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Neck and superior mediastinal granular cell tumor excised via a combined approach Junko Kusano MDa, Fukuichiro Iguchi MD, PhDa, Yuka Takahashi MDa, Yasuji Terada MD, PhDb, Norihiko Murai MD, PhDa,* a b
Department of Otolaryngology, Kyoto-Katsura Hospital, Yamada Hirao cho 17, Nishikyou-ku, Kyoto, 615 8256 Japan Department of Thoracic Surgery, Kyoto-Katsura Hospital, Yamada Hirao cho 17, Nishikyou-ku, Kyoto, 615 8256 Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 8 April 2014 Accepted 1 September 2014 Available online xxx
Granular cell tumor (GCT) is an uncommon tumor of Schwann cell origin. GCT occurs in various sites throughout the body, but mediastinal GCT is very rare. We present an extremely rare case of GCT of the neck and superior mediastinum. A 36-year-old man with a 3-month history of cough was investigated at our hospital. CT and MRI revealed a spindle-shaped mass in the left neck and superior mediastinum, with features suggesting a neurogenic tumor. The tumor was successfully excised via combined neck incision and video-assisted thoracoscopic surgery. Histopathological examination showed proliferation of polygonal and spindled cells with eosinophilic granule-rich cytoplasm. These cells were S-100 protein positive, and the cytoplasmic granules were periodic acid-Schiff positive. Based on these histopathological and immunohistochemical findings, a diagnosis of GCT was established. The patient developed hoarseness immediately after the operation, and laryngoscopy revealed the left vocal cord palsy in the paramedian position, which resolved after about 3 months. The tumor did not recur during the following 10 months. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Granular cell tumor Neurogenic tumor Neck Mediastinum Neck incision Video-assisted thoracoscopic surgery
1. Introduction Granular cell tumor (GCT) is an uncommon tumor that was first described by Abrikossoff as a benign neoplasm [1], which is characterized by abundant periodic acid-Schiff positive fine eosinophilic granules in the cytoplasm and S-100 immunoreactivity. Although first considered to be derived from muscle cells, demonstration of S-100 immunoreactivity currently favors Schwann cell origin. We present here an extremely rare case of GCT that arose in the neck and superior mediastinum and was successfully excised via combined neck incision and video-assisted thoracoscopic surgery (VATS). 2. Case report A 36-year-old man with a 3-month history of cough was investigated in the Department of Thoracic Surgery at KyotoKatsura Hospital. Chest CT showed a cervico-thoracic tumor. Because of the location of the lesion, the patient was reviewed by
* Corresponding author. Tel.: +81 75 391 5811; fax: +81 75 381 0090. E-mail address: [email protected] (N. Murai).
the otolaryngology team. A firm mass was noted in the left lower neck, lateral and posterior to the left lobe of the thyroid gland. Fiberscopic examination of the pharynx and larynx revealed no abnormalities. Contrast-enhanced CT revealed a poorly enhanced mass with clear margins in the left neck and superior mediastinum, measuring 4.6 cm 3.3 cm 3.2 cm (Fig. 1A and B). The tumor was located inferior and posterior to the inferior pole of the left lobe of the thyroid gland, and was surrounded by the left carotid artery, left brachiocephalic vein, left subclavian artery, aortic arch, trachea, esophagus, and vertebral body. There was no continuity between the tumor and the thyroid gland. Positron emission tomography showed moderate hypermetabolism (maximum standardized uptake value 4.3) in the mass. No other hypermetabolic foci were found (Fig. 1C and D). Neck MRI showed a mass that was isointense on T1-weighted images and had low signal intensity on T2-weighted images (Fig. 2). These radiographic findings suggested a neurogenic tumor. Surgical excision was planned by a team including otolaryngologists and thoracic surgeons via combined neck incision and VATS, to obtain a satisfactory operative field for extracapsular excision of a neurogenic tumor arising from a vital nerve such as the vagus or phrenic nerve. A left hemi-collar neck incision, approximately 7 cm in length, was made one finger-width above the clavicle.
