Fine-needle aspiration cytology of mammary analog secretory carcinoma masquerading as low-grade mucoepidermoid carcinoma: case report with a review of the literature.

Novel Insights from Clinical Practice Acta Cytologica 2014;58:501–510 DOI: 10.1159/000368070

Received: April 25, 2014 Accepted after revision: September 1, 2014 Published online: October 23, 2014

Fine-Needle Aspiration Cytology of Mammary Analog Secretory Carcinoma Masquerading as Low-Grade Mucoepidermoid Carcinoma: Case Report with a Review of the Literature Jaya Bajaj a Cecilia Gimenez a Farah Slim a Mohamed Aziz b Kasturi Das b a

Department of Pathology, North Shore-LIJ Health System, and b Department of Pathology, Hofstra-North Shore-LIJ School of Medicine, Lake Success, N.Y., USA

Established Facts • Mammary analog secretory carcinoma (MASC) is a malignant salivary gland neoplasm characterized by histologic and immunophenotypic resemblance to secretory carcinoma of the breast with the presence of ETV6-NTRK3 translocation.

Novel Insights • MASC should be included in the differential diagnosis of mucinous salivary lesions with cystic changes on fine-needle aspiration cytology. • We elaborate on the cytologic features of MASC. • We discuss pertinent immunohistochemistry for the differentiation of cytomorphologic mimics of MASC.

Abstract Background/Aim: The primary role of fine-needle aspiration cytology (FNAC) of salivary gland masses is to determine the underlying process and guide further management. The objective of our study is to provide a comprehensive review of cytologic features and ancillary studies of mammary analog secretory carcinoma (MASC), discuss differential diagnosis and review recent advances in the understanding of its bio-

© 2014 S. Karger AG, Basel 0001–5547/14/0585–0501$39.50/0 E-Mail [email protected] www.karger.com/acy

logic behavior. Case: A 23-year-old female underwent ultrasound-guided FNA of a slowly enlarging parotid mass. Smears displayed branching clusters of bland vacuolated polygonal cells in a secretory proteinaceous background. Eosinophilic cells with eccentric nuclei and inconspicuous nucleoli were also noted. Based on positive intracellular mucin staining and the lack of extracellular-matrix material, the cytologic diagnosis rendered was ‘suspicious for low grade mucoepidermoid carcinoma’. Superficial parotidectomy revealed an MASC confirmed by fluorescence in situ hybridization (FISH) studies for ETV6 translocation. Conclusion: MASC should be included in the differential diagnosis of mucinous salivary lesions with cystic changes on FNA. Immunohistochemistry for

Correspondence to: Dr. Kasturi Das Department of Pathology Hofstra-North Shore-LIJ School of Medicine 6 Ohio Drive, Suite 202, Lake Success, NY 11042 (USA) E-Mail kdas1 @ nshs.edu

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Key Words Mammary analog secretory carcinoma · Salivary gland · Fine-needle aspiration · ETV6-NTRK3

mammaglobin and S-100 helps in excluding morphologic mimics. FISH helps to confirm the diagnosis. Age alone should not be a deterrent in diagnosing a carcinoma. © 2014 S. Karger AG, Basel

sected surgical specimen. Sections were stained with mucicarmine and periodic acid-Schiff (PAS) with and without diastase. Immunohistochemical stains of mammaglobin, S-100, keratin cocktail (AE 1/3), smooth-muscle actin (SMA) and p63 were performed on the paraffin sections according to standard laboratory protocols.

Introduction Results

Case Report A 23-year-old female presented with a slowly enlarging left parotid mass. Ultrasound examination demonstrated a 2.2 × 2.0 × 1.6 cm heterogeneous hypoechoic nodule without significant internal vascularity in the superficial portion of the left parotid gland. The patient underwent an ultrasound-guided FNA biopsy. A total of 4 passes using a 22-gauge needle were obtained. The smears were hypercellular and showed a predominant population of polygonal cells with vacuolated cytoplasm and bland nuclei in a background of proteinaceous material. Based on positive mucin staining and the lack of matrix material, the cytologic diagnosis rendered was ‘suspicious for low grade mucoepidermoid carcinoma’. However, as there were no definitely identifiable epidermoid and intermediate cells, a differential diagnosis including mucinous metaplasia in benign neoplastic or chronic inflammatory processes was also suggested. The patient underwent a left superficial parotidectomy, which revealed a 2.5 × 2.0 cm solid, cystic mass. Materials and Methods A total of 6 aspirate smears – 3 air-dried and stained with DiffQuik and 3 alcohol-fixed and stained with Papanicolaou (PAP) stain – and a cell block (from needle rinse formalin) were prepared. Mucicarmine staining was performed on the cell-block section. Hematoxylin and eosin (HE)-stained, 5-μm-thick sections were obtained from the formalin-fixed, paraffin-embedded re-

