Carcinoma In Pleomorphic Adenoma Research Articles

Risk of Carcinoma in Pleomorphic Adenomas of the Parotid

Surgery is the mainstay of treatment for pleomorphic adenomas (PAs) of the parotid to prevent further growth and potential future malignant transformation. While historical case series have reported transformation rates as high as 10%, there is a lack of contemporary methodologically sound data. To examine the rate of carcinoma ex pleomorphic adenoma (CXPA) detection in untreated PAs and investigate factors associated with malignant neoplasm. This cohort study reviewed all cases of primary PAs managed at a quaternary referral center between December 1990 and January 2015. Patients whose clinical presentation was compatible with a primary benign PA and whose history indicated tumor duration of over 1 year were included. Data were analyzed from January to April 2023. Untreated PA. Rate of CXPA detection among untreated PAs and association of tumor duration with rates of CXPA detection. Pathology slides of patients who underwent surgery were reviewed by a single expert pathologist for the presence of CXPA. Univariable logistic regression was performed to evaluate possible factors associated with CXPA. A total of 260 patients (median age, 47 years [IQR, 38-60 years]; 174 [66.9%] female) had a median tumor duration of 3.2 years (range, 1-30 years; mean [SD], 5.7 [5.5] years). Patients were divided into 4 groups by tumor duration: 1 to 4 years (158 [60.7%]), 5 to 9 years (47 [18.1%]), 10 to 14 years (27 [10.4%]), and 15 to 30 years (28 [10.8%]). In 156 of 170 patients who underwent preoperative fine-needle aspiration (91.8%), a benign tumor was diagnosed; 5 of these patients (3.2%; 95% CI, 1.4%-7.3%) were later diagnosed with CXPA on pathology after eventual excision, and the rate of high grade CXPA was 1.3%. None of the patients had permanent facial nerve paralysis. Tumor size at presentation (odds ratio [OR], 1.66; 95% CI, 1.22-2.24) and incremental (per year) increase in age (OR, 1.04; 95% CI, 1.01-1.08) were found to be associated with CXPA, whereas tumor duration was not (OR, 1.00; 95% CI, 1.00-1.01). In this study, the rate of malignant neoplasm detection among initially untreated PA was 3.2%. The results suggest that tumor size and older age are associated with the development of CXPA, while tumor duration is not. Observation of PA for longer periods was not associated with serious permanent complications.

Clinico-Epidemiological Analysis of Most Prevalent Parotid Gland Carcinomas in Poland over a 20-Year Period

(1) Background: Malignant tumours of the salivary glands have different clinical and histopathological characteristics. They most commonly involve the parotid gland. Histopathologically, the most common are mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (AcCC), adenocarcinoma, carcinoma in pleomorphic adenoma (CPA), and squamous cell carcinoma (SCC). (2) Methods: We analysed 2318 patients with malignant parotid gland tumours reported to the National Cancer Registry (NCR) in Poland over 20 years (1999–2018). The demographic characteristics of patients, clinical factors, and overall survival (OS) were analysed. (3) Results: The average age was 61.33 ± 16.1 years. The majority were males (55%) and urban citizens (64%). High percentage of carcinomas was diagnosed in locoregional (33.7%) and systemic (10.4%) stadium. The most prevalent diagnoses were SCC (33.3%) and adenocarcinoma (19.6%). Surgical resection with adjuvant RT (42.1%) was the most common treatment. The OS analysis showed a median survival time of 5.6 years. The most favorable median OS was found in patients with AcCC (18.30 years), the worst for SCC (1.58 years). (4) Conclusion: AcCC has the best prognosis and SCC the worst. Tumour stadium, treatment, and demographic factors affect prognosis. Improvements in diagnosis and re-evaluation of treatment standards are necessary to enhance the outcome of patients with parotid gland cancers in Poland.

