolateral Border of Tongue

18×13×11 mm

---

Asymptomatic

Transoral

Surgery

Unknown

Magnetic Resonance Imaging (MRI):

Well-circumscribed mass isointense on T1, hyperintense on T2

 

 

77

Male

Right Lateral of Tongue

7×5×5 mm

---

Asymptomatic

Transoral

Surgery

Unknown

----

Patil et al.

(2009)

(17)

India

23

Female

Right Mandibular Body

2.5×2  cm

6 Months

Asymptomatic

Resection with reconstruction using autologous iliac crest bone graft

Unknown

Unencapsulated lesion, Antoni A and B regions arranged in a palisading pattern

 

Immunohistochemical Evaluation:

S-100 protein positive

López-Jornet et al.

(2005)

(18)

Spain

39

Male

Right Side of Tongue

8×8 mm

5 Months

Moderate Pain

Antibiotic Treatment

One Year

Well-defined neo-formation surrounded by fibrous connective tissues

Immunoperoxidase Staining:  S-100 protein positive

Naidu et al.

(2010)

(19)

Nepal

12

Male

Right Side of Tongue

20×10 mm

15 Days

Bleeding, Paresthesia and Dysgeusia

Surgical Excision

3 Months

Predominant spindle cells and  mixed inflammatory cell infiltration

Immunohistochemical Evaluation:

Strong Reactivity

Lacerda et al.

(2006)

(20)

Brazil

11

Male

Permanent Mandibular Incisors

---

3 Years

Asymptomatic

Surgical Excision

5  Years

Histopathological Examination:

Neoplastic connective tissue arranged in short fascicles

Rahpeyma et al.

(2012)

(21)

Iran

12

Female

Soft Palate

3× 2×1 cm

3 Months

Asymptomatic

Lesion removed under general anaesthesia

6 Months

Microscopic Evaluation:  Encapsulated

Immunohistochemical Evaluation:

Positive for S-100 Protein

Pandarakalam et al.

(2005)

(22)

India

25

Male

Gingival

3×2 cm

---

Asymptomatic

Complete Resection

----

Predominant benign spindle cells in several intersecting bundles

Sivasankari et al.

2015

(23)

India

38

Male

Left Side of Palate

5×3 cm

3 Months

Difficulty in swallowing and changes in voice

Complete Resection,  antibiotic and anti- inflammatory therapy

One Year

Histopathological Examination:

Schwannoma

Shetty et al.

(2012)

(24)

India

70

Female

Right Posterior Palate

2 cm

2 Years

Discomfort  during Mastication

Complete Resection

8 Months

Antoni A type with parallel arrangement of spindle-shaped, curled nuclei

Kumar et al.

(2012)

(25)

India

18

Male

Left Hard Palate

3×2.5 cm

----

Asymptomatic

Excised under Local

Anesthesia

----

Histopathological Examination:

Neural

lesion surrounded by fibrous capsule

Shah et al.

(2011)

(26)

India

35

Female

Right Zygomatic Region

5×3 ×2 cm

2 Years

Asymptomatic

Alkayat Bramley Incision under General Anesthesia

1 year

Tumor composed of interlacing fascicles of compact spindle cells with twisted nuclei

Khiavi et al.

(2014)

(27)

Iran

21

Male

Midline of Palate

2×2cm

2 Months

Asymptomatic

Complete Resection

6 Months

Proliferation of spindle cells with palisaded arrangements around central acellular Immunohistochemical Evaluation:

S-100 protein positive

Sardinha et al.

(2005)

(28)

 

Brazil

13

Male

Tongue

1.4×0.6

Cm

---

Asymptomatic

Excised under Local Anesthesia

12 Months

Positive for S-100 Protein

Histopathological Examination:

Proliferation of spindle cells with palisaded arrangements around central acellular

Martins et al.

(2009)

(4)

 

Brazil

44

Female

Left Maxillary Vestibule (3×2 cm)

3×2 cm

20 Years

 

Asymptomatic

Surgical Excision

4 Years

Diagnosis established based on clinical, histopathological, and immunohistochemical findings

Arda et al.

