Abstract
Background: Schwannomas are solitary neurogenic tumors originating from the myelin sheath of peripheral nerves. Extracranial hypoglossal schwannomas comprise <5% of all head and neck schwannomas and can mimic submandibular salivary gland tumors. Case Report: We report the diagnostic imaging, surgical treatment, and histopathological findings of a rare case of extracranial schwannoma of the hypoglossal nerve in a 73-year-old female, presented with an asymptomatic swelling in the left submandibular region that had been persisted for approximately three years. Conclusion: Accurate diagnosis of this rare clinical entity requires comprehensive diagnostics. The optimal therapeutic strategy is nerve-sparing surgical excision, although it can be challenging.
Schwannomas are solitary, benign, slow-growing, and well-encapsulated neurogenic neoplasms originating from the myelin-producing Schwann cells of the peripheral nerves (1-6). They can involve the cranial nerves, such as V, VII, X, XI, and XII or sympathetic and peripheral nerves (7-11). Approximately 25-45% of extracranial schwannomas are located in the head and neck region (7-9, 12, 13).
Extracranial schwannomas that manifest clinically in the submandibular region mostly originate from the hypoglossal nerve and comprise less than 5% of all head and neck schwannomas (1, 2). De Martel first described them in 1933, and only a few cases have been reported in the international literature since then (1, 5, 14). As shown in Table I, a review of the literature revealed only a small number of publications on this topic. Kaye et al. proposed a classification system based on the location of the schwannoma as intracranial (type A), intracranial/extracranial (type B), or extracranial (type C) (15).
Individual study characteristics.
Hypoglossal schwannomas are typically found in middle-aged patients, with a slight female predominance (12). They are usually solitary, encapsulated tumors that grow slowly and appear attached or surrounded by a nerve (13). Imaging characteristics of hypoglossal schwannomas are often similar to those of submandibular salivary gland tumors or paragangliomas (2, 12). Submandibular tumors are typically asymptomatic masses. However, depending on the size and location of the tumor, some patients may experience symptoms, such as dysphagia, tongue atrophy, and ipsilateral tongue paresis (2, 13). It is important to note that patients with small-sized lesions may remain asymptomatic for extended periods, making diagnosis challenging.
Radiological diagnostic imaging, through computed tomography (CT) or magnetic resonance imaging (MRI), is essential in the preoperative assessment of extracranial hypoglossal schwannomas. This provides information about the tumor’s nature, size, and anatomical relationships with adjacent soft tissue structures and nerve courses (1, 7-9, 12, 16). However, accurate preoperative diagnosis can be impeded by the rarity of these entities, leading to a lack of specific radiological features (12). Therefore, the definitive diagnosis depends on the histopathological examination of the surgical specimen (12). Here, two types of schwannomas cells are demonstrated. The Antoni A type consists of narrow elongated bipolar cells arranged in a pattern of parallel rows (nuclear palisading) while the Antoni type B cells are loose reticulated cells scattered in a fibrillary microcystic matrix (1, 3, 4, 13, 17). Most schwannomas contain a mixture of both types of cells (1, 3, 13).
Based on international consensus recommendations, surgical resection is the first-line treatment modality for extracranial hypoglossal schwannomas (1, 1, 3, 4, 7, 9). Nerve-preserving surgery can be very challenging for head and neck surgeons and may not always be possible due to the difficulty in accurately diagnosing the condition before surgery and the complexity of the surgical site (2, 12). In cases of nerve transection, direct nerve reconstruction can be considered to minimize potential functional neural morbidity postoperatively (2, 3). Although this rare tumor entity is mostly benign, regular postoperative follow-up is crucial due to sparse reports of malignant transformation and local recurrence (12, 18). Previous reports have emphasized the significance of a multidisciplinary approach in the diagnosis and treatment of rare neoplasms to ensure the best possible outcome (12, 19, 20).
Here we present a rare case of an extracranial schwannoma that originates from the left hypoglossal nerve. The aim is to discuss the diagnostic and management challenges associated with this type of tumor, along with a review of the pertinent literature.
