A systematic review of 1143 parapharyngeal space tumors reported over 20 years

Oral Oncology 50 (2014) 421–430

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Review

A systematic review of 1143 parapharyngeal space tumors reported over 20 years Faruque Riffat a,b,⇑, Raghav C. Dwivedi a, Carsten Palme b, Brian Fish a, Piyush Jani a a b

Department of Otolaryngology–Head and Neck Surgery, Cambridge University Hospitals, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK Department of Surgery, University of Sydney, Sydney, NSW 2145, Australia

a r t i c l e

i n f o

Article history: Received 25 December 2013 Received in revised form 9 February 2014 Accepted 11 February 2014 Available online 28 February 2014 Keywords: Parapharyngeal space Tumors Pleomorphic adenoma Salivary tumors Paraganglioma Schwanoma Neurogenic tumors Surgery Cervical approach

s u m m a r y Parapharyngeal space tumours are rare and most clinicians will only see a small number during their career. We performed a systematic review of 1143 parapharyngeal space tumors published in the past 20 years to increase cumulative experience. A systematic literature review was performed and data on histological diagnosis, presentation, surgical approach and postoperative complications of cases published between 1989 and 2009 were compiled and reviewed. The systematic review identified a total of 1143 parapharyngeal space tumors presented in 17 studies. A majority (82%) were benign and 18% were malignant. The most common presentation was a cervical mass (50%) or an intraoral mass (47%). Approximately 70 different histologic subtypes of parapharyngeal space tumors were reported in the cumulative series. The most common primary lesion was a pleomorphic adenoma (34%). Ninety-five percent of patients underwent surgery. The most frequent approach and used to excise the lesions was the cervical approach (48%) and the commonest complication was the vagus nerve injury seen in 14% of the cases. Crown Copyright Ó 2014 Published by Elsevier Ltd. All rights reserved.

Introduction Parapharyngeal space tumors (PPST) account for 0.5% of all head and neck masses but they are common enough to warrant a high index of suspicion. The anatomical relationships and histological diversity of PPST present difficult diagnostic and management challenges. Since lesions of the parapharyngeal space are rare they should be treated in a tertiary referral centre. Ever since the earliest reports of parapharyngeal space lesions in the early 20th century [1] the relevant literature is growing but is still limited to case reports and case series which are mostly small. The parapharyngeal space is a complex potential space in the suprahyoid neck, classically described as an inverted pyramid with the base formed by the skull base and the apex pointing to the greater cornu of the hyoid bone (Olsen) [2]. The fascia running posteriorly from the styloid process to the tensor veli palatini muscle divides the parapharyngeal space into the prestyloid (anterior) and ⇑ Corresponding author at: Department of Surgery, University of Sydney, Westmead Hospital, Hawkesbury Road, Westmead, Sydney, NSW 2145, Australia. Tel.: +61 298456022; fax: +61 298937440. E-mail addresses: [email protected] (F. Riffat), [email protected] (R.C. Dwivedi), [email protected] (C. Palme), brian.fish@addenbrookes. nhs.uk (B. Fish), [email protected] (P. Jani). http://dx.doi.org/10.1016/j.oraloncology.2014.02.007 1368-8375/Crown Copyright Ó 2014 Published by Elsevier Ltd. All rights reserved.

the poststyloid (posterior) compartments. It is useful to determine whether the tumour is in either the pre- or poststyloid compartment as knowledge of this is helpful in determining the possible diagnosis (Table 1). The poststyloid compartment contains the internal carotid artery, internal jugular vein, cranial nerves IX, X, XI, XII, the cervical sympathetic chain and lymph nodes. Poststyloid tumours can arise from each of these structures and equally these structures are at risk during surgery involving the parapharyngeal space. The prestyloid compartment is composed largely of fat, part of the retromandibular portion of the deep lobe of the parotid gland and lymph nodes. The vast majority of histopathologies in this compartment are salivary gland in origin. Contention between authors over the exact boundaries of the parapharyngeal space has resulted in confusion over what is considered a parapharyngeal space lesion. Several case series incorrectly consider all deep lobe parotid tumours to be parapharyngeal space tumors. It is our belief that only lesions affecting at least the retromandibular part of the deep lobe of the parotid should be considered parapharyngeal in etiology. Lesions at the foramen ovale are occasionally considered as part of the prestyloid compartment although they should be considered as part of the infratemporal fossa [3]. Similarly carotid body paragangliomas should only be included in parapharyngeal space masses if they

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F. Riffat et al. / Oral Oncology 50 (2014) 421–430

Table 1 Contents and primary lesions of the parapharyngeal space.

Contents Primary lesions of the parapharyngeal space

Prestyloid compartment

Poststyloid compartment

Deep lobe of parotid gland, minor salivary glands, lymph nodes and parapharyngeal fat Salivary gland lesions, lymphomas and lipomas

Carotid artery, jugular vein, cranial nerves IX, X, XI and XII, lymph nodes, cervical sympathetic chain and glomus tissue Paragangliomas, nerve sheath tumours, lymphomas, connective tissue tumours, carotid aneurysms and ganglioneuromas

are located above the posterior belly of the digastric muscle. Case series with high incidences of deep lobe parotid tumours, infratemporal fossa tumours and carotid body tumours may be explained by these discrepancies in anatomical classification. Precisely defining whether a lesion lies in the parapharyngeal space is not arbitrary as it may influence the surgical approach used to remove the lesion. In this article we have reviewed the literature to compile the data on presentation, histological diagnoses, surgical approach and postoperative complications for parapharyngeal space tumors reported in case series published in the last 20 years (1989–2009). Reported in the 17 case series in this review are a total of 1143 cases, the most comprehensive to date.

