Pleural-based granular cell tumor

Abstract

Granular cell tumors are rare tumors of Schwann cell origin that arise from tissues of neural crest and mesenchymal origin. We report the clinical, radiographic, and pathological features of a pleural-based granular cell tumor in a 60-year-old African American man.

Granular cell tumors are mostly benign tumors of Schwann cell origin and occur mostly in the skin, subcutis, and along mucosal surfaces and occasionally within skeletal muscle, the gastrointestinal tract, and the respiratory tract. A granular cell tumor was originally reported by Abrikossoff in 1926 (1). Clinical manifestations depend on the involved body part and whether the tumor is benign or malignant. These tumors exhibit a characteristic histologic appearance on routine hematoxylin and eosin–stained sections, and the diagnosis can be confirmed by immunohistochemical coexpression of S100 and CD68 by the tumor cells, among other markers (2).

CASE PRESENTATION

A 60-year-old black man with a past medical history of schizophrenia, hepatitis B, and tobacco abuse presented to our clinic for evaluation of a right lung mass. He had presented earlier to his primary care physician with complaints of a chronic cough and chest congestion prompting a computed tomography (CT) scan of his chest for further evaluation. Cough was intermittent, present for about 1 to 2 years, and worsening in the prior 3 to 4 months. There was no hemoptysis, but there was production of yellow-green sputum. He denied any dyspnea, fevers, or chills. He smoked two packs of cigarettes daily for over 30 years and still smoked about 1 pack daily. He had no occupational exposures and no family history of lung disease or malignancy. He was on clozapine, benztropine, and fluphenazine. His physical examination was remarkable for finger clubbing.

CT scan of the chest showed a 2.6 cm smooth right paraspinal pleural-based mass and radiologic evidence of centrilobular emphysema with microblebs predominating in the upper lobes bilaterally (Figure 1). Pulmonary function tests showed a forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) ratio of 71%; FEV₁ of 2.6 L, or 112% of predicted; FVC of 3.67 L, or 121% of predicted; slow vital capacity (SVC) of 4.67 L; residual volume of 5.56 L, or 297% of predicted; and total lung capacity of 10.23 L, or 183% of predicted. These findings were consistent with possible obstructive ventilatory defect with significant hyperinflation and air trapping. F18-fluorodeoxyglucose positron emission tomography scan showed an increase in metabolic activity for the pleural-based mass at 3.8 SUV. There was a destructive lesion at the left aspect of the T4 vertebral body, which showed increased metabolic activity with a maximum SUV of 5.7.

Figure 1.

CT of the chest showing a 2.6 cm smooth right paraspinal pleural-based mass and radiologic evidence of centrilobular emphysematous disease.

The patient underwent CT-guided fine needle aspiration (FNA) and core biopsies of the pleural-based mass (Figure 2). The FNA cytology was positive for a neoplasm composed of benign-appearing cells with abundant granular cytoplasm, and the hematoxylin and eosin–stained FNA cell block and core biopsy sections demonstrated closely packed and uniformly bland polygonal cells with similarly abundant eosinophilic cytoplasm. Immunohistochemical stains performed on the core biopsy showed that the tumor cells were negative for pan keratin, smooth muscle actin, HMB-45, and MART-1. The tumor cells were positive for S100, CD68, vimentin, inhibin, and SOX 10, with a low proliferative rate (<5%) on Ki 67. These results were consistent with a granular cell tumor.

Figure 2.

(a) Hematoxylin and eosin stain of the fine needle aspiration cell block. (b) S100 stain of the core biopsy. (c) CD68 stain of the core biopsy.

The patient underwent magnetic resonance imaging of the brain, which did not show any metastatic deposits. Further histologic evaluation of the lesion on the left aspect of T4 was negative for malignancy (scant fibrous tissue and bone). However, this sample was not felt to be adequate, and since the lesion had increased SUV activity the multidisciplinary team suggested a surgical corpectomy and vertebroplasty of the T4 lesion. A myeloma panel was negative.

Our patient had severe emphysematous changes on his CT scan and continued to smoke, which were most likely contributing to his chronic cough.

DISCUSSION

Granular cell tumors were originally called granular cell myoblastomas, as they were thought to be of myogenic origin. However, recent ultrastructural, immunohistochemical, and histologic studies revealed that they are more likely to be of Schwann cell origin (1–3). They can be benign or malignant. Granular cell tumors are rare, and the literature describing them is in the form of case reports and series. Our search of the literature did not reveal any prior report describing a pleural-based occurrence of a granular cell tumor. Malignant granular cell tumors are even rarer (3), accounting for about 1% to 2% of all granular cell tumors, although there remains some controversy regarding the true incidence, as there is disagreement regarding the histologic classification (4).

A study that attempted to describe the morphologic spectrum and immunohistochemical analysis of 12 granular cell tumors (10 benign and 2 malignant) demonstrated S100 reactivity in 9 patients who had it performed, CD68 positivity in 10 cases who had it performed, vimentin in 5 cases, and inhibin in 3 of the 6 cases performed. The two cases that were not positive for S100 involved old paraffin blocks. Immunohistochemically, most granular cell tumors express S100, neuron-specific enolase, and CD68. Calretinin positivity and protein gene product 9.5 and inhibin expression have been documented as possible additional markers that could be used for substantiating the diagnosis of granular cell tumors. Calretinin expression has been attributed to a neural cell lineage, while the reasons for inhibin positivity are not clear (2).

In a series of 73 cases of granular cell tumor, Fanburg-Smith et al defined malignancy as the presence of three or more of six criteria that included necrosis, spindling of tumor cells, presence of vesicular nuclei with large nucleoli, increased mitotic rate (>2 mitoses/10 high-power fields at 200× magnification), a high nuclear-to-cytoplasmic ratio, and pleomorphism (4).

In the chest and respiratory tract, Kutuya and Akiduki described an asymptomatic young woman who had an ill-circumscribed mass with peripheral infiltration in the medial right upper lung field on chest radiograph (5). CT showed an intrabronchial mass that was found to be benign with the granules positive for S100. A right upper lobectomy and lymphadenectomy were done.

In a 10-year review of tracheobronchial granular cell tumors in the Dutch Network and National Database for Pathology, 31 tumors were registered in 30 patients. About half of the patients were asymptomatic. All the tumors described were benign. Eighteen of the 30 patients received no specific treatment. The other patients received either surgery, electrocautery, or Nd-YAG laser treatment. The surgical treatments offered were tracheal resection and subsequent reconstruction (for tracheal tumors) and pneumonectomy or lobectomy for bronchial tumors. The patients who had surgery had remission for up to 10 years, and those with residual disease remained stable (6). Multiple reports have described tumors at myriad other locations (7–10).