International Journal of Otolaryngology and Head & Neck Surgery, 2013, 2, 174-178 Published Online September 2013 (
Mammary Analogue Secretory Carcinoma of the
Soft Palate: A Report of Two Cases
Denrick Cooper1, Brian Burkey1, Deborah Chute2, Joseph Scharpf1*
1Department of Otolaryngology, Head and Neck Surgery, Cleveland Clinic, Cleveland, USA
2Department of Anatomic Pathology, Cleveland Clinic, Cleveland, USA
Email: *
Received June 3, 2013; revised June 30, 2013; accepted July 10, 2013
Copyright © 2013 Denrick Cooper 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.
Mammary analogue secretory carcinoma (MASC) is a recently identified salivary tumor that shares morphological fea-
tures of secretory carcinoma of the breast, salivary acinic cell carcinoma, low grade cystadenocarcinoma and mucoepi-
dermoid carcinoma. To date, a majority of cases have been reported in the major salivary glands with very few seen in
the palate. We present 2 single institu tion cases of MASC of the soft palate to help further characterize this novel tumor.
Keywords: Mammary Analogue Secretory Carcinoma; ETV6-NTRK3; Secretory Carcinoma
1. Introduction
Salivary gland tumors are relatively rare malignancies
with a worldwide annual incidence of 3 per 100,000 peo-
ple [1]. In the US, salivary gland cancer comprises 6% of
all head and neck cancers and 0.3% of all malignancies
[2]. Mammary analogue secretory carcinoma (MASC)
has been a recently described salivary tumor that shares
morphological features of secretory carcinoma of the
breast, salivary acinic cell carcinoma, low grade cysta-
denocarcinoma and mucoepidermoid carcinoma [3]. Be-
fore its discovery, MASC was often misinterpreted as
acinic cell carcinoma due to similarities in their mor-
phologic appearance [4]. In 2010, Skalova et al. distin-
guished MASC from acinic cell carcinoma based on dis-
tinctive molecular alteration. The ETV6-NTRK3 gene
fusion, caused by a genetic translocation involving chro-
mosomes 15 and 12, specifically t(12; 15) (p13; q25), has
become a hallmark factor for differentiating MASC tu-
mors from other salivary gland carcinomas [3,5]. Even
with the influx of research on MASC, there is still very
little known about the tumor. To date, there have been
approximately 70 reported cases of MASC5. A majority
of cases have been reported in the major salivary glands
(parotid and submandibular), with very few arising from
minor glands. Currently, only six cases have been re-
ported in the palate [6]. In this paper, we present 2 single
institution cases of MASC of the soft palate to further
elucidate this novel cancer.
2. Case Reports
2.1. Case 1
A 43-year-old Caucasian gentleman presented to the
Cleveland Clinic Head and Neck Institute with a several
week history of a non-painful, slow growing, left palatal
lesion with a bluish hue. The patient could not further
specify how long the lesion had been present. He de-
scribed no difficulty swallowing; however, he did report
a feeling of mass effect. The patient had a medical his-
tory significant for lung carcinoma with right pneumo-
nectomy (2004) and recurrent papillomatosis of the lar-
ynx and trachea, status post three laser surgeries. His
physical examination revealed a 2.5 cm cystic-appearing
lesion with a bluish hue on the left soft palate. There was
no impingement of the airway. The nose and nasophar-
ynx were free of disease. The neck was without any
masses, adenopathy nor thyroid nodules bilaterally.
A computerized tomography scan with contrast,
sh owed a hypodense lesion in the posterior lateral aspect
of the left soft palate measuring 2.1 × 1.7 cm (Figure 1).
No pathological lymphadenopathy was appreciated. con-
firm that you have the correct template for your paper
Fine needle aspiration of the mass revealed cytological
findings that were negative for malignant cells but with
limited cellularity and consisted primarily of cyst con-
*Corresponding author.
opyright © 2013 SciRes. IJOHNS
Figure 1. Axial computerized tomography scan with con-
trast. The black arrow identifies the mass in the left soft
tents. Surgical excision and reconstruction with a right
hard palate mucoperiosteal palatal flap was performed in
August 2011. Intraoperative evaluation revealed low
grade salivary gland malignancy, with definitive classi-
fication deferred to permanent section, with negative
hard palate and anterior mucosal margins. There ha s been
no disease recurrence in the 14 months since surgery.
