International Journal of Otolaryngology and Head & Neck Surgery, 2013, 2, 165-173
http://dx.doi.org/10.4236/ijohns.2013.25036 Published Online September 2013 (http://www.scirp.org/journal/ijohns)
Adenoid Cy s tic Carci noma of the H ead and Neck:
Epidemiology and Predictors of Prognosis
Daniel Monteiro1*, João Lino1, Teresa Bernardo1, João Fernandes2, Eurico Monteiro2
1Department of Otorhinolaryngology and Head and Neck Surgery, Saint Antonio Hospital, Porto, Portugal
2Department of Otorhinolaryngology and Head and Neck Surgery, Portuguese Institute of Oncology, Porto, Portugal
Received June 8, 2013; revised July 3, 2013; accepted July 23, 2013
Copyright © 2013 Daniel Monteiro et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Objectives: The biologic behavior of the adenoid cystic carcinoma (ACC) and the factors predicting outcome for these
tumors are still poorly understood. Our objective is to analy ze the predictin g factors and the value of differen t treatment
possibilities, since none sole treatment has been stan dardized. Methods: A retrospective analysis of the epidemiologic,
clinical and histologic aspects of ACC, as well as treatment options and o ther pr ognostic factors of all the cases of ACC
of the head and neck treated at this In stitution were analyzed. From 1974 until 2011, 152 patien ts were diagnosed with
ACC and treated at the Portuguese Institute of Oncology (Porto Centre). Main outco me measures: overall survival, local
recurrence and distant metastasis were calculated by the Kaplan-Meier method. Factors predictive of outcome were
identified by univariate and multivariate analysis. Results: The mean age at diagnosis was 55.8 years (range, 19 - 83
years). Incidence was higher in the female population, with a female to male ratio of 1.7:1 respectively. The primary
tumor location was hard palate and submandibular region in 56 cases, 28 in each location (24.6%), parotid gland (17
cases, 14.9%) and oral cavity excluding palate (16 cases, 14%).Distributions according to T stage were: T1 (29.8%); T2
(30.7%); T3 (17.5%); T4 (22%). The overall 1-year, 5-year and 10-year survival for all patients were 94.6%, 60.5%,
41.6%, respectively. Conclusions: Univariate survival analysis revealed that age older than 60 years (p = 0.002), solid
histologic subtype (p = 0.042), advanced clinical stage (p < 0.001) and the presence of perineural invasion (p = 0.036)
were correlated with a poor survival. Multivariate analysis confirmed that age and advanced clinical stage were worst
independent predicators of overall survival as well as perineural invasion for local recurrence and distant metastasis. In
our analysis, radiotherapy did not have a relevant impact on survival, except in cases of solid histologic subtype. To
analyze distant metastatic capacity, long term follow-up was necessary, since distant metastasis way occurs even after
10 years, which has the case with 4 patients.
Keywords: Adenoid Cystic Carcinoma; Head and Neck Cancer; Prognostic Factors
1. Introduction
Adenoid cystic carcinoma (ACC), also known as cylin-
droma, a rare adenocarcinoma arising within secretory
glands, occurs mainly in the minor salivary glands of the
palate, and in the major glands [1-5]. Besides the oral ca-
vity, other locations may be affected in accordance to the
anatomical distribution of the minor salivary glands, as
for example nasal cavity, paranasal sinus, pharynx, eso-
phagus, larynx, tracheobronchial tree, eye and external
auditory canal [1,3]. ACC of the head and neck is re-
sponsible for 0.5% - 1% of malignancies in this area and
for 7.5% - 10% of salivary gland tumors [1-3,6]. In fact,
the largest epidemiological study that included 2611
cases from European countries, found an ACC (ICD-0-2
Code 8200) inciden ce of 0.5% [2].
The biological behavior of ACC of head and neck is
clinically represented by a slow and indolent growth gen-
erally in sub mucosal localization, making these tumors
hard to diagnose [1,4,6]. It is frequ ently associated w ith a
late recurrence rate and distant metastasis, especially to
the lungs, and they are associated with poor progno sis [1,
3,6].
Histologically, three subtypes of ACC (cribriform, tu-
bular and solid) have been described, with tubular sub-
types having a better prognosis in contrast to solid pat-
tern histolo gy [ 1,3].
Standard treatment for patients diagnosed with ACC is
surgical, in some cases associated with radiotherapy, al-
*Corresponding author.
