Metastatic glomus jugulare: Long-term followup DENNIS I. BOJRAB, MD, SANJAY A. BHANSALI, MD, and MICHAEL E. GLASSCOCK 111, MD.
Royal Oak and Detroit, Michigan. and Nashville. Tennessee
S i n c e the first report of a glomus jugulare tumor by Rosenwasser‘ in 1945, there has been a continuing evolution in our understanding of the clinical behavior, histologic appearance, prognosis, and treatment of this interesting tumor. These extra-adrenal paragangliomas are classified as benign neoplasms, but they invade bone and soft tissue and can metastasize.’ Previous reports indicate that patients with metastatic glomus jugulare tumor have a rapid decline in their clinical condition, with progression of disease leading to death within a year of diagnosis.’ Our patient had a metastatic glonius jugulare tumor and is now alive and well 5 years later, with no evidence of active disease. We discuss earlier reports of metastatic glomus jugulare tumor and the factors that may be related to the successful outcome of our patient. CASE REPORT A 25-year-old woman was first seen in March 1977. w i t h a 2-year history of pulsatile tinnitus of the right ear and a 6-
month history of right facial weakness and paresthesia. A transniastoidlfacial recess approach was used for removal of a glonius jugulare tunior and at a second stage the facial nerve was resected and grafted. Results of chest x-ray examination at that time were normal. One year later, there was some recovery of facial function. Three years later. she noted recurrent pulsatile head noise, fever. nonproductive cough, and severe fatigue. An evaluation revealed anemia (hemoglobin value. 7.1 gm/dl). despite no identifiable source of bleeding, and chest x-ray film showed bilateral diffuse nodular infiltrates at the base of the skull. Schwartz and Israel‘ found adequate iron stores with an inappropriately depressed serum erythropoietin level and confirmed (by biopsy) the presence of a metastatic paraganglioma
From the Department of Otolaryngology, Wayne State University (Drs. Bojnb and Bhansnli). EAR Consultants of Michigan (Dr. Bojrab). and The Otology Group. Nashville (Dr. Glasscock). Supported by EAR Consultants of Michigan. Presented at the Annual Meeting of the American Neurotology Society, Siin Francisco, Calif., April l . 1989. Received for publication Oct. 25. 1989; accepted July 20. 1990. Reprint requests: Dennis I . Bojrab. MD. 3535 West 13 Mile Road. Suite 205. Royal Oak, MI 48073. 2314124056
Fig. I . Frontalview arteriogram shows ipsilateral vascular neck lesion. Open arrow shows metastatic glomus tumor blush; closed arrow shows gold weight In ipsilateral eyelid. Dental work is also apparent. in the lungs. She was treated with nadrolone decanoate and blood transfusions. In October 1982. a right posterior neck mass was excised that proved to be a paraglanglionia. She subsequently began to experience worsening right otalgia and facial weakness, and the anemia and poor pulmonary function iilso became more severe. In February 1984, she was started on a regimen of etoposide (VP- 16) chemotherapy. In February 1985, she was referred to the senior author (M.E.G.) because of progressive disease of the skull base. Physical examination revealed complete right facial paralysis and perforation of the right tympanic membrane. Results of 261
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OtolaryngologyHead and Neck Surgery
262 Case Reports
Flg. 2. Chest x-ray film shows diffuse bilateral metastatic glomus jugulare nodules.
oropharyngeal examination were normal and both vocal cords were mobile. Four-vessel angiography showed tumor involvement of the right skull base and two ipsilateral vascular neck lesions (Fig. 1). Chest x-ray film revealed bilateral pulmonary nodules (Fig. 2). A right radical neck dissection and infratemporal fossa resection of the entire tumor was performed. The previous facial nerve graft was infiltrated by tumor, and it was resected and grafted again. Cranial nerves XI and XI1 were sacrificed. One high jugulodigastric lymph node and two periparotid lymph nodes were involved with the mctastatic paraganglioma. The parotid gland itself was not involvcd. The 3%-month postoperative course was complicated by vagus nerve paralysis, pneumonia, and gastric statis. The patient required a temporary tracheotomy and feeding jejunostomy, ipsilateral vocal cord injection, and cricopharyngeal myotomy. Microscopic examination showed many polyhedral cells and occasional spindle cells, consistent with paraganglioma. Figure 3, from the primary tumor site, shows stromal proliferation with cords of tumor infiltration and patchy areas of vascularity. The lymph nodes appeared more well differentiated. The typical “Zellballen” (tumor nest) pattern was noted within the center of the lymph nodes (Fig. 4). Five years postoperatively, our patient has had resolution of the anemia and pulmonary nodules. She is currently alive and well, has no difficulty with speech or deglutition. and . ~ sings in her church has grade 111 facial nerve f ~ n c t i o nShe choir and leads a productive life.