2.2. Case 2
A previously healthy, 26-year-old Caucasian female pre-
sented to Cleveland Clinic with a 7 month history of a
raised, violaceous mass on her right soft palate at the
junction of the hard palate and soft palate. The asymp-
tomatic mass had slightly increased in size over the prior
6 months before presentation. The patient was previously
evaluated by an oral surgeon where an incisional biopsy
had been performed. The biopsy was initially interpreted
at an outside hospital as acinic cell carcinoma, and ex-
tended to the edge of the 1 × 0.5 cm specimen. The pa-
tient was sent to Cleveland Clinic for further manage-
A computerized tomography scan of the head and neck
with contrast revealed neither gross tissue abnormalities
nor significant lymphadenopathy.
Definitive surgical excision of the mass was performed
in April 2011, using a trans-oral robotic surgical ap-
proach. The resected specimen measured 1.2 × 0.5 × 0.3
cm. The final pathologic analysis revealed resid ual tumor
measuring 0.7 cm in size. Intraoperative evaluation
showed negative circumferential and deep margins. There
has been no disease recurrence in the 24 months since
3. Results
3.1. Case 1
Pathologic examination of the palate resection demon-
strated a well circumscribed, partially cystic, submucosal
mass measuring 1.4 cm. Microscopically, the nodule was
comprised of microcystic, tubular and papillary struc-
tures with a lobulated growth pattern. Abundant eosino-
philic luminal material was present. The cells had low-
grade vesicular nuclei with centrally located nucleoli,
surrounded by finely vacuolated eosinophilic cytoplasm
(Figure 2(a)). Rare mitotic figures were identified. A
portion of the tumor had undergone hemorrhagic cystic
degeneration. No tumor necrosis, pleomorphism, or aty-
pical mitotic figures were identified.
The tumor was sent to the University of Pittsburgh
Medical Center for confirmatory fluorescence in situ hy-
bridization (FISH) studies. According to the University
of Pittsburgh’s report, the ETV6 FISH analysis (ETV6
dual-color break apart probe, Abbot Molecular, Des
Plains IL) showed 53.6% of tumor cells (69 counted)
were positive for the translocation, and 20.3% of tumor
cells had a complex arrangement involving ETV6. The
MAML FISH analysis (MEC Dual color break-apart
probe, ZytoVision, Bremerhaven, Germany) showed
96.8% of tumor cells (63 counted) were negative for the
translocation, which is considered negative. These results
confirmed the diagnosis of MASC.
3.2. Case 2
Pathologic examination of the palate resection demon-
strated a well circumscribed submucosal nodule measur-
ing 0.7 cm. Microscopically, the nodule was comprised
of anastomosing tubular structures with abundant eosi-
nophilic secretory material within the luminal spaces
(Figure 2(b)). The cells had low-grade vesicular nuclei
with centrally located nu cleoli, surrounded by finely gra-
nular eosinophilic cytoplasm. Rare mitotic figures were
identified, with up to 3 mitotic figures per 10 high power
fields. No necrosis, pleomorphism, or atypical mitotic
figures were identified.
Immunohistochemical stains demonstrated the neo-
plastic cells were strongly and diffusely positive for
CAM5.2, S-100, and vimentin, and focally positive for
CK5/6 and epithelial membrane antigen. The cells were
negative for DO G-1, p63, SMA, SMMS-1, and androgen
receptor. PAS and PAS with diastase highlighted the lu-
minal secretory material, but were negative within the
cell cytoplasm. A mucicarmine stain was negative for
intracytoplasmic mucin.
