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      Carcinoma ex Pleomorphic Adenoma of the Salivary Glands: Distinct Clinicopathologic Features and Immunoprofiles Between Subgroups According to Cellular Differentiation

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          Abstract

          In carcinoma ex pleomorphic adenoma (CXPA), pleomorphic adenoma (PA) and diverse carcinoma components showing luminal (ductal) or non-luminal (myoepithelial) differentiation coexist. To elucidate the clinicopathological implications of cellular differentiation in CXPA and the potential role of p53, vascular endothelial growth factor (VEGF), c-erbB-2, c-kit, and glucose transporter 1 (Glut-1) in carcinogenesis, we analyzed 11 CXPAs with luminal differentiation (CXPAs-LD) and 6 CXPAs with non-luminal differentiation (CXPAs-NLD) and compared protein expressions in residual PAs and carcinomas by immunohistochemistry. Among the CXPAs-LD, 5 were invasive and 8 were histologically high-grade tumors. The 5-year survival rate was 72.7%. P53, c-erbB-2, VEGF, and Glut-1 were more immunoreactive in carcinoma components than in PAs ( P = 0.008, 0.004, 0.002, and 0.024, respectively); c-erbB-2 overexpression was associated with high histological grade ( P = 0.024). Carcinoma components frequently lacked c-kit expression ( P = 0.009). CXPAs-NLD were all low-grade and invasive with a larger mean tumor size (5.2 cm) than CXPAs-LD (3.3 cm) ( P = 0.040). The patients remained disease-free without significant immunohistochemical expression. The immunoprofiles and clinical course of CXPA differed according to cellular differentiation. Therefore, it is important to report the histological subtype and to assess potential biomarkers in diagnostic and therapeutic trials.

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          Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases.

          Randolph V. Lewis, K Olsen, Thomas Sebo (2001)
          Pathologic factors of predictive value for carcinoma ex pleomorphic adenoma (CXPA), an aggressive salivary gland malignancy, are poorly defined. Because residual mixed tumor may be relatively inconspicuous and various carcinoma subtypes are encountered, misdiagnosis is common. To describe the pathologic features and identify potential prognostic factors, we retrospectively examined 73 cases of CXPA of the major salivary glands treated at Mayo Clinic. Paraffin section immunostaining for keratins (AE1/AE3, CK7, CK20), epithelial membrane antigen, carcinoembryonic antigen, vimentin, actin, S-100 protein, glial fibrillary acidic protein, and p53 and c-erbB-2 oncoproteins was performed in 69 cases. DNA content and proliferation indices were determined by digital image analysis of Feulgen- and MIB-I-stained sections, retrospectively. Survival was calculated by the Kaplan-Meier method, and prognostic variables were analyzed with the log-rank test. The carcinoma component was predominant in 82% of tumors. Adenocarcinoma not otherwise specified (31 cases) and salivary duct carcinoma (24 cases) were the most frequent histologic subtypes. Sixty-two tumors were high grade (Broders 3 or 4). Residual mixed tumor was extensively hyalinized in 54 cases. Pathologic features significantly associated with overall survival included pathologic stage (P =.009), tumor size (P =.012), grade (P =.005), proportion of carcinoma (P =.004), extent of invasion (P =.002), and proliferation index of carcinoma (P =.03). Of 4 patients with intracapsular (noninvasive) carcinoma, none had an adverse outcome. The immunohistochemical profile of CXPA included positive staining reactions in the malignant component for AE1/AE3 in 97% of cases, CK7 in 94%, epithelial membrane antigen in 86%, carcinoembryonic antigen in 75%, vimentin in 52%, and S-100 protein in 29%. Expression of p53 and c-erbB-2 oncoproteins was detected in 41% and 30% of the carcinomas, respectively, but neither was associated with decreased survival. High-grade salivary adenocarcinoma that is difficult to classify should raise the suspicion of possible CXPA. Intracapsular carcinoma has a benign clinical course. Significant prognostic factors in CXPA include tumor stage, grade, proportion of carcinoma, extent of invasion, and proliferation index. Copyright 2001 by W.B. Saunders Company.
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            Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 25 patients.

