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REVIEW URRENT C OPINION
Branchial cleft cyst carcinoma: fact or fiction? Paula T. Bradley a and Patrick J. Bradley b
Purpose of review With the recent changes in the cause of head and neck cancer and the association of cystic metastatic neck squamous cell carcinoma with human papilloma virus (HPV), patients who are diagnosed with a cystic lesion in their upper neck need thorough investigation before commencing any treatment. Recent findings The differential diagnosis of a cystic mass in the upper neck of an adult over the age of 40 years is a branchial cleft cyst, cystic metastatic squamous cell carcinoma or a branchial cleft cyst carcinoma (BCCC). Investigation must include diagnostic imaging, biopsy or excision biopsy of likely primary sites, such as oropharyngeal sub-sites, and testing for HPV, Epstein-Barr Virus immunological status. Summary The existence of BCCC is an exceptional diagnosis, with less than 40 cases considered proven. Consensus agreement has been proposed on making such a diagnosis. The diagnosis of a BCCC should be one of exclusion rather than presumption, after all other possible diagnoses have been considered and excluded. Keywords branchial cleft cyst carcinoma, branchial cyst, cystic metastatic neck disease
INTRODUCTION The nature and diagnosis of branchial cleft cyst carcinoma (BCCC) has generated much discussion. The subject has divided the head and neck surgical world into those who doubt its very existence [1–5] and those who consider that at least in theory that a true clinicopathological entity could exist [6–10]. Branchial cleft cysts are common presenting in the upper neck at any age, but are most frequently seen in young adults between 20 and 40 years old. A diagnosis of a BCCC can only be made after the excision of the lesion followed by a thorough histologic examination of the mass with a demonstration that the cystic lesion is associated with a well defined sinus tract [11,12]. Others suggest that the cyst wall must demonstrate the areas of transition to dysplasia with the features of carcinoma in situ and small focal invasion of the epithelial structures into lymphoid tissue [7]. An adult patient with a possible BCCC will present with an upper neck swelling in a similar fashion to any other benign or malignant cystic lesion. All will require examination, investigation and some form of surgery to confirm the exact nature of the lesion. The confusion about the existence of a BCCC relies on the understanding of the other differential diagnosis of cystic lesions that may present in a similar location and manner.
Anatomic location, age at onset, duration of the neck lump and associated symptoms can allow for most neck masses to be broadly divided into inflammatory, congenital or neoplastic. Greater than 90% of all paediatric neck masses will be inflammatory (infectious), whereas the incidence of a malignant neck mass increases exponentially after 40 years of age. Patients, older than 40 years, who present with a neck mass tend to follow the ‘rule of 80’, that is, roughly 80% of all nonthyroid neck masses will be neoplastic, and of these neoplastic lesions, approximately 80% will be malignant [13]. In an adult patient, a neck mass that has been present for longer than 3–4 weeks with no evidence of an infectious cause warrants further diagnostic evaluation. Following a thorough clinical examination, modern diagnostic imaging ultrasound, computer tomography (CT), or magnetic resonance imaging a Department of ORL-HNS, The Freeman Hospital, Newcastle-upon-Tyne and bDepartment of ORL-HNS, Nottingham University Hospitals, Nottingham University, Nottingham, UK
Correspondence to Professor Patrick J. Bradley, MBA, FRCS, FACS, FRCSLT (Hon), FRACS (Hon), 37 Lucknow Drive, Mapperley Park, Nottingham, NG3 5EU, England, UK. Tel: +44 115 9607031; e-mail:
[email protected] Curr Opin Otolaryngol Head Neck Surg 2013, 21:000–000 DOI:10.1097/MOO.0b013e32835cebde
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(MRI) are used, almost as a routine to aid making or possibly confirming a diagnosis. Ultrasound is the most frequently used in the paediatric age group, whereas CT is used most frequently in adults, and the addition of guided needle aspiration cytology of the fluid or biopsy of the solid tissue is frequently included by modern radiologists [14,15]. MRI is helpful, particularly when there is need for additional assessment of the deeper tissue planes. MRI is also useful in delineating the lesions considered to be of neural or vascular origin. Positron emission tomography (PET) is not universally available, but when available is generally reserved for staging malignancies prior to and monitoring the responses to treatment.
