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Year : 2015  |  Volume : 4  |  Issue : 3  |  Page : 368-371

Carcinoma in a gigantic preexisting pleomorphic adenoma

Department of Surgery, Gandhi Medical College, Bhopal, Madhya Pradesh, India

Date of Web Publication13-May-2015

Correspondence Address:
Vaibhav Vikas
S/o Dr. H.G. Agrawal, 62 A.P. Colony, Gaya 823 001, Bihar
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2278-0513.155990

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Carcinoma ex pleomorphic adenoma (CEPA) is a rare malignancy arising from a primary or recurrent pleomorphic adenoma. Peak incidence is seen in octogenarian females. Delay in diagnosis of CEPA can be attributed to patients negligence owing to a mild nature of symptoms. CEPA is an aggressive tumor occurring mainly is major salivary glands such as parotid and submandibular glands.

Keywords: Carcinogenesis, carcinoma ex pleomorphic adenoma, genes

How to cite this article:
Vikas V, Sharma V, Ahmad Z, Sharma A. Carcinoma in a gigantic preexisting pleomorphic adenoma. Clin Cancer Investig J 2015;4:368-71

How to cite this URL:
Vikas V, Sharma V, Ahmad Z, Sharma A. Carcinoma in a gigantic preexisting pleomorphic adenoma. Clin Cancer Investig J [serial online] 2015 [cited 2021 May 16];4:368-71. Available from:

  Introduction Top

The most frequent type of malignant salivary gland tumors is adenoid cystic carcinoma, followed by adenocarcinoma and carcinoma ex pleomorphic adenoma (CEPA). [1] CEPA is defined as carcinoma arising (CA) from a primary or recurrent pleomorphic adenoma (PA). [2],[3] It is a relatively rare malignancy, which constitutes approximately 3.6% of all salivary gland neoplasms, 6.2% of all mixed tumors and 11.2% of all malignant neoplasms of salivary glands. [2] Prevalence is 56 cases/million and yearly incidence is 0.17 tumors per million persons. [2] Peak age of incidence is sixth to eighth decades of life with slight female preponderance. [2] The macroscopic features that suggest malignant transformation in PA include poorly defined and/or infiltrative tumor margins, the presence of foci of hemorrhage, and necrosis. [1] Difficulty in clinical and pathological diagnosis as well as patients' negligence for seeking treatment makes CEPA a rare but important entity. Herein we discuss a case of 85-year-old female with long standing (20 years) parotid swelling, presenting with a recently developed pain in the swelling which proved out to be CEPA after histological examination. We shall also discuss about the clinical, pathological and molecular perspective along with the causes of delay in treatment.

  Case report Top

An 85-year-old lady presented with the complaint of swelling on the right side of the face for more than 20 years. Swelling initially was about 1 cm × 1 cm in size and noticed just below the ear lobule. It was gradually increasing in size until 2 months when it showed exponential growth in size. Since then she also developed pain in the swelling which was sudden in onset, dull aching, continuous in nature and used to get relieved with analgesics. Pain was associated with a sudden increase in the size of swelling by about 20%.

On clinical examination, a mass of size 22 cm × 10 cm × 10 cm was found over right parotid area, extending up to midline below the chin, hanging up to 8 cm below the right clavicle. Ear lobe was raised upwards. Surface was irregular and bosselated with variegated consistency (firm and cystic). Skin over the swelling was normal in shine and texture except at the lower end where congested veins were present. No signs of facial nerve palsy were found [Figure 1].
Figure 1: Completely excised tumor

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Preoperative fine needle aspiration cytology (FNAC) revealed PA. Computed tomography (CT) scan revealed a large, heterogeneously enhancing solid and cystic mass arising from right parotid gland with maintained surrounding fat planes, with no obvious evidence of infiltration into adjacent tissues and the parapharyngeal space was maintained.

The tumor was excised under general anesthesia. Lazy "S" incision along with the creation of skin flaps to provide sufficient tissue for closure were done. Skin flaps from the surface of the tumor were raised. Facial nerve was found to be embedded within the tumor mass. Lower branches of the facial nerve were divided, and tumor was removed en bloc [Figure 2]. Primary closure was done with a negative suction drain placed in the wound. Postoperatively, facial nerve palsy was evident, which was treated symptomatically [Figure 3].
Figure 2: Postoperative appearance with obvious facial nerve palsy on the affected side

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Figure 3: Black arrow - infiltration of the glandular elements by malignant cells with prominent nucleoli. White arrow - Stroma of the parotid gland showing infiltration by malignant cells. Blue arrow yknotic/dead cells

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Macroscopically the tumor measured 20 cm × 10 cm × 8 cm. On cut section, large lobulated, globular mass with cystic and myxoid degeneration filled with mucoid material and areas of hemorrhage measuring 19 cm × 9 cm × 4 cm were present.