http://dx.doi.org/10.1016/j.anl.2014.09.001 0385-8146/ß 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Kusano J, et al. Neck and superior mediastinal granular cell tumor excised via a combined approach. Auris Nasus Larynx (2014), http://dx.doi.org/10.1016/j.anl.2014.09.001
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Fig. 1. Chest CT and 18-FDG-positron emission tomography. (A) Contrast-enhanced chest CT, axial section. The black arrow indicates a poorly enhanced mass with clearly demarcated margins measuring 4.6 cm 3.3 cm 3.2 cm. White arrow, left carotid artery; black arrowhead, left brachiocephalic vein; white arrowhead, left subclavian artery; asterisk, thyroid gland. The proximal end of the tumor was posterior to the inferior pole of the left lobe of the thyroid gland, but was not close to the thyroid gland. (B) Contrast-enhanced chest CT, coronal section. The white arrow indicates the tumor. White arrowhead, aortic arch. Positron emission tomography, axial section (C) and coronal section (D). The white arrow indicates the tumor with moderate hypermetabolism (maximum standardized uptake value 4.3). No other hypermetabolic foci were found.
Trocars were placed in the second intercostal space in the midclavicular line, the fourth intercostal space in the midaxillary line, and the fifth intercostal space in the anterior axillary line (Fig. 3A and B). In the neck field, the tumor was located lateral and posterior to the trachea, and medial and posterior to the common carotid artery and internal jugular vein (Fig. 3C). No extensive adhesions were observed, but dissection of the lower end of the tumor from the adjacent tissues was not easy. In the thoracoscopic field, the tumor was exposed after blunt dissection of the mediastinal pleura anterior to the subclavian artery and superior to the aortic arch (Fig. 3D). Communication was established
between the neck incision and the thoracic cavity, and the tumor was eventually removed via the neck incision. No cord-like structures suggesting the involvement of a nerve with the tumor were identified. Macroscopic examination of the excised specimen showed an egg-shaped mass with a smooth surface, with a homogeneous milky-white color on cross-section. Pathological examination showed proliferation of polygonal and spindled cells with eosinophilic granule-rich cytoplasm (Fig. 4A and B). The cytoplasmic granules were periodic acid-Schiff positive (Fig. 4C). Immunohistochemical examination showed that the cell cytoplasm and nuclei
Fig. 2. Chest MRI. (A) T1-weighted image, coronal section, and (B) T2-weighted image, coronal section. The 4.6 cm 3.3 cm 3.2 cm tumor (white arrows) was isointense on T1-weighted images and had low signal intensity on T2-weighted images.
Please cite this article in press as: Kusano J, et al. Neck and superior mediastinal granular cell tumor excised via a combined approach. Auris Nasus Larynx (2014), http://dx.doi.org/10.1016/j.anl.2014.09.001
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Fig. 3. Operative findings. (A and B) A 7-cm left hemi-collar incision was made one finger-width above the left clavicle (a). Trocars were placed in the second intercostal space in the midclavicular line (b), the fourth intercostal space in the midaxillary line (c), and the fifth intercostal space in the anterior axillary line (d). (C) The neck field. White arrows, tumor; white asterisk, left sternocleidomastoid muscle. (D) The thoracoscopic field. White arrows, tumor; black asterisk, aortic arch; white asterisk, subclavian artery.
were positive for S-100 protein (Fig. 4D), and negative for CD1a, CD68, alpha-SMA, MelanA, and HMB-45. Based on these histopathological and immunohistochemical findings, the tumor was diagnosed as GCT. The patient developed hoarseness immediately after the operation, and laryngoscopy revealed left vocal cord palsy in the paramedian position. The hoarseness and vocal cord palsy gradually resolved over 3 months. No Horner’s sign or elevation of the diaphragm was observed. There was no sign of tumor recurrence during the 10-month follow-up period. 3. Discussion GCT can occur almost anywhere in the body. The head and neck are affected most commonly, accounting for 45–65% of the cases, of which 70% occur in the oral cavity. The skin and subcutaneous tissues are affected in 30% of the cases, the breasts in 15%, the respiratory system in 10%, and the gastrointestinal tract in 4–6% [2]. Mediastinal GCT, especially involving both the neck and superior mediastinum, is very rare. To the best of our knowledge, only 11 cases of mediastinal GCT have previously been reported in
the English literature (Table 1) [3–6]. Six of these tumors originated from the sympathetic trunk, and in the other seven cases no nerve of origin was identified. Because of the location of the tumor in our patient, we consider that the nerve of origin was probably a first or second intercostal nerve branch to the parietal pleura. Most GCTs are benign, with malignant GCTs accounting for only 1–2% of all cases [7,8]. The diagnostic criteria for malignant GCT are necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (>2 mitoses/10 high-power fields, 200 magnification), high nuclear/cytoplasmic ratio, and pleomorphism. GCT is considered to have malignant histological features if more than three of these criteria are present [7]. In our patient, only one of these criteria was observed (spindling), and the tumor was classified as atypical. Some GCTs that are initially described as having benign or atypical features become clinically malignant, developing local recurrence, distant metastasis, and/or lymph node metastasis [8]. The features of clinically malignant tumors include: diameter >4 cm, rapid growth, distant metastasis, local invasion, and early recurrence after treatment of the primary
Please cite this article in press as: Kusano J, et al. Neck and superior mediastinal granular cell tumor excised via a combined approach. Auris Nasus Larynx (2014), http://dx.doi.org/10.1016/j.anl.2014.09.001
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Fig. 4. Histopathological findings. (A and B) Hematoxylin and eosin staining. There was proliferation of polygonal and spindled cells with eosinophilic granule-rich cytoplasm. Bar: 50 mm (A), 20 mm (B). (C) Periodic acid-Schiff staining. The cytoplasmic granules stained positive. (D) Immunohistochemical staining for S-100 protein. The cytoplasm and nuclei of the tumor cells stained positive.