C
opyright © 2013 SciRes. IJOHNS

D. MONTEIRO ET AL.
166
though the benefit of this last option has not been un-
equivocally proven [1,3]. Radiotherapy has been consid-
ered for patients with criteria of poor prognosis, as per-
ineural invasion, positive margins and advanced stages
[7,8].
Albeit ACC has been the subject of many epidemiol-
ogical studies on several populations, predictive and
prognostic factors in this type of cancer are scarce. The
objective of this retrospective study was to characterize
epidemiologically your population of patients in a tertiary
cancer-institution, and analyze factors involved in local
control, treatment failure, distant metastasis and other
prognostic variables associated with overall survival.
2. Material and Methods
2.1. Patients
A retrospective analysis including all patients with ACC
diagnosed and treated at the Oporto Oncologic Institute
between 1974 and 2011 was conducted. This study was
approved by the Institution’s Ethics Committee. Of the
152 ACC patients initially identified, 38 were excluded
due to insufficien t clinical data (Figure 1). Demographic
and clinical in formation (age, gender, initial symptoms
and its duration, histologic subtype, location of primary,
perineural invasion, distant metastasis, staging and treat-
ment options) was obtained from the remaining 114 pa-
tients.
Anatomical distribution of these tumors was grouped
as tumors with origin in minor or major glands, though
different locations were registered. Staging was per-
formed in accordance with the 2010 American Joint
Committee on Cancer (AJCC) staging system. In some
cases, there were more than one histologic subtype in the
tumor, but the characterization has been made according
to the most predominant subtype. Margin statuses after
surgery were not analyzed in all patients due to in suffi-
cient information in clinical charts. Only 101 patients
submitted to surgery followed or not by radiotherapy
were subject to further analysis. Primary and secondary
end-points analyzed were overall survival (OS), defined
as the time from diagnosis until death or last clinical visit,
and disease free survival, defined as the time-to-locore-
gional recurrence (TTR), or time-to-distant metastasis
(TTM) determined as the time interval, in months, be-
tween diagnosis and local recurrence or distant metasta-
sis.
2.2. Statistical Analysis
Global analysis included only 101 patients, those that
were submitted to surgery followed or not by radiother-
apy. Tertiles of age at diagnosis were used for analyses.
For time-to-event analyses, univ ariate Kaplan-Meier with
Submitted to Surgery or Surgery
followed by Radiotherapy
N
=101 cases
Hospital Database (1974-2011)
152 cases of A CCH
Cases analyzed for clinical and
pathologic variations N = 114
13 cases excluded due to
having been submitted to
exclus ively QT, RT,
symptomatic or refused
treatment
38 cas es ex cluded du e to
insufficient data
Figure 1. Diagram depicting the analysis criteria of the
population.
log-rank tests and multivariate Cox proportional hazards
model were used, to identify predictors of overall survi-
val, local recurrence and distant metastasis. Hazard ratios
(HR) and 95% confidence intervals (CIs) were used for
estimating the association between clinical and patho-
logical characteristics with each of the outcomes of in-
terest. Selection of variables to include in the multivari-
ate model was submitted to empirical evaluation through
univariate analysis. Variables with p-values lower than
0.10 on univariate analysis were included in the multi-
variate model. SPSS version 17 was used for statistical
analysis.
3. Results
3.1. Clinical Features
Table 1 outlines the clinical characteristics of the 114 pa-
tients. Mean age at diagnosis was 55.8 years (range 19 to
83 years). The incidence in the female gender was higher
than in men, 63.2% and 36.8% respectively.
The main symptom at the time of diagnosis was a no-
dular mass (52.6%), followed by pain associated to a no-
dule (18.4%), nasal symptoms (14%) (nasal obstruction,
hemorrhagic rhinorrhea). Other symptoms less frequent
were dyspnea, odynophagia, otalgia, facial paralysis and
hearing impairment.
Median time elapsed between onset of symptoms and
diagnosis was 10 months, with a minimum of 0 months
and a maximum of 144 months. Eighty one percent of the
patients were diagnosed in the first 24 months after-
symptom initiation. ACC was diagnosed less frequently
in major salivary glands (39.5%) than in anatomic loca-
tions where minor salivary glands are represented ( 60 .5 %) .
