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Recurrent pleomorphic adenoma of the parotid gland: a prospective histopathological and immunohistochemical study.

OBJECTIVES/HYPOTHESIS: Histopathological characteristics and proliferation indices of recurrent pleomorphic adenoma were described in a series of 31 patients who were referred to the authors' clinic for revision surgery. STUDY DESIGN: Prospective series of 31 patients. METHODS: Serial sections of surgical specimen using the whole-organ sectioning technique were carried out for light microscopic examination after total parotidectomy and periparotid fat resection. The nodules were examined with special reference to localization, amount, size, histological subtypes, capsular alterations, and the amount of nodule spilling. Expression of proliferation markers (Ki67/MIB-1) according to the size and histological subtypes of the nodules was also investigated. RESULTS: Most recurrences were multinodular, and the number of nodules was much higher than expected, ranging from 1 to 157. The myxoid subtype was predominant. Eighty percent of the patients exhibited widely distributed nodules also lying outside the scar. These nodules contained only a thin pseudocapsule and often lacked complete encapsulation. The majority of multinodular recurrences of parotid pleomorphic adenoma consisted of small nodules (less than 1 mm in diameter). Smaller nodules showed similar or higher levels of proliferative activity than larger nodules. CONCLUSION: The extended multifocal distribution of tumor recurrences after insufficient resection of pleomorphic adenoma (most often after enucleation) can explain a high incidence of further recurrences. Therefore, a total parotidectomy including removal of surrounding fat tissue seems to be appropriate for the initial treatment of recurrent pleomorphic adenoma.

Adenoma, Pleomorphic↗

Nasopharyngeal pleomorphic adenoma in the adult.

INTRODUCTION: Salivary gland tumors account for less than 5% of all neoplasms in the head and neck, with pleomorphic adenoma being the most common type. These typically arise in the palate, but we report a rare case of nasopharyngeal pleomorphic adenoma in an adult. MATERIALS AND METHODS: The authors conducted a case report and literature review. RESULTS: The patient presented with unilateral otalgia, tinnitus, and aural fullness. Nasal endoscopy revealed a pedunculated mass adjacent to the left torus tubarius and he was treated with an excisional biopsy. Histologic evaluation demonstrated pleomorphic adenoma. DISCUSSION: Pleomorphic adenomas seldom present as nasopharyngeal masses and have a nonspecific appearance on endoscopy. Microscopic examination has characteristic features to aid in an accurate diagnosis. Treatment is surgical and recurrence is unlikely.

Adenoma, Pleomorphic↗

'Metastasizing pleomorphic salivary adenoma' should now be considered a low-grade malignancy with a lethal potential.

PURPOSE OF REVIEW: To review the current knowledge on the clinical entity of metastasizing pleomorphic adenoma. RECENT FINDINGS: Using case studies, the literature continues to explore the potential to identify a chromosomal abnormality that might explain the clinical entity, and may constitute a submicroscopic malignant transformation with molecular genetic alterations. Presently there are no agreed histopathological parameters that can identify or confirm a difference in behavior between the 'common' pleomorphic adenoma from the metastasizing pleomorphic adenoma. SUMMARY: The evidence supports that metastasizing pleomorphic adenoma is most likely to be an unrecognized and as yet unclassified malignant neoplasm and as such must be considered a low-grade, potentially lethal malignant disease when it presents, which may constitute a submicroscopic malignant transformation with molecular genetic alterations. Further research is required to answer the many questions.

Adenoma, Pleomorphic↗

Immunocytochemical localization of bone morphogenetic proteins (BMPs) in salivary gland pleomorphic adenoma.

The localization of bone morphogenetic protein (BMP)-1, -2, -3 and transforming growth factor (TGF)-beta in normal salivary gland and pleomorphic adenoma of the salivary gland has been examined immunocytochemically. Tumor cells with BMP immunostaining in pleomorphic adenoma were associated with some solid cellular and tubuloglandular patterns, and with stellate cells in the myxoid area. In addition, in the chondroid area of three pleomorphic adenomas, chondrocyte-like cells were positive for BMPs. It is speculated that BMPs secreted by the tumor cells play a role in the formation of the chondroid component in pleomorphic adenoma by inducing some tumor cells, probably neoplastic myoepithelial cells, to differentiate to chondrocytes by metaplastic change. No tumor cells specifically immunostained with TGF-beta were found. TGF-beta was positive in fibrous and hyalinized stroma. In the submandibular gland, only anti-BMP-1 antibody specifically reacted to apical portions of degenerated serous acinar cells.

