Benign Granular Cell Tumor of Interarytenoid Fold: A Case Report and Comprehensive Review in South Korea

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J Korean Soc Laryngol Phoniatr Logop. 2024;35(2):70-74

Publication date (electronic) : 2024 August 30

doi : https://doi.org/10.22469/jkslp.2024.35.2.70

Min Seok Moon, Seung Hoon Woo

Department of Otolaryngology-Head and Neck Surgery, Dankook University College of Medicine, Cheonan, Korea

Corresponding Author Seung Hoon Woo, MD, PhD Department of Otorhinolaryngology-Head and Neck Surgery, Dankook University College of Medicine, 201 Manghyang-ro, Dongnam-gu, Cheonan 31116, Korea Tel +82-41-550-1781 Fax +82-41-550-7837 E-mail lesaby@hanmail.net

Received 2024 June 10; Revised 2024 July 30; Accepted 2024 August 21.

Abstract

INTRODUCTION

Granular cell tumor (GCT) is a rare type of soft tissue tumor that accounts for approximately 0.5% of all soft tissue tumor [1]. Nearly half of GCT occur in head & neck, most commonly in tongue accounting 33%, but rarely in larynx accounting for 3%–10% [2]. GCT mimics squamous cell carcinoma (SCC) due to its histopathological characteristic of pseudoepitheliomatous hyperplasia [3]. Misdiagnosis can be prevented via immunohistoschemistry with the use of S-100 protein, neuron-specific enolase, vimentin, myelin-associated glycoprotein (Leu-7) and CD 68 (KP-1) [4-6]. Symptoms may present hoarseness, cough, stridor, hemoptysis, dysphagia, or even asymptomatic. Our clinical facility happened to encounter such rare case in 2023 as GCT in patient with chief complain of hoarseness, thereby report our case in this literature along with some comparisons with cases of GCT of larynx reported in South Korea.

CASE REPORT

A 24-year-old female patient visited our Head & Neck Clinic with chief complaint of hoarse voice and cough lasting for more than 6 months. The patient had no other symptoms. She was taking medicine for major depressive disorder. She was a 8 pack-year smoker and an alcoholic who drinks heavily more than 5 days a week. She had no other disease or past medical history. Laboratory blood test showed no specific abnormality. Physical examination was performed but there was no palpable mass in neck, and no specific findings grossly. Radiologic lung image showed no abnormality.

Examination with laryngoscope showed whitish, round mass about 0.2 cm in diameter (Fig. 1A). The mass was located on interarytenoid fold, slightly embedded. The margin was well circumscribed but not encapsulated. The mass grossly showed no invasion to the vocal cord. The vocal cord movement was intact with scanty amount of sputum near vocal cord and piriform sinus. There were both vocal cord nodules symmetrically. Storoboscopy showed impaired mucosal wave and incomplete glottis closure mainly due to both vocal nodules present at the anterior portion of true vocal cord. The patient showed posterior glottic swelling which suggested the possibility of larngopharyngeal reflux disease (LPRD). The patient was initially diagnosed with laryngeal mass with both vocal cord nodules with concurrent LPRD. Although endoscopic finding suggested benign lesion rather than malignant, patient wanted invasive and quick procedure due to non-resolving hoarse voice that lasted for more than 6 months. Microscopic surgery with biopsy was planned for treatment. Proton pump inhibitor was also prescribed for 2 months.

Fig. 1.

Suspension laryngoscopic view. Interarytenoid mass with whitish surface indicated with arrow. Postoperative 1 week follow-up laryngoscope (A). Postoperative 1 month laryngoscope (B). No recurrence occurred. Operative site indicated with arrow (C).

Under general anesthesia, microscopic examination of larynx with suspension laryngoscope was performed. Both vocal cord nodules and 0.2 cm×0.2 cm sized whitish mass on interarytenoid fold was identified. Both vocal cord nodules were excised with microscopic scissors. Mass was removed with monopolar instrument with resection margin of 2 mm. Frozen biopsy was performed only for the mass but was diagnosed with ‘non-diagnostic of carcinoma’. Histopathologic biopsy diagnosed both vocal cord specimen as ‘vocal cord nodules, bilateral’ and the mass on arytenoid was diagnosed with GCT with large polygonal cells with small nuclei and intensely eosinophilic granular cytoplasm (Fig. 2A). S-100 and CD68 stain was diffusely positive and Cytokeratin was negative (Fig. 2B).

Fig. 2.

Microphotograph of the tumor reveals sheets of large polygonal cells with small nuclei and intensely eosinophilic granular cytoplasm (original magnification ×200, hematoxylin-eosin stain) (A). S100 immunohistochemistry is diffusely and strongly positive in tumor cells (original magnification ×200, immunohistochemistry) (B).

One week after surgery the patient’s voice was improved and cough reduced as the result of tumor removal (Fig. 1B) After 1 month, the surgically removed arytenoid fold was well healing with no sign of recurrence (Fig. 1C). The patient had no recurrence during 2 months of follow-up and has not been visiting our clinic for more than 4 months.