The most common location was the oral cavity with 44
cases (38.6%), 28 cases of which in the hard palate. The

D. MONTEIRO ET AL. 167
second most frequent location was the submandibular
gland with 28 cases (24.6%), followed by the parotid
gland (17 cases, 14.9%), the paranasal sinus (12 cases,
10.5%) and the larynx (7 cases, 6.1%). Other locations
seldom involved include the parapharyngeal space, the
scalp, the external auditory meatus and the nasopharynx
(Table 1).
3.2. Pathologic Characteristics
The pathologic characteristics of the ACC resected are
outlined in Table 2. Histologic sub classification was
only determined in 68 patients, 29.4% were predomi-
nantly tubular, 44.1% primarily cribriform and 26.5%
mainly solid.
Sixty one patients (53.5%) had perineural invasion of
Table 1. Population characteristics.
Cases Percent
Age
<52 years 40 35.1
52 until 64 years 32 28.1
>64 years 42 36.8
Gender
Female 72 63.2
Male 42 36.8
Initial symptom
Nodular mass 60 52.6
Nodular mass and pain 21 18.4
Nasal symptoms 16 14.0
Dyspnea and dysphonia 6 5.3
Odynophagia 4 3.5
Cervical adenopathy 2 1.8
Otalgia 2 1.8
Facial Paralysis a nd nodular mass 2 1.8
Hipoacusis 1 0.9
Location
Hard Palate 28 24.6
Submandibular 28 24.6
Parotid 17 14.9
Sublingual glands and minor glands
of the oral cavity 16 14.0
Paranasal sinus 12 10.5
Larynx 7 6.1
Others (scalp 2, p a rapharyngeal space 2,
external acoustic meatus 1, nasopharynx 1) 6 5.3
Table 2. Pathologic chara cterist ics.
Cases Percent
Histology
Tubular 20 29.4
Cribriform 30 44.1
Solid 18 26.5
Total 68 100.0
Invasion
Perineural invasion 61 53.5
No invasion 48 42.1
No Perineural invasion but with other type
of invasion (lymphatic, vascular, bone) 5 4.4
Total 114 100
which 32 cases had exclusive perineural invasion and in
the remaining, vascular (18 cases), lymphatic (18 cases)
and bone invasion (11 cases) were also present. Perineu-
ral invasion was present more frequently in tumors of
major salivary glands (30/43) than in minor glands (28/
58) a finding with statistical significance (p = 0.031).
3.3. Staging
TNM classification and stages can be observed in Table
3. Of all tumors, 10.5% had regional metastasis and only
6.1% had distant metastases at the time of diagnosis
(lungs in 5 cases and bone in 1 case). Approximately half
of the patients were diagnosed at an initial stage (I and
II).
3.4. Treatment
The distribution of patients according to treatment op-
tions is shown in Ta ble 4. Of the 114 patients, 4 refused
treatment and 9 were considered inoperable and were
selected for supportive care or palliative treatment with
radiotherapy or chemotherapy. These 13 patients were
excluded from further analysis. Of the 101 patients sub-
mitted to surgery, 58 cases were proposed for subsequent
radiotherapy (RT). Many factors interfered with the deci-
sion of post-operative RT such as the surgeon’s option,
location, presence of positive margins and perineural
invasion. The average time from diagnosis until surgery
was 2.3 mont h s .
3.5. Univariate and Multivariate Survival
Analysis for Overall Survival
Univariate analysis of the clinical, epidemiologic and
pathologic variables analyzed for overall survival (Table
5) revealed that older patient’s had a worse outcome.

D. MONTEIRO ET AL.
168
Table 3. TMN stage according to AJCC.
Cases Percent
Size of tumor (T)
T1 34 29.8
T2 35 30.7
T3 20 17.5
T4a 20 17.5
T4b 5 4.5
Regional metastasis (N)
N0 102 89.5
N+ 12 10.5
Distant metastasis
M0 108 93.9
M1 6 6.1
Stage
I 29 25.4
II 31 27.2
III 24 21.1
IVa 18 15.8
IVb 5 4.4
IVc 7 6.1
Total 114
Table 4. Distribution of treatment options.
Treatment Cases Percent
Surgery and radiotherapy 58 50.9
Surgery 43 37.7
Exclusive chemotherapy,
radiotherapy or no treatment 13 11.4
Total 114 100.0
Though not significant (p = 0.064), females seem to sur-
vive for a longer periods than males, with a median dif-
ference of 4 years. There was no statistical significance
on overall survival between tumors appearing from mi-
nor or major salivary glands (Figure 2). Comparing spe-
cific locations (Table 6) lower survival was observed in
tumors localized in the nasal cavity and larynx, but the
differences were not statistically significant (p > 0.082).
