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PubMed1990

Metastasizing pleomorphic adenoma of the nasal septum.

Pleomorphic adenoma is the most common benign tumor of glandular tissue occurring in the head and neck region. There have been several reports of metastasis of this benign-appearing tumor from the salivary glands to distant sites, suggesting hematogenous spread and implantation. Although occurrence of pleomorphic adenoma on the nasal septum has been described, to our knowledge this is the first reported case of recurrent septal pleomorphic adenoma with histologically benign tissue in an enlarged metastatic ipsilateral submandibular lymph node, suggesting lymphatic spread. The literature concerning the subject is reviewed. Wide septal excision and modified neck dissection is the recommended treatment.

Adenoma, Pleomorphic↗
PubMed1998

Epithelial-mesenchymal transdifferentiation and extracellular matrix gene expression in pleomorphic adenomas of the parotid salivary gland.

Mesenchymal and epithelial cell differentiation are assumed to be dichotomic primary events in embryonic development. In this study, pleomorphic adenomas of the parotid gland were analysed as a model which shows morphological features of both epithelial and mesenchymal tissue types. Using matrix gene expression profiles as a supplementary criterion for the identification of cellular phenotypes, areas with unequivocal epithelial and mesenchymal differentiation could be demonstrated. Many areas displayed a transitional phenotype with cells showing both epithelial and mesenchymal features. The data provide evidence that epithelial-mesenchymal transitions represent the basic principle of the tisuse heterogeneity in pleomorphic adenomas. Thus, pleomorphic adenomas demonstrate the potential of adult (neoplastic) epithelial cells to transdifferentiate into mesenchymal cells in vivo.

Adenoma, Pleomorphic↗
PubMed1996

Demonstration of monoclonal origin of human parotid gland pleomorphic adenoma.

BACKGROUND: Parotid gland pleomorphic adenoma is histologically comprised of epithelial and mesenchymal elements. It remains to be established whether this neoplasm arises from epithelial and mesenchymal elements, or solely from the epithelial element. METHODS: In an attempt to resolve this issue, we have conducted clonal analysis on five pleomorphic adenomas. The method for clonal analysis was based on the trinucleotide repeat polymorphism of the x-chromosome-linked androgen receptor gene and on random inactivation of this gene by methylation. The epithelial and mesenchymal elements were obtained separately from the paraffin sections of the pleomorphic adenomas using a microdissection technique and then subjected to clonal analysis. RESULTS: Clonal analysis revealed that both epithelial and mesenchymal elements were monoclonal. In addition, the same allele of the androgen receptor gene was inactivated in both elements in every case. CONCLUSIONS: It is unlikely that the epithelial and mesenchymal elements of different origin happen to inactivate the same allele of the androgen receptor gene in all five tumors. Rather, it is more reasonable to consider that these two elements have a common single cell origin.

Adenoma, Pleomorphic↗
PubMed1996

Molecular characterization of a novel cancer cell line established from human carcinoma in pleomorphic adenoma (CaPA-4).

A cultured cell line (CaPA-4), derived from an undifferentiated carcinoma in a pleomorphic adenoma of the submandibular gland, was established through xenografted tumors in nude mice. Geneticin treatment eliminated surrounding mouse fibroblasts and yielded enriched tumor cells at an early stage of cell passage. In vitro, the line grew in a cobblestone pattern, revealing its epithelial origin. Chromosomal analysis by Giemsabanding confirmed its human origin, while electron microscopic examination showed its squamous-cell characteristics. CaPA-4 cells stained positive for the c-myc and Ha-ras antibodies. Molecular analysis showed over-expression of both c-myc and Ha-ras mRNA, with point mutation of p53 at codon 248 and of Ha-ras at codon 61. Amplification and rearrangement of the Ha-ras gene were observed; however, no loss of heterozygosity (LOH) of the p53 gene was detected by Southern blotting. This sequence of cancer-related gene activation may represent the malignant transformation from benign pleomorphic adenoma. This report describes the establishment and molecular characterization of this novel cell line from carcinoma in pleomorphic adenoma exhibiting squamous-cell differentiation. This could represent a useful model for investigating the cause of malignant transformation from human salivary-gland mixed tumors.