Copyright © 2013 SciRes. IJOHNS
Figure 2. (a) The tumor from Case 1 contains anastomosing
tubular structures composed of low-grade cells with vesicu-
lar nuclei and shows abundant eosinophilic secretory mate-
rial within the luminal spaces (Hematoxylin and Eosin,
400×). The tumor from Case 2 (b) shows microcystic and
tubular structures composed of cells with low-grade vesicu-
lar nuclei surrounded by finely vacuolated eosinophilic cy-
toplasm, as well as abundant eosinophilic secretory material
within the luminal spaces (Hematoxylin and Eosin, 200×).
The tumor was sent to the University of Pittsburgh
Medical Center for confirmatory fluorescence in situ hy-
bridization (FISH) studies. According to the University
of Pittsburgh’s report, the ETV6 FISH analysis (EVT6
dual-color break apart probe, Abbott Molecular, Des
Plains IL), showed 81.7% of tumor cells (60 counted)
were positive for the translocation. These results con-
firmed the diagnosis of MASC.
4. Discussion
MASC represents a relatively new tumor classification
for malignancies previously commonly classified as aci-
nic cell cancers [4]. Histologically, MASC bears resem-
blance to secretory breast cancer and some salivary gland
tumors, particularly acinic cell carcinoma and mucoepi-
dermoid carcinoma. This should not be surprising since
salivary and breast tissues derive from the same ecto-
dermal embryonic origin and perform similar functions
in the body.
Since the designation of MASC, there have been over
70 clinical cases in the literature. A majority of the cases
present in the major salivary gland s, primarily the parotid.
Very few cases have been seen in th e soft palate (6 in all)
[5,7,8]. This report adds an additional two cases of
MASC of the soft palate to the literature. Both patients
presented with tumors which appeared cystic and lobu-
lated on physical examination. Microscopically, the tu-
mor cells were arranged in microcystic, glandular and
papillary patterns with abundant vacuolated eosinophilic
cytoplasm. This morphology is consistent with MASC as
previously describ ed in the literature [5,8-11]. In additio n,
FISH studies demonstrated the ETV6-NTRK3 gene fu-
sion diagnostic for MASC in both cases.
Due to its novel nature, the clinical and pathological
features of MASC are still being fully elucidated. How-
ever, retrospective studies have found clinical presenta-
tions similar to the two presented in our study. MASC
can occur over a very wide age range, from 14 - 77 years
old, and often presents as a painless mass for a varied
amount of time, ranging from 2 months to several years.
MASC is more common in men, with a male:female ratio
of 1.5:1. Currently, the literature has not shown a predi-
lection towards race. Patients from Cases 1 and 2 pre-
sented with nodules described as painless and slowly
growing for several weeks and 7 months respectively [5-
7,11,12]. The violaceous and blue hues of the masses,
seen on physical exam, have not been recorded in prior
MASC of the soft palate reports.
Risk factors for this malignancy remain unknown.
Both patients in this report had no prior history of smok-
ing, alcohol intake or other risk factors associated with
oral cancers. The patient from Case 1, did however, have
a history of respiratory papillomatosis of the larynx,
caused by human papilloma virus.
In addition to AciCC, the differential diagnosis for
MASC includes polymorphous low-grade adenocarci-
noma (PLGA) and low-grade cribriform cystadenocarci-
noma (LGCCC). Similar to MASC, PLGA can arise fro m
the minor salivary glands and has an indolent growth pat-
tern with rare invasion into local structures [13]. Grossly,
PLGA is well circumscribed, unencapsulated and usually
not seen with hemorrhage or necrosis [14]. Its micro-
scopic presentation makes it especially difficult to dif-
ferentiate because of the mixture of tubular, papillary,
cribriform, cystic and solid growth patterns that can be
seen at presentation. Histologically, both MASC and
PLGA stain for S-100 and cytokeratin In contrast to
PLGA, MASC is largely eosinophilic and weakly stains
for Ki-67, while PLGA strongly stains for Ki-67 and
GFAP [9,15,16]. The genetics of PLGA are still poorly
understood causing genetic markers to be useless in its
Copyright © 2013 SciRes. IJOHNS
diagnosis. The ETV-NTRK3 fusion transcript is pathog-
nomonic for MASC.