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Acta Cytologica 2014;58:501–510 DOI: 10.1159/000368070

Cytologic Findings Cytology slides showed a moderately cellular specimen displaying abundant sheets, complex branching clusters (some with traversing vessels) and single, intermediate-sized, polygonal cells with abundant vacuolated cytoplasm (fig. 1a–c). The vacuoles ranged from fine microvesicular to large macrovesicular single vacuoles pushing and indenting the nucleus (fig. 1d). Occasional clusters were composed of cells with vacuolated cytoplasm admixed with cells with denser cytoplasm (fig. 2a). There were also clusters of cells with granular eosinophilic cytoplasm with eccentrically located and inconspicuous nuclei (fig. 2b) and delicate, eosinophilic, abundant cytoplasm with centrally located, bland, round nuclei (fig. 2c). Single columnar and spindled bipolar cells were noted scattered in the background. On closer examination, these cells had the same bubbly vacuolated cytoplasm as those in the clusters (fig. 3a). The nuclei appeared spindled as a result of shearing. The background demonstrated granular proteinaceous material better visualized on PAP stain (fig. 3b). No dense or fibrillar matrix material or significant inflammation was observed. Numerous macrophages were noted (fig. 3c). The cell block showed clusters of polygonal cells with eosinophilic cytoplasm with round, uniform, centrally located nuclei with smooth nuclear contours. Pale-blue luminal secretory material was present (fig. 4a). Mucicarmine stain performed on the cell-block material demonstrated scattered intracytoplasmic mucin-positive cells (fig. 4b). Histologic Findings The tumor was circumscribed and nonencapsulated with adjacent benign seromucinous salivary gland tissue. The lining of the collagenized cyst wall was focally attenuated and focally solid (fig. 5a). The tumor was composed of solid, microcystic, macrocystic and follicular architectural patterns (fig. 5b). The cells contained eosinophilic to focally clear and vacuolated cytoplasm and pale intraluminal secretions (fig. 5c). No significant mitosis or necrosis was detected. The tongues of the tumor infilBajaj /Gimenez /Slim /Aziz /Das


The primary role of fine-needle aspiration cytology (FNAC) in a patient with a salivary gland mass is to determine the underlying process, i.e. inflammatory or neoplastic, and, to the extent possible, arrive at a specific diagnosis. In the case of neoplastic lesions, a preoperative diagnosis – of benign or low-grade malignant neoplasms versus high-grade carcinomas – assists in planning surgery and establishing if lymph node dissection is necessary. One of the main challenges in FNAC of salivary gland lesions is that various pathologic processes exhibit diverse and often overlapping cytologic features. The objective of our study is to discuss pitfalls and provide tips to overcome the challenges in the cytologic diagnosis of mammary analog secretory carcinoma (MASC), to alert practicing cytopathologists to this recently described entity, and provide a review of the literature.

Color version available online

a

b

c

d

Fig. 1. Cytologic findings of the parotid mass. a Cohesive clusters with arborizing branches. Diff-Quik. ×100. b Clusters with traversing vessels. PAP. ×100. c Clusters of


polygonal cells with bubbly vacuolated cytoplasm. Diff-Quik. ×200. d Cells with larger vacuoles and a signet-ring appearance. Diff-Quik. ×400.

b

Fig. 2. Cytologic features observed in MASC which pose potential pitfalls. a Clusters of cells with vacuolated cytoplasm admixed with

c

cells with denser cytoplasm mimicking MEC. Diff-Quik. ×200. b Clusters mimicking AcCC showing cells with granular eosino-

philic cytoplasm with eccentrically located nuclei with centrally located inconspicuous nucleoli. PAP. ×200. c Larger cells with abundant cytoplasm similar to the oncocytes observed in WT. Diff-Quik. ×400.