            K Sloman, D Klimstra, Andrew Huvos … (2000)
            Salivary gland carcinomas displaying exclusively myoepithelial differentiation (myoepithelial carcinoma) are considered rare. Their histopathologic features, immunohistochemical profile, and clinical behavior are not well characterized. The authors reviewed the clinicopathologic features of 25 salivary gland tumors fulfilling two fundamental histologic criteria: unequivocally malignant and exclusively myoepithelial. For most of these, the original diagnosis was malignant mixed tumor. Thirteen men and 12 women aged 24 to 77 years (mean age, 55 yrs) participated in the study, and most presented with a painless mass. The parotid gland was the most common site (n = 15). Tumors ranged from 2.1 to 5.5 cm, arising either in association with a benign mixed tumor (n = 15) or de novo (n = 10). Histologically, all the tumors displayed infiltrative growth and most had a characteristic multinodular architecture with a cellular periphery and central necrotic/myxoid zones. Epithelioid, hyaline, spindle, clear, or mixed cell types were noted with accompanying myxoid and/or hyalinized extracellular matrix. Ten tumors were high grade cytologically and 15 were low grade. The mitotic rate ranged from three to 51 mitoses per 10 high-power fields. Necrosis was present in 15 tumors and perineural and vascular invasion were identified in 11 and four neoplasms respectively. Immunoreactivities included CAM5.2 (89%), AE1:AE3 (100%), 34betaE12 (92%), cytokeratin 7 (21%), cytokeratin 14 (53%), vimentin (100%), S-100 protein (100%), smooth muscle actin (50%), calponin (75%), muscle-specific actin (31%), glial fibrillary acidic protein (31%), carcinoembryonic antigen (0%), and epithelial membrane antigen (21%). Ultrastructural examination of three tumors showed myoepithelial features. Ten patients developed recurrences, mostly multiple. Follow up of 17 patients showed that eight patients (47%) developed metastases (six high grade, two low grade) and five patients (29%) died of disease (four high grade, one low grade) after a mean of 32 months. Two patients were alive with disease (19 and 49 mos). Ten patients (59%) were without any evidence of disease after a mean of 42.2 months. Myoepithelial carcinomas exhibit a wide spectrum of cytomorphologic features and diverse clinical outcomes. As a result of their morphologic heterogeneity, they can be confused easily with many tumors. Myoepithelial carcinomas have been underrecognized in the past, primarily by being lumped under a broader category of "malignant mixed tumor." Awareness of their unique cytoarchitectural patterns and immunohistochemical profile is crucial for accurate identification.
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              Carcinoma ex pleomorphic adenoma: a clinicopathologic review.

              Helen J Lewis, K Olsen (2001)
              Carcinoma ex pleomorphic adenoma (CXPA) is an aggressive, poorly understood salivary gland malignancy. Misdiagnosis is common, because the residual mixed tumor component may be small, and various carcinoma subtypes are possible. We retrospectively reviewed the medical records of 73 patients with major salivary gland CXPA treated at our institution from 1960 to 1994. Of the 73 patients, 66 had primary tumors and 7 had recurrent tumors; 47 were men, and 26 were women; the mean age was 61 years. Adenocarcinoma (31 cases) and salivary duct carcinoma (24 cases) were the most common malignant subtypes. All patients were treated surgically, and 32 also had radiation therapy. Of 66 patients with primary tumors, 23% had local recurrence. Metastasis (either initial or delayed) occurred regionally in 56% and distantly in 44%. Thirty-six patients (55%) died of the disease. At 3 years, overall survival was 39% and at 5 years, 30%. Important prognostic factors include tumor size, grade, and clinical and pathologic stage. Patients with minimally invasive tumors (<5 mm) should do well with appropriate surgical treatment. Copyright 2001 John Wiley & Sons, Inc.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Korean Med Sci
                Journal ID (publisher-id): JKMS
                Title: Journal of Korean Medical Science
                Publisher: The Korean Academy of Medical Sciences
                ISSN (Print): 1011-8934
                ISSN (Electronic): 1598-6357
                Publication date (Print): October 2011
                Publication date (Electronic): 01 October 2011
                Volume: 26
                Issue: 10
                Pages: 1277-1285
                Affiliations
                [1 ]Department of Pathology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul, Korea.
                [2 ]Department of Pathology, Chung-Ang University College of Medicine, Chung-Ang University Hospital, Seoul, Korea.
                [3 ]Department of Otorhinolaryngology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
                [4 ]Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
                Author notes
                Address for Correspondence: Kyung-Ja Cho, MD. Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82.2-3010-4545, Fax: +82.2-420-7898, kjc@ 123456amc.seoul.kr
                Article
                DOI: 10.3346/jkms.2011.26.10.1277
                PMC ID: 3192337
                PubMed ID: 22022178
                SO-VID: 3629269b-dcdc-49b4-888c-d0d9d49f9133
                Copyright © © 2011 The Korean Academy of Medical Sciences.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 02 May 2011
                Date accepted : 17 August 2011
                Categories
                Subject: Original Article
                Subject: Oncology & Hematology

                ScienceOpen disciplines: Medicine
                Keywords: p53,glucose transporter 1,c-erbb-2,prognosis,carcinoma ex pleomorphic adenoma,vascular endothelial growth factor,c-kit,histological types
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: p53, glucose transporter 1, c-erbb-2, prognosis, carcinoma ex pleomorphic adenoma, vascular endothelial growth factor, c-kit, histological types

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