SUMMARY
Adenoid cystic carcinoma (ACC) is a relatively rare tumour of the minor and major salivary glands. It is uncommon in the parotid gland while it is much more frequent in the submandibular gland and in minor salivary and mucinous glands (oral cavity, oropharynx, and paranasal sinuses). ACC may also arise in secretory glands located in other tissues, such as in the tracheobronchial tree, oesophagus, breast, lungs, prostate, uterine cervix, lachrymal and Bartholin’s glands, and skin. The natural history of ACC is characterised by an indolent growth rate, a relatively low probability of regional lymph node metastases and a high likelihood of haematogenous dissemination. ACC has been traditionally subdivided into three histological groups (cribriform, tubular, and solid) based on solid components of the tumour. Some studies have shown that tumours with a solid growth component have a rapid fatal course, compared to tumours without a solid growth component, but other studies have failed to correlate growth patterns with clinical course. The purpose of this review is to analyse the very large number of studies (sometimes contradictory) on ACC. In this first part, the aetiology, epidemiology, histopathology, clinical behaviour and diagnostic workup are examined.
KEY WORDS: adenoid cystic carcinoma, salivary gland tumours, head and neck cancer, prognostic factors
RIASSUNTO
Il carcinoma adenoide cistico (ACC) è un tumore relativamente raro ad origine dalle ghiandole salivari minori e maggiori. È poco frequente nella parotide mentre lo è molto di più nella ghiandola sottomandibolare, nelle ghiandole salivari minori e in quelle mucinose del cavo orale, orofaringe e seni paranasali. Esso può anche insorgere nelle ghiandole secretrici localizzate in altri tessuti come l’albero tracheo-bronchiale, l’esofago, la mammella, il polmone, la prostata, la cervice uterina, la cute, le ghiandole lacrimali e quelle del Bartolini. La sua storia naturale è caratterizzata da una lenta crescita, da rare metastasi linfonodali e da frequenti metastasi a distanza. Dal punto di vista istologico esso è stato tradizionalmente suddiviso in tre forme (cribriforme, tubulare e solido). Alcuni studi hanno dimostrato che i tumori con una prevalente componente solida hanno una prognosi peggiore rispetto a quelli con prevalente componente cribriforme o tubulare ma altri studi hanno contestato questa affermazione. Il proposito di questa review è quello di analizzare il grande numero di pubblicazioni (talvolta contraddittorie) sul carcinoma adenoide cistico. In questa prima parte saranno discusse l’eziologia, l’epidemiologia, l’istopatologia, la presentazione clinica e l’iter diagnostico.
PAROLE CHIAVE: carcinoma adenoide cistico, tumori ghiandole salivari, carcinoma testa e collo, fattori prognostici
Introduction
Adenoid cystic carcinoma (ACC) represents 3-5% of head and neck malignancies 1 and 5-15% of sinonasal malignancies. It is characterised by an indolent but aggressive clinical course, the presence of early perineural invasion, frequent local recurrence and a high rate of delayed distant metastasis. This tumour was pointed out as a specific entity in the middle 19th century. Stell PM, in a fascinating “History of surgery of the upper jaw” 2, wrote: “It is often said that adenoid cystic carcinoma was first described by Billroth in 1859 by the term Zylindrome. This is untrue: the tumour was first described by two Frenchmen, Robin & Laboulbene, as “tumeur heteradenique”, in 1853”. However, the histopathologic term for ACC was “cylindroma” for many years, based on the histologic appearance of cylinders of epithelial/secretory cells and a hyaline stroma. Spiro and Huvos 3 wrote that only in 1953 Foot and Frazell 4 classified the tumour as an adenocarcinoma, coining the term “adenoid cystic carcinoma”. The aim of the first part of this review is to provide an update on the current understanding of aetiology, epidemiology, clinical behaviour, pathology, molecular biology and diagnostic work up of ACC. Treatment and prognosis will be analysed in the second part.
Aetiology
Few studies to date have examined the possible aetiologic factors conclusively associated with the development of salivary gland cancers. Some factors have been implicated as potential causes for these malignancies, especially exposure to ionising radiation (atomic bomb survivors 5 and patients treated with radiotherapy for a previous tumour 6, especially childhood cancer). Three population-based case-control studies reported elevated odds ratios among agricultural 7, nickel and rubber 8 workers, women employed as hairdressers and those working in beauty shops 9. Horn-Ross et al. 10 made a population-based case-control study and found that vitamin C intake of > 200 mg/day compared with ≤ 100 mg/day was associated with a 60% decrease in salivary gland cancer risk, and intake of fibres from bean sources > 1.4 g/day was associated with a 51% decrease in risk.
