A Case of Mediastinal Granular Cell Tumor with Horner’s Syndrome

Abstract

Granular cell tumor (GCT) is found in various organs but is rare in the mediastinum. We report a case of mediastinal GCT in a 19-year-old woman who presented with left ptosis and miosis. CT and MRI revealed a 29-mm well-circumscribed tumor located close to the first thoracic vertebra with features suggesting a neurogenic tumor. The tumor was completely excised using single-port video-assisted thoracoscopic surgery. Histopathological and immunohistochemical analysis revealed that the tumor was a benign GCT. Postoperatively, left ptosis and miosis had improved slightly. To our knowledge, this is the first report regarding mediastinal GCT presenting with preoperative Horner’s syndrome.

Introduction

Granular cell tumor (GCT), although typically observed in the digestive system, head, neck, breast and skin regions, can occur almost anywhere in the body; >5% of patients have multiple lesions.¹⁾ At the time of diagnosis, most patients are aged 30–50 years; there is a 2:1 female to male ratio.²⁾ The occurrence of GCTs in the mediastinum is extremely rare,³⁾ and Horner’s syndrome has not been previously described as a symptom of GCT. We report a rare case of mediastinal GCT with preoperative Horner’s syndrome.

Case Report

A 19-year-old woman gave her informed consent for the publication of this study. She was referred to our hospital for extended examination of a superior mediastinal mass that had been detected using a chest X-ray and a CT scan. She had no previous history of significant illness. On physical examination left ptosis and miosis were noted, but anhidrosis was not clear. The results of clinical laboratory tests were within the normal range. A CT scan showed a well-circumscribed and homogeneous mass measuring 29 mm × 22 mm and located close to the vertebral column (Th1; Fig. 1A and 1B). Both T1- and T2-weighted MRIs showed inhomogeneous low intensity regions inside the tumor, and high intensity regions on the tumor surface (Fig. 2A and 2B). The location of the tumor and symptoms suggested that it had a neurogenic origin with complicating Horner’s syndrome.

Fig. 1.

Contrast-enhanced chest CT image. (A) Axial section showing a poorly enhanced well-circumscribed 29 mm × 22 mm × 17 mm mass, closely attached to the vertebral column. (B) Coronal section.

Fig. 2.

Chest MRI. The tumor exhibited inhomogeneous low intensities. High intensities were found on tumor surface on T1- and T2-weighted images. (A) Coronal section: T1-weighted image. (B) Coronal section: T2-weighted image.

The patient underwent single-port video-assisted thoracoscopic resection of the tumor. Resection was performed through a 2.5-cm skin incision located in the fourth intercostal space in the middle axillary line using a rigid 5-mm thirty-degree thoracoscope. A solid circumscribed tumor was found on the first costeovertebral joint attached to the sympathetic nerve. The tumor was completely excised without sympathetic nerve injury. Postoperatively, no complications developed and the left Horner’s syndrome improved slightly. The patient’s left miotic pupillary diameter increased from 2.5 mm to 3 mm, and the diameter of her left palpebral fissure improved from 7 mm to 8 mm. She was discharged on the third postoperative day.

The excised tumor was a solid encapsulated whitish mass measuring 30 mm × 18 mm. Histopathological examination revealed that the mass was mostly composed of sheets of rounded or short spindle cells with eosinophilic cytoplasmic granular structures (Fig. 3A and 3B), and was partly composed of normal ganglion cells at its periphery (Fig. 3C). Immunohistochemical studies revealed strong and diffuse cell reactivity for S-100 (Fig. 3D), and partial reactivity for neuron-specific enolase (NSE). Staining was negative for c-KIT, chromogranin-A, synaptophysin, CD56 and neurofilaments. The MIB-1 labeling index was <2%. Based on these findings, the tumor was diagnosed as a benign granular cell tumor (GCT) arising from sympathetic ganglion tissue. There was no sign of tumor recurrence during the 4-month follow-up period.

Fig. 3.

Hematoxylin-eosin (HE) stained tumor sections (A) with diffuse proliferation of spindle to oval-shaped cells (×100), and (B) with abundant cytoplasm filled with numerous eosinophilic granules (×400). Non-tumorous ganglion cells can be seen in the peripheral area. (C) and (D) Immunohistochemically stained tumor sections. The tumor cells are strongly positive for S-100 protein (×40).

Discussion

In immunohistochemical studies, most GCTs show positivity for both S-100 protein and NSE, supporting the view that GCTs have a Schwann cell origin.^4,5) Although, there is a considerable difference between GCTs and schwannoma at the ultrastructural level, they are common benign tumors of Schwann cell origin that contain numerous granules in their cytoplasm. A recent study by Shintaku⁶⁾ revealed that this morphological difference merely reflects the accelerated formation of autophagosomes in GCTs. Therefore, GCTs can be regarded as a special form of schwannoma, and naturally share most of the clinical features of schwannomas.⁶⁾

To the best of our knowledge, only 13 cases of mediastinal GCTs have been previously reported. The patients ranged in age from 11 to 66 years. Three of the 13 reported cases were malignant, and all malignant GCT patients presented with symptoms that included cough, dyspnea or chest pain. Conversely, 7 of 10 benign GCT patients were asymptomatic. Two benign GCT patients presented with cough, and one patient had both a cough and chest pain.^3,7,8) Thus, Horner’s syndrome, as a symptom of GCT, has not been previously described. The present patient may have gradually developed unilateral Horner’s syndrome as a result of stellate ganglion compression caused by the slow growth of the superior mediastinal GCT.

GCTs are generally benign lesions, and malignant GCTs with metastatic or invasive characteristics are rare. However, some GCTs that initially have benign features can become clinically malignant, and develop local recurrence, distant metastasis and/or lymph node metastasis.⁷⁾ Lack et al.¹⁾ reported that 5 of 24 (20.8%) GCT patients with incomplete tumor resection developed local recurrence. Consequently, complete excision of tumor is necessary to prevent local recurrence. Generally, it is difficult to pathologically confirm all cases of mediastinal tumor before surgery, but clinicians and pathologists should consider the likelihood of GCT while diagnosing and managing a mediastinal mass.

Conclusion

A rare case of mediastinal GCT with Horner’s syndrome was reported. Considering the likelihood of clinical malignancy, complete excision of the tumor should be considered as the best and standard treatment procedure.

Disclosure Statement

We do not have any financial support or relationships that may pose conflict of interest.