Materials and methods A systematic review of published literature on parapharyngeal space tumors was conducted. The term ‘parapharyngeal’ was used to search the online PUBMED, MEDLINE, EMBASE, SCI and CINAL databases for publications written in English on human subjects from January 1989 to December 2009. Only case series evaluating tumours primarily affecting the parapharyngeal space were included. Case series reporting on other tumours of the head and neck, those reporting less than five cases or focussed on diagnostic radiological techniques or fine needle aspiration cytology (FNAC) were excluded. Case series which primarily described a surgical approach but did not adequately report the tumour subtypes were also excluded. Single case reports or reports on infections of the parapharyngeal space were also excluded. Full length manuscripts of the remaining publications were obtained and data on the histological diagnosis, presentation, surgical approach and postoperative complications was retrieved, compiled and reviewed. Data on clinical presentation was only reviewed for manuscripts that included details of both signs and symptoms. Data was reviewed in aggregate to create a cumulative review.

Results A thorough literature search retrieved 741 articles. Four hundred fifty-six articles were excluded because they were not related to tumors affecting the parapharyngeal space. Two hundred thirtyeight single case reports on parapharyngeal space tumors were excluded. After reviewing the abstracts, 47 case series on parapharyngeal space tumors were excluded because they selected for specific histological types of parapharyngeal masses, or included only benign or malignant tumors. Three series which had less than five cases were excluded. The remaining 17 case series fulfilled our inclusion criteria. In total these 17 reports contained 1143cases (1118 primary and 25 metastatic papapharyngeal space lesions). Two series did not report metastatic lesions [4,5]. All 17 series provided data on histological diagnosis. Of these, eight case series (536 cases) provided data on both signs and symptoms, 14 provided complete data on the surgical approach used, and 15 provided data on postoperative complications.

Details of the parapharyngeal space lesion pathology in the cumulative series are presented in Table 2. Excluding the metastatic lesions from the whole series, there are 1118 primary cases of which 913 (82%) are benign and 205 (18%) are malignant. Approximately 70 different histologic types of parapharyngeal space pathologies are reported in this cumulative series. Cumulative data on clinical presentation of cases were reported in the eight series in the literature review that provided detailed information on both signs and symptoms (Table 3). There are a total of 537 cases in the eight series. The most frequent presenting symptoms are cervical mass or an intraoral swelling, which are present in 293 cases (55%). The commonest sign is an intraoral swelling, reported in 266 cases (50%), and a cervical mass, reported in 254 cases (47%). Symptoms related to mass effect of the tumour such as dysphagia (11%) and dysphonia (9%) or regional neural invasion were also common (18%). Surgical approaches adapted to excise parapharyngeal space lesions were reported in 14 series (Table 4). In total 686 cases underwent surgery to remove a parapharyngeal space lesion in these series. Overall the commonest surgical approach used was the cervical approach, which was used in 328 cases (48%). Complications as a result of parapharyngeal space tumor surgery reported were reported in 15 series, which altogether include 867 cases which underwent surgery (Table 5). Overall the commonest complications were cranial nerve injuries. The vagus nerve being the most commonly affected, and was injured in 124 patients (14%). The facial nerve was the next commonly injured (12%). Discussion The parapharyngeal space is an anatomically and functionally complex region of the neck. Tumors that develop in this region are made up of a diverse group of varying histopathologies, which can present a significant diagnostic dilemma for the treating physician. Our comprehensive review of the literature has identified approximately 70 different histologic subtypes of lesions (Table 2). In the cumulative series of 1118 cases, 913 (82%) lesions were benign, while 205 (18%) were malignant parapharyngeal space masses. Salivary gland tumours (prestyloid) were the most common primary lesions, with 499 cases (45%), followed by neurogenic lesions (poststyloid), with 455 cases (41%). The rest of the primary lesions comprised of a miscellaneous group of 138 cases (12%). Twenty-six (2%) lesions arose from lymph nodes. Salivary gland tumors Most prestyloid tumors arise from the salivary glands, with a total of 15 different histological types reported in the cumulative series. The vast majority of salivary gland lesions were benign, accounting for 77% of the 499 salivary gland lesions. Pleomorphic adenomas were the most common parapharyngeal space lesion, accounting for 34% of all primary parapharyngeal lesions and 64% of all salivary gland lesions in the series. Malignant salivary gland lesions accounted for 23% of all salivary gland lesions in the cumulative series. Adenoid cystic carcinomas and mucoepidermoid carcinomas were the commonest reported salivary gland

Table 2 Cumulative series: Parapharyngeal space mass histological diagnosis. Pathology

No. of patients Cohen et al. [6] n = 166

Carrau et al. [7] n = 54

Hughes et al. [4] n = 172

Hazarika Ulku Miller Attia et al. [8] et al. [9] et al. [10] et al. [11] n = 41 n = 18 n = 51 n = 25

Shahab Tincani Olsen Khafif Malone Zhi et al. Pang Stanley Allison et al. [17] et al. [18] et al. [5] et al. [15] et al. [16] [2] et al. [13] [14] [12] n = 114 n = 26 n = 44 n = 47 n = 33 n = 162 n = 31 n = 13 n = 23

