Carcinoma Ex Pleomorphic Adenoma Research Articles

Carcinoma ex pleomorphic adenoma of the parotid gland

Carcinoma ex pleomorphic adenoma (CXPA) is a rare aggressive epithelial malignancy arising from a primary or recurrent benign mixed tumor. Only a few case reports describing the radiologic features of CXPA have been published. To describe and characterize the magnetic resonance (MR) imaging findings of CXPA in the parotid gland and correlate them with pathologic findings. The MR images of surgically proven CXPA in the parotid gland of five men and five women ranging in age from 28 to 75 years (mean 52 years) were retrospectively reviewed. All MR images were evaluated with emphasis on the size, margin characteristics, extraparotid infiltration, the presence of an encapsulated component, and signal intensity on T2-weighted or short-inversion-time inversion recovery (STIR) images. The average maximal diameter was 4.3 cm. All 10 tumors had ill-defined boundaries, and seven tumors showed extraparotid infiltration, reflecting invasive growth of the malignant component identified on histological examination. Eight tumors had a round encapsulated component and seven of those signal intensities were a mixture of hypo- and hyperintensity on T2-weighted or STIR images. Histological correlation of these components revealed fibrously encapsulated tumors containing hyalinization and myxoid tissue, suggesting degenerated pleomorphic adenoma. Invasive malignant components had non-specific and various signal intensities. An invasive parotid mass co-existing with a round encapsulated component is suggestive of carcinoma ex pleomorphic adenoma.

Malignant change in a massive pleomorphic adenoma resembling the presentation of advanced inflammatory breast cancer

Massive tumours of the parotid are uncommon as due to their site, they are usually removed at an earlier stage. We present a bizarre case of a carcinoma ex-pleomorphic adenoma which mimicked an advanced breast cancer, complete with a ‘nipple-like’ extension and peau d’orange changes in the overlying skin as a result of a dense dermal inflammatory response. A procedure akin to a mastectomy with facial nerve preservation was carried out for removal. To our knowledge, peau d’orange has not been reported before in parotid tumours.

Increased expression of MDM2 and NM23 are associated with malignant transformation of pleomorphic adenoma

Abstract This study was designed to correlate the expression of both MDM2 and NM23 in pleomorphic adenoma (PA) to clinical background, histological features, local recurrence, and metastatic potentiality in this tumor. Expression of MDM2 and NM23 was studied immunohistochemically in 23 cases of PA. Our results demonstrated MDM2 and NM23 overexpression in almost all cases of PA. There was a significant difference of the MDM2 and NM23 mean values between benign PA and both carcinoma-ex PA and metastasizing PA. The results of this study show that the overexpression of NM23 and MDM2 oncoproteins could be used as reliable predictors of malignant progression as well as metastatic potentiality of PA.

Low-grade malignant myoepithelioma arising in a pleomorphic adenoma: a rare case

Malignant myoepithelioma is a very rare salivary gland tumor that can arise de novo or within a pre-existing pleomorphic adenoma. We report a case of malignant myoepithelioma most probably arising in a pre-existing pleomorphic adenoma of the left parotid gland. The patient was a 60-year-old man who presented with a multinodular mass lesion over left side of the face and neck. He had undergone removal of a pleomorphic adenoma of the left parotid gland twice (8 and 22 years ago). Histological examination showed locally concentrated highly invasive myoepithelial cells with bland-looking morphology and no evidence of mitosis or necrosis. Immunohistochemistry confirmed the myoepithelial differentiation (S-100+, SMA+) and a low Ki-67 labeling index (<5%).

A proposal of an in vitro model which mimics in situ areas of carcinoma

The curious situation of in situ carcinoma where there is a direct contact between malignant cells with normal or benign cells has led us to look for an in vitro model which mimics this condition. In ductal carcinoma of the breast, this interaction occurs between malignant cells (epithelial luminal) and normal cells (myoepithelial cells) and, in salivary gland carcinoma ex-pleomorphic adenoma between the malignant cells and benign myoepithelial cells. This model raises the possibility of investigating the mechanism that controls cancer invasion. It was inspired by an in vivo study of in situ areas of carcinoma ex-pleomorphic adenoma where the modification of benign myoepithelial cells phenotype, provoked by epithelial cells malignant transformation was demonstrated, revealing that there was a cross-talking between them (Araujo et al. 2006; Martinez et al. 2012). The purpose of this model is to allow future investigators to evaluate data that could contribute to answering the great question: How do the malignant cells win the suppressor effect of myoepithelial cells and finally invade the tissue?

