Recurrent Pleomorphic Adenoma Research Articles

Dendritic cell subpopulations in carcinoma ex-pleomorphic adenoma: A multicenter study.

Carcinoma ex-pleomorphic adenoma (CEXPA) represents a malignant transformation from a recurrent or primary pleomorphic adenoma (PA), and the immune response may be essential in this process. Therefore, in this study, we aimed to identify and quantify subpopulations of dendritic cells (DCs) in CEXPA, residual PA in CEXPA (rPA), and PA. A multicenter study was performed collecting salivary gland tumor (SGT) samples from three Oral and Maxillofacial Pathology Centers. A tissue microarray containing 41 samples of CEXPA and 22 samples of PA was included in this study and submitted to immunohistochemical reactions against CD1a, CD83, CD207, and Ki67 antibodies. Both PA and rPA showed a higher quantification of CD207+ and CD83+ cells when compared to CEXPA (p < 0.001 and p < 0.01, respectively). There was also a difference when comparing the cell proliferation index between PA/rPA and CEXPA using the Ki-67 marker (p = 0.043). However, there was no difference in the DC population regarding clinical parameters such as sex, anatomical location, size, and metastases (p > 0.06). Immunohistochemical profile of DC subpopulations and cell proliferation biomarkers in SGTs can contribute as an important tool in the differentiation of benign and malignant tumors or detection of initial areas with malignant transformation.

MicroRNA copy number alterations in the malignant transformation of pleomorphic adenoma to carcinoma ex pleomorphic adenoma.

This study used array comparative genomic hybridization to assess copy number alterations (CNAs) involving miRNA genes in pleomorphic adenoma (PA), recurrent pleomorphic adenoma (RPA), residual PA, and carcinoma ex pleomorphic adenoma (CXPA). We analyzed 13 PA, 4 RPA, 29 CXPA, and 14 residual PA using Nexus Copy Number Discovery software. The miRNAs genes affected by CNAs were evaluated based on their expression patterns and subjected to pathway enrichment analysis. Across the groups, we found 216 CNAs affecting 2261 miRNA genes, with 117 in PA, 59 in RPA, 846 in residual PA, and 2555 in CXPA. The chromosome 8 showed higher involvement in altered miRNAs in PAs and CXPA patients. Six miRNA genes were shared among all groups. Additionally, miR-21, miR-455-3p, miR-140, miR-320a, miR-383, miR-598, and miR-486 were prominent CNAs found and is implicated in carcinogenesis of several malignant tumors. These miRNAs regulate critical signaling pathways such as aerobic glycolysis, fatty acid biosynthesis, and cancer-related pathways. This study was the first to explore CNAs in miRNA-encoding genes in the PA-CXPA sequence. The findings suggest the involvement of numerous miRNA genes in CXPA development and progression by regulating oncogenic signaling pathways.

Intraoperative Facial Nerve Involvement in Parotid Tumours - A Retrospective Analysis in a Tertiary Care Centre.

The study aims to provide a comprehensive overview of the various malignant and benign parotid tumours and evaluate the predictive factors for intraoperative nerve involvement leading to facial palsy (FP). It is a single-centre retrospective analysis for reviewing the involvement of facial nerve in post- parotidectomy patients. The clinical database from January 2012 to December 2020 was included in the study with a follow-up period of a minimum of 2 years. To maintain homogeneity, all squamous cell carcinomas of level 2 nodes involving parotid or residual/recurrent disease of the oral cavity requiring parotid dissection were excluded. A total of 248 patients (171 benign; 77 malignant) were evaluated with a mean age of 46.48 ± 10.76 years. The presence of malignancy increases the risk of FP (p = 0.027). 37 (14.92%) patients with FP were detected which included 34 with partial [32.35% in malignant; 62.16% in recurrent pleomorphic adenoma (RPA)] and 3 with total paralysis (66.67% in malignant; 33.33% in RPA). The recurrence of pleomorphic adenoma increases FP. While old age, larger size, hard fixed swelling with masseteric space (MS) infiltration appeared as risk factors for FP in malignant tumours (p = 0.047; p = 0.004; p < 0.00001 respectively). Tumour size, malignancy, hard fixed mass, masseteric space infiltration, recurrence, and age > 45yrs have been statistically significant predictive factors for intraoperative facial nerve involvement leading to FP. The study also revealed that FP occurred more commonly when there was concurrent involvement of both superficial and deep lobes but was not statistically significant.