Pensak et al. [19] n = 123

Salivary gland lesions total

33 – – – 1 – – –

14 – – – – – – –

68 1 – 1 – 1 – –

4 – – – – – – –

20 – – – – – – –

5 – – – – – – –

9 3 – – – – – –

2 – – – – – – –

13 – – – – – – –

57 3 5 – – – – –

12 – – 1 – – 1 –

16 – – – – – – –

11 – – – – – – –

17 1 – – – – – –

5 – – – – – – –

34 – – – – – – 8

114 (23) 33 21 12 12

(Malignant) Adenoid cystic carcinoma Mucoepidermoid carcinoma Squamous cell carcinoma Carcinoma ex pleomorphic adenoma Adenocarcinoma Acinic cell carcinoma Myoepithelial carcinoma Undifferentiated carcinoma Unspecified malignant Neurogenic lesions

1 1 – 1

1 – – 1

10 – 3 7

– 4 – –

1 – 2 –

1 1 2 1

– 1 – –

1 1 – –

1 – – 1

2 3 1 –

2 1 – –

1 2 – 1

4 – 1 –

3 3 – –

– 1 3 –

5 3 – –

– – – –

3 1 3 1 –

– – – – –

1 2 – – –

– – – 2 –

– 1 – – –

– – – – –

– – – – –

– – – – –

2

2 1 – – –

– – – – –

– – – – –

– – – – –

– – 1 – –

– – – – –

– – – – 4

– – – – 12

– – –

(Benign) Vagal paraganglioma Carotid body tumour Glomus jugulare Sympathetic paraganglioma Paraganglioma not specified Schwannoma Neurofibroma Unspecified benign PNSTe

61 2 – 4 0 16 7 –

7 14 – – – 3 2 –

24 9 1 – – – – 24

– – – – 3 1 3 –

6 2 – – – 9 1 –

– – – – – 4 – –

– – – – 3 17 1 –

– 1 1 – – 4 – –

– 1 – – 2 1 – –

– – – – 8 36 18 –

– 1 – – – 6 – –

(Malignant) Unspecified malignant PNST Malignant paraganglioma Miscellaneous lesions

3 1 – – – – – –

6 6 – – – 4 – –

– 5 – – 1 7 4 –

– 5 – – – – – 6

16 17 – – 2 11 3 –

8 9 7 – – 6 2 –

– – 2

2 2

6 –

– –

– –

– –

1 –

– –

– –

3 3

– –

– –

1 1

2 –

– –

– –

– –

(Benign) Anuerysm Branchial cleft cyst Hemangioma Meninigioma Lipoma

6 2 1 1 1

– – – 4 –

– – 1 2 –

– 1 – – –

– 1 – – 1

– – – 1 2

– 1 – 1 –

– 1 – – –

– – – – –

4 4 5 – –

– 1 2 – –

– – – – –

1 1 – –

– – – – –

1 – – – –

– – – 2 –

2 1 1 – 2

8 5 4 3 16 455 (41) 432 (95) 131 73 9 4 19 125 41 30

F. Riffat et al. / Oral Oncology 50 (2014) 421–430

– – – – – – – 39

499 (45) 385 (77) 320 8 5 2 1 1 1 47

(Benign) Pleomorphic adenoma Warthin’s tumour Basal cell adenoma Lymphoepithelial lesion Myoepithelioma Monomorphic adenoma Granulomatous parotitis Unspecified benign

Total (%)a

23 (5) 15 8 138 (12) 93 (67) 14 12 11 11 6 423

(continued on next page)

424

Table 2 (continued) Pathology

No. of patients Cohen et al. [6] n = 166

Inflammatory pseudotumour Cystic hygroma Otherb

– 1 7

Carrau et al. [7] n = 54 – – –

Hughes et al. [4] n = 172 – 2 2

Hazarika Ulku Miller Attia et al. [8] et al. [9] et al. [10] et al. [11] n = 41 n = 18 n = 51 n = 25

Shahab Tincani Olsen Khafif Malone Zhi et al. Pang Stanley Allison et al. [17] et al. [18] et al. [5] et al. [15] et al. [16] [2] et al. [13] [14] [12] n = 114 n = 26 n = 44 n = 47 n = 33 n = 162 n = 31 n = 13 n = 23

– – –

– – –

1 – –

1 – –

– – 1

– – 1

– – 4

– – 2

– – –

– – 1

– – –

– – 5

– – 5

Pensak et al. [19] n = 123

6 5 28

– – – 3 1 3 – – 1

45 (33) 6 6 6 4 4 4 3 2 10

0 1 0 1 0 1 – – 1

– – – – 1 – – – 1

1 – – – – – 1 – 2

– 1 – – 2 – – – 1

– – – – – – – – 1

– – – – – – – – –

– 1 – – – – – 1 1

2 – – – – – – – –

– – – – – – – 1 –

– 3 – – – – – – –

3 – – – – – – – –

– – – – – – 1 – 1

– – – – – – 1 – –

– – – – – – – – 1

– – 4 – – – – – –

– – 2 – – – – – –

4 – – –

26 (2) 23 1 1 1 1118 (100) 25 5 3

Lymphoid lesions Lymphoma Lymphoid hyperplasia Reactive lymphoid tissue Castleman’s disease

– – – 1

1 – – –

3 – – –

3 – – –

4 1 – –

– – – –

– – – –

– – – –

– – – –

4 – – –

– – – –

– – – –

– – 1 –

1 – – –

1 – – –

2 – – –

Primary total Metastatic lesions Metastatic thyroid carcinoma Metastatic squamous cell carcinoma Otherd Metastatic total a