Rare carcinoma ex pleomorphic adenoma of the buccal minor salivary gland causing a therapeutic dilemma

Carcinoma ex pleomorphic adenoma (CXPA), as a group, constitutes 12% of malignant salivary gland tumors. We present a case of CXPA of the buccal mucosa in a 17-year-old patient. The buccal mass was of a size of 3.0 cm located in the right cheek. Pleomorphic adenoma was the provisional diagnosis. The tumor was excised under local anesthesia. Histopathological evaluation revealed a pre-existing pleomorphic adenoma. However, on magnification, certain areas showed islands of dysplastic epithelial cells’ invading the fibrous capsule and CXPA was diagnosed. The patient was recalled and secondary surgery of the site performed. No tumor tissue could be detected in the secondary resection specimen. There is no sign of recurrence since 2 years.

Canine Mammary Mixed Tumours: A Review

Mammary mixed tumours are the most frequent neoplasias in female dogs. In humans, mixed tumours are frequently found in the salivary glands and are known as pleomorphic adenomas. In addition to their histomorphologic similarities, mixed tumours and pleomorphic adenomas have the potential to become malignant and give rise to carcinomas in mixed tumours and carcinomas ex-pleomorphic adenoma, respectively. The factors associated with malignant transformation are still poorly known in the case of canine mixed tumours. However, this form of neoplasia tends to be associated with a better prognosis than other malignant histological types. This paper discusses the main features associated with female canine mammary mixed tumours.

Carcinoma ex pleomorphic adenoma of the upper lip

Carcinoma ex pleomorphic adenoma (CXPA) is a rare salivary gland malignancy most often reported within the parotid gland. Of the salivary gland tumours that occur within the minor salivary glands at least 50% are reported to be malignant. This proves to be inaccurate when describing salivary gland tumours within the upper lip which are usually benign. A Medline search of the English language literature yields only one case report of a CXPA located within the upper lip. The authors present a second case report of CXPA within the upper lip and a review of its pathologic features and management.

Carcinoma ex pleomorphic adenoma with special reference to the prognostic significance of histological progression: a clinicopathological investigation of 41 cases

To investigate a large series of cases of carcinoma ex pleomorphic adenoma (CEPA) to determine prognostic factors. Thirty cases of CEPA associated with primary pleomorphic adenoma (PA) and 11 cases of CEPA associated with recurrent PA were investigated. The median follow-up was 57.7 months, and ranged from 4 to 156 months. Purely intraductal carcinoma was found in 15 cases. Intraductal and extraductal intracapsular carcinoma together was found in one case. Extracapsular carcinoma was found in 25 cases. Prognosis was good for CEPA that was purely intraductal, extraductal intracapsular, or up to 5 mm extracapsular, and poor for CEPA that was 8 mm or more extracapsular. There were relatively more cases of CEPA with extracapsular invasion of 8 mm or more from recurrent PA than from primary PA, and the prognosis for CEPA associated with recurrent PA was worse than that for CEPA associated with primary PA. The threshold for distinguishing minor extracapsular invasion with good prognosis from wide extracapsular invasion with poor prognosis is 5 mm. The worse prognosis for CEPA associated with recurrent PA indicates the necessity for close surveillance of patients with recurrent PA.

P41. Carcinoma ex pleomorphic adenoma in a minor salivary gland of the upper lip

Introduction: We present the first case report of carcinoma ex pleomorphic adenoma (CXPA) arising in a minor salivary gland of the upper lip.Methods: We present the case of a 55 year old female with CXPA in an unusual site and a literature review of the relevant issues.Results: A 55 year old female presented with a 30 year history of a painless lump in her upper left labial sulcus. An excisional biopsy revealed a yellow glistening mass that appeared to be well encapsulated. Histopathology review identified features of CXPA.A wide local excision and local flap repair was undertaken. Microscopically no residual tumor was identified. The case was discussed at the local head and neck multidisciplinary team meeting, and owing to the small volume of disease and wide margins, it was agreed that radiotherapy was not indicated. At 18 months the patient remained disease free.Discussion: Oral lumps are common and are often given low priority by patients, as demonstrated in this case. Unfortunately the longer a pleomorphic adenoma (PA) remains untreated, the greater the risk of malignanat transformation to CXPA. Johns and Goldsmith report a 1.6% incidence of malignant transformation in tumors of 5 years duration compared with 9.4% in tumors present for 15 years. This highlights the importance of early surgical review and definitive treatment of PAs.A wide surgical excision with adequate margins is essential for a favorable outcome in patients with malignant minor salivary gland tumors. Postoperative radiotherapy is reserved for patients with high grade tumor histology, large primary lesions, perineural invasion, bone invasion, cervical lymph node metastasis, and positive margins, although clear-cut survival advantage has not been proven. Recurrence, especially regional and distant metastases, portends an extremely poor prognosis.Although this case had a favorable outcome, it highlights the need for early surgical review and management of oral lesions of uncertain and/or unpredictable nature. Patients with known or suspected PA should be encouraged to undergo definitive surgical treatment early in their disease to avoid malignant transformation to CXPA at a later date.