Optimizing Facial Function in Patients With High-Risk Recurrent Pleomorphic Adenoma and a History of Facial Nerve Injury.

Parotid pleomorphic adenoma (PA) patients present significant diagnostic and surgical challenges rendering them high risk for facial nerve injury. Recurrent PA patients often present with history of facial nerve injury or previous reanimations making salvage of the facial nerve or previous reanimations significantly more complex. The study aim is to share our experience with this high risk for facial nerve injury population and review the literature. Adult patients with recurrent PA and history of facial nerve injury with at least 3 months of follow-up were analyzed for demographics, facial palsy history, previous head and neck surgeries, previous facial paralysis reconstruction, preoperative imaging, surgical approach, and postoperative outcomes. Four female patients were identified with an average age of 62 years. All patients underwent an initial protective dissection of the facial nerve or previous reanimation reconstruction by the facial nerve reconstructive team followed by the extirpative team. The average number of previous head and neck surgeries was 5, the number of recurrences was 2, and follow-up was 20 months. Half had prior dynamic facial reanimation. Two patients underwent complete preextirpative dissection of the facial nerve resulting in neuropraxia, which recovered completely after an average of 143 days. A third patient presented with 2 recurrences, both during and after reanimation with a dually innervated free functional muscle transfer. The reconstruction was salvaged, and motion was achieved. A fourth patient presented with benign preoperative findings, but intraoperative findings confirmed malignancy, necessitating facial nerve sacrifice, followed by immediate intratemporal grafting of the facial nerve and masseteric nerve transfer. Motion appeared 139 days postoperatively. A multidisciplinary effort should be implemented in this high risk for facial nerve injury population with the primary goal of protecting the facial nerve or any previous reanimation procedures, yet with preparedness to apply any reconstructive strategy based on intraoperative findings.

Recurrent pleomorphic adenoma of submandibular gland — a rare entity

BackgroundAmong benign salivary gland tumors, pleomorphic adenoma is one of the most common tumor involving submandibular gland, but it is rare to encounter recurrent pleomorphic adenoma in submandibular gland after submandibular gland excision.Case presentationWe present a case of 22-year-old female patient who presented to us with recurrent pleomorphic adenoma of submandibular gland region after 10 years of removal of submandibular gland, diagnosis was established with the help of ultrasound and fine-needle aspiration cytology, and thereafter, patient was taken up for surgical excision under general anesthesia. Histopathology confirmed the diagnosis.ConclusionsThis case report highlights the importance of special caution in removal of submandibular gland along with its capsule especially in pediatric population where due to small facial structures, chances of capsular breech are high, which can result in tumor seedling and future recurrence of tumor.

Partial response to RC-48 as palliative treatment in a patient with locallocally advanced carcinoma ex pleomorphic adenoma harboring a HER2 mutation: a case report

BackgroundCarcinoma ex pleomorphic adenoma (CXPA) is a neoplasm of the salivary gland that causes 3.6% of salivary gland tumors and 12% of salivary gland malignancies. Its prognosis is determined by the histological progression beyond the adenoma capsule. CXPA is thought to be a malignant transformation of a primary or recurrent pleomorphic adenoma and is associated with both benign and malignant lesions. Salivary gland cancers represent a rare heterogeneous group of neoplasms with complex clinicopathological characteristics and distinct biological behavior. Case descriptionThis case report summarizes the treatment of a 57-year-old male patient with CXPA of the left parotid gland, harboring HER2 amplification with poor prognosis. The overall survival of the patient has been > 3.5 years. The application and outcome of an immune checkpoint inhibitor and targeted therapy combination regimens in the treatment of CXPA carcinoma are discussed. ConclusionTargeted therapy combined with immunotherapy has long-term clinical benefits and targeted therapy which has a high clinical response rate (immunotherapy + dual-targeting three-drug regimens) may present an ideal choice for the treatment of patients with rare and/or refractory tumors without compromising patient safety.