Adenoma, Pleomorphic↗
PubMed1997

Clinically aggressive metastasizing pleomorphic adenoma: report of two cases.

BACKGROUND: It has been suggested that metastasizing pleomorphic adenomas may represent unrecognized malignancy. METHODS: The cytologic and clinical characteristics of two metastasizing pleomorphic adenomas diagnosed by fine-needle sampling are reported. RESULTS: Both showed malignant evolution: the primary tumors arose from the palate and the parotid salivary glands, respectively. Metastases occurred simultaneously with local recurrence in the first patient and after a second local recurrence in the second patient. Both patients were treated by surgery and radiotherapy but died of disseminated disease 8 and 4 years after initial diagnosis. No histologic evidence of malignancy was observed on cytology smears or histology sections in either case. CONCLUSION: Clinically, our cases support the hypothesis that metastasizing pleomorphic adenomas represent unrecognized malignancy, because the biologic course of two tumors led to unequivocally lethal outcome.

Adenoma, Pleomorphic↗
PubMed1999

Pleomorphic adenoma of the salivary glands: prospective clinicopathologic and flow cytometric study.

BACKGROUND: Primary surgery is the appropriate treatment for most pleomorphic adenomas of the salivary glands. However, no reliable criteria have been established to predict tumors with aggressive features. METHODS: In 44 patients treated for salivary pleomorphic adenoma, clinicopathologic features and flow cytometric findings were recorded. S-phase fractions were classified as low (0%-1%), intermediate (1.1%-5%), and high (>5%). The relationship between clinicopathologic parameters and flow cytometric DNA analysis was assessed with the Pearson's correlation coefficient. RESULTS: The mean tumor size was 24.4 mm. Microscopically, myxoid structures predominated in 61.4% of cases. Only five specimens showed high S-phase fractions. All samples were DNA diploid (mean coefficient of variation 3.2%). S-phase fraction and tumor size correlated significantly (r = 0.73, P = 0.003). Two patients with recurrent tumors had high S-phase fractions both on the first resected specimens and at the time of the second operation. CONCLUSIONS: The S-phase fraction may be a valuable predictor of aggressive behavior in salivary pleomorphic adenomas. High S-phase fractions were associated with higher tumor size and a greater tendency to recur.

Adenoma, Pleomorphic↗
PubMed1981

Cytologic localization of antigens from human saliva in pleomorphic adenomas of salivary glands.

Twenty pleomorphic adenomas of human salivary glands were studied by means of specific immunohistochemical methods. Material reacting with antihuman saliva antiserum has been detected in epithelial structures of all pleomorphic adenomas. The myxoid stroma was immunohistochemically negative. Both PAS and immunohistochemical reactions in the same section indicate that there is no close relationship between the results of these procedures. This study suggests that the pleomorphic adenomas can be considered epithelial tumors of salivary distal gland cells retaining or developing specific exocrine capability.

Adenoma, Pleomorphic↗
PubMed1986

Influence of local surgery and radiotherapy on the natural history of pleomorphic adenomas.

We have analysed the interval between first treatment and tumour recurrence in 65 patients with parotid pleomorphic adenomas which had recurred following local excision. Our results indicate that 5 years is an inadequate period of follow-up and that 10-20 years may be more realistic. Radiotherapy given to 17 patients after local excision of their tumours was found to have had no significant advantageous effect in terms of recurrence-free interval either before or following formal parotidectomy or in limiting the ultimate surgery required. Major complications directly attributable to radiotherapy developed in at least 3 of these 17 patients. Malignant transformation of the pleomorphic adenoma has occurred in three patients, two of whom had been subjected to radiotherapy. We advise that caution is exercised in the interpretation of results of local excision and radiotherapy in this disease. In view of the fact that an alternative and apparently superior treatment is available in the form of formal parotidectomy, we urge that this should be universally adopted for the management of both primary and recurrent pleomorphic adenomas.

