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Year : 2018  |  Volume : 14  |  Issue : 3  |  Page : 706-708

Dedifferentiated adenoid cystic carcinoma ex pleomorphic adenoma of the parotid

Department of Pathology, Post Graduate Institute of Medical Education and Research, Dr. RML Hospital, New Delhi, India

Date of Web Publication12-Jun-2018

Correspondence Address:
Dr. Prajwala Gupta
40/22, Ground Floor, East Patel Nagar, New Delhi - 110 008
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.179522

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 > Abstract 

Carcinoma ex pleomorphic adenoma (Ca ex PA) is defined as a carcinoma arising from a primary (de novo) or recurrent benign pleomorphic adenoma. The most common histological subtype is adenocarcinoma, not otherwise specified, salivary duct carcinoma, mucoepidermoid carcinoma, and adenoid cystic carcinoma (ACC). Few case reports of de novo dedifferentiation in ACC are there in the literature, mostly involving minor salivary glands. The dedifferentiated adenoid cystic carcinoma arising in a pleomorphic adenoma of the parotid gland has not been reported earlier. The present case highlights this rare histological subtype seen in Ca ex PA and the role of extensive histopathological examination and immunohistochemistry.

Keywords: Adenoid cystic, carcinoma ex pleomorphic adenoma, dedifferentiation, immunohistochemistry, parotid

How to cite this article:
Bhardwaj M, Gupta P. Dedifferentiated adenoid cystic carcinoma ex pleomorphic adenoma of the parotid. J Can Res Ther 2018;14:706-8

How to cite this URL:
Bhardwaj M, Gupta P. Dedifferentiated adenoid cystic carcinoma ex pleomorphic adenoma of the parotid. J Can Res Ther [serial online] 2018 [cited 2020 Jul 8];14:706-8. Available from: http://www.cancerjournal.net/text.asp?2018/14/3/706/179522

 > Introduction Top

Carcinoma ex pleomorphic adenoma (Ca ex PA) is a carcinoma that shows histologic evidence of arising in a pleomorphic adenoma or carcinoma arising in a site previously involved by pleomorphic adenoma. Adenocarcinoma, not otherwise specified (NOS), is the most common histological subtype, whereas salivary duct carcinoma, mucoepidermoid carcinoma, and adenoid cystic carcinoma (ACC) can also be identified. Few case reports of de novo dedifferentiation in ACC are there in the literature, mostly involving minor salivary glands and submandibular gland.[1] We report a rare case of Ca ex PA of the parotid gland, which required extensive histopathological examination and immunohistochemistry (IHC) in establishing the diagnosis.

 > Case Report Top

A 40-year-old male presented with the right parotid swelling measuring 2.5 cm × 3 cm in size for the past 8 years. There was an increase in the size of swelling for the past 2 months. It was firm, immobile, and nontender. There was no facial palsy or lymphadenopathy. Clinicoradiological diagnosis was of pleomorphic adenoma. Fine-needle aspiration cytology (FNAC) was performed, and slides were fixed in alcohol and air dried and stained with Papanicolaou and Giemsa stain, respectively. The smears were cellular with round to oval cells arranged in tightly cohesive clusters embedded in myxoid matrix, loosely cohesive clusters, and singly scattered. There was a moderate degree of pleomorphism with granular chromatin and prominent nucleoli in many of the cells [Figure 1]a. Cytoplasm was scant to moderate in amount. Background showed necrotic material and dense myxoid stromal fragments. The cytological impression was of a poorly differentiated carcinoma.
Figure 1: (a) Fine-needle aspiration smear showing dispersed population of pleomorphic cells with prominent nucleoli (Giemsa, ×400) (b) foci of chondromyxoid stroma with surrounding benign epithelial component (H and E, ×40) (c) transition between the adenoid cystic carcinoma (right) and the dedifferentiated component (H and E, ×100)

