Paraganglioma Presenting as a Nasal Septal Mass: Case Report and Literature Review.
Paragangliomas are rare, slow-growing neuroendocrine tumors arising from cells of neural crest origin. They typically originate from the adrenal gland, but occur extraadrenally in 5-10% of cases . In the head and neck region, paragangliomas make up only 0.6% of all tumors, most commonly in the carotid body and jugular-tympanic regions [1-3]. Though rare, there are few reported cases of paragangliomas arising in the nasal cavity and paranasal sinuses [4-8]. To our knowledge, there has only been one previously reported case of a paraganglioma originating from the nasal septum .
2. Case Report
A 70-year-old female complaining of persistent nasal congestion and obstruction presented to our clinic for evaluation. She denied any headache or epistaxis. Nasal endoscopy was performed which showed a posterior septal mass approaching the sphenoid sinuses bilaterally and partially obstructing the view of the nasopharynx. The overlying mucosa was intact except for a small area superiorly which showed a soft granulomatous mass protruding into the left nasal cavity.
The patient was taken to the operating room for septoplasty with biopsy of the mass at an outside institution. Microscopic examination of the biopsy specimen demonstrated clusters of epithelioid-appearing cells separated by bands of fibrillary stroma. The epithelioid cells were noted to have abundant amphophilic cytoplasm, uniform, rounded nuclei with "salt and pepper" chromatin, and small nucleoli. No mitotic activity, invasion, necrosis, or calcification was seen. Immunohistochemical staining demonstrated positivity for neuron-specific enolase (NSE), chromogranin A, synaptophysin, and CD56 cell markers within the epithelioid cells. Fibrillary cells were positive for NSE, chromogranin A, S-100, glial fibrillary acid protein (GFAP), and CD56 cell markers. Based on the histological appearance and immunohistochemical staining, a diagnosis of paraganglioma was made.
The patient was referred to our institution for further management. Preoperative CT imaging showed a smoothly marginated, soft tissue density mass centered at the posterior nasal septum with extension into the nasopharynx and bulging into the right sphenoid sinus (Figure 1). Severe thinning and smooth remodeling of the anterior wall of the sphenoid sinus and anterior clivus were seen. MRI imaging demonstrated hyperintense signaling of the mass on T1weighted images with a peripheral rim of hypointense signaling on T2-weighted imaging suggestive of a capsule.
An endoscopic resection of the mass was performed. Intraoperatively, a large mass was seen in the posterior aspect of the septum, bulging into the bilateral nasal cavities and extending into the sphenoid sinuses (Figure 2). Erosion of the bone of the rostrum and anterior face of the sphenoid were also seen. Complete resection of the mass was achieved through a posterior septectomy and bilateral sphenoidotomy with tissue removal. Postoperative histologic analysis of the specimen was consistent with a paraganglioma (Figure 3).
The patient has been symptom free without local recurrence 3 months following tumor resection.
Paragangliomas arising from the nasal cavity and nasal sinuses are extremely rare. Only 48 total cases of paragangliomas occurring in the nasal cavity or paranasal sinuses have been reported to date, occurring in patients with ages ranging between 8 and 89 years old, with an average age of 49 years old. These tumors are slightly more prevalent amongst females (60.4%). Twelve were reported to be malignant in nature, demonstrating either intracranial extension or metastasis to the cervical lymph nodes, brain, and bone. These masses were most frequently reported to originate from the ethmoid sinuses, middle turbinate, and maxillary sinuses. Other less common locations of origin reported include the superior and inferior turbinates, and the sphenoid and frontal sinuses. To the best of our knowledge, there has only been one other reported case of a paraganglioma originating from the nasal septum (Table 1) .
The most commonly reported symptoms included nasal obstruction, headache, and recurrent epistaxis. The vast majority of reported cases were functionally inactive, with no evidence of catecholamine or adrenocorticotropic hormone (ACTH) secretion. However, there have been a few reported cases of metabolically active tumors secreting ACTH and catecholamines, causing hypertension and other cushingoid features in the affected patient [12, 13, 30]. As such, testing for catecholamine and metanephrines is recommended in symptomatic patients [29, 33].