Case Report
History and examination. A 73-year-old female consulted our clinic of oral and maxillofacial surgery with a complaint of indolent swelling in the left submandibular region near to the mandibular angle that had been present for approximately three years. Physical examination revealed a single ovoid palpable mass, approximately to the left mandibular angle. The swelling was slightly mobile, neither dolent nor tender in palpation, with a hard elastic consistency as well as well-defined margins (Figure 1). No palpable laterocervical lymphadenopathy was detected and cranial nerve function appeared normal. Additionally, no abnormalities were found in the function of the facial and hypoglossal nerves. Salivary flow intraorally was normal. The patient’s history did not indicate any treatment with anti-inflammatory medications or antibiotics. Laboratory tests did not reveal any signs of inflammation.
Preoperative view of the left lateral neck: Well-defined and slightly mobile lesion of hard elastic consistency in the left submandibular region.
Diagnostic imaging. Ultrasonography revealed a well-defined, hypoechoic solid lesion with evidence of peri- and intralesional vascularization per Doppler signal, located posteriorly to the left submandibular salivary gland. Contrast-enhanced CT showed a well-circumscribed spherical 2.2×2.4 cm mass with heterogeneous density in the left submandibular region, with slight projection to the posterior mouth floor (Figure 2A). Strong enhancement of intratumoral blood vessels was also demonstrated (Figure 2B). The mass was located laterally to the genioglossus and hypoglossus muscles without compressing the submandibular salivary gland (Figure 2C). An enlarged left submandibular gland was also observed compared to the contralateral side. A few larger but sub-centimeter cervical nodes were visualized in Level II compared to the contralateral side. No outward dislocation of the major neck vessels was demonstrated, and no fine needle aspiration cytology was performed.
Axial and coronal views of the contrast-enhanced computed tomography (CT) scan of the head and neck. A) Orange arrow demonstrates a well-defined hypodense lesion with inhomogeneous density in the left submandibular region, approximately to the mandibular angle. B) Arrows demonstrate enhancement of intratumoral blood vessels. C: Coronal view of the contrast-enhanced CT scan of the head and neck demonstrates the neoplasm located lateral to the genioglossus and hypoglossus muscles. The submandibular gland appears displaced inferiorly.
Differential diagnosis. The differential diagnosis primarily considered adenomas of the parotid or submandibular salivary gland and lymphomas due to the indolent growth of the lesion. Other conditions, such as chronic sialadenitis, lymphadenopathy, infectious diseases, cysts, and nodal metastasis were also considered, but they typically present with inflammation symptoms, which were unlikely in this case. Additionally, neurogenic tumors, such as schwannomas should be included in the differential diagnosis.
Based on the clinical and radiological findings, a benign submandibular salivary gland neoplasm such as a pleomorphic adenoma was suspected. The patient was scheduled for total surgical excision under general anaesthesia after informed consent was obtained.
Surgical treatment. The oral and maxillofacial surgeon performed surgical resection via a transcervical approach, anterior to the sternocleidomastoid muscle. The internal jugular vein and carotid artery were visualized. Several lymph nodes of undermined significance were excised at Level Ib. The fascia overlying the submandibular gland was incised and the facial vessels were identified and ligated. The marginal mandibular branch of the facial nerve was preserved through the Hayes-Martin maneuver. The neoplasm was located in the deep portion of the digastric muscle, following the posterior tracking of the muscle to the mastoid tip. The soft surrounding tissues were gently displaced to expose the mass on the external surface of the muscle. The mass was easily detached in the anterior, posterior, and inferior directions. Neuromonitoring was used to identify the hypoglossal nerve, which appeared well-encapsulated and continuous with the mass. The hypoglossal nerve’s distal portion was transected near the mass with sufficient surgical margins after confirming that the tumor originated from the nerve. The neoplasm was mobilized without damaging the hypoglossal nerve sheath, thus sparing the parent nerve. However, a minor nerve injury could not be ruled out. The dissection continued in the submandibular region near the mandibular angle, and the mass was detached from the mylohyoid muscle. The surgical procedure preserved the submandibular salivary gland and lingual nerve. Macroscopic examination revealed no cystification or necrosis degeneration. Following hemostasis, a suction drainage tube was placed in the surgical field.
Clinical outcome and follow-up. Postoperatively, the patient experienced a moderate degree of ipsilateral tongue weakness, but without any difficulties in swallowing or speech. This was completely resolved in the follow-up examination, which took place 4 weeks after surgery. The suction drainage was maintained for 48 h, and the patient did not experience any postoperative wound complications. The patient resumed eating on the second day, and regular outpatient follow-up visits were scheduled. At the three-month follow-up, there were no clinical signs of local recurrence. Postoperative radiographic examination was not carried out.
