Carcinoma ex Pleomorphic Adenoma (CXPA)-A rare parotid malignancy
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1 Indian Journal of Mednodent and Allied Sciences, pp Indian journals.com Case Report Carcinoma ex Pleomorphic Adenoma (CXPA)-A rare parotid malignancy Vani Padmaja GJ 1 *, Sireesha A 2, Sunderi Devi T 3 and Vijaya Nirmala B 4 ABSTRACT Carcinoma ex pleomorphic adenoma (CXPA) is a rare parotid malignancy and its prognosis is poorer than other parotid malignancies. Invasive tumours tend to behave in a more aggressive fashion. These tumours are seen in patients in the sixth to seventh decades of their life. We present a 38-year-old male with a right-sided parotid gland swelling, which was present for the past 3 to 4 years and gradually increasing in size, with a solitary pulmonary nodule in the left upper lobe. On Fine Needle Aspiration Cytology (FNAC) of the parotid gland, a diagnosis of CXPA was given. This was confirmed by histopathology as CXPA with the malignant component of mucoepidermoid carcinoma and ductal carcinoma and with comedo pattern of necrosis. KEYWORDS: Pleomorphic adenoma, Mucoepidermoid carcinoma, Ductal carcinoma, Vascular emboli, Invasion, Metastasis INTRODUCTION The carcinoma ex pleomorphic adenoma (CXPA) was first described by Beahrs et al.[1] in It is defined as a carcinoma that arises in the epithelial and or myoepithelial component of a pleomorphic adenoma. In most instances (75%), the luminal epithelial cells undergo malignant change. It constitutes 99% of all the cases of malignant mixed tumours. It develops in 6% of all pleomorphic adenomas. It constitutes 3.6-4% of all salivary gland tumours and 12% of all malignant salivary gland tumours[2,3]. The CXPA is commonly seen in patients in the sixth to seventh decades of their life[1]. The average median age at onset is years; this median age at onset is years older than the median age of patients with pleomorphic adenoma, lending support to the view that long-standing tumours are more prone to malignant change[1,4]. It more commonly occurs in the major salivary glands than in the minor salivary glands. The CXPA is most frequently seen in the parotid gland (67%), whereas the submandibular gland is less frequently involved (15%). The sublingual gland is involved in only 1% of the cases[2]. Fine-needle aspiration is generally one of the first steps taken in diagnosing a salivary gland mass. It is interesting to note that CXPA tends to occur in the deep lobe of the parotid gland, in contrast to most pleomorphic adenomas, which tend to occur in the superficial lobe. This fact may account for the low preoperative diagnostic accuracy and sensitivity of fine-needle aspiration in diagnosing CXPA. It has the highest false-negative rate of 35.3% of all malignant salivary gland tumours[5]. The patient usually presents with a history of a slowly growing, painless mass[6] that suddenly or over a short period enlarges rapidly. Patients usually present with symptoms and signs suggesting malignancy, e.g. fixation to surrounding structures[4], occasional pain, skin infiltration, trismus, facial nerve weakness or palsy. Facial nerve weakness 1 Associate Professor, 2,3,4 Assistant Professor, Department of Pathology, Gandhi Medical College, Secunderabad, Andhra Pradesh, India Corresponding author id: *drvanipadmaja@yahoo.co.in; 2 sireesharam@gmail.com; 3 sunderi_ devi19@yahoo.com; 4 neongate@hotmail.com 54
2 Carcinoma ex Pleomorphic Adenoma (CXPA)-A rare parotid malignancy or palsy has been detected in approximately 23-40% of cases. The CXPAs vary considerably in size; sizes may range from 1 cm to greater than 20 cm. Macroscopic features that suggest malignant transformation in pleomorphic adenoma include poorly defined and/or infiltrative tumour margins[2], the presence of foci of haemorrhage and necrosis. However, some malignant tumours are well-circumscribed[6] (e.g. non-invasive or minimally invasive varieties). Tumours that invade beyond the capsule into the surrounding tissue by less than 1.5 cm are considered minimally invasive; overall, patients with this form of disease have an excellent prognosis. Those tumours that invade beyond 1.5 cm are considered invasive; with such tumours, prognosis varies in accordance with tumour stage, grade, histological