Keywords head and neck paraganglioma - sinonasal paraganglioma - endoscopic skull base resection
- succinate dehydrogenase mutation
Paragangliomas of the head and neck are uncommon tumors arising from specialized neural
crest cells associated with autonomic ganglia. They account for only 0.6% of all tumors
within the head and neck region with functioning paragangliomas seen in only 1 to
3% of those cases.[1 ]
[2 ] The distribution of paragangliomas tends to parallel the course of the autonomic
system. They can be categorized into two types based on their functionality: catecholamine-secreting
chromaffin tumors and the nonfunctional nonchromaffin tumors. The majority of head
and neck paragangliomas belongs to the latter group. Carotid body tumors are the most
common paraganglioma of the head and neck region followed by jugulotympanic and vagal
paragangliomas. Head and neck paragangliomas have also been reported in the larynx,
trachea, orbit, and sinonasal cavities.[3 ] Succinate dehydrogenase (SDH) complex (A to D) mutations have been associated with
increased risk of tumors including paragangliomas and pheochromocytomas. Tumors associated
with the SDHB mutations tend to be extra-adrenal and can occur in the head and neck
region.[4 ]
There have been approximately only 35 reported cases of paragangliomas originating
from the sinonasal region.[5 ] Pathologic studies have shown paraganglionic tissue to be present in the pterygopalatine
fossa as well as the close anatomic relation with the pterygoid ganglion.[6 ] There have been only three reported cases of functional sinonasal paragangliomas
since 1957.[7 ]
[8 ]
[9 ] We present a case of a rare functioning sinonasal paraganglioma of the skull base
presenting with labile hypertension.
Case Report
The patient is a 50-year-old man with a history of a left adrenal pheochromocytoma
and para-aortic paraganglioma which was surgically resected 21 years before his presentation.
He did not undergo any prior genetic testing. Initial presentation began with recent
episodic hypertension which was referred to a nephrologist based on his history. He
had a 24-hour urine metanephrine study which showed normal urine metanephrine level,
but threefold increase in plasma chromogranin A levels and an eightfold increase in
plasma normetanephrine levels. He was started on phenoxybenzamine, an α adrenergic
receptor antagonist, and metyrosine, a tyrosine hydroxylase inhibitor, for management
of his hypertension from presumed recurrent abdominal paraganglioma. The patient underwent
a metaiodobenzylguanidine (MIBG) scan which showed a single large focus of uptake
at the right skull base corresponding to the known mass.
At this point, he was referred to our service for an otorhinolaryngologic evaluation.
On a review of systems, the patient noted occasional right-sided epistaxis and nasal
congestion. He did not have any cranial neuropathies. Nasal endoscopy showed a right-sided
mass with mucosal hypervascularity extending from the region of the sphenopalatine
foramen. The patient underwent a brain magnetic resonance imaging (MRI) scan demonstrating
a 3.0 × 4.1 × 3.9 cm right sinonasal skull base mass with intracranial extension partially
encasing the internal carotid artery ([Fig. 1 ]). Subsequent computed tomography (CT) examination revealed bony remodeling of the
maxillary sinus and widening of the pterygomaxillary fissure as well as bony destruction
of the middle cranial fossa, lateral wall of the sphenoid sinus, and pterygoid bone
([Fig. 2 ]). Histopathologically, biopsy of this mass demonstrated nests of cells with small,
smooth contoured nuclei, and granular chromatin. Immunohistochemical stains were positive
for chromogranin, synaptophysin, and S-100, most consistent with a paraganglioma.
Figure 1 Magnetic resonance imaging of orbit with gadolinium enhancement (A, B) coronal sections
demonstrating a lobular, solidly enhancing mass arising from the right skull base
involving the right sphenopalatine foramen extending into the right nasal passage,
masticator space, and parapharyngeal space. Associated osseous remodeling of the skull
base can be seen. (C, D) Axial sections showing mass extending into right orbital
apex, cavernous sinus with the cavernous segment of the right internal carotid artery
partially encased. The mass obliterates the right foramen rotundum and vidian canal.
Figure 2 Computed tomography (CT) of the sinuses (A) coronal and (B) axial sections of the
right sinonasal mass centered at the skull base with bony destruction of the lateral
sphenoid wall as well as middle fossa. (C) Metaiodobenzylguanidine-fused CT scan showing
large focus of uptake corresponding to the skull base mass.