Adenoma, Pleomorphic↗

Immunohistochemical localization of fibroblast growth factors (FGFs) and FGF receptor-1 in human normal salivary glands and pleomorphic adenomas.

Basic and acidic fibroblast growth factors (bFGF and aFGF) are heparin-binding growth factors, and promote fibrogenesis and angiogenesis. We investigated the immunohistochemical localization of bFGFE, aFGF, and FGF receptor-1 in pleomorphic adenomas. In the normal salivary glands, bFGF was localized in the basement membranes of intercalated ducts, acini and basal cells of the excretory ducts, while aFGF was localized focally in the intercalated ductal cells and basal cells of the excretory ducts. In pleomorphic adenomas, bFGF was immunolocalized in the basement membranes around the solid nests of myoepithelial cells, around the neoplastic myoepithelial cells in the myxoid areas, and in the lacuna cells in the chondroid areas. In contrast, chondroid areas exhibited no immunoreactivity with aFGE. Positive signals for aFGF were localized in luminal cells of the tubuloglandular structures in pleomorphic adenomas. FGF receptor-1 immunolocalized in the lacuna cells and myoepithelial cells in the solid and myxoid areas. These observations suggest that bFGF and FGF receptor-1 produced by myoepithelial cells inhibited terminal differentiation and enchondral ossification in pleomorphic adenomas. These results also suggest important roles for FGFs in the formation of various structures with mesenchymal-like histology.

Adenoma, Pleomorphic↗

Cytologic findings of a pleomorphic adenoma of the breast: a case report.

BACKGROUND: Pleomorphic adenoma of the breast is a rare benign tumor. Only a few cases have been reported. The histologic features have been described well. However, the cytologic findings have been described in only a few papers. CASE: A 47-year-old female presented with a left breast mass of several months' duration. The clinical and mammographic findings were highly suspicious for malignancy. Following an aspiration biopsy diagnosis of "positive for malignancy," the mass was excised. The histologic diagnosis was pleomorphic adenoma (mixed tumor of salivary gland type) rather than carcinoma. CONCLUSION: The cytologic presentation of pleomorphic adenoma of the breast can masquerade as that of a malignant tumor, in this case colloid carcinoma. This case delineates the cytomorphologicfeatures of pleomorphic adenoma, which may mimic carcinoma.

Adenocarcinoma, Mucinous↗

Infarction after fine needle aspiration biopsy of pleomorphic adenoma of the parotid gland.

BACKGROUND: Fine needle aspiration (FNA) is a well-established and safe method for the rapid diagnosis of pleomorphic adenoma. A few clinically important complications, including bleeding, infection and inflammatory reactions, result from FNA. In a small number of cases FNA has been followed by varying degrees of necrosis in some organs. In the literature there are a few reports associated with necrosis in a pleomorphic adenoma of the parotid gland following FNA. CASE: A 27-year-old female had a two-year history of a right parotid mass. FNA revealed pleomorphic adenoma. A histologic diagnosis of pleomorphic adenoma of the right parotid with infarction was made. CONCLUSION: Necrosis associated with infarction may cause diagnostic problems. It is not a sufficient sign of malignant transformation.

Adenoma, Pleomorphic↗

Magnetic resonance imaging of pleomorphic adenoma arising from the external auditory canal.

Pleomorphic adenoma arising from the external auditory canal is a very rare neoplasm, and there has been no report on magnetic resonance (MR) imaging of pleomorphic adenoma of the external auditory canal. We report here a case of 65-year-old male with this tumour, measuring 12 mm in a diameter. Histopathology was confirmed from the specimen obtained at the surgical excision. MR revealed that the tumour had a well-defined margin showing hypointensity on T1-weighted images and hyperintensity on T2-weighted images relative to the parotid gland. The tumour was well enhanced by contrast material. No invasion to the surrounding tissue was observed. These MR findings were compatible with pleomorphic adenoma of the salivary gland origin. In treating pleomorphic adenoma of the external auditory canal, complete surgical excision is essential for the prevention of recurrence. It can be concluded that MR imaging is helpful for making a differential diagnosis of external auditory canal tumours and selection of adequate treatment.

