10.14639/0392-100X-N1379
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.
text/xml
1827-675X
1379
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Giulio Cantù
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ACTA Otorhinolaryngologica Italica
prognostic factors
Adenoid cystic carcinoma. An indolent but aggressive tumour. Part A: from aetiopathogenesis to diagnosis
Text.Serial.Journal
https://www.actaitalica.it/
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Reviews
2021-07-07
2021-01-12
2021-07-08
2021-07-08
206-214
1
Giulio Cantù
2021/07/07
10.14639/0392-100X-N1379
206
Former Director of Otorhinolaryngology and Cranio-Maxillo-Facial Unit, Fondazione I.R.C.C.S. Istituto Nazionale dei Tumori, Milan, Italy
1827-675X
prognostic factors
214
Adenoid cystic carcinoma. An indolent but aggressive tumour. Part A: from aetiopathogenesis to diagnosis
https://www.actaitalica.it/article/download/1379/618
41
ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41:206-214; doi: 10.14639/0392-100X-N1379




Review


Adenoid cystic carcinoma. An indolent but aggressive
tumour. Part A: from aetiopathogenesis to diagnosis
Carcinoma adenoide cistico. Un tumore indolente ma aggressivo.
Parte A: dalla eziopatogenesi alla diagnosi
Giulio Cantù
Former Director of Otorhinolaryngology and Cranio-Maxillo-Facial Unit, Fondazione I.R.C.C.S. Istituto Nazionale dei Tumori, Milano, Italy


SUMMARY
Adenoid cystic carcinoma (ACC) is a relatively rare tumour of the minor and major sali-
vary 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 stud-
ies 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.
                                                                                                 Received: January 12, 2021
KEY WORDS: adenoid cystic carcinoma, salivary gland tumours, head and neck cancer,               Accepted: May 3, 2021
prognostic factors
                                                                                                 Correspondence
RIASSUNTO                                                                                        Giulio Cantù
Il carcinoma adenoide cistico (ACC) è un tumore relativamente raro ad origine dalle              via Milano 36, 20846 Macherio (MB), Italy
                                                                                                 E-mail: gcantu43@gmail.com
ghiandole salivari minori e maggiori. È poco frequente nella parotide mentre lo è mol-
to di più nella ghiandola sottomandibolare, nelle ghiandole salivari minori e in quelle
                                                                                                 Funding
mucinose del cavo orale, orofaringe e seni paranasali. Esso può anche insorgere nelle
                                                                                                 None.
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
                                                                                                 Conflict of interest
quelle del Bartolini. La sua storia naturale è caratterizzata da una lenta crescita, da rare     The Author declares no conflict of interest.
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              How to cite this article: Cantù G. Adenoid cyst-
peggiore rispetto a quelli con prevalente componente cribriforme o tubulare ma altri studi         ic carcinoma. An indolent but aggressive tumour.
hanno contestato questa affermazione. Il proposito di questa review è quello di analizzare         Part A: from aetiopathogenesis to diagnosis. Ac-
                                                                                                   ta Otorhinolaryngol Ital 2021;41:206-214. https://
il grande numero di pubblicazioni (talvolta contraddittorie) sul carcinoma adenoide cisti-
                                                                                                   doi.org/10.14639/0392-100X-N1379
co. In questa prima parte saranno discusse l’eziologia, l’epidemiologia, l’istopatologia, la
presentazione clinica e l’iter diagnostico.
                                                                                                 © Società Italiana di Otorinolaringoiatria
PAROLE CHIAVE: carcinoma adenoide cistico, tumori ghiandole salivari, carcinoma                  e Chirurgia Cervico-Facciale
testa e collo, fattori prognostici
                                                                                                                OPEN ACCESS