lesion [7–10]. Three of the 12 reported cases of mediastinal GCT were malignant, and these tumors were all >4 cm in diameter (5.4 cm, 13 cm, and 15 cm). Four of the nine benign mediastinal GCTs were also >4 cm in diameter. The local recurrence rate of
GCTs in various organs is generally very low, with a reported rate of 2–9%. However, incomplete excision is associated with a high local relapse rate (20.8%) [6]. Early relapse suggests malignant potential even if the tumor has benign histological features, and complete
Table 1 Clinicopathological features of 12 cases of mediastinal granular cell tumor F, female; M, male; Pos, posterior mediastinum; Lt. Sup, left superior mediastinum; Size, maximum diameter; NA, not available; Sympathetic, sympathetic nerve. Case
Age
Sex
Location
Size (cm)
Histology
Origin nerve
S-100
Harrer (1972) Rosenbloom (1975) Abenoza (1987) Smith (1998) Aisner (1988) Robinson (1988) Machida (2003) Angeles (2005) Ponce (2011) Nakao (2012) Luca (2013) This case
59 11 18 53 27 27 21 43 28 66 64 36
F M F F F M M F F M F M
Pos Pos Pos Pos Pos Pos Pos Pos Sup Sup Sup Lt. Sup
13 5 4 11.5 4.4 2.4 2 3 2.5 5.4 15 4
Malignant Benign Benign Benign Benign Benign Benign Benign Benign Malignant Malignant Benign
NA Sympathetic NA NA Sympathetic NA Sympathetic NA NA Sympathetic Sympathetic NA
NA NA + + + NA + + NA + + +
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tumor excision is necessary to prevent local recurrence. Sixteen percent of the patients with benign GCTs were reported to have multiple GCTs at first presentation, indicating the importance of differentiating between multiple benign GCTs and metastasis [11]. Malignant GCT has a poor prognosis, with 39–50% of the patients dying from their disease after a median period of 3 years [7]. At present, the only accepted radical treatment is complete excision. Effective chemotherapy and radiation therapy regimens have not yet been established for malignant GCT. However, some case reports have suggested that chemotherapy and/or radiotherapy may be beneficial in cases of unresectable recurrence or metastasis. One reported case of tracheal malignant GCT with mediastinal metastasis responded to postoperative radiotherapy [8]. Rosenthal et al. [12] reported a patient with recurrent GCT in the buttock who was successfully treated by salvage surgery and subsequent radiotherapy. Kanat et al. [13] reported a case of multiple metastatic malignant GCT of the skin that was successfully treated with gemcitabine and paclitaxel followed by radiotherapy. In retrospect, tumor excision in our patient may have been possible via the neck incision alone, although visualization of the mediastinal side of the tumor would have been very limited. However, it may be impossible or very risky to excise such a mass blindly, identify the nerve of origin of the tumor, or attempt extracapsular excision in a restricted operative field via a neck incision, particularly if there are adhesions between the tumor and the lung or major blood vessels. We decided to operate via combined neck incision and VATS to ensure complete and safe tumor excision. Neck dissection combined with VATS is believed to be safer than neck incision without VATS [14,15]. Although it may be unclear whether the neck incision or VATS should be performed first [14], we believe that this should depend on the size and location of the tumor. 4. Conclusion A rare case of GCT in the neck and mediastinum was reported. To completely and safely excise such a potentially malignant neurogenic tumor, a surgical approach via combined neck incision and VATS is recommended. As GCT may have a clinically malignant course even if the initial histological features are benign, careful follow-up is required.