4 –

1 –

– –

– –

– –

– –

– –

– –

– –

– –

– –

– –

– 2

– 1

– –

– –

– –

1

–

–

–

–

–

–

–

–

–

–

3

2

–

–

–

11

17 25

Total percentages calculated from the 1118 primary parapharyngeal space lesions. The remaining percents are calculated from subclasses. Other includes single cases of: lymphangioma [2], leiomyoma [19], osteolipoma [11], hemangioma–lymphangioma [16], fibromatosis [16], desmoid tumour [4], fibromyxoma [16], fibrous tumour [6], Kimura’s disease [15], oncocytic cyst [6], angioma [4], epidermoid cyst [6], sclerosing cervicitis [19], thorotrast granuloma [6], unspecified abcess [13], unspecified benign cyst [16], unspecified skeletal muscle lesion [16], parotid cutaneous fistula [6], encephalocele [6], dermoid cyst [19], 2 rhabdomyomas [6,19] and five unspecified miscellaneous benign lesions [5]. c Other includes single cases of: angiosarcoma [19], liposarcoma [7], malignant branchial cyst [8], spindle cell sarcoma [16], porocarcinoma [17], lymphoepithelioma [4], osteosarcoma [4], and an unspecified lesion [6] and 2 synovial sarcomas [9,11]. d Other includes single cases of: metastatic nasopharyngeal carcinoma [2], metastatic esthesioneuroblastoma [6], metastatic osteogenic sarcoma [2], and 14 unspecified metastatic lesions [16,19]. e Peripheral nerve sheath tumour (PNST). b

F. Riffat et al. / Oral Oncology 50 (2014) 421–430

4 2 –

(Malignant) Undifferentiated carcinoma Chondrosarcoma Sarcoma not specified Hemangiopericytoma Fibrosarcoma Rhabdomyosarcoma Chordoma Malignant fibrous histiocytoma Otherc

Total (%)a

425

F. Riffat et al. / Oral Oncology 50 (2014) 421–430 Table 3 Cumulative series: Signs and symptoms. Symptoms

No. of patients Cohen et al. [6]

External or intraoral mass Otalgia Dysphagia Dysphonia Pain (facial) Hearing loss Foreign body sensation Tinnitus Facial muscle weakness Trismus Painful throat Tongue parasthesias Aspiration Headaches Eustachian tube dysfunction Otherb

Carrau et al. [7]

Hughes et al. [4]

Attia et al. [8]

Miller et al. [9]

Ulku et al. [10]

Hazarika et al. [11]

Stanley [12]

Total (%)a

–

30

145

25

30

18

34

11

– 12 12 10 6 – 8 – – – – – – –

2 7 4 10 – 3 – – 1 – – – – –

62 22 18 11 19 – 3 7 – 4 3 2 2 –

6 2 – – – – – – – – – – – –

3 7 8 9 – 9 – – 5 – – – – –

2 5 3 4 – – – – 2 – – – – –

1 5 5 1 – 1 1 – – – – – – 2

1 – 1 1 – – – 1 – – – – – –

293 (55) 77 (14) 60 (11) 51 (9) 46 (9) 25 (5) 13 (2) 12 (2) 8 (1) 8 (1) 4 (1) 3 (1) 2 (0) 2 (0) 2 (0)

5

1

3

2

–

–

1

–

12 (2)

Signs Intraoral mass

42

26

113

2

34

–

24

12

External mass

51

32

99

25

17

8

10

12

38 14 – – 3 – 7 6 1 166

9 – 1 – – 2 – – 2 51

22 9 19 15 3 3 – – – 172

4 – – – 1 – – – – 25

12 – – – 3 4 – – – 51

6 – – –

4 – – – 1 – – – – 41

– – – – – – – – – 13

266 (50) 254 (47) 95 (18) 23 (4) 20 (4) 15 (3) 11 (2) 11 (2) 7 (1) 6 (1) 3 (1) 537

Cranial nerve deficit Palatal weakness Pulsation over mass Hearing loss Horner’s syndrome Trismus Shoulder weakness Serous otitis media Other unspecified n

2 – – – 18

a

Percentages calculated from all 537 patients in the 8 series that reported both signs and symptoms. Other includes single cases of tiredness [7], dysarthria [8], nasal obstruction [8], syncope [4], snoring [6], choking [6], coughing [6], dyspnea [6], nasal regurgitation [6], lightheadedness [4], hypertension [4] and epistaxis [11]. b

Table 4 Cumulative series: Surgical approaches. Surgical approach

a

No. of patients Cohen et al. [6]

Carrau et al. [7]

Attia et al. [8]

Miller et al. [9]

Ulku et al. [10]

Hazarika et al. [11]

Allison et al. [13]

Zhi et al. [14]

Pang et al. [15]

Malone et al. [16]

Olsen [2]

Khafif et al. [17]

Tincani et al. [18]

Total (%)a 328 (48) 186 (27) 44 (6) 64 (9) 4 (1) 10 (1) 2 (0)

Cervical

89

42

10

31

8

17

–

51

13

30

–

19

18

Cervical– parotid Parotid

20

–

10

–

–

8

–

93

–

–

33

22

–

–

6

–

14

5

–

5

–

14

–

–

–

–

Mandibulotomy

3

–

2

4

3

16

–

18

–

3

9

1

5

Transoral Transoral– cervical Transoral– parotid Infratemporal fossa Suboccipital craniotomy Cervical– mastoid Composite unspecified Total number of operations n

– 3

– –

– –

– –

– –

– –

3 7

– –

1 –

– –

– –

– –

– –

–

–

–

–

–

–

2

–

–

–

–

–

–

–

3

–

2

1

–

–

–

–

–

–

6

3

–

–

–

–

–

–

–

–

–

–

2

–

–

30

–

–

–

–

–

–

–

–

–

–

–

–

–

1

–

–

–

–

–

–

–

–

–

–

–

30 (4) 1 (0)

145

52

22

51

17

41

17

162

28

33

44

48

26

686

166

54

25

51

18

41

23

162

31

33

44

47

26

721

Percentages calculated from the 686 patients that underwent a surgical procedure in the 14 series that reported the surgical approach used.

