Intralaryngeal paraganglioma workup and discussion of surgical approach

Abstract

Laryngeal paragangliomas are an uncommon presentation of head and neck paragangliomas, with laryngeal paragangliomas along with a synchronous paraganglioma being exceptionally rare. We present two challenging cases of laryngeal paragangliomas with extralaryngeal extension, completely resected through a transcervical approach without endolaryngeal disruption, with one case having synchronous bilateral carotid body tumours. Both patients had excellent results with complete tumour resection and no resultant functional impact. The surgical approaches for large laryngeal paraganglioma are discussed with considerations for endolaryngeal, transcervical and combined approaches as well as decision-making when approaching these rare lesions in the setting of synchronous head and neck paragangliomas.

BACKGROUND

Paragangliomas are neuroendocrine neoplasms with 85% developing within the abdomen, 12% in the chest and 3% in the head and neck. Head and neck paragangliomas are mostly found around the carotid body, jugular foramen, glossopharyngeal nerve along with its tympanic branch and the vagus nerve.¹ They are typically hypervascular, with 60% arising sporadically and 40% linked to hereditary syndromes, the most common being succinate dehydrogenase (SDH) mutations followed by multiple endocrine neoplasia types 2A and 2B. Most present as either painless masses or incidental findings on imaging studies. Histologically, all paragangliomas contain neurosecretory granules; however, only 1%–3% secrete clinically relevant hormones such as catecholamines.² Paragangliomas account for 0.6% of all head and neck tumours, while paragangliomas arising within the larynx are exceptionally rare, with about 70 reported cases in the literature.³ Laryngeal paragangliomas have a 3:1 female predilection with average age of presentation at 44 years.⁴ Paragangliomas within the larynx are not typically reported within syndromic patients. There have been a total of three cases of laryngeal paragangliomas with a synchronous paraganglioma.^3–5

We present the clinical cases of two patients with extensive intralaryngeal paragangliomas, one of which is presented with synchronous bilateral carotid body tumours. We discuss the successful surgical management of these lesions via an external approach without the need for embolisation or tracheotomy highlighting the preoperative decision-making, surgical technique and excellent results.

Case 1

Case presentation

This 47-year-old woman presented with several months of dysphonia and dysphagia. Physical examination demonstrated no cranial neuropathies, and the flexible nasopharyngoscopy identified submucosal fullness of the right aryepiglottic fold and false vocal fold with mobile vocal folds with evidence of healing from the previous biopsy (figure 1A). CT and MRI revealed a 3.2 cm right neck mass (figure 1B, C). Her referred physician performed direct laryngoscopy with biopsy requiring significant cautery for haemostasis. Final pathology revealed paraganglioma. Urine metanephrines were normal and octreotide scan revealed no other lesions. She was in otherwise good health with no family history of paraganglioma. A modified barium swallow demonstrated normal swallow function.

Figure 1.

Patient 1—(A) flexible fibreoptic examination showing previous biopsy site superior to the right false vocal cord with submucosal mass lesion. (B) Axial CT with 3.2 cm submucosal mass in right supraglottis with avid contrast enhancement. (C) Contrast-enhanced axial MRI shows avid enhancement with gadolinium. (D) Three-month postoperative stroboscopic findings show complete resection of the lesion with fully mobile bilateral vocal cords.

Investigations

The patient received numerous recommendations nationally regarding treatment options including surgery, observation and radiation. The patient was recommended transoral endoscopic, transoral robotic and open transcervical approaches at various centres. Given the patient’s relatively young age and good health, and in light of the symptomatic nature of the paraganglioma, we offered surgical resection through a transcervical approach with the advantage of improved vascular control relative to a transoral approach. She was counselled on surgical risks, including the possible need for tracheostomy. A staged approach was considered to minimise risk of pharyngocutaneous fistula formation should the tumour prove difficult to separate from the pharyngeal mucosa. Preoperative embolisation was deferred due to the risk of airway oedema with possible resultant need for tracheostomy, and the transcervical approach offered immediate access to the primary feeding vessels.