(2003)

(29)

Turkey

34

Female

Beneath Tongue on the Left Side

 

3×3 cm

3 Months

Asymptomatic

Surgical Excision under

General Anesthesia

 

---

Encapsulated

lesion

Nuclei arranged in a streaming fashion in routine hematoxylin

Salehinejad et al.

(2009)

(30)

Iran

40

Male

Gingival of Left Mandible

19×17 mm

6 Months

Asymptomatic

Surgical Excision

5 Years

Immunohistochemical Evaluation:

Positive for S-100 Protein

Proliferation of spindle cells with palisaded arrangements around central acellular

Pfeifle et al

2001

(31)

USA

30

Female

Right Tip of Tongue

 

1.0×0.9 cm

2 months

Asymptomatic

Surgical Excision

---

Confirmatory S-100 Immunoperoxidase Stain: Strongly Positive

 

 

18

Male

Tongue Swelling

2

Cm

2 years

Asymptomatic

Surgical Excision

---

Immunoperoxidase Stain: Positive

Salehinejad et al.

(2010)

(32)

Iran

23

Female

Lower Mandible

1×3×5 cm

4 Months

Pain

Surgical Excision

10 Months

Proliferation of spindle cells with palisaded arrangements

 

Immunohistochemical Evaluation:

S-100 protein positive

Shetty et al.

(2011)

(33)

India

42

Male

Left Side of Lower Mandible

5×7 cm

4 Years

 

Resected

6 Months

Spindle cells with elongated nuclei arrangement

 

 

 

Discussion

Schwannomas are normally asymptomatic lesions; however, they might be associated with pain and discomfort, especially while involving the submucosal areas. Etiology of schwannoma is still unknown. These tumors are usually benign with a slow growth rate, starting as capsulated nodules; however, they might be malignant in some cases (8-10%) (7). In general, the majority of extracranial and intracranial schwannomas are benign, and the rate of malignancy is estimated at 5%. Approximately 9-14% of malignant schwannomas are spotted in the head and neck (34), which may cause pain, hoarseness, dysphagia, cranial nerve neuropathies, and even Horner syndrome depending on the site and complications of the lesion (35).

Schwannomas were first discussed by Verocay in 1908 (1). Accordingly, schwannomas originate from the vagus nerve and sympathetic fibers in the extracranial regions of the head and neck, and about 10-40% of these tumors are of unknown origins. In some cases, schwannomas are detected in the peripheral cranial or autonomic nerves. Normally, schwannomas appear on the flexor surfaces of the body, have centrifugal arrangements and are accompanied by pain and paresthesia (29).

According to the literature, about half of schwannomas are directly correlated with a certain nerve, and a quarter of all schwannomas occur in the head and neck. Intraoral schwannomas are rare, with the prevalence rate of 1%, and the majority of these tumors are spotted in the tongue, while the palate, buccal mucosa, lips and gingiva are other regions frequently affected by these lesions (31).

According to one study by Sanchis et al., out of 52 reported cases of schwannoma in the head and neck, only seven tumors were detected in the oral cavity (36). Furthermore, only nine intraoral schwannomas were reported in one study performed in two hospitals of Madrid and Bilbao, Spain during 17 years (37). Another study revealed that oral schwannomas constituted 0.04% of all intraoral lesions, so that only 4 cases out of 9000 biopsies were diagnosed with schwannoma during 38 years (38).

 

Assessment of Age, Tumor Size and Gender in Patients with Oral Schwannoma

Size of schwannomas is approximately 1-4 cm, while they might be larger if located in the mediastinal and retroperitoneal regions. In one study by Arda et al., size of the tumors was larger than the average in a case presented with intraoral schwannoma, It means Extra oral lesions was greater than intra oral ones (29). According to the findings of the present study, size of these lesions ranged between 8 mm and 5 cm in the reported cases.

In the current study, effects of gender in the occurrence of oral schwannoma were not reviewed, and only a few studies have discussed this correlation. According to some of these researches, gender has no significant correlation with the occurrence of oral schwannoma (4,7,12,16,23,31,39,52). Consistent with other studies, frequency of gender was equal in our review, and no differences were observed between male and female patients regarding the incidence of oral schwannoma. However, some of the studies in this regard were conducted on female patients only (5,13,32,36,37).

