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  Table of Contents    
CASE REPORT  
Year : 2021  |  Volume : 64  |  Issue : 4  |  Page : 783-787
Cytomorphological features of Mammary Analog secretory carcinoma of parotid gland: Report of 3 cases and review of literature


1 Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of ENT and Head and Neck Surgery, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

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Date of Submission03-Aug-2020
Date of Decision12-Sep-2020
Date of Acceptance09-Dec-2020
Date of Web Publication20-Oct-2021
 

   Abstract 


Mammary analog secretory carcinoma (MASC) of salivary gland is a recently described entity. Due to its rarity and cytomorphological overlap with other salivary gland tumors, it is often difficult to recognize on cytology. Here we describe three such cases with their histopathological correlation. All the three tumors arose in the parotid gland. They were misdiagnosed as mucoepidermoid carcinoma, acinic cell carcinoma and salivary duct adenocarcinoma, respectively. Final diagnosis of MASC was established on their follow-up histopathology and immunochemistry evaluation. Cytosmears of these tumors showed high cellularity with papillary architecture lying within fluid background rich in foamy macrophages. Nuclear atypia varied from minimal to marked with frequent mitosis and presence of necrosis. Cytoplasmic vacuolation was a consistent finding. Although the cytomorphological features of MASC are not specific, a diagnosis of MASC should be strongly considered in the presence of papillary architecture, prominent cytoplasmic vacuolations of the tumor cells and a background of cyst fluid. Immunohistochemistry on cell block may be done to confirm the diagnosis.

Keywords: Cytopathology, FNA, MASC, parotid gland, salivary gland

How to cite this article:
Jha S, Samal S, Ayyanar P, Mishra P, Purkait S, Sable MN, Pradhan P, Adhya AK. Cytomorphological features of Mammary Analog secretory carcinoma of parotid gland: Report of 3 cases and review of literature. Indian J Pathol Microbiol 2021;64:783-7

How to cite this URL:
Jha S, Samal S, Ayyanar P, Mishra P, Purkait S, Sable MN, Pradhan P, Adhya AK. Cytomorphological features of Mammary Analog secretory carcinoma of parotid gland: Report of 3 cases and review of literature. Indian J Pathol Microbiol [serial online] 2021 [cited 2021 Nov 28];64:783-7. Available from: https://www.ijpmonline.org/text.asp?2021/64/4/783/328586





   Introduction Top


Mammary analog secretory carcinoma (MASC) is relatively rare and cytologists are unfamiliar with its cytomorphology. Owing to its rarity, varied cytomorphology, and overlapping of features with other salivary gland tumors, MASC is a potential cause of diagnostic dilemma. It is frequently misdiagnosed as mucoepidermoid carcinoma, acinic cell carcinoma, mucin-producing adenocarcinoma, sebaceous carcinoma, myoepithelial carcinoma, salivary gland papillary neoplasm, and benign salivary aspirate. We describe three cases of MASC with complete cytohistological correlation and immunohistochemistry profile and discuss its morphological differential diagnosis.


   Case History Top


Case 1

A 33-year-old female patient presented with a 4 cm × 3 cm mass in the parotid region. It was a slowly growing painless mass. Fine needle aspiration (FNA) from the mass yielded dirty mucoid material. Cytosmears showed abundant cellularity with papillae like clusters and singly scattered cells in a dirty mucoid background. The cells were large, polygonal with prominent cytoplasmic vacuolations and distinct cell borders. They showed round centrally placed nuclei with single prominent nucleoli and vesicular chromatin. There was a mild nuclear pleomorphism and occasional mitosis. Many singly lying polygonal tumor cells and numerous foamy cyst macrophages were noted in the background [Figure 1]. A cytological diagnosis of malignant salivary gland tumor was made and possibility of mucoepidermoid carcinoma was suggested.
Figure 1: Cytomorphology of case 1: (a) large cohesive papillary cell clusters in a dirty background showing mucin and cyst macrophages, MGG, 200x. (b) Tumor cells showing cytoplasmic vacuolations and prominent cell borders, MGG, 400x. (c) round centrally placed nuclei with prominent single nucleolus and vesicular chromatin. Cytoplasm is dense granular, Pap stain, 400x. Histopathology of case 1: (d) papillary tumor with cystic area, cells show eosinophilic cytoplasm, centrally placed nuclei and prominent nucleoli, focal hob nail appearance. HE stain, 200x. (e) positivity for GCDFP and (f) S-100

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The tumor was surgically resected. Gross examination of the parotid gland showed a well-circumscribed tumor with central cystic area filled with mucoid fluid. The tumor cells were arranged in papillary architecture which showed prominent hob nailing at places. The cells were large, polygonal, and had abundant eosinophilic cytoplasm. They had centrally placed round nucleus with a single central nucleolus and vesicular chromatin [Figure 1]. There was no evidence of squamous or mucinous differentiation. Focal invasion into the adjacent parotid parenchyma was noted. There were no lymphovascular emboli. The regional lymph nodes did not show any tumor metastasis. Tumor cells were immunopositive for CK7, EMA, S100, and GCDFP while negative for CEA, DOG1, P63, SMA, CK20. ER, PR, and Her-2-neu, thus confirming the diagnosis of MASC.