Estrogen, Progesterone and Androgen Receptor in Primary and Recurrent Pleomorphic Salivary Adenomas.

Our study aimed to characterize alteration in the immunohistochemical expression of estrogen, progesterone and androgen receptor in the tumour cells of primary pleomorphic adenomas and recurrent pleomorphic adenomas. A retrospective study of data including 30 cases of primary pleomorphic adenomas (PA) without recurrences and 15 cases of recurrent pleomorphic adenomas were examined (RPA). RPA included 8 males and 7 females. Immunohistochemical expression of estrogen, progesterone and androgen receptor was examined in the selected cases. The percentage of slides was semi-quantitatively assessed by two independent observers and scores were given. The statistical analysis included the use of descriptive statistics and proportional frequencies. AR expression was identified in 12 (40. %) out of 30 cases of (PA) pleomorphic adenomas and 7 of 15 cases recurrent pleomorphic adenomas (RPA) (46 %). The results showed that ER and PR expression were negative in PA and RPA. Androgen receptors might have role in pathogenesis of PA and RPA. Estrogen and progesterone receptors have no role in development of recurrent pleomorphic salivary adenoma.

Clinical parameters predictors of malignant transformation of recurrent parotid pleomorphic adenoma

Malignant transformation (MT) in recurrent parotid pleomorphic adenomas (PAs) is rare; therefore its occurrence lacks reliable predictive factors. Our goal was to clarify the predictors for MT of recurrent parotid PAs based on preoperative clinical parameters. Patients with a clinical diagnosis of recurrent parotid PA were retrospectively enrolled. The association between clinicopathologic variables and MT of PA was assessed using univariate and multivariate analyses. MT occurred in 11.8% of the 467 patients. In univariate analysis, three or more previous recurrences, newly developed facial nerve paralysis, difficulty in mouth opening, tumors with the largest tumor diameter ≥ 2.4 cm, and abnormal neck lymph node enlargement were associated with MT occurrence. Further, multivariate analysis showed that three or more previous recurrences, newly developed facial nerve paralysis, difficulty in mouth opening, and abnormal neck lymph node enlargement were independently related to MT. MT of recurrent PA was not uncommon. Clinical signs of malignancy included newly developed facial nerve paralysis, difficulty in mouth opening, three or more previous recurrences, and abnormal neck lymph node enlargement.

Clinico-histopathological review of 255 patients who underwent parotidectomy for pleomorphic adenoma: a 10-year retrospective study—a proposal for an optimal diagnostic and therapeutic algorithm for patients with recurrent pleomorphic adenoma

PurposePleomorphic adenoma (mixed tumor) is the most common neoplasm of the parotid gland and one of the most frequent types of salivary gland tumor, generally with benign behavior and relatively slow growing. The adenomas could arise from the superficial, deep or from both superficial and deep parotid’s lobes.MethodsThe aim of this review is to retrospectively analyze the surgical management of patients with pleomorphic adenoma of the parotid gland performed at the Department of Otorhinolaryngology (Department of Sense Organs of “Azienda Policlinico Umberto I” in Rome), from 2010 to 2020, with a focus on the percentage of recurrence and on the complication related to surgery to suggest an optimal diagnostic and therapeutic algorithm for patients with recurrent pleomorphic adenoma. The analysis of the complications observed in case of different surgical approaches was performed using the X2 test.ResultsThe choice of a surgical approach (superficial parotidectomy—SP, total parotidectomy—TP, extracapsular dissection—ECD) depends on several elements, such as the location and the size of the adenoma, the availability of existing technical facilities and the professional experience of the surgeon. A transient facial palsy was present in 37.6%, 2.7% reported a permanent facial nerve palsy, 1.6% developed a salivary fistula, 1.6% a post-operative bleeding and 2.3% showed Frey Syndrome.ConclusionThe surgical management of this benign lesion is required, even in asymptomatic cases, to prevent the progressive growing and to reduce the risk of malignant transformation. The goal of surgical excision is to obtain the complete resection to minimize the risk of tumor recurrence and avoiding facial nerve disability. Therefore, an accurate preoperative study of the lesion and the choice of the most appropriate surgical treatment are essential to minimize the rate of recurrence.