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Introduction                                                                                     the CC-BY-NC-ND (Creative Commons Attribution-Non-
                                                                                                 Commercial-NoDerivatives 4.0 International) license. The
Adenoid cystic carcinoma (ACC) represents 3-5% of head and neck malignan-                        article can be used by giving appropriate credit and mentio-
                                                                                                 ning the license, but only for non-commercial purposes and
cies 1 and 5-15% of sinonasal malignancies. It is characterised by an indolent                   only in the original version. For further information: https://
but aggressive clinical course, the presence of early perineural invasion, fre-                  creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                                                            Adenoid cystic carcinoma




quent local recurrence and a high rate of delayed distant          cies. On the contrary, analysis of different cancer registries
metastasis. This tumour was pointed out as a specific entity       has shown that women diagnosed with breast cancer have
in the middle 19th century. Stell PM, in a fascinating “Histo-     an increased incidence of subsequent salivary gland can-
ry of surgery of the upper jaw” 2, wrote: “It is often said that   cer 12. However, the analysis of the possible aetiologic fac-
adenoid cystic carcinoma was first described by Billroth in        tors associated with ACC is complicated by the fact that
1859 by the term Zylindrome. This is untrue: the tumour            some epidemiologic studies report salivary gland cancers
was first described by two Frenchmen, Robin & Laboul-              without subdivision according to histologic type 9.
bene, as “tumeur heteradenique”, in 1853”. However, the            Although smoking and alcohol drinking are two well-
histopathologic term for ACC was “cylindroma” for many             known strong carcinogens in many tumours, few stud-
years, based on the histologic appearance of cylinders of          ies have examined the effect of these factors on the risk
epithelial/secretory cells and a hyaline stroma. Spiro and         of ACC. In a case-control study, Sawabe et al. 13 investi-
Huvos 3 wrote that only in 1953 Foot and Frazell 4 clas-           gated the association between smoking and major salivary
sified the tumour as an adenocarcinoma, coining the term           gland cancers and found that smoking was associated with
“adenoid cystic carcinoma”. The aim of the first part of this      a significantly increased risk of salivary gland tumours
review is to provide an update on the current understanding        overall, especially in heavy smokers compared with never-
of aetiology, epidemiology, clinical behaviour, pathology,         smokers. When stratified by histological subtype, no im-
molecular biology and diagnostic work up of ACC. Treat-            pact of smoking was observed among patients with mu-
ment and prognosis will be analysed in the second part.            coepidermoid carcinoma (MEC). In contrast, smoking
                                                                   demonstrated a significantly increased risk of cancers other
Aetiology                                                          than MEC, specifically for adenocarcinoma. Although not
