Journal of Medical Imaging

and Radiation Sciences

Journal de l’imagerie médicale

et des sciences de la radiation
Journal of Medical Imaging and Radiation Sciences xx (2014) 1-4
www.elsevier.com/locate/jmir

Adenoid Cystic Carcinoma of the Lacrimal Gland: A Case Report with a

Review of the Literature
Steve Stanford, MDa*, Caleb P. Canders, MDa, Michael Linetsky, MDb, Chi K. Lai, MDc,
Elliot Abemayor, MD, PhDd and Claudia Kirsch, MDe
a
Department of Emergency Medicine, University of California Los Angeles, Los Angeles, California, USA
b
Department of Radiology, University of California Los Angeles, Los Angeles, California, USA
c
Department of Pathology, University of California Los Angeles, Los Angeles, California, USA
d
Department of Otolaryngology Head and Neck Surgery, University of California Los Angeles, Los Angeles, California, USA
e
Department of Radiology, The Ohio State University Medical Center, Columbus, Ohio, USA

ABSTRACT
Adenoid cystic carcinomas, the most common malignancies of the
lacrimal gland, are rare overall. We describe a patient who presented
with right periorbital swelling developing over 5 months and mag-
netic resonance imaging findings of a soft tissue mass in the lacrimal
fossa with invasion of the adjacent bone. The patient underwent
right lateral orbitotomy with tumor debulking. Pathologic analysis
showed neoplastic cells in a predominantly cribriform pattern, and
the patient was diagnosed with an adenoid cystic carcinoma of the
lacrimal gland. We review the clinical, radiographic, and histopath-
ologic features of these rare, aggressive malignancies as well as treat-
ment options with reference to the current literature.
Keywords: adenoid cystic carcinoma; lacrimal; oncology; pathology; tumor


RESUM

E
Le carcinome ad
eno€ıde kystique, la plus commune des tumeurs ma-
lignes des glandes lacrymales, demeure quand m^eme rare. Nous
d
ecrivons le cas d’un patient pr
esentant un œdeme p
eriorbital de
l’œil droit d
evelopp
e sur une p
eriode de cinq mois et les conclusions
de l’examen IRM d’une masse de tissu mou dans la fosse lacrymale
avec invasion de l’os adjacent. Le patient a subi une orbitotomie
lat
erale droite avec r
eduction tumorale. L’analyse pathologique a
montr
e la pr
esence de cellules n
eoplasiques en pr
esentation princi-
palement cribriforme, et le patient a reçu un diagnostic de carcinome
ad
eno€ıde kystique de la glande lacrymale. Nous examinons les car-
act
eristiques cliniques, radiographique et histopathologiques de ces
tumeurs malignes rares et agressives ainsi que les options de traite-
ment, avec des r
ef
erences a la documentation scientifique actuelle.