DISCUSSION
Glomus jugulare tumors (jugular paragangliomas) are uncommon, and metastatis of such tumors is even more uncommon (3%).* Because histologic criteria do not predict the clinical behavior of paragangliomas, malignancy is defined by clinical evidence of metastasis. Given the tendency of these tumors to have a multicentric origin and given their association with other malignant tumors, suspicious lesions should undergo biopsy.* Many earlier reports of metastatic glomus jugulare tumors lacked proper evidence of metastasis, inasmuch as biopsy of metastatic lesions was not always performed or reported. Zak and Lawson* have documented 27 cases of metastatic glomus jugulare tumor reported before 1980. Our review of the world literature has uncovered an additional five cases,6’10and we report the thirty-third case. It is generally believed that metastatic glomus jugulare tumor leads to rapid death, but there are reports that suggest a variable course. Gabrail et al.” reported a patient who survived 4 years with bony and visceral metastatic disease. Sakakura et al.’ reported a patient who lived 5 years with metastatic disease. Metastases from glomus jugulare tumors have been reported most frequently to the lungs and cervical lymph nodes, but skeletal and visceral metastases have
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Volume 104 Number 2 February 1991
Case Reports 263
Fig. 3. Primary glomus jugulare tumor with sclerotic stroma and cords of tumor infiltrating soft tissue.
Fig. 4. Metastatic glomus tumor in lymph node shows typical Zellballen (tumor nest) pattern.
also been noted.' Our patient had metastases to the lungs and cervical nodes. The metastatic cervical lymph nodes showed a more well-differentiated histologic pattern than the primary tumor. Earlier reports have suggested that the metastatic tumor may not resemble the primary tumor, and may even resemble carcinoma." In
questionable cases, the current literature recommends electron microscopy and immunocytochemical study with a panel of neuroendocrine markers. I' Patients with metastatic glomus jugulare tumor have usually been treated with radiation therapy or chemotherapy.'.'.'.'" Our patient did not receive radiation ther-
Downloaded from oto.sagepub.com at NANYANG TECH UNIV LIBRARY on June 5, 2016
OtolaryngologyHead and Neck Surgery
264 Case Reports
apy and did not respond to chemotherapy. Although Gabrail et al. lo achieved some clinical improvement with radiation therapy for bony metastases, the effect was temporary, and their patients died of widespread metastatic disease. Most patients with metastatic glomus jugulare have received chemotherapy, with no discernible improvement.’ Inexplicable anemia, as seen in our patient, has been noted in patients with metastatic head and neck paragangliomas; this finding has been addressed by Schwartz and I s ~ a e l . ~ We are unable to explain the apparent complete remission of our patient’s systemic disease (anemia and pulmonary nodules) after total surgical removal of the primary tumor and neck metastases, but we believe this aggressive control of head and neck disease is the most important factor in her successful outcome. It has been hypothesized that there may be some as yet undiscovered compound secreted by glomus tumors that induces distant tumor growth in cases of metastases. In 1950, LattesI3 mentioned the possible existence of an unknown factor that produced a neoplastic change in the paraganglia, based on his observation of synchronous paragangliomas. Because of the endocrinologic nature of paragangliomas, we believe that the primary treatment should be complete surgical removal of glomus jugulare tumors. Metastatic disease should prompt thorough evaluation for recurrent primary tumor, and the treatment of choice for recurrent and metastatic head and neck disease remains surgical.
