Granular cell tumors arising nearly simultaneously in the larynx and subcutaneous cervical region.
Granular cell tumors are benign, relatively rare lesions that can occur in any organ in the body. Tumors are known to occasionally arise in two or more different organs. We report the case of a 60-year-old woman in whom granular cell tumors arose almost simultaneously in her subcutaneous cervical region and her larynx. The two tumors were surgically resected and examined histopathologically, and they exhibited the same histopathologic features. The tumor of the larynx was resected with the help of a carbon dioxide laser. Immunohistochemical staining revealed that both were positive for S-100 protein and neuron-specific enolase. Cases of the nearly simultaneous appearance of granular cell tumors in the neck and larynx are rather unusual. The results of immunohistochemical staining suggested that this tumor originates in nerve tissue.
Granular cell tumors are benign, relatively rare lesions that can arise in any organ in the body. They were first reported by Abrikossoff in 1926.  They have a predilection for the skin and tongue, but can also arise in the larynx. Granular cell tumors occasionally arise at two or more sites simultaneously. However, it is relatively rare for multiple granular cell tumors to arise almost simultaneously in the larynx and in an extralaryngeal region.
In this report, we describe the case of a patient with multiple granular cell tumors that developed almost simultaneously in the subcutaneous cervical region and in the larynx. We also discuss the clinical and histopathologic aspects of this type of tumor.
Clinical course. The patient was a 60-year-old woman who first noticed a subcutaneous mass in her left supraclavicular area 2 years earlier. She did not consult a physician at the time. As the lesion gradually increased in size, she eventually sought care and was examined in the Department of Surgery at the Tokyo Metropolitan Ohtsuka Hospital.
The patient's history was unremarkable. Her physical examination revealed the presence of a hard, 3-cm spherical mass, which had an extremely smooth surface and which was palpated under the skin in her left supraclavicular area. The tumor was subsequently identified on contrast-enhanced computed tomography (figure 1). The patient was admitted in March 1997, and the mass was surgically removed under general anesthesia. Histopathologic examination revealed a granular cell tumor.
The patient did not have any specific complaints related to her upper aerodigestive tract, including the pharynx and larynx. Nevertheless, upper gastrointestinal endoscopy and bronchoscopy were performed to look for other tumors. No abnormal findings were detected in the esophagus, stomach, trachea, or bronchi, but an exophytic lesion was discovered in the larynx, and the patient was examined in the Department of Otolaryngology in April 1997.
Flexible rhinolaryngeal fiberscopy revealed the presence of a small, grayish-white exophytic lesion in the posterior portion of the right ventricular fold. No abnormal findings were detected in the oral cavity, nasal cavity, or pharynx, nor were any similar lesions detected anywhere else. The patient was readmitted in August 1997, and the tumor was resected by endolaryngeal microscopic laryngosurgery with a direct laryngoscope under general anesthesia. The mass was a grayish-white, angular, exophytic 5-mm tumor located at the posterior end of the right ventricular fold in the right supraglottic area (figure 2). The tumor was extremely firm and difficult to resect with forceps. The periphery of the tumor was vaporized with 10 W of noncontinuous irradiation delivered by a carbon dioxide laser, and the tumor was completely resected (figure 3). The patient had an uneventful postoperative course, and she has been followed ever since, with no sign of a recurrence of the laryngeal tumor.
Histopathologic findings. The tumor resected from the neck measured 30 x 30 x 25 mm, and the cut surface was solid and grayish-white. Hematoxylin and eosin staining revealed the absence of any capsule enveloping the tumor cells, although the tumor was subdivided by fibrous tissue. The cells had small hyperchromatic nuclei that did not contain nucleoli. The cytoplasm of these cells contained acidophilic granules. The large tumor cells had a "foamy" appearance (figure 4). Pseudoepitheliomatous hyperplasia was not observed. Immunohistochemical staining was positive for S-100 protein (figure 5) and neuron-specific enolase.
The laryngeal tumor exhibited histopathologic characteristics similar to those observed in the neck tumor. Based on these findings, both tumors were histopathologically diagnosed as benign granular cell tumors.