Introduction prognosis. In general, adenoid cystic carcinomas are aggressive

tumors with poor prognoses. Treatment most commonly in-
Malignant tumors of the lacrimal gland are rare and have an
cludes surgery with or without radiation and chemotherapy.
estimated incidence of 0.073 per 100,000 individuals annu-
We describe a patient who presented with right periorbital
ally [1]. Adenoid cystic carcinomas are the most common
swelling and MRI findings of an irregular, soft tissue mass in
type of lacrimal gland malignancy. Patients with adenoid
the lacrimal fossa with globe deformation and bone invasion.
cystic carcinomas may present with asymmetric facial pain
The tumor was resected, and pathologic analysis showed an
or swelling, diplopia, decreased visual acuity, or ptosis [2,
adenoid cystic carcinoma of the lacrimal gland. We review
3]. Magnetic resonance imaging (MRI) is the preferred imag-
the clinical, radiographic, and pathologic features of these
ing modality and often shows a nodular, irregular mass that
rare malignant tumors as well as treatment options.
may invade adjacent nerves or bone. Adenoid cystic carci-
nomas have specific pathologic features that correlate with
Case Presentation
* Corresponding author: Steve Stanford, MD, Department of Emergency
Medicine, David Geffen School of Medicine at UCLA, 924 Westwood A 39-year-old man with no past medical history presented
Boulevard, Suite 300, Box 951777, Los Angeles, CA 90095-1777. with swelling around his right eye that had progressively wors-
E-mail address: sstanford@mednet.ucla.edu (S. Stanford). ened over the preceding 5 months. He had been experiencing
1939-8654/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jmir.2014.01.002
diffuse headaches for 1 year and double vision for 3 weeks. He
denied localized pain or numbness around his eye, weakness
in his face, or decreased vision. On examination, the patient
had proptosis of the right orbit and nontender edema of his
right eyelids and periorbital soft tissue. He had dysconjugate
upward gaze. Visual acuity was 20/20 in both eyes, and visual
fields were intact. His pupils were equally round and reactive,
and the fundoscopic examination was unremarkable. He had
no lymphadenopathy. A computed tomography (CT) scan of
the face showed a lacrimal mass with bony remodeling. MRI
found an enhancing, T1-isointense and T2-hyperintense
irregular soft tissue mass in the right lacrimal fossa associated
with deformation of the posterolateral globe, downward
displacement of the right superior rectus muscle, and invasion
of the adjacent orbital walls (Figures 1 and 2).
There was no perineural or intracranial extension. Imaging
was performed on a 1.5T GE Genesis Signa scanner using a
standard orbital protocol including fat-suppressed T2-
weighted and post-contrast T1-weighted images obtained at Figure 2. T2-weighted fat-suppressed MRI showing a hyperintense, irregular
3-mm slice thickness in the axial and coronal planes. The mass with linear septations (arrowhead).
patient underwent right lateral orbitotomy and tumor debulk-
ing. It was noted intraoperatively that there was no clear On histologic analysis, the tumor appeared to infiltrate the
demarcation between tumor and normal tissue. Based on adjacent benign lacrimal gland tissue. It contained round,
the invasion and erosion of nearby bone, the tumor was given pseudocystic structures filled with basophilic glycosaminogly-
a T4 classification. cans and eosinophilic, hyalinized basal lamina (Figure 3).
Neoplastic cells were predominantly in a cribriform pattern,
and less than 30% were in solid sheets. Occasional tubular
structures were noted. Smooth muscle actin and CD117
staining identified a predominant myoepithelial cell popula-
tion (Figure 4), confirming the diagnosis of intermediate-
grade lacrimal gland adenoid cystic carcinoma. No perineural
or lymphovascular invasion was identified.
Postoperatively, the patient was referred for radiation
therapy. He was subsequently lost to follow-up. The cribri-
form growth pattern of his tumor and the absence of neural

Figure 1. T1-weighted post-gadolinium fat-suppressed MRI showing an Figure 3. Malignant basaloid cells with hyperchromatic nuclei and sparse
enhancing soft tissue mass (arrow) in the right lacrimal fossa with downward cytoplasm in nests (arrow) and multiple, adjacent pseudocystic structures
displacement of the right superior rectus muscle (arrowhead) and invasion of (arrowhead) characteristic of the cribriform pattern of adenoid cystic carci-
the adjacent bone. noma (hematoxylin-eosin, 200).