The origin of paragangliomas in the nasal cavity and paranasal sinuses remains unclear. Although paraganglionic tissue has never been demonstrated in the nasal cavity, a wider distribution ofparaganglionic tissue is thought to exist in fetuses and neonates, degenerating after birth [42, 43]. Some authors have suggested that the migration of these embryonic paraganglionic cells accounts for the occurrence of paragangliomas in areas with no known paraganglionic tissue like the nasal cavity [13,29,42,44]. Additionally, it has been shown that paraganglionic tissue exists around the terminal portion of the maxillary artery in infants and could possibly represent a point of origin for paragangliomas in the nasal cavity due to its anatomic proximity [19, 45]. Others have suggested that the paraganglionic tissue may exist in the pterygopalatine fossa due to the close relationship of paraganglionic tissue with arteries and cranial nerves [18, 19, 22].
In contrast, chondrocytes of the cartilaginous septum develop from neural crest cells between the nasal cavities by the ninth week of embryonic development [46, 47]. This is evident by the expression of various neural crest stem cell markers in nasal septum progenitor cells . Several studies have demonstrated that these neural crest-derived chondrocytes in an adult septum retain pluripotent properties, with the capacity for osteogenic, chondrogenic, and neurogenic differentiation [48, 49]. It is possible that the neural crest origin of septal chondrocytes plays an important factor in the development of nasal septal paragangliomas. Despite the neural crest origins of nasal chondrocytes, paragangliomas arising from the nasal septum are extremely rare.
Masses arising from the nasal septum represent a broad spectrum of diagnoses including polyps, chondromas, hematomas, and hemangiomas. Less common septal lesions include sarcomas, melanomas, and other neoplasms [46, 50]. Patients with septal masses typically present with nonspecific symptoms of nasal obstruction or epistaxis, making it difficult to diagnose these masses based on clinical evaluation alone. CT imaging and MR imaging are useful tools in determining exact locations and boundaries of lesions, as well as identifying any erosion or extension into surrounding structures, though imaging features of most masses are nondiagnostic. Diagnosis of such masses requires a combination of clinical history and histopathologic findings. Although paragangliomas of the nasal septum are extremely rare, they should be included in the differential diagnosis when evaluating a septal mass.
The classical histologic appearance of a paraganglioma features an alveolar pattern of well-defined clusters of epithelioid chief cells with round nuclei and eosinophilic cytoplasm. These cells form a "zellballen" pattern of nests separated by vascular stroma and spindle-shaped sustentacular cells [28, 43]. Immunohistochemical staining of paragangliomas generally demonstrates positive markers for NSE, synaptophysin, and chromogranin within the chief cells and S-100 and GFAP within the sustentacular cells [8, 25, 43].
Although the majority of reported nasal paragangliomas are benign, 12 of the cases presented in this review (25.0%) were reported to be malignant, demonstrating intracranial invasion and/or metastasis to the brain, cervical lymph nodes, and bones. It is widely accepted that malignancy cannot be diagnosed by histology alone, but requires evidence of bony invasion or distant metastasis [18, 19, 22]. Certain histological features such as mitotic figures, cellular pleomorphism, necrosis, and vascular invasion can be suggestive of malignancy, though none of these features have been shown to be reliable predictors of malignancy [19, 51]. As such, evaluation with CT imaging and MRI imaging plays a key role in both localization of the primary tumor and identification of local invasion or metastasis.
Almost all of the cases presented in this review were treated surgically. Suggested management of sinonasal paragangliomas involves surgical excision with close followup, as several cases of recurrence have been reported [4, 22, 29]. Due to the rich vascularity of these masses, preoperative embolization of the vessels supplying the tumor has been suggested to reduce bleeding during surgery [4,22,24]. Many authors suggest the use of radiation therapy to slow the rate of recurrence, although radiation therapy alone has not been shown to be curative [3, 22, 33]. Chemotherapy as a primary treatment for these tumors has been shown to be largely ineffective, though 3 cases reported in this review reported the use of chemotherapy in addition to surgery and radiation therapy in the management of malignant sinonasal paragangliomas [4, 22].
We present a rare case of a paraganglioma presenting as a septal mass. To the best of the authors' knowledge, only one other case of nasal septal paragangliomas has been reported. Clinically, these lesions cause symptoms of obstruction, congestion, headache, and epistaxis. Recognizing that paragangliomas can arise from the nasal septum is crucial to accurately diagnose these tumors when evaluating septal lesions. A diagnosis of a paragangliomas can be confirmed based on the histopathologic imaging. These tumors are usually benign but require additional imaging as malignancy cannot reliably be ruled out on the basis of histology alone. Treatment of these tumors requires surgical resection, though radiation therapy has been to show slow growth and decrease recurrence.