type and the proliferative index[7]. Tumours should be carefully evaluated with regard to the degree of invasion of tumour, because treatment will vary accordingly. Perineural[6] and angiovascular invasion are commonly encountered in the invasive types; necrosis is prominent in the high-grade types. Tumours in the invasive category tend to behave in a more aggressive fashion; up to 25-50% of the patients experience recurrence[2] and up to 60-70% of the patients develop local or distant metastasis[2]. Metastatic sites[8] include lymph nodes, bone (especially vertebral bodies) and the brain. Malignant transformation[1,4] may occur up to 50 years after a pleomorphic adenoma is first diagnosed; the average period before malignant transformation is 20 years. The exact aetiologic factors associated with malignant transformation are largely ill-defined; however, exposure to radiation is thought to be a factor. It is also thought that malignant change may result from the development and accumulation of genetic instabilities within the tumour. Interestingly, the rate of occurrence seems to increase with increase in the period during which the pleomorphic adenoma is left untreated[4]. According to some investigators, the rate of malignant change is 1.5% in the first year in which the adenoma goes untreated; it increases to 9.5% after 15 years. On histopathologic examination, the malignancy has an epithelial appearance. It may be a wellrecognised variant of salivary gland carcinomas, such as mucoepidermoid carcinoma and adenoid cystic carcinoma, but this had rarely been the case in the experience of others[2]. In the series of Tortoledo et al.[9], the malign counterpart was classified as salivary duct carcinoma in 13 cases, undifferentiated carcinoma in 10, terminal duct carcinoma in 3 and unclassified in 2 cases. Most of the tumours have a poorly differentiated appearance. As a matter of fact, whenever there is a high-grade adenocarcinoma that is difficult to classify and is found in the salivary gland, the possibility of it having risen from a benign mixed turn should be considered. CASE REPORT A 38-year-old male complained of swelling in front of the right ear. It was present for the past 3-4 years and was gradually increasing in size, but was not associated with pain. All the routine investigations were within normal limits. The X-ray of the chest showed a solitary pulmonary nodule of 2 cm size in the left upper lobe, which was suggestive of tuberculoma radiologically. On examination, there was a single irregular swelling on the right side of the angle of the mandible measuring 6 x 5 cm. It was firm, fixed and non-tender. Skin over-swelling was normal. A clinical diagnosis of pleomorphic adenoma was made. FNAC was done and the smears from the aspirated blood mixed mucoid and myxoid material showed sheets of discohesively scattered duct epithelial cells, along with few ovoid plasmacytoid cells, with the mucoid and myxoid areas in a haemorrhagic background. A large number of duct epithelial cells showed marked pleomorphisim and atypia. Features were in favour of pleomorphic adenoma. However, Indian Journal of Mednodent and Allied Sciences 55
3 Vani Padmaja GJ, Sireesha A, Sunderi Devi T and Vijaya Nirmala B Figure 1: Cytology smears showing features of Pleomorphic Adenoma Figure 2: Cytology smears showing features of malignancy. Figure 4: Histopathological Examination (HPE) showing features of pleomorphic adenoma. Figure 3: Grossly showing irregular grey-brown friable mass along with solid lobulated areas. Figure 5: Histopathological Examination (HPE) showing lymph node with secondary deposit. Figure 6: Histopathological Examination (HPE) showing features of mucoepidermoid carcinoma and comedo type of duct cell carcinoma. 56