2 S. Stanford et al./Journal of Medical Imaging and Radiation Sciences - (2014) 1-4


Figure 4. Positive stain for tyrosine kinase receptor CD117 (c-kit) (400).
invasion were associated with a better prognosis. However, his
overall prognosis was poor, given the tumor’s invasion of adja-
cent bone, positive surgical margins, and the low survival rate
of patients with adenoid cystic carcinoma in general.
Discussion
The incidence of lacrimal gland tumors is estimated to be
less than one per 1,000,000 individuals annually [4]. Patients
with lacrimal gland tumors may present with periorbital pain,
asymmetric facial swelling, diplopia, vision changes, ptosis, or
loss of eye motility [2, 3]. Roughly half of lacrimal gland
tumors are malignant [5]. Adenoid cystic carcinoma is the
most common type of malignant lacrimal gland tumor; has
a peak incidence in the fourth decade; and is a slow-
growing, aggressive tumor [2, 6–8]. Up to 80% of patients
with adenoid cystic carcinomas present with facial pain or
numbness secondary to nerve and extraocular muscle invasion
[2, 5, 9]. Metastases are common and can be found in the
lungs, liver, bone, brain, and kidney [8]. Although the etiol-
ogy of adenoid cystic carcinomas is likely multifactorial, the
chromosomal translocation (6; 9)(q22-23; p23–24) has been
identified in many of the tumors [9–12].
Imaging is useful to distinguish between benign and malig-
nant lacrimal gland tumors and to determine the extent of
tumor invasion. On contrast-enhanced CT of the orbits,
benign lacrimal gland tumors often appear round and well
defined, whereas adenoid cystic carcinomas may appear
nodular and irregular [5, 13]. Most malignant lacrimal gland
tumors also show bone erosion and calcification [5]. Contrast-
enhanced CT is useful to detect the extent of lacrimal gland
tumors; however, MRI is the preferred modality to evaluate
for perineural spread and bone invasion [14]. Adenoid cystic
carcinomas typically appear T1 isointense and T2 hyperintese
with enhancement [5].
Pathologic analysis is needed to differentiate lacrimal gland
tumors. Adenoid cystic carcinomas consist of modified myoe-
pithelial and ductal cells that grow in four different patterns:
S. Stanford et al./Journal of Medical Imaging and Radiation Sciences
cribriform, basaloid/solid, sclerosing, and tubular [2]. Multi-
ple growth patterns may be seen in a single tumor. Cribriform
growth, the most common pattern, is characterized by cyst-
like structures containing accumulations of basophilic, amor-
phous glycosaminoglycans or eosinophilic, hyalinized basal
lamina. On the other hand, basaloid/solid growth is character-
ized by a predominance of basaloid myoepithelial cells. The
5-year survival rate of patients with basaloid/solid patterns is
21% compared with a 5-year survival rate of 71% in patients
with nonbasaloid patterns [2, 7, 15]. In addition, increased
numbers of cells expressing tyrosine kinase receptor c-kit
(CD117), a protein found in most adenoid cystic carcinomas,
is associated with a worse prognosis [5, 16].
Given their rarity, there are limited data on the treatment
of malignant lacrimal gland tumors. Most agree that initial
treatment should include surgery, with or without bone
removal or orbitectomy [17–19]. Some studies have shown
significant benefit to orbital exenteration, whereas others
have shown that eye-sparing surgery does not compromise
regional or metastatic disease control [6, 20]. Postoperative
radiation therapy may improve outcomes if adequate surgical
margins cannot be achieved or if there is intracranial invasion
[20, 21]. External beam radiotherapy, brachytherapy, stereo-
tactic radiosurgery, and neutron radiotherapy have been
used to treat adenoid cystic carcinomas [17, 20–27]. One
study found that all patients with malignant lacrimal gland
tumors who did not receive postoperative radiotherapy devel-
oped local or regional recurrence compared with less than
25% patients who received radiotherapy [20]. Patients with
tumors that are difficult to resect may also benefit from neo-
adjuvant chemotherapy [5, 28–30]. Intra-arterial platinum-