                                                                   significant, the odds ratios for smoking among patients
Few studies to date have examined the possible aetiologic          with ACC were above unity. The authors also pointed out
factors conclusively associated with the development of            7 previous studies on the same topic, with 4 indicating a
salivary gland cancers. Some factors have been implicated          positive association 8,9,14,16 and 3 demonstrating no appreci-
as potential causes for these malignancies, especially ex-         able association 7,15,17. The question is even more doubtful
posure to ionising radiation (atomic bomb survivors 5 and          because some studies, analysing the association between
patients treated with radiotherapy for a previous tumour 6,        smoking and tracheobronchial ACC, did not find any asso-
especially childhood cancer). Three population-based case-         ciation, even though these anatomical sites are surely more
control studies reported elevated odds ratios among agri-          exposed to the possible carcinogenic action of smoke than
cultural 7, nickel and rubber 8 workers, women employed            the major salivary glands 18,19. With regard to alcohol con-
as hairdressers and those working in beauty shops 9. Horn-         sumption, an association with major salivary glands ACC
Ross et al. 10 made a population-based case-control study          was not found 7,13. Miller et al. 20 investigated the possible
and found that vitamin C intake of > 200 mg/day compared           association of human papilloma virus (HPV) in sinonasal
with ≤ 100 mg/day was associated with a 60% decrease in            ACC and found that it is rare (11%).
salivary gland cancer risk, and intake of fibres from bean
sources > 1.4 g/day was associated with a 51% decrease
                                                                     Aetiology
in risk.
With regards to previous tumours, Spitz et al. 7, found that         • Exposure to ionising radiation (atomic bomb survi-
the most common site for previous malignancy among their               vors and patients treated with radiotherapy for a pre-
patients with salivary gland cancer was the skin (odds ratio           vious tumour, especially skin and childhood cancers).
11.41). However, the authors specified that many of their            • Low vitamin C intake.
patients with previous skin cancer underwent radiothera-             • Women diagnosed with breast cancer have increased
py. Falchook et al. 11 evaluated the incidence of salivary             incidence of subsequent salivary gland cancer.
gland cancer among patients with a history of cancer, and            • In a case-control study, although not significant, the
explored the potential significance of index breast cancer             odds ratios for smoking among patients with ACC
on the subsequent risk of salivary gland malignancy. They              were above unity.
found that in patients with a previous cancer diagnosis, the         • An association between alcohol consumption and
risk of subsequent salivary gland malignant tumour was                 major salivary glands ACC was not found.
greater in women than men. However, women with previ-                • The association of human papilloma virus (HPV) in
ous breast cancer were not more likely to develop salivary             sinonasal ACC is rare (11%).
gland cancer than women with other previous malignan-