5
Conflicts of interest None. Acknowledgment The authors are grateful to Dr. Yumiko Yasuhara (Department of Pathology, Kyoto-Katusra Hospital).
References [1] Abrikossoff AL. Uber Myome ausgehend von der quergestreiften willkurlichen Muskulatur. Virchows Arch Pathol Anat 1926;260:215–33 [German]. [2] Becelli R, Perugini M, Gasparini G, Cassoni A, Fabiani F. Abrikossoff’s tumor. J Craniofac Surg 2001;12:78–81. [3] De Luca G, Luciano A, Benincasa G, Sessa R, Petteruti F. Giant malignant granular cell tumor (GCT) of the posterior mediastinum. J Thorac Oncol 2013;8:1107–8. [4] Nakao M, Hishida T, Ishii G, Yoshida J, Nishimura M, Nagai K. Malignant granular cell tumor of the posterior mediastinum with dissemination. Asian Cardiovasc Thorac Ann 2012;20:71–3. [5] Ponce FA, Killory BD, Wait SD, Theodore N, Dickman CA. Endoscopic resection of intrathoracic tumors: experience with and long-term results for 26 patients. J Neurosurg Spine 2011;14:377–81. [6] Machida E, Haniuda M, Eguchi T, Kurai M, Yamanda T, Amano J, et al. Granular cell tumor of the mediastinum. Intern Med 2003;42:178–81. [7] Fanburg-Smith JC, Meis-Kindblom JM, Fante R, Kindblom LG. Malignant granular cell tumor of soft tissue: diagnostic criteria and clinicopathologic correlation. Am J Surg Pathol 1998;22:779–94. [8] Burton DM, Heffner DK, Patow CA. Granular cell tumors of the trachea. Laryngoscope 1992;102:807–13. [9] Curtis BV, Calcaterra TC, Coulson WF. Multiple granular cell tumor: a case report and review of the literature. Head Neck 1997;19:634–7. [10] Angeles RM, Papari M, Malecki Z. Pathologic quiz case: a 43-year-old woman with an incidentally detected posterior mediastinal mass. Granular cell tumor of the posterior mediastinum. Arch Pathol Lab Med 2005;129. [11] Fumagalli I, Penel N, Wacrenier A, El Bedoui S, Adenis A. Advanced Abrikossoff tumour: a metastatic or a multifocal malignancy. Acta Oncol 2012;51:133–5. [12] Rosenthal SA, Livolsi VA, Turrisi 3rd AT. Adjuvant radiotherapy for recurrent granular cell tumor. Cancer 1990;65:897–900. [13] Kanat O, Yalcinkaya U, Akbunar T, Kurt E, Evrensel T, Manavoglu O. Gemcitabine plus paclitaxel may be a promising chemotherapy regimen for metastatic granular cell tumour. Clin Oncol (R Coll Radiol) 2008;20:93–6. [14] Al-Mufarrej F, Margolis M, Tempesta B, Strother E, Gharagozloo F. Novel thoracoscopic approach to difficult posterior mediastinal tumors. Gen Thorac Cardiovasc Surg 2010;58:636–9. [15] Yamaguchi M, Yoshino I, Kameyama T, Osoegawa A, Tagawa T, Maehara Y. Thoracoscopic surgery combined with a supraclavicular approach for removing a cervico-mediastinal neurogenic tumor: a case report. Ann Thorac Cardiovasc Surg 2006;12:194–6.