15 (2) 2 (0)

426

Table 5 Cumulative series: Postoperative complications. Complications

No. of patients Cohen et al. [6]

Hughes et al. [4]

Attia et al. [8]

Miller et al. [9]

Ulku et al. [10]

Hazarika et al. [11]

Stanley [12]

Allison et al. [13]

Zhi et al. [14]

Pang et al. [15]

Malone et al. [16]

Olsen [2]

Khafif et al. [17]

Tincani et al. [18]

Total (%)a

Vth CN injury VIIth CN injury

– 19

– 7

– 19

– 2

– 14

– 3

– 1

– 1

– 1

– 7

– 8

– –

1 10

1 5

– 5

Xth CN injury

45

3

41

–

11

–

2

–

–

–

–

4

7

11

–

IXth CN injury XIth CN injury XIIth CN injury Horner’s syndrome First bite syndrome Shoulder weakness Trismus Heamatoma Vascular injury Dysphagia Dysphonia Palatal insufficiency Frey’s syndrome Otherb Total number of operations n

– – 15 12

– 2 8 1

4 12 15 11

– – – –

– – 3 –

– – – –

– – – 1

– – – –

– – – –

– – – 5

– – – 1

– – 6 1

– 1 3 2

– – – 1

– – – 2

2 (0) 102 (12) 124 (14) 4 (0) 15 (2) 50 (6) 37 (4)

18

–

–

–

–

–

–

–

–

–

–

–

1

–

–

19 (2)

18

–

–

–

–

–

–

–

–

–

–

–

–

–

–

18 (2)

6 2 – – – 33

– 2 3 – – –

– – 6 – – –

– – – – – –

– 1 – – – –

– 0 – 1 – –

– 0 – 1 4 –

– 1 – – – –

2 – – – – –

– – – – 8 –

– – – – – –

4 – – 7 – 1

– 4 – – – –

– – – – – –

– – – – – –

12 (1) 10 (1) 9 (1) 9 (1) 12 (1) 34 (4)

– 10 145

– 4 52

– – 170

– – 22

1 – 51

– – 17

– 6 41

– – 11

2 3 17

– – 162

4 1 28

1 – 33

– 3 44

1 2 48

– – 26

9 (1) 29 (3) 867

166

51

172

25

51

18

41

13

23

162

31

33

44

47

26

903

Percentages calculated from the 867 patients that underwent a surgical procedure in the 15 series that reported on postoperative complications. b Other includes pneumonia [6,13], orocutaneous fistula [6], cerebrospinal fluid leak [6], endocarditis [6], gastrointestinal complications [6], CVA [7], respiratory infection [7], heart failure [7], disarticulation [11], parotid fistula [11], blindness [11], wound abscess [13], intraoral wound dehiscence [13], stitch granuloma [15], infection [2], decubitus wound [17], necrosis of skin flap [17].

F. Riffat et al. / Oral Oncology 50 (2014) 421–430

a

Carrau et al. [7]

F. Riffat et al. / Oral Oncology 50 (2014) 421–430

malignancies, contributing to 7% and 4% of salivary gland lesions respectively.

427

type or primary site. Of the named metastatic lesions, metastatic thyroid carcinoma was the commonest lesion, accounting for 20% of all metastatic lesions.

Neurogenic tumors Clinical presentation The neurogenic group of parapharyngeal space tumors (prestyloid) consists of five main histological types; paragangliomas, neurofibromas, schwannomas, malignant peripheral nerve sheath tumours (PNSTs) and malignant paragangliomas. Ninety-five percent of the 455 neurogenic tumours in the cumulative series were benign. The most common benign lesions being paragangliomas, accounting for 52% of all neurogenic tumours, followed by schwannomas (27%) and neurofibromas (9%). Malignant neurogenic tumours form 5% of all neurogenic lesions. Malignant schwannomas and neurofibrosarcomas are known as malignant peripheral nerve sheath tumours (PNSTs). Malignant PNSTs are the commonest malignant neurogenic lesions in the cumulative series, followed by malignant paragangliomas. These findings differ from other cumulative series by John et al. [20] and Dankle [21], in which schwannomas were reported to be the most common neurogenic tumour. In the cumulative series the commonest paragangliomas of the parapharyngeal space were derived from the vagus nerve followed by carotid body tumours and glomus jugulare tumours. Paragangliomas are rarely fatal but can cause cranial nerve deficits and extend intracranially if untreated. Malignant transformation of paragangliomas has been reported. Familial paragangliomas are rare but should be suspected if the patient is young, has multiple paragangliomas or if other family members have a paraganglioma. Mutations of the SDHD, SDHC and SDHB genes have been identified as causing various familial paragangliomas syndromes (PGL 1, 3, 4 respectively) [22]. Patients suspected to have a familial paragangliomas should undergo genetic testing and if they are positive for a mutation then close family members should also be offered genetic testing. Cranial nerves IX to XII and the cervical sympathetic chain give rise to schwannomas in the parapharyngeal space. They usually do not cause injury to their nerve of origin but as they enlarge they can present as a mass and affect the function of adjacent nerves. Treatment involves enucleation and usually it is possible to preserve the involved nerve. Neurofibromas may occur as multiple lesions and are closely involved with the nerve of origin. Removal of a neurofibroma usually involves sacrificing the nerve from which it arises. Lymphoid and miscellaneous lesions The miscellaneous group of parapharyngeal space pathology in the cumulative series contains 40 different types of lesions, consisting largely of soft tissue tumours, bone tumours and inflammatory lesions. Benign lesions form 67% of the 138 lesions in this group. The commonest miscellaneous masses found in the parapharyngeal space include internal carotid artery aneurysms (10%), branchial cleft cysts (9%), hemangiomas (8%) and meningiomas (8%). Malignant miscellaneous lesions account for 33% of miscellaneous lesions in the cumulative series. The lymphoid group of primary parapharyngeal space lesions consists of 26 cases of which the majority are lymphomas (88%). Metastatic lesions Metastatic disease is a rare differential diagnosis for a parapharyngeal space mass. Out of the 15 studies in the cumulative series that did not exclude metastatic lesions, there are a total of 857 patients of which only 3% were metastatic lesions. The majority of these cases are from reports that did not specify the histological