REFERENCES
1. Rosenwasser H. Carotid body tumor of the middle ear and mastoid. Arch Otolaryngol 1945;41:64-7. 2. Zak FG, Lawson W. Glomus jugulare tumors. In: The paraganglionic chemoreceptor system. New York Springer-Verlag, 19821339-91. 3. McCabe BF, Fletcher M. Selection of therapy of glomus jugulare tumors. Arch Otolaryngol 1969;89:182-5. 4. Schwartz ML, Israel HL. Severe anemia as a manifestation of metastatic jugular paraganglioma. Arch Otolaryngol 1983;109: 269-72. 5. Facial nerve grading system. Bull Otolaryngol Head Neck Surg 1985;4:1. 6. Davis JM, Davis KR, Hesselink JR, et al. Malignant glomus jugulare tumor: a case with two unusual radiographic features. J Comput Assist Tomcgr 1980;4:415-7. 7. El Fiky FM, Paparella MM. A metastatic glomus jugulare tumor. A temporal bone report. Am J Otol 1984;5:197-200. 8. Sakakura T, Makita Y, Nabeshima S, et al. Chemodectoma of the glomus jugulare with multiple metastases. Neurol Med Chir (Tokyo) 1986;26:701-5. 9. Takahashi N, Nakashima S, Kumanishi T, et al. Paragangliomas of the craniocervical region. Acta Neuropathol (Berl) 1987;73: 227-32. 10. Gabrail N, Mikhail R, Mukkamala A, et al. Malignant paraganglioma treated successfully with chemotherapy. [Abstract]. Fifth International Conference on the Adjuvant Therapy of Cancer, March 11-14, 1987:78. 11. Taylor DM,Alford BR, Greenberg SD. Metastases of glomus jugulare tumors. Arch Otolaryngol 1965;82:5-13. 12. Johnson TI, Zarbo RJ, Lloyd RV, et al. Paragangliomas of the head and neck immunohistochemical neuroendocrine and intermediate filament typing. Mod Pathol 1988;1:216-23. 13. Lanes R. Nonchromaffin paraganglioma of ganglion nodosum, carotid body, and aortic-arch bodies. Cancer 1950;3:667-94.
W e wish to thank Richard Zarbo, M D , for the photomicrographs and Mark May, M D , for his assistance in compiling records.
Downloaded from oto.sagepub.com at NANYANG TECH UNIV LIBRARY on June 5, 2016
Royal Oak and Detroit, Michigan. and Nashville. Tennessee
S i n c e the first report of a glomus jugulare tumor by Rosenwasser‘ in 1945, there has been a continuing evolution in our understanding of the clinical behavior, histologic appearance, prognosis, and treatment of this interesting tumor. These extra-adrenal paragangliomas are classified as benign neoplasms, but they invade bone and soft tissue and can metastasize.’ Previous reports indicate that patients with metastatic glomus jugulare tumor have a rapid decline in their clinical condition, with progression of disease leading to death within a year of diagnosis.’ Our patient had a metastatic glonius jugulare tumor and is now alive and well 5 years later, with no evidence of active disease. We discuss earlier reports of metastatic glomus jugulare tumor and the factors that may be related to the successful outcome of our patient. CASE REPORT A 25-year-old woman was first seen in March 1977. w i t h a 2-year history of pulsatile tinnitus of the right ear and a 6-
month history of right facial weakness and paresthesia. A transniastoidlfacial recess approach was used for removal of a glonius jugulare tunior and at a second stage the facial nerve was resected and grafted. Results of chest x-ray examination at that time were normal. One year later, there was some recovery of facial function. Three years later. she noted recurrent pulsatile head noise, fever. nonproductive cough, and severe fatigue. An evaluation revealed anemia (hemoglobin value. 7.1 gm/dl). despite no identifiable source of bleeding, and chest x-ray film showed bilateral diffuse nodular infiltrates at the base of the skull. Schwartz and Israel‘ found adequate iron stores with an inappropriately depressed serum erythropoietin level and confirmed (by biopsy) the presence of a metastatic paraganglioma
From the Department of Otolaryngology, Wayne State University (Drs. Bojnb and Bhansnli). EAR Consultants of Michigan (Dr. Bojrab). and The Otology Group. Nashville (Dr. Glasscock). Supported by EAR Consultants of Michigan. Presented at the Annual Meeting of the American Neurotology Society, Siin Francisco, Calif., April l . 1989. Received for publication Oct. 25. 1989; accepted July 20. 1990. Reprint requests: Dennis I . Bojrab. MD. 3535 West 13 Mile Road. Suite 205. Royal Oak, MI 48073. 2314124056
Fig. I . Frontalview arteriogram shows ipsilateral vascular neck lesion. Open arrow shows metastatic glomus tumor blush; closed arrow shows gold weight In ipsilateral eyelid. Dental work is also apparent. in the lungs. She was treated with nadrolone decanoate and blood transfusions. In October 1982. a right posterior neck mass was excised that proved to be a paraglanglionia. She subsequently began to experience worsening right otalgia and facial weakness, and the anemia and poor pulmonary function iilso became more severe. In February 1984, she was started on a regimen of etoposide (VP- 16) chemotherapy. In February 1985, she was referred to the senior author (M.E.G.) because of progressive disease of the skull base. Physical examination revealed complete right facial paralysis and perforation of the right tympanic membrane. Results of 261
Downloaded from oto.sagepub.com at NANYANG TECH UNIV LIBRARY on June 5, 2016
OtolaryngologyHead and Neck Surgery
262 Case Reports
Flg. 2. Chest x-ray film shows diffuse bilateral metastatic glomus jugulare nodules.