With regards to previous tumours, Spitz et al. 7, found that the most common site for previous malignancy among their patients with salivary gland cancer was the skin (odds ratio 11.41). However, the authors specified that many of their patients with previous skin cancer underwent radiotherapy. Falchook et al. 11 evaluated the incidence of salivary gland cancer among patients with a history of cancer, and explored the potential significance of index breast cancer on the subsequent risk of salivary gland malignancy. They found that in patients with a previous cancer diagnosis, the risk of subsequent salivary gland malignant tumour was greater in women than men. However, women with previous breast cancer were not more likely to develop salivary gland cancer than women with other previous malignancies. On the contrary, analysis of different cancer registries has shown that women diagnosed with breast cancer have an increased incidence of subsequent salivary gland cancer 12. However, the analysis of the possible aetiologic factors associated with ACC is complicated by the fact that some epidemiologic studies report salivary gland cancers without subdivision according to histologic type 9.
Although smoking and alcohol drinking are two well-known strong carcinogens in many tumours, few studies have examined the effect of these factors on the risk of ACC. In a case-control study, Sawabe et al. 13 investigated the association between smoking and major salivary gland cancers and found that smoking was associated with a significantly increased risk of salivary gland tumours overall, especially in heavy smokers compared with never-smokers. When stratified by histological subtype, no impact of smoking was observed among patients with mucoepidermoid carcinoma (MEC). In contrast, smoking demonstrated a significantly increased risk of cancers other than MEC, specifically for adenocarcinoma. Although not significant, the odds ratios for smoking among patients with ACC were above unity. The authors also pointed out 7 previous studies on the same topic, with 4 indicating a positive association 8,9,14,16 and 3 demonstrating no appreciable association 7,15,17. The question is even more doubtful because some studies, analysing the association between smoking and tracheobronchial ACC, did not find any association, even though these anatomical sites are surely more exposed to the possible carcinogenic action of smoke than the major salivary glands 18,19. With regard to alcohol consumption, an association with major salivary glands ACC was not found 7,13. Miller et al. 20 investigated the possible association of human papilloma virus (HPV) in sinonasal ACC and found that it is rare (11%).
Aetiology.
Exposure to ionising radiation (atomic bomb survivors and patients treated with radiotherapy for a previous tumour, especially skin and childhood cancers).
Low vitamin C intake.
Women diagnosed with breast cancer have increased incidence of subsequent salivary gland cancer.
In a case-control study, although not significant, the odds ratios for smoking among patients with ACC were above unity.
An association between alcohol consumption and major salivary glands ACC was not found.
The association of human papilloma virus (HPV) in sinonasal ACC is rare (11%).
Epidemiology
ACC arises mainly from the minor salivary glands and the submandibular gland, whereas it is uncommon in the parotid. The sites of origin in the head and neck are the tongue, paranasal sinuses, palate, nasopharynx, larynx, lacrimal glands and external auditory canal. ACC may also arise in secretory glands located in other tissues, such as in the tracheobronchial tree, oesophagus, breast, lungs, prostate, uterine cervix, Bartholin’s glands and skin. In an historical study, Ranger et al. 21 wrote that the hard and soft palate are the most involved sites in the oral cavity and that there are about 400 glands distributed over the hard and soft palates and the uvula.
Owing to the rarity of these tumours, there is little data on whether specific ethnic, geographic, or other factors predispose to development of the disease 22. Concerning the distribution of ACC across the sites, there is no great difference between USA 23 and Europe 24, while there is an important difference in comparison with a Chinese study 25, especially for oral cavity (30% vs 7.5%), major salivary glands (46% vs 22%), nasal cavity and paranasal sinuses (10% vs 30%), and lung and bronchus (4% vs 24%). Mu 25 also reported a difference between an American cohort of 1,285 patients extracted from the Surveillance, Epidemiology and End Results (SEER) database and the Chinese cohort for age < 60 years (53.7% vs 75.4%). In the study by Li et al. 23, patients with ACC of the eye and orbit were significantly younger at presentation than patients with ACC of the major salivary glands, while patients with tumours of the female genital system, skin and breast were significantly older. For all sites, except the lung and bronchus, more females than males were affected. The proportion of African Americans was significantly higher among patients with ACC of the female genital system or eye and orbit than among patients with ACC of major salivary glands. In the study by Spitz et al. 7, the ethnic distribution of patients was white non-Hispanic 86%, black 9.4% and Hispanic 4.6%.