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ANL-1904; No. of Pages 5 Auris Nasus Larynx xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Neck and superior mediastinal granular cell tumor excised via a combined approach Junko Kusano MDa, Fukuichiro Iguchi MD, PhDa, Yuka Takahashi MDa, Yasuji Terada MD, PhDb, Norihiko Murai MD, PhDa,* a b
Department of Otolaryngology, Kyoto-Katsura Hospital, Yamada Hirao cho 17, Nishikyou-ku, Kyoto, 615 8256 Japan Department of Thoracic Surgery, Kyoto-Katsura Hospital, Yamada Hirao cho 17, Nishikyou-ku, Kyoto, 615 8256 Japan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 8 April 2014 Accepted 1 September 2014 Available online xxx
Granular cell tumor (GCT) is an uncommon tumor of Schwann cell origin. GCT occurs in various sites throughout the body, but mediastinal GCT is very rare. We present an extremely rare case of GCT of the neck and superior mediastinum. A 36-year-old man with a 3-month history of cough was investigated at our hospital. CT and MRI revealed a spindle-shaped mass in the left neck and superior mediastinum, with features suggesting a neurogenic tumor. The tumor was successfully excised via combined neck incision and video-assisted thoracoscopic surgery. Histopathological examination showed proliferation of polygonal and spindled cells with eosinophilic granule-rich cytoplasm. These cells were S-100 protein positive, and the cytoplasmic granules were periodic acid-Schiff positive. Based on these histopathological and immunohistochemical findings, a diagnosis of GCT was established. The patient developed hoarseness immediately after the operation, and laryngoscopy revealed the left vocal cord palsy in the paramedian position, which resolved after about 3 months. The tumor did not recur during the following 10 months. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Granular cell tumor Neurogenic tumor Neck Mediastinum Neck incision Video-assisted thoracoscopic surgery
1. Introduction Granular cell tumor (GCT) is an uncommon tumor that was first described by Abrikossoff as a benign neoplasm [1], which is characterized by abundant periodic acid-Schiff positive fine eosinophilic granules in the cytoplasm and S-100 immunoreactivity. Although first considered to be derived from muscle cells, demonstration of S-100 immunoreactivity currently favors Schwann cell origin. We present here an extremely rare case of GCT that arose in the neck and superior mediastinum and was successfully excised via combined neck incision and video-assisted thoracoscopic surgery (VATS). 2. Case report A 36-year-old man with a 3-month history of cough was investigated in the Department of Thoracic Surgery at KyotoKatsura Hospital. Chest CT showed a cervico-thoracic tumor. Because of the location of the lesion, the patient was reviewed by
* Corresponding author. Tel.: +81 75 391 5811; fax: +81 75 381 0090. E-mail address: [email protected] (N. Murai).
the otolaryngology team. A firm mass was noted in the left lower neck, lateral and posterior to the left lobe of the thyroid gland. Fiberscopic examination of the pharynx and larynx revealed no abnormalities. Contrast-enhanced CT revealed a poorly enhanced mass with clear margins in the left neck and superior mediastinum, measuring 4.6 cm 3.3 cm 3.2 cm (Fig. 1A and B). The tumor was located inferior and posterior to the inferior pole of the left lobe of the thyroid gland, and was surrounded by the left carotid artery, left brachiocephalic vein, left subclavian artery, aortic arch, trachea, esophagus, and vertebral body. There was no continuity between the tumor and the thyroid gland. Positron emission tomography showed moderate hypermetabolism (maximum standardized uptake value 4.3) in the mass. No other hypermetabolic foci were found (Fig. 1C and D). Neck MRI showed a mass that was isointense on T1-weighted images and had low signal intensity on T2-weighted images (Fig. 2). These radiographic findings suggested a neurogenic tumor. Surgical excision was planned by a team including otolaryngologists and thoracic surgeons via combined neck incision and VATS, to obtain a satisfactory operative field for extracapsular excision of a neurogenic tumor arising from a vital nerve such as the vagus or phrenic nerve. A left hemi-collar neck incision, approximately 7 cm in length, was made one finger-width above the clavicle.
http://dx.doi.org/10.1016/j.anl.2014.09.001 0385-8146/ß 2014 Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: Kusano J, et al. Neck and superior mediastinal granular cell tumor excised via a combined approach. Auris Nasus Larynx (2014), http://dx.doi.org/10.1016/j.anl.2014.09.001
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Fig. 1. Chest CT and 18-FDG-positron emission tomography. (A) Contrast-enhanced chest CT, axial section. The black arrow indicates a poorly enhanced mass with clearly demarcated margins measuring 4.6 cm 3.3 cm 3.2 cm. White arrow, left carotid artery; black arrowhead, left brachiocephalic vein; white arrowhead, left subclavian artery; asterisk, thyroid gland. The proximal end of the tumor was posterior to the inferior pole of the left lobe of the thyroid gland, but was not close to the thyroid gland. (B) Contrast-enhanced chest CT, coronal section. The white arrow indicates the tumor. White arrowhead, aortic arch. Positron emission tomography, axial section (C) and coronal section (D). The white arrow indicates the tumor with moderate hypermetabolism (maximum standardized uptake value 4.3). No other hypermetabolic foci were found.