Adenoma, Pleomorphic↗
PubMed2002

Schwannomas: a pitfall in the diagnosis of pleomorphic adenomas on fine-needle aspiration cytology.

Fine-needle aspiration cytology (FNAC) is being employed with increasing frequency for the preoperative diagnostic workup of salivary gland lesions. Although most cases show morphologic features very characteristic of specific entities, few lesions, both benign and malignant, can cause problems in interpretation. We report four cases initially diagnosed on FNA as spindle-cell tumors, possibly benign nerve sheath tumors (BNST) in the salivary gland region. These cases were later diagnosed on histologic examination as schwannoma (two cases) and as pleomorphic adenoma (two cases). Review of the cytomorphology of these four cases enabled the correct diagnosis of pleomorphic adenoma in the two cases misinterpreted as BNST. Benign peripheral nerve sheath tumors should always be considered in the differential diagnosis of pleomorphic adenoma. A diligent search for epithelial elements is recommended prior to diagnosing BNST in the head and neck region.

Adenoma, Pleomorphic↗
PubMed2003

Fine-needle aspiration biopsy of a cystic pleomorphic adenoma with extensive adnexa-like differentiation: differential diagnostic pitfall with mucoepidermoid carcinoma.

Although fine-needle aspiration biopsy (FNAB) is a highly accurate tool for the diagnosis of pleomorphic adenomas, even this common salivary gland neoplasm can be diagnostically challenging and cause pitfalls in cytodiagnosis. In particular, the presence of either cystic degeneration or squamous and mucinous metaplasia can lead to a false positive diagnosis of malignancy. Here we present the case of a 16-year-old female who presented with a painless, slowly growing mass in the superficial lobe of the right parotid gland. Magnetic resonance imaging of the parotid demonstrated a mass with heterogeneous postcontrast enhancement and a central, nonenhancing area suggestive of necrosis. FNAB of the lesion yielded proteinaceous debris and numerous whorls of keratin, small cohesive clusters of basaloid and squamoid epithelial cells, and many vacuolated and foamy cells. Initially and after consultation at an outside institution, the FNAB was reported as an "atypical neoplasm, cannot exclude mucoepidermoid carcinoma." A total, nerve-sparing parotidectomy and level II neck dissection revealed a pleomorphic adenoma with central cystic degeneration and extensive mixed appendageal differentiation. While foci of squamous metaplastic changes may occur in pleomorphic adenomas, the combination of cystic degeneration and extensive appendageal differentiation with numerous keratotic cysts is rare, and it presents the potential for misinterpretation of the FNAB as indicative of malignancy in general, and mucoepidermoid carcinoma in particular.

Adenoma, Pleomorphic↗
PubMed2004

Bilateral synchronous pleomorphic adenoma diagnosed by fine-needle aspiration.

Pleomorphic adenoma is the most common benign neoplasm of the parotid gland. However, bilateral synchronous pleomorphic adenomas occur infrequently. We report a case of bilateral synchronous pleomorphic adenoma involving the parotid gland in a 50-yr-old man diagnosed by fine-needle aspiration biopsy.

Adenoma, Pleomorphic↗
PubMed2005

Nodular fasciitis of parotid region: a pitfall in the diagnosis of pleomorphic adenomas on fine-needle aspiration cytology.

