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ORIGINAL ARTICLE
Year : 2017  |  Volume : 6  |  Issue : 1  |  Page : 19-23

Paragangliomas of the head and neck region: A single center experience


Department of Pathology, Government ENT Hospital, Koti, Hyderabad, Telangana, India

Date of Web Publication20-Mar-2017

Correspondence Address:
Kumudachalam Pindicura
6-1-111/4, Khairatabad, Hyderabad - 500 004, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JDRNTRUHS.JDRNTRUHS_5_17

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  Abstract 

Background: Head and neck paragangliomas are slowly growing, highly vascular, mostly benign tumors that commonly occur at the carotid bifurcation at the jugular bulb, in the tympanic cavity, or as vagal paragangliomas. Unlike the adrenal counterpart, a vast majority of them are nonsecretory.
Aims and Objectives: To study the clinicopathological aspects of paragangliomas arising in the head and neck region.
Materials and Methods: This study was conducted in a tertiary care centre for head and neck diseases between 2008 and 2016. Clinical data were retrieved from the records. Morphological examination was the mainstay of diagnosis.
Results: Twenty-three cases of head and neck paragangliomas were diagnosed by morphological examination. Paragangliomas constituted 0.20% of all head and neck lesions. The age group ranged between 18 and 60 years, with a mean age of 44 years. Most common age at presentation was fourth and fifth decades. Majority of cases occurred in females, with male: female ratio of 1:4. Out of 23 cases, 19 cases (82.60%) involved the jugulotympanic region, 2 cases (8.69%) were laryngeal paragangliomas, and 2 cases (8.69%) were carotid body paragangliomas.
Conclusion: Paragangliomas of the head and neck are uncommon lesions. The most common site in the head and neck region was the jugulotympanic region. Most cases of jugulotympanic paraganglioma presented in the fifth decade and later. Laryngeal paraganglioma presented clinically earlier in the second decade. Jugulotympanic and laryngeal paraganglioma showed dominance of tumor vasculature histologically. There was a rare case of laryngeal paraganglioma with lateral neck extension in this study.

Keywords: Carotid body, jugulotympanic, laryngeal, paraganglioma


How to cite this article:
Pindicura K, Arikeri RP, Dandala SR, Rajarikam N, Vivekan N. Paragangliomas of the head and neck region: A single center experience. J NTR Univ Health Sci 2017;6:19-23

How to cite this URL:
Pindicura K, Arikeri RP, Dandala SR, Rajarikam N, Vivekan N. Paragangliomas of the head and neck region: A single center experience. J NTR Univ Health Sci [serial online] 2017 [cited 2017 Apr 30];6:19-23. Available from: http://www.jdrntruhs.org/text.asp?2017/6/1/19/202582




  Introduction Top


Head and neck paragangliomas (HNPs) are rare neuroendocrine tumors arising from the neural crest-derived tissue. The incidence of all paraganglion system tumors has been estimated to be approximately 1/300,000.[1] A majority of extra-adrenal paragangliomas (70%) arise in the head and neck region, specifically from the parasympathetic nervous system. HNPs are slowly growing, highly vascular, and mainly benign tumors that commonly occur at the carotid bifurcation at the jugular bulb, in the tympanic cavity, or as vagal paragangliomas.[1] Unlike the adrenal counterpart, pheochromocytoma (PHEO), which often secretes catecholamines, a vast majority of head and neck paragangliomas (PGLs) are nonsecretory (>95%).[2]


  Materials and Methods Top


This study was conducted at a tertiary care center for head and neck diseases between 2008 and 2016. Clinical data including age, sex, and clinical presentation, were retrieved from the records. Site of each tumor was determined by evaluating clinical and radiological findings. Histopathological examination was the mainstay of diagnosis. Two cases were diagnosed based on cytological examination and radiological (Doppler–ultrasonography and computed tomography) findings. Immunohistochemistry was done wherever required.