trated the peritumoral soft tissue into the salivary parenchyma (fig. 5d). Basophilic cytoplasmic granules were not seen. Special stain with PAS with and without diastase highlighted the intraluminal secretory material (fig. 6a, b). Zymogen granules were not highlighted. Mucicarmine stain showed rare intracellular positivity, in addition to faintly staining the luminal secretory mate-

rial (fig. 6c). On immunohistochemical staining, the neoplastic cells were positive diffusely for mammaglobin, S-100 (fig. 6d, e) and AE 1/3, and negative for p63 and SMA. The tumor was sent to the University of Pittsburgh Medical Center for confirmatory fluorescence in situ hybridization (FISH) studies. According to their report, ETV6 FISH analysis (LSI ETV6 Dual Color Break Apart

Tips to Unmask MASC on FNA: Case Report and Review of the Literature


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a


a

b

Fig. 3. Background of the FNA smears. a Single columnar and

a

b

a

b

c

d


Fig. 4. Cell-block section. a Cluster of polygonal cells with eosinophilic cytoplasm and round, uniform, centrally located nuclei. HE. ×200. b Tumor cells were positive for mucicarmine stain. ×100.

aceous material. PAP. ×40. c Scattered macrophages. Diff-Quik. ×400.


spindled cells with the same bubbly vacuolated cytoplasm as those in the clusters. PAP. ×400. b Abundant, granular, wavy protein-

c

were microcystic, macrocystic, solid and follicular with pale-blue, extracellular secretory material. ×100. c Cells had eosinophilic to focally clear and vacuolated cytoplasm. ×400. d Tumor infiltrating into salivary gland parenchyma. ×200.

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Fig. 5. Tissue sections of resected parotid mass. HE. a Sections showed cystic and solid areas. ×200. b Architectural patterns


a

c

b

d

secretory material. ×400. On immunohistochemical staining, the neoplastic cells were positive diffusely for mammaglobin (d) and S-100 (e). ×400.


Fig. 6. a, b Special stains and immunostaining pattern of a tumor. Special stain with PAS, with and without diastase highlighted the intraluminal secretory material. ×400. c Mucicarmine stain showed rare intracellular positivity and faint focal staining of the luminal

e

Fig. 7. ETV6 FISH analysis (LSI ETV6 Dual Color Break Apart



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probe) for the 12q13 cytogenetic location showed positive translocation. Green and red arrows show split signals, indicating break of the ETV6 gene. Yellow arrows point to yellow (red/green fusion) signals from intact chromosomes.

Cytologic diagnosis

Number of cases [ref.]

MASC LG MEC Low-grade neoplasm High-grade carcinoma with extensive necrosis AcCC PA PA vs. MEC Benign salivary epithelium AcCC vs. MEC vs. sebaceous-gland neoplasm Not specified

1 [5] 2 [4, 6] 4 [5] 1 [7] 8 [4, 12] 2 [4, 8] 1 [4] 1 [5] 1 [4] 2 [3, 13]

probe) for the 12q13 cytogenetic location showed that 59 of 60 cells analyzed (98.3%) were positive for the translocation, which supported the diagnosis of a lowgrade MASC (fig. 7). Five periparotid lymph nodes examined were negative for tumor. The pathologic stage was pT2N0Mx.

Discussion

MASC, first described in 2010 by Skalova et al. [1], is a malignant salivary gland neoplasm characterized by its histologic and immunohistochemical resemblance to secretory carcinoma of the breast, which harbors a t(12; 15) (p13;q25) translocation resulting in an ETV6-NTRK3 fusion oncogene. This oncogene encodes for a protein composed of an ETS family transcription factor and the protein tyrosine kinase domain of NTRK3. This chimeric protein has been reported to have transformative activity in the epithelial and myoepithelial cells of the mouse mammary gland [2]. The transformation has been shown to be mediated through the activation of the c-Jun/Fos1 AP1 complex [2]. Nearly 90 cases of MASC have been published in the last couple of years [1, 3–13]. In nearly two thirds of the reported cases, MASC presents as a painless, slow-growing mass involving the parotid gland, followed by the minor oral and submandibular salivary glands, with a slight male predominance. The age of presentation ranges from 13 to 78 years with the mean age being in the 5th decade [14]. The current cytology literature is limited to a few reported cases [1, 3–13]. The original cytologic diagnoses of all but 1 of the 23 cases reported in the literature ranged from be506