Analyses of overall survival showed that there was no
difference between treatment options. A trend was ob-
served towards surgery alone although we could presume
that the worst cases were the ones that were indicated for
RT and there forth may have a poorer prognosis (Figure
3). In univariate analysis, advanced disease, solid his-
tologic subtype and perineural invasion were statistically
Figure 2. Survival of patients according to location.
Figure 3. Overall survival for patients according to omis-
sion or inclusion of postoperative radiation therapy.
significant (p = 0.001, p = 0.042, p = 0.036 respectively).
Increased T and solid histologic subtype were also asso-
ciated with decreased survival, as presented respectively
in Figures 4 and 5 resp ectively.
When patients only submitted to surgery or surgery
followed by RT were analyzes separately, it was ob-
served that RT was relevant to the prognosisin some his-
tologic subtypes. We observed a similar survival in all
histologic subtypes that were submitted to radiotherapy
(p = 0.410), but patients that had only surgery had sig-
nificant (p = 0.04) differences of survival according to
histologic subtypes, with the prognosis of the solid sub-
type being considerably lower. As may be seen on Table
7, mean survival of patients with solid pattern that were
treated only with surgery have a lower survival in about
100 months in comparison with the other. The same is
not verified in patients treated with surgery and radio-
therapy. In this group, probably with worse prognosis to
begin with, the solid subtype had a higher overall sur-
vival than patients treated with surgery alone and similar
to the other subtypes. This data suggests the eventual
recommendation for radiotherapy in the solid histologic

D. MONTEIRO ET AL.
169
Table 5. Time-to-event univariate analysis for clinicopathological variables according to mortality, local recurrence and dis-
tant metastasis.
Overall survival Local recurrence Distant metastasis
Events Median95% CI p EventsMedian95% CI p Events Median 95% CI p
Age, yrs*
<52 14 168 77.8 - 258.3 22 102 59.0 - 145.0 10 264 48.5 - 49.5
52 - 64 25 64 44 - 84 20 79 57.3 - 100.7 9 144 53.9 - 234.2
>65 23 73 66.6 - 79.4 0.002 20 82 74.4 - 89.6 0.347 6 - - 0.800
Gender
Female 33 126 74.6 - 177.4 39 91 67.8 - 114.2 13 264 -
Male 30 76 58.8 - 93 .2 0.064 23 79 73.3 - 84.7 0.305 12 119 - 0.172
Tumor location
Minor glands 38 76 62.6 - 89.4 24 87 69.0 - 105.0 10 - -
Major glands 25 126 76.5 - 175.5 0.715 28 79 69.8 - 88.2 0.247 15 108 72.0 - 144.00.056
Clinical stage
Initial 29 142 105.7 - 178.3 39 91 69.9 - 112.4 11 - -
Advanced 34 63 40.3 - 8 5.7 0.001 24 76 45.9 - 106.10.103 14 99 56.1 - 141.90.04
Treatment
Surgery plus RT 39 77 66.9 - 87.1 40 77 68.9 - 85.1 18 108 83.4 - 132.6
Surgery 24 168 72.4 - 263.6 0.056 22 99 20.0 - 177.90.336 7 - - 0.290
Histology
Tubular 11 79 18.1 - 139.9 10 91 71.2 - 110.8 5 99 -
Cribriform 15 113 73.7 - 152.3 17 80 37.3 - 122.7 9 119 70.9 - 167.2
Solid 14 51 33.1 - 68.9 0.042 8 38 27.3 - 48.7 0.397 4 - - 0.899
Perineural invasion
No 23 126 31.5 - 220.5 24 102 32.4 - 171.6 5 - -
Yes 37 73 51.2 - 94.8 0.036 34 76 30.7 - 121.30.006 18 102 65.9 - 138.10.001
RT—radioth erapy; HR—hazard rati o; Ref—Reference. Ev ents calculated as deaths at the ti me of last follo w-up. Median referred in months. Cut off used for
multivaria te analysis was 0.10. Covariates included in multivariate model: age, gender, stage, treatment and pe rineural inva sion.