Low-grade cribiform cystadenocarcinoma (LGCCC)
also has a similar clinical course, the architecture and
staining pattern compared to MASC. Both share indolent
courses and can vary in architecture presenting with cys-
tic, solid, cribiform and papillar structures. LGCCC and
MASC both stain positive for S10 0 and CK7. In contrast,
the myoepithelial markers, SMA and calponin are spe-
cific to LGCCC [17,18]. As previously mentioned, the
ETV6-NTRK3 translocation is specific to MASC
Since most MASC cases were previously diagnosed as
acinic cell carcinomas, many were treated with the same
surgical intervention as if acinic cell carcinoma. Similar
to previous cases of MASC, the current two patients
were treated with surgical excision and reconstruction
with no recurrence of the disease following at least 1.5
years follow-up. In a retrospective study done by Chio sea
et al. (n = 27), the disease free survival of conventional
MASC versus acinic cell carcinoma showed no signifi-
cant statistical difference [7]. Rare recurrences (8 in all),
and one case of metastasis have been reported [5]. How-
ever, it is not yet known whether these cases were caused
by a more aggressive form of MASC.
With the small number of cases published, it is diffi-
cult to draw conclusions regarding the treatment of
MASC. Surgical intervention has been the primary treat-
ment thus far. Research has focused on a molecular level
and on the ETV6-NRTK3 translocation. Tognon et al.,
found that the IGF1R axis is vital for the oncogenic
transformation of fibroblasts containing the translocation.
Moreover, IGIFR/INSR kinase inhibitors have been pro-
ven to be effective in significantly reducing tumor grow-
th in vivo and in vitro. These treatments p otentially cou ld
allow for a targeted therap y management strategy fo r this
In summary, this report adds two additional cases of
MASC, involving the soft palate, that the body of litera-
ture is currently available for this n ewly described entity.
The clinical presentations and morphologies of these
cases are similar to previously reported MASC cases.
However, the bluish and violaceous hues, seen in Cases 1
and 2 respectively have not been reported in previous
MASC cases of the soft palate. These observations will
help further characterize this novel tumor.
[1] D. M. Parkin, J. Ferlay, M. P. Curado, et al., “Fifty Year s
of Cancer Incidence: CI5 I-IX,” International Journal of
Cancer, Vol. 127, No. 12, 2010, pp. 2918-2927.
[2] L. A. G. Ries, B. F. Hankey, B. A. Miller, et al., “Cancer
Statistics Review 1973-88,” National Cancer Institute,
Bethesda, 1991.
[3] C. Tognon, S. R. Knezevich, D. Huntsman, et al., “Ex-
pression of the ETV6-NTRK3 Gene Fusion as a Primary
Event in Human Secretory Breast Carcinoma,” Cancer
Cell, Vol. 2, No. 5, 2002, pp. 367-376.
[4] S. I. Chiosea, et al., “The Profile of Acinic Cell Carci-
noma after Recognition of Mammary Analog Secretory
Carcinoma,” American Journal of Surgical Pathology,
Vol. 36, No. 3, 2012, pp. 343-350.
[5] A. Skalova, T. Vanecek, R. Sima, et al., “Mammary Ana -
logue Secretory Carcinoma of Salivary Glands, Contain-
ing the ETV6-NTRK3 Fusion Gene: A Hitherto Unde-
scribed Salivary Gland Tumor Entity,” American Journal
of Surgical Pathology, Vol. 34, No. 5, 2010, pp. 599-608.
[6] F. J. Kratochvil 3rd, J. C. Stewart and S. R. Moore,
“Mammary Analog Secretory Carcinoma of Salivary
Glands: A Report of 2 Cases in the Lips,” Oral Surgery,
Oral Medicine, Oral Pathology and Oral Radiology, Vol.
114, No. 5, 2012, pp. 630-635.
