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.

BACKGROUND: Carcinoma 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 DESCRIPTION: This 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. CONCLUSION: Targeted 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.

Pathology Mimicking Orofacial Pain.

A case of a 64-year-old woman is reported, who developed new-onset pain over a preexisting area of right mandibular fullness. Clinical examination, MRI, and fine-needle aspiration cytology confirmed the diagnosis of a benign parotid gland tumor-pleomorphic adenoma, which was treated by total parotidectomy with complete removal of the tumor. When evaluating a patient with orofacial pain, oral health care providers should be cognizant of all potential differential diagnoses, especially in the setting of red flags such as persistent or enlarging facial swelling/fullness.

Supporting the use of adjuvant radiotherapy in recurrent pleomorphic adenoma of the parotid.

BACKGROUND: The use of adjuvant radiotherapy remains controversial in the treatment of recurrent pleomorphic adenomas. AIMS/OBJECTIVES: The aim of this study was to provide the highest level of evidence possible by performing a systematic review and meta-analysis of the literature. MATERIAL AND METHODS: We searched the English-language literature between 1985 and 2019.Inclusion criteria included any study on the treatment and outcome of recurrent pleomorphic adenomas. Exclusion criteria included the use of radiotherapy for residual tumors, case reports, and pleomorphic adenomas not arising from the parotid. RESULTS: A total of 522 abstracts were studied, data analyzed from 14 studies, on a total of 697 patients. When the data werepooled, the overall risk of further recurrence was 21%. In studies where surgery alone was undertaken this increased to 26% and decreased to 10% in those receiving adjuvant radiotherapy (p = .000). There were 21 recurrences in 159 patients in the radiotherapy group, and 151 recurrences out of 538 patients in the surgery group (p < .0001). CONCLUSIONS: These data support the use of radiotherapy to decrease the risk of re-recurrence in recurrent pleomorphic adenoma. SIGNIFICANCE: This study is the highest level of evidence currently available in guiding management of recurrent pleomorphic adenoma.

Survival and prognostic factors of salivary gland malignant mixed tumor-not otherwise specified: A population-based analysis.

OBJECTIVE: Malignant mixed tumors of the salivary gland are a group of neoplasms comprised of carcinoma-ex-pleomorphic adenoma, carcinosarcoma, and metastasizing pleomorphic adenoma. An alternative classification, malignant mixed tumor-not otherwise (MMT-NOS), is a diagnosis of exclusion for neoplasms that do not fit the previous histologically profiled subtypes. The objective was to provide a comprehensive assessment of MMT-NOS and determine prognostic factors. METHODS: This retrospective cohort study queried the Surveillance, Epidemiology, and End Results database for patient and tumor characteristics of US patients with MMT-NOS of the major salivary glands from 1973 to 2016. Kaplan-Meier and Cox regression analysis were performed to determine 5-year survival and prognostic factors. RESULTS: 434 patients were identified with a mean age at diagnosis of 61.5 years. The majority of neoplasms were high grade and stage (70.8% grade III/IV; 63.8% stage III/IV). Extraparenchymal extension (40.6%) and lymph node involvement (28.5%) were common; distant metastases (2.4%) were rare. Treatment included surgery (93.0%), radiation (51.6%), and chemotherapy (10.4%). Facial nerve sacrifice was common (50.8%). Median survival was 66.5 months. 5-year overall and disease-specific survival were 65.7% and 83.0%, respectively. In multivariate analysis, nodal involvement (HR 7.0; P < 0.001), surgery-radiation-chemotherapy (HR 6.1; P = 0.02), extraparenchymal extension (HR 2.50; P = 0.04), and tumor size >4 cm (HR 1.3; P = 0.03) were prognostic factors. CONCLUSION: Despite high stage and grade at diagnosis, MMT-NOS portends