Histopathological examination. Histopathologic examination was carried out on the surgical specimen after fixation in 10% neutral-buffered formalin, embedding in paraffin, sectioning to a thickness of 5 μm, and staining with haematoxylin and eosin (H&E). Microscopically, the lesion was formed by fused elements, occasionally structured in interlaced bundles, with a central mucous matrix. The specimen presented a combination of Antoni type A and Antoni type B patterns. Antoni type A was the predominant pattern, characterized by spindle-shaped Schwann cells with elongated nuclei arranged in strings and nuclear palisades known as Verocay bodies. Antoni type B, on the other hand, was less prevalent and consisted of fewer spindle cells and a myxoid background. The diagnosis of a benign schwannoma, possibly originating from the hypoglossal nerve, was established based on the identified immunohistochemical positivity to S-100 and SOX10 protein, in addition to the presented evidence (Figure 3A-C). No atypical mitoses, necrosis, or mitoses were found.
Histopathological examination under microscope. A) Encapsulated tumour showing alternate hypercellular (Antoni A) and hypocellular (Antoni B) areas (H&E, ×100). B) hypercellular areas showing bland spindle cells with evidence of wavy nucleus and nuclear palisading (H&E, ×200). Antoni type A is composed of spindle shaped Schwann cells with elongated nuclei arranged in streams and nuclear palisades known as Verocay bodies. Antoni type B consists of less spindle cells and has a myxoid background. C) Immunohistochemistry: neoplastic cells are diffusely and strongly stained for S-100 and SOX10. SOX10: SRY-related HMG-box 10.
Discussion
Schwannomas are rare benign neoplasms, originating from myelin-producing Schwann’s cells, with predilection for sensory nerves (1, 3-5). They represent less than 1% of the neoplasms seen in the head and neck region. Non-vestibular schwannomas constitute less than 0.5% of all intracranial tumors and may be presented in the cervical region, hypoglossal canal and jugular foramen (6, 9, 12). Hypoglossal schwannomas are typically found in middle-aged women, with a mean age of 44.6 years, unlikely to our patient who was quite older (20). These schwannomas are rare, accounting for only about 5% of non-vestibular schwannomas (1, 3). Lesions are most commonly located intracranially, developing in the cerebellopontine angle from the origin of the nerve or in the hypoglossal canal, with a secondary extracranial extension, typically in the submandibular region (3). A grading scale based on imaging results can aid in guiding surgical management for this rare neoplasm. Nonaka et al. proposed a classification system for hypoglossal nerve lesions. The system includes three types: type A for intradural tumors, type B for transdural and extradural dumbbell-shaped tumors, and type C for extracranial base tumors (21).
The study concentrated on extracranial hypoglossal schwannomas. To the best of our knowledge, the English literature has reported approximately 42 cases of extracranial hypoglossal schwannomas to date, which are summarized in Table I.
Clinical features and symptomatology. Extracranial schwannomas typically present as a solitary, slow-growing, asymptomatic masses in the submandibular or parapharyngeal area, like in our patient (2, 4, 7). Due to their slow growth pattern, they may remain asymptomatic for a prolonged period. Neurological signs and symptoms are usually absent when the tumor is small (<2 cm). In cases where lesions are larger than 2 cm or of intracranial origin, various degrees of hypoglossal nerve paresis may be present. This is characterized by ipsilateral deviation, hemiatrophy, and fasciculations of the tongue (3, 6, 12). The resulting tongue dysfunction can lead to dysarthria and dysphagia, which may persist postoperatively, particularly in cases of intraoperative nerve injury (3, 12). Our patient was asymptomatic without any compressive symptoms. Neurological symptoms are exceedingly rare in patients with exclusive peripheral schwannomas due to their ability to expand in the adjacent cervical soft tissues (9). Lee et al. reported a rare case of hypoglossal schwannoma, located at the bifurcation of the common carotid, which mimicked a carotid body tumor (22). In cases of intracranial origin, the hypoglossal nerve may present various degrees of paresis, which manifests as ipsilateral deviation, hemiatrophy, and fasciculations of the tongue (3).