  Results Top


During the 8-year study period, 23 cases of HNPs were diagnosed. Paragangliomas constituted 0.20% of all head and neck lesions. The cases occurred between the age group of 18 and 60 years with a mean age of 44 years. Most common age at presentation was the fourth and fifth decade. Majority of the cases occurred in females with a male: female ratio of 1:4. Out of 23 cases, 82.60% (19 cases) involved the jugulotympanic region, 8.69% (2 cases) were laryngeal paragangliomas, and 8.69% (2 cases) were carotid body paraganglioma. Most common location of paraganglioma was the jugulotympanic region.

Jugulotympanic paragangliomas (JTP) accounted for 82.60% (19 cases) of the cases. Most of these cases occurred in females. Twelve cases presented in the auditory canal, 2 cases in the middle ear, and 5 cases in the mastoid region. Most cases of JTP presented in the fifth decade and later [Table 1]. On gross examination, the lesions from the auditory canal were polypoidal gray-white to gray-brown masses. JTP arising from the mastoid attic and antrum presented as gray-white to gray-brown soft tissue mass, with cut surface showing cyst-like spaces filled with hemorrhage.
TABLE 1: DEMOGRAPHIC DATA OF HEAD AND NECK PARAGANGLIOMAS

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Microscopic examination of all JTPs revealed highly vascular submucosal tumor tissue arranged in nests, alveolar pattern, organoid/zellballen pattern separated by thin fibrous septae containing thin walled, cavernous, dilated congested, and vascular channels. The tumor cells with moderate-to-abundant clear to amphophilic granular cytoplasm and uniform appearing nuclei with fine stippled chromatin were present. Focal vascular dominance with compressed, atrophic tumor component was noted in all JTPs [Figure 1].
Figure 1: Jugulotympanic paraganglioma: A1 and A2: H and E stained sections (low power) showing foci of vascularity. B1 and B2: H and E stained sections showing foci of classical paraganglioma with cell nest pattern separated by fibrovascular stroma

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Laryngeal paragangliomas constituted two cases (8.69%). Equal sex predisposition was seen with a M:F ratio of 1:1. Laryngeal paragangliomas present early in life in the second decade [Table 1].

Right vocal cord and right aryepiglottic folds (AE fold) are the sites of involvement. One case, the right vocal cord lesion, revealed reddish soft tissue mass measuring 4 × 2 × 1 cm in the supraglottis extending into the glottis with obliteration of the laryngeal space. The other case in the right aryepiglottic folds presented as a mass measuring 4.5 × 4 × 3 cm. Histopathological examination of both the cases revealed histological features of paraganglioma. Focal areas showed thin-walled, congested, dilated vascular channels akin to cavernous hemangioma. Immunohistochemistry with chromogranin, synaptophysin, S-100 positivity, and pan-cytokeratin negativity confirmed the diagnosis. There was a rare case of laryngeal paraganglioma in a 18-year-old female, in the right AE fold, with lateral neck extension, mimicking clinically a metaststatic lymph node (Case no 20 in [Table 1]). In this case, congested, dilated vascular channels along with tumor tissue was prominent in the submucosal part of the tumor than in lateral neck mass [Figure 2].
Figure 2: Lateral mass of laryngeal paraganglioma; (a) Gross picture showing polypoidal gray-brown mass; (b) H and E stained section in low power; (c) H and E stained microscopic section (high power) showing cells arranged in nests and zellballen pattern; (d) IHC-chromogranin positivity seen in the nests of chief cells

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Cervical or carotid body paragangliomas constituted two cases (8.69%). The cases presented as painless slow growing neck masses. In one case, CT scan of right upper cervical mass revealed large hypervascular enhancing mass lesion measuring 8.7 × 3.7 × 3.7 cm in the right carotid canal extending into jugular foramen displacing carotid vessels and indenting pharyngeal mucosal space. Color Doppler studies revealed features suggestive of the left carotid body tumor in another case. Fine needle (26G) by nonaspiration of the lesion yielded blood elements with sparse cells. Both the cases were diagnosed on cytology with clinicoradiological correlation [Figure 3].
Figure 3: Carotid body paraganglioma: (a) Clinical picture of a 62-year-old male patient with pulsatile lateral neck mass; (b) USG-color Doppler of the same showing hypervascularity of the tumor with an abundance of intratumoral flow sign