based chemotherapy followed by surgical resection and
postoperative radiation has been shown to increase disease-
free survival and decrease recurrence compared with resection
alone [28].
The American Joint Committee on Cancer (AJCC) classifi-
cation defines a TNM staging system but not a stage grouping
for adenoid cystic carcinomas of the lacrimal gland. In the sixth
edition of the AJCC Cancer Staging Manual, tumor size was the
main determinant of T classification [31]. Some studies have
found that patients with tumors  T3 at presentation had
shorter overall survival and time to metastasis [6]. In the sev-
enth edition of the AJCC Cancer Staging Manual, tumors of
any size are classified as T4 if periosteum or bone is involved
[32]. This change in classification has not been shown to corre-
late with risk of death or time to metastasis for adenoid cystic
carcinomas of the lacrimal gland [33]. Overall 10-year survival
of patients diagnosed with adenoid cystic carcinomas is esti-
mated at 20% to 30% although some tumors follow a pro-
longed course [5, 33, 34]. The recurrence rate of adenoid
cystic carcinomas is up to 70% [5, 6]. A worse prognosis is
associated with neural invasion, basaloid growth pattern, and
tumor size > 4 cm at the time of diagnosis [5].
In summary, we describe a 39-year-old man presenting
with right periorbital swelling who was found to have an
adenoid cystic carcinoma of the lacrimal gland. MRI showed
- (2014) 1-4 3
classic features of this rare tumor, including irregular margins
and bony invasion. Surgical resection, with or without
orbitectomy, is recommended in all cases of adenoid cystic
carcinomas. Pathologic analysis of our patient’s tumor
revealed neoplastic cells in a cribriform pattern without peri-
neural or lymphovascular invasion. Our patient may have
benefitted from radiation therapy and neoadjuvant chemo-
therapy, given the bony invasion by the tumor and positive
surgical margins; however, the overall prognosis is generally
poor in patients with adenoid cystic carcinoma.
References
[1] Lacrimal Gland Tumor Study Group (2005). An epidemiological survey
of lacrimal fossa lesions in Japan: number of patients and their sex ratio
by pathological diagnosis. Jpn J Ophthalmol 49, 343–348.
[2] Wright, J. E., Rose, G. E., & Garner, A. (1992). Primary malignant
neoplasms of the lacrimal gland. Br J Ophthalmol 76, 401–407.
[3] Font, R. L., Smith, S. L., & Bryan, R. G. (1998). Malignant epithelial
tumors of the lacrimal gland: a clinicopathologic study of 21 cases. Arch
Ophthalmol 116, 613–616.
[4] Von Holstein, S. L., Therkildsen, M. H., Prause, J. U., Stenman, G.,
Siersma, V. D., & Heegaard, S. (2013). Lacrimal gland lesions in
Denmark between 1974 and 2007. Acta Ophthalmol 91, 349–354.
[5] Von Holstein, S. L., Coupland, S. E., Briscoe, D., Le Tourneau, C., &
Heegaard, S. (2013). Epithelial tumours of the lacrimal gland: a clinical,
histopathological, surgical and oncologic survey. Acta Ophthalmol 91,
195–206.
[6] Ahmad, S. M., Esmaeli, B., & Williams, M., et al. (2009). American Joint
Committee on Cancer classification predicts outcome of patients with
lacrimal gland adenoid cystic carcinoma. Ophthalmology 116, 1210–1215.
[7] Bernardini, F. P., Devoto, M. H., & Croxatto, J. O. (2008). Epithelial
tumors of the lacrimal gland: an update. Curr Opin Ophthalmol 19,
409–413.
[8] Esmaeli, B., Ahmadi, M. A., & Youssef, A., et al. (2004). Outcomes in
patients with adenoid cystic carcinoma of the lacrimal gland. Ophthal
Plast Reconstr Surg 20, 22–26.
[9] Seethala, R. R., Cieply, K., Barnes, E. L., & Dacic, S. (2011). Progres-
sive genetic alterations of adenoid cystic carcinoma with high-grade
transformation. Arch Pathol Lab Med 135, 123–130.
[10] Mitani, Y., Li, J., & Rao, P. H., et al. (2010). Comprehensive analysis of
the MYB-NFIB gene fusion in salivary adenoid cystic carcinoma: inci-
dence, variability, and clinicopathologic significance. Arch Pathol Lab
Med 16, 4722–4731.
[11] Brill, L. B., Kanner, W. A., & Fehr, A., et al. (2011). Analysis of MYB
expression and MYB-NFIB gene fusions in adenoid cystic carcinoma
and other salivary neoplasms. Mod Pathol 24, 1169–1176.
