Vol. 106 No.

2 August 2008

ORAL AND MAXILLOFACIAL PATHOLOGY Editor: Mark W. Lingen

Fine-needle aspiration biopsy as an auxiliary diagnostic tool on

intraoral minor salivary gland adenoid cystic carcinoma
Juliana de Noronha Santos Netto, DDS,a Águida Maria Menezes Aguiar Miranda, DDS, MSc,b
Henrique Martins da Silveira, DDS, PhD,c
Teresa Cristina Ribeiro Bartholomeu dos Santos, DDS, MSc,d and
Fábio Ramôa Pires, DDS, PhD,e Rio de Janeiro, Brazil
ESTÁCIO DE SÁ UNIVERSITY

Background. Fine-needle aspiration biopsy (FNAB) is useful in diagnosis of major salivary gland adenoid cystic
carcinoma (ACC), but it has been rarely reported on minor salivary gland ACC.
Objective. The aim of this study was to report the utility of FNAB on diagnosis of ACC involving minor salivary
glands.
Study design. Three patients presenting ACC involving the palate (2 cases) and buccal mucosa (1 case), with a mean
age of 36 years and 2:1 female-to-male ratio, were included in the study. All of the patients were submitted to FNAB
for diagnostic purposes.
Results. All smears were stained with hematoxylin-eosin, Papanicolaou, and Diff-Quik and showed the presence of
small polyhedral cells with hyperchromatic nuclei and extracellular basophilic globular amorphous substance,
compatible with ACC. Diagnosis of the 3 cases was subsequently confirmed through histopathology.
Conclusion. The FNAB was easy to perform and cost-effective, and proved to be an useful adjunctive tool in diagnosis
of intraoral ACC. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;106:242-5)

Adenoid cystic carcinoma (ACC) is considered to be
the second most common malignant salivary tumor,
presenting clinically as long-lasting swellings, which
can be painful and ulcerated, involving more fre-
quently intraoral minor salivary glands and the sub-
mandibular gland.1-3 Microscopically, ACC is com-
posed of a proliferation of small polyhedral cells
with angulated hyperchromatic nuclei, disposed in 3
different patterns: cribriform, tubular and solid. Tu-
mor cells produce a lightly basophilic extracellular
a
Specialist in Stomatology.
b
Professor, Stomatology.
c
Professor, Oral Surgery
d
Professor, Oral Pathology.
e
Professor, Stomatology and Pathology.
Received for publication Oct. 26, 2007; returned for revision Apr. 13,
2008; accepted for publication Apr. 17, 2008.
1079-2104/$ - see front matter
© 2008 Mosby, Inc. All rights reserved.
doi:10.1016/j.tripleo.2008.04.015
secretion material, variably arranged among the neo-
plastic cells in proliferation.1,4
Diagnosis of ACC is usually rendered through
incisional biopsy, but fine-needle aspiration biopsy
(FNAB) is useful on diagnosis of ACC, especially in
major salivary glands.5-7 In these locations, ACC
cytological features have been frequently described
and can exhibit a straight correlation with its his-
topathological features, specially on the cribriform
variant.8,9 Nevertheless, few studies focusing ACC
cytology have included intraoral minor salivary
gland tumors, what prompted us to report the cyto-
logical features of three intraoral ACC submitted to
FNAB as a diagnostic procedure.
MATERIAL AND METHODS
Three patients submitted to FNAB as a diagnostic
procedure on intraoral submucosal nodules were in-
cluded in the study. All of the cases were submitted to
FNAB using 23- or 25-gauge needle and 10- to 20-mL
syringes linked to a metallic syringe holder specifically

242
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Volume 106, Number 2 Netto et al. 243

Fig. 1. Clinical pictures of both irregularly shaped swellings covered by erythematous and telangiectatic mucosa on the palate.

indicated for the method. All obtained smears were

extended in glass histologic slides, immediately im-
mersed in absolute alcohol or air-dried, and stained in
hematoxylin and eosin (HE), Diff-Quik, and Papanico-
laou.
All 3 cases were independently evaluated by 2 of the
authors under light microscopy. The 3 cases were also
submitted to incisional biopsies under local anesthesia,
and the obtained material was immediately immersed in
10% formalin. The specimens were stained in HE and
independently analyzed by the same authors under light
microscopy.

