Curious case of swelling in the thigh: Benign granular cell tumor

INTRODUCTION

Granular cell tumors (GCTs) are rare, benign soft tissue neoplasms of neural origin, accounting for approximately 0.5% of all soft tissue tumors. These tumors are typically solitary and present most frequently in the head-and-neck region, with the tongue being a common site of involvement. Although GCTs are generally benign, <1% of cases have been reported as malignant, underscoring the importance of differentiating between benign and malignant forms. Malignant GCTs are known for their aggressive behavior and poor prognosis, making accurate diagnosis and management crucial. In most cases, GCTs are asymptomatic and grow slowly, which can sometimes delay diagnosis. While these tumors are commonly located in the head and neck, they are rarely found in the extremities. In this report, we present the case of a 52-year-old male who was diagnosed with a benign GCT in the left thigh, a less common site for this condition. This case highlights the need for clinicians to consider GCTs in the differential diagnosis of long-standing soft tissue swellings, even in unusual locations.

CASE REPORT

We present the case of a 52-year-old male who presented with an 8-month history of painless swelling in his left thigh. On clinical examination, the swelling measured approximately 2 × 3 cm in size. An excision biopsy was performed to obtain tissue for further evaluation. Histopathological examination revealed a lesion consisting of sheets of cells separated by thin collagenous bands. The individual tumor cells were round to polygonal in shape, exhibiting mild nuclear atypia and abundant eosinophilic cytoplasm containing coarse granules [Figure 1a]. In addition, the overlying epithelium showed focal pseudoepitheliomatous hyperplasia. Immunohistochemical (IHC) analysis revealed strong positivity for SOX-10 and inhibin [Figure 1b and c]. The final diagnosis was consistent with a benign GCT. The histopathological examination revealed no evidence of increased mitotic activity or necrosis, which, along with the lack of any other signs of malignancy, strongly suggested that the tumor was benign. The Ki-67 index was <7%, further confirming the benign nature of the lesion [Figure 1d]. As a result, the patient was scheduled for a wide local excision of the GCT of the left thigh. After obtaining anesthetic fitness, the procedure was successfully performed. The intraoperative period was uneventful. Postoperatively, the patient tolerated a regular diet and had no issues with voiding. On post-operative day 3, the left thigh wound was inspected and found to be healing well. The surgical site healed unremarkably. The patient reported symptomatic improvement and was subsequently discharged. The patient has been regularly followed up after discharge, and there have been no signs of recurrence.

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Figure 1:

(a) Hematoxylin and eosin (H&E) stain at ×200 magnification showing tumor cells with abundant granular eosinophilic cytoplasm. Red arrow indicates the granular appearance of the cytoplasm. (b) Immunohistochemistry (IHC) for Inhibin at ×200 showing positive cytoplasmic staining, highlighted by the red arrow. (c) IHC for SOX-10 at ×200 demonstrating nuclear positivity in tumor cells, as indicated by the red arrow. (d) IHC for Ki-67 at ×200 showing a low proliferation index (<7%), with scattered positive nuclei marked by the red arrow.

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DISCUSSION

GCTs are primarily derived from Schwann cells. These tumors are typically solitary, although 10–15% may be multifocal. While it is uncommon for GCTs to occur in the extremities, case reports have documented their presence in peripheral nerves such as the lateral femoral cutaneous nerve, sciatic nerve, and ulnar nerve, highlighting the association of GCTs with peripheral nerves. As observed in this case, GCTs often present as asymptomatic, slowly growing, benign solitary lesions. In the clinical evaluation of a subcutaneous GCT, differential diagnoses include lipoma, dermatofibroma, adnexal tumors, schwannoma, and neurofibroma. These conditions can be distinguished through histopathological analysis and IHC profiling.^[1] Histopathologically, GCTs are characterized by tumor cells that have abundant eosinophilic, granular cytoplasm, which is attributed to lysosome accumulation. These cells are typically polygonal in shape and contain small, centrally located nuclei. A notable feature often associated with cutaneous and mucosal GCTs is pseudoepitheliomatous hyperplasia, commonly observed in the overlying epithelium. As far as IHC is concerned, S-100 is a key marker for GCTs, as these tumors show strong positivity, supporting their Schwann cell origin. SOX10 is also a typical marker for GCTs, given that these tumors arise from Schwann cells of neural crest origin. In addition, GCT’s stain is positive for cluster of Differentiation 68 (CD68), CD56, CD57, PGP9.5, neuron-specific enolase, calretinin, inhibin, transcription factor 3 (TFE3), and vimentin.^[2]

Malignant GCTs are typically larger, often exceeding 3–5 cm in size, and the primary indication of malignancy is the development of metastatic disease. Common metastatic sites include regional lymph nodes, lungs, and bones. Histopathologic criteria to diagnose malignant GCTs include:^[2]

1. Presence of necrosis

2. Spindled tumor cells

3. prominent nucleoli and vesicular nuclei

4. Increased mitotic activity (≥2 mitoses per 10 high-power fields)

5. High nuclear-to-cytoplasmic ratio 6. Nuclear pleomorphism.

In the absence of these features, the tumor is considered benign, as in the case presented. It is important to differentiate benign from malignant GCTs, as the treatment and prognosis differ significantly. The prognosis for benign GCTs is excellent. Although rare, there have been reports of metastatic lesions arising from histologically benign GCTs, underscoring the need for careful monitoring and follow-up.^[3] For benign GCTs, complete surgical resection remains the only effective and curative treatment. Radiation and chemotherapy are not indicated for benign cases. The recurrence rate for benign GCTs is low, ranging from 2 to 8%, but incomplete excision increases the risk to 21–50%.^[4] Most local recurrences, where the tumor arises in the same or adjacent location, are directly linked to incomplete excision. In this case, despite the benign nature of the tumor, wide local excision (re-surgery) was performed because the margins were involved. This was done to minimize the risk of recurrence.

CONCLUSION

Due to the absence of characteristic clinical features, GCTs are not always included in the initial differential diagnosis. However, it is important to consider GCTs when encountering soft tissue swelling, particularly one that is long-standing. Assessing the involvement of surgical margins in benign conditions is crucial, and if necessary, do not hesitate to reoperate to ensure clear margins and prevent recurrence.