CYSTIC LESIONS IN THE ADULT NECK An adult presenting with a clinical cystic swelling of the upper part of the anterior triangle of the neck may prove to have a branchial cyst, a cystic metastatic malignancy, or a BCCC [16]. Other lesions that can present as a cystic mass in the upper neck include cystic necrotic schwannoma, lymph node with necrotic granulomatous inflammation, lymphangioma, venous malformation and lymphoma with cystic degeneration [15]. Metastatic papillary thyroid carcinoma may also present as a cystic metastasis [17–19]. A series of 121 patients identified in Pittsburgh [20], with an initial diagnosis of lateral cervical cyst were reviewed. The mean age of patients was 38 years (range 18–69 years). A diagnosis of branchial cleft cyst was confirmed after surgical excision in 90% (109 of 121). These patients had a mean age of 36 years (range 18–69 years). Metastatic squamous cell carcinoma was demonstrated on histology in 12 patients (9.9%), with a mean age of 53 years (range 44–61 years). The mean age of patients with malignant cysts was significantly higher than that of those with benign cysts (P < 0.0001). The overall incidence of malignancy was 9.9% (12 of 121) and in patients over 40 years of age, the incidence was 23.5% (12 of 51). Another retrospective review of medical records and radiological images looked at196 consecutive cases [15]. These patients had presented to the Department ORL-HNS, Helsinki University, with a solitary lateral cervical cystic neck lesion between January 2000 and December 2007. Patients under 17 years of age were excluded and the group had a mean age of 40 years (range 17–79 years). One hundred and eighty-nine cases (96.4%) after surgical excision and histopathological analysis were proven to be benign lesions. Metastatic squamous cell carcinoma was proven in seven (3.6%) cases: in four 2
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of these cases, the primary site was oropharynx (two tonsils and two posterior tongue); in two cases, no primary tumour was identified; and one case was proven papillary thyroid carcinoma. None of these seven cases were clinically or radiologically malignant prior to surgery or histological examination.
CYSTIC METASTATIC SQUAMOUS CELL CARCINOMA Cystic metastatic squamous cell carcinomas are reported at a rate of 33–62% [5,21–24] and are associated with human papilloma virus (HPV). Almost all such nodes containing HPV-DNA are identical to that of the primary disease which is most commonly located in the oropharynx. A mechanism of the cyst production has been suggested: it is proposed that the metastatic cells undergo ductal differentiation [25] and amongst the malignant cells are salivary gland-type cells. The fluid within these metastatic pseudocysts has keratin and cellular debris as distinct from true cysts that have eosinophilic fluid, as there is an active transport mechanism across the epithelium which relates to ductal differentiation, with the presence of cytokeratin 7 as a marker for this process. The tendency for cyst formation in oropharyngeal metastatic disease is intrinsic to the epithelial cells that are identified within the crypts of the posterior tongue and tonsils [21,26].