RESULTS
The 3 patients included 2 women and 1 man, with a
mean age of 36 years, varying from 19 to 48 years. All
patients complained of painful firm submucosal swell-
ings located on hard palate (2 cases) or buccal mucosa
(1 case), with mean size of 3.2 cm, varying from 1.5 to
4.0 cm (Figs. 1 and 2). Clinically, 1 lesion was mobile
and well defined (buccal mucosa), and 2 lesions exhib-
ited superficial mucosal erythema (palate). Clinical di-
agnosis particularly included salivary gland tumor and
lymphoma for the palatal tumors and salivary gland
tumor and benign mesenchymal lesion for the lesion on
buccal mucosa. Panoramic radiographs did not show
any bony alteration in the 3 cases, but 1 of the palatal
cases showed a slight bone resorption on upper occlusal
radiograph, probably due to cortical bone pressure by
the lesion.
Microscopically, all smears revealed the presence of
small polyhedral cells with hyperchromatic rounded
and angulated nuclei, indistinct or partially distinct
nucleoli, scanty basophilic cytoplasm arranged in is-
lands, and cords in variable proportions. There was a
basophilic amorphous substance among the tumoral
cells, sometimes interposing the cellular islands, some-
times involving isolated cells (Fig. 3). This substance
Fig. 2. Clinical picture of the left buccal submucosal nodule.
presented distinct patterns of deposition, including the
formation of mucoid or hyaline metachromatic glob-
ules when stained with Diff-Quik and common cylin-
dric structures in 2 cases. Cytologic diagnosis was
compatible with ACC in all of the cases, and his-
topathologic analysis of the 3 cases revealed a diagno-
sis of cribriform ACC in 2 cases and tubular ACC in 1
case. Metachromatic globules and cylindric structures
were also found in the tubular ACC, although they were
present in only some smears.
DISCUSSION
The FNAB sensitivity and specificity rates in sali-
vary gland lesions range from 87% to 100% and 84% to
99%, respectively, and ACC is probably the most cy-
tologically representative malignant salivary gland tu-
mor from this group.8-14 However, it is important to
emphasize that although ACC has well defined cyto-
logic diagnostic criteria, the literature reports FNAB
false-negative results of up to 33% and specificity of