nign salivary epithelium to high-grade salivary gland carcinoma, the most common diagnosis being acinic cell carcinoma (AcCC) followed by ‘low grade neoplasm’ and mucoepidermoid carcinoma (table 1). We aimed here to provide a comprehensive review of cytologic features, diagnostic pitfalls and potential useful tips for differentiating MASC from the entities listed in differential diagnoses that mimic it closely. Cytomorphologic Features of MASC Reported in the Literature The common cytologic findings reported in the literature are cellular smears with sheets and clusters of polygonal cells with vacuolated cytoplasm. Cytoarchitectural patterns ranging from papillary, acinar-like to tubuloglandular structures are seen. The background is described as clean [3] to granular. Our case had secretory granular proteinaceous material seen better on the PAP stain (fig. 3). This material could easily be mistaken for mucin; however, it did not have the wispy characteristic of mucin and was not visualized on the Diff-Quik stain. Unlike some of the reports [5, 6], no significant metachromatic, extracellular-matrix fibrillar material typically associated with pleomorphic adenoma (PA) was detected. Occasionally, these cases are reported to be cystic leading to the presence of scattered macrophages with and without hemosiderin in the background. In our case, the neoplastic cells had a characteristic abundant vacuolated cytoplasm giving a bubbly to signet-ring appearance (fig. 1). Other cells with granular eosinophilic cytoplasm were seen. The nucleus was bland with smooth nuclear contours and inconspicuous nucleoli. Pisharodi [3] and Sethi et al. [7] have described prominent red nucleoli. Spindled bipolar single cells have been reported [6]. Isolated columnar and spindled bipolar cells were noted in the background in our case and, on closer examination, these had the same bubbly vacuolated cytoplasm as those in the clusters (fig. 4a). The nuclei appeared spindled as a result of the shearing artifact. There was no evidence of necrosis, mitosis or significant cellular atypia. The characteristic cytologic features of MASC reported in the literature are summarized in table 2. Differential Diagnosis It is important to entertain MASC as a possibility when evaluating low-grade malignant salivary gland neoplasms with solid, cystic features, background secretory material and clusters of polygonal cells with vacuolated cytoplasm and bland nuclei. However, one should be cautious about including MASC amongst the possibilities of benign leBajaj /Gimenez /Slim /Aziz /Das


Table 1. Original cytologic diagnosis of the 23 cases reported in the literature

Table 2. Summary of cytologic findings reported in the literature Cellularity

Bishop [4], 2013

Hypercellular

Architecture

Background

Tumor cells Cytoplasm

Nucleus

Sheet-like or papillary fragments

Granular or cystic Naked nuclei No matrix tissue No stromal spindled cells No recognizable mucin

Vacuolated

Open chromatin Irregular envelopes Mild anisonucleosis Inconspicuous nucleoli

Pisharodi [3], Richly 2013 cellular

Clusters and singly dispersed cells

Clean Abundant single cells No cystic change No naked nuclei

Abundant and finely vacuolated

Centrally placed around nuclei Occasional plasmacytoid or signet-ring appearance Prominent red nucleoli

Griffith [5], 2013

Cellular

Acinar-like arborizing papillary transgressing vessels, tubuloglandular

Extracellular mucin Dense eosinophilic debris Metachromatic globular material

Finely granular eosinophilic to abundant vacuolated Signet-ring cells, some containing mucin

Uniform, round, many eccentric Occasionally larger nuclei Mildly irregular nuclear membrane Occasional binucleation

Levine [6], 2014

Extremely cellular

Sheets Crowded clusters

Bright-pink filamentous matrix Bipolar cells

Finely bubbly/denser amphophilic, some with small intracytoplasmic mucin vacuoles No signet-ring cells

Round or oval; smooth contours Slight variation in size Fine chromatin Pinpoint nucleoli Low N/C ratio

Sethi [7], 2014

Cellular

Crowding

Vacuolated

Enlarged nuclei Prominent nucleoli

Petersson [8], Low-to-mo- Loosely cohesive 2012 derate small sheets cellularity Vague acinar structures

Secretory (colloid-like) material of variable staining intensity admixed with tumor cells