Pleomorphic Adenoma of the External Auditory Canal From Ceruminous Gland Adenoma: Case Report and Review of the Literature.

We describe a right external auditory canal (EAC) recurrent ceruminous pleomorphic adenoma (CPA) accompanied by itching and review the clinical features and histopathology of this disease. A female in her 70s presented with a right EAC mass accompanied by itching. We initially diagnosed the mass as a ceruminous gland adenoma (CGA) following excisional biopsy. Two years and nine months later, the tumor recurred at the same site. A preoperative computed tomography (CT) scan demonstrated no bone destruction, and magnetic resonance imaging (MRI) showed a 1 × 1 cm mass with a clearly defined margin in the right EAC. We completely excised the recurrent tumor using a transmeatal approach under general anesthesia. Histopathology demonstrated haphazard proliferation of tubule-glandular structures lined by two layers of the epithelium in the hypocellular stroma composed of a mucoid matrix. The recurring tumor was diagnosed as a CPA. Here, an EAC tumor-originally diagnosed as a CGA following excisional biopsy-recurred and was subsequently diagnosed as a CPA. CPA can be considered an unusual variant of CGA.

Audit of Risk Factors to Predict the Recurrence of Salivary Gland Pleomorphic Adenomas

Recurrent pleomorphic adenomas (rPA) are often numerous, multifocal, and located distant from their original tumour site, despite their benign nature. There is a lack of consensus on the management of recurrences. This study is the largest case series published to date. This study aims to characterise the time-to-recurrence rPA, associated risk factors and multinodular nature.

A Case of Recurrent Pleomorphic Adenoma of the Buccal Region Resected by Transoral Approach

A Case of Recurrent Pleomorphic Adenoma of the Buccal Region Resected by Transoral Approach

Recurrent pleomorphic adenoma of the parotid gland: A population-based study with emphasis on re-recurrence and malignant transformation.

This study aimed to analyze the prognostic determinants for re-recurrence and malignant transformation of parotid recurrent pleomorphic adenoma (RPA). Between January 2011 and December 2020, all the cases of RPA of the parotid gland at our single institution were reviewed. A total of 168 patients were included in this study, with a median age of 41.5 years, and 20 (11.9%) patients developed re-recurrence during follow-up. It has been evidenced that recurrence times (single or multiple) was an independent prognostic factor for recurrence-free survival (p=0.0264). A total of 26 (15.48%) patients experienced malignant transformation of parotid RPA, and older age (>45 year old), male sex, and higher clinical tumor staging (T3-T4) were significantly associated with malignant transformation of parotid RPA. Recurrence times was an independent prognostic factor for re-recurrence of parotid RPA, and older male with high T-stage may more easily develop malignant transformation.

4. Audit of Risk Factors to Predict the Recurrence of Salivary Gland Pleomorphic Adenomas

Recurrent pleomorphic adenomas (rPA) are often numerous, multifocal, and located distant from their original tumour site, despite their benign nature. There is a lack of consensus on the management of recurrences. This study is the largest case series published to date. This study aims to characterise the time-to-recurrence rPA, associated risk factors and multinodular nature.

Modern Outcomes of Pediatric and Young Adult Patients with Parotid Gland Tumors Treated with Highly-Conformal Radiation Therapy