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The patient underwent total parotidectomy and specimen subjected to histopathological examination. On gross examination, the tumor measured 6 cm × 4 cm × 2 cm. Extensive grossing and sectioning revealed occasional foci of chondromyxoid stroma with the surrounding stroma showing the presence of benign ducts lined by inner flattened to cuboidal epithelium surrounded by spindle myoepithelial cells [Figure 1]b. The tumor was partially encapsulated and highly cellular with cells arranged in sheets, nests, cribriform pattern, and tubules at places. Tumor cells were round to oval with scant cytoplasm, hyperchromatic nucleus, and many with nucleoli as seen in ACC. The dedifferentiated area was seen separately from the differentiated ACC with a transition zone in between [Figure 1]c. Dedifferentiated cells had a large vesicular nucleus with prominent nucleoli and moderate amount of cytoplasm. Many of the cell nests in the dedifferentiated areas showed comedonecrosis, brisk mitosis, and foci of calcification. Intervening stroma showed hyalinization and myxoid change. The tumor was widely invasive into the adjacent normal salivary gland parenchyma. All the resection margins were positive for tumor. Three intraparotid lymph nodes identified were free of tumor and no lymphovascular emboli or perineural invasion was noted.

The IHC showed strong positivity for c-kit (Biogenex, USA), higher Ki-67 index (Dako, Denmark), moderate p53 (Biocare, USA) staining, weak positivity for Her2/neu (Thermoscientific, USA), and strong positive staining for cyclin-D1 (Dako, Denmark) in dedifferentiated areas [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. The differentiated ACC showed strong c-kit positivity, lower Ki-67 index (in <10% of cells compared to 40% of cells in the dedifferentiated area), less p53 staining (in <10% cells compared to 40% of cells in the dedifferentiated area), absence of Her2-neu, and cyclin D1 overexpression. CEA (Diagnostic Biosystems, USA) and p63 (Dako, Denmark) were negative in both the components. The final diagnosis was of dedifferentiated ACC ex PA (Stage III; T3N0M0). The FNA slides were reviewed for ACC-like areas and the only feature noted was the focal presence of relatively uniform looking basaloid cells.
Figure 2: The dedifferentiated area revealing: (a) Strong C-kit positivity (b) p53 positivity (c) weak positivity of Her2/neu (d) strong cyclin D1 positivity (a-d: DAB, ×400)

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 > Discussion Top

Ca ex PA is defined as a carcinoma arising from a primary (de novo) or recurrent benign pleomorphic adenoma and constitutes 12% of malignant salivary gland tumors.[1],[2],[3] Most often, the carcinomatous element is adenocarcinoma, NOS, but occasionally, a specific histological type such as salivary duct carcinoma, mucoepidermoid carcinoma, and ACC can be identified.[1],[4] The other less common histological subtypes include acinic cell carcinoma, epithelial-myoepithelial carcinoma, basal cell carcinoma, myoepithelial carcinoma, squamous cell carcinoma, and clear cell carcinoma.

Dedifferentiation in salivary gland is characterized by areas of conventional carcinoma associated with the concomitant presence of undifferentiated or poorly differentiated carcinoma.[3],[5] However, this has not yet been included in the grading schemes for salivary ACC. Few case reports are there in the literature, mostly involving minor salivary glands and submandibular gland, whereas involvement of parotid is rare.[2],[6]

At least three major criteria are required for dedifferentiation in ACC; proliferation of tumor cells with at least a focal loss of myoepithelial cells surrounding tumor nests, nuclear size at least 2–3 times the size of tubular/cribriform ACC nuclei, thickened irregular nuclear membranes, and prominent nucleoli in a majority of cells.[6] The squamous areas, micropapillary, and the loss of myoepithelial differentiation are considered unique morphological findings in the area transformed.

Similar to the dedifferentiated component, cellular atypia, occasional comedo-like necrosis, and frequent mitotic figures may be seen in the solid type of ACC. However, in the solid type of ACC, solid cell nests are commonly intermixed with cribriform and tubular structures throughout the tumor, instead of being clearly separated from them as in dedifferentiated ACC.[7],[8] In contrast to basaloid cells of solid type, dedifferentiated carcinoma cells have larger, more pleomorphic, and vesicular nuclei with a moderate nucleocytoplasmic ratio. Furthermore, the solid type of ACC may retain focal myoepithelial differentiation.