BRANCHIAL CLEFT CYST Hunczowski [27] described the first branchial cyst in 1789. Many theories have been proposed on the cause of branchial cleft cysts. Von Asherson in 1832 [28] proposed that branchial cysts were due to incomplete obliteration of the branchial cleft mucosa (branchial theory). His [29] proposed the ‘precervical sinus theory’ which submits that branchial cysts exist because of incomplete obliteration of the cervical sinus. In 1912, Wenglowski [30] proposed that branchial cysts developed from incomplete obliteration of the thymopharyngeal duct. In the mid-1950s, King [31] and separately Bhasker and Bernier [32] suggested the theory of cystic transformation of lymph nodes. It was also proposed that cystic alteration of the cervical lymph node was stimulated by ‘trapped’ epithelium, and the term ‘inclusion theory’ was coined [32]. The pathological findings summarized by Maran and Buchanan [33] showed that the cysts are lined by epithelium, which in 77% was of squamous type and occasionally keratinizing. The thickness of the epithelium varied in different parts of the cyst, varying from one cell thickness to a more Volume 21 Number 00 Month 2013
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stratified form. In 13% the lining epithelium, there were areas of columnar respiratory type epithelium where goblet cells were found to alternate with stratified squamous epithelium. Damage to the epithelial lining resulted either in patchy or widespread desquamation, with replacement by granulation tissue, or variable metaplastic changes with alteration of epithelium either to a transitional form or to a cuboidal or flattened configuration. More than 90% had abundant subepithelial lymphoid tissue in diffuse bands or in prominent follicular pattern with germinal centres. In a proportion of cases, the appearance of the lymphoid infiltrate in the wall resembled that of an organized lymph node tissue with the suggestion of subcapsular or medullary sinusoids and the presence of germinal centres. The authors concluded that a proportion of ‘branchial cysts’ do not arise from the branchial apparatus, but may do so from epithelial inclusions within lymph nodes. Howie and Proops [34] in their publication reported that the terminology used on ‘branchial apparatus lesions’ was confusing in the description of the clinicopathological features and there had been no explicit definition agreed. They reviewed 57 lateral cervical lesions and proposed a definition that branchial cysts ‘are lesions found behind the angle of the mandible in the anterior triangle of the neck at the junction of the upper third and lower two-thirds of the sternocleidomastoid muscle. They have a lining of stratified squamous epithelium resting on a complete or incomplete band of lymphoid tissue, and part of the cyst wall resembles a lymph node’. Branchial anomalies compose approximately 30% of congenital neck masses and can present as cysts, sinuses or fistulae [35]. They are equally common in men and women. First, second, third and fourth cleft anomalies are described. The first cleft accounts for only 1–8% of branchial cleft anomalies and can present as cysts, sinuses or fistulae located between the external auditory canal and the submandibular area, and these are classified as type I and II lesions. Type I lesions are cysts or sinuses in the parotid presenting in early adult life and type II presenting in the anterior triangle of the neck and with a communication to the external auditory canal [36]. The second cleft anomalies are the most common, representing 95% of all branchial cleft anomalies, and these are classified into four types depending on their location to the cervical fascia and proximity to the carotid artery complex. The second cleft anomalies present as a fistula or as cysts. Fistulae are usually diagnosed in infancy or childhood, whereas cysts are more commonly diagnosed in adults during the third and fifth decades [14]. Third and fourth branchial anomalies are rare,
present in a similar fashion as the second anomalies, with cysts and fistulae presenting at any age with lesions located in the lower neck around the piriform sinus [35,36]. A review [37] of 91 branchial cysts presenting in the northeast of England during a 6-year period between June 1999 and September 2005 was performed. The average age of the patients at the time of surgery was 32 years (range 8 months to 80 years; median age 31 years). This study comprised of 79 adults (at least 16 years old) and 12 children, 42 men and 49 women. Another study from Denmark [38 ] reported a series of 100 diagnosed over a 9-year period. The median age at surgery was 33.3 years (range 10.0–79.4 years). There were 52 men and 48 women. &