<h3>Purpose/Objective(s)</h3> Parotid tumors in the pediatric and young adult (PYA) population are a rare entity with a paucity of data available regarding treatment outcomes and toxicities. Most reports are long-term results of small series of patients treated with a wide variety of historical techniques. We aim to report our experience with modern highly-conformal radiation techniques for this unique population. <h3>Materials/Methods</h3> IRB approved retrospective review of 9 PYA patients (defined as age 0-25 at diagnosis) with parotid tumors treated with radiation therapy (RT) at one institution. Tumor characteristics, treatment modality, disease status, dosimetry, and acute and late toxicities were collected from the medical record. <h3>Results</h3> Nine PYA patients (5 female, 4 male) with received RT for parotid gland tumors from 2015-2022. The median age at diagnosis was 22 years (range 12-24). Median follow up was 34.4 months from RT completion. No patient had metastasis at diagnosis. Tumor histologies were: 4 mucoepidermoid carcinomas (n=1 sclerosing subtype); 1 acinic cell carcinoma, 1 adenocarcinoma, 1 NUT midline carcinoma, and 2 benign recurrent pleomorphic adenomas. All underwent total parotidectomy before RT. Three had disease involving only the deep lobe, 3 had only superficial involvement, and 3 had multifocal disease. Six patients underwent unilateral neck dissection at the time of parotidectomy; only 1 patient with a malignant tumor did not. Three patients had lymph node positive disease. The median time from surgery to RT was 6.7 weeks (range 4.7-10.7). Seven patients were treated using intensity modulated proton RT (IMPT), 1 started with intensity modulated RT (IMRT) for the first 20 of 30 fractions (fx) and transitioned to IMPT, and 1 was treated with IMRT alone. The most common dose and fractionation was 60 Gy in fx (n=7). One patient was treated using 66 Gy in 33 fx and n=1 with recurrent unresected gross disease received 69.96 Gy in 33 fx. The most common acute toxicities were grade 1-2 xerostomia, RT dermatitis, mucositis, alopecia, dysgeusia, and fatigue. No patient required a feeding tube or hospitalization during RT. One patient with NUT midline carcinoma histology received concurrent chemotherapy with cisplatin and etoposide. The most common late toxicities were grade 1-2 trismus, RT fibrosis, alopecia, lymphedema, and hearing loss. Two patients required thyroid supplementation after completing treatment – both received IMRT. There were no reported instances of osteoradionecrosis or extensive dental caries. All patients were alive at the time of data collection. There were no locoregional recurrences, and one patient (NUT midline carcinoma) developed distant metastatic disease. <h3>Conclusion</h3> Highly conformal proton/IMRT following surgical resection provides excellent local control with an acceptable toxicity profile for PYA patients with parotid gland tumors.

Increased MIB-1 expression in salivary gland pleomorphic adenoma that recurs and undergoes malignant transformation

The objective of this retrospective study was to explore possible changes in histopathological features and expression of cyclin D1 and MIB-1 in salivary gland pleomorphic adenoma (PA) that recur or undergo malignant transformation. Knowledge of these characteristics might help to guide the management of these rare tumors. The histopathology and immunohistochemical staining characteristics of such tumors were analyzed in a cohort of 65 patients constituting three different groups of tumors: PA, recurrent pleomorphic adenoma (RPA) and carcinoma ex PA (CxPA). The RPAs were divided into two subgroups: primary PA that were known to recur later (PA-prim) and recurrent tumors appearing after a primary tumor (PA-rec). RPAs and CxPAs were compared with PAs without recurrence, which served as a control group. In our study, CxPA and PA-rec, but not PA-prim, showed increased MIB-1 expression compared with the control group. Neither cyclin D1 expression nor any histopathological features showed any association in statistical analyses. CxPA showed increased mitotic activity, squamous metaplasia, and nuclear atypia. Tumor multifocality was more frequent in PA-rec and CxPA. The different MIB-1 expression in CxPA and PA-rec in comparison to PA-prim suggests that the changes in expression could develop after the primary tumor.

Comparative Longitudinal Analysis of Malignant Transformation in Pleomorphic Adenoma and Recurrent Pleomorphic Adenoma.

Background: Recurrence in pleomorphic adenoma (PA) has been debated as a risk factor for malignant transformation (MT). In this study, we investigated whether recurrence is a risk factor for MT, by longitudinally analyzing cases with recurrent PA (RPA), and carcinomas from PA (CXPA) or RPA (CXRPA). Methods: The study population included 24 CXPA, 24 RPA, 6 CXRPA, and 386 PA cases (study period 2010–2018). Time and event data were collected from the medical documents to identify the time–event sequences. Results: The time interval to MT in CXRPA was significant longer than that of benign recurrence (median 342.0 vs. 109.5 months). In CXRPA, the recurrence intervals were not shorter than those in RPA according to recurrence frequency. Crudely, the MT rate was 5.9% among primary cases and 20.0% among recurrent cases. However, the time-adjusted MT rates increased up to 11.4% (incubation time > 60 months) and 20.0% (>120 months) in primary cases, which were not different from recurrent cases. Conclusion: In these longitudinal analyses, we did not find any clinical evidence that recurrence facilitates MT in the background of PA. Instead, a long incubation time seems to be a key factor for MT of underlying RPA.