Table 6. Survival according to location.
Variable No. Survival, %
Location 5 years 10 yearsp-Value
Hard Palate 24 70.5 54.6 0.082
Submandibular 26 86.2 64.2
Parotid 17 85.6 52.5
Minor glands of the oral
cavity (except hard palate) 14 78.6 53
Nasal cavity 12 56.8 45.5
Larynx 5 40
Others 3 66.7 66.7
Treatment
Surgery and radiotherapy 58 62.2 39.9 0.056
Surgery 43 76.4 55.2
Table 7. Overall survival in different histologic subtypes for
different treatments.
Surgery and Radiotherapy Surgery
Mean95% CI p value Mean 95% CI p value
Tubular99.663.6 - 135.60.41 166 66.8 - 265.20.004
Cribriforme70.543.5 - 97.4 179.4 72.1 - 286.6
Solid 72. 135.6 - 108.5 50.7 26.5 - 74.8
subtype. All other variables subject to analysis between
these two groups did not show a statistical difference.
Multivariate analysis (Table 8 ) confirmed significance
of univariate analysis in th e cases of age (p = 0.001) an d
tumor stage (p = 0.020) as independent predicators. The
hazard ratio for people older than 52 and 64 years old is
3.6 and 3.5 respectively. The hazard ratio for advanced

D. MONTEIRO ET AL.
170
Table 8. Multivariate analysis with predictive variables for mortality, local recurrence and distant metastasis.
Overall survival Local recurrence Distant metastasis
HR 95% CI p HR 95%CI p HR 95% CI p
Age, yrs *
<52 Referent Referent Referent
52 - 64 3.6 1.7 - 7.6 0.0011.4 0.7 - 2.8 0.318- - -
>65 3.5 - 0.0021.7 0.8 - 3.4 0.138- - -
Gender
Female Referent Referent Referent - -
Male 1.2 0.7 - 2.1 0.4501.1 0.6 - 1.9 0.864
Tumor location
Minor glands Referent 1.3 1.7 - 2.4 1.6 0.7 - 3.9 0.293
Major glands 1.0 0.6 - 1.8 0.987Referent 0.493Referent
Clinical stage
Initial Referent 1.2 1.8
Advanced 2.0 1.1 - 3. 6 0.020Referent 0.7 - 2.4 0.493Referent 0.8 - 4.3 0.185
Treatment
Surgery plus RT Referent 1. 0
Surgery 1.0 0.5 - 1 .7 0.864Referent 0.6 - 1.9 0.9 49Referent - -
Histology
Tubular
Cribriform - - -
Solid - - - - - -
Perineural invasion
No Referent 2.1 1.1 - 3.9 0.028Referent
Yes 1.6 0.9 - 2.8 0.107Referent 3.5 1.2 - 10.3 0.025
Cut off used for multivariate analysis was 0.10. Covariates included in multivariate model: Age, gender, stage, treatment, perineural invasion. Histology sub-
types not included due to low number.
Figure 4. Overall survival according to T.
Figure 5. Survival rates according to histologic type (gradin g).

D. MONTEIRO ET AL. 171
stage is 2.0 with a 95% confidence interval of 1.1 to 3.6.
3.6. Follow-Up and Global Survival Rates
No definite policy on follow-up was observed, but the
median follow-up period was 90 months (95% CI 42.7 -
137.3). The overall su rvival rates were 68.2%, 45.7% and
19.4% for 5 years, 10 years and 20 years respectively.
The disease free survival rates for 5 years and 10 years
was 52.9% and 34.4%.Surv ival at 5 and 10 years dep end-
ing on variables (gender, perineural invasion, stage and
treatment) and the results can be observed in Table 9.
3.7. Univariate and Multivariate Survival
Analysis of Local Recurrence and
Distant Metastasis
Following the initial treatment, four patients had persis-
tent disease and have been submitted to chemotherapy or
supportive treatment. Thirty-five patients (34.7%) had lo-
cal recurrence after a mean time of 42.2 months. Patients
were selected for palliative treatment (5 cases), chemo-
therapy (5 cases) and surgery with or without radiother-
apy (25 cases) and, survival following treatment was
51.6 months, 40.4 months and 63.4 months, respectively.
These results suggest that chemotherapy has no indica-
tion in the recurrence of ACC and the treatment should
be secondary surgery followed or not by radiotherapy
when possible.