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G. Cantù




Epidemiology
                                                                    Epidemiology
ACC arises mainly from the minor salivary glands and the
submandibular gland, whereas it is uncommon in the parot-           • ACC arises mainly from the minor salivary glands of
id. The sites of origin in the head and neck are the tongue,          the head and neck (tongue, paranasal sinuses, palate,
paranasal sinuses, palate, nasopharynx, larynx, lacrimal              nasopharynx, larynx, lacrimal glands, and external
glands and external auditory canal. ACC may also arise                auditory canal). It is common in the submandibular
in secretory glands located in other tissues, such as in the          gland, whereas it is uncommon in the parotid.
tracheobronchial tree, oesophagus, breast, lungs, prostate,         • ACC may also arise in secretory glands located in
uterine cervix, Bartholin’s glands and skin. In an historical         other tissues, such as in the tracheobronchial tree,
study, Ranger et al. 21 wrote that the hard and soft palate are       oesophagus, breast, lungs, prostate, uterine cervix,
the most involved sites in the oral cavity and that there are         Bartholin’s glands and skin.
                                                                    • For all sites, except lung and bronchus, more fe-
about 400 glands distributed over the hard and soft palates
                                                                      males than males are affected by ACC. It is very
and the uvula.
                                                                      rare in children and adolescents.
Owing to the rarity of these tumours, there is little data on
whether specific ethnic, geographic, or other factors predis-
pose to development of the disease 22. Concerning the distri-     Histopathology
bution of ACC across the sites, there is no great difference
                                                                  Salivary gland malignancies represent one of the most
between USA 23 and Europe 24, while there is an important
                                                                  complex group of tumours from a pathological point of
difference in comparison with a Chinese study 25, espe-
                                                                  view. According to the World Health Organization (WHO)
cially for oral cavity (30% vs 7.5%), major salivary glands
                                                                  classifications (2005) 31, 24 malignant histotypes are recog-
(46% vs 22%), nasal cavity and paranasal sinuses (10% vs
                                                                  nised, almost all characterised by specific morphological
30%), and lung and bronchus (4% vs 24%). Mu 25 also re-
                                                                  and genetic features as well as by particular clinical be-
ported a difference between an American cohort of 1,285
                                                                  haviour. The last WHO classification (2017) 32 counts 23
patients extracted from the Surveillance, Epidemiology and
                                                                  malignant histotypes, No other site in the head and neck has
End Results (SEER) database and the Chinese cohort for            such a large variety of malignant tumours. This variety as
age < 60 years (53.7% vs 75.4%). In the study by Li et al. 23,    well as the rarity of some of them needs a skilled patholo-
patients with ACC of the eye and orbit were significantly         gist for diagnosis. Although ACC is one of the most com-
younger at presentation than patients with ACC of the major       mon carcinomas of the salivary gland, in many pathology
salivary glands, while patients with tumours of the female        departments it is relatively uncommon, making it difficult
genital system, skin and breast were significantly older. For     for general pathologists to gain expertise in the field. Thus,
all sites, except the lung and bronchus, more females than        the pathological diagnosis of ACC remains a challenge, es-
males were affected. The proportion of African Americans          pecially in problematic cases. A study from 15 reference
was significantly higher among patients with ACC of the           hospitals in Japan 33 demonstrated that, after a central pa-
female genital system or eye and orbit than among patients        thology review, the original diagnosis of ACC was changed
with ACC of major salivary glands. In the study by Spitz          to non-ACC in 21/219 cases (9.6%). Moreover, 6 cases
et al. 7, the ethnic distribution of patients was white non-      (2.7%) were re-diagnosed as benign tumours; 3 of these
Hispanic 86%, black 9.4% and Hispanic 4.6%.                       patients had undergone useless postoperative radiotherapy.
Salivary gland carcinomas are rare in children and adoles-        Both WHO classifications define ACC as a tumour that man-
cents and few large series have been published. In a series       ifests a variety of tubular and cribriform structures with vari-
of 29 paediatric cases 26 there were: 22 low-grade MEC, 4         ably solid components. ACC has been traditionally subdivid-
acinic cell cancers, 1 ACC, 1 adenocarcinoma not otherwise        ed into 3 histological groups (cribriform, tubular, and solid)
specified and 1 sialoblastoma. In another series of 57 pa-        based on solid components of the tumour 34. Some studies
tients aged 20 years or younger 27, the histologic types of the   have demonstrated that tumours with a solid growth compo-
38 carcinomas were MEC 19, acinic cell carcinoma 7, ACC           nent have a rapid fatal course, compared to tumours without
6, secretory carcinoma (mammary analogue) 4 and myoepi-           a solid growth component 34, but other studies have failed to
thelial carcinoma 2. Moreover, it is possible to find in the      correlate growth patterns with clinical course 3. Moreover,
literature some case reports of unusual locations of ACC in       no universally accepted grading system exists and no repro-
childhood: an 8-year-old girl with ACC of the external audi-      ducibility studies of the existing grading systems have been
tory canal 28, a 15-year-old boy with ACC of the larynx 29        performed. In fact, Therkildsen et al. examined the repro-
and a 12-year-boy with ACC of the pyriform sinus 30.              ducibility of grading based on semi-quantitative assessment