Case 2

A 34-year-old male patient presented with a left parotid swelling. FNAC smears showed high cellularity with large cohesive papillary clusters along with scattered smaller ball-like clusters of cells. The cells were large with abundant vacuolated cytoplasm. The nuclei showed vesicular chromatin and prominent nucleoli. Occasional mitosis was noted. Few necrotic fragments and scattered foamy macrophages were noted in the background. A diagnosis of acinic cell carcinoma was suggested [Figure 2]. Histopathology of the resected specimen revealed a well circumscribed tumor. It was partly cystic and partly solid. The solid areas showed papillary, acinar, and large solid nodule like patterns [Figure 2]. The cells were polygonal, having well-defined cytoplasmic borders, abundant eosinophilic to amphophilic cytoplasm [Figure 2]. Mitosis were few. There was a small area of necrosis. The tumor cells were immunopositive for EMA, S-100, GCDFP, and negative for CEA, DOG1. A diagnosis of MASC was thus confirmed.
Figure 2: Cytomorphology of case 2: (a) cohesive clusters of tumor cells in a dirty hemorrhagic background. Cells are large, round to polygonal with abundant vacuolated cytoplasm with hobnail appearance MGG, 400x (b) cohesive clusters, straight anatomical borders, abundant eosinophilic cytoplasm and numerous cyst macrophages, HE stain, 200x. (c) indistinct cell borders, moderately pleomorphic nuclei, prominent nucleoli. Histopathology of case 2: (d) solid nests of cells with moderately pleomorphic vesicular nuclei and prominent nucleoli. HE stain, 200x. (e) EMA. (f) GCDFP and (g) S100 immunopositivity

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Case 3

A 17-year-old female presented with right parotid swelling. FNAC smears were highly cellular. They showed large papillary clusters of tumor cells. The cells were large with vacuolated cytoplasm. There were moderate nuclear atypia and prominent nucleoli. Background showed numerous cyst macrophages and singly scattered tumor cells were also noted [Figure 3]. The tumor cells showed moderate to marked nuclear pleomorphism and necrotic fragments. A cytological diagnosis of malignant salivary gland tumor was made, and possibility of salivary duct adenocarcinoma was suggested. Histopathological evaluation of the resected specimen showed a malignant tumor composed of tumor cells arranged in cystic, papillary, and solid architecture. There were areas of tumor necrosis. The cells were large with abundant eosinophilic to vacuolated cytoplasm [Figure 3]. There were moderate nuclear pleomorphism, prominent nucleoli, and frequent mitosis. Invasion into the adjacent parenchyma was noted. The cells were immunopositive for Mammaglobin, GCDFP, S-100, and EMA, and immunonegative for CEA, DOG1, P63, SMA, and CK20. A diagnosis of MASC was made.
Figure 3: Cytomorphology of case 3: (a) papillary clusters in a dirty background and cyst macrophage, MGG, 100x. (b) cells with columnar to polygonal appearance, HE stain, 200x. (c) papillary clusters of cells with hobnail appearance. The nuclei are vesicular with prominent nucleoli and cytoplasm is eosinophilic to vacuolated. HE stain, 400x. Histopathology of case 3: (d) cystic tumor with papillary architecture. Large cells with vacuolated cytoplasm with some larger intracytoplasmic vacuoles, HE stain, 400x. (e) negative for mucicarmine stain, 400x. diffuse positivity for (f) S100 and (g) Mammaglobin

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   Discussion Top


Mammary analog secretory carcinoma, or secretory carcinoma of salivary gland is a relatively recently described entity. It shares many of its histological, immunohistochemical, and genetic features with the secretory carcinoma of breast.[1] It is characterized by a recurrent genetic translocation t(12;15) (p13;q25), forming a fusion gene between ETV6 gene on chromosome 12 and the NTRK3 gene on chromosome 15.[2] It is believed that many cases previously reported as acinic cell carcinoma were MASC.[1],[2]