Fine needle aspiration cytology in management of chronic salivary gland swellings

Neoplasms of salivary gland are an interesting diverse group of tumours. They form a fascinating subject for the head and neck surgeons. The relative infrequency combined with considerable histological and behavioral diversities and their regional anatomic relationship make them unusually interesting and challenging. The material of the study was obtained from 129 patients who underwent fine needle aspiration of the salivary glands during the period of two years. The smears were collected in the cytology laboratory. Medical College hospital. The clinical details were collected directly from the patients. The study confines itself to patients above the age of 12 years. The FNAC smear of the case diagnosed as carcinoma in pleomorphic adenoma showed large cell clusters having pleomorphism and vesicular nuclei with prominent nucleoli. The FNAC smear of the case diagnosed as chronic sialadenitis showed a cluster or lymphocytes and polymorphs.

Tumeurs malignes de la parotide : épidémiologie au Togo

We had for aim to determine the epidemiological profile of malignant parotid tumors in sub-Saharan country: Togo. We retrospectively studied the files of patients seen and treated for malignant parotid tumors, from January 1989 to December 31, 2008, at the Tokoin teaching hospital. Patients treated for another malignant tumor at the same time were excluded from the study. Ninety-six patients were included. Thirty-one tumors (32.29%) were malignant, in 18male and 13female patients with a sex ratio of 1.38. The average age was 39years (range 24-70years of age). Two patients could not undergo surgery. Histologically, there were 10cases of squamous cell carcinoma (32.26%), 6cases of adenoid cystic carcinoma (19.4%), 6cases of adenocarcinoma (19.4%), 4cases of carcinoma in pleomorphic adenoma (12.90%), 3cases of mucoepidermoid carcinoma (9.7%), 1case of acinar carcinoma (3.2%), and 1case of cystadenocarcinoma (3.2%). Squamous cell carcinoma was the most frequent histological type observed in Togo, contrary to literature data for which mucoepidermoid carcinoma is the most frequent malignant parotid tumor.

Myoepithelial carcinoma ex pleomorphic adenoma: a rare intraosseous entity

After reading the article by Damin Zhao et al. on primary central carcinoma ex pleomorphic adenoma (CXPA), which was quite interesting and informative, I think there are some controversies and ambiguities that need to be discussed. 1The author titled the paper as concerning primary central CXPA.1Zhao D. He H. Fang M. Liu M. Ji B. He Z. Primary central carcinoma ex pleomorphic adenoma of the mandible: report of a rare case and literature review.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011; 112: e24-e28Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar I think that the word “primary” is inappropriate here, because the primary tumor that arose at the site was a benign pleomorphic adenoma. The carcinoma had not developed de novo. The authors stated that 80% of the histologic picture was that of myoepithelial carcinoma and that a benign component of pleomorphic adenoma was also seen. Therefore I humbly suggest that the case should be listed as myoepithelial CXPA of the mandible and that the word “primary” should be dropped. One case that shares similar behavior has been reported in an infant.2Asai S. Tang X. Ohta Y. Tsutsumi Y. Myoepithelial carcinoma in pleomorphic adenoma of salivary gland type, occurring in the mandible of an infant.Pathol Int. 1995; 45: 677-683Crossref PubMed Scopus (16) Google Scholar It could be hypothesized that the heterotropic salivary tissue entrapped in the mandible gave rise to a pleomorphic adenoma first, which then transformed into a myoepithelial carcinoma. Demonstration of a residual focus of pleomorphic adenoma, as in this case, can be considered as histologic evidence that the lesion arose from an intraosseous pleomorphic adenoma.3McCluggage W.G. Primrose W.J. Toner P.G. Myoepithelial carcinoma (malignant myoepithelioma) of the parotid gland arising in a pleomorphic adenoma.J Clin Pathol. 1998; 51: 552-556Crossref PubMed Scopus (29) Google Scholar2Two masses were mentioned. The sentence, “during surgery, another mass was found connected to the mandibular mass,” does not specify if both were intraosseous or if there was a cortical perforation between 2 separate lesions. If both of the tumors were not related to each other, it could be interpreted as separate benign and a malignant entities occurring synchronously.4Curry J.L. Petruzzelli G.J. McClatchey K.D. Lingen M.W. Synchronous benign and malignant salivary gland tumors in ipsilateral glands: a report of two cases and a review of literature.Head Neck. 2002; 24: 301-306Crossref PubMed Scopus (42) Google Scholar If there was perforation of the cortical plate, it may represent invasion of soft tissue salivary gland neoplasms into the mandible.5Johnston N.J. Lutterloch M.J. Lutterloch M.J. Cystadenocarcinoma of salivary gland presenting as a cystic lesion in the mandible.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006; 101: 201-204Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar3It is interesting to note that despite the aggressive behavior of the lesion, there was no lymph node involvement noticed clinically, whereas the frozen-section evaluation of nodes revealed malignant epithelial tumor.4There is no mention of the use of immunohistochemical markers that could be used to identify myoepithelial cells, e.g., smooth muscle protein markers such as alpha-SMA, SMMHC, h-caldesmon, basic calponin, keratins 14, 15, and 17, alpha1-beta1-integrin, and vimentin.6Ogawa Y. Immunocytochemistry of myoepithelial cells in the salivary glands.Prog Histochem Cytochem. 2003; 38: 343-426Crossref PubMed Scopus (88) Google Scholar Primary central carcinoma ex pleomorphic adenoma of the mandible: report of a rare case and literature reviewOral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and EndodonticsVol. 112Issue 2PreviewWe 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. Full-Text PDF