Twenty five patients (24.8%) had distant metastasis
after a mean time of 67.6 months (median of 48 months).
Twenty one of these patients had lung metastasis) and in
5 of these, there were also metastasis to other locations
namely, liver (2 cases), bone, kidney and brain with one
each. In the remaining 4 patients, 1 had bone metastasis,
1 had liver metastasis and 2 had both these locations.
Even though distant metastasis was observed, patients
had prolonged survival after their identification, with a
mean time survival of 40 months (range 3 - 133 months).
Survival times were similar in spite of different metasta-
sis location. The 5 patients that had metastasis in more
than 1 location had a mean survival time of 61 months.
When comparing treatment of distant metastasis, secon-
dary surgery followed or not by radiotherapy prolonged
lifetime for an average of 70 months, while only chemo-
therapy prolonged life for 36 months and patients only
treated symptomatically survived on an average of 20
months. This finding supports the need for treatment of
distant metastasis with surgery followed or not by radio-
therapy.
Univariate and multivariate analyses for local recur-
rence and distant metastasis revealed that perineural in-
vasion was significantly associated with local recurrence
rate and distant metastasis (Tables 5 and 7). In univariate
analysis, advanced disease was statistically (p = 0.04) as-
Table 9. Survival at 5 and 10 years (gender, perineural in-
vasion, clinical stage, treatment).
Variable Survival, %
5 years 10 years
Gender
Female 72.1 52.4
Male 62.7 35.9
Perineural invasion
Yes 58.2 40.5
No 77.9 52.4
Clinical stage
I and II 79.3 63.3
III and IV (a e b) 53.1 23.3
Treatment
Surgery + RT 62.2 39.0
Surgery 76.4 55.2
sociated to a poorer prognosis with earlier distant me-
tastasis. Distant metastasis developed in all histologic
subtypes with no statistical difference between them, but
is important to note that the solid histologic subtype re-
curs much earlier than the other 2 subtypes of ACC (me-
dian 38 mont h s ).
The main reason for death in these patients was local-
recurrence and distant dissemination, but location of the
primary was not relevant neither for local recurrence nor
for distant metastasis. Local recurrence occurred in 7 pa-
tients after 5 years and in 2 patients after 10 years. Con-
sidering distant metastasis 12 cases occurred after 5 years
and 2 after 10 years.
4. Discussion
There are doubts that the prevalence of ACC is gender
related, none the less some studies claim a higher fre-
quency and better prognosis in the female population, has
was found in our series [1,2,4,9,10]. According to the
literature available, there is a great variability on the age
of onset, from 10 to 99 years, with more frequency above
the age of 64 years, which is coherent with our findings.
[2,4,6,11]. Symptoms in [12] most cases are unspecific
and vary in accordance to the location of the tumor [6].
Manifestations in cases of oral and major salivary glands
tumors are nodular mass, often associated with pain,
which is usually related to perineural invasion [1]. The
most frequent location is the hard palate (34%) due to the
greater number of minor salivary glands, followed by the
submandibular and the parotid glands, concordant to our
series [4,8,10].
The median time from the first complain until diagno-

D. MONTEIRO ET AL.
172
sis was 10 months, nonetheless, as shown in our findings,
some cases may take several years to be diagnosed due to
slow and indolent growth pattern of these tumors. In
spite of delayed diagnosis, in our series, patients rarely
had regional or distant metastasis at the time of diagnosis,
as reported by other investigators [13].
It was verified that tubular and cribriform subtypes
had a greater time interval between first symptom and
diagnosis than the so lid subtype, probably due to a faster
growth pattern or a greater invasive capacity. Tubular
subtype is expected to have a better prognosis, although
our data demonstrated a greater median survival time for
the cribriform subtype [1,3,4,14]. This aspect may be at-
tributed to different percentages of the histologic sub-
types in the tumors, emphasizing the importance of a cor-
rect histologic classification. Different prognosis and be-
havior patterns have been referred between histologies,
however subtypes are often not registered by pathologists.
Cribriform subtype was the most common in our series
(44.1%), coherent with the literature, that states that this
subtypeis responsible for 50% of the cases and the tubu-
lar and the solid patterns for 25% each [1,3,13]. Our data
suggests that all cases of solid histologic subtype should
be submitted to radiotherapy, due to the finding of simi-
lar life expectancy in patients of different histologic sub-
types, treated with surgery followed by radiotherapy as
opposed to patients treated exclusively with surgery,
which had differences of 100 mont h s.