BRANCHIAL CLEFT CYST CARCINOMA BCCC is where a cancer (squamous cell carcinoma) arises from cells within the cyst wall. It is a rare entity with fewer than 40 cases fulfilling the strict criteria initially described by Martin et al. [39]. The existence of primary carcinoma arising from branchial cleft cyst was first suggested by von Volkmann [40] using the term ‘branchiogenic carcinoma’. He described three cases which he believed to be cystic carcinomas arising from remnants of the branchial apparatus. In 1950, Martin et al. [39] reviewed the published literature of some 250 cases and found that this diagnosis was questionable in most cases. They suggested that an occult head and neck primary cancer could not be excluded because of lack of long-term follow-up. This review recommended strict criteria for establishing the diagnosis of primary branchial cleft carcinoma. The criteria needed to support such a diagnosis are location of the tumour along the anterior border of the sternocleidomastoid muscle, histological findings consistent with tissue originating from a branchial vestige, histological evidence of carcinoma arising in the wall of an epithelial-lined cyst and no evidence of a primary cancer source during a minimum of 5 years of follow-up. Khafif et al. [41] reviewed the published literature of all 67 cases reported in the English literature since the publication of Martin’s criteria. They emphasize as had been suggested previously in 1976 [42], that the most important element in establishing a diagnosis is the ‘demonstration of a squamous cell carcinoma developing in the epithelial lining of a cyst. The transition from the normal nonneoplastic epithelium to malignancy through dysplasia and in-situ carcinoma’. They concluded from their review that it seems ‘unequivocal that epidermoid carcinoma may, and in fact does,
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occur in congenital branchial cleft cysts’ and that the incidence of BCCC is extremely low, with no more than 20–30 cases reported. They modified the criteria suggested by Martin et al. and recommend that to consider such a diagnosis must include location of the tumour in the anatomic region of a branchial cleft cyst, histological appearance consistent with its origin from branchial vestiges – squamous cell carcinoma, presence of the carcinoma within the lining of an identifiable epithelial cyst, identification of transition from normal squamous epithelium of the cyst to carcinoma and the absence of any identifiable primary malignancy tumour after exhaustive evaluation of the patient. Singh et al. [10] suggested that a diagnosis of BCCC should not be used in patients who have been treated by radiotherapy and who have been found to have squamous cell carcinoma in the upper aerodigestive tract within 5 years, as metastatic disease to the upper jugular lymph nodes is more common. They suggest that patients treated with radiotherapy should satisfy a 5-year disease-free survival. Mallet et al. [6] take the issue with the no registered tumour after 5 years as simply not applicable because the clinical scenario will inevitably lead to adjuvant radiation therapy after node dissection. With radiation therapy, all chances of discovering a primary site are virtually dismissed. Because of the shared anatomic region of a BCCC with a metastatic occult primary of the upper aerodigestive tract and the difficulty in histologically distinguishing a BCCC from the cystic degeneration of a metastatic lymph node, there are barriers making the proper diagnosis [43]. Thompson and Heffner [26], in their review of 136 cases from the Armed Forces Institute of Pathology, did not find one case of true BCCC. They concluded that almost all presumed BCCC is actually a metastatic primary from Waldeyer’s ring, and that these carcinomas are clinically distinct subsets that behave differently than most oropharyngeal squamous cell carcinomas.
RECOMMENDATION FOR THE INVESTIGATION OF LEVEL IIA/III NECK CYSTIC LESIONS The diagnosis of a cystic lesion will in general have been made by the use of needle aspiration of fluid either alone or as a finding when attempting to perform a fine-needle aspiration cytology or fineneedle aspiration biopsy (FNAC or FNAB) of a neck mass, or a finding after imaging investigation of an upper anterior triangle neck mass. All fluid should be aspirated and sent for cytology. The fluid aspirated will often be reported as mature squamous 4