[12] West, R. B., Kong, C., & Clarke, N., et al. (2011). MYB expression and
translocation in adenoid cystic carcinomas and other salivary gland tu-
mors with clinicopathologic correlation. Am J Surg Pathol 35, 92–99.
[13] Perez, D. E., Pires, F. R., Almeida, O. P., & Kowalski, L. P. (2006).
Epithelial lacrimal gland tumors: a clinicopathological study of 18 cases.
Otolaryngol Head Neck Surg 134, 321–325.
[14] Vaidhyanath, R., Kirke, R., Brown, L., & Sampath, R. (2008).
Lacrimal fossa lesions: pictorial review of CT and MRI features. Orbit
27, 410–418.
4 S. Stanford et al./Journal of Medical Imaging and Radiation Sciences
[15] Gamel, J. W., & Font, R. L. (1982). Adenoid cystic carcinoma of the
lacrimal gland: the clinical significance of a basaloid histologic pattern.
Human Pathol 13, 219–225.
[16] Zhou, Q., Chang, H., Zhang, H., Han, Y., & Liu, H. (2012). Increased
numbers of p63-positive/CD117-positive cells in advanced adenoid
cystic carcinoma give a poorer prognosis. Diagn Pathol 7, 119.
[17] Byers, R., Berkeley, R., Luna, M., & Jesse, R. (1975). Combined
therapeutic approach to malignant lacrimal gland tumors. Am J
Ophthalmol 79, 53–55.
[18] Wright, J. E. (1982). Factors affecting the survival of patients with
lacrimal gland tumours. Can J Ophthalmol 17, 3–9.
[19] Wilson, K. F., Ward, D. P., Spector, M. E., & Marentette, L. J. (2011).
Orbitocranial approach for treatment of adenoid cystic carcinoma of the
lacrimal gland. Ann Otol Rhinol Laryngol 120, 397–400.
[20] Skinner, H. D., Garden, A. S., & Rosenthal, D. I., et al. (2011). Out-
comes of malignant tumors of the lacrimal apparatus. Cancer 117,
2801–2810.
[21] Brada, M., & Henk, J. (1987). Radiotherapy for lacrimal gland
tumours. Radiother Oncol 9, 175–183.
[22] Schenck, N. L., Ogura, J. H., & Pratt, L. L. (1973). Cancer of the
lacrimal sac: presentation of 5 cases and review of the literature. Ann
Otol Rhinol Laryngol 82, 153–161.
[23] Spaeth, E. B. (1970). A surgical technique for lacrimal sac malignancy.
Trans Ophthalmol Soc U K 89, 351–354.
[24] Ryan, S. J., & Font, R. L. (1973). Primary epithelial neoplasms of the
lacrimal sac. Am J Ophthalmol 76, 73–88.
[25] Shields, J., Shields, C., Freire, J., Brady, L., & Komarnicky, L. (2003).
Plaque radiotherapy for selected orbital malignancies: preliminary obser-
vations. The 2002 Montgomery lecture, part 2. Ophthal Plast Reconstr
Surg 19, 91–95.
[26] Douglas, J. G., Laramore, G. E., Austin-Seymour, M., Koh, W.,
Stelzer, K., & Griffin, T. W. (2000). Treatment of locally advanced
adenoid cystic carcinoma of the head and neck with neutron radio-
therapy. Int J Radiat Oncol Biol Phys 46, 551–557.
[27] Kim, M., Park, K., Kim, J. H., Kim, Y., & Lee, J. (2008). Gamma knife
radiosurgery for orbital tumors. Clin Neurol Neurosurg 110, 1003–1007.
[28] Tse, D. T., Benedetto, P., Dubovy, S., Schiffman, J. C., & Feuer, W. J.
(2006). Clinical analysis of the effect on intraarterial cytoreductive
chemotherapy in the treatment of lacrimal gland adenoid cystic carci-
noma. Am J Ophthalmol 141, 44–53.
[29] Meel, R., Pushker, N., & Bakhshi, S. (2009). Adjuvant chemotherapy
in lacrimal gland adenoid cystic carcinoma. Pediatr Blood Cancer 53,
1163–1164.
[30] Meldrum, M. L., Tse, D. T., & Benedetto, P. (1998). Neoadjuvant
intracarotid chemotherapy for treatment of advanced adenocystic carci-
noma of the lacrimal gland. Arch Ophthalmol 116, 315–321.
[31] Edge, S. B., Byrd, D. R., Compton, C. C., Fritz, A. G.,
Greene, F. L., & Trotti, A. (2009). AJCC cancer staging manual,
(7th ed.). (pp. 569–571) New York: Springer.
[32] Rootman, J., & White, V. A. (2009). Changes in the 7th edition of the
AJCC TNM classification and recommendations for pathologic analysis
of lacrimal gland tumors. Arch Pathol Lab Med 133, 1268–1271.
[33] El-Sawy, T., Savar, A., Williams, M. D., De Monte, F., & Esmaeli, B.
(2012). Prognostic accuracy of the seventh edition vs sixth edition of the
American Joint Committee on Cancer tumor classification for adenoid
cystic carcinoma of the lacrimal gland. Arch Ophthalmol 130, 664–666.
[34] Aristodemou, P. (2010). Lacrimal gland tumor outcomes. Opthalmology
117, 196.
- (2014) 1-4