The most important prognostic factors of poor overall
survival referred in literature are advanced initial stage,
advanced age, histologic subtype (solid), location and in-
complete surgical resection [1-3,12 ,14]. We found in our
series that the first two were statistically significant (p =
0.001 and p = 0.002 respectively). Concerning the loca-
tion, a large overall survival difference was observed be-
tween sites, namely for the larynx and paranasal sinus
with a poorer survival, which results are coherent with
the study of Ciccolallo, although in our series the results
did not achieve statistical significance due to the scarce
number of cases (Table 6). Accepted factors predicting
recurrence are tumor stage at the time of diagnosis, posi-
tive surgical margins and perineural invasion [2,3,8,12].
Perineural invasion was observed in 53.5% of our pa-
tients, confirming the reported neurotropism of this tu-
mor [1,3]. Our study emphasizes the importance of per-
ineural invasion, which was considered an independent
prognostic factor for all outcomes. In our series other re-
ferred prognostic factors did not achieve significance
value due maybe to small amount of patients analyzed.
Our exclusion of some cases (152-to-101) was made in
an attempt to eliminate in sufficient data and selection
bias for treatment modalities, since patients with ad-
vanced or unresectable disease tend to be treated with
palliative measures. Our findings suggest that th ere is no
benefit in submitting patients to post-operative radiother-
apy (p = 0.056) which is coherent with the studies pub-
lished by Silverman et al. (2004) e Chen A.M. et al.
(2006), with the exception of patients with solid histolo-
gic subtype [5,7,8,15]. The best treatment option is sur-
gery with wide safe margins, with special attention to sub
mucosal expansion, perineural and lympho-vascular in-
vasion [3,6,8,12-14,16]. Chemotherapy in ACC has not
been proved as beneficial [12].
Recurrence disease in our population (34.7%) was not
as rare as described in the literature (10% - 20%) [3,11].
Concerning distant metastasis these may occur in 16% -
35% of the cases, which is similar to our results (2 7.7%)
[3,13]. Distant metastasis are located predominantly in
the lungs (78.6% in our series), in few patients in the
liver and bones (21% each in our series) and rarely in the
kidneys and brain (3.5% each) [1,3,4,6,12,14]. Tumor as-
sociated survival was poor, with a 15 - 20 year prognosis
inferior to 20% [1,7,1 7]. Du e to the tu moral behavior and
the possibility of late recurrences and of distant metasta-
sis after many years, it is important to have a longer fol-
low-up peri od [1 3, 1 4,18].
5. Conclusion
In summary, increased age and advanced clinical stage
were independent significant prognostic factors for over-
all survival in our series. Perineural invasion was an in-
dependent significant prognostic factor for local recur-
rence and distant metastasis. Our study advises clinicians
to request different subtype characterization from the pa-
thologist, due to different growth patterns and survivals.
We recommend radiotherapy only in patients with solid
histologic subtypes. Our findings indicate that patients
with local recurrence and/or distant metastasis survive
longer if submitted to secondary surgery followed or not
by radiotherapy, so we recommend salvage surgery for
all possible cases. Multi-center studies are necessary in
order to determine with certainty which are the b est treat-
ment options.
REFERENCES
[1] D. C. Perez, F. A. Alves, I. N. Nishimoto, O. P. Almeida,
et al., “Prognostic Factors in Head and Neck Adenoid
Cystic Carcinoma,” Oral Oncology, Vol. 42, No. 2, 2006,
pp. 139-146.
[2] L. Ciccolallo, L. Licitra, G. Cantú, G. Gatta, et al., “Sur-
vival from Salivary Glands Adenoid Cystic Carcinoma in
European Population,” Oral Oncology, Vol. 45, No. 8,
2009, pp. 669-674.
doi:10.1016/j.oraloncology.2008.10.010
[3] S. Chummun, N. R. McLean, C. G. Kelly, P. J. Dawas, et
al., “Adenoid Cystic Carcinoma of the Head and Neck,”
British Journal of Plastic Surgery, Vol. 54, No. 6, 2001,
pp. 476-480. doi:10.1054/bjps.2001.3636

D. MONTEIRO ET AL.
173
[4] N. M. Rodriguez, I. L. Berrocal, L. R. Alonso, O. A.