The cytomorphology of Mammary analog secretory carcinoma (MASC) has been described in the literature previously.[3],[4],[5],[6],[7],[8],[9],[10],[11],[12] [Table 1]. Cellularity is generally high in most cases. True papillary architecture with transgressing vessels is the most consistent architectural pattern as demonstrated by these researchers. In addition, large cohesive cell clusters and singly scattered cells are also seen in most cases. Rarely, loosely cohesive cell clusters and follicular structures have also been noted.[10] Our cases conform to these findings. In addition, one of our cases had prominent knobby or hobnail appearance of cells at the peripheral borders of the cell clusters [Figure 3].
Table 1: Cytomorphology of MASC described in literature

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The tumor cells are generally large and polygonal. Variable degree of cytoplasmic vacuolation is a consistent feature of all MASC. In addition to the vacuolated cytoplasm many cells also show cytoplasmic granularity and oncocytic appearance.[9] Squamoid appearance of the cells is also described.[7] Most cases show enlarged, vesicular, round centrally placed nucleus with prominent single central nucleolus or multiple small nucleoli. Anisonucleosis is often prominent.

Presence of a fluid background with cyst macrophages and scattered tumor cells has been found to be common in this tumor as most of these tumors are cystic. The fluid is mostly thin serous type fluid but, presence of mucin has also been noted by Griffith et al.[6] and Higuchi et al.[10] A colloid like background is sometimes found.[8] Hemosiderin laden macrophages are also a common finding in these cases. Our cases in addition, showed presence of necrotic debris and dirty background.

Jung et al.[3] showed that the cytomorphology of MASC varies from predominance of individual cells to papillary clusters or predominance of irregular fragments. The cytomorphology fairly correlates with the histological features (papillary, solid, or micropapillary patterns) of the given tumor. Unusual cytomorphological features of MASC include cohesive cell clusters with small cells having hyperchromatic nuclei and absence of cytoplasmic vacuolation, papillae formation, and a clean background.

MASC bears morphological similarities with many salivary gland tumors such as acinic cell carcinoma, mucoepidermoid carcinoma, salivary duct carcinoma, mucin-producing adenocarcinoma, sebaceous carcinoma, myoepithelial carcinoma, salivary gland papillary neoplasm, and benign salivary gland tumors such as pleomorphic adenoma,[3],[4],[5],[6] thus creating a diagnostic dilemma both on cytology as well as on histopathology of resected specimen. This diagnostic problem is highlighted by our cases. Case number 1 was misdiagnosed as a mucoepidermoid carcinoma. The presence of a dirty fluid background with cyst macrophages, large polygonal cells resembling squamoid cell and vacuolated cells resembling mucinous epithelium led to the misdiagnosis. These findings suggest that in the absence of typical mucinous epithelial cells, a diagnosis of mucoepidermoid carcinoma must be avoided.

In the second case, presence of the cytomorphological features such as large polygonal cells, vacuolated cytoplasm, and centrally placed round nuclei and prominent nucleoli led to the misdiagnosis of acinic cell carcinoma. There is no cytomorphological feature which can reliably distinguish between the two. Hence, a diagnosis of “malignant salivary gland neoplasm” and a differential diagnosis of acinic cell carcinoma/MASC would have been appropriate in this case. High-grade nuclear morphology with presence of necrosis led to the confusion with salivary duct adenocarcinoma or other poorly differentiated carcinomas in the 3rd case. Cytoplasmic vacuolations may lead to confusion with sebaceous carcinoma.

Our cases show that there are no cytomorphological features which would enable a confident diagnosis of MASC to be made. Kai et al.,[11] in their survey of 109 cytopathologists with a case of MASC originating from the minor salivary gland, found that the differential diagnosis varied from benign lesions to malignant tumors, and concluded that the cytodiagnosis of MASC is difficult as its nuclear atypia and increased chromatin are often mild. In our experience, adequate cellularity is obtained in most cases and the cytomorphological features are suggestive enough to make a confident diagnosis of malignancy. If the Milan system of reporting of salivary gland neoplasm is used, most of these cases would be categorized in category V/VI. Few of these cases may yield cyst fluid and cyst macrophages only and would thus be categorized in Milan category I/III.[14] A definitive diagnosis of MASC would require use of Immunohistochemistry with a panel of antibodies including Pan CK, EMA, S-100, DOG1, c-KIT, Mammaglobin, GCDFP, Her-2-neu, SMA, and p63.[15] Pan-CK and EMA will establish the epithelial nature of the tumor whereas SMA and p63 negativity will exclude the salivary gland tumors with dual epithelial and myoepithelial/basal cell differentiation. Mammaglobin and/or GCDFP will confirm the diagnosis of MASC whereas negativity for DOG1 will rule out acinic cell carcinoma, which is its closest morphological mimicker. Hence cell blocks for immunohistochemistry may be prepared in all suspected cases of salivary gland malignancies.

