Granular cell tumors (GCTs) are relatively uncommon neoplasms that can be found in many locations including the oral cavity, orbit, skin, skeletal muscle, gastrointestinal tract, breast, external genitals, respiratory tract, biliary system, and peripheral and cranial nerves. Only about 5-11% of all GCTs arise in the gastrointestinal tract and of these, one-third occur in the esophagus. Esophageal GCTs are most commonly observed in the fifth decade of life with a female predilection. The majority of patients with GCTs of the esophagus do not report any symptoms attributable to the tumor and the lesion is discovered during the course of investigation for unrelated gastrointestinal issues. In patients who present with symptoms related to the GCT, the most commonly reported symptom is dysphagia.
Although the majority of cases of GCT are diagnosed by core needle biopsy, diagnosis by image-guided FNA has been reported. On Papanicolaou-stained preparations, tumor cells are arranged singly or in fragments with ill-defined cell margins, abundant basophilic granular cytoplasm, and bland-appearing round or spindle-shaped nuclei. Granules within the cell cytoplasm stain positive with Periodic Acid-Schiff as well as S-100 and CD68 immunostaining. The granular cytoplasm is thought to contain numerous hydrolytic enzyme-containing lysosomes. GCTs are characterized histologically by large cells with abundant granular cytoplasm, bland nuclei, and indistinct nucleoli. Signs of malignancy include an infiltrative growth pattern, size larger than 4 cm, evidence of rapid growth, recurrence after primary resection, nuclear pleomorphism, tumor cell necrosis, spindling, and 2 or more mitoses per 10 high power fields. GCTs of the skin, larynx, and esophagus are known to induce pseudoepitheliomatous hyperplasia in the overlying epithelium, a feature that may simulate squamous cell carcinoma.
The vast majority of GCTs of the esophagus have an indolent clinical course. The optimum treatment for these lesions is dependent upon the size of the tumor and the presence or absence of symptoms. A conservative approach with regular endoscopic follow-up is recommended for tumors <10 mm in diameter. Tumors >20 mm, those causing symptoms, or those clinically concerning for malignancy should be surgically excised. Endomucosal resection has been shown to effectively and safely remove tumors that meet specific criteria (<20 mm without attachment to the muscle layer).
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Joseph Hatem, MD
Gordon Yu, MD
Hospital of University of Pennsylvania,
Department of Pathology and Laboratory Medicine