Granular cell tumors are rare subcutaneous or subepithelial lesions that arise in a variety of organs throughout the body. The most common anatomic sites are the skin, including the subcutaneous regions, and the tongue.  These tumors might also arise at locations in the airway, including the larynx, trachea, and bronchi. [4,7] About 200 cases of granular cell tumors of the larynx have been reported in the English-language literature, [8,11] and they account for more than 10% of all granular cell tumors. [12,13] Granular cell tumors of the larynx usually occur during the fourth to seventh decades, and their incidence is twice as high in men as in women. [2,8,13] By contrast, the sex incidence of this tumor in the rest of the body is just the opposite: about twice as high in women as in men.  The most common sites of occurrence within the larynx are the posterior third of the vocal folds and the posterior glottis. [8,12,4] The laryngeal tumor in our case arose in the supraglottic posterior portion of the ventricular fold. Although this site is adjacent to the posterior glottis, the supraglottis is considered a relatively uncommon site for these tumors. [13,15]
The incidence of multiple granular cell tumors has been reported to account for between 5.4 and 16% of all cases of granular cell tumors. [2,16-18] There have been relatively few reports of multiple granular cell tumors arising in the larynx and extralaryngeal sites; when they do occur almost simultaneously, they usually involve the larynx and the trachea or bronchi. [5,6] There have also been case reports of simultaneous multiple tumors of the upper aerodigestive tract that involved the larynx. [6,9] Accordingly, it is more proper to define simultaneous multiple tumors that include the larynx as "multicentric lesions in the region of the airway or upper aerodigestive tract." Multiple granular cell tumors that arise simultaneously in the subcutaneous cervical region and in the larynx, as in our case, appear to be relatively rare.
Granular cell tumors are usually grayish-white and extremely hard. [10,16] Histopathologically, they are unencapsulated, they demonstrate the proliferation of large cells possessing cytoplasm that contains an abundance of acidophilic granules, and they are subdivided by fibrous tissue.  Moreover, the presence of the acidophilic granules gives the tumor cells a foamy appearance  and a diastase-resistance periodic acid Schiff reaction. [8,9] Prominent squamous epithelial hyperplasia is sometimes observed in the epithelium covering the tumor. This is referred to as pseudoepitheliomatous hyperplasia, [2,3,16-18] and it is especially common in the larynx. [19,20] When this site is biopsied, it can be difficult to distinguish this tumor from squamous cell carcinoma. [2,18] In our patient, the histopathologic findings were associated with these characteristics in both the subcutaneous cervical tumor and the laryngeal tumor, but pseudoepitheliomatous hyperplasia was not observed.
The origin of granular cell tumors has not yet been clearly identified. However, on immunohistochemical staining, most of them are positive for S-100 protein and neuron-specific enolase, which suggests that these tumors originate in nerve tissue. Specifically, these findings support the hypothesis that these tumors originate in peripheral nerve Schwann cells. [21,22] Recent immunohistochemical studies have shown that the expression of the lysosome-associated glycoprotein CD68 is common to both granular cell tumors and schwannomas, which lends even more support to the hypothesis that granular cell tumors arise from Schwann cells.  Malignant transformation of granular cell tumors is rare (1 to 2% of all cases), and only 35 cases have been reported in the English-language literature. 
The treatment of choice for granular cell tumors is surgical resection, with histologically negative margins. In the larynx, relatively small tumors can be resected by endolaryngeal microscopic laryngosurgery with a direct laryngoscope. Large tumors should be resected by a laryngofissure approach. The recurrence rate following appropriate resection has been reported to be 8%.  However, in cases of positive-margin resections, recurrence rates in the head and neck have been as high as 21 to 50%. 
The laryngeal tumor in our case was resected by endolaryngeal microscopic laryngosurgery. Because the tumor was extremely hard, it was difficult to resect it completely using only forceps. Accordingly, we attempted to excise it while vaporizing the surrounding mucous membrane with a carbon dioxide laser. There was little bleeding, and we were able to ensure an adequate margin of resection.
We conclude that laser surgery is extremely useful for resecting granular cell tumors of the larynx. More than 2 years after surgically resecting the laryngeal tumor in our patient, we have seen no evidence of recurrence. Even so, long-term followup is necessary. Finally, whenever a granular cell tumor is found in one organ, other organs throughout the body should be closely examined for other tumors.
From the Departments of Otolaryngology, Tokyo Metropolitan Ohtsuka Hospital (Dr. Kawaida), Keio University School of Medicine, Tokyo (Dr. Fukuda), and the National Defense Medical College, Tokorozawa, Japan (Dr. Kohno).
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|Publication:||Ear, Nose and Throat Journal|
|Article Type:||Brief Article|
|Date:||Mar 1, 2000|
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