In conclusion, although the cytomorphological features of MASC are not specific, a diagnosis of MASC should be strongly considered in the presence of papillary architecture and prominent cytoplasmic vacuolations of the tumor cells in a background of cyst fluid. In presence of these characteristic features and in conjunction with the appropriate clinical and radiological features, a diagnosis of MASC is possible on FNAC. In difficult cases, immunohistochemistry on cell block may solve the diagnostic dilemma.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Chiosea SI, Griffith C, Assaad A, Seethala RR. Clinicopathological characterization of mammary analog secretory carcinoma of salivary glands. Histopathology 2012;61:387-94.  Back to cited text no. 1
    
2.
Skálová A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, et al. Mammary analog secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: A hitherto undescribed salivary gland tumor entity. Am J Surg Pathol 2010;34:599-608.  Back to cited text no. 2
    
3.
Jung JM, Nam SY, Choi SH, Baek JH. Aspiration cytology of mammary analog secretory carcinoma of the salivary gland. Diagn Cytopathol 2015;43:287-93.  Back to cited text no. 3
    
4.
Kapatia G, Kithan LS, Rohilla, M, Gupta N, Srinivasan R, Dey P, et al. Secretory carcinoma: Fine needle aspiration cytology of a rare parotid gland tumour. Cytopathol 2020;31:243-5.  Back to cited text no. 4
    
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Pisharodi L. Mammary analog secretory carcinoma of salivary gland: Cytologic diagnosis and differential diagnosis of an unreported entity. Diagn Cytopathol 2013;41:239-41.  Back to cited text no. 5
    
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Griffith CC, Stelow EB, Saqi A, Khalbuss WE, Schneider F, Chiosea SI, et al. The cytological features of mammary analog secretory carcinoma: A series of 6 molecularly confirmed cases. Cancer Cytopathol 2013;121:234-41.  Back to cited text no. 6
    
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Levine P, Fried K, Krevitt LD, Wang B, Wenig BM, et al. Aspiration biopsy of mammary analog secretory carcinoma of accessory parotid gland: Another diagnostic dilemma in matrix-containing tumors of the salivary glands. Diagn Cytopathol 2014;42:49-53.  Back to cited text no. 7
    
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Gonzalez MF, Akhtar I, Manucha V. Additional diagnostic features of mammary analog secretory carcinoma on cytology. Cytopathol 2018;29:100-3.  Back to cited text no. 8
    
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Al-Husseinawi E, Hamidpour S, Omoscharka E. Mammary analog secretory carcinoma of salivary gland diagnosed on submandibular gland cytology: A case report and review of the literature. Cytopathol 2019;30:318-22.  Back to cited text no. 9
    
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Higuchi K, Urano M, Takahashi RH, Oshiro H, Matsubayashi J, Nagai T, et al. Cytological features of mammary analog secretory carcinoma of salivary gland: Fine-needle aspiration of seven cases. Diagn Cytopathol 2014;42:846-55.  Back to cited text no. 10
    
11.
Kai K, Minesaki A, Suzuki K, Monji M, Nakamura M, Tsugitomi H, et al. Difficulty in the cytodiagnosis of mammary analog secretory carcinoma: Survey of 109 cytologists with a case originating from a minor salivary gland. Acta Cytol 2017;61:469-76.  Back to cited text no. 11
    
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Gaopande VL, Kulkarni MM, Khandeparkar SG, Joshi AR. Mammary analog secretory carcinoma parotid gland: Case report of a recently described tumor with review of literature. Asian J Oncol 2017;3:139-43.  Back to cited text no. 12
  [Full text]  
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Bishop JA, Yonescu R, Batista DA, Westra WH, Ali SZ. Cytopathologic features of mammary analog secretory carcinoma. Cancer Cytopathol 2013;121:228-33.  Back to cited text no. 13
    
14.
Rossi ED, Baloch Z, Pusztaszeri M, Faquin, WC. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC): An ASC-IAC-sponsored system for reporting salivary gland fine-needle aspiration. J Am Soc Cytopathol 2018;7:111-8.  Back to cited text no. 14
    
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Steven TM, Parekch V. Mammary analog secretory carcinoma. Arch Pathol Lab Med 2016;140:997-1001.  Back to cited text no. 15
    

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Correspondence Address:
Amit Kumar Adhya
Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Bhubaneswar - 751 019, Odisha
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_948_20

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