The comprehensive evaluation of parapharyngeal space lesions must begin with a thorough history making a detailed inquiry into the state of the upper aerodigestive tract function including airway, speech and swallow. A complete head and neck examination including nasopharyngoscopy and cranial nerve assessment is paramount. Parapharyngeal space lesions are palpable as a neck lump usually only when the mass exceeds 2.5–3.0 cm [7,23] making early detection difficult. Bimanual palpation and ballottement of the lesion is important to assess tumour mobility and size. Maran et al. [24] stated that parotid lesions typically distort the tonsil, whilst neurogenic lesions distort the posterior pharynx and posterior tonsillar pillar. Parapharyngeal space lesions enlarge medially and inferiorly; medial enlargement results in an asymmetric intraoral swelling which is typically smooth and not ulcerated [25], downward growth manifests as a mass at the angle of the mandible [13]. The presence of a parotid mass as well as an intraoral mass suggests a ‘dumbbell’ shaped deep lobe parotid tumour. The commonest signs and symptoms amongst the cumulative data of the eight series of 537 cases published in the last 20 years are an intraoral mass and a cervical mass (Table 3). In the cumulative series an intraoral swelling and a cervical mass was present in 50% of patients and 44% of patients respectively. These findings should alert the clinician to the possibility of a parapharyngeal space lesion. A cranial nerve examination should be performed and nasopharyngoscopy is essential to investigate vocal cord function. Lesions expanding into the poststyloid compartment may compress cranial nerves IX through to XII and in the cumulative series cranial nerve neuropathy was the third most common sign, which was reported in 95 cases (18%). Of the case series reporting cranial neuropathies, the vagus nerve was the most commonly affected, seen in 7% of cases. A Horner’s syndrome was seen in 11 cases (2%) in the cumulative series. Cranial nerve deficits and medial enlargement of masses may lead to symptoms of dysphagia and dysphonia, which were common symptoms occurring in 60 cases (11%) and 51 cases (9%) respectively. Superior enlargement of masses can compress the opening of the eustachian tube [24] leading to effusions of the middle ear and its resulting sequelae. In the cumulative series hearing loss was present in 25 cases (5%). These symptoms warrant further audiologic investigation and examination of the nasopharynx. Investigations Cross-sectional imaging is vital in the workup of any patient suspected of a PPST. This will take the form of both a CT scan and MRI scan in the majority of cases. Both these modalities are complimentary in the evaluation of the tumor-host interface, major neurovascular structures, glandular tissue and the relationship to the craniofacial skeleton including the skull base. Poststyloid lesions are reported to displace the internal carotid artery anteromedially whilst prestyloid lesions displace the internal carotid artery posteriorly [25]. The presence of a fat plane between the parotid and a lesion differentiates an extraparotid lesion from a deep lobe parotid lesion. CT is a practical first choice and can demonstrate bony involvement and calcification within lesions. MRI is able to better outline the position of the great vessels relative to the lesion, to delineate soft tissue and to demonstrate intracranial extension. Some lesions such as paragangliomas have a characteristic ‘’salt and pepper’’ appearance on MRI. Features

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on CT and MRI which suggest malignancy include invasion of the adjacent muscle and fat, bone destruction, irregular tumour margins, obliterated fascial planes and lymphadenopathy. Both CT and MRI are invaluable for all types of PPST particularly those that are extensive, potentially malignant or in the setting of disease recurrence. Selective preoperative angiography is usually recommended for large vagal paragangliomas, carotid body tumours and other enhancing, vascular lesions [23]. It defines the blood supply and screens for multicentric lesions. Feeding vessels may be identified and can be considered for preoperative embolisation. Angiography can be diagnostic of some lesions. Carotid body tumours situated in the carotid bifurcation demonstrate the Lyre sign [25,26]. In which there is splaying of the carotid bifurcation. Angiography combined with the balloon carotid occlusion test is indicated when carotid infiltration is suspected or if the internal carotid artery is likely to be sacrificed [2]. Carotid artery occlusion assesses the collateral cerebral circulation and identifies those at risk of a cerebral infarction if the internal carotid artery is scarified. If a paraganglioma is suspected, 24 h urine screening for metanephrine, vanilymandelic acid and normetaphrine must be performed to exclude a functional paragangliomas, however one has to be selective in the testing as only 10% might be secretory [2]. If catecholamine levels are positive, a metaiodobenzylguanidine (MIBG) scan should be performed to investigate catecholamine uptake and storage. The use of transcervical fine needle aspiration cytology (FNAC) is widely recommended by many authors. Results with FNAC are variable amongst different authors with Shahab et al. [5] finding that all 19 FNAC results were accurate whilst Luna-Ortiz et al. [27] found all four FNAC results inconclusive. Our approach has been to perform ultrasonography FNAC on non-vascular lesions. We find that radiographic imaging in combination with ultrasound guided biopsy provides sufficient information for determining the surgical approach. Surgery Complete surgical excision with minimal morbidity remains the main aim of parapharyngeal space mass treatment. In the cumulative series 95% of patients underwent surgery. Patients should be well informed about the potential for cranial nerve palsies resulting from surgery. Surgery is not appropriate if the risks of surgery outweigh nonoperative management. Such cases may include elderly patients with asymptomatic, slow growing benign tumours, such as neurogenic lesions which are at high risk of cranial nerve damage if operated on. A gradual loss of cranial nerve function is usually better tolerated by elderly patients than sudden loss due to surgery, so observation or delayed removal is recommended in these patients. Most prestyloid lesions can usually be treated regardless of age. Patients with malignant lesions, and those with internal carotid artery involvement who have failed the balloon occlusion test may be not be suitable for surgery. Patients with pre-existing contralateral deficits of the vagus and hypoglossal nerves may not be suitable for surgery due to the risk of bilateral deficits causing problems with swallowing and the airway. Radiotherapy is usually the primary modality of treatment for patients with unresectable lesions or who are unsuitable for surgery. If surgery is to be undertaken any of the following three external surgical approaches are suitable for the majority of lesions. The choice of approach is guided by the tumour size, suspicion of malignancy and position with regards to the tumour’s superior extent and proximity to the skull base as well as relationship to major neurovascular structures and proximity to the skull base. The cervical approach is indicated for the resection of most parapharyngeal space tumours situated in the inferior portion of