Moderately abundant with a slightly bubbly appearance

Focal nuclear membrane Irregularities Finely dispersed chromatin Occasional minute nucleoli

Higuchi [12], Cellular 2014

Loosely cohesive syncytial clusters Papillary clusters

Extracellular mucinous material Small lymphocytes admixed with cell clusters

Vacuolated with varying sizes of vacuoles Signet-ring cells

Round-to-oval small-tomedium nuclei

Takeda [13], 2014

Hypercellular

Sheet-like or papillary fragments

Foam cells and inflammatory cells

Abundant granular cytoplasm No vacuoles

Round nuclei, coarse chromatin

Our study

Cellular

Branching clusters

Granular wavy proteinaceous material No fibrillar matrix

Vacuolated Some eosinophilic

Round or oval Smooth contours Inconspicuous nucleoli

sions, as the definitive surgery for MASC may not be enucleation as is currently advocated for benign lesions. Benign and low-grade malignancies of the parotid are typically treated with excision of the mass, whereas highgrade carcinomas require total parotidectomy, often with lymph node dissection. MASC is currently considered to be a low-grade carcinoma, but experience of this entity is still relatively limited and there is some evidence that it is more aggressive than other low-grade carcinomas. At present, it remains uncertain whether more aggressive clinical management may be warranted. The dif-

ferential diagnosis of MASC includes cystic and mucinous lesions of the salivary gland in addition to lesions with eosinophilic, granular, delicate-to-dense cytoplasm. These include malignant neoplasms such as AcCC, lowgrade mucoepidermoid carcinoma (LG MEC) and benign tumors including PA with mucinous metaplasia and Warthin tumor (WT). Table 3 summarizes the clinical presentations, radiologic findings, cytologic features and immunostaining patterns of common differential diagnostic entities.



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First author [Ref.], year

Table 3. Comparison of common differential diagnostic entities

Imaging features Clinical presentation Cytologic features Cellularity Background Cell type

LG MEC

AcCC

WT

PA with mucinous metaplasia

17 – 78 years Parotid, followed by submandibular, buccal mucosa, palate, lip Solid/cystic

All age groups Parotid, followed by buccal mucosa, palate Solid/cystic well-circumscribed

Children and adults Parotid, followed by minor salivary glands

5th–7th decade Parotid

Children and adults Parotid, followed by minor salivary glands

Solid/cystic Nonspecific features

Solid/cystic Well-circumscribed

Slow-growing mass Rarely pain/facial paralysis

Slow-growing painless mass

Slow-growing mass with or without pain

Enlarging painless mass

Well-circumscribed, may appear cystic Dystrophic calcifications Slow-growing painless mass

Cellular Granular, proteinaceous Cystic Medium-sized, polygonal

Hypocellular Thick mucin Cystic Mucinous, inter-mediate, squamous Mucin vacuoles, dense, waxy Oval, indented

Moderate to high Stripped nuclei Cystic Serous acinar, vacuolated, clear, ductal

Variable Lymphocytes dirty Granular Oncocytes

Cellular Metachromatic fibrillar matrix Myoepithelial, metaplastic Mucinous

Abundant, granular Eosinophilic Enlarged, round-tooval central nucleus Distinct nucleolus

Vacuolated

Indistinct

Abundant vacuolated Basophilic to eosinophilic Uniform, round, eccentric Variable

Negative/positive Negative negative/positive

Negative Negative /positive Negative/negative

Negative Negative Negative/negative

Negative Positive Positive/positive

Cytoplasm

Vacuolated to eosinophilic

Nuclei Nucleoli

Round, uniform, central Indistinct

Immunostain Mammaglobin S-100 SMA/p63

Positive Positive Negative/negative

Low-Grade Mucoepidermoid Carcinoma LG MEC and MASC cells share the features of vacuolated cytoplasm, macrophages/muciphages and proteinaceous material in the background (fig. 2c, d, 4c). However, LG MEC have typically hypocellular smears, unlike all reported cases of MASC so far. LG MEC may be composed of more than one population of cells with a predominance of mucinous and occasional intermediate cells, which are smaller with a metaplastic squamous appearance. Cells with features of both mucinous and epidermoid differentiation are considered to be diagnostic of LG MEC [15]. In our case, we noted clusters of cells with vacuolated cytoplasm admixed with cells with denser cytoplasm as well as single larger cells with eosinophilic cytoplasm, i.e. features mimicking MEC (fig. 2a). Our study, among others, did not detect the characteristic, abundant, thick-to-wispy mucin that stains pale purple with Diff-Quik and pale blue with PAP stain [3, 4, 8]. However, HE-stained sections of the cell block showed luminal, pale-blue, mucin-like material (fig. 4a). The ability to differentiate the wavy, granular proteinaceous material which showed only weak focal positive staining for 508