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  Discussion Top


HNPs are neuroendocrine neoplasms arising from chief cells of the paraganglia, and is typically seen in close association with vascular structures, ganglia, and nerve branches of the autonomic nervous system, especially along the cranial and thoracic branches of the glossopharyngeal and vagus nerves. Four major parasympathetic paraganglia have been defined in the head and neck region – (1) Carotid body paraganglia, (2) JTP, (3) vagal paraganglia, and (4) laryngeal paraganglia.[3] The incidence of all paraganglion system tumors has been estimated to be approximately 1/300,000.[1]

The majority of tumors exhibit the classic “Zellballen” described in normal paraganglia by the anatomist Alfred Kohn in the late 19th century.[4] These structures are nests of tumor cells separated by peripheral capillaries. A second cell population called sustentacular cells can be demonstrated at the periphery of the nests by immunohistochemical staining for S100 protein. Variations in tumor architecture include diffuse and trabecular growth patterns, extensive sclerosis creating patterns that mimic invasive carcinoma, and unusual vascular patterns that can mimic angiomas. Cavernous blood vessels can be particularly prominent in HNPs.[4]

JTP are deeply seated lesions that are extremely vascularized and involve vital neurovascular skull base structures. In a large study of 75 cases of jugular foramen paragangliomas, the most common initial presenting symptom was pulsatile tinnitus in 58 (77.3%) patients followed by hearing loss in 52 (69.3%) patients. The mean age of presentation was 41.1 years (range 23–61 years). Most series report a predominance of females.[5],[6] Other features of a paraganglioma in the ear are red mass (the rising sun behind the drum) in the middle ear, cranial nerve palsy including otalgia, and aural bleeding in some cases. The tumors are usually benign or of low malignancy, however, they can be locally invasive with destruction of bones and adjacent structures.[7] Preoperative evaluation includes high-resolution CT to obtain a good analysis of the bony structures of the skull base, tumor size, and areas of bone erosion. Gadolinium-enhanced MRI and angiography allow the study of tumor vascularization, extension, and its relationship to the surrounding structures.[6]

This study encountered 19 cases of JTP, accounting for 82.60% of the cases. Most of the cases (12 cases) presented in the auditory canal, two cases in middle ear, and five cases in the mastoid region. Most cases of JTP presented in the fifth decade and later, and occurred in females [Table 1]. Microscopically, JTP had dominant vascularity, areas of hemorrhage that undermines the tumor cells. Cavernous blood vessels can be particularly prominent in HNPs.[4]

Laryngeal paragangliomas are rare and three times more common in women, and have been described in patients aged 5–83 years (median 44 years). The vast majority (82%) occur in the supraglottic larynx, presumably arising from the superior pair of laryngeal paraganglia, and present as a submucosal mass in the region of the aryepiglottic fold – false vocal cord. Only 15% occur in the subglottis and 3% in the glottis.[8] The right side of the larynx is more often involved than the left in a ratio 2.3:1. Multiple paragangliomas of the head and neck with laryngeal involvement have also been recorded.[8] Laryngopharyngeal paragangliomas typically originate along the paired paraganglia, which course with the superior and inferior laryngeal arteries and nerves.[9] Subglottic paragangliomas are believed to arise from the inferior laryngeal paraganglia. They may present secondary to airway compromise or as neck or thyroid masses.[10]

In our study, laryngeal paragangliomas constituted of two cases (8.69%) and M:F ratio was 1:1. The age of presentation was second decade. Both the cases occurred on the right side of the larynx in concordance with literature.[8] There was a rare case of laryngeal paraganglioma in 18 years female, in right AE fold, with lateral neck extension, mimicking clinically, a metastatic lymph node (Case no. 20 in [Table 1]). In this case, congested, dilated vascular channels along with tumor tissue was prominent in the submucosal part of the tumor than in lateral neck mass.

