An axillary granular cell tumor: A rare neoplasm at an unusual site

Granular cell tumors (GCTs) are rare [1-6], first described by Abrikossoff in 1926 [7]. Immunohistochemical and ultrastructural studies have demonstrated their Schwannian differentiation [8]. A slight female to male and black to white predominance exists [1,3,6,9,10]. GCTs occur in adults between the fourth and sixth decade of life [3,7,10,11]. They develop mainly in the head and neck. As for the oral cavity, the tongue is most affected in up to 65% of cases [1,3,6,9,10,12,13]. Cases of GCTs of the digestive tract, back, and vulva have been reported as well [1,3,4,11,14-16]. The pathogenesis of the GCT has not yet been elucidated [1,6,12]. GCTs may also develop at unusual anatomic sites and can, therefore, be taken for other tumors, essentially malignant. The breast and axillary extension are unusual sites also affected by GCTs in almost 5–8% of cases [5,6,13,17,18]. Such a tumor can clinically and/or radiographically mimic an invasive carcinoma.

Herein, we report a new case of an axillary GCT in a young male patient.

CASE REPORT
A 30-year-old male patient without a particular medical history presented himself to the department of dermatology with an axillary nodule. A physical examination revealed a firm painless axillary subcutaneous tumor on ulcerated skin, initially presumed to be a lymphoma or a metastatic lymph node. An imaging survey and laboratory tests were within normal limits. The nodule was surgically removed. Upon gross examination, it was a mass 1 cm in diameter. A microscopic examination revealed a wellcircumscribed proliferation occupying the dermis. The overlying epidermis showed pseudoepitheliomatous hyperplasia and was focally ulcerated. Large and polygonal tumor cells had abundant eosinophilic and granular cytoplasm with small nuclei in a central position (Fig. 1). There was no nuclear pleomorphism or tumor necrosis. The tumor cells stained positively for S100 (Fig. 2). Surgical margins were clear. No recurrence has been observed within a 6-month follow-up period.
Histologic diagnosis of GCTs is usually unchallenging. These tumors present themselves as well-circumscribed or infiltrative proliferations polygonal in shape with abundant and granular cytoplasm. Their nuclei are small and have a central position. GCTs are usually separated by thin bands of connective tissue [1,[4][5][6]9,10,12], and, although they are usually reported as benign, malignant forms exist, even if rare, accounting for less than 3% of all cases of GCTs reported in the literature [7,9,10,12]. Most cases of GCTs in the breast and axillary region were histologically diagnosed as malignant GCTs [8,18,19]. The unique criteria confirming malignancy is the presence of metastasis [7]. However, some classification systems have been established to predict the malignant potential of GCTs. Fanburg-Smith et al. were the first to establish a classification system of six items defining three categories of GCTs: benign, malignant, and atypical [7,10,12]. In order to refine this classification, Nasser et al. reviewed 48 cases of GCTs, concluding that necrosis and mitotic activity were most correlated with malignancies. They also showed that Ki67 may be helpful in cases difficult to classify [7]. Conventional GCT cells stain positively for S100, CD68, and neuronspecific enolase [1,6,10,11]. Immunohistochemistry is of great help to rule out differentials and mimickers of GCTs, such as atypical fibroxanthoma, rhabdomyoma, dermatofibroma, and hibernoma [7]. Benign GCTs require surgical removal with negative margins to prevent recurrence [1,2,5,7]. Malignant forms with metastases complicate survival and increase mortality rates, which may reach 40% [4,7,12]. The benefits of adjuvant therapies after surgical excision have not been proven so far [12].
To conclude, the clinical presentation observed in our case eventually confirmed the diagnosis of malignancy. The negative results of the imaging survey and laboratory tests prompted surgical removal of the tumor mass. A diagnosis of a benign GCT with negative margins was reached and spared our patient from overtreatment.

Consent
The examination of the patient was conducted according to the principles of the Declaration of Helsinki.
The authors certify that they have obtained all appropriate patient consent forms, in which the patients gave their consent for images and other clinical information to be included in the journal. The patients understand that their names and initials will not be published and due effort will be made to conceal their identity, but that anonymity cannot be guaranteed.