Case Report
Myoepithelial Carcinoma of the Nasal Cavity: A Case Report
Jeong-Hwa Kwon1, Min Jeong Song1, Joon Seon Song1, Seung-Ho Choi2 and Kyung-Ja Cho1*
1Departments of Pathology, University of Ulsan College of Medicine, Korea
2Departments of Otorhinolaryngology, University of Ulsan College of Medicine, Korea
*Corresponding author: Kyung-Ja Cho, Departments of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88, OLYMPIC-RO 43-GIL, SONGPA-GU, SEOUL 05505, Korea
Published: 14 Jan, 2017
Cite this article as: Kwon J-H, Song MJ, Song JS, Choi
S-H, Cho K-J. Myoepithelial Carcinoma
of the Nasal Cavity: A Case Report. Ann
Clin Case Rep. 2017; 2: 1237.
Abstract
Background: Myoepithelial carcinoma is a rare epithelial tumor typically originates in the salivary
gland tissues. We report a case of myoepithelial carcinoma arising in nasal cavity.
Methods: A 53-year-old man presented with a 2-month history of symptoms of nasal obstruction
and epistaxis. Computed tomography revealed an enhancing mass occupying entire left nasal cavity,
with obstructive sinusitis in paranasal sinuses. Medial maxillectomy was performed.
Results: Microscopic analysis revealed multi nodular tumor with solid, reticular, trabecular,
and pseudoacinar growth patterns. Tumor cells were monomorphic round to oval cells, with
eosinophilic cytoplasm and round hyperchromatic nuclei. Clear cells were rare. The tumor cells
showed diffuse immunoreactivity for calponin, smooth muscle actin, p40 and p63, and immuno
negativity for PLAG1. Electron microscopy demonstrated intracytoplasmic myofilaments in tumor
cells. The tumor did not harbor EWSR1 gene rearrangement by break-apart FISH.
Conclusion: This is an additional rare case of sinonasal myoepithelial carcinoma, especially with
ultrastructural and molecular study.
Keywords: Myoepithelial carcinoma; Malignant; Nasal cavity; Sinonasal
Introduction
Myoepithelial carcinoma (MC) is an uncommon neoplasm of the salivary gland, and especially rare in non-salivary gland tissues [1,2] MC of the sinonasal tract is as rare as that of the lung, and only 11 cases have been reported in the English literature. Recently, EWSR1 gene rearrangement has been identified in salivary gland MCs, especially in clear cell and rhabdoid variants. Herein, we report an additional case of sinonasal myoepithelial carcinoma with ultrastructural and molecular study.
Case Presentation
A 53-year-old man was admitted with symptoms of nasal obstruction and epistaxis, anosmia,
postnasal drip, and headache of 2-month duration. He had a history of chemoradiation therapy
for poorly differentiated carcinoma of both nasal cavities 6 years earlier. Paranasal sinus computed
tomography revealed a 4.2 x 3.1 x 2.7-cm enhancing mass occupying the entire left nasal cavity, with
destruction of the nasal septum and involvement of the right nasal cavity (Figure 1, Panel A and B).
Obstructive sinusitis in the maxillary, sphenoidal, and ethmoidal sinuses were also present. Regional
lymph node metastasis was not identified on CT scan. Fusion whole body F-18 fluorodeoxyglucose
positron emission tomography (PET) identified a hypermetabolic mass in both nasal cavities.
Medial maxillectomy was performed for suspected nonkeratinizing carcinoma. Main mass resection
including medial maxillary sinus wall, nasal floor, perpendicular plate and vomer was performed
and other parts of maxillary sinus wall were reserved. Multiple resection margins were identified
by frozen section during surgery, and all submitted resection margins were confirmed to be free of
tumor.The resected mass consisted of multiple fragmented soft tissues. The cut surface of the tumor
was grayish white, soft, and granular (Figure 1, Panel C).
Microscopically, the tumor was a well-defined non-encapsulated multi nodular mass (Figure 1,
Panel D). It contained solid, reticular, and sheet-like structures, with trabecular and pseudoacinar
growth patterns (Figure 1, Panel E). Myxoid matrix occupied the intercellular spaces.
The tumor consisted of monomorphic round to oval cells, with eosinophilic cytoplasm and hyperchromatic nuclei. Cytoplasmic clearing was not evident.
The tumor cells showed mild nuclear pleomorphism, high mitotic
activity (56/10 high-power fields) (Figure1, Panel F), and perineural
invasion (Figure 1, Panel G). The peculiar growth pattern and
intercellular myxoid matrix suggested myoepithelial differentiation.