Differential diagnosis

Establishing an accurate diagnosis is crucial for laryngeal neuroendocrine tumours, with the natural history, treatment and prognosis varying widely for the four types—paraganglioma, typical carcinoid, atypical carcinoid tumour and small cell neuroendocrine carcinoma.^{6 7} Preoperative imaging was suggestive of paraganglioma. However, the distinction is made on histology and immunohistochemistry as paragangliomas are neural in origin and the others are epithelial in origin. Laryngeal paragangliomas classically have chief cells in distinctive clusters called zellballen, surrounded by sustentacular cells with rare mitoses. In contrast, the malignant pathologies have hyperchromatic nuclei with prominent nucleoli and frequent mitoses. Management increases in intensity as aggressive behaviour increases along with this spectrum.^{6 8}

Treatment

Intraoperatively, the surgery began with direct laryngoscopy, revealing no mucosal change or significant interval growth from the clinic fibreoptic examination. A cervical skin incision was placed in a horizontal neck crease at the level of the superior cornu of the thyroid cartilage. Subplatysmal flaps were raised allowing identification of the anterior border of the sternocleidomastoid muscle, digastric muscle, carotid artery, internal jugular vein and hypoglossal nerve. The superior lateral aspect of the tumour was identified, and dissection around the tumour began laterally and superiorly. Large vascular branches from the superior thyroid artery were ligated and divided as they were found to be feeding the tumour. Ligation of these branches allowed for improved haemostasis during the resection. The tumour was found passing deep to the thyroid cartilage through the thyrohyoid membrane. The fascia overlying the greater cornu of the thyroid cartilage was incised and the thyroid cartilage was elevated with a double hook to allow access to its deep surface. A combination of bipolar electrocautery and blunt dissection was used to carefully separate the deep attachments of the tumour, which was highly vascular. Every effort was made to remain directly on the tumour capsule to avoid penetration into the pharynx. Malleable retractors as well as Cottle and Freer elevators facilitated the dissection. Once the deep attachment was freed, the tumour was removed and sent for pathologic assessment. The wound was irrigated, and no pharyngotomy was identified. A drain was placed, and the incision was closed. Laryngoscopy was again performed at the conclusion of the case, revealing interval resolution of supraglottic fullness without any evidence of endolaryngeal injury. Intraoperative photos are depicted in figure 2.

Figure 2.

(A) Intraoperative depiction of the wound cavity after tumour excision with thyrohyoid membrane (asterisk) dilated by tumour and the thyroid cartilage (white arrow) retracted anteriorly. (B) Ex vivo tumour next to a ruler. (C) Endoscopic view of the larynx after excision, revealing normal contour of the supraglottis without pharyngotomy (asterisk).

Outcome and follow-up

The patient experienced an uncomplicated postoperative recovery and noted resolution of her symptoms in clinical follow-up. Stroboscopic examination obtained 3 months postoperatively demonstrated complete resection of the lesion with fully mobile bilateral vocal cords (figure 1D). Pathologic assessment of the mass revealed a highly vascular, nested tumour architecture (figure 3A). Tumour cells had monomorphic nuclei, abundant cytoplasm and salt-and-pepper nuclear chromatin without prominent nucleoli. Immunohistochemistry had S100 positive in sustentacular cells (figure 3B), positive chromogranin (figure 3C) and positive diffuse and strong synaptophysin. Ki-67 immunostain revealed a proliferation index of less than 1% (figure 3D). SDH subunit B (SDHB) expression was retained in the tumour (figure 3E). Cytokeratin via keratin AE1-3 and CAM5 was negative (figure 3F).

Figure 3.

Intermediate magnification H&E stain (A) reveals a highly vascular, nested tumour architecture with zellballen pattern. S100 immunostain (B) highlights sustentacular cells with positive chromogranin immunostain (C) showing tumour among the stoma. Ki-67 immunostain revealed a proliferation index of less than 1% (D). Succinate dehydrogenase subunit B expression was retained in the tumour (E). Cytokeratin via keratin AE1-3 and CAM5 was negative (F).

Case 2

Case presentation

This 59-year-old woman presented with fullness in the neck for several months. CT and MRI demonstrated bilateral carotid body masses and a left supraglottic mass resembling the carotid body lesions and consistent with paraganglioma (figure 4). Physical examination revealed bilateral fullness of the jugulodigastric regions, no cranial nerve deficits and fullness of the left aryepiglottic fold without deficit in vocal fold mobility on flexible nasopharyngoscopy. She was in generally good health with no family history of paraganglioma.