There are reports of such two components in literature. Brandwein et al.[11] reported a case of inferior laryngeal paraganglia derived laryngeal paraganglioma in a 35-year-old male patient presenting with dyspnoea, which on CT showed a dumbbell-shaped tumor situated below the cricoid ring with an intratracheal component. Ojha et al.[12] reported a case of extradural, dumbbell-shaped paraganglioma, having the intraspinal portion extending from C2 to C5 on the left side and the extraspinal portion in the carotid triangle.

Paraganglioma arising from the carotid body are relatively rare tumors but constitute majority of head and neck paragangliomas (60–70%).[13] Carotid body paraganglioma often present as slow growing, nontender neck masses located just anterior to the sternocleidomastoid muscle at the level of the hyoid.[13] The carotid body paraganglioma is more common in women.[13]

In the present study, two cases of carotid body paraganglioma were encountered (8.69%), with a M:F ratio of 1:1. The cases occurred in the second and fourth decades. One case presented as painless slow growing neck mass. CT scan of the right upper cervical mass revealed large hypervascular enhancing mass lesion measuring 8.7 × 3.7 × 3.7 cm in right carotid canal extending into the jugular foramen displacing carotid vessels and indenting pharyngeal mucosal space; in another case, Color Doppler studies revealed features suggestive of left carotid body tumor. Fine needle (26G) by nonaspiration of the lesion yielded blood elements with sparse cells. Both the cases were diagnosed on cytology with radiological correlation.

Patients with cervical paragangliomas are usually asymptomatic with catecholamine levels within normal limits. Imaging is most helpful in the preoperative diagnosis of paragangliomas. Ultrasonography with Doppler is most helpful in assessing neck paragangliomas. Digital subtraction angiography enables diagnosis and acts as a guide for embolization. Octreotide scintigraphy is a very sensitive method for the detection of HNPs.[6],[14]

The incidence of metastasis in carotid body tumors ranges from 6.4% to 12.5%. Germline and somatic mutations of the succinate dehydrogenases (SDH) – SDHB, SDHC, and SDHD genes were reported in the hereditary and sporadic forms of paragangliomas and pheochromocytomas. Mutations of the SDHD gene were associated with multiple tumors, and those of the SDHB gene were associated with malignancy. Following and treating these patients after surgery remains a problem.[14],[15]

The differential diagnosis of paragangliomas include neuroendocrine neoplasms, amelanotic mucosal melanoma, renal cell carcinoma, medullary thyroid carcinoma, and hemangiopericytoma.[9] Immunohistochemistry is helpful in establishing the correct diagnosis as the distinction between paraganglioma and atypical carcinoid/neuroendocrine carcinoma may prove difficult on light microscopy. The presence of chromogranin and S-100 protein positivity excludes non-neuroendocrine neoplasms.[8] The cytokeratin marker is the most useful for distinguishing paraganglioma and neuroendocrine carcinoma.[10]SDHA immunohistochemistry on paraffin-embedded tumors can reveal the presence of SDHA germline mutations and allow the identification of SDHA-related tumors in at least 3% of the patients affected by apparently sporadic (para) sympathetic paragangliomas and pheochromocytomas.[15] Advanced diagnosis and cellular differentiation techniques have increased understanding of their benign nature and allowed a less aggressive surgical approach. Currently, organ-preservation techniques are the preferred treatment modality.[9]


  Conclusion Top


HNPs are uncommon lesions. In this study, the most common site of presentation of HNP was the jugulotympanic area. Most cases of JTP presented in the fifth decade and later, and were most common in females JTP showed dominance of tumor vasculature histologically. Laryngeal paraganglioma presented clinically earlier, i.e., in the second decade. There is a rare case of laryngeal paraganglioma with lateral neck extension encountered in this study. Congested, dilated vascular channels along with tumor tissue were prominent in the submucosal part of the tumor than in the lateral neck mass. The submucosal JTP and laryngeal paraganglioma show predominant cavernous vascular channels histologically, and may mimic vascular tumors.