Mena, a new available marker in tumors of salivary glands?

Mena (mammalian Ena) is an actin regulatory protein involved in cell motility and adhesion. Based on its potential role in malignant transformation revealed in other organs, we analyzed the Mena expression in normal salivary glands (SG) and salivary tumors. Mena expression was determined in normal SG (n=10) and also benign (n=20) and malignant (n=35) lesions of SG. For the immunohistochemical staining we used the anti-Mena antibody. All normal SG and the benign lesions (10 pleomorphic adenomas, 10 Warthin's tumors) were Mena negative. Salivary duct carcinomas (n=5), carcinomas in pleomorphic adenoma (n=5), acinic cell carcinomas (n=5), squamous cell carcinomas (n=10) and high-grade mucoepidermoid carcinomas (n=2) were positive. The lymphomas (n=5) and low-grade mucoepidermoid carcinomas (n=1) were Mena negative. In one case the lymphoblastic cells stained positive for Mena. Some of the endothelial cells, in the peritumoral vessels, were Mena positive. To the best of our knowledge, this is the first study in the literature about Mena expression in salivary tumors. Our study suggests that Mena protein seems to play a role in malignant transformation and its intensity is correlated with the type and grade of tumor and also with vascular invasion. Its positivity in endothelial cells may suggest its potential role in tumor angiogenesis.

Expression of CD44V6 in parotid pleomorphic adenoma and carcinoma ex pleomorphic adenoma

Background: Change in expression of CD44 variant (CD44v) has been observed in several types of aggressive carcinomas. This pattern of expression might be associated with carcinogenesis of parotid pleomorphic adenoma (PPA) which is not widely studied. In this study, we aimed to investigate the expression of CD44v6 in the PPA before and after recurrence, between non-recurrent PPA, recurrent PPA, and PPA with carcinogenesis so as to identify whether the expression differences have existed before the recurrence and its significance for predicting the recurrence. Methods: Expression differences of CD44v6 were detected by immunohistochemistry in samples of non-recurrent PPA, PPA before and after the recurrence, carcinoma in pleomorphic adenoma (CPA) and normal parotid. Results: The expression of CD44v6 was significantly higher in the group before the recurrence than that after the recurrence (p < 0.05). The expression of CD44v6 after recurrence was significantly lower than that in the non-recurrent group (p < 0.05) while the high level of CD44v6 expression in the non-recurrent group, was significantly lower than in the group with CPA (p < 0.05). However, no significant difference was observed between the group after recurrence and CPA. Conclusion: The decrease of CD44v6 expression promoted the recurrence and carcinogenesis of PPA, and the expression was decreased further in the process. The expression differences of CD44v6 had appeared before the recurrence.