Microscopically sections revealed partially encapsulated tumor composed of solid nests of large pleomorphic malignant epithelial cells with central vesicular nuclei and prominent nucleoli. There were cords and nests of benign epithelial cells enveloped by mantle of myoepithelial cells, in the amphophillic chondromyxoid stroma. At some places, chondroid metaplasia was also seen. Mitotic count was low.

  Discussion Top

Malignant PA is of three types: (1) First is a benign PA, which metastasizes as benign PA. (2) Second type is a carcinosarcoma. (3) Third, the most common type, CEPA develops in association with a benign primary or recurrent PA and accounts for most of the reported cases of malignant PA. [1]

Carcinoma ex pleomorphic adenoma is an aggressive tumor with high overall mortality, occurring mainly is major salivary glands such as parotid and submandibular glands. It mainly occurs in sixth to eighth decades of life, predominantly in females. Most common presenting symptom is a slow growing firm parotid mass. Many a times, it can be asymptomatic as most cancers are not widely invasive and may present like PAs. [4],[5] Facial palsy may or may not be present. [5] In the study by Olsen and Lewis facial nerve involvement was present in approximately one-third of patients. [5] Skin ulceration, tumor fungation, skin fixation, palpable lymphadenopathy, dysphagia, [3],[5] swollen jaw, dental pain and loss of vitality [6] are some other symptoms that may be associated. Pain with rapid enlargement of tumor points toward malignancy. [5]

The risk of malignant transformation in PAs is 1.9-23.3% [7] which increases with long duration, recurrences, advanced age and location in major salivary gland. [8] Risk of malignancy increases from 1.6% in tumors of duration < 5 years, to 9.5% for those with a history of >15 years. [9]

On molecular basis, development of CEPA follows the model of carcinogenesis with loss of heterozygosity at chromosomes 8q (most common), then 12q and finally at 17p [10] associated with mutation in tumor suppressor genes like p53 and p21. [11],[12],[13] Various studies support dysregulation of COX-2 gene [14] and role of cell adhesion molecules (CAM) like E-cadherin, neural-CAM and beta catenin [15],[16],[17],[18] in the development of CEPA.

Gross appearance is greyish-blue and transparent to yellowish if PA component is dominant, with areas of necrosis and hemorrhage if the dominant component is malignant. [2],[5],[19] Microscopically the tumors may be noninvasive, minimally invasive and invasive on the basis of invasion of carcinomatous component outside the fibrous capsule. [20],[21] Malignant component may be adenocarcinoma not otherwise specified (most commonly), adenoid cystic carcinoma, mucoepidermoid carcinoma or salivary duct carcinoma type. [7],[19],[22],[23]

Histological examination is a gold standard for diagnosis. FNAC, commonly used for diagnosis preoperatively, shows a low sensitivity. [3],[7] Combination of FNAC, ultrasonography, CT-scan and magnetic resonance imaging should be used as none of these modalities are of high accuracy when used alone. [24]

Treatment for CEPA is parotidectomy (superficial, total or radical, based on invasiveness of tumor and involvement of adjacent structures like facial nerve, mandible or mastoid). Superficial parotidectomy is done for CEPA localized to the superficial lobe of the parotid gland. Total parotidectomy involves the resection of both the deep and superficial lobes of the parotid, in cases of invasive cancers, with an attempt to preserve the facial nerve. Radical parotidectomy, in cases of facial nerve involvement by the tumor, involves en bloc resection of the tumor along with the facial nerve. Postoperatively chemo-radiotherapy is given. However, there is limited literature on the effectiveness of chemotherapy in the management of CEPA. [3],[22] Neck dissection may or may not be done depending upon presence or absence of metastasis to cervical lymph nodes. [3],[5]

Removal of the specimen may be followed by an immediate reconstructive surgery if required. Sural nerve grafting may be performed in cases where facial nerve has been removed. However, this is not undertaken in the case of longstanding preoperative facial nerve palsy. Rarely, radial forearm free flap, a sternomastoid flap or a cervical rotation flap is performed. According to Gnepp, the 5 years survival rates of the patients of CEPA ranges from 25% to 65%. [2]