Small spindle to round Indistinct

mucicarmine is a helpful clue for diagnosing MASC over LG MEC. Although the cytological characteristics of the neoplastic cells in MASC closely mimic LG MEC, the hypercellularity, presence of secretory material and uniformity of the neoplastic cells should prompt the consideration of MASC in the differential diagnosis. Acinic Cell Carcinoma Cellular smears composed of large polygonal cells with granular or abundant vacuolated cytoplasm in loose clusters with bland nuclei are observed in both AcCC and MASC. A mucicarmine stain revealed occasional positive intracytoplasmic mucin in MASC (fig. 4b) as opposed to negative staining in AcCC. Cell-block preparation demonstrating the purple, granular staining cytoplasm of AcCC [15] is helpful in appreciating acinic cell differentiation. Cell blocks of MASC, on the other hand, demonstrated cells with eosinophilic, delicate cytoplasm and extracellular, mucin-like proteinaceous material (fig. 4). Naked nuclei, reported by Bishop et al. [4], can be observed in AcCC, but we (among other studies) did not detect these (table 2). Polygonal cells with vacuolated cyBajaj /Gimenez /Slim /Aziz /Das


Age Site

MASC

Pleomorphic Adenoma Mucous metaplasia observed in benign neoplasms such as PA leads to muciphages which mimic the cells with vacuolated cytoplasm of MASC. Typical chondromyxoid extracellular-matrix material was observed by Levine et al. [6]. The secretory material in MASC has been variably described as ‘colloid-like’ [8], ‘granular’ [4], and ‘dense eosinophilic’ [5]. We did not observe the typical magenta, fibrillar extracellular matrix seen on Diff-Quik stain in PA. The isolated spindled and bipolar cells that we observed had the same bubbly cytoplasm as the polygonal cells in the clusters. We attribute the spindled appearance to the shearing artifact. There is one report of spindle cells intermixed with fibrillar matrix material [6]. There are no other reports in the literature of background spindle cells. Smears with a predominance of cell clusters with vacuolated cytoplasm and secretory material with either absent or minimal chondromyxoid stroma admixed with spindle cells favor a diagnosis of MASC over PA with mucinous metaplasia.

sion in 2 of their 7 cases of MASC; however, localization of the stain, i.e. cytoplasmic or nuclear, was not clarified. Cytoplasmic but not nuclear expression of p63 was observed by Mariano et al. [17]. Diffuse, strong nuclear staining for STAT5a (signal transducer and activator of transcription 5a) was detected in MASC cases reported by Skalova et al. [1]. This finding was corroborated by Mariano et al. [17], but they observed focal low-intensity staining in 37.5% of the AcCC cases. Fortunately, none of their MEC cases expressed STAT5a. The large-droplet adipophilin staining pattern observed in all cases of MASC as opposed to the minute-droplet staining pattern in some cases of AcCC and MEC has been reported as helpful in differentiating MASC from these other entities [17]. There is not always adequate cell-block material for obtaining unlimited numbers of antibodies. Keeping in mind the various cytomorphologic mimics, the proposed immunohistochemistry panel includes mammaglobin, S-100 and a myoepithelial marker of choice like SMA. Differential staining patterns are summarized in table 3.

