Granular cell tumours of the gastrointestinal tract: expression of nestin and clinicopathological evaluation of 11 patients

Aims: Granular cell tumours (GCTs) in the gastrointestinal (GI) tract are rare, with few series reported in the literature. Nestin is a recently identified intermediate filament protein that is expressed in neuroectodermal stem cells and skeletal muscle progenitor cells and has been shown to be expressed in gastrointestinal stromal tumours (GISTs) and GI schwannomas. Herein, we describe the clinicopathological and immunohistochemical features of 11 GI GCTs, introducing nestin as an additional marker that identifies these tumours. Methods and results: The archives of the departments of pathology at London Health Sciences Centre (London, Ontario) and St Michael's Hospital (Toronto, Ontario) were searched for GCTs occurring in the GI tract, yielding 11 cases. Histological features were assessed and immunohistochemistry was performed with S100 protein, nestin, glial fibrillary acidic protein (GFAP), CD34, desmin, CD117, and inhibin-alpha. Charts were reviewed for clinical information. Ages at diagnosis ranged from 31 to 73 years; there were six males and four females. All GCTs were solitary, six in the oesophagus, three in the caecum, one in the rectum and one perianal. Most lesions were discovered incidentally. The size of the GCTs ranged from 4 mm to 30 mm. All were submucosal, typically firm, with a white-yellow appearance. Histologically, the GCTs showed moderate cellularity, predominantly solid growth with areas of nesting. While lesional cells were mainly plump and polygonal, areas of spindling were present in several tumours, more frequently in the colorectum. Margins were circumscribed. Nuclei were round to oval, with even chromatin and small nucleoli. Mitoses were rare to absent and necrosis was absent in all cases. Staining with periodic acid-Schiff, with diastase predigestion, showed globular and diffuse positivity within the cytoplasm. Moderate to strong expression of S100 protein and nestin was observed in 11 of 11 and seven of seven tumours, respectively. GFAP, CD34, desmin, CD117 and inhibin-alpha were negative. While patients were variably managed with resection or observation, all remain clinically well, without disease progression. Conclusions: Although rare, GI GCTs have characteristic clinicopathological features. Nestin may be a useful immunohistochemical marker for identifying these tumours; the presence of this persistent stem cell cytoskeletal filament within GI GCTs suggests that these lesions may arise from a multipotential stem cell in the GI tract.