Granular cell tumor (GCT) is a rare benign tissue neoplasm of unknown etiology It was first described by Abrikossoff in 1926 [1]. Despite being called granular cell myoblastoma because of its association between granular cells and skeletal muscle, a designation of “granular cell tumor” is now most commonly used [2].

According to immunohistochemistry studies, this lesion originates from neural cells, particularly Schwann cells. Clinically, it is a solitary, painless, slow-growing, well-delimited lesion. In more than 50% of cases, this tumor appears in the head and neck region. The most common location in the oral cavity is the tongue [3]. There is a 2% GCT population reported as malignant. This type of tumor can develop at any age [4]. However, it most often appears between the 4th and 6th decades of life [5]. Although studies suggest a female preference, this prevalence is not unanimously accepted [6].

The ideal treatment for GCTs may be controversial. However, current treatment options are as follows: conservative approach with regular follow-up of tumors less than 10 mm in diameter without evidence of malignancy and surgical excision for tumors more than 20 mm in diameter or benign tumors that cause symptoms or suspected cases of malignancy [6].

We report a case of a 43-year-old female patient, referred to the stomatology consultation of the Coimbra Hospital and University Centre by her general and family medicine doctor, for the observation of a two-year-old lesion on the tongue. The patient reported that the lesion was painless and slow growing. She had no relevant personal history or relevant usual medication. There were no smoking and/or alcohol habits.

Physical examination revealed a firm, well-circumscribed whitish lesion of about 1.5 cm in diameter, located at the posterior limit of the middle third of the dorsum of the tongue (Figure 1). Thus, an incisional biopsy was performed, whose histological study revealed the diagnosis of granular cell tumor in the dorsal region of the tongue. Given the result, we opted to perform an excisional biopsy under local anesthesia (Figure 2). The macroscopic sample had the dimensions of 1.5 × 0.9 × 0.4 cm, with whitish surface (Figure 3). Its anatomopathological study confirmed the diagnosis of granular cell tumor in the dorsal region of the tongue, and it also reported a submucosal lesion, consisting of proliferation of polygonal cells with large clarified granular cytoplasm PAS+, and with central, oval and monotonous nucleus (Figure 4). Regarding immunohistochemical analysis, the cells had marked and diffuse immunostaining for S100 protein (Figure 5).

In the postoperative period the patient evolved without intercurrences and the suture was removed two weeks after surgery. The patient was treated with analgesic therapy, namely ibuprofen 600 mg 12/12 hours and acetaminophen 1000 mg 8/8 hours for five days. There are no signs of recurrence of the lesion 6 months after the surgery, and the patient is regularly checked by her assistant physician at follow-up appointments.

Granular cell tumor, also known as Abrikossoff’s tumor, is characteristically asymptomatic, with slow growth and is often accidentally detected. It is characterized by the presence of a small, well-defined, submucosal nodular mass, about 1 to 3 cm in size, of firm consistency and usually covered by intact mucosa [7].

GCTs can develop in almost any part of the body, including skin, subcutaneous tissue, larynx, trachea, bladder, uterus, vulva, and central nervous system, and are most commonly found on the tongue, accounting for almost 30% to 60% of all the GCTs [3].

A wide range of cells has been proposed as the source for granular cells, including histiocytes, myofibroblasts, neural cells, neuroendocrine cells, and undifferentiated mesenchymal cells [1]. Abrikossoff described the lesion composed of lenticular and myoblast tissues, sometimes presenting longitudinal and transverse striations, or containing dark granules.

The most plausible hypothesis for the appearance of this lesion is related to altered Schwann nerve cell metabolism. The persistence of the presence of S-100 protein (pathognomonic marker for peripheral nerve sheath tumors) associated with anatomical similarities with peripheral nerve fibers supports this theory. In this case, the immunohistochemical analysis showed a positive chain for protein S-100, which is considered sufficient for the proposed diagnosis [5]. (Figure 5) Pseudoepitheliomatous hyperplasia (PH) (of the covering epithelium) is present in about 50% of GCT cases [7]. It has been suggested that stimulation of basal cell proliferation occurs through interaction between granular cells and neighboring epithelial cells [8](8). In this case, the presence of labelled HP could initially mimic a squamous cell tumor (SQT). However, SQT is not compatible with the diagnosis due to the absence of several malignant features such as nuclear pleomorphism, mitotic figures or hyperchromatism, for example. The anatomopathological study should be carefully carried out to avoid an incorrect diagnosis of this type of tumor. Up until now, no oral cavity granular cell tumor has been associated with a squamous cell tumor and the dorsum of the tongue is one of the least likely sites for the development this type of cancer [7]. There is a single case of squamous cell tumors involving a granular cell tumor reported by Hee Young Son et al. [9], which leads us to believe that it would be interesting to have more studies on the relationship between granular cell tumors and other tumors.

Clinically, the granular cell tumor can be confused with other connective tissue lesions. Neurofibroma, schwannoma and palisade encapsulated neuroma should be the main considerations for tongue injuries. Tumors of salivary glands, lipoma and other benign mesenchymal neoplasms may present intraorally as asymptomatic nodules similar to the granular cell tumor. Traumatic fibroma is a common reactive lesion that should be included in the differential diagnosis.

Recurrence of GCT, when diagnosed as benign, is uncommon, and is often the result of incomplete excision of the original lesion [10], with 15% of recurrent cases due to incomplete excision being reported [11]. Complete excision of the lesion may not be always possible due to absence of capsule [12]. Therefore, it is advisable to perform an excision with sufficient safety margin (>10 mm) to reduce the probability of recurrence. There are other surgical methods involving the use of laser or electric scalpel that effectively remove the lesion and, if available, could be used. However, they should be preceded by incisional biopsy because the use of these surgical means may increase the risk of compromising the microscopic diagnosis [13].

This case demonstrates the importance of the relationship between clinical and histological and immunohistochemical aspects, all of which are essential to establish the correct diagnosis of GCT [14,15]. In addition, immunohistochemical analysis makes it possible to deepen the knowledge of the etiopathogenesis of GCT, as well as the possible association with other tumors, such as squamous cell tumor. Thus, all available diagnostic tools should be orchestrated to improve the robustness of clinical decision to perform a correct medical-surgical approach to this type of injury.