FNAC is commonly used preoperatively to diagnosis Ca ex PA. The sensitivity, however, is low related to sampling error because of the small residual mixed tumor component. In our case, there was no history of previously diagnosed pleomorphic adenoma and the FNAC smears predominantly revealed areas of dedifferentiation. On reviewing the slides, there was an occasional area of relatively uniform looking basaloid cells representing the differentiated ACC, but there was the absence of cribriform, tubular areas, and basement membrane material. Thus, FNAC had its limitation in diagnosing ACC.

The immunohistochemistry markers to analyze the biological behavior of dedifferentiated ACC include CD117 (c-kit), Her2/neu, p53, E-Cadherin, and cyclin D1.[2],[8] The index case had strong immunoreactivity for CD117(c kit), p53, and cyclin D1, whereas Her2/neu was weakly positive.

Vascular invasion, high mitotic rate, and histological subtype are found to correlate with recurrence in Ca ex PA and poor outcome with widely invasive neoplasm.[9]

The case highlights the importance of extensive histopathological examination in diagnosing Ca ex PA in a patient with the absence of the previous history of pleomorphic adenoma. De novo dedifferentiated ACC is of uncommon occurrence, this case brings about the rare association of the dedifferentiated ACC arising in a pleomorphic adenoma of parotid. It also reasserts the positive IHC markers responsible for the biological behavior resulting in dedifferentiation and poor outcome.

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Conflicts of interest

There are no conflicts of interest.

 > References Top

Antony J, Gopalan V, Smith RA, Lam AK. Carcinoma ex pleomorphic adenoma: A comprehensive review of clinical, pathological and molecular data. Head Neck Pathol 2012;6:1-9.  Back to cited text no. 1
Ide F, Mishima K, Yamada H, Saito I. Adenoid cystic carcinoma ex pleomorphic adenoma of the parotid gland. Head Neck Pathol 2009;3:159-62.  Back to cited text no. 2
Malhotra KP, Agrawal V, Pandey R. High grade transformation in adenoid cystic carcinoma of the parotid: Report of a case with cytologic, histologic and immunohistochemical study. Head Neck Pathol 2009;3:310-4.  Back to cited text no. 3
Lewis JE, Olsen KD, Sebo TJ. Carcinoma ex pleomorphic adenoma: Pathologic analysis of 73 cases. Hum Pathol 2001;32:596-604.  Back to cited text no. 4
Cheuk W, Chan JK, Ngan RK. Dedifferentiation in adenoid cystic carcinoma of salivary gland: An uncommon complication associated with an accelerated clinical course. Am J Surg Pathol 1999;23:465-72.  Back to cited text no. 5
Costa AF, Altemani A, Hermsen M. Current concepts on dedifferentiation/high-grade transformation in salivary gland tumors. Patholog Res Int 2011;2011:325965.  Back to cited text no. 6
Seethala RR. Histologic grading and prognostic biomarkers in salivary gland carcinomas. Adv Anat Pathol 2011;18:29-45.  Back to cited text no. 7
Nagao T, Gaffey TA, Serizawa H, Sugano I, Ishida Y, Yamazaki K, et al. Dedifferentiated adenoid cystic carcinoma: A clinicopathologic study of 6 cases. Mod Pathol 2003;16:1265-72.  Back to cited text no. 8
Katabi N, Gomez D, Klimstra DS, Carlson DL, Lee N, Ghossein R. Prognostic factors of recurrence in salivary carcinoma ex pleomorphic adenoma, with emphasis on the carcinoma histologic subtype: A clinicopathologic study of 43 cases. Hum Pathol 2010;41:927-34.  Back to cited text no. 9


  [Figure 1], [Figure 2]


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