DISCUSSION

GCT was first described by Russian pathologist Abrikossoff. It was initially named myoblastoma based on the thought that it was muscle originated [7]. Due to recent development of immunohistochemistry, it is mainly accepted that GCT is of schwann cell origin because it shows positive stain for S-100 protein & neuron-specific enolase and negative stain for muscle cell related markers [8,9]. However, some case reports proved that some GCTs are neuron-specific enolase negative [10-12]. Therefore, there remain still some controversies about where granular cell originate from.

For GCT in larynx, the most common symptom is hoarseness. Cough, dysphagia, stridor, hemoptysis, and even dyspnea could happen if the mass is big enough which is presented in case no. 12 with the largest GCT size among the Table 1. The most common location of GCT in larynx is known to be true vocal cord, followed by arytenoid, anterior commissure and false vocal folds [5]. Table 1 shows some features of benign GCT in larynx that were reported in South Korea from 2002. The most common location of GCT in South Korea was true vocal cords as well. Females and children were rarely reported.

Table 1.

Case reports of granular cell tumor of larynx in South Korea

Differential diagnosis include SCCs, papillomas, polyps, granulomas, cysts, neuromas, and neurofibromas, and lipoma [2]. Benign lesion such as papilloma, granuloma, polyp can be distinguished by their gross feature, but histological confirm is always important because they may look similar. Among the differential diagnosis, distinguishing SCC is of utmost importance. Gross morphology of GCT is nonencapsulated, well-circumscribed and small in size usually less than 2 cm [5]. Histologically, overlying pseudoepitheliomatous hyperplasia is the main histologic feature of GCT which can mislead to diagnosis of squamous cell cancer, but GCT can be differentiated with features such as lack of nuclear pleomorphism and presence of granular cell with immunohistochemistry stain. GCTs usually have polygonal or elongated cell with eosinophil granules and no mitotic figure. Immunohistochemistry for GCT is known to be positive for vimentin, S100, NSE and CD68 but negative for cytokeratin, actin (smooth muscle), desmin, GFAP, EMA, CD34, HMB45 and NF-LH [1]. Ki-67 which is positively presented by SCC does not usually show positivity in GCT, however positive expression of Ki-67 in GCT may suggest malignant granular cell tumor (MGCT) [3]. Our patient’s result was positive for S-100 & CD68 but negative for multiple cytokeratin which was typical result for benign GCT.

The generally accepted treatment of choice for benign granular cell tumor of larynx is surgical excision. The recurrence rate of surgically removed laryngeal GCT is 2%–3% if completely removed. Checking frozen section is recommended to secure negative resection margin. When surgical margins are positive, the recurrence rate is reported up to 50%. Case no.5 who went through microscopic resection was later found with recurrence within 4 months but after re-excision with laser, no recurrence was reported [13]. Most cases in Korea (Table 1) used suspension laryngoscope with CO2 laser. The surgical extent is based on location and the size of the tumor, so if the mass is large, laryngofissure or partial laryngectomy may be the appropriate choice [2].

MGCT account for only 2% of GCT with metastasis most commonly to lungs, liver and bones [14]. Radiation therapy and chemotherapy are not considered effective for MGCT, and there is no consensus on using chemoradiation for these patients. However there exists a case report of successful use of pazopanib in patient with orbital MGCT [15]. MGCT in larynx has not been reported yet in South Korea, thus not listed on the Table 1.

Our patient was young female, rare compared to cases in Korea where mostly male patients were reported. Among 13 patient listed in the Table 1 only 2 patient were females. Our patient smoked 2 pack of cigarettes everyday for 4 consecutive years. According to this Table 1, 6 patients were indicated with smoking history. The size of tumor and pack-year amount of smoking does not seem to correspond according to the Table 1, yet there are limitation of small number of patients in Korea to hypothesize such correlation. Since smoking is known predisposing risk factor for SCC of larynx, it is important to distinguish the 2 diseases in heavy smokers so that appropriate treatment could be done. In case of GCT, surgical removal with negative margin rather than chemoradiation should be performed. Our patient was too young to consider SCC. However, confirming diagnosis with immunohistochemistry should be considered most important in GCT of larynx. When considering age on the Table 1, 6-year-old patient was the youngest and 63-year-old patient was oldest. Also, 10 patients among 13 patients were less than 50-year-old including 3 patients who are not adults. This may suggest that unlike SCC, GCT is not necessarily correlated with old age. Although small in number of patient which is difficult to derive statistically significant results, our literature made the first attempt to organize rare cases of GCT of larynx reported in Korea with features such as age, sex, size, symptoms, location, recurrence and relation with smoking. The result was high prevalence in male, true vocal cord as most common lesion, variable size usually smaller than 2 cm, most case with no recurrence with surgical removal, and relatively young age. Further collection of cases with GCT patients may be studied in the future for more statistical analysis in South Korea.

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