Immunohistochemical examination confirmed the myoepithelial
differentiation by diffuse positivity for smooth muscle actin (SMA)
(1:200, Dako, Glostrup, Denmark) (Figure 2, Panel A), calponin
(1:1,000, Neomarkers, Califonia, USA) (Figure 2, Panel B), p40
(1:100, Biocare, Califonia, USA) (Figure 2, Panel C), and p63 (1:200,
Dako, Glostrup, Denmark) (Figure 2, Panel D). Immunostaining for
low-molecular-weight cytokeratin (LMW CK) (1:500, Cell Marque,
Califonia, USA) and CD117 (1:400, Dako, Glostrup, Denmark) was
performed for differential diagnosis. LMW CK-positive cells were only sparsely identified (Figure 2, Panel E), and no CD 117-positive
cells were present (Figure 2, Panel F), unlike in cases of epithelial–
myoepithelial carcinoma or adenoid cystic carcinoma, respectively.
Result of immunohistochemical staining for PLAG-1 (1:25, Novus,
Missouri, USA) was also negative. Break-apart fluorescent in situ
hybridization for EWSR1 was performed with commercially available
probe (Vyvis, Downer’s Grove, IL, USA). The results were evaluated by
fluorescence microscopy by scoring tumor cells at 1000 magnification
field. We evaluated tumor nuclei in 5 fields and calculated average
percent of split signals. The result of the space between two signals
greater than two signal distance was considered a split signal and this
interpretation was based on generally accepted guidelines of Vysis.
In our case, 5 fields of total 1200 cells were counted for split signals,
which comprised 6% in average (Figure 3). This result was interpreted as negative for EWSR1 rearrangement. Electron microscopy was
performed using formalin-fixed and paraffin-embedded tissue,
and revealed that the tumor included longitudinally oriented fine
cytoplasmic microfilaments with focal dense bodies and pinocytotic
vesicles (Figure 4). The diagnosis of myoepithelial carcinoma without
EWSR1 gene rearrangement was determined. The patient received no
more adjuvant treatment and has been well for 9 months after the
operation.
Figure 1
Figure 1
Paranasal sinus CT shows an enhancing mass (red arrows) throughout the left nasal cavity with obstructive sinusitis in the paranasal sinuses. (A)
Coronal view and (B) transverse view. (C) Gross examination revealed that the specimen consisted of multiple fragmented soft masses. (D) The tumor is nonencapsulated
but well defined. It was invading adjacent tissue. (E) The tumor showed multinodular architecture with gland-like growths and thin fibrous septa. (F)
Tumor cells are round to oval shape and have eosinophilic cytoplasm with nuclear polymorphism, and prominent mitotic activity (arrow). (G) The tumor has invaded
the adjacent nerve tissue.
Figure 2
Figure 2
The tumor shows strong immunopositivity for SMA (A), calponin (B), p40 (C) and p63 (D). And the tumor shows lower immunoreactivity for LMW CK (E), and shows immunonegativity for CD117 (F) Immunohistochemistry analysis revealed that the Ki-67 labeling index was 50–60% (G).
Figure 3
Figure 3
On fluorescent in situ hybridization for EWSR1, MC comprised
6% in average and was interpreted as negative for EWSR1 rearrangement.
Figure 4
Figure 4
On electron microscopy, the tumor includes longitudinally oriented fine cytoplasmic microfilaments with focal dense bodies and pinocytic vesicles.
Table 1
Discussion
Myoepithelial carcinoma (MC) is a rare epithelial tumor that can
originate de novo, from benign myoepithelioma, or as carcinoma ex
pleomorphic adenoma [3]. MC can occur in various sites throughout
the body, including the breast, lung, head, and neck [4], but most
cases (75%) arise in the parotid gland [5].
Myoepithelial cells have dual features of epithelial and smooth
muscle cells. When neoplastic, myoepithelial cells can appear as
diverse cell types, including spindle, epithelioid, stellate, and hyaline.
The characteristic architecture of myoepithelial carcinoma includes
multilobulated, solid, reticular, pseudoacinar, and trabecular growth
patterns [5]. Different cell types and architectural patterns can be
found within the same tumor. In general, determination of the
myoepithelial nature of MC can be difficult by hematoxylin and
eosin staining alone due to the wide variety of cellular and histologic
features [2]. Our patient had undergone chemoradiotherapy for
the first diagnosis of poorly differentiated carcinoma, and medial
maxillectomy was performed for nonkeratinizing carcinoma.