Salivary gland carcinomas are rare in children and adolescents and few large series have been published. In a series of 29 paediatric cases 26 there were: 22 low-grade MEC, 4 acinic cell cancers, 1 ACC, 1 adenocarcinoma not otherwise specified and 1 sialoblastoma. In another series of 57 patients aged 20 years or younger 27, the histologic types of the 38 carcinomas were MEC 19, acinic cell carcinoma 7, ACC 6, secretory carcinoma (mammary analogue) 4 and myoepithelial carcinoma 2. Moreover, it is possible to find in the literature some case reports of unusual locations of ACC in childhood: an 8-year-old girl with ACC of the external auditory canal 28, a 15-year-old boy with ACC of the larynx 29 and a 12-year-boy with ACC of the pyriform sinus 30.
Epidemiology.
ACC arises mainly from the minor salivary glands of the head and neck (tongue, paranasal sinuses, palate, nasopharynx, larynx, lacrimal glands, and external auditory canal). It is common in the submandibular gland, whereas it is uncommon in the parotid.
ACC may also arise in secretory glands located in other tissues, such as in the tracheobronchial tree, oesophagus, breast, lungs, prostate, uterine cervix, Bartholin’s glands and skin.
For all sites, except lung and bronchus, more females than males are affected by ACC. It is very rare in children and adolescents.
Histopathology
Salivary gland malignancies represent one of the most complex group of tumours from a pathological point of view. According to the World Health Organization (WHO) classifications (2005) 31, 24 malignant histotypes are recognised, almost all characterised by specific morphological and genetic features as well as by particular clinical behaviour. The last WHO classification (2017) 32 counts 23 malignant histotypes, No other site in the head and neck has such a large variety of malignant tumours. This variety as well as the rarity of some of them needs a skilled pathologist for diagnosis. Although ACC is one of the most common carcinomas of the salivary gland, in many pathology departments it is relatively uncommon, making it difficult for general pathologists to gain expertise in the field. Thus, the pathological diagnosis of ACC remains a challenge, especially in problematic cases. A study from 15 reference hospitals in Japan 33 demonstrated that, after a central pathology review, the original diagnosis of ACC was changed to non-ACC in 21/219 cases (9.6%). Moreover, 6 cases (2.7%) were re-diagnosed as benign tumours; 3 of these patients had undergone useless postoperative radiotherapy.
Both WHO classifications define ACC as a tumour that manifests a variety of tubular and cribriform structures with variably solid components. ACC has been traditionally subdivided into 3 histological groups (cribriform, tubular, and solid) based on solid components of the tumour 34. Some studies have demonstrated that tumours with a solid growth component have a rapid fatal course, compared to tumours without a solid growth component 34, but other studies have failed to correlate growth patterns with clinical course 3. Moreover, no universally accepted grading system exists and no reproducibility studies of the existing grading systems have been performed. In fact, Therkildsen et al. examined the reproducibility of grading based on semi-quantitative assessment of the solid growth pattern in ACC. Two different grading systems were assessed by 3 observers on 59 ACC. Interobserver agreement was poor, except for the category “solid component constituting 50% or more of the tumour” 35.
In spite of its rarity, several studies have analysed molecular pathogenesis, genetic mutations and protein overexpression in ACC of the head and neck 22,36,37. Recent whole genome and exome sequencing has dramatically improved our understanding of ACC pathogenesis. A balanced translocation resulting in the MYB-NFIB fusion gene appears to be a fundamental signature of ACC. In addition, sequencing has identified a number of other driver genes mutated in downstream pathways common to other well-studied cancers 36. A study on 12 ACCs of the breast 38, demonstrated that the mutational burden and mutational repertoire of breast ACCs are more similar to those of salivary gland ACCs than to other types of breast cancer.
Histopathology.
ACC is one of the most common carcinomas of the salivary gland, among 23 histotypes.
Pathological diagnosis of ACC remains a challenge, especially in problematic cases.
ACC has been traditionally subdivided into 3 histological groups (cribriform, tubular, and solid) based on solid components of the tumour, although no universally accepted grading system exists and no reproducibility studies of the existing grading systems have been performed.
In spite of its rarity, several studies have analysed molecular pathogenesis, genetic mutations and protein overexpression in ACC of the head and neck.