Trocars were placed in the second intercostal space in the midclavicular line, the fourth intercostal space in the midaxillary line, and the fifth intercostal space in the anterior axillary line (Fig. 3A and B). In the neck field, the tumor was located lateral and posterior to the trachea, and medial and posterior to the common carotid artery and internal jugular vein (Fig. 3C). No extensive adhesions were observed, but dissection of the lower end of the tumor from the adjacent tissues was not easy. In the thoracoscopic field, the tumor was exposed after blunt dissection of the mediastinal pleura anterior to the subclavian artery and superior to the aortic arch (Fig. 3D). Communication was established
between the neck incision and the thoracic cavity, and the tumor was eventually removed via the neck incision. No cord-like structures suggesting the involvement of a nerve with the tumor were identified. Macroscopic examination of the excised specimen showed an egg-shaped mass with a smooth surface, with a homogeneous milky-white color on cross-section. Pathological examination showed proliferation of polygonal and spindled cells with eosinophilic granule-rich cytoplasm (Fig. 4A and B). The cytoplasmic granules were periodic acid-Schiff positive (Fig. 4C). Immunohistochemical examination showed that the cell cytoplasm and nuclei
Fig. 2. Chest MRI. (A) T1-weighted image, coronal section, and (B) T2-weighted image, coronal section. The 4.6 cm 3.3 cm 3.2 cm tumor (white arrows) was isointense on T1-weighted images and had low signal intensity on T2-weighted images.
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Fig. 3. Operative findings. (A and B) A 7-cm left hemi-collar incision was made one finger-width above the left clavicle (a). Trocars were placed in the second intercostal space in the midclavicular line (b), the fourth intercostal space in the midaxillary line (c), and the fifth intercostal space in the anterior axillary line (d). (C) The neck field. White arrows, tumor; white asterisk, left sternocleidomastoid muscle. (D) The thoracoscopic field. White arrows, tumor; black asterisk, aortic arch; white asterisk, subclavian artery.
were positive for S-100 protein (Fig. 4D), and negative for CD1a, CD68, alpha-SMA, MelanA, and HMB-45. Based on these histopathological and immunohistochemical findings, the tumor was diagnosed as GCT. The patient developed hoarseness immediately after the operation, and laryngoscopy revealed left vocal cord palsy in the paramedian position. The hoarseness and vocal cord palsy gradually resolved over 3 months. No Horner’s sign or elevation of the diaphragm was observed. There was no sign of tumor recurrence during the 10-month follow-up period. 3. Discussion GCT can occur almost anywhere in the body. The head and neck are affected most commonly, accounting for 45–65% of the cases, of which 70% occur in the oral cavity. The skin and subcutaneous tissues are affected in 30% of the cases, the breasts in 15%, the respiratory system in 10%, and the gastrointestinal tract in 4–6% [2]. Mediastinal GCT, especially involving both the neck and superior mediastinum, is very rare. To the best of our knowledge, only 11 cases of mediastinal GCT have previously been reported in
the English literature (Table 1) [3–6]. Six of these tumors originated from the sympathetic trunk, and in the other seven cases no nerve of origin was identified. Because of the location of the tumor in our patient, we consider that the nerve of origin was probably a first or second intercostal nerve branch to the parietal pleura. Most GCTs are benign, with malignant GCTs accounting for only 1–2% of all cases [7,8]. The diagnostic criteria for malignant GCT are necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (>2 mitoses/10 high-power fields, 200 magnification), high nuclear/cytoplasmic ratio, and pleomorphism. GCT is considered to have malignant histological features if more than three of these criteria are present [7]. In our patient, only one of these criteria was observed (spindling), and the tumor was classified as atypical. Some GCTs that are initially described as having benign or atypical features become clinically malignant, developing local recurrence, distant metastasis, and/or lymph node metastasis [8]. The features of clinically malignant tumors include: diameter >4 cm, rapid growth, distant metastasis, local invasion, and early recurrence after treatment of the primary
Please cite this article in press as: Kusano J, et al. Neck and superior mediastinal granular cell tumor excised via a combined approach. Auris Nasus Larynx (2014), http://dx.doi.org/10.1016/j.anl.2014.09.001
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Fig. 4. Histopathological findings. (A and B) Hematoxylin and eosin staining. There was proliferation of polygonal and spindled cells with eosinophilic granule-rich cytoplasm. Bar: 50 mm (A), 20 mm (B). (C) Periodic acid-Schiff staining. The cytoplasmic granules stained positive. (D) Immunohistochemical staining for S-100 protein. The cytoplasm and nuclei of the tumor cells stained positive.