Adenoma, Pleomorphic↗

A cell line from pleomorphic adenoma of the rat salivary gland.

Pleomorphic adenoma of rat salivary gland is extremely rare, and culture of cells obtained from rat salivary gland tumors has not been reported. We have established a long-term cell line from a pleomorphic adenoma of a Sprague-Dawley rat submaxillary gland. The pleomorphic adenoma was composed of oval or spindle-shaped cells occasionally forming a small duct. Alcian blue-positive intercellular matrices, consisting mainly of glycosaminoglycans, were abundant. The cultured cells showed characteristics similar to those of the original tumor. This cell line should be useful for biological and biochemical studies of glycosaminoglycan-synthesis of pleomorphic adenoma cells.

Adenoma, Pleomorphic↗

Carcinoma ex pleomorphic adenoma of the palate--a case report.

A case of squamous cell carcinoma ex pleomorphic adenoma in a palate is presented and comments on diagnostic criterias are described. The patient was 36-year-old male presenting with an ovoid elevated palate mass for 6 months. The tumor located in the junctional area of soft and hard palate. The mucosa was diffusely ulcerated and the mass focally tightly adherent to adjacent tissue. The initial cytologic and pathological diagnosis by fine needle aspiration biopsy and open biopsy was benign pleomorphic adenoma. After total removal, histologic examination revealed that tumor was composed partly of benign pleomorphic adenoma and partly of an squamous cell carcinoma component with areas of necrosis and capsular invasion. Immunohistochemical staining in the carcinoma area revealed positive reaction for low and high molecular weight cytokeratin, and epithelial membrane antigen, but negative for desmin, actin, GFAP and S-100 protein. In situ hybridization using biotinylated Epstein-Barr virus probe was done and the neoplastic cells were negative. Our case in an unusual partially encapsulated carcinoma ex pleomorphic adenoma in the palate and is not related in EBV infection.

Adenoma, Pleomorphic↗

The specific distribution of dendritic interstitial cells at the tumor border of major salivary gland pleomorphic adenomas.

To investigate the role of stromal cells at the tumor border of major salivary gland pleomorphic adenomas, we performed immunohistochemical analysis for detecting CD34-positive stromal cells (dendritic interstitial cells) and alpha smooth muscle actin (ASMA) -positive stromal cells (myofibroblasts) at the periphery of the tumor. We examined 21 pleomorphic adenomas of major salivary glands. All of the 21 pleomorphic adenomas examined had both dendritic interstitial cells and myofibroblasts at the tumor border. The ratio between the two cell types varied, and they exhibited a bilayered capsular structure; myofibroblasts were located in the inner layer of the tumor capsule, whereas dendritic interstitial cells derived from nearby vascular structures and nerves were located in the outer layer of the capsule. On the basis of the specific distribution of the dendritic interstitial cells in the present study, there is a possibility that dendritic interstitial cells are associated with the tumor growth regulation of major salivary gland pleomorphic adenomas.

Actins↗

Molecular genetic alterations in carcinoma ex-pleomorphic adenoma: a putative progression model?

To determine the genetic changes associated with the development of carcinoma ex-pleomorphic adenoma (Ca Ex-PA), we analyzed 15 microsatellite loci at chromosome arms 8q, 12q, and 17p on DNA from 26 neoplasms (including 8 microdissected benign and malignant components), and 13 pleomorphic adenomas for comparison. Pleomorphic adenomas and the adenoma component of Ca Ex-PAs showed a higher incidence of loss of heterozygosity (LOH) at chromosome arms 8q (52%) and 12q (28%) than at 17p (14%) loci. In the carcinoma component, the combined LOH at chromosome arm 8q, 12q, and 17p regions was 69%, 50%, and 69%, respectively; within these chromosomal regions, 8q11.23-q12 (42%), 12q23-qter (39%), 17p13 (41%), and 17p11 (45%) loci manifested the highest incidence of LOH. Eight carcinomas (30.7%) showed loss at all three chromosomal arms tested. Of the eight microdissected Ca Ex-PAs analyzed, four adenoma and corresponding carcinoma components (50%) had the same LOH at 12q loci and additional LOH at 17p loci only in carcinomas. Chromosome arm 17p alterations correlated significantly with high disease stage and an increased proliferative rate in these tumors. Our results indicate that alterations at regions on chromosome arms 8q and/or 12q may constitute early events associated with pleomorphic adenomas; that LOH at 12q loci may identify a subset of adenoma with potential progression to carcinoma; that acquisition of additional alterations at chromosome arm 17p loci might represent an event preceding malignant transformation and progression; and that 8q, 12q, and 17p regions may harbor tumor suppressor genes involved in the genesis of PA and Ca Ex-PA. Genes Chromosomes Cancer 27:162-168, 2000.