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cells and atypical squamous cells, and may not be cytologically associated with any malignancy. It has been reported that FNAC of such cystic metastasis carries a high false-negative rate (38–63%) causing diagnostic problems [20,21,44,45]. It has been suggested that the mass should be aspirated to dryness, and then under image guidance a needle aspirate of the solid component be made [46 ]. The use of flow cytometry DNA analysis of FNAC samples can help to distinguish branchial cleft cyst from the cystic metastatic disease of the head and neck [44]. In cases with inconclusive cytology, this technique reveals DNA aneuploidy in cells from cystic metastases and a diploid karyotype in benign lesions. Molecular analysis of the fluid for HPV-DNA should also be considered as HPV has been reported to be present in 87% of cystic metastases [5]. As previously mentioned, most of these patients will already have had radiological imaging by CT and MRI, and imaging should be reviewed at the Head and Neck Multidisciplinary meeting with the aim of identifying possible or likely primary malignant tumour source for a cystic metastases. The CT and MRI appearances of a branchial cleft cyst are variable depending on the protein content of the cyst and whether it has been infected or not [15,38 ]. Diagnosis of a possible malignancy of a cystic lesion is determined by the finding of atypical features such as the presence of internal vascularization, intracystic solid components or irregular outer wall [47 ]. The use of PET has been used in the work-up for head and neck carcinoma of unknown primary. However, in adults with suspicious cystic neck masses, the primary tumour may be very small and both false-negative and false-positive PET results have been observed. Therefore, combined PET–CT may not add to the diagnostic power of traditional methods of imaging and these plus head and neck examination in these patients may be the preferred investigations of choice [48,49,50 ]. Most authors would recommend it is essential to perform a panendoscopy of the upper aerodigestive tract in this group of patients and this may reveal a primary tumour. In the case of a node metastasis of a squamous cell carcinoma, 72–90% of the primary tumours when detected are located in Waldeyer’s ring (base of tongue, palatine tonsils and nasopharynx) [20,21,26]. Other possible sites are the larynx, the hard palate, thyroid gland, salivary glands and sinuses, but reported cases are rare [26,45]. Because cystic metastasis are most frequently identified in the ipsilateral tonsil, tonsillectomy with multilevel biopsies of the base of tongue as well as the nasopharynx is indicated [21,26,51]. &
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Ultimately, an excision of the neck mass, as a single mass or as a selective neck dissection, with histopathologic examination may be the only means that remains by which to establish the true accurate histologic type of the tumour, although its source in case of a metastasis may remain uncertain [1,6,48,51].
CONCLUSION The existence of BCCC is real but remains exceptional. It is recommended that the term BCCC should not be used in the differential diagnosis of a cystic metastasis of squamous cell carcinoma. By doing so will ensure that the risks of a less than thorough investigation, inadequate therapeutic management or a too brief follow-up are brought to a minimum. All cystic neck lesions in an adult patient should be presumed to be cancer until proven otherwise. Acknowledgements None. Conflicts of interest Both authors (P.J.B. and P.T.B.) declare that they have no conflict of interest in the production or preparation of this manuscript. Both authors (P.J.B. and P.T.B.) declare that they had not received any funding or honoraria from any organizations in the preparation of this manuscript
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 000–000). 1. Jereczek-Fossa B, Casadio C, Jassem J, et al. Branchiogenic carcinoma: conceptual or true clinic-pathologic entity? Cancer Treatment Rev 2005; 31:106–114. 2. Richard J, Micheau C. Malignant cervical adenopathies from carcinoma of unknown origin. Tumori 1977; 63:249–258. 3. Micheau C, Cachin Y, Caillou B. Cystic metastases in the neck revealing occult carcinoma of the tonsil. Cancer 1974; 33:228–233. 4. Micheau C, Klijanienko J, Luboinski B, Richard J. So-called branchiogenic carcinoma is actually cystic metastasis in the neck from tonsillar primary. Laryngoscope 1990; 100:878–883. 5. Goldenberg D, Sciubba J, Koch WM. Cystic metastasis from head and neck squamous cell cancer: a distinct disease variant? Head Neck 2006; 28:633– 638. 6. Mallet Y, Lallemant B, Robin YM, Lefebvre JL. Cystic lymph node metastases of head and neck squamous cell carcinoma: pitfalls and controversies. Oral Oncol 2005; 41:429–434. 7. Devaney KO, Rinaldo A, Ferlito A, et al. Squamous carcinoma arising in a branchial cleft cyst: have you ever treated on? Will you? J Laryngol Otol 2008; 122:547–550. 8. Briggs RD, Pou AM, Schnadig VJ. Cystic metastasis versus branchial cleft carcinoma: a diagnostic challenge. Laryngoscope 2002; 112:1010–1014. 9. Maturo SC, Michaelson PG, Faulkner JA. Primary branchiogenic carcinoma: the confusion continues. Am J Otolaryngol 2007; 28:25–27. 10. Singh B, Balwally AN, Sundaram K, et al. Branchial cleft cyst carcinoma: myth or reality? Ann Otol Rhinol Laryngol 1998; 107:519–524.