Immunohistochemical analysis of P53and bcl-2 in benign and malignant salivary glands tumors

Salivary glands tumors are relatively uncommon neoplasm with widely variable histopathologic and biologic characteristics. Alteration in some proto-oncogenes and tumor suppressor genes may lead to the development and progression of these tumors. The purpose of this study was to analyze the immunohistochemical expression of P(53) and bcl-2 in some salivary gland tumors in relation to tumor size, histologic grade, and extent of invasion. The sample consisted of 22 formalin-fixed paraffin embedded blocks of benign and malignant salivary glands tumors. P(53) and bcl-2 immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40x magnification and recorded as percentage of P(53) or bcl-2 positive tumor cells over the total number of cells examined in the same area. Percentage scores were subsequently categorized using the 5% cut-off point for positive staining. Pleomorphic adenoma (PA) showed negative expression of P(53) and bcl-2 in 70% of cases, whereas all malignant salivary glands tumors were positive for P(53) and bcl-2. P(53) positive/bcl-2 positive immunostaining reaction was week in small size PA and was totally absent in larger lesions. However, all malignant tumors expressed P(53), with the highest record in low-grade adenocarcinoma (76%) and the lowest score was observed in both low-grade carcinoma in PA and adenocystic carcinoma. bcl-2 immunostaining was also assessed, the highest recorded score was in high-grade adeno cystic carcinoma (90%) and the lowest in both low-grade carcinoma ex-PA and low-grade cystic mucoepidermoid carcinoma (3%). P(53)/bcl-2 immunostaining reactivity could be helpful in demonstrating salivary glands tumor behavior in terms of progression and extent of invasion.

Establishment and characterization of pleomorphic adenoma cell systems: an in-vitro demonstration of carcinomas arising secondarily from adenomas in the salivary gland

BackgroundAmong the salivary gland carcinomas, carcinoma in pleomorphic adenoma has been regarded as a representative carcinoma type which arises secondarily in the background of a pre-existent benign pleomorphic adenoma. It is still poorly understood how and which benign pleomorphic adenoma cells transform into its malignant form, carcinoma ex pleomorphic adenoma.MethodsWe have established five cell systems from a benign pleomorphic adenoma of the parotid gland of a 61-year-old woman. They were characterized by immunofluorescence, classical cytogenetics, p53 gene mutational analysis, fluorescence in-situ hybridization, and histopathological and immunohistochemical examinations of their xenografts, to demonstrate their potency of secondary transformation.ResultsWe established and characterized five cell systems (designated as SM-AP1 to SM-AP5) from a benign pleomorphic adenoma of the parotid gland. SM-AP1 to SM-AP3 showed polygonal cell shapes while SM-AP4 and SM-AP5 were spindle-shaped. SM-AP1-3 cells were immunopositive for keratin only, indicating their duct-epithelial or squamous cell differentiation, while SM-AP4/5 cells were positive for both keratin and S-100 protein, indicating their myoepithelial cell differentiation. Chromosome analyses showed numeral abnormalities such as 5n ploidies and various kinds of structural abnormalities, such as deletions, translocations, derivatives and isodicentric chromosomes. Among them, der(9)t(9;13)(p13.3;q12.3) was shared by all five of the cell systems. In addition, they all had a common deletion of the last base G of codon 249 (AGG to AG_) of the p53 gene, which resulted in generation of its nonsense gene product. Transplanted cells in nude mice formed subcutaneous tumors, which had histological features of squamous cell carcinoma with apparent keratinizing tendencies. In addition, they had ductal arrangements or plasmacytoid appearances of tumor cells and myxoid or hyaline stromata, indicating some characteristics of pleomorphic adenoma.ConclusionThis study demonstrates in vitro that certain cell types from pleomorphic adenoma are able to clone and survive over a long term and develop subcutaneous tumors in nude mice. The histological features of squamous cell carcinoma from the transplanted cell systems in nude mice might suggest a secondary onset of malignancy from a pre-existing benign adenoma.