oropharyngeal examination were normal and both vocal cords were mobile. Four-vessel angiography showed tumor involvement of the right skull base and two ipsilateral vascular neck lesions (Fig. 1). Chest x-ray film revealed bilateral pulmonary nodules (Fig. 2). A right radical neck dissection and infratemporal fossa resection of the entire tumor was performed. The previous facial nerve graft was infiltrated by tumor, and it was resected and grafted again. Cranial nerves XI and XI1 were sacrificed. One high jugulodigastric lymph node and two periparotid lymph nodes were involved with the mctastatic paraganglioma. The parotid gland itself was not involvcd. The 3%-month postoperative course was complicated by vagus nerve paralysis, pneumonia, and gastric statis. The patient required a temporary tracheotomy and feeding jejunostomy, ipsilateral vocal cord injection, and cricopharyngeal myotomy. Microscopic examination showed many polyhedral cells and occasional spindle cells, consistent with paraganglioma. Figure 3, from the primary tumor site, shows stromal proliferation with cords of tumor infiltration and patchy areas of vascularity. The lymph nodes appeared more well differentiated. The typical “Zellballen” (tumor nest) pattern was noted within the center of the lymph nodes (Fig. 4). Five years postoperatively, our patient has had resolution of the anemia and pulmonary nodules. She is currently alive and well, has no difficulty with speech or deglutition. and . ~ sings in her church has grade 111 facial nerve f ~ n c t i o nShe choir and leads a productive life.
DISCUSSION
Glomus jugulare tumors (jugular paragangliomas) are uncommon, and metastatis of such tumors is even more uncommon (3%).* Because histologic criteria do not predict the clinical behavior of paragangliomas, malignancy is defined by clinical evidence of metastasis. Given the tendency of these tumors to have a multicentric origin and given their association with other malignant tumors, suspicious lesions should undergo biopsy.* Many earlier reports of metastatic glomus jugulare tumors lacked proper evidence of metastasis, inasmuch as biopsy of metastatic lesions was not always performed or reported. Zak and Lawson* have documented 27 cases of metastatic glomus jugulare tumor reported before 1980. Our review of the world literature has uncovered an additional five cases,6’10and we report the thirty-third case. It is generally believed that metastatic glomus jugulare tumor leads to rapid death, but there are reports that suggest a variable course. Gabrail et al.” reported a patient who survived 4 years with bony and visceral metastatic disease. Sakakura et al.’ reported a patient who lived 5 years with metastatic disease. Metastases from glomus jugulare tumors have been reported most frequently to the lungs and cervical lymph nodes, but skeletal and visceral metastases have
Downloaded from oto.sagepub.com at NANYANG TECH UNIV LIBRARY on June 5, 2016
Volume 104 Number 2 February 1991
Case Reports 263
Fig. 3. Primary glomus jugulare tumor with sclerotic stroma and cords of tumor infiltrating soft tissue.