Immunohistochemistry is the best way to identify MC. On
immunohistochemical staining, MC shows immunoreactivity for
cytokeratin and at least one of the myoepithelial markers, smooth
muscle actin (SMA), glial fibrillary acidic protein (GFAP), CD10 and
calponin, etc [5]. Kane et al. [6] found that MC cells in most patients were immunopositive for vimentin, calponin, and S100 protein (positive in
82–100% of cases). In other studies, SMA and p63 expression rates
were less common (35% and 28%, respectively), and Ki-67 labeling
indices were low (4–10%). In our case, the tumor cells showed diffuse
and strong immunoreactivity for calponin and p40. Moreover, tumor
cells in our case showed very strong immunopositivity for SMA, p63,
and high Ki-67 labeling index (50–60%) unlike cases reported in the
literature. The PLAG1 (pleomorphic adenoma gene 1) is a protooncogene,
and its chromosomal aberrations result in gene fusion
with CTNNB1, CHCHD7, LIFR, and TCEA [7] Transcriptional
upregulation and the protein overexpression of PLAG1 had reported
in case of pleomorphic adenomas and myoepitheliomas. Diagnostic
value of PLAG1 immunostaining as diagnostic marker in salivary
gland tumors is limited, [7] and immunohistochemical study about
PLAG1 of myoepithelial carcinoma in salivary gland has not been
reported, yet. In our study, the tumor cells showed immunonegativity
for PLAG1. Electron microscopy has shown that myoepithelial cells
include longitudinally oriented fine cytoplasmic microfilaments
with focal dense bodies and pinocytotic vesicles, desmosome and
intermediate filaments [5] In our case, myofilaments typical of MC
were identified by electron microscopy.
MC should be differentiated from adenoid cystic carcinoma,
polymorphous low-grade adenocarcinoma (PLGA), and basaloid
squamous cell carcinoma [6,8]. Adenoid cystic carcinoma is
usually strongly positive for c-KIT (CD117) [9] and our case was
immunonegative for c-KIT. Cells of PLGA have bland edges, rare
mitotic figures and are negative for myoepithelial markers [10].
In basaloid squamous cell carcinoma, tumor cells have minimal
cytoplasm, and single cell necrosis and comedonecrosis are common,
and the cells are immunonegative for S100 protein, SMA and GFAP
[11]. Recently, EWSR1 gene rearrangement has been identified in
clear cell and rhabdoid variant MC of the salivary gland [12]. EWSR1 gene is a frequently rearranged gene that is fused with various
partners in many sarcomas [12]. Among the salivary gland tumors,
hyalinizing clear cell sarcoma was first found to harbor EWSR1-ATF
fusion. Skalova et al. [13] analyzed 94 salivary gland carcinomas with
prominent clear cell component and found rearranged EWSR1 in 26
cases of 83 myoepithelial-derived carcinomas with clear cell change,
and found poorer prognosis of EWSR1 rearrangement cases. EWSR1
gene rearrangement in non-salivary MC is not well known, except
for soft tissue cases [14]. We were prompted to confirm EWSR1 gene
status in our sinonasal MC, and the present non-clear cell type MC
did not show EWSR1 rearrangement.
In the English literature, 11 cases of myoepithelial carcinoma of
the sinonasal tract were reported (Table 1). Almost all patients were
in middle age, with no gender predilection. The tumors usually had
firm, solid, and non-encapsulated features, and the mean size was
about 4–7 cm. The growth patterns were solid sheet like, trabecular,
cord-like, and multinodular. Tumor cells were usually round to
oval, with eosinophilic cytoplasm and mild nuclear pleomorphism.
The treatment of choice was surgical excision and some patients
underwent adjuvant chemo-radiation therapy. Two of 11 cases had
tumor recurrences.
MC is a locally aggressive neoplasm that exhibit diverse clinical
outcomes [3]. The treatment of choice is complete surgical excision,
and selective neck dissection may be indicated if nodal metastases
are suspected [15]. Efficacy of radiation therapy and chemotherapy
has not been established. In our case, the patient has presented with
local recurrence 6 years after first manifestation. This relatively
slow progress might be related with absence of EWSR1 gene
rearrangement. Since there was no evidence of metastasis, medial
maxillectomy was performed but the lesion could not be completely
excised. Although the patient has been well for 9 months after the
operation, the probability of disease progression is supposed.
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