Expression of CD44V6 in parotid pleomorphic adenoma and carcinoma in pleomorphic adenoma

Expression of CD44V6 in parotid pleomorphic adenoma and carcinoma in pleomorphic adenoma

Carcinomas arising in the submandibular gland: High propensity for systemic failure

Cancers of the submandibular gland are uncommon and only a few small series have reported patient survival and prognosis. We examined the treatment outcomes of 62 patients with surgically treated submandibular gland carcinomas. All patients underwent surgical excision with/without neck dissection, and 41 received postoperative radiotherapy for high-grade, invasive, positive margin, or regionally metastatic tumors. The locoregional control and survival rates were calculated by the Kaplan-Meier method and prognostic factors were calculated from uni- and multivariate analyses. Of the 62 submandibular gland carcinomas, 19 were adenoid cystic, 11 were mucoepidermoid, and 10 were salivary duct carcinomas, and 8 were carcinomas in pleomorphic adenoma. Actuarial 5-year locoregional control, distant metastasis-free survival, disease-free and overall survival rates were 69.7%, 65.8%, 52.8%, and 56.8%, respectively. In multivariate analysis, T category and histological grading were prognostic for disease-free survival (P < 0.01), and T category and resection margins were prognostic for locoregional control (P < 0.02). Distant metastases were found in 21 patients (33.9%) at initial staging (n = 2) or follow-up (n = 19). Despite effective locoregional treatment, approximately one-third of patients with submandibular gland carcinomas may fail systemically, resulting in poor survival. New, more effective therapies may be required for these patients.

Update on Diagnostic Difficulties in Lesions of the Minor Salivary Glands

Update on Diagnostic Difficulties in Lesions of the Minor Salivary Glands

A retrospective study of 12 cases with carcinoma in pleomorphic adenoma

A retrospective study of 12 cases with carcinoma in pleomorphic adenoma

Mucoepidermoid Carcinoma Arising From Pleomorphic Adenoma of the Soft Palate

Carcinoma arising in pleomorphic adenoma is a rare entity. A case of mucoepidermoid carcinoma in pleomorphic adenoma occurring in the soft palate of a 40-year-old woman is reported. An intraoral excision of the tumor was performed. Histopathological examination revealed high-grade mucoepidermoid carcinoma proliferated in pleomorphic adenoma with free surgical margin. The patient received adjuvant neck radiotherapy. She remains free of disease 16 months post-treatment.

唾液腺腫瘍１５１例の臨床統計的検討

One hundred fifty-one patients with salivary gland tumors histologically diagnosed at the Department of Oral and Maxillofacial Surgery, Kyushu University Hospital from 1982 through 2001 were clinicostatistically studied. The following results were obtained: 1. Of the total, 56.3% had benign tumors and 43.7% had malignant tumors.2. Pleomorphic adenomas were most common, comprising 47.8% of all tumors and 84.7 % of benign tumors.3. Both benign tumors and malignant tumors occurred more frequently in women.4. The average age of the patients with malignant tumors (56.6 years) was higher than that of the patients with benign tumors (49.3 years).5. With respect to the primary site, parotid gland tumors were most common, comprising 33.8% of all tumors. All sublingual gland tumors (100%) were malignant.6. The cause-specific cumulative survival rate for all patients with malignant tumors was 67.6% at 5 years and 61.7% at 10 years. Mucoepidermoid carcinoma had a good outcome, but adenoid cystic carcinoma and carcinoma in pleomorphic adenoma had poor outcomes. According to primary site, submandibular gland tumors were associated with a significantly lower cumulative survival rate than minor salivary gland or parotid gland tumors.

TP53 mutations in salivary gland neoplasms

Many studies have demonstrated that loss of TP53 gene function has an important role in the genesis of many neoplasms, including salivary gland neoplasms. The purpose of this study was to examine the mutation profile of the TP53 gene in salivary gland neoplasms. Genomic DNA was extracted from paraffin-embedded tissues of pleomorphic adenoma, carcinoma in pleomorphic adenoma, mucoepidermoid carcinoma, adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. Exons 5 to 8 of the TP53 gene were amplified by polymerase chain reaction (PCR) to perform single-stranded conformational polymorphism (SSCP) analysis. Band shifting was observed in exons 5, 6 and 8 in 9 out of 18 neoplasms. The results of this study suggest that mutations in TP53 gene are related to salivary gland neoplasms pathogenesis and that exons 5 and 8 are most frequently involved.