Clinical behaviour
ACC is uncommon in the parotid gland. Its incidence in the historical large series presented by Eneroth (802 cases) 39 and by Foote and Franzell (776 cases) 4 lies between 2% and 5% of all tumours and between 6% and 15% of all malignancies. On the contrary, ACC is much more frequent in the submandibular gland. In 2 series studied by Spiro et al. 40 and by Eneroth et al. 41 the incidence of ACC was 42/121(35%) and 25/62 (40%), respectively. It is difficult to define the incidence of ACC arising in the mucosal glands because of the heterogeneity of the series presented in many studied (major and minor salivary gland together). In an historic and weighty article, Osborn 42 gathered the data from 21 major and minor series with a total of 1,712 mucosal gland malignant tumours of all types, of which 557 (32.5 %) were ACC. Osborn introduced the expression “cribriform adenocarcinoma, as being more appropriate to its origin, morphology, and behaviour”.
The signs and symptoms of ACC at presentation are not specific and depend on the anatomic site of involvement. Typically, a parotid ACC in the superficial lobe presents as a pre-auricular swelling, commonly less mobile than a pleomorphic adenoma because, even when it is circumscribed, it is unencapsulated. Deep lobe tumours are comparatively rare, given that the deep lobe accounts for only 10% to 20% of parotid tissue, and ACC is even more rare. In a study by Cohen et al. 43, among 166 parapharyngeal space masses only 45 (27.1%) were of salivary gland origin and only one was an ACC. Deep lobe tumours often present as an asymptomatic submucosal swelling of the lateral oropharyngeal wall and/or soft palate. Tumours presenting in the paranasal sinuses are associated with mild pain and pre-maxillary or palatal submucosal swelling with the overlying mucosa fixed to the tumour. The duration of these symptoms may range from months to several years. The slow growth and the absence or paucity of symptoms often result in delayed diagnosis and many patients present with advanced disease.
Mainly for ACC, the late and soft symptoms may be a mild pain and paraesthesia, because “one of the most outstanding feature of this neoplasm, regardless of its site of origin, is its marked tendency to invade nerves. In our own surgical experience, invasion of the nerves is an almost constant microscopic finding. Although extension of neoplasm through nerves is not peculiar to the adenoid cystic carcinoma, this neoplasm certainly manifests this morbid finding more often than other epithelial neoplasms in the head and neck” 44. Osborn 42 wrote that this well-known characteristic feature of ACC was reported since 1934. The involved nerves may be the facial nerve for parotid tumours and the lingual nerve for submandibular location. For tumours in the paranasal sinuses or oral cavity, perineural spread is usually along the second and/or third branch of the trigeminal nerve. The foramens ovale and rotundum may be involved with extension of the tumour to the Gasserian ganglion 44.
It is difficult to establish the real incidence of regional lymph node metastases from ACC because of the heterogeneity of the series presented in many studied (different sites of origin and all histologic types together). Regarding the parotid, Xiao et al. 45 performed a thorough study on a series of 22,653 patients with parotid malignancy from the National Cancer Data Base (NCDB). Patients were considered to have positive nodal disease if there was at least one positive lymph node confirmed by biopsy or neck dissection as part of diagnosis or treatment or if they had clinical evidence of nodal disease during follow-up. The authors divided histologic types in low and high grade according to Seethala 46. For ACC (2,045 cases, 9% of the series), the incidence of nodal metastases was 14.2% at presentation and 7% during follow-up (occult nodal disease). Interestingly, while for MEC, acinar cell carcinoma, salivary ductal carcinoma and adenocarcinoma not otherwise specified there was a great difference in the incidence of occult nodal disease between high and low grade, for ACC this difference was small (9.6% vs 6.3%). Regarding the paranasal sinuses, it is even more difficult to draw reliable data from the literature. Amit et al. 47 reviewed 16 relevant articles, of which 13 presented very small series (≤ 35 cases). The remaining 3 studies presented 64, 99 and 105 cases. Moreover, all studies included patients with tumours of both sinuses and the nasal cavity, and one study presented ACCs of the nasopharynx. The rate of node metastases at presentation ranged between 2% and 13%. To the best of my knowledge, the only study dealing with tumours of the only paranasal sinuses and their regional metastases is that by Cantù et al. 48. Among as many as 704 malignancies of the paranasal sinuses there were 115 ACCs (91in the maxillary sinus and 24 in the ethmoid sinus). Only 2 patients presented with node metastases, and only 3 patients developed regional metastases during follow-up, together with a relapse of the primary tumour.