Schwannomas are caused by the proliferation of Schwann cells from motor and sensory peripheral nerve sheaths and normally occur within the second and third decades of life. However, age distribution of patients with schwannoma is variable since these lesions could be present for several years before becoming symptomatic (31). In the current study, the majority of patients were within the age range of 30-50. 

 According to a study by Salla et al., risk of schwannoma is comparatively higher in female patients, and the majority of tumors appear within 10-40 years (39). In another study by Chi et al., mean age of the patients with mandibular schwannoma was estimated at 34 years (40), while it was reported to be 23.7 years in patients with intraoral schwannoma in the study by Salla et al. (39), 38.2 years in the study by Lacosta et al. (41), and 27.1 years in the study by Sanchis et al. (36). In the present review, mean age of the patients with schwannoma was 30 years. In these patients, age could be affected by different variables, such as the location of schwannoma. For instance, tongue is most frequently affected by schwannoma in children ageing 10-13 years (19, 42).

Long-standing schwannoma, also known as ancient schwannoma, is usually benign and slow-growing and commonly spotted on the mouth floor (8, 43-45).These lesions cannot be distinguished from other types of schwannoma; therefore, they may be confused with other malignant tumors due to the presence of nuclear atypia and hyperchromasia, or misdiagnosis of myxoid neurofibroma and nerve sheath myxoma (46). Mean age of the patients with oral ancient schwannoma is higher than other types of schwannoma. Ancient schwannomas are usually benign in the oral cavity, while they may be malignant at other locations. Surgical excision is commonly performed for the treatment of ancient schwannomas (8).

Ancient schwannomas may appear in the form of solid masses, fluctuant cysts or a composition of both. In a case report by Chen et al., the studied lesions were reported to be solid and cystic (8). The first case of intraoral ancient schwannoma was reported by Eversole and Howell in 1971 (47), and Chen et al. reported a case of ancient schwannoma located in the oral cavity (8). Unlike Chen et al., all cases of oral ancient schwannoma were reported in female patients in some studies (43-45, 47, 48). Furthermore, the case reported by Chen et al. had the longest duration of oral ancient schwannoma (18 years), and diameter of the tumor was between 0.9-5.5 cm (8). Despite the fact that patients with ancient schwannoma are usually older than other cases presented with these tumors, cases ageing above 70 or 80 years are extremely rare (12, 24, 49).

Location and Complications of  Oral Schwannoma

For the most part, oral schwannomas are located in the tongue. In their research, Gallo et al. estimated the rate of intraoral schwannomas at 11.7%, equally spotted in the tongue and pharynx (50). Occurrence of tongue schwannoma is associated with the hypoglossal nerve; these lesions have a slow growth rate and may cause pain, loss of taste, and motor function disorders. Although these lesions are solitary, multifocal lesions could appear in localized multiple neurilemmomas in association with neurofibroma in Von Recklinghausen’s disease and schwannomatosis (1).

In a study in this regard, Bansal et al. described a case with schwannoma on the ventral surface of the right side of the tongue. According to their observations, the lesion had been present for 4 years, and the patient was admitted due to paresthesia and difficulty in phonation (1).

In another study by Wright and Jackson, the tongue was involved in almost half the cases of intraoral schwannoma, and either buccal or vestibular mucosa were involved in approximately one-fifth of the cases. In addition, soft palate was involved in 8.9% of the lesions, and one lesion was spotted in the gingiva and lips (51).

Schwannomas may involve any part of the tongue, as one case was observed in the ventral part of the tongue in a study by Mevio et al. (52). Moreover, another case was detected at the base and tip of the tongue by Dreher et al. (53) and Robert et al. (54), respectively. In several reports, intraosseous schwannoma is described as slightly painful, and without paresthesias (17, 24, 55, 56), which is often detected in the mandible, especially in the posterior segment of the body and ramus (9).

