Four cases of patients with gastrointestinal granular cell tumors.
Key Words: granular cell tumors, submucosal lesions, endoscopic ultrasound, S-100 protein
A 47-year-old black female had an esophagogastroduodenoscopy (EGD) performed for complaints of dysphagia that showed a 7 mm nodule in the esophagus at 29 cm. Biopsies revealed granular cell tumor (GCT) with immunohistochemical stain positive for S-100. CT scan of the thorax showed a 21 mm X 21 mm soft tissue mass in the anterior mediastinum. Endoscopic ultrasound (EUS) showed a 2.5 cm heterogeneous lesion in the mediastinum adjacent to and involving the esophagus, consistent with a GCT of the anterior mediastinum involving the esophagus. Fine needle aspirate (FNA) of a mediastinal lymph node was negative for malignancy. PET scan was negative for malignant disease. The patient was referred for surgical resection of the GCT but elected for conservative management. She has remained stable in subsequent follow-up clinic visits.
A 51-year-old black female who underwent an EGD for GERD was found to have a whitish to yellow 7 mm nodule in the distal esophagus (Fig. 1). EUS showed that the lesion was submucosal and hypoechoic. Forceps biopsy confirmed GCT with a positive stain for S-100 (Fig. 2). The lesion was completely removed and the patient has remained asymptomatic.
A 56-year-old white female undergoing screening colonoscopy showing a 1 cm submucosal-appearing lesion in the transverse colon. No prior EUS was performed. The lesion was completely removed by hot biopsy with histology confirming GCT with a positive stain for S-100. The patient has remained asymptomatic.
A 54-year-old white male underwent EGD to evaluate GERD. EGD showed a 3 X 2 cm smooth nodule in the gastric cardia with biopsies showing a GCT with positive stain for S-100. No prior EUS was performed. The patient underwent surgical wedge resection of the GCT with at least 1 cm margins. No recurrence was seen on subsequent endoscopies.
The incidence of gastrointestinal submucosal lesions (SML) is about 0.3%. Granular cell tumors (GCTs) are a type of gastrointestinal SML that appear as firm, pale-yellow nodules usually not greater that 2 cm that originate from the deep mucosa or submucosa. (1,2) GCTs can occur in any organ but are most often seen in the skin, tongue, and subcutaneous tissues of the chest and upper extremities. (3-12) Approximately 1 to 11% of GCTs are found in the GI tract, most commonly in the esophagus and large intestine. (3,7,10,13-16) In one series in Poland, GCTs in the esophagus were found in 0.012% out of 31,674 EGDs over 11 years. (14)
GCTs are usually asymptomatic but have been reported to cause clinical symptoms such as dysphagia, abdominal pain, gastric outlet obstruction, or GI tract bleeding. (10,15,16) They occur most commonly in the fourth to sixth decades of life and are twice as common in women compared with men. In one series, two-thirds of patients with GCT were African-American. Primary GCTs may occur in multiple sites at the time of initial presentation in 4 to 16% of patients. (1,7-10,17)
The tumor usually presents as a small nodule or plaque with grayish-white to yellow color endoscopically. (3,8,10,16) In the esophagus, it may resemble an erupting molar tooth. (17,18) The tumor is often associated with mucosal ulceration. (11) Because the lesions are submucosal, endoscopic biopsy achieves a definitive diagnosis in only 50% of cases. (8) On EUS, GCTs usually arise in the second (lamina propria or deep mucosa) or third (deep mucosa) layers of the GI tract, are usually <3 cm, hypoechoic, mildly inhomogeneous, and have smooth margins if benign. They are usually slightly more echogenic than leiomyomas. They are most common in the middle and distal esophagus. (3,8,17,19,20)
[FIGURE 1 OMITTED]