Irimia, et al., “Epidemiology and Treatment of Adenoid
Cystic Carcinoma of the Minor Salivary Glands: A Meta-
Analytic Study,” Medicina Oral Patologia Oral y Cirugia
Bucal, Vol. 16, No. 7, 2011, pp. 884-889.
doi:10.4317/medoral.17200
[5] A. J. Khan, M. P. DiGiovanna, D. A. Ross, C. T. Sasaki,
et al., “Adenoid Cystic Carcinoma: A Retrospective Cli-
nical Review,” Radiation Oncology Investigations, Vol.
96, No. 3, 2001, pp. 149-158.
[6] H. Wang, L. Xu and F. Li, “Subglottic Adenoid Cystic
Carcinoma Mistaken for Asthma,” Journal of Zhejiang
University Science B, Vol. 10, No. 9, 2009, pp. 707-710.
doi:10.1631/jzus.B0920071
[7] A. M. Chen, M. K. Bucci, V. Weinberg, J. Garcia, et al.,
“Adenoid Cystic Carcinoma of the Head and Neck
Treated by Surgery with or without Postoperative Ra-
diotion Therapy: Prognostic Features of Recurrence,” In-
ternational Journal of Radiation Oncology Biology Phys-
ics, Vol. 66, No. 1, 2006, pp. 152-159.
[8] N. G. Iyer, L. Kim, I. J. Nixon, F. Palmer, et al., “Fac-
tores Predicting Outcome in Malignant Minor Salivary
Gland Tumors of the Oropharynx,” Archives of Otolar-
yngology—Head and Neck Surgery, Vol. 136, No. 12,
2010, pp. 1240-1247.
[9] C. L. Ellington, M. Goodman, S. A. Kono, W. Grist, et al.,
“Adenoid Cystic Carcinoma of the Head and Neck: Inci-
dence and Survival Trends Based on 1973-2007 Surveil-
lance, Epidemiologym and End Resuls Data,” Cancer,
Vol. 118, 2012, pp. 4444-4451. doi:10.1002/cncr.27408
[10] F. A. Oliveira, E. C. B. Duarte, C. T. Taveira, A. A.
Máximo, et al., “Salivary Gland Tumor: A Review of 599
Cases in a Brazilian Population,” Head and Neck Pa-
thology, Vol. 3, No. 4, 2009, pp. 271-275.
doi:10.1007/s12105-009-0139-9
[11] R. Srivastava and N. Bhatia, “Adenoid Cystic Carcinoma
of Larynx,” IJO & HNS, Vol. 49, No. 3, 1997, pp. 280-
281.
[12] P. B. Zald, M. W. Weber and J. Schindler, “Adenoid Cy-
stic Carcinoma of Subglotic Larynx: A Case Report and
Review of the Literature,” Ear Nose Throat Journal, Vol.
89, No. 4, 2010, p. E27.
[13] A. D. Negro, E. Ichihara, A. J. Tncani and A. Altemani,
“Laryngeal Adenoid Cystic Carcinoma: Case Report,”
São Paulo Medical Journal, Vol. 125, No. 5, 2007, pp.
295-296. doi:10.1590/S1516-31802007000500010
[14] E. Zvrko and M. Golubovic, “Laryngeal Adenoid Cystic
Carcinoma,” Acta Otorhinolaryngologica Italica, Vol. 29,
No. 5, 2009, pp. 279-282.
[15] D. A. Silverman, T. P. Carlson, D. Khuntia, et al., “Role
for Postoperative Radiation Therapy in Adenoid Cystic
Carcinoma of the Head and Neck,” Laryngoscope, Vol.
114, No. 7, 2004, pp. 1194-1199.
doi:10.1097/00005537-200407000-00012
[16] A. T. N. N. Alves, F. D. Soares, A. S. Junior, Medeiros,
et al., “Carcinoma Adenóide Cístico: Revisão da Litera-
tura e Relato de Caso Clínico,” Brasileiro de Patologia e
Medicina Laboratorial, Vol. 40, 2004, pp. 421-424.
[17] S. C. Lee and J. T. Johnson, “Salivary Glands Neo-
plasms,” eMedicine Specialties, 2009.
http://emedicine.medscape.com/article/852373-overview
[18] www.cancer.net.
http://www.cancer.net/patient/Cancer+Types/Adenoid+C
ystic+Carcinoma?sectionTitle=Overview