208
                                                                                                             Adenoid cystic carcinoma




of the solid growth pattern in ACC. Two different grading         duced the expression “cribriform adenocarcinoma, as being
systems were assessed by 3 observers on 59 ACC. Interob-          more appropriate to its origin, morphology, and behaviour”.
server agreement was poor, except for the category “solid         The signs and symptoms of ACC at presentation are not
component constituting 50% or more of the tumour” 35.             specific and depend on the anatomic site of involvement.
In spite of its rarity, several studies have analysed molec-      Typically, a parotid ACC in the superficial lobe presents as
ular pathogenesis, genetic mutations and protein overex-          a pre-auricular swelling, commonly less mobile than a pleo-
pression in ACC of the head and neck 22,36,37. Recent whole       morphic adenoma because, even when it is circumscribed,
genome and exome sequencing has dramatically improved             it is unencapsulated. Deep lobe tumours are comparatively
our understanding of ACC pathogenesis. A balanced trans-          rare, given that the deep lobe accounts for only 10% to 20%
location resulting in the MYB-NFIB fusion gene appears to         of parotid tissue, and ACC is even more rare. In a study by
be a fundamental signature of ACC. In addition, sequenc-          Cohen et al. 43, among 166 parapharyngeal space masses
ing has identified a number of other driver genes mutated         only 45 (27.1%) were of salivary gland origin and only one
in downstream pathways common to other well-studied               was an ACC. Deep lobe tumours often present as an asymp-
cancers 36. A study on 12 ACCs of the breast 38, demon-           tomatic submucosal swelling of the lateral oropharyngeal
strated that the mutational burden and mutational repertoire      wall and/or soft palate. Tumours presenting in the parana-
of breast ACCs are more similar to those of salivary gland        sal sinuses are associated with mild pain and pre-maxillary
ACCs than to other types of breast cancer.                        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
  Histopathology
                                                                  the absence or paucity of symptoms often result in delayed
  • ACC is one of the most common carcinomas of the               diagnosis and many patients present with advanced disease.
    salivary gland, among 23 histotypes.                          Mainly for ACC, the late and soft symptoms may be a mild
  • Pathological diagnosis of ACC remains a challenge,            pain and paraesthesia, because “one of the most outstand-
    especially in problematic cases.                              ing feature of this neoplasm, regardless of its site of origin,
  • ACC has been traditionally subdivided into 3 histo-           is its marked tendency to invade nerves. In our own surgical
    logical groups (cribriform, tubular, and solid) based         experience, invasion of the nerves is an almost constant mi-
    on solid components of the tumour, although no                croscopic finding. Although extension of neoplasm through
    universally accepted grading system exists and no             nerves is not peculiar to the adenoid cystic carcinoma, this
    reproducibility studies of the existing grading sys-          neoplasm certainly manifests this morbid finding more of-
    tems have been performed.                                     ten than other epithelial neoplasms in the head and neck” 44.
  • In spite of its rarity, several studies have analysed         Osborn 42 wrote that this well-known characteristic feature
    molecular pathogenesis, genetic mutations and pro-            of ACC was reported since 1934. The involved nerves may
    tein overexpression in ACC of the head and neck.              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
Clinical behaviour                                                foramens ovale and rotundum may be involved with exten-
ACC is uncommon in the parotid gland. Its incidence in the        sion of the tumour to the Gasserian ganglion 44.
historical large series presented by Eneroth (802 cases) 39 and   It is difficult to establish the real incidence of regional lymph
by Foote and Franzell (776 cases) 4 lies between 2% and 5%        node metastases from ACC because of the heterogeneity of
of all tumours and between 6% and 15% of all malignancies.        the series presented in many studied (different sites of ori-
On the contrary, ACC is much more frequent in the subman-         gin and all histologic types together). Regarding the parot-
dibular gland. In 2 series studied by Spiro et al. 40 and by      id, Xiao et al. 45 performed a thorough study on a series of
Eneroth et al. 41 the incidence of ACC was 42/121(35%) and        22,653 patients with parotid malignancy from the National
25/62 (40%), respectively. It is difficult to define the inci-    Cancer Data Base (NCDB). Patients were considered to
dence of ACC arising in the mucosal glands because of the         have positive nodal disease if there was at least one positive
heterogeneity of the series presented in many studied (major      lymph node confirmed by biopsy or neck dissection as part
and minor salivary gland together). In an historic and weighty    of diagnosis or treatment or if they had clinical evidence of
article, Osborn 42 gathered the data from 21 major and minor      nodal disease during follow-up. The authors divided histo-
series with a total of 1,712 mucosal gland malignant tumours      logic types in low and high grade according to Seethala 46.
of all types, of which 557 (32.5 %) were ACC. Osborn intro-       For ACC (2,045 cases, 9% of the series), the incidence of