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Conflicts of interest

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  References Top

1.
Anttila T, Häyry V, Nicoli T, Hagström J, Aittomäki K, Vikatmaa P, et al. A Two-Decade Experience Of Head And Neck Paragangliomas In A Whole Population-Based Single Centre Cohort. Eur Arch Otorhinolaryngol 2004;272:2045-53.  Back to cited text no. 1
    
2.
Williams MD, Rich TA. Paragangliomas Arising In The Head And Neck. Surg Pathol Clin 2014;7:543-57.  Back to cited text no. 2
    
3.
Toshitetsu H, Mete O. Head And Neck Paragangliomas: What Does The Pathologist Need To Know? Diagn Histopathol 2014;20:316-25.  Back to cited text no. 3
    
4.
Tischler AS, deKrijger RR. 15 Years Of Paraganglioma: Pathology of pheochromocytoma And Paraganglioma. Endocr Relat Cancer 2015;22:T123-33.  Back to cited text no. 4
    
5.
Makiese O, Chibbaro S, Marsella M, Tran Ba Huy P, George B. Jugular Foramen Paragangliomas: Management, Outcome And Avoidance Of Complications In A Series Of 75 Cases. Neurosurg Rev 2011;35:185-94.  Back to cited text no. 5
    
6.
Ramos Macías A, Bueno Yanes J, Bolaños Hernández P, Lisner Contreras I, Osorio Acosta A, Vicente Barrero M, et al. Temporal Paragangliomas. A 12-Year Experience. Acta Otorrinolaringol Esp 2011;62:375-80.  Back to cited text no. 6
    
7.
Kundu I, Goswami S, Barman D, Biswas S. Paraganglioma Of External Auditory Canal. Indian J Otolaryngol Head Neck Surg 2001;53:304-6.  Back to cited text no. 7
    
8.
Dhakhwa R, Toran C, Kafle S, Lakhe M. Paraganglioma Of The Larynx. J Pathol Nepal 2012;2:245-7.  Back to cited text no. 8
    
9.
Mehta V, Fischer T, Levi G, Wang B, Urken ML. Hypopharyngeal Paraganglioma: Case Report And Review Of The Literature. Head Neck 2012;35:E205-8.  Back to cited text no. 9
    
10.
Peterson KL, Fu YS, Calcaterra T. Subglottic Paraganglioma. Head Neck 1997;19:54-6.  Back to cited text no. 10
    
11.
Brandwein M, Levi G, Som P, Urken ML. Paraganglioma of the Inferior Laryngeal Paraganglia A Case Report. Arch Otolaryngol Head Neck Surg 1992;118:994-6.  Back to cited text no. 11
    
12.
Ojha BK, Sharma MC, Rastogi M, Chandra A, Husain M, Husain N. Dumbbell-Shaped Paraganglioma Of The Cervical Spine In A Child. Pediatr Neurosurg 2006;43:60-4.  Back to cited text no. 12
    
13.
Davidovic LB, Djukic VB, Vasic DM, Sindjelic RP, Duvnjak SN. Diagnosis and Treatment of Carotid Body Paraganglioma: 21 Years of Experience at a Clinical Center of Serbia. World J Surg Oncol 2005;3:10.  Back to cited text no. 13
    
14.
Kimura N, Tateno H, Saijo S, Horii A. Familial Cervical Paragangliomas With Lymph Node Metastasis Expressing Somatostatin Receptor Type 2A. Endocr Pathol 2009;21:139-43.  Back to cited text no. 14
    
15.
Korpershoek E, Favier J, Gaal J, Burnichon N, van Gessel B, Oudijk L. SDHA Immunohistochemistry Detects Germline SDHA Gene Mutations In Apparently Sporadic Paragangliomas And Pheochromocytomas. J Clin Endocrinol Metab 2011;96:E1472-6.  Back to cited text no. 15
    


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