The patient subsequently underwent an endoscopic skull base resection of the paraganglioma
with preoperative embolization of the internal maxillary artery ([Fig. 3 ]). The patient was continued on his phenoxybenzamine and metyrosine for control of
labile hypertension intra- and perioperatively. The tumor was dissected off the skull
base, infratemporal fossa, and pterygoid musculature. It was traced intracranially
where it was freely dissected from the dura. However, it was found to be adherent
to the internal carotid artery in the region of the cavernous sinus. The decision
was made to observe the cavernous carotid artery segment of tumor as a complete resection
was not possible. The patient’s postoperative course was unremarkable. Following the
procedure, he was treated with therapeutic 131 I-MIBG and external beam radiation therapy (5940 cGy). His plasma normetanephrine
levels have decreased from 1190 to 394 pg/mL (normal range <148 pg/mL) and chromogranin
A levels decreased from 58.0 to 28.0 ng/mL (normal range 1.9 to 15.0 ng/mL). Additionally,
the patient was referred to a medical geneticist given his recurrent extra-adrenal
paraganglioma. Genetic testing revealed a mutation in the SDHB gene.
Figure 3 (A) Triplanar computed tomography (CT) scan with endoscopic intraoperative image
in lower right side. The tumor (circle) extends into the right nasal cavity from the
sphenopalatine region and is submucosal in nature. (B) Postresection triplanar CT
scan image. Endoscopic resection extended posteriorly to the petrous segment of the
internal carotid artery and laterally into the pterygopalatine fossa.
Discussion
Sinonasal paragangliomas are extremely rare tumors that can arise along the skull
base from the nasal cavity or the paranasal sinuses. Nasal paragangliomas originate
from the middle turbinate, lateral nasal wall, or superior nasal vault. Paranasal
sinus paragangliomas most often arise from the ethmoid cells and rarely from the sphenoid
sinus. The origin of these tumors is believed to involve the pterygoid ganglion, sphenopalatine
ganglion, and pterygoid fossa.
Only 1 to 3% of head and neck paragangliomas are functional catecholamine-secreting
tumors. To date, there have been only three reported cases of secretory sinonasal
paragangliomas, and no cases of a secreting skull base sinonasal paraganglioma in
a patient with prior paragangliomas. Although uncommon, patients with secretory paragangliomas
may present with labile hypertension which requires a complete workup including serum
and 24-hour urine catecholamine and metanephrine. In these patients, surgical intervention
may be catastrophic without perioperative α adrenergic blockade. Additionally, evaluation
for synchronous lesions using CT and/or MRI scan as well as MIBG scan is important,
especially in patients with history of SDHB mutations. Patients with SDHB mutations
tend to develop extra-adrenal paragangliomas with increased risk for developing tumor
in the head and neck region as well as malignant and metastatic disease. SDHB has
also been associated with hereditary paraganglioma and pheochromocytoma syndrome and
familial genetic testing is recommended.[10 ]
Surgical resection, open or endoscopic, is the treatment of choice for paraganglioma.
Complete resection of the tumor is recommended due to the potential for locally aggressive
and destructive nature of sinonasal paragangliomas as well as potential for metastasis.
As in this case, skull base tumors may be difficult to completely resect with clear
margins due to intracranial extension or involvement of critical neurovascular structures.
In these cases, postoperative high-precision radiotherapy and radionuclide 131 I-MIBG can be used as adjuvant therapy.[1 ] Although radiation therapy alone has been shown to achieve local control and symptomatic
improvement, it has not been shown to achieve complete remission.[11 ] In patients with MIBG-avid disease, radionuclide 131 I-MIBG therapy can provide with symptomatic relief and tumor control through interactions
with active uptake-1 mechanism at the cell membrane and neurosecretory storage granules
in the cytoplasm of neuroendocrine cells.[12 ] Phase II clinical trials have shown that 131 I-MIBG therapy was effective in producing a sustained complete or partial remission
in patients who have good MIBG uptake on diagnostic scanning.[13 ] This patient underwent both postoperative intensity-modulated radiation therapy
and therapeutic 131 I-MIBG postoperatively due to tumor location and MIBG avidity.
Long-term follow-up is essential following treatment of head and neck paragangliomas.
Interval biochemical assessment of urine and plasma catecholamine and metanephrine
levels as well as follow-up imaging including MRI and MIBG scans can be used to assess
for local and distant tumor control. This is especially important for patients with
genetic mutations such as SDHB mutation who have higher probability of metastatic
and metachronous tumors.
Conclusion
This case is an unusual presentation of a secreting skull base paraganglioma presenting
with labile hypertension in a patient with history of prior paragangliomas and undiagnosed
SDHB mutation. Complete workup for these lesions in patients with SDHB mutations should
include biochemical evaluation of catecholamine and metanephrine as well as CT, MRI,
and MIBG imaging of head and neck as well as thorax and abdomen for synchronous or
metastatic tumor. Preoperative adrenergic blockade and angiography and embolization
of the tumor are important to avoid intraoperative complications. Skull base paragangliomas
may preclude complete surgical resection. In these instances, postoperative high-precision
radiation and 131 I-MIBG are viable adjuvant therapies. Long-term follow-up is essential for patients
with SDHB mutations as they may develop recurrent paragangliomas.
