Granular Cell Tumor of the Tongue: 2 Cases Report and Review of the Literature

Granular cell tumor, also known as Abrikossoff tumor, is a rare lesion that arises from the nervous system. Most of these tumors are benign and only 1-2% are malignant. Although they can be found in any part of the human body, 45-65% appears in the head and neck region, mainly in the oral cavity. Here, we report 2 cases of granular cell tumor of the tongue, diagnosed by excisional biopsy. Until the present moment, both patients remain with no recurrence.


Introduction
Case 1 Granular cell tumor (GCT) was first described by Abrikossoff in 1926 [1,2]. The etiology was controversial, but it has now been determined that GCT has a neuroectodermal origin [1,[3][4][5]. GCTs areun common soft tissue tumors, with a prevalence ranging from 0.019% to 0.03% of all tumors [4,6,7].   A healthy 51-year-old Caucasian 30 woman, with no smoking or drinking habits, was referred to our Stomatology Department with a seven-month history of a painless nodule located in the tongue. An intra-oral examination identified a whitish, painless, elastic nodule on the right border of the tongue, measuring approximately 1 cm in diameter. No ulcerations were seen ( Figure 1).
Excisional biopsy was performed. Histopathologic analysis revealed a neoplastic lesion with pseudo epitheliomatous hyperplasia, large and polygonal cells with eosinophilic and granular cytoplasm (Figure 2 and 3) and S100 protein positivity ( Figure 4). The diagnosis was GCT with tumor free-margins. Ten months after excision, the patient still has no recurrence.

CASE 2
A healthy 60-year-old male patient was referred to our department with anasymptomatic tongue lump known for two years. The patient related this lesion to denture induced trauma. On oral examination, a solitary, reddish, non-ulcerated, 1 cm sized lesion was seen in theleft dorsal surface of the tongue. Excisional biopsy was consistent with GCT ( Figure 5 and 6), even though with positive surgical margins. The patient refused further surgery. 1 year after excision, there is no visible tumor growth.
GCT is covered by intact mucosa, however bigger lesions may have an ulcerated surface and simulate a malignant tumor [1]. It is unencapsulated and has a poorly defined margin [1,11]. Imaging has a significant role in the diagnosis of soft tissue tumors of the head and neck.When there is an obvious or suspected head and neck tumor, Computed tomography (CT) is often the first diagnostic imaging examination performed [9]. Magnetic Resonance Imaging (MRI) has higher soft tissue resolution, allowingdifferentiation and characterization of soft tissue tumors [9]. Physiologic imaging techniques, such as PET/CT and diffusion-weighted MRI can help differentiating malignant and benign soft tissue tumors however, they aren't usually diagnostic [9].
GCT is a slow growing solitary tumor and can be multiple in 5 to16% of the cases [10]. 45% to 65% of all GCTs are in the head and neck region and 70% of 52 these are found in the oral cavity (mainly in the tongue, oral mucosa and hard palate) [1]. Generally, it is an asymptomatic nodular lesion and a pinkish or yellowish surface [1,11].
Compared to TC and MRI, intraoral ultrasonography of the tongue masses, complemented by Doppler, is suitable and can show the internal structure and vascularity of the masses, without metal artifacts [12]. Theextraoralultrasonographydoesn'tprovideacceptableimagesofthetongueandpalate [12].
Regarding our clinical cases, CT and MRI weren't performed because both lesions were superficial and small. Intraoral ultrasonography is not available in our hospital. So, surgical excision was mandatory as histopathology remains the gold standard for definitive diagnosis of soft tissue tumors and the excision of the entire lesions, with a safety margin, possible. Most of the GCTs are benign, and only 1% to 2% have a malignant transformation, being reported in literature in less than 30 cases [11]. The most common metastasis sites are lymph nodes and lungs [13]. According to some authors, the GCT does not undergo malignant transformation but may coexist with carcinoma [3].
Fanburg-Smith and colleagues proposed six criteria for a histological diagnosis of malignancy: necrosis, spindle cells, and vesicular nuclei with large nucleoli, increased mitotic activity, increased nucleocytoplasmic ratio 63 and pleomorphism [3]. If three or more of these are present, the tumor is considered malignant [3].

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Despite its low prevalence, GCT should be considered in the differential diagnosis of oral lesions, especially in the tongue. Histopathology is the gold standard for the diagnosis of GCT. The prognosis is good as less than 2% are malignant. However, when tumor excision is not complete, local recurrence is frequent. Adequate surgical margins are necessary as the tumor has no capsule and invades surrounding structures. Follow-up must be extended and regular to allow appropriate management in case of recurrence.
Immunohistochemical studies suggest a neuroectodermal origin, supported by specific neuronal markers positivity, such as S100 protein and enolase [1]. Nowadays, it is accepted that tumor cells arise from Schwann cells or their precursors [1]. Differential diagnosis should include any intraoral soft tissue masses, such as fibroepithelial polyp, neurofibroma, dermoid cyst, minor salivary gland tumor, lipoma and others [6,14]. Surgical excision is the treatment of choice [3]. When tumor resection is complete, the recurrence rate is low (approximately 2 to 8%) [1,15]. The lack of capsule, frequently, compromises the ability to obtain tumor-free margins (as observed in case 2), so excision should have wide margins [13]. Incomplete resection often results in local recurrence, with a 20% recurrence rate [13,15].