Adenocarcinoma↗

Immunohistochemical detection of cytokeratin 18 and its neo-epitope in human salivary glands and pleomorphic adenomas.

An immunohistochemical method using a monoclonal antibody M30 (MAb M30), which reacts with the product released by the cleavage of cytokeratin 18 (CK18) by activated caspase, was used to investigate the extent of apoptosis in human salivary glands and pleomorphic adenomas. The distribution of CK18 in the salivary glands and adenomas was also determined and compared with that of the product detected by MAb M30. CK18 was detected in the cytoplasm of serous acinar and ductal cells in normal human salivary glands. In pleomorphic adenomas, CK18 was observed mainly in the tumor cells of duct-like structures, but not in those of myxomatous or chondroid tissues. Positive MAb M30 reaction products were found in the cytoplasm of acinar cells in the restricted lobules of normal salivary glands and in the luminal contents of duct-like structures in pleomorphic adenomas. These results suggest that a mechanism which suppresses apoptosis may be linked to the growth of human pleomorphic adenomas.

Adenoma, Pleomorphic↗

[Expression of S-100 proteins and intermediate filament proteins in pleomorphic adenoma].

OBJECTIVE: To observe immunohistochemical expression of S-100A1, S-100A2, S-100A4, S-100A6, S-100B, K8.12, KL1, Vimentin, GFAP and NSE in pleomorphic adenoma of salivary gland, and to evaluate the differential localization of S-100 proteins and biological behaviour of neoplastic myoepithelial cells. METHODS: 23 cases of normal salivary gland and 60 cases of pleomorphic adenoma were embedded, in paraffin and were routinely diagnosed on the basis of hematoxylin and eosin-stained sections. Serial sections at 4 microns from the paraffin embedded blocks were used for the immunohistochemical studies. RESULTS: Normal salivary glands had positive immunoreactivity for S-100A families, K8.12 and KL1 in the ductal cells, while S100B, GFAP and NSE were observed in peripheral nerve fibers innervating the gland. In pleomorphic adenomas, luminal tumor cells in duct-like structures had positive immunoreactivity for S-100A subfamilies and keratin. Nonluminal tumor cells had positive immunoreactivity for S-100B, as well as Vimentin, keratins detected by monoclonal K8.12 and KL1, GFAP and NSE. CONCLUSIONS: These findings may suggest that the neoplastic myoepithelial cells contain Ca2+ binding proteins which may have a role in the regulation of calcium ions or calcium signaling mechanisms in the modulation of extracellular matrix deposition in pleomorphic adenoma which may in turn affect the extracellular matrix synthesis as well as histomorphology of the tumor.

Adenoma, Pleomorphic↗

[Pleomorphic adenoma of the nasal cavity: a case arising from the wall of the maxillary sinus].

INTRODUCTION: Pleomorphic adenoma is a common and benign tumour, originating from sero-mucous glands. Location in the nasal cavity and particularly on the medial wall of the maxillary sinus is very rare. PATIENTS AND METHODS: One patient with a pleomorphic adenoma of the nasal cavity and a review of literature are reported in order to describe the diagnostic and therapeutic management of this tumour. RESULTS: A 63-year-old woman was referred to our institution for evaluation of an unilateral nasal tumour. Clinical and radiological studies revealed an intra-nasal tumour, slightly lytic in nature, arising from the mucosa of the medial wall of the maxillary sinus. More than 2 years after complete excision of the tumour using an endoscopic procedure, the nasal cavity was free of tumour. DISCUSSION: Pleomorphic adenoma of the nasal cavity is a rare and benign tumour, usually presenting as a unilateral nasal tumour. Prognosis of this tumour is mainly linked to recurrences in cases of incomplete resection and to possible metastasis, such as an eventual malignant evolution. The gold standard treatment is complete surgical resection. After a complete imaging study for patient selection (CT scan and MRI), endonasal endoscopic surgery seems to be a reliable therapeutic treatment. CONCLUSION: Intra-nasal pleomorphic adenoma originates from nasal seromucous glands. Radiological study reveals a slightly lytic tumour developed from the septum of the medial wall of the maxillary sinus. Resecton can be performed with endoscopic endonasal surgery as long as the orbital bony framework and the ethmoidal roof are free of tumour. Whatever technique is employed, long term follow-up has to be used to detect any recurrence.