Primary central carcinoma ex pleomorphic adenoma of the mandible: report of a rare case and literature review

We report a rare case of primary carcinoma ex pleomorphic adenoma (CXPA) of the mandible. A 13-year-old girl presented with a large mass, measuring about 30 cm in its greatest dimension, involving the mandible. She was referred to our department for surgery, and her postoperative course was uneventful; she is currently free from the disease 48 months after surgery. Primary CXPAs located centrally within the jawbones are rare with only 10 cases reported in the English and Chinese literature. This case illustrates 2 key facts regarding the diagnosis and therapy of CXPA. First, clinicians should be aware of this possibility and should emphasize the need for submission of so-called cystic lytic lesions for histopathologic analysis. Second, tumors should be excised en bloc with adjuvant postoperative radiotherapy when local recurrence and regional metastasis are suspected clinically.

Carcinoma ex Pleomorphic Adenoma of the Nasal Cavity

Carcinoma ex pleomorphic adenoma (CXPA) is a malignant epithelial neoplasm arising in a benign mixed tumor (i.e., pleomorphic adenoma or PA); it accounts for approximately 3-4% of all salivary gland neoplasms. CXPA is exceedingly rare in the nasal cavity, with only three cases previously documented. We report two cases of women presenting with masses of the nasal cavity. The tumors were resected and evaluated grossly and by routine microscopy. Both patients presented with nasal obstruction, and one patient reported epistaxis. Grossly, the tumors were 2.5 and 3cm in greatest dimension, respectively. In each case, microscopic examination of the tumor revealed an infiltrating carcinoma arising in association with foci of benign PA. The carcinoma types were adenoid cystic carcinoma and high grade adenocarcinoma, not otherwise specified. Both cases were widely (i.e., >1.5mm) invasive beyond the preexisting PA. The findings were diagnostic of CXPA. Carcinomatous transformation of a PA in the nasal cavity is extremely rare, but does occur. Accordingly, PAs of this site should be thoroughly sampled and closely examined to exclude the possibility of malignant transformation.

Comprehensive management of a rare carcinoma ex pleomorphic adenoma of the lacrimal gland with a modified lateral orbitotomy access osteotomy. A case report

Complete management of extraconal ocular tumors may require the joint efforts of a maxillofacial surgeon to provide access and an ophthalmic surgeon to completely excise the lesion. Pleomorphic adenoma is the most common benign tumor of the lacrimal glands, representing around 12% of the lacrimal fossa lesions. They may however undergo malignant changes. Carcinoma ex pleomorphic adenoma (CXPA), a type of malignant mixed tumor of the lacrimal gland has been rarely reported. We report a case of CXPA of the lacrimal gland in a 35-year-old male. He was managed by a modified lateral orbitotomy access osteotomy with complete removal of the lesion and showed postoperative uneventful recovery. Accurate clinical diagnosis of a neoplasm in the orbital cavity is important for correct therapeutic management. This paper emphasises on the comprehensive management of these lesions with a special emphasis on diagnosis and surgical technique.

S100P Expression in Ductal Type of Carcinoma ex Pleomorphic Adenoma

Pleomorphic adenoma (PA) is known to occasionally progress to carcinoma, but the mechanisms of its malignant transformation have not been fully elucidated. S100P, an EF-hand calcium-binding protein, has recently been proposed as an initiator of carcinogenesis in some kinds of epithelial tumors. In this study, we aimed to elucidate the potential role of S100P in tumorigenesis and stepwise progression of carcinoma ex pleomorphic adenoma (CXPA) with ductal differentiation. In 31 ductal type CXPAs (8 in situ, 5 intracapsular, and 18 extracapsular) and 28 PAs (21 conventional and 7 atypical) of the salivary gland, we examined the protein expression of S100P, androgen receptor (AR), HER2/neu, p53, and Ki-67 by immunohistochemistry. HER2 expression, p53 expression, and the Ki-67 labeling index were higher in CXPAs than in atypical PAs and conventional PAs, whereas the AR expression level was relatively high even in atypical PAs. S100P overexpression was significantly more prevalent in CXPAs (27 cases; 87.1%) than in atypical PAs (2 cases; 28.6%) and conventional PAs (1 case; 4.8%) (P<0.05). High prevalence of S100P expression was observed in each intraductal, extraductal-intracapsular, and extracapsular component of CXPAs. In addition, equivalent, high-level S100P expression was observed in all histologic subtypes of the malignant component of CXPAs. These results indicate that S100P may play an important role in malignant transformation of ductal cells of PA, and that immunohistochemical staining for S100P would be a useful diagnostic marker for identifying the early phase of CXPA, in combination with AR, HER2, p53, and Ki-67.