An institutional review of recurrent pleomorphic adenoma of the parotid gland.

Surgical resection is standard treatment for pleomorphic adenoma (PA) of the parotid gland. A small number (2-5%) of these tumors recur. Recurrence usually necessitates reoperation, which is technically challenging and puts the facial nerve (FN) at risk. The aim of this study is to characterize the recurrent parotid PA population and compare outcomes after surgery for singly recurrent and multiply recurrent tumors. This study was a retrospective chart review of patients at a single tertiary care academic medical center who underwent operations for recurrent PA of the parotid gland between 2007 and 2020. Demographic data, details of surgical interventions, pre- and postoperative FN function, and recurrence rates were studied. These factors were compared between patients with singly and multiply recurrent tumors. Thirty-eight patients met criteria: 4 patients presented for primary PA and subsequently recurred, 26 with a first recurrence, 7 with a second recurrence, and 1 with a fourth recurrence. Multiply recurrent PAs were more likely to require at least partial nerve sacrifice at the time of reoperation (P = 0.0092). Significantly worse long-term FN outcomes were seen following surgery for multiply recurrent PA (P = 0.008). There was no significant difference between the rate of re-recurrence following first revision surgery vs second-fourth revision surgery. Time to reoperation was significantly shorter between the first and second revision surgery than between the primary surgery and first revision (P = 0.0017). Surgery for recurrent PA incurs high risk to the FN, and this risk appears to increase in the setting of multiple recurrences.

Audit of Risk Factors to Predict the Recurrence of Salivary Gland Pleomorphic Adenomas

Recurrent salivary gland pleomorphic adenomas are a complex oncological challenge, despite their benign nature. These tumours are often numerous, multifocal, and located distant from their original tumour site. Current recurrence rates stand at 2% however the management and surgical approach for recurrences are unclear. This study aims to characterise, for the first time, risks factors that predict the rate at which recurrent nodules emerges.

Minor Salivary Gland Tumors: A Retrospective Study of 37 Cases

Salivary gland tumors represent 2% - 6.5% of all head and neck tumors. Since salivary gland tumors have various clinical features and histological types, it is often difficult to diagnose and treat them. The aim of this study was to conduct a retrospective clinical-statistical analysis of 37 minor salivary gland tumors (MSGTs) treated in the Department of Oral Surgery at Nihon University School of Dentistry at Matsudo over a 16-year period. The frequencies and distributions of sex, age, occurrence site, preoperative examination (fine needle cytology and/or biopsy), treatment, and prognosis of the tumors were analyzed and compared with previous reports. The average age at diagnosis was 58.1 years (range 22 - 91 years). The peak occurrence of tumors was in the sixties (10 cases, 27.0%), followed by the forties (8 cases, 21.6%) and the seventies (7 cases, 18.9%). The average age of patients with benign tumors was 56.8 years (range 22 - 91 years). For malignant tumors, the average age was 61.7 years (range 42 - 81 years). The male-female ratio was 1:2.1 for all minor salivary gland tumors, 1:2.4 for benign tumors, and 1.5:1 for malignant tumors. There were 27 (73.0%) benign and 10 (27.0%) malignant tumors. Pleomorphic adenoma (PA) was the most common tumor (24 (64.9%) cases). Most salivary gland tumors originated from the palate (21 cases, 56.8%); the second most common site was the buccal mucosa (14 cases, 37.8%). For most patients, an intraoral mass was the primary presentation, and the second most common symptom was swelling. Surgical treatment was performed for all cases, both benign and malignant tumors. There was one case of local recurrence of PA, as well as one of multiple lung metastases after surgery for adenoid cystic carcinoma. Diagnosis and treatment of MSGTs are often delayed because the patients have few symptoms, and it is difficult to distinguish benign from malignant tumors. More cases need to be examined in the future, and the diagnostic accuracy of imaging and histopathological diagnosis needs to be improved.