ACC is generally recognised for its frequent and often silent distant metastases. They are rare at presentation, but at 10 years account for approximately 30% to 40%. The commonest sites are lung, bone, liver and brain.
Clinical behaviour.
The incidence of ACC in the parotid gland is between 2% and 5% of all tumours and between 6 and 15% of all malignancies. It is much more frequent in the submandibular gland (35%-40%). In a large study on mucosal gland malignant tumours of all types, 32% were ACC.
Typically, a parotid ACC in the superficial lobe presents as a pre-auricular swelling, commonly less mobile than a pleomorphic adenoma. Deep lobe tumours often present as an asymptomatic submucosal swelling of the lateral oropharyngeal wall and/or soft palate. ACC of the submandibular gland presents as a swelling in the submandibular region.
Those tumours located in the paranasal sinuses present as a pre-maxillary or palatal submucosal swelling with the overlying mucosa fixed to the tumour.
One of the most outstanding feature of ACC, regardless of its site of origin, is its marked tendency to invade nerves. The involved nerves may be the facial nerve for parotid tumours and the lingual nerve for submandibular location. For tumours in the paranasal sinuses or oral cavity, perineural spread is usually along the second and/or third branch of the trigeminal nerve. The foramens ovale and rotundum may be involved with extension of the tumour to the Gasserian ganglion. Hence, the late and soft symptoms may be a mild pain and paresthesia and the duration of these symptoms may range from months to several years.
Regional lymph node metastases from ACC of the parotid gland are rare (14.2% at presentation and 7% during follow up). The rate of node metastases from ACC of the paranasal sinuses at presentation ranged between 2% and 13%.
ACC is generally recognised for its frequent and often silent distant metastases. They are rare at presentation, but at 10 years they account for approximately 30% to 40%. The commonest sites are lung, bone, liver and brain.
Diagnostic workup
In front of a parotid or submandibular gland swelling, after an anamnesis about the time of onset and speed of growth, accurate physical examination may help to distinguish an inflammatory disease from a tumour. It is advisable to look for possible skin scars on the scalp, face and external ear, as a result of resection of previous skin carcinoma or melanoma. Local pain at light palpation may be the symptom of an ACC, even in the absence of more advanced clinical indicators of malignancy (fixity to surrounding structures, nerves weakness or paralysis, presence of neck nodes). An ACC that develops in the minor salivary glands of the oral cavity almost always present as an asymptomatic submucosal mass, most commonly on the palate.
One must be careful of possible transformation into ACC of a recurrent pleomorphic adenoma after prior surgical resection. Among 106 patients with recurrent pleomorphic adenoma of the parotid gland, Yin et al. 49 found 13 (12.3%) patients with carcinoma, of which only 4/13 (31%) had clinical features suspicious for malignancy. Toluie et al. 50 analysed 89 cases of sinonasal ACC from the files of the Tumor Registry of the Armed Forces Institute of Pathology (AFIP) and found 9 cases with the presence of an antecedent or contemporaneous pleomorphic adenoma.
Imaging
Radiological imaging is not mandatory for small, mobile and superficial parotid tumours. Ultrasound (US) examination with colour Doppler imaging has gained widespread acceptance as an economic, safe and useful method to detect and assess parotid gland masses. However, its diagnostic accuracy in distinguishing malignant from benign tumours does not reach a satisfactory diagnostic level 51. Elastography is a relatively new way of tissue imaging associated with US. Some studies have found that malignant tumours are generally stiffer than benign ones. Shear wave elastography (SWE) is a novel elastographic method that offers the advantage of quantitative measurements and lower operator-dependence. It is well established in breast and thyroid gland lesions, but the results of elastography in salivary gland lesions have been rather poor so far 52. Imaging with either CT or MRI is mandatory when there is the clinical suspicion of malignancy or when the lesion is thought to extend into or to arise from the deep lobe of the parotid gland or the parapharyngeal space. US examination or CT-MRI must be extended at least to the upper levels of the neck. MRI and/or CT is mandatory for sinonasal ACC and must be extended to the skull base. The patient must also undergo a chest CT.