On the other hand, the majority of reported cases of ancient schwannoma were identified on the anterior portion of the tongue (9). Intraosseous schwannoma on the posterior segment of the body and ramus was reported in 28 cases in the study by Chi et al. (40). Degenerative changes of ancient schwannoma could be associated with increased size and duration of the tumor (46).

In their research, Salehinejad et al. presented a case with large intraosseous schwannoma, which extended from the lingula to the mandibular second molar (9). In another case reported by Arda et al., submaxillary region was involved (29), and the first case with schwannoma of the submandibular gland was reported by Sodagar and Daneshbod (57). Furthermore, a case of painless sublingual gland schwannoma was described in the study by Arda et al. (29).

Swelling and pain are the most common complications caused by intraoral schwannoma (58). In the present review, only 3 cases of painful schwannoma were found in the studied articles (7, 18, 33). However, discomfort caused by swelling of the palate (3, 24) and tongue was reviewed in several cases (19, 42, 59).

 

Diagnosis and Treatment

Schwannomas could occur in association with different somatic and sympathetic nerves (49). Schwannomas originating from the parasympathetic nerve of the sublingual gland were reported by Arda et al. for the first time (29). In another study, Sutay et al. detected schwannomas originating from the hypoglossal nerve (60), while they originated from the submandibular gland in the study by Sato et al. (61). Based on the aforementioned findings, it could be concluded that diagnosis of schwannoma is relatively easier than similar lesions.

In general, schwannomas are indistinguishable from other encapsulated benign tumors (4, 7). Neurofibroma, traumatic neuroma, fibroma, lipoma and leiomyoma are among the main differential diagnoses of schwannoma (1).

Definitive diagnosis of schwannoma is difficult to establish (62); according to a study by Wang et al., out of 26 biopsied schwannomas, 8 lesions were misdiagnosed as tongue fibromas, dermoid cysts and salivary gland tumors (63). Out of 12 cases described by Sanchis et al., the initial diagnosis was fibroma in four cases, and vascular lesion in two cases (36). Also, eight cases in the study by Lopez and Ballestin were initially misdiagnosed (37).

Many lesions such as lipoma, eosinophilic granuloma, hemangioma, epidermoid and dermoid cysts, epithelial hyperplasia, granular cell tumor, leiomyoma, and lymphangioma may be proposed as the differential diagnoses for schwannoma (64).

Clinically, schwannomas are asymptomatic, slow-growing masses rarely manifested as wounds (64). This is the main reason behind the delayed diagnosis of these tumors, which occasionally takes several years after they appear (59, 65). The results of the current review revealed that the majority of reported schwannomas were diagnosed about one year after they started to grow (4,24,26).

Radiological approaches, such as computed tomography (CT) and magnetic resonance imaging (MRI), should be used for the differential diagnosis of schwannoma, especially to evaluate different neoplastic processes involving the mouth floor. Panoramic X-ray is a complementary diagnostic measure for oral schwannoma; as such, this method was used in all the reviewed studies (29).

On the same note, MRI is an essential element in the diagnosis of these lesions due to the mucus and exophytic nature of schwannomas and could provide reliable information about these cases. Furthermore, this method could be useful in cases with enlarged tumors or uncertain diagnostic biopsy. However, it is possible that tumor borders are not accurately defined or separated from the peripheral tissue (29).

Schwannomas might be confused with neurofibromas, whereas neurofibromas have a centripetal nature and are typically unencapsulated, originating from different parts of the nervous system, such as Schwann cells, fibroblast, and their neurons. On the other hand, intraosseous schwannoma may be confused with odontogenic cysts or ameloblastoma. While radiological findings cannot distinguish between these lesions, CT-scan could provide an accurate diagnosis (29).

By and large, MRI is the most efficient imaging method to examine the base of the tongue since the resulting image is clear and well-demarcated (7). Through methods such as CT-scan and MRI, valuable data could be obtained for the accurate diagnosis of schwannoma, while biopsy and histopathological examination are essential to the definitive diagnosis of these lesions. A case of schwannoma of the hard palate was reported by Lollar et al., and the diagnosis was confirmed through histopathological and immunohistochemical examinations (3).