Fine-needle aspiration cytology (FNAC) is routinely employed for the preoperative diagnosis of salivary gland lesions. Although most cases show morphologic features characteristic of specific entities, some lesions can be diagnostically challenging. We report two parotid aspirates, initially diagnosed as pleomorphic adenoma on FNA. The patients, a 33-yr-old white man, and a 24-yr-old white woman, presented with indurated lesions arising in the parotid gland region. The aspirates from both patients were markedly hypercellular. Smears showed a mixture of spindle cells with a well-demarcated cytoplasm showing occasional long cytoplasmic process; and cells with abundant cytoplasm with round to oval eccentric nuclei, giving the impression of plasmacytoid cells of pleomorphic adenoma. The nuclear chromatin was evenly distributed and finely granular with one or two occasional small nucleoli. Intermingled with the tumor cells were scattered neutrophils, eosinophils, and macrophages. Aggregates of spindle cells were also seen embedded in a mucoid background with occasional small tufts of a fibrillar mucoid stroma. These fibrillar tufts were magenta red in the Diff-Quik stain, giving the impression of matrix of pleomorphic adenoma. Both cases were later diagnosed on histologic examination as nodular fasciitis. Nodular fasciitis should be considered in the differential diagnosis of a mass arising in association with the parotid gland.

Adenoma, Pleomorphic↗
PubMed1990

Mucin production by pleomorphic adenomas of the parotid gland: a cytologic spectrum.

Mucinous salivary gland aspirations represent a special differential diagnostic problem. Considerations include pleomorphic adenoma, Warthin's tumor, chronic obstructive sialadenitis, and low-grade mucoepidermoid carcinoma. We herein discuss three cases that illustrate a spectrum of mucin production by pleomorphic adenomas. The literature is reviewed, and the possible distinction of pleomorphic adenoma from low-grade mucoepidermoid carcinoma is considered.

Adenoma, Pleomorphic↗
PubMed1994

Submicroscopic deletions of 3p sequences in pleomorphic adenomas with t(3;8)(p21;q12).

A subgroup of benign pleomorphic adenomas of the salivary glands is characterized by translocations, or on rare occasions deletions, with breakpoints at 3p21. We have applied restriction fragment length polymorphism (RFLP) analysis to assess the frequency of allelic losses at four different loci located within 3p21-->p25 in 35 pleomorphic adenomas, 18 of which were also karyotyped. Parallel analysis of constitutional and tumor DNAs in informative tumors revealed that all patients retained heterozygosity in their tumor DNA at the D3S2 and RAF1 loci. Among the 29 tumors informative for THRB three showed loss of heterozygosity (LOH). All three tumors had a t(3;8)(p21;q12). Of the 23 tumors informative for D3F15S2, one showed LOH. This tumor also had a t(3;8)(p21;q12). To further map the deletions in relation to the 3p21 translocation breakpoint, we also sublocalized the THRB locus. Using in situ hybridization we assigned the gene to 3p24.1-3. The fact that none of the tumors with loss of 3p alleles showed cytogenetic evidence of deletions indicates that the losses are submicroscopic, probably interstitial, and in most cases distal to the 3p21 breakpoint. This was confirmed in one case with loss of a THRB allele where both proximal (D3F15S2) and distal (RAF1) markers retained heterozygosity. Our results suggest that deletion of 3p sequences might be of progressional importance in a subset of pleomorphic adenomas with t(3;8)(p21;q12).

Adenoma, Pleomorphic↗
PubMed2003

A histological comparison of deep and superficial lobe pleomorphic adenomas of the parotid gland.

BACKGROUND: Excision of parotid superficial lobe pleomorphic adenomas requires removal of a surrounding cuff of normal parotid tissue. Less aggressive dissection in removing pleomorphic adenomas that occur in the deep lobe of the parotid gland does not seem to compromise prognosis in these patients. We attempted to define histologic characteristics, differentiating superficial and deep lobe tumors, in an attempt to explain this clinical phenomenon. METHOD: Thirty-one pleomorphic adenomas, 12 deep-lobe tumors, and 19 superficial lobe tumors were analyzed and compared, looking at tumor size, capsule thickness, penetration of tumor through capsule, and predominant cell types present. RESULTS: The superficial lobe tumors had significantly thinner capsules (p =.02). There was increased extracapsular extension of tumor in the superficial lobe group compared with the deep lobe group (79% and 58%, respectively). The tumors were larger in patients with deep lobe lesions (2.6 cm vs 3.6 cm). There was no difference in predominant cell types. CONCLUSIONS: The anatomic location of deep lobe tumors is a likely explanation for the histologic differences observed in this study. These important differences allow less aggressive dissection in deep lobe tumors without compromising prognosis.