244 Netto et al.
Fig. 3. A, B, Fine-needle aspiration biopsy from intraoral adenoid cystic carcinoma showing ovoid and rounded amorphous
globules with interspersed tumoral cells (A: HE; B: Papanicolaou; original magnification ⫻120). C, D, Details of the amorphous
globules surrounded by small cells with scanty cytoplasm and hyperchromatic nuclei (Papanicolaou; original magnification: A
⫻120 and B ⫻160).
near 50% for this tumor.11,14 The smears obtained
through FNAB in the present cases showed findings
similar to those in the literature, presenting small poly-
hedral cells with hyperchromatic nuclei and scanty
cytoplasm, associated with extracellular basophilic
globular material.6,8,9,13 However, some other salivary
gland tumors, especially pleomorphic adenoma (PA),
basal cell adenoma (BCA), basal cell adenocarcinoma,
and polymorphous low-grade adenocarcinoma (PLGA),
can be cytologically misinterpreted as ACC, even con-
sidering the typical findings of the latter on
FNAB.6,13,14 Cytologically, all of these tumors and
some lymphomas are characterized by the proliferation
of small blue cells, which can be highly homogeneous
and present monotonous and uniform nuclei.13 Curi-
ously, owing to its homogeneous cellularity, about one-
third of all ACC are cytologically interpreted as benign
neoplasms, especially PA, and several authors have
called attention to the importance of evaluating the
stromal component of ACC, a hallmark of its cytologic
differential diagnosis.9,11,14 Kawahara et al.5 reinforced
that the metachromatic globules are typical of ACC, not
reported in PLGA, and highly uncommon in PA. Nev-
ertheless, it is worthwhile to reinforce that these glob-
ules are common in the cribriform variant of ACC,
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August 2008
which represents about 50% of the cases,2 being sparse
or even absent in the other half of these tumors.
There is a great cytologic similarity between ACC
and BCA, and both aspirates present a plentiful cellular
content that consists almost exclusively of small and
uniform blue cells, with scanty cytoplasm, showing few
indications of malignancy (in the case of ACC), making
both tumors frequently indistinguishable.7,13 Differen-
tial diagnosis is even more difficult when ACC present
few metachromatic spheres and cylinders, both consid-
ered to be hallmarks of this tumor.13 Compared with
ACC, BCA present cells with narrower intercellular
space, abundant eosinophilic cytoplasm, smaller nuclei,
evident chromatin, more indistinct nucleoli, and minor
atypia.7 It is also necessary to include PA as cytologic
differential diagnosis of ACC, but this tumor frequently
shows plasmacytoid, ovoid, and spindle-shaped cells
with dense and abundant cytoplasm, and the metachro-
matic substance is more fibrilar and irregular.8,13 Some
cytologic features have been suggested to aid differen-
tiation of PA and ACC: The embedding of the neoplas-
tic cells within the extracellular matrix is characteristic
of PA, in contrast to the smooth interface between
tumor cells and intercellular matrix that forms the
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Volume 106, Number 2
spheres and cylinders in ACC,7,13 although these fea-
tures are not always easily identifiable.
The most important cytologic differential diagnosis
of intraoral minor salivary gland ACC is PLGA. Even
in histopathologic sections, particularly for incisional
biopsies, sometimes it is difficult to differentiate these
2 neoplasms, although the latter has been characterized
by cytologic uniformity associated with a variety of
histologic patterns.15 This differentiation is essential,
especially because of their biologic, behavioral, clini-
cal, treatment, and prognostic differences. Both tumors
present small cells and formation of tubules with hya-
line globules; ACC present more abundant globules,
and the nuclei are larger, hyperchromatic, and angu-
lated, in contrast to PLGA, where cytoplasm is more
abundant, nuclei are more rounded, ovoid, or even
spindle-shaped, and the globules and the myxoid/
fibrilar matrix are more scattered.15
Although it has been suggested that some immuno-
markers, such as glial fibrillary acidic protein, vimen-
tin, cytokeratins, and integrins, would be useful in
distinguishing PA and PLGA from ACC, their use is
still not fully used in daily practice.13,16
Incisional biopsy is the most common and accepted
diagnostic method for intraoral minor salivary gland
ACC. However, because FNAB is technically easy,
cost-effective, and less invasive, as well as showing
high specificity, it has been shown to be a useful tool in
diagnosis of these tumors in major salivary glands.5-7 In
addition, FNAB has been shown to be useful in diag-
nosis of ACC involving other anatomic sites, such as
breast, lacrimal gland, nasopharynx, maxillary sinus,
and prostate,10-12 and in diagnosis of metastatic ACC of
primary known and unknown sites.12 In contrast to its
utility in these situations, FNAB cytologic features of
intraoral minor salivary gland ACC have been rarely
reported in the literature.7 The present observations
indicate that they are probably similar to those of other
regions, suggesting their usefulness as an additional
diagnostic tool also in the oral cavity, but other larger
series including intraoral minor salivary gland ACC
should be reported to support these findings.
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Reprint requests:
Professor Fábio Ramôa Pires, DDS, PhD
Stomatology and Pathology
Estácio de Sá University
Av. Alfredo Baltazar da Silveira, 580 / cobertura
CEP: 22790-701
Recreio dos Bandeirantes—Rio de Janeiro/RJ
Brazil
ramoafop@yahoo.com