Figure 4.

Patient 2—(A) octreotide scanning showing multifocal uptake in head and neck and without tumours outside of the head and neck. Axial MRI without (B) and with (C) contrast showing avidly enhancing multifocal lesions of the head and neck with internal flow voids, consistent with bilateral carotid body tumours and a left laryngeal paraganglioma.

Investigations

Urine metanephrine and catecholamine testing were negative, and octreotide scanning revealed no other masses (figure 4). Similar preoperative counselling was offered to the patient as discussed in the prior case.

Differential diagnosis

Similar to case 1, preoperative imaging suggested paraganglioma. Determination between paraganglioma, typical carcinoid, atypical carcinoid tumour and small cell neuroendocrine carcinoma was done via surgical pathology.

Treatment

She underwent excision of bilateral carotid body and left supraglottic paragangliomas in a staged fashion, beginning with simultaneous excision of the laryngeal paraganglioma and the left carotid body tumour, which was chosen due to its larger size and its proximity to the laryngeal tumour. Preoperative embolisation was not performed due to the small tumour size. The excision of the carotid body tumour was completed with the vascular surgery service in the standard fashion. This led to easy identification of the superior laryngeal pedicle to the laryngeal tumour, which was ligated and divided. Following this, the tumour was followed medially through the thyrohyoid membrane and carefully dissected away from the superior laryngeal nerve, which was maintained intact with the exception of one small branch that was directly adherent to the tumour. In a similar fashion to the previously described case, the thyroid ala was retracted superficially, and the tumour was dissected free using blunt dissection and bipolar cautery, taking care not to enter the larynx. The wound was closed as previously described. After removal of the tumour, laryngoscopy revealed intact endolaryngeal mucosa.

Outcome and follow-up

The patient underwent an uneventful recovery and maintained full vocal fold function. Pathology demonstrated a 2.8 cm carotid body paraganglioma and 1.7 cm laryngeal paraganglioma, with the laryngeal paraganglioma light microscopy and immunostains being depicted in figure 5. Both tumours stained positive for chromogranin and S100 in the sustentacular cells, and both had loss of SDHB in the tumour cells, consistent with familial type paraganglioma. The patient returned 8 months postoperatively for excision of the contralateral carotid body tumour, which was removed without issue and measured 1.3 cm on permanent pathology. She has continued to follow with our clinic at regular intervals and is now seen annually without any evidence of new or recurrent tumours. Genetic testing and counselling were offered due to the SDHB mutation but were declined by the patient.

Figure 5.

Low (A) and high (B) magnification H&E stain of tumour with zellballen pattern. S100 immunostain (C) highlights sustentacular cells with chromogranin immunostain (D) demonstrating the tumour cells among the stromal environment. There is a loss of succinate dehydrogenase subunit B expression (E) in the tumour. Ki-67 immunostain (F) shows a low proliferative index (3%) tumour.

Discussion

We present two cases of laryngeal paragangliomas with extralaryngeal extension who underwent resection. The case of bilateral carotid body tumours and synchronous laryngeal paraganglioma is only the fourth case of its kind. Herein, we focus on the surgical management of intralaryngeal paragangliomas, distinct from lesions on the mucosal surface in the laryngotracheal complex, including approach considerations and management of multifocal tumours.

Workup should begin with physical examination including fibreoptic laryngoscopy. Axial imaging with contrast CT or MRI of the neck will readily identify hypervascular lesions suspicious for paraganglioma while giving details of anatomic extent. Biopsy can be obtained through laryngoscopy if there is mucosal involvement but can usually be deferred avoiding untoward tumour disruption and bleeding. Octreotide scanning may be obtained to further confirm paraganglioma and evaluate for other lesions. Gallium-68 dotatate positron emission tomography–CT may be used to identify other synchronous lesions.^{9 10} Urine catecholamines and metanephrines are also collected to identify rare vasoactive secreting tumours.

In our case of an isolated laryngeal lesion, preoperative biopsy was diagnostic of paraganglioma but was not necessary to proceed with treatment. In the second case of multifocal tumours, the classic imaging characteristics and synchronous carotid body tumours were sufficient to diagnose paraganglioma without tissue sampling.