Conflicts of Interest
The authors declare that there are no conflicts of interest or financial disclosures.
The authors thank Dr. David Yau for providing the histopathology images and Dr. John Go for reviewing the radiology images.
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James H. Kim [ID], (1) Nathan Tu, (2) and Bozena Barbara Wrobel (3)
(1) Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA
(2) University of Southern California LAC+USC Medical Center Department of Otolaryngology, Los Angeles, CA, USA
(3) Associate Professor of Clinical Otolaryngology Head and Neck Surgery, Keck School of Medicine, Los Angeles, CA, USA
Correspondence should be addressed to James H. Kim; email@example.com
Received 7 August 2018; Accepted 19 November 2018; Published 6 December 2018
Academic Editor: Richard T. Miyamoto
Caption: FIGURE 1: Axial CT image showing a soft tissue mass centered at the posterior nasal septum with extension into the nasopharynx.
Caption: FIGURE 2: Intraoperative image of the mass protruding from the posterior septum within the left nasal cavity.
Caption: FIGURE 3: (a) H&E of the septal mass showing a "zellballen" pattern of clusters of epithelioid cells between bands of fibrillary stroma (20x). IHC staining showing positivity for (b) chromogranin A within epithelioid cells (40x), (c) synaptophysin within epithelioid cells (20x), and (d) S-100 within fibrillary cells (20x).
TABLE 1: Review of reported cases of sinonasal paragangliomas. Case Author Year Sex Age 1 Harkins  1957 F 52 2 Moran  1962 F 89 3 Lack  1976 F 50 4 F 50 5 M 8 6 Gosavi  1978 M 65 7 Apple  1982 F 50 8 Koegel  1982 F 71 9 Himelfarb  1985 M 41 10 Straehler  1985 M 42 11 Ueda  1985 F 31 12 Watson  1988 M 56 13 Branham  1989 F 25 14 Kuhn  1989 M 62 15 Shimoda  1989 M 58 16 Talbot  1990 F 17 17 Nguyen  1995 F 32 18 Biswas  1999 F 45 19 Sharma  1999 M 33 20 Welkoborsky  2000 F 54 21 F 56 22 M 57 23 Scott  2001 M 24 24 Lecuna  2002 F 72 25 Ketabchi  2003 F 72 26 Mouadeb  2003 M 72 27 Lieberum  2003 M 64 28 Askar  2003 M 47 29 Rocha  2005 M 45 30 Liess  2007 F 64 31 Morales  2007 F 41 32 Jin  2008 F 23 33 Fasunla  2008 F 39 34 Kisser  2012 F 36 35 Zainine  2012 F 43 36 Papaspyrou  2013 F 33 37 M 64 38 F 56 39 F 80 40 M 57 41 F 54 42 Granato  2013 F 61 43 Michel  2013 M 47 44 Amiraraghi  2013 M 29 45 Arora  2014 F 40 46 Yamaguchi  2015 F 66 47 Aydin  2015 F 32 48 Srivastava  2016 M 60 Case Location Biological behavior 1 Ethmoid sinus Benign 2 Nasal cavity Benign 3 High nasal vault Benign (local recurrence x3) 4 Middle turbinate Benign 5 Middle turbinate Benign 6 Middle turbinate Benign 7 Ethmoid, sphenoid, Benign; ectopic and maxillary sinuses ACTH production 8 Maxillary and Malignant (extension sphenoid sinuses into temporal lobe); catecholamine secretion 9 Middle turbinate Benign 10 Maxillary sinus Benign 11 Maxillary and Benign ethmoid sinuses 12 Inferior turbinate Benign 13 Maxillary and Malignant ethmoid sinuses (brain metastasis) 14 Superior nasal cavity, Benign ethmoid sinus 15 Ethmoid sinus and Malignant (cervical bilateral frontal fossa lymph nodes metastasis) 16 Maxillary sinus Benign 17 Ethmoid sinus Malignant (bone metastasis) 18 Middle turbinate Benign 19 Frontal sinus (primary); Malignant orbit, optic nerve, (recurrence, cavernous sinus, intracranial maxillary and ethmoid invasion) sinuses (recurrent) 20 Nasal