Recurrent pleomorphic adenoma of the parotid gland

Background Surgery of recurrent pleomorphic adenoma presents an increased risk of facial nerve injury and a considerable re-recurrence rate. Methods A series of 33 patients with first recurrence of pleomorphic adenoma of the parotid gland was analyzed. The data were derived from medical records as well as from interviews and clinical examinations of all living patients. Histologic material of the initial and recurrent tumor were reviewed. Results Multifocal recurrence and carcinoma in pleomorphic adenoma were observed in 73% and 9% of patients, respectively. The incidence of permanent partial facial nerve injury after surgery was 23% in patients with initial enucleation and 14% in those with initial superficial parotidectomy (including 1 patient with facial nerve resection and 1 patient with a partial facial paresis before recurrence surgery). A subsequent recurrence occurred in 6 patients, all with initial enucleation after a mean time interval of 9 years. Conclusions The preservation of the facial nerve was possible in all but 1 patient treated for the first recurrence with a relatively low rate of permanent partial facial paresis because of the use of the operating microscope and facial nerve monitor. To evaluate the re-recurrence rate, a follow-up of at least 10 years is necessary.

Intraoral minor salivary gland tumors: a clinicopathological study of 82 cases

We present a retrospective study of 82 patients with intraoral minor salivary gland tumors which were diagnosed from 1979 to 2003 in Gifu University Hospital. The histological diagnoses were reevaluated according to the 1991 WHO classification. A total of 82 tumors, consisting of 55 benign and 27 malignant tumors, were found in 28 male and 54 female Japanese patients; the male-to-female ratio was 1:1.9. The mean age of the patients was 51.4 ± 18.1 years. The tumors affected the palate ( n = 64), the buccal region ( n = 10), the upper lip ( n = 6), the floor of the mouth ( n = 1), and the retromolar region ( n = 1). Histologically, the tumors were classified as pleomorphic adenoma ( n = 54), papillary cystadenoma ( n = 1), adenoid cystic carcinoma ( n = 10), mucoepidermoid carcinoma ( n = 8), acinic cell carcinoma ( n = 3), adenocarcinoma ( n = 2), basal cell adenocarcinoma ( n = 1), papillary cystadenocarcinoma ( n = 1), and carcinoma in pleomorphic adenoma ( n = 2). From the results of the present study and review of the literature, it is suggested that the minor salivary gland tumors in Japan may be characterized by a higher incidence of benign tumors, especially of pleomorphic adenoma; a more marked tendency for female predominance; a higher incidence of palatal involvement; and a rarer occurrence of polymorphous low grade adenocarcinoma, in comparison with those reported in the literature from outside of Japan.

Flow cytometric DNA ploidy in salivary gland tumours

This study on 279 tumours of the salivary glands was conducted to analyse whether the assessment of DNA ploidy by flow cytometry may assist histopathology in discriminating benign from malignant types of tumours. The group of benign tumours included 164 pleomorphic adenomas, 51 Warthin's tumours, 7 basal cell adenomas, 2 lipomas as well as 5 other different tumours. All of the 229 benign tumours were diploid. The malignant tumours consisted of 18 adenoid cystic adenomas, 10 mucoepidermoid carcinomas, 5 acinic cell carcinomas, 5 carcinoma in pleomorphic adenoma as well as of 12 other malignancies belonging to 7 different tumour entities. Twelve of 50 malignant salivary gland tumours were aneuploid. There was no significant relationship between the DNA ploidy status and histopathological grading, lymph node metastasis and local recurrence development, respectively. In three cases which initially were taken for pleomorphic adenomas by routine histological examination, aneuploid cell populations exposed by DNA flow cytometric analysis gave rise to a closer inspection of the suspect lesions. Examination of consecutive slides actually revealed small assemblies of carcinoma cells that required a final diagnosis as non-invasive carcinoma in pleomorphic adenoma. The most obvious value of DNA flow cytometry in salivary gland tumours is thus its contribution to assist histopathology in identifying potentially malignant lesions.

Movable carcinoma in pleomorphic adenoma of the palate with a pedicle base

Movable carcinoma in pleomorphic adenoma of the palate with a pedicle base