the parapharyngeal space. Most extraparotid lesions such as neurogenic tumours can be removed by this route [26]. A transverse incision is made at the level of the hyoid bone and the stylohyoid, styloglossus, stylomandibular ligament and posterior digastric muscles are divided. The tumour is bluntly dissected free. Although this approach is not adopted by all authors we would argue this approach is very useful for direct access to the inferior portion of the parapharyngeal space, good visualization of the cranial nerves and control of the great vessels. It also avoids any risk to the facial nerve. The cervical approach allows conversion to the cervical– parotid approach should unexpected findings make more exposure necessary such as potential damage to the facial nerve. In the cumulative series, the cervical approach was the most commonly used (Table 4). In total the approach was used for 328 cases (48%) out of the 686 surgical patients in the 14 series. The cervical–parotid approach is recommended for lesions involving the facial nerve, including deep lobe parotid lesions and minor salivary gland lesions [2]. The approach can be also used for many poststyloid tumours, such as neurogenic tumours positioned in the mid to upper portion of the parapharyngeal space and some malignant lesions. The cervical approach is combined with a parotid approach by using a parotidectomy incision. The cervical incision provides exposure to the parapharyngeal part of the lesion and the parotidectomy incision enables the facial nerve to be identified and exposure to the deep lobe of the parotid. Olsen also recommends division of the styloid process to increase access [2]. The approach allows adequate vascular control and enables a deep lobe parotid lesion to be resected with a cuff of deep lobe parotid tissue under direct vision by sharp and blunt dissection. In total the approach was used in 27% of cases in the cumulative review. The cervical–parotid or cervical approach with a mandibulotomy is indicated for large, recurrent or malignant tumours requiring maximum exposure especially when there are concerns regarding the potential involvement of major neck vasculature . Such lesions include those positioned in the superior portion of the parapharyngeal space, lesions which necessitate distal control of the internal carotid artery at the skull base and vascular lesions with superior extension. The approach is also useful for large malignant tumours for which exposure at the skull base is required to facilitate removal. A median or paramedian mandibulotomy anterior to the mental foramen is recommended as it allows the preservation of the inferior alveolar nerve. A horizontal incision is made at the level of the hyoid bone and the lip is split. After the midline osteotomy the excision is continued along the floor of the mouth towards the anterior tonsillar pillar. The hypoglossal and lingual nerves are identified and preserved and lateral retraction of the mandible exposes the parapharyngeal space. A tracheostomy may be necessary due to the risk of postoperative airway obstruction. The approach requires a longer hospital stay and a delay in oral nutrition. It carries additional risks of mandibular malunion or non-union, loss of dentition and temporomandibular joint dysfunction. A mandibulotomy was performed in 9% of the patients in the cumulative review. Non-lip splitting mandibulotomy omitting the procedure of lower lip-splitting incision for selected malignant lesions of oral, oropharyngeal, and parapharyngeal areas to improve the aesthetic results and to decrease the possible functional morbidities of the lower lip. An oral incision was made at the reflected labial mucosa just above the labiogingival sulcus on the anterior aspect of the mandible. Subperiosteal dissection was performed through the oral incision site down to the periosteal incision site at the lower border of the mandible. All the soft tissue attachments were elevated laterally from the ipsilateral mental foramen to the contralateral mental foramen, with care being taken so that there was no injury to the mental nerves. Once the midline tunneling