11. Park SS, Karmody CS. The first branchial cleft carcinoma. Arch Otolaryngol Head Neck Surg 1992; 118:969–971. 12. Roche J, Younes MN, Funkhouser WK, Weissler MC. Branchiogenic carcinoma of a first branchial cleft cyst. Otolaryngol Head Neck Surg 2010; 143:167–168. 13. Alvi A, Johnson JT. The neck mass. A challenging differential diagnosis. Postgrad Med 1995; 97:87–97. 14. Papadogeorgakis N, Petsinis V, Parara E, et al. Branchial cleft cysts in adults; diagnostic procedures and treatment in a series of 18 patients. Oral Maxillofac Surg 2009; 13:79–85. 15. Pietarinen-Runtti P, Apajalahti S, Robinson S, et al. Cystic neck lesions: clinical, radiological and differential diagnostic considerations. Acta Otolaryngol 2010; 130:300–304. 16. Shinkwin C, Robson AK, Whitfield BCS. Branchial cysts: congenital or acquired? Ann R Coll Surg Engl 1991; 73:379–380. 17. Nakagava T, Takashima T, Tomiyama K. Differential diagnosis of a lateral cervical cyst and solitary cystic lymph node metastases of occult thyroid papillary carcinoma. J Laryngol Otol 2001; 115:240–242. 18. Seven H, Gurkan A, Cinar U, et al. Incidence of occult thyroid carcinoma metastases in lateral cervical cysts. Am J Otolaryngol 2004; 25:11–17. 19. Lanzafame S, Caltabiano R, Puzzo L, Cappellani A. Thyroid transcription factor 1 (TTF-1) and p63 expression in two primary thyroid papillary carcinomas of branchial cleft cysts. Virchows Arch 2006; 449:129–133. 20. Gourin CG, Johnson JT. Incidence of unsuspected metastases in lateral cervical cysts. Laryngoscope 2000; 110:1637–1641. 21. Regauer S, Mannweiller S, Anderhuber W, et al. Cystic lymph node metastases of squamous cell carcinoma of Waldeyer’s ring origin. Br J Cancer 1999; 79:1437–1442. 22. Verma K, Mandal S, Kapila K. Cystic change in lymph nodes with metastatic squamous cell carcinoma. Acta Cytol 1995; 39:478–480. 23. Gildenberg D, Begum S, Westra WH, et al. Cystic lymph node metastasis in patients with head and neck cancer: an HPV-associated phenomenon. Head Neck 2008; 30:898–903. 24. McHugh JB. Association of cystic neck metastases and human papillomavirus: positive oropharyngeal squamous cell carcinoma. Arch Pathol Lab Med 2009; 133:1798–1803. 25. Mokhtari S. Mechanisms of cyst formation in metastatic lymph nodes of head and neck squamous cell carcinoma. Diagn Path 2012; 7:6. 26. Thompson DR, Heffner DK. The clinical importance of cystic squamous cell carcinoma in the neck. Cancer 1998; 82:944–956. 27. Hunczowski JN. Branchiogenic or branchial fistulae. Am Med 1789; 41:324. 28. Von Ascherson FM. De fistulis colli congenitis adjecta fissurarum branchialium in mammalibus avibusque historia succincta. Bertolini: Apud C.H. Jonas; 1832. 29. His W. Ueber der sinus praecervicalis und uber die thymusanlage. Arch Anat Entwickelungsgesch 1886; 9:421–433. 30. Wenglowski R. Ueber die Halsfisteln und Cysten. Langenbeck. Arch Klin Chir 1912; 98:151. 31. King E. The lateral lympho-epithelial cyst of the neck (‘branchial cyst’). Aust N Z J Surg 1949; 21:109–121. 32. Bhasker S, Bernier J. Histogenesis of branchial cysts; a report of 468 cases. Ann J Pathol 1959; 35:407–414. 33. Maran AGD, Buchanan DR. Branchial cysts, sinuses and fistulae. Clin Otolaryngol 1978; 3:77–92. 34. Howie AJ, Proops DW. The definition of branchial cysts, sinuses and fistulae. Clin Otolaryngol 1982; 7:51–57. 35. Acierno SP, Waldhausen JHT. Congenital cervical cysts, sinuses and fistulae. Otolaryngol Clin North Am 2007; 40:161–176. 