4 Carcinoma ex Pleomorphic Adenoma (CXPA)-A rare parotid malignancy in view of the loose discohesive cells with marked pleomorphism and atypia, an excision biopsy was advised to rule out malignancy. Following parotidectomy, a single irregular grey-white to grey-brown friable soft tissue mass measuring 5 x 4 x 3 cm was received. The surface was nodular with areas of haemorrhage and necrosis. The cut surface was grey-white with mucoid areas, areas of haemorrhage and necrosis, with cystic areas along with normal salivary gland tissue at the periphery. Multiple sections from the tumour tissue studied showed acini of normal salivary gland, mononuclear inflammatory infiltrate, mucoid, myxoid and chondroid areas along with sheets of benign duct epithelial cells, suggestive of Pleomorphic adenoma. Tumour tissue also showed cells arranged in sheets, clusters and as small ducts. The individual cells were highly pleomorphic, with marked atypia, anaplasia and with abnormal mitoses. Some cells had clear cytoplasm, while some cells had squamoid differentiation. In many areas a comedo pattern of necrosis was observed. The tumour tissue is seen infiltrating into the acini of the normal salivary gland. The features were suggestive of malignancy along with features of Pleomorphic Adenoma. There were vascular tumour emboli. The intraparotid lymph node showed metastatic tumour deposit. With the above-mentioned morphological features, a diagnosis of CXPA with the malignant component showing histological features of ductal carcinoma and mucoepidermoid carcinoma with vascular tumour emboli and lymph nodal metastasis was made. DISCUSSION The CXPA is a rare complication[2,3] of recurrent pleomorphic adenoma of the parotid gland. It is known to occur in the elderly, aged above 60 years. It is also known to occur when the benign lesion, pleomorphic adenoma, is recurrent and of long-standing duration, i.e. more than 10 years, with an average of 20 years[1,4]. It is also known to occur after repeated surgeries for the above-mentioned neoplasm. Clinically, it occurs as a slow growing, painless mass[6]. In the present case, the carcinoma was observed in a 38-year-old male in the parotid gland, which was present for the past 3-4 years. The tumour size was only 5 x 4 x 3 cm 3 [7]. It was not a recurrent tumour and no prior surgeries were performed on the patient. FNAC[5] was the diagnostic procedure of choice; but, in view of the short duration and younger age, a biopsy was advised. On histopathologic examination, a comedo pattern of duct cell carcinoma with areas showing mucoepidermoid carcinoma was observed[9]. There were vascular tumour emboli and the intraparotid lymph node showed tumour deposit[8]. The pulmonary lesion was reviewed and was thought to be a distant metastatic lesion. Hence, it was concluded that CXPA can occur at a younger age without recurrent pleomorphic adenoma and a conclusive diagnosis can be made on FNAC, which can be later confirmed by histopathology. ACKNOWLEDGEMENT We are grateful to our Professor Dr. P. Jijiya Bai (HOD) and Professor Dr. O. Shravan Kumar for their guidance, Ms Shoba Rani, Histotechnician, and Mr. Francis Xavier, Cytotechnician, for their assistance. REFERENCES 1. Beahrs OH, Woolner LB, Kirklin JW, Devine KD. Carcinomatous transformation of mixed tumors of the parotid gland. AMA Arch Surg (1957). 75(4):605-13; discussion Lewis JE, Oslen KD, Sebo TJ.Carcinoma ex pleomorphic adenoma: pathological analysis of 73 cases. Hum Pathol (2001). 32: Gnepp DR, Wenig BM. Malignant mixed tumors. In: Ellis GL, Auclair PL, Gnepp DR, editors. Surgical pathology of salivary the glands. Philadelphia: Saunders; (1991). pp Spiro RH, Huvos AG, Strong EW. Malignant mixed tumor of salivary origin: a clinicopathologic study of 146 cases. Cancer (1977). 39(2): Indian Journal of Mednodent and Allied Sciences 57
5 Vani Padmaja GJ, Sireesha A, Sunderi Devi T and Vijaya Nirmala B 5. Nagao K, Matsuzaki O, Saiga H, Sugano I, Shigematsu H, Kareko T, et al Histopathologic. studies on carcinoma in pleomorphic adenoma of the parotid gland. Cancer (1981). 48(1): Livolsi VA., Peizin KH.Malignant mixed tum or arising in salivar gland.i. Carcinoma arisin in benign mixed tumo. A clinicopathologic study. Cancer (1977). 39: Klinj anieko J, EL-Naggar AK, Vielh P,Fine needle sampling findings in 26. Carcinoma ex pleomorphic adenomas: diagnostic pit falls and clinical considerations. Diagn Cytopathol (1999). 21: Moberger JG, Eneroth C-M. Malign mixed tumor of major salivary glands. Special refence to the histologic structure in metastases. Cancer (1968). 21: Tortoledo ME, Luna MA, Batsakis JG.Carcinoma ex pleomorphic adenoma and malignant mixed tumor. Histomorphologic indexes. Arch Otolaryngol (1984). 110:
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