Fine-needle aspiration biopsy (FNAC) and ultrasound-guided core biopsy (USCB)
Studies on aspiration biopsy with large needles were performed as early as the 1930s 44, but the technique has not been accepted by most head and neck surgeons for the possible risk of tumour dissemination or implantation. A series of Scandinavian studies on patients with long follow-up after aspiration biopsy and surgical removal of the tumour demonstrated no local recurrence 53,54. Nowadays, FNAC has become a commonly performed diagnostic test in the initial evaluation of a major salivary glands mass. The advantage of this technique is that it can be performed in the outpatient setting with a low risk of complications. A potential disadvantage is that it has been associated with variable sensitivity and specificity in distinguishing malignant from benign disease and with variable rates of non-diagnostic and indeterminate cytology 55-57. Liu et al. 58 analysed 70 studies with as many as 6,784 FNAC. Among these, there were 518 non-diagnostic and 385 indeterminate results, constituting 13.3% of FNAC performed. The authors concluded that FNAC of the parotid gland has moderate sensitivity and high specificity in differentiating malignant from benign disease. However, FNAC has a low diagnostic potential for tumour typing and grading. Lindberg et al. 59 and Zbaren et al. 60 found that the exact correlation between primary cytological reports and final histological diagnoses was about 63% and 71%, respectively. Frable et al. 61 analysed several series of FNAC of salivary gland malignant tumours and found that the percentage of correct diagnosis for ACC was 66%.
More recently, USCB has been increasingly used in preoperative workup of salivary glands . It is performed under ultrasound guidance after local anaesthesia with a 20-17 gauge needle 62. Naturally, USCB obtains a larger sample size for analysis than FNAC, which lowers the rate of sample inadequacy. However, the use of large bore needles in core biopsies has been associated with tumour seeding along the needle tract in some reports 63. Moreover, USCB is more expensive and time-consuming than FNA. FNA combined with ultrasound imaging should continue to be the investigation method of first choice for salivary gland lesions, reserving USCB for those cases in which surgery is not suitable or after repeated failures of FNA to provide an adequate diagnosis 64. Finally, Schmidt et al. 65 conducted a systematic review of diagnostic test accuracy of 95 studies on needle biopsy (FNAC and USCB) of salivary gland lesions. They concluded that such studies overestimate the sensitivity and underestimate the specificity of FNAC. Moreover, studies on USCB had a lower rate of verification bias than FNAC studies and may have overestimated the advantage in diagnostic accuracy of USCB relative to FNA.
Diagnostic work-up.
Physical examination
In front of a parotid or submandibular gland swelling, after an anamnesis about the time of its onset and the speed of growing, an accurate physical examination may help to distinguish an inflammatory disease from a tumour. It is advisable to look for possible skin scars on the scalp, face and external ear, as result of resection of previous skin carcinoma or melanoma. Local pain at light palpation may be the symptom of an ACC, even in the absence of more advanced clinical indicators of malignancy. An ACC that develops in the minor salivary glands of the oral cavity almost always present as an asymptomatic submucosal mass, most commonly on the palate.
Imaging
Radiological imaging is not mandatory for small, mobile, and superficial parotid tumours. Ultrasound (US) examination with colour Doppler imaging is an economic, safe and useful method to detect and assess parotid gland masses. However, its diagnostic accuracy in distinguishing malignant from benign tumours does not reach a satisfactory diagnostic level.
Elastography is a relatively new way of tissue imaging associated with US. Some studies have found that malignant tumours are generally stiffer than benign ones.
Imaging with either CT or MRI is mandatory when there is the clinical suspect of malignancy or when the lesion is felt to extend into or to arise from the deep lobe of the parotid gland or the parapharyngeal space. US examination or CT-MRI must be extended at least to the upper levels of the neck. MRI and/or CT are mandatory for sinonasal ACC and must be extended to the skull base. The patient must also undergo a chest CT.
Fine-needle aspiration biopsy (FNAC) and ultrasound-guided core biopsy (USCB)
FNAC has become a commonly performed diagnostic test in the initial evaluation of a major salivary glands mass. The advantage of this technique is that it can be performed in the outpatient setting with low risk of complications. A potential disadvantage is that it has been associated with variable sensitivity and specificity in distinguishing malignant from benign disease and with variable rates of non-diagnostic and indeterminate cytology. FNAC has a low diagnostic potential for tumour typing and grading. The exact correlation between the primary cytological reports and the final histological diagnoses is about 63% and 71% respectively.
USCB obtains a larger sample size for analysis than FNAC, which lowers the rate of sample inadequacy. However, the use of large bore needles in core biopsies has been associated with tumour seeding along the needle tract in some reports.
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