  References Top

Ariyoshi Y, Shimahara M, Konda T, Tsuji M. Carcinoma ex pleomorphic adenoma of the sublingual gland: A case report. Int J Oral Sci 2012;4:50-3.  Back to cited text no. 1
Gnepp DR. Malignant mixed tumors of the salivary glands: A review. Pathol Annu 1993;28 Pt 1:279-328.  Back to cited text no. 2
Nouraei SA, Hope KL, Kelly CG, McLean NR, Soames JV. Carcinoma ex benign pleomorphic adenoma of the parotid gland. Plast Reconstr Surg 2005;116:1206-13.  Back to cited text no. 3
Zbären P, Zbären S, Caversaccio MD, Stauffer E. Carcinoma ex pleomorphic adenoma: Diagnostic difficulty and outcome. Otolaryngol Head Neck Surg 2008;138:601-5.  Back to cited text no. 4
Olsen KD, Lewis JE. Ca ex PA: A clinicopathological review. Head Neck 2001;23:705-12.  Back to cited text no. 5
Dewan K, Owens J, Silvester K. Maintaining a high level of suspicion for recurrent malignant disease: Report of a case with periapical involvement. Int Endod J 2007;40:900-7.  Back to cited text no. 6
Kuroishikawa M, Kiyosawa M, Akashi T, Mochizuki M. Case of lacrimal gland carcinoma ex adenoma. Jpn J Ophthalmol 2004;48:181-2.  Back to cited text no. 7
Malata CM, Camilleri IG, McLean NR, Piggot TA, Kelly CG, Chippindale AJ, et al. Malignant tumours of the parotid gland: A 12-year review. Br J Plast Surg 1997;50:600-8.  Back to cited text no. 8
Byrne MN, Spector JG. Parotid masses: Evaluation, analysis, and current management. Laryngoscope 1988;98:99-105.  Back to cited text no. 9
El-Naggar AK, Callender D, Coombes MM, Hurr K, Luna MA, Batsakis JG. Molecular genetic alterations in carcinoma ex-pleomorphic adenoma: A putative progression model? Genes Chromosomes Cancer 2000;27:162-8.  Back to cited text no. 10
Fowler MH, Fowler J, Ducatman B, Barnes L, Hunt JL. Malignant mixed tumors of the salivary gland: A study of loss of heterozygosity in tumor suppressor genes. Mod Pathol 2006;19:350-5.  Back to cited text no. 11
Righi PD, Li YQ, Deutsch M, McDonald JS, Wilson KM, Bejarano P, et al. The role of the p53 gene in the malignant transformation of pleomorphic adenomas of the parotid gland. Anticancer Res 1994;14:2253-7.  Back to cited text no. 12
Tarakji B, Nassani MZ, Sloan P. Immunohistochemical expression of estrogens and progesterone receptors in carcinoma ex pleomorphic adenoma-undifferentiated and adenocarcinoma types. Med Oral Patol Oral Cir Bucal 2010;15:e432-6.  Back to cited text no. 13
Katori H, Nozawa A, Tsukuda M. Increased expression of cyclooxygenase-2 and Ki-67 are associated with malignant transformation of pleomorphic adenoma. Auris Nasus Larynx 2007;34:79-84.  Back to cited text no. 14
Economopoulou P, Hanby A, Odell EW. Expression of E-cadherin, cellular differentiation and polarity in epithelial salivary neoplasms. Oral Oncol 2000;36:515-8.  Back to cited text no. 15
Saleh ER, França CM, Marques MM. Neural adhesion molecule (N-CAM) in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma. J Oral Pathol Med 2003;32:562-7.  Back to cited text no. 16
Genelhu MC, Gobbi H, Arantes DC, Cardoso SV, Cassali GD. Immunolocalization of beta-catenin in pleomorphic adenomas and carcinomas ex-pleomorphic adenomas of salivary glands. Appl Immunohistochem Mol Morphol 2007;15:273-8.  Back to cited text no. 17
de Araújo VC, Furuse C, Cury PR, Altemani A, Alves VA, de Araújo NS. Desmoplasia in different degrees of invasion of carcinoma ex-pleomorphic adenoma. Head Neck Pathol 2007;1:112-7.  Back to cited text no. 18
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. 19
Barnes L, Eveson JW, Reichart P, Sidranski D. WHO Classification of Tumours. Pathology and Genetics of Head and Neck Tumours. Lion: IARC Press; 2005.  Back to cited text no. 20
Altemani A, Martins MT, Freitas L, Soares F, Araújo NS, Araújo VC. Carcinoma ex pleomorphic adenoma (CXPA): Immunoprofile of the cells involved in carcinomatous progression. Histopathology 2005;46:635-41.  Back to cited text no. 21
Lüers JC, Wittekindt C, Streppel M, Guntinas-Lichius O. Carcinoma ex pleomorphic adenoma of the parotid gland. Study and implications for diagnostics and therapy. Acta Oncol 2009;48:132-6.  Back to cited text no. 22
Negahban S, Daneshbod Y, Shishegar M. Clear cell carcinoma arising from pleomorphic adenoma of a minor salivary gland: Report of a case with fine needle aspiration, histologic and immunohistochemical findings. Acta Cytol 2006;50:687-90.  Back to cited text no. 23
Raine C, Saliba K, Chippindale AJ, McLean NR. Radiological imaging in primary parotid malignancy. Br J Plast Surg 2003;56:637-43.  Back to cited text no. 24


  [Figure 1], [Figure 2], [Figure 3]


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