Surgery is curative for intralaryngeal paragangliomas and should be strongly considered, particularly if the mass is causing symptoms such as hoarseness, dysphagia or airway compromise.^{3 4 6} There are multiple surgical approaches to consider based on the unique characteristics of each case. Transoral laser excision (via endoscopy or microlaryngoscopy) has been reported on,¹¹ however, it has fallen out of favour due to difficulty in controlling bleeding and in achieving gross total resection.⁷ In fact, endoscopic excision has been reported to result in higher rates of local recurrence.^{7 12} Transoral robotic techniques have more recently been reported but face the same natural limitations as other transoral approaches.¹³ These techniques may be reserved for small and isolated mucosal lesions.

Transcervical approaches are more commonly employed. Historically, partial or even total laryngectomy was the surgery of choice; however, with advances in surgical technique and in our understanding of the benign nature of the disease, a more conservative resection is now the standard as it provides adequate disease control while preserving function.¹⁴ This may involve thyrotomy, either by laryngofissure or a lateral approach. If a lateral approach is possible, it is more favourable as it can be accomplished without the need for tracheostomy.¹⁵ Finally, as in other head and neck paragangliomas, preoperative carotid artery embolisation is a consideration. However, it is not generally necessary in laryngeal paragangliomas as these tumours are usually supplied by branches of the superior thyroid artery that are easily ligated intraoperatively, as was accomplished in these cases.

Both of the presented cases demonstrated a highly vascular mass originating in the supraglottic larynx and extending through the thyrohyoid membrane with no endolaryngeal component. Thus, the decision was made to first pursue a transcervical approach, with plans for a second stage transoral endolaryngeal approach if the initial surgery achieved less than gross total resection. Staging the procedures would additionally allowing healing for 6–8 weeks to prevent subcutaneous emphysema, a laryngeal sinus tract, laryngocutaneous fistula or deep neck space infection. Secondary endoscopic procedures were not required in either case.

Important additional surgical considerations arise during bilateral paragangliomas resections, as in our second case. In such cases, we usually stage surgery of the carotid body lesions to minimise the risk of bilateral cranial neuropathies and/or disruption to cerebral circulation. The question of which side to treat first is debated without decisive evidence. Often the first side to treat is dependent on the size of each lesion and its symptomatology. A review by Moore et al determines which tumour to resect first based on perceived risk to adjacent cranial nerves.⁸ They advocate when one tumour is large, the smaller size is removed first to ensure no cranial nerve deficits or dysphagia. If resection is difficult and there are neuropathies, observation or radiation to the second tumour is strongly considered. However, radiation is not curative and tumours may still progress, as such surgery remains the first-line treatment. If both tumours are relatively small, the larger of the two is removed first as the smaller tumour could be observed or radiated if cranial nerves were injured during the first operation. They do not define what constitutes a small versus large tumour, but based on our carotid body institutional experience, a size parameter of >4 cm would be considered large. Importantly, bilateral and multiple head and neck paragangliomas carry a higher risk of underlying mutation and recurrence, and long-term follow-up is necessary.¹⁶

In this patient with multiple lesions, we chose to remove the left-sided carotid body tumour and the ipsilateral intralaryngeal paraganglioma first, because if significant neural praxia had occurred, a single lesion would be left to follow or radiate. If an initial right-sided carotid body tumour resected had resulted in neuropraxia, two lesions would be left to follow or radiate.

Critical to the decision to proceed with solely, an external approach in these cases was the true extraluminal location and their significant extension into the lateral neck. The external approach allows excellent access as well as direct control of supplying vasculature. Although other centres did offer management with transoral endoscopic or robotic approaches, the limits of such approaches include management of the lateral extralaryngeal extent, control of supplying vasculature and resultant airway oedema. The external approach in the presented cases allowed for completed resection, excellent hemostatic control, avoidance of tracheotomy and excellent function.

Learning points.

• Laryngeal paragangliomas with extralaryngeal extension are uncommon, especially with synchronous head and neck paragangliomas.

• Highlights of a completely external approach include addressing the lateral extralaryngeal component, direct access to contributing vasculature and avoidance of tracheostomy with minimal resultant airway oedema.

• When synchronous lesions are encountered, the size and laterality of each tumour are considered to minimise the risk of cranial neuropathies in order to proceed for staged surgical resection of the contralateral side.