Increased mucin 1 expression in recurrence and malignant transformation of salivary gland pleomorphic adenoma

Pleomorphic adenoma (PA) is the most common salivary gland tumour with a tendency to recur (RPA) and a risk of malignant transformation. Mucin 1 (MUC-1) plays a role in the progression of many tumours and may be a marker to predict RPA. The aim of this study was to evaluate MUC-1 expression in different phases of the adenoma to carcinoma sequence. Twenty-one cases of PA, 18 cases of RPA, three cases of RPA with focal transformation (TRPA) and 11 cases of carcinoma ex-pleomorphic adenoma (CXPA) were analysed immunohistochemically for MUC1 expression using an antibody to MUC1/DF3. MUC1 reactivity in RPA was stronger than that observed in PA and, in all the different carcinoma groups, MUC-1 expression was significantly higher in carcinoma than in RPA and PA. This study has confirmed that MUC-1 is related to the recurrence of PA and that this molecule is associated with malignant transformation of PA with carcinoma cells overexpressing MUC-1.

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

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.

Immunohistochemical expression of pRb in pleomorphic adenoma and carcinoma ex pleomorphic adenoma

This study aimed to characterize alteration in the immunohistochemical expression of pRb in normal tissue of the salivary gland surrounding pleomorphic adenoma, the tumor cells of pleomorphic adenomas, and carcinoma arising in pleomorphic adenoma. A selected series of 29 cases of pleomorphic adenomas, and 27 cases of carcinoma ex-pleomorphic adenoma (undifferentiated and adenocarcinoma types) were examined. The results showed that pRb expression was negative in the components of normal tissue of the salivary gland surrounding pleomorphic adenoma. PRb expression in pleomorphic adenomas shows that 2 cases out of 29 (6.9%) strongly expressed in the duct cells, 7/29 (24.1%) cases showed moderate staining. pRb nuclear staining in myxochondroid was identified in 10/29 (34.5%) cases of pleomorphic adenomas with weak staining, 6/29 (20.7%) with moderate staining. pRb was strongly expressed in carcinoma cells in 19 out of 27 cases (70.4%). This study suggests the alteration of pRb expression would increase from pleomorphic adenoma to carcinoma arising in pleomorphic adenomas (6.9% versus 70.4%).

FGF-2 is overexpressed in myoepithelial cells of carcinoma ex-pleomorphic adenoma in situ structures

Increasing emphasis has been placed on the role of myoepithelial cells, the contractile components of secretory glands, in the in situ to invasive carcinoma transition. These cells are placed at the interface between luminal epithelial cells and the stromal compartment, which favors their cross-talk with all other cell types comprising the tumor micro-environment. To obtain some clues about this cross-talk and also to better understand our previous immunoprofile study of myoepithelial cells in salivary gland carcinoma ex-pleomorphic adenoma (CXPA), we investigated FGF-2 expression in CXPA in situ structures as well as in cells cultured under conditions attempting to simulate the cellular interactions of this tumor stage. We have observed by immunohistochemistry that myoepithelial cells of CXPA in situ structures overexpress FGF-2. In addition, our results supported by qPCR and Western blotting, demonstrated that the expression of FGF-2 in the benign myoepithelial cells was in fact increased by stimulation with the conditioned medium from malignant cells. Low molecular weight FGF-2, known to be primarily released from the cells to exert its biological activity through receptors, was the predominant FGF-2 form detected in the benign myoepithelial cells. Specific FGF-2 receptors were found in the malignant epithelial but not in the benign myo-epithelial cells of CXPA, indicating a paracrine role for benign myoepithelial cell-derived FGF-2. Abnormal paracrine myo-epithelial/epithelial cell interactions and also myoepithelial/ stromal cell interactions could favor tumor growth, invasion and metastasis.

Malignant Mixed Tumor of the Lacrimal Gland in a Teenager

A 17-year-old boy presented with a painless, right superotemporal orbital mass. Imaging demonstrated a lacrimal gland mass extending into the temporalis muscle through the lateral orbital wall. The patient underwent an orbital exenteration. Histopathology revealed malignant mixed tumor (carcinoma ex-pleomorphic adenoma) of the lacrimal gland with perineural and vascular invasion.

Primary Pulmonary Carcinoma Ex-pleomorphic Adenoma of the Salivary Gland Type

Pleomorphic adenoma is also called a mixed tumor and it most commonly occurs in the salivary gland. This neoplasm has a low grade malignant potential, but it may also show aggressive clinical behavior like recurrence or metastasis. We report here on a case of a tumor that was confirmed to be primary pulmonary carcinoma ex-pleomorphic adenoma by the pathologic examination after complete resection, and it had the characteristics of malignant neoplasms, such as multiple metastases.