Adenoma, Pleomorphic↗
PubMed1985

Immunohistochemical localization of alpha 1-antitrypsin and alpha 1-antichymotrypsin in salivary pleomorphic adenomas.

Immunohistochemical identification of alpha 1-antitrypsin (alpha 1-AT) and alpha 1-antichymotrypsin (alpha 1-ACh) in pleomorphic adenomas of salivary glands is reported in order to compare their distribution profiles with those of lysozyme and lactoferrin, already described elsewhere. Normal salivary glands indicated positive alpha 1-AT staining in ductal segments and had no alpha 1-ACh in any glandular cell. Pleomorphic adenomas displayed moderate positivity to alpha 1-AT staining in duct-like, tubular and glandular epithelia which was particularly intense in luminal cells. The limited number of tumour cells which showed duct-like structures with a single cellular layer arrangement, displayed the highest staining to alpha 1-ACh. Strongly alpha 1-AT positive tumour cells located on the inner side of luminal cavities were also markedly positive to alpha 1-ACh. Spindle shaped tumour cells existed outside tubular and ductal structures and were negative to alpha 1-AT and alpha 1-ACh. Distribution of alpha 1-AT in salivary glands was similar to that of lysozyme as is usual in ductal segments or their transformed cells, and occurrence of alpha 1-ACh localization rather resembled that of lactoferrin, with occurrence in acinar compartments and changed epithelia within acini. The biological role of a specific immunohistochemical distribution of alpha 1-AT and alpha 1-ACh in pleomorphic adenomas may be associated with a self regulating mechanism which inhibits degradation by tissue proteinases.

Adenoma, Pleomorphic↗
PubMed1997

Pleomorphic adenoma of the breast: report of a case.

We present herein the case of a 74-year-old woman found to have a pleomorphic adenoma, or so-called mixed tumor, of the breast. The patient presented with a hard mass, 3 cm in diameter, located just beneath the left areola. Physical examination suggested a diagnosis of breast carcinoma; however, the findings of both ultrasonography and mammography indicated a benign neoplasm. Aspiration biopsy cytology was evaluated as class III and the diagnosis of pleomorphic adenoma was finally confirmed by examination of an excisional biopsy specimen. As it is a rare benign tumor, pleomorphic adenoma of the breast has been mistaken for a malignant tumor clinically, mammographically, cytologically, and even by frozen section. Thus, an awareness of this disease in the breast will help to prevent misdiagnosis and overaggressive surgery.

Adenoma, Pleomorphic↗
PubMed2007

[Epidemiology, diagnosis, and treatment of giant pleomorphic adenomas of the parotid gland].

Pleomorphic adenomas of the parotid gland can be slowly growing over the course of many years and may reach an enormous and disfiguring size associated with significant morbidity of the patients. To our knowledge, over the last 80 years 20 cases of giant pleomorphic adenomas (weight 1.2-26.5 kg) have been reported. These tumors occurred predominantly in women (90%). The mean period from initial clinical manifestation until definitive surgical treatment was 20.7 years. The mean age of the patients at the time of surgery was 58.9 years. Malignant transformation occurred in 15.8% of cases. It is likely that the reasons for delayed treatment are the patient's fear of surgery on the one hand, and insufficient medical advise on the other. We report on a 77 year old female who had a 40-year history of a growing parotid tumor that weighed 3.9 kg after resection. The implications of this case for diagnosis and treatment of giant pleomorphic adenomas, and a review of the world literature on these unusual parotid tumors, are presented.

Adenoma, Pleomorphic↗