Histopathologically, schwannoma tissues are categorized into two patterns of Antoni A and Antoni B. Antoni A regions have high cellularity and are composed of densely packed, spindle cells arranged in palisades. On the other hand, Antoni B regions have more myxoid structures and two nuclear palisades with nuclear alignment in rows in an eosinophil zone, consisting of frills cytoplasmic, basal lamina, and collagen fibers in between, which are called Verocay bodies (30).( Fig 1 and 2)

 

Thin reticulin fibres, fusiform cells and curled nuclei are visible in the Antoni A region, consisting of a variety of cells without evident borders. In general, Antoni A region is composed of different cells without apparent borders (3, 7, 8). In the Antoni B region, tissues of Shawn cells are spotted in a random arrangement (30). (figure 1 and 2)

In the presence of alternating patterns of Antoni A and B regions, histopathological diagnosis of schwannoma is usually unequivocal; this finding was observed in all the studied articles. In a study by Bansed et al., schwannoma was diagnosed upon the identification of the cells located under Antoni A and B patterns. In the Antoni A area, cells were in a close arrangement, forming short bundles and interlacing fascicles. In addition, parallel rows were observed around the palisading nuclei (Verocay bodies), and in the Antoni B area, cells were arranged haphazardly within loosely-textured matrixes (1). Similar to other studies, Martins et al. reported the histopathological findings as thin fibrous capsules with Antoni A type, and Schwann cells with haphazard arrangement in Antoni B region (4).

Schwannomas rarely occur in the oral cavity; therefore, diagnosis of these lesions should be confirmed through microscopic examination (31). According to one study, intensity scores of tumoral cells with Antoni A type were higher compared to Antoni B type (66). In another article, Attie et al. described a case of schwannoma originating from the lingual nerve (67). (Fig 1 and 2)

Definitive diagnosis of schwannoma is established via histopathological examination of the lesion, based on two typical tissue patterns (Antoni A and B) (36). By showing protein S-100 and nuclear export signal, fusiform Schwann cells could be used to identify the neural origin of different lesions. Therefore, immunostaining analysis is essential to the accurate diagnosis of schwannoma (4). According to several studies, protein S-100 (a specific neural tissue marker) is reported to be immunohistochemically positive (9, 36). 

Fig 1 and 2 around is here.

In case of solitary, slow-growing lesions, excisional biopsy is recommended as an effective diagnostic measure. In their study, Martins et al. evaluated one female patient suspected with schwannoma within the fifth decade of her life. According to the findings, the lesion was accurately distinguished from other benign lesions based on the slow growth rate and circumscribed swelling without any particular features. The patient was referred for biopsy due to the presence of solitary, slow-growing lesions (4).

For the most part, treatment of schwannomas involves the surgical removal of the tumor, with preservation of the neighboring structures (36). If schwannomas are completely excised, there is a low risk of recurrence (4, 7).

 

 

 

 

 

 

 

Antoni A

Antoni B

Figure 1. Photomicrograph showing histological section of oral schwannoma cells composed of proliferating groups of Schwann nuclei in Antoni A and Antoni B tissues forming Verocay bodies. (H & E. Original magnification ×100)(Department of Oral and Maxillofacial pathology, Mashhad University of Medical Sciences)

 

 

Figure 2. Photomicrograph showing histological section of oral schwannoma cells composed of proliferating groups of Schwann nuclei in Antoni A and Antoni B tissues forming Verocay bodies. Fibrosis (capsulated) tissue separated tumor cells from oral mucosa. (H & E. Original magnification ×40) (Department of Oral and Maxillofacial pathology, Mashhad University of Medical Sciences)

 

Conclusion

According to the results of this study, evaluation of the differential diagnoses of schwannoma is of paramount importance since these tumors are normally indistinguishable from other benign lesions. In conclusion, histopathological examination and immunohistochemical analysis are essential to the accurate diagnosis of schwannoma. As for the treatment of these lesions, surgical excision of the tumor with preservation of the neighboring structures is the method of choice. 

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