On cut section, GCTs are usually pale, yellow-tan or yellow-gray. The cells are of Schwann cell origin, rounded, polygonal or spindled, and have a small/rounded nucleus. (2,3,8-10,16,18) The cytoplasm of the cells is abundant, granular, eosinophilic, PAS-positive, and diastase resistant. (2) Immunohistochemical analysis is positive for S-100 protein and myelin proteins but negative for desmin, actin, CD 34 and c-kit. (2,4,21) Neuroectodermal tissue, including nerves and melanocytes, expresses S-100 protein. (22)
In a series of SMLs, 13% of tumors are malignant and 8% are potentially malignant. (19) Malignancy occurs in 1 to 3% of GCTs. (2,15,18) Characteristics of malignant GCTs are local recurrence, large size (>4 cm), rapid growth, invasion of adjacent organs, and involvement of multiple layers in the GI tract. (7,15) Histologic features of malignant GCTs include necrosis, spindling, vesicular nuclei with prominent nucleoli, high nucleocytoplasmic ratio, cellular pleomorphism, and mitotic figures (>2 mitoses/10 HPF). (2,7,8,11,16) Tumors with three or more of these histologic features are considered malignant and carry an approximately 40% mortality risk. (2) EUS features of malignancy include extraluminal growth pattern, involvement of the muscularis propria, abnormal 5-layer architecture at the margin of the lesion, larger size, irregular borders, inhomogeneous echogenicity, and eroded surfaces. (1,18) Malignant tumors usually recur locally within less than one year after resection before there is metastasis. (2,20) GCTs can cause pseudoepitheliomatous hyperplasia that can be confused with squamous cell carcinoma without adequate biopsies. (3,7)
[FIGURE 2 OMITTED]
GCTs are a subset of gastrointestinal submucosal lesions. Endoscopically, the tumors present as a small nodule or plaque with grayish-white to yellow color that may resemble an erupting molar tooth. (3,8,10,16,17,18,23) Endoscopic biopsy achieves a definitive diagnosis in only 50% of cases. (8) EUS is very helpful in evaluating GCTs to obtain tissue diagnosis and to evaluate for possible resection of the tumor. Malignancy occurs in 1 to 3% of GCTs. (2,15,18) As GCTs as small as 10 mm have been found to be malignant, (18) resection is the recommended treatment. (3,16,23) EUS is recommended before resection within reach of the endoscope in the stomach, duodenum, and colon to ensure that the tumor is suitable for endoscopic removal: <2 cm and not involving the muscularis propria. (1,3,8,14,17,18,23) Recurrence is rare (5-10%) after resection of benign tumors. (2,5,8,15) For colonic GCTs, colonoscopic resection of the GCT and strict endoscopic follow-up is recommended with limited surgical resection for cases in which endoscopic removal is not possible. (6)
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Douglas L. Lowe, MD, Ayaz J. Chaudhary, MD, FACG, Jeffrey R. Lee, MD, Sherman M. Chamberlain, MD, FACG, Robert R. Schade, MD, FACG, and Urias Cuartas-Hoyos, MBBS, FACG
From the Department of Internal Medicine, Section of Gastroenterology/Hepatology, and the Department of Pathology, Medical College of Georgia and Veterans Administration Medical Center, Augusta, GA.
Reprint requests to Dr. Ayaz Chaudhary, The Medical College of Georgia, Section of Gastroenterology/Hepatology, 1120 15th Street, BBR2538, Augusta, GA 30912-3120. Email: email@example.com
Accepted September 22, 2006.
RELATED ARTICLE: Key Points
* Granular cell tumors (GCTs) occur in several areas including the gastrointestinal tract in 1-8% of cases.
* Studies suggest that endoscopic ultrasound and endoscopic removal is the treatment of choice for esophageal GCTs if they are small in size (<2 cm) and do not involve the muscularis propria.
* Although most GCTs are benign and can be followed endoscopically, the malignant potential warrants evaluation with endoscopic ultrasound for possible endoscopic or surgical resection.