cavity Benign 21 Ethmoid sinus Malignant (brain metastasis) 22 Ethmoid sinus Benign 23 Nasal cavity, Benign ethmoid sinus 24 Ethmoid sinus (primary); Malignant (recurrence, maxillary sinus (recurrent) submandibular lymph nodes metastasis) 25 Nasal cavity Benign 26 Ethmoid sinus Benign 27 Frontal and Benign; ectopic ethmoid sinuses ACTH production 28 Middle turbinate Benign 29 Nasal cavity Benign 30 Sphenoid sinus, sella, Benign cavernous sinus 31 Sphenoid and Benign ethmoid sinuses 32 Superior turbinate Malignant (questionable transformation simulating Ewing's sarcoma/primitive neuroectodermal tumor) 33 Lateral nasal wall Benign 34 Maxillary sinus Benign 35 Middle turbinate Benign 36 Nasal cavity Benign 37 Ethmoid sinuses, anterior Malignant (recurrent, skull base, frontal lobe intradural metastases) dura (primary); ethmoid, sphenoid, cavernous sinus, orbit (recurrent) 38 Ethmoid sinus Malignant (brain metastasis) 39 Nasal cavity, Malignant (recurrent, maxilloethmoidal angle, intracranial invasion) maxillary, ethmoid, and sphenoid sinuses (primary); nasal cavity, anterior skull base, frontal lobe (recurrent) 40 Ethmoid sinus Benign 41 Nasal cavity Benign 42 Nasal cavity Benign 43 Maxillary sinus Malignant (cervical lymph node metastasis) 44 Cribriform plate and Benign fovea ethmoidalis presenting as nasal polyps 45 Lateral nasal wall Benign 46 Ethmoid sinus Benign 47 Nasal cavity, ethmoid sinus Benign (local recurrence x2) 48 Anterior nasal septum Benign Case Therapy Follow-up 1 Exc, RT, lig ECA NED at 1 year 2 Exc, ligation of NED at 2 years external carotid artery 3 Exc, ligation of NED at 11 years external carotid following artery final exc 4 Exc No f/u 5 Exc NED at 7 years 6 Exc, RT NED at 2 years (incomplete cycle) 7 Exc, RT, hormonal NED at 6 years pharmacotherapy 8 RT No follow-up available 9 Exc NED at 1 year 10 Exc No follow-up available 11 Exc NED at 2.5 years 12 Exc, RT NED at 3 years 13 Exc, RT, CT DOD at 3 years 14 Exc NED at 1 year 15 Exc, RT NED at 2 years 16 Embolization of NED at 3 months internal maxillary artery, exc 17 Exc, RT DOD at 15 years 18 Exc NED at 1 month 19 CT, RT, exc; DOD at 19 months vessel embolization, exc 8 months later for recurrence 20 Exc NED at 3 years 21 Exc, RT DOD at 28 months 22 Exc, RT NED at 2 years 23 Exc NED at 15 months 24 Exc No follow-up available 25 Exc NED at 8 months 26 Exc NED at 4 years 27 Exc NED at 2 years 28 Exc NED at 2 years 29 Exc NED at 5 months 30 Partial exc, RT Residual tumor stable at 2 years 31 No information No follow-up available available 32 Exc NED at 3 years 33 Exc NED at 1 year 34 Exc NED at 1 year 35 Exc NED at 2 years 36 Exc NED at 15 years 37 2 exc, RT, CT DOD at 60 months 38 Exc, RT DOD at 28 months 39 Exc DNOD 17 months after 2nd surgery 40 Exc NED at 2 years 41 Exc NED at 3 years 42 Exc NED at 2 years 43 Exc, RT NED at 1 year 44 Exc NED at 3 years 45 Exc NED at 2 years 46 Exc NED at 1 year 47 Exc NED 5 years after final exc 48 Exc NED at 18 months RT, radiation therapy; CT, chemotherapy; Exc, surgical excision; NED, no evidence of disease; DOD, died of disease.
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|Title Annotation:||Case Report|
|Author:||Kim, James H.; Tu, Nathan; Wrobel, Bozena Barbara|
|Publication:||Case Reports in Otolaryngology|
|Date:||Jan 1, 2018|
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