36. Schhroder JW, Mohyuddin N, Maddalozzo J. Branchial anomalies in the paediatric population. Otolaryngol Head Neck Surg 2007; 137:289–296. 37. Doshi J, Anari S. Branchial cyst side predilection: fact or fiction? Ann Otol Rhinol Laryngol 2007; 116:112–114. 38. Guldfred L-A, Philipsen BB, Siim C. Branchial cleft anomalies: accuracy of & preoperative diagnosis, clinical presentation and management. J Laryngol Otol 2012; 126:598–604. A retrospective review of the accuracy of preoperative diagnosis of branchial cleft anomalies and reported a positive predictive value of 86%. They emphasize that cystic lesions in the neck in adults should be presumed to be cancer until proven otherwise. 39. Martin H, Morfit HM, Ehrlich H. The case for branchiogenic cancer. Ann Surg 1950; 132:867–887. 40. Von Volkmann R. Das tiefe branchiogege Halskarcinom. Zentralbl Chir 1882; 9:49–63. 41. Khafif RA, Prichep R, Minkowitz S. Primary branchiogenic carcinoma. Head Neck 1989; 11:153–163. 42. Bernstein A, Scardino PT, Tomaszewski M-M, Cohen MH. Carcinoma arising in a branchial cleft cyst. Cancer 1976; 37:2417–2422. 43. Ohri A, Makins R, Smith S, et al. Primary branchial cleft carcinoma. J Laryngol Otol 1997; 111:80–82. 44. Nordemar S, Tani E, Hogmo A, et al. Image cytometry DNA-analysis of fine needle aspiration cytology to aid cytomorphology in the distinction of branchial cleft cyst from cystic metastasis of squamous cell carcinoma: a prospective study. Laryngoscope 2004; 114:1997–2000. 45. Flanagan PM, Roland NJ, Jones AS. Cervical nodal metastasis presenting with features of branchial cysts. J Laryngol Otol 1994; 108:1069–1071.
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Head and neck oncology 46. Rees G. Role of fine needle aspiration cytology in the preoperative investigation of branchial cysts [Letter]. ANZ J Surg 2012; 82:476–477. A short response to an article on FNAC and branchial cysts and the need for a cautious approach when dealing with adult patients. 47. Goyal N, Zacharia TT, Goldenberg D. Differentiation of branchial cleft cysts && and malignant cystic adenopathy of pharyngeal origin. Am J Radiol 2012; 199:W216–W221. This study emphasizes that using CT scanning in the evaluation of an adult cystic neck mass, there is a need to differentiate between a congenital or secondary to inflammation or infection. Some additional criteria can be considered when making that judgment such as the presence of absence of septations, the presence or absence of extracapsular spread and the presence or absence of homogeneity within the cyst. Recognition of imaging overlap must be done, hence the need for a high index of suspicion of malignancy with the additional use of other diagnostic modalities. &
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48. Ferris RL, Branstetter BF, Nayak JV. Diagnostic utility of positron emission tomography–computed tomography for predicting malignancy in cystic neck masses in adults. Laryngoscope 2005; 115:1979– 1982. 49. Hudgins PA, Gillison M. Editorial: Second branchial cleft cyst: NOT! Am J Neuroradiol 2009; 30:1628–1629. 50. Corey AS, Hudgins PA. Radiographic imaging of human papillomavirus & related carcinomas of the oropharynx. Head Neck Pathol 2012; 6 (Suppl. 1): S25–S40. A review emphasizing that with imaging techniques HPV plus SCC (squamous cell carcinoma) may be misdiagnosed as a second branchial cleft carcinoma. 51. Bath AP, Murty GE, Bradley PJ. Branchial cyst: to endoscope or not? J Laryngol Otol 1991; 106:1006–1007.
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