[7] S. I. Chiosea, C. Griffith, A. Assaad and R. R. Seethala,
“Clinicopathological Characterization of Mammary Ana-
logue Secretory Carcinoma of Salivary Glands,” Histo-
pathology, Vol. 61, No. 3, 2012, pp. 387-394.
[8] A. Fehr, T. Loning and G. Stenman, “Mammary Ana-
logue Secretory Carcinoma of the Salivary Glands with
ETV6-NTRK3 Gene Fusion,” American Journal of Sur-
gical Pathology, Vol. 35, No. 10, 2011, pp. 1600-1602.
[9] F. Petersson, D. Lian, Y. P. Chau and B. Yan, “Mammary
Analogue Secretory Carcinoma: The First Submandibular
Case Reported Including Findings on Fine Needle Aspi-
ration Cytology,” Head and Neck Pathology, Vol. 6, No.
1, 2012, pp. 135-139. doi:10.1007/s12105-011-0283-x
[10] L. Pisharodi, “Mammary Analog Secretory Carcinoma of
Salivary Gland: Cytologic Diagnosis and Differential Di-
agnosis of an Unreported Entity,” Diagnostic Cytopatho-
logy, Vol. 41, No. 3, 2012, pp. 239-243.
[11] S. Ito, E. Ishida, A. Skalova, K. Matsuura, H. Kumamoto
and I. Sato, “Case Report of Mammary Analog Secretory
Carcinoma of the Parotid Gland,” Pathology Interna-
tional, Vol. 62, No. 2, 2012, pp. 149-152.
[12] J. C. Rastatter, K. R. Jatana , L. J. Jennings and H. Melin-
Aldana, “Mammary Analogue Secretory Carcinoma of
the Parotid Gland in a Pediatric Patient, Otolaryngology
—Head and Neck Surgery, Vol. 146, No. 3, 2012, pp.
514-515. doi:10.1177/0194599811419044
[13] S. D. Vincent, H. L. Hammond and M. W. Finkelstein,
“Clinical and Therapeutic Features of Poly morphous Low-
Grade Adenocarcinoma,” Oral Surgery, Oral Medicine,
Oral Pathology, Vol. 77, No. 1, 1994, pp. 41-47.
[14] R. González-García, F. J. Rodríguez-Campo, M. F. Mu-
ñoz-Guerra, S. H. Nam-Cha, J. Sastre-Pérez and L. Na-
Copyright © 2013 SciRes. IJOHNS
Copyright © 2013 SciRes. IJOHNS
val-Gías, “Polymorphous Low-Grade Adenocarcinoma of
the Palate: Report of Cases,” Auris, Nasus, Larynx, Vol.
32, No. 3, 2005, p. 275. doi:10.1016/j.anl.2005.03.019
[15] J. T. Castle, L. D. Thompson, R. A. Frommelt, B. M.
Wenig and H. P. Kessler, “Polymorphous Low Grade
Adenocarcinoma,” Cancer, Vol. 86, No. 2, 1999, pp.
[16] I. A. El-Naaj, Y. Leiser, A. Wolff and M. Peled, “Poly-
morphous Low Grade Adenocarcinoma: Case Series and
Review of Surgical Management,” Journal of Oral and
Maxillofacial Surgery, Vol. 69, No. 7, 2011, pp. 1967-
1972. doi:10.1016/j.joms.2010.10.010
[17] M. Brandwein-Gensler and D. R. Gnepp, “Low-Grade
Cribriform Cystadenocarcinoma,” World Health Organi-
zation Classification of Tumours, Pathology & Genetics,
Head and Neck Tumours, 2005.
[18] L. Wang, Y. Liu, X. Lin, D. Zhang, Q. Li, X. Qiu and E.
H. Wang, “Low-Grade Cribriform Cystadenocarcinoma
of Salivary Glands: Report of Two Cases and Review of
the Literature,” Diagnostic Pathology, Vol. 8, No. 1,
2013, pp. 1-6. doi:10.1186/1746-1596-8-28