Imaging and diagnosis. Due to the rarity of extracranial hypoglossal nerve schwannomas and their resemblance to submandibular salivary gland neoplasms, paragangliomas, lymphomas and infectious diseases, a comprehensive diagnostic workup is essential. The correct diagnosis also has essential prognostic consequences for the surgical planning, since they may transform to malignancy in 2% of the cases, according to Plitt et al. (2). The diagnostic work-up can include neck sonography, fine needle aspiration cytology (FNAC), and radiographic imaging using CT and MRI.
We concur with Plitt et al. and Das et al. that preoperative FNAC is an unreliable method for diagnosing schwannoma. In our case, FNAC was not performed (2, 9). However, Parisi et al. suggested the significance of preoperative cytology, which can provide indications of a benign spindle cell process, but does not lead to a specific diagnosis (12).
From a surgical perspective, precise localization of a lesion defined by CT or MRI is crucial for complete tumor resection while preserving adjacent anatomical structures. It is also important to have a thorough understanding of the hypoglossal nerve’s anatomy, particularly its extracranial portion, in each individual case (3, 12). Although MRI is considered the most effective imaging method for detecting masses and assessing their extent, in some cases, such as ours (2, 8), patients undergo CT scans. Schwannomas are visible on CT scans as well-defined tumors with low or soft tissue attenuation and homogeneous or heterogeneous contrast enhancement, depending on the predominance of Antoni B fibers (1, 8, 12). On MRI, schwannomas show low signal intensity on T1-weighted images and high signal intensity on T2-weighted images (9). The T2-weighted image shows a characteristic target signal with increased peripheral signal intensity and decreased central signal intensity. The hyperintensity on T2-weighted images can be attributed to the predominance of Antoni B fibers due to their higher water content than Antoni A fibers (9). We did not consider MRI in our case as our primary clinical diagnosis was submandibular salivary gland malignancy.
Treatment. Based on the preoperative diagnostic and intraoperative clinical findings, we performed a complete tumor resection through a transcervical approach without involving the submandibular salivary gland. The hypoglossal nerve was preserved and no permanent neurological deficits observed postoperatively.
For isolated extracranial lesions, especially those originating from the descending loop of the hypoglossal nerve, surgical excision by an experienced surgeon is recommended as the first-line treatment modality (2, 3, 7, 9). The primary objective is the complete tumor resection with meticulous dissection from the nerve fascicles. Studies have shown that intracapsular enucleation preserves nerve function without recurrence (5, 23). En bloc resection of the nerve has been suggested to reduce the risk of recurrence and potential for sarcomatous transformation (24). Adjuvant radiotherapy may be recommended in cases of residual tumor (2). Our approach was to perform en bloc resection of the tumor and its origin tissue. In cases that require a total or partial excision of the nerve, a reconstruction with graft from the greater auricular nerve is feasible (5, 8).
Early intervention is crucial for accurate diagnosis as histological examination is necessary even if the clinical and imaging diagnosis is precise (3). Additionally, the slow growth tendency of the lesions can lead to compression of surrounding structures, requiring a more delicate surgical approach with a higher risk of complications. It is important to note that schwannomas are radioresistant and therefore radiotherapy is not beneficial (3). Accurate preoperative identification is crucial to prevent nerve damage and postoperative neurological morbidity. Plitt et al. highlighted the great importance of the intraoperative neuromonitoring, particularly in lesions located near the carotid bifurcation, for favourable surgical outcomes and function preservation (2). Intraoperative monitoring can also aid in nerve-sparing resection by tracking residual tumors intraoperatively (2). In cases of malignant schwannomas with infiltrating behaviour, complete or partial nerve resection is often unavoidable (3). Subsequently, reconstruction techniques of direct microsurgical end-to-end anastomosis or with nerve grafts, for example of the great auricular nerve, or biocompatible scaffolds can be applied to limit morbidity (3). In cases of postoperative longstanding facial palsy, the sternocleidomastoid flap transfer can be regarded as a reliable and effective procedure to achieve moderate improvement of the oral commissure excursion with moderate donor site morbidity (25).