                                                                                                                                209
G. Cantù




nodal metastases was 14.2% at presentation and 7% dur-           Diagnostic workup
ing follow-up (occult nodal disease). Interestingly, while for
MEC, acinar cell carcinoma, salivary ductal carcinoma and        In front of a parotid or submandibular gland swelling, after
adenocarcinoma not otherwise specified there was a great         an anamnesis about the time of onset and speed of growth,
difference in the incidence of occult nodal disease between      accurate physical examination may help to distinguish an
high and low grade, for ACC this difference was small (9.6%      inflammatory disease from a tumour. It is advisable to look
vs 6.3%). Regarding the paranasal sinuses, it is even more       for possible skin scars on the scalp, face and external ear,
difficult to draw reliable data from the literature. Amit et     as a result of resection of previous skin carcinoma or mela-
al. 47 reviewed 16 relevant articles, of which 13 presented      noma. Local pain at light palpation may be the symptom
very small series (≤ 35 cases). The remaining 3 studies pre-     of an ACC, even in the absence of more advanced clinical
sented 64, 99 and 105 cases. Moreover, all studies included      indicators of malignancy (fixity to surrounding structures,
patients with tumours of both sinuses and the nasal cavity,      nerves weakness or paralysis, presence of neck nodes). An
and one study presented ACCs of the nasopharynx. The rate        ACC that develops in the minor salivary glands of the oral
of node metastases at presentation ranged between 2% and         cavity almost always present as an asymptomatic submu-
13%. To the best of my knowledge, the only study dealing         cosal mass, most commonly on the palate.
with tumours of the only paranasal sinuses and their regional
                                                                 One must be careful of possible transformation into ACC
metastases is that by Cantù et al. 48. Among as many as 704
                                                                 of a recurrent pleomorphic adenoma after prior surgical
malignancies of the paranasal sinuses there were 115 AC-
                                                                 resection. Among 106 patients with recurrent pleomorphic
Cs (91in the maxillary sinus and 24 in the ethmoid sinus).
Only 2 patients presented with node metastases, and only         adenoma of the parotid gland, Yin et al. 49 found 13 (12.3%)
3 patients developed regional metastases during follow-up,       patients with carcinoma, of which only 4/13 (31%) had
together with a relapse of the primary tumour.                   clinical features suspicious for malignancy. Toluie et al. 50
ACC is generally recognised for its frequent and often si-       analysed 89 cases of sinonasal ACC from the files of the
lent distant metastases. They are rare at presentation, but at   Tumor Registry of the Armed Forces Institute of Pathology
10 years account for approximately 30% to 40%. The com-          (AFIP) and found 9 cases with the presence of an anteced-
monest sites are lung, bone, liver and brain.                    ent or contemporaneous pleomorphic adenoma.



  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.



210
                                                                                                        Adenoid cystic carcinoma




Imaging                                                         salivary gland lesions have been rather poor so far 52. Im-
Radiological imaging is not mandatory for small, mobile         aging with either CT or MRI is mandatory when there is
and superficial parotid tumours. Ultrasound (US) examina-       the clinical suspicion of malignancy or when the lesion is
tion with colour Doppler imaging has gained widespread          thought to extend into or to arise from the deep lobe of the
acceptance as an economic, safe and useful method to de-        parotid gland or the parapharyngeal space. US examination
tect and assess parotid gland masses. However, its diag-        or CT-MRI must be extended at least to the upper levels of
nostic accuracy in distinguishing malignant from benign         the neck. MRI and/or CT is mandatory for sinonasal ACC
tumours does not reach a satisfactory diagnostic level 51.      and must be extended to the skull base. The patient must
Elastography is a relatively new way of tissue imaging as-      also undergo a chest CT.
sociated with US. Some studies have found that malignant
tumours are generally stiffer than benign ones. Shear wave      Fine-needle aspiration biopsy (FNAC)
elastography (SWE) is a novel elastographic method that         and ultrasound-guided core biopsy (USCB)
offers the advantage of quantitative measurements and           Studies on aspiration biopsy with large needles were per-
lower operator-dependence. It is well established in breast     formed as early as the 1930s 44, but the technique has not
and thyroid gland lesions, but the results of elastography in   been accepted by most head and neck surgeons for the pos-




  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) ex-
    amination 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 satis-
    factory 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 ma-
    lignant 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.



                                                                                                                           211
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