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between the anterior mandible and the soft tissue including the entire lower lip was created, an ipsilateral paramedian mandibulotomy was performed between the lateral incisor and the canine teeth in a vertical plane with a stepladder or wedge fashion. The submental skin incision could be extended to the inferior chin area to improve the surgical view [28,29]. Outside of these main surgical approaches the transoral approach [7] has been described for the resection of small benign lesions presenting as an intraoral mass. In total it was used in only 2% of the surgical cases in the cumulative review. The limited exposure of this approach means that direct visualization of the great vessels is not possible, and there is a higher risk of tumour rupture, incomplete removal, uncontrollable haemorrhage from major vessel damage and facial nerve injury. The infratemporal approach combined with the cervical–parotid or cervical approach is indicated for malignant parapharyngeal space lesions involving the skull base or jugular foramen or with intracranial extension. Adjuvant radiotherapy should be used in patients in which wide surgical margins cannot be obtained [30]. Radiotherapy Primary radiotherapy is an option if patients have a high surgical risk, if a large lesion is unresectable. Although it was historically believed that radiotherapy was useful for growth arrest, there is increasing evidence that radiotherapy gives comparable prognostic results to surgery, without the risk of surgery-associated complications. Observational studies demonstrate long-term control rates (defined as stable disease or partial regression with no evidence of growth) for paragangliomas of 95–96%.Given the rarity of the condition, there are no randomised controlled trials yet to compare surgery with radiotherapy for parapharyngeal lesions [31,32]. Complications Potential complications should be explained to patients before surgery and any complication needs to be managed appropriately to facilitate rehabilitation. The commonest complication in the cumulative series (Table 5) was injury to an associated cranial nerve or the sympathetic chain. The nerves most at risk are cranial nerves VII, IX, X, XI and XII. Neurogenic and malignant lesions have a greater risk of cranial nerve injury. Other complications include jaw pain as a result of first bite syndrome which is the development of pain in the parotid region that occurs after the first bite of a meal. Loss of sympathetic innervations from the superior cervical ganglion to the parotid gland has been proposed as a cause [33]. Vocal cord palsy results from injury to the vagus nerve and patients should receive speech and language therapy to improve speech and swallowing function. Injury to the vagus nerve was the commonest complication as noted in the cumulative series affecting 124 (14%) patients although in post-styloid parapharyngeal space tumours this could be considered an expected sequelae of surgery. Isolated vagus nerve injury may be well tolerated by patients, but if both the vagus and hypoglossal nerves are damaged the impairment of swallowing and speech is usually far worse. These patients usually require vocal cord medialisation. A tracheostomy should be performed for any patient at risk of aspiration and a nasogastric tube should be inserted if necessary until patients are able to swallow adequately. Usually some degree of compensation occurs after isolated cranial nerve injury. For isolated vagus nerve injury delaying further treatment until after any compensation has occurred to allow the final position of the vocal cord to be known, seems to be a reasonable approach. If patients have poor speech and swallowing function that has not resolved

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adequately, medialisation of the paralysed vocal cord should be considered either with thyroplasty or endoscopic augmentation. The facial nerve is at low risk of injury during removal of parotid lesions of inadvertent injury and can be minimised by the use of facial nerve monitoring. Dynamic and static facial animation techniques may be required if the facial nerve is sacrificed because of tumour involvement. Haemorrhage or stroke resulting from vascular injury is a serious but rare complication of parapharyngeal space surgery. Malignant lesions, vascular lesions and carotid body tumours involving the carotid artery increase the risk of vascular complications. All patients should be followed up postoperatively to check for recurrence. Recurrence of benign parapharyngeal space lesions is low however malignant parapharyngeal space lesions tend to recur and have a worse prognosis. Despite the poorer prognosis of malignant parapharyngeal space lesions, radical surgical resection and adjunctive radiotherapy may still be indicated. Several limitations regarding our systematic review exist. The studies included in the systematic review were performed in different centres and were of different sizes. Also different case series have used different criteria and terms to describe equivalent signs, symptoms and histological types. Several series omit details on the exact histological diagnosis of the tumours that are reported. The definitions of what constituted a parapharyngeal space mass varied slightly from author to author. Nevertheless the presented work provides useful cumulative information on histological types, presentations, surgical approaches and complications for this diverse group of tumor. Conclusion Tumours of the parapharyngeal space are rare. Most cases are treatable and high index of suspicion is needed to diagnose them at an early stage. Parapharyngeal space tumors must be included in the differential diagnosis of patients who have medial enlargement or displacement of the oropharyngeal wall. The majority of parapharyngeal space tumors are benign and complete surgical resection is the mainstay of treatment. Appropriate use of the cervical and cervical-parotid approaches with or without a mandibulotomy can enable the surgeon to achieve these aims. Cranial nerve deficits are the most common expected sequelae and clinicians must counsel their patients pre-operatively about potential outcomes. Conflict of interest statement None declared. References [1] Bond JW. Encapsulated tumor removed from region of left tonsil and soft palate. Proc R Soc Med Lond 1916;9(4). [2] Olsen KD. Tumors and surgery of the parapharyngeal space. Laryngoscope 1994;104(5 Pt 2 Suppl 63):1–28. [3] Curtin HD. Separation of the masticator space from the parapharyngeal space. Radiology 1987;163(1):195–204. [4] Hughes 3rd KV, Olsen KD, McCaffrey TV. Parapharyngeal space neoplasms. Head Neck 1995;17(2):124–30. [5] Shahab R, Heliwell T, Jones AS. How we do it: a series of 114 primary pharyngeal space neoplasms. Clin Otolaryngol 2005;30(4):364–7. [6] Cohen SM, Burkey BB, Netterville JL. Surgical management of parapharyngeal space masses. Head Neck 2005;27(8):669–75. [7] Carrau RL, Myers EN, Johnson JT. Management of tumors arising in the parapharyngeal space. Laryngoscope 1990;100(6):583–9. [8] Attia A, El-Shafiey M, El-Shazly S, Shouman T, Zaky I. Management of parapharyngeal space tumors at the National Cancer Institute, Egypt. J Egypt Natl Canc Inst 2004;16(1):34–42. [9] Miller FR, Wanamaker JR, Lavertu P, Wood BG. Magnetic resonance imaging and the management of parapharyngeal space tumors. Head Neck 1996;18(1):67–77.

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