Immunohistochemistry Ancillary studies with immunohistochemistry performed on cell-block material, if available, may be a useful tool in rendering a diagnosis of MASC from FNA biopsy specimens. The neoplastic cells of MASC showed strong, diffuse, positive staining for mammaglobin, S-100 (fig. 6d, e) and keratin cocktail AE 1/3. Staining for p63 and SMA was negative. This pattern of staining has been observed by most authors [1, 3–13]. However, there have been reports of other salivary gland tumors expressing mammaglobin and S-100. Patel et al. [16] reported that 73% of their MEC cases expressed mammaglobin and 20% expressed S-100. Mammaglobin staining was observed in 11% of the MEC and 6% of the PA cases studied by Bishop et al. [4]. Higuchi et al. [12] reported focal p63 expres-

Clinical Course and Management Generally, the clinical course of conventional MASC is characterized by a moderate risk of local recurrences (15%) and lymph node metastases (20%) and a low risk of distant metastases (5%) [9]. Distant dissemination and tumor-related deaths are often preceded by local recurrence, the risk of which is higher after simple enucleation than after parotidectomy [11]. Clinical stage at diagnosis is the most powerful predictor of prognosis [9]. On the basis of a few cases with follow-up data, MASC is currently regarded as a low-grade carcinoma, and its overall prognosis seems to be favorable. However, Skalova et al. [11] recently reported 3 patients with MASC of the parotid gland in which high-grade transformation was characterized by an accelerated clinical course and a poor outcome. The high-grade component revealed strong membrane staining for EGFR and β-catenin, cytoplasmic/nuclear staining for S-100 protein and nuclear staining for cyclin-D1, while HER-2/neu was absent. They reported that high grade-transformed MASC may have a high propensity for cervical lymph node metastases. In view of the aggressive nature of high grade-transformed MASC, radical surgery with neck dissection and adjuvant radiotherapy are recommended. This study also highlights the need for thorough sampling of all resected MASC specimens to avoid overlooking any high-grade component, particularly in recurrence. Keeping this in mind, it is prudent to sample multiple areas while performing FNA biopsy.



Warthin Tumor The oncocytes and granular background of WT can easily mimic cystic MASC, with clusters of polygonal cells with delicate, eosinophilic cytoplasm (fig. 2c). Fortunately, lymphocytes are not readily seen in the background of MASC, and typical MASC cells with vacuolated cytoplasm are not observed in WT. Age may be a useful distinguishing feature, with patients presenting with WT being typically in their fifth to seventh decade.

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toplasm, extracellular, mucin-like proteinaceous material and an absence of numerous naked nuclei are features that favor MASC over AcCC.

Acknowledgements

Conclusion

MASC should be included in the differential diagnosis of mucinous salivary lesions with cystic changes on FNAC. Immunohistochemistry for mammaglobin and S-100 help in excluding morphologic mimics. FISH helps to confirm the diagnosis. Age alone should not be a deterrent in diagnosing a carcinoma.

The authors thank Dr. Sanja Dacic, MD, PhD (UPMC Presbyterian, Pittsburgh, Pa., USA) for performing and providing photomicrographs for the FISH test.

Disclosure Statement The authors have no conflicts of interest or outside income or any substantive financial support to report.

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Mandibular central mucoepidermoid carcinoma: a case report and review of the literature.

Mucoepidermoid carcinoma of the lung: a case report and literature review.

[Mammary analog secretory carcinoma of the parotid gland].

Mammary Analog Secretory Carcinoma (MASC) Involving the Thyroid Gland: A Report of the First 3 Cases.

Unusual combined thymic mucoepidermoid carcinoma and thymoma: a case report and review of literature.

Primary cutaneous mucoepidermoid carcinoma: a case study with a review of the literature.

Bronchial mucoepidermoid carcinoma: A case report.

Central mucoepidermoid carcinoma of the jaw with distant metastasis: a case report and review of the literature.

Primary Mesenteric Undifferentiated Pleomorphic Sarcoma Masquerading as a Colon Carcinoma: A Case Report and Review of the Literature.

Juxtaoral Organ of Chievitz, an Obscure Anatomical Structure Masquerading as Perineural Invasion of Mucoepidermoid Carcinoma: Case Report and Review of Literature.

Mammary filariasis masquerading as breast carcinoma.

Incidental diagnosis of filariasis in association with carcinoma of gall bladder: Report of a case evidenced on ultrasound-guided fine-needle aspiration cytology with review of the literature.

Sclerosing mucoepidermoid carcinoma with eosinophilia of thyroid gland in a male patient: a case report and literature review.

Cytological features of mammary analogue secretory carcinoma of the parotid gland in a 15-year-old girl: a case report with review of the literature.

Mucoepidermoid carcinoma of the esophagus: report of two cases and review of the literature.