Fig. 4. Metastatic glomus tumor in lymph node shows typical Zellballen (tumor nest) pattern.
also been noted.' Our patient had metastases to the lungs and cervical nodes. The metastatic cervical lymph nodes showed a more well-differentiated histologic pattern than the primary tumor. Earlier reports have suggested that the metastatic tumor may not resemble the primary tumor, and may even resemble carcinoma." In
questionable cases, the current literature recommends electron microscopy and immunocytochemical study with a panel of neuroendocrine markers. I' Patients with metastatic glomus jugulare tumor have usually been treated with radiation therapy or chemotherapy.'.'.'.'" Our patient did not receive radiation ther-
Downloaded from oto.sagepub.com at NANYANG TECH UNIV LIBRARY on June 5, 2016
OtolaryngologyHead and Neck Surgery
264 Case Reports
apy and did not respond to chemotherapy. Although Gabrail et al. lo achieved some clinical improvement with radiation therapy for bony metastases, the effect was temporary, and their patients died of widespread metastatic disease. Most patients with metastatic glomus jugulare have received chemotherapy, with no discernible improvement.’ Inexplicable anemia, as seen in our patient, has been noted in patients with metastatic head and neck paragangliomas; this finding has been addressed by Schwartz and I s ~ a e l . ~ We are unable to explain the apparent complete remission of our patient’s systemic disease (anemia and pulmonary nodules) after total surgical removal of the primary tumor and neck metastases, but we believe this aggressive control of head and neck disease is the most important factor in her successful outcome. It has been hypothesized that there may be some as yet undiscovered compound secreted by glomus tumors that induces distant tumor growth in cases of metastases. In 1950, LattesI3 mentioned the possible existence of an unknown factor that produced a neoplastic change in the paraganglia, based on his observation of synchronous paragangliomas. Because of the endocrinologic nature of paragangliomas, we believe that the primary treatment should be complete surgical removal of glomus jugulare tumors. Metastatic disease should prompt thorough evaluation for recurrent primary tumor, and the treatment of choice for recurrent and metastatic head and neck disease remains surgical.
REFERENCES
1. Rosenwasser H. Carotid body tumor of the middle ear and mastoid. Arch Otolaryngol 1945;41:64-7. 2. Zak FG, Lawson W. Glomus jugulare tumors. In: The paraganglionic chemoreceptor system. New York Springer-Verlag, 19821339-91. 3. McCabe BF, Fletcher M. Selection of therapy of glomus jugulare tumors. Arch Otolaryngol 1969;89:182-5. 4. Schwartz ML, Israel HL. Severe anemia as a manifestation of metastatic jugular paraganglioma. Arch Otolaryngol 1983;109: 269-72. 5. Facial nerve grading system. Bull Otolaryngol Head Neck Surg 1985;4:1. 6. Davis JM, Davis KR, Hesselink JR, et al. Malignant glomus jugulare tumor: a case with two unusual radiographic features. J Comput Assist Tomcgr 1980;4:415-7. 7. El Fiky FM, Paparella MM. A metastatic glomus jugulare tumor. A temporal bone report. Am J Otol 1984;5:197-200. 8. Sakakura T, Makita Y, Nabeshima S, et al. Chemodectoma of the glomus jugulare with multiple metastases. Neurol Med Chir (Tokyo) 1986;26:701-5. 9. Takahashi N, Nakashima S, Kumanishi T, et al. Paragangliomas of the craniocervical region. Acta Neuropathol (Berl) 1987;73: 227-32. 10. Gabrail N, Mikhail R, Mukkamala A, et al. Malignant paraganglioma treated successfully with chemotherapy. [Abstract]. Fifth International Conference on the Adjuvant Therapy of Cancer, March 11-14, 1987:78. 11. Taylor DM,Alford BR, Greenberg SD. Metastases of glomus jugulare tumors. Arch Otolaryngol 1965;82:5-13. 12. Johnson TI, Zarbo RJ, Lloyd RV, et al. Paragangliomas of the head and neck immunohistochemical neuroendocrine and intermediate filament typing. Mod Pathol 1988;1:216-23. 13. Lanes R. Nonchromaffin paraganglioma of ganglion nodosum, carotid body, and aortic-arch bodies. Cancer 1950;3:667-94.
W e wish to thank Richard Zarbo, M D , for the photomicrographs and Mark May, M D , for his assistance in compiling records.
Downloaded from oto.sagepub.com at NANYANG TECH UNIV LIBRARY on June 5, 2016