Adenoma, Pleomorphic↗

Expression and amplification of neu oncogene in pleomorphic adenomas of salivary gland.

Amplification of the neu oncogene and overexpression of its product was found to be a potential marker for aggressive biological behavior in breast cancer. However, the expression of the neu oncoprotein in normal breast ducts and myoepithelial cells has also been demonstrated. Hence, we examined normal salivary gland tissue and 15 cases of pleomorphic adenoma for the expression of the neu oncoprotein by immunohistochemistry using two polyclonal antibodies and 12 cases for the amplification of the neu oncogene using slot blot hybridization. Immunohistochemistry in the normal salivary gland revealed positive staining of all ductal cells. In the pleomorphic adenomas all cellular elements stained to a variable degree. The positive staining was seen in the ductal cells, in the solid sheets, and in chondroid, myxoid, and metaplastic foci. The normal salivary gland and 11 of 12 cases of pleomorphic adenoma showed no increase in copy number of the neu oncogene, whereas one case showed threefold amplification. These results indicate that the neu oncoprotein is expressed but the neu copy number is not increased in normal salivary gland epithelium and in most pleomorphic adenomas. The threefold amplification of the gene in one case may indicate an aggressive biological behavior.

Adenoma, Pleomorphic↗

[A case of pleomorphic TSH-producing pituitary adenoma with calcification].

We reported a rare case of pleomorphic TSH-producing pituitary adenoma with calcification and reviewed the literature. A 25-year-old female was admitted to our hospital with a complaint of anterior neck swelling. An endocrinological examination demonstrated elevated serum levels of free triiodothyronine (FT3: 5.6 pg/ml), free thyroxin (FT4: 2.2 ng/dl), TSH (5.85 microIU/ml), and TSH a-subunit (5.9 ng/ml), whereas a physical examination revealed no goiter. CT scan showed a suprasellar isodensity mass with dense calcification. Contrast-enhanced T1-weighted images revealed a less enhancing tumor extending from the left upper portion of pituitary fossa into suprasellar cistern. The patient underwent gross total removal of the tumor via the right pterional approach. Microscopically, medium-sized to enlarged tumor cells with marked pleomorphism and prominent calcification were observed. The tumor cells displayed positive reaction for TSH (beta-subunit). The MIB-1 index averaged 2.9%. The histological diagnosis was a pleomorphic TSH-producing pituitary adenoma. Postoperatively, the serum levels of FT3, FT4, TSH, and TSH alpha-subunit decreased to normal range. Follow-up MR images showed no evidence of recurrent tumor 3 years after the resection. All of six patients with densely calcified TSH-producing pituitary adenoma, previously reported in the literature, remained well without tumor recurrence. We suggest that this type of TSH-producing pituitary adenoma may be associated with favorable prognosis despite histologically pleomorphic appearance.

Adenoma, Pleomorphic↗

[The effects of HSV-tk suicide gene and wild-type p53 gene on pleomorphic adenoma cells of salivary gland].

OBJECTIVE: To study the therapeutic effects of combined gene therapy of wild type p53 (wt-p53) and herpes simplex virus thymidine kinase (HSV-tk) gene on pleomorphic adenoma cells of salivary gland. METHODS: Wild type p53 and HSV-tk gene were transfected into human pleomorphic adenoma cells of salivary gland by using recombinant adenovirus vector. The efficiency of transfection was checked and gene was expressed by RT-PCR methods. The cell inhibition after transfected was verified by light microscope and MTT. RESULTS: The proliferation of the pleomorphic adenoma cells transfected wt-p53 and HSV-tk gene was inhibited and the cell survival rate decreased to 54% and 38% respectively in 5 days. However, when wt-p53 gene combined with HSV-tk/GCV system, the killing effects was significantly stronger (P < 0.05) and the cell survival rate decreased to 20%. CONCLUSION: Combining p53 gene with HSV-tk/GCV system for gene therapy in pleomorphic adenoma cells of salivary gland is a valuable method.

Adenoma, Pleomorphic↗