lesion [7–10]. Three of the 12 reported cases of mediastinal GCT were malignant, and these tumors were all >4 cm in diameter (5.4 cm, 13 cm, and 15 cm). Four of the nine benign mediastinal GCTs were also >4 cm in diameter. The local recurrence rate of
GCTs in various organs is generally very low, with a reported rate of 2–9%. However, incomplete excision is associated with a high local relapse rate (20.8%) [6]. Early relapse suggests malignant potential even if the tumor has benign histological features, and complete
Table 1 Clinicopathological features of 12 cases of mediastinal granular cell tumor F, female; M, male; Pos, posterior mediastinum; Lt. Sup, left superior mediastinum; Size, maximum diameter; NA, not available; Sympathetic, sympathetic nerve. Case
Age
Sex
Location
Size (cm)
Histology
Origin nerve
S-100
Harrer (1972) Rosenbloom (1975) Abenoza (1987) Smith (1998) Aisner (1988) Robinson (1988) Machida (2003) Angeles (2005) Ponce (2011) Nakao (2012) Luca (2013) This case
59 11 18 53 27 27 21 43 28 66 64 36
F M F F F M M F F M F M
Pos Pos Pos Pos Pos Pos Pos Pos Sup Sup Sup Lt. Sup
13 5 4 11.5 4.4 2.4 2 3 2.5 5.4 15 4
Malignant Benign Benign Benign Benign Benign Benign Benign Benign Malignant Malignant Benign
NA Sympathetic NA NA Sympathetic NA Sympathetic NA NA Sympathetic Sympathetic NA
NA NA + + + NA + + NA + + +
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tumor excision is necessary to prevent local recurrence. Sixteen percent of the patients with benign GCTs were reported to have multiple GCTs at first presentation, indicating the importance of differentiating between multiple benign GCTs and metastasis [11]. Malignant GCT has a poor prognosis, with 39–50% of the patients dying from their disease after a median period of 3 years [7]. At present, the only accepted radical treatment is complete excision. Effective chemotherapy and radiation therapy regimens have not yet been established for malignant GCT. However, some case reports have suggested that chemotherapy and/or radiotherapy may be beneficial in cases of unresectable recurrence or metastasis. One reported case of tracheal malignant GCT with mediastinal metastasis responded to postoperative radiotherapy [8]. Rosenthal et al. [12] reported a patient with recurrent GCT in the buttock who was successfully treated by salvage surgery and subsequent radiotherapy. Kanat et al. [13] reported a case of multiple metastatic malignant GCT of the skin that was successfully treated with gemcitabine and paclitaxel followed by radiotherapy. In retrospect, tumor excision in our patient may have been possible via the neck incision alone, although visualization of the mediastinal side of the tumor would have been very limited. However, it may be impossible or very risky to excise such a mass blindly, identify the nerve of origin of the tumor, or attempt extracapsular excision in a restricted operative field via a neck incision, particularly if there are adhesions between the tumor and the lung or major blood vessels. We decided to operate via combined neck incision and VATS to ensure complete and safe tumor excision. Neck dissection combined with VATS is believed to be safer than neck incision without VATS [14,15]. Although it may be unclear whether the neck incision or VATS should be performed first [14], we believe that this should depend on the size and location of the tumor. 4. Conclusion A rare case of GCT in the neck and mediastinum was reported. To completely and safely excise such a potentially malignant neurogenic tumor, a surgical approach via combined neck incision and VATS is recommended. As GCT may have a clinically malignant course even if the initial histological features are benign, careful follow-up is required.
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Conflicts of interest None. Acknowledgment The authors are grateful to Dr. Yumiko Yasuhara (Department of Pathology, Kyoto-Katusra Hospital).
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Please cite this article in press as: Kusano J, et al. Neck and superior mediastinal granular cell tumor excised via a combined approach. Auris Nasus Larynx (2014), http://dx.doi.org/10.1016/j.anl.2014.09.001