Neuropathological features. Extracranial hypoglossal schwannomas can be classified as benign or malignant lesions (3). Benign schwannomas are enclosed in the epineurium and manifest as distinct masses in asymmetrical orientations, either attached to or separated from the originating nerve. Several histological subtypes have been described: melanocytic, plexiform, microcystic-reticular, cellular, ancient, epithelioid and psammomatous (3, 12). Malignant schwannomas are typically malignant neoplasms and are classified as peripheral nerve malignancies within the category of neurofibromatosis (3). They tend to become malignant over time, often recurring after resection and cannot be distinguished from malignant neurofibromas and neurofibromatosis (3). Unlike benign schwannomas, malignant schwannomas can present as eccentric or non-delimited nerve masses. Clinically, malignant schwannomas tend to infiltrate adjacent structures, resulting in necrosis and polymorphic components. Histologically, they resemble fibrosarcomas as they are composed of cells with elongated nuclei arranged in fascicles and show frequent mitotic events (3).
The histopathologic report following the operation revealed an encapsulated neoplasm that originated from the left hypoglossal nerve. The neoplasm exhibited alternating hypercellular and hypocellular areas. The hypercellular areas contained bland spindle cells with wavy nuclei and nuclear palisading. This confirmed the classical diagnosis of hypoglossal schwannoma, which is composed of two distinctive cellular patterns in varying proportions: Antoni A type which is compact and hypercellular with elongated spindle cells and nuclei aligned in parallel termed ‘palisades’, separated by hyaline bands (known as Verocay bodies); Antoni B type, which is polymorphic, loose, and hypocellular and exhibits mucus and microcystic degeneration. Degenerative phenomena such as fatty degeneration may occur and the vessels may appear telangiectatic, sinusoidal, or with thickened walls (3). The cells generally appear elongated with regular, ovoid nuclei. Due to the displacement of the original nerve during growth, lesions of this type do not contain axons, as evidenced by silver staining and immunohistochemical testing of neurofilaments. Thrombosis, bleeding, and calcification may also be visible (3). Furthermore, immunohistochemical analysis typically shows positivity for S100 protein, which is highly expressed in Schwann cells, particularly in Antoni type A areas (3, 10, 13). This information can be helpful in confirming a diagnosis of schwannoma, as in our case.
Outcome. Extracranial hypoglossal schwannomas have a generally positive prognosis (5). Recurrence is rare, particularly in cases of incomplete resection, and malignant transformation is also uncommon (12). For small benign lesions without symptoms, clinicians may consider conservative treatment without immediate intervention. This may involve watchful waiting with regular follow-up appointments and imaging studies, radiation therapy, or stereotactic radiosurgery. Radiation therapy is typically used for malignant tumors, but it may also be preferred for benign lesions in cases where surgery is not feasible due to the lesion’s unfavourable location or the patient’s health condition (12). However, stereotactic radiosurgery is generally reserved for intracranial schwannomas, as it allows for precise radiation dosing to the neoplasm while minimizing exposure to surrounding healthy tissues (12). In this case, the tumor was completely removed while preserving the nerve using a transcervical approach. This allowed for optimal exposure and prevented any long-term adverse neurological effects post-surgery. There have been no reported clinical recurrences in the 3-year follow-up.
Conclusion
This case report discusses the diagnostic challenges presented by extracranial hypoglossal schwannomas due to their rarity and similarity to other submandibular pathologies. Achieving an accurate diagnosis requires correlating preoperative imaging characteristics, intraoperative findings, and histopathological characteristics. The optimal therapeutic strategy is nerve-sparing complete surgical excision, although this can be challenging. Further research is needed to standardize therapy and evaluate long-term outcomes.
Acknowledgements
The Authors would like to thank the patient for accepting to participate in this study.
Footnotes
Authors’ Contributions
Spyridoula Derka and Andreas Sakkas drafted the manuscript. Andreas Sakkas is the corresponding author. Spyridoula Derka and Spiros Stavrianos contributed to the protocol preparation and guidance of the study. Marcel Ebeling extracted and validated the clinical and radiological findings and was involved in drafting the manuscript and finalizing it for submission. Georgia Vairaktari and Sebastian Pietzka revised the relevant literature and helped in editing the manuscript. All Authors read and approved the final manuscript.
Funding
This research received no external funding.
Conflicts of Interest
The Authors declare that they have no competing or financial interests in relation to this study.
- Received January 17, 2024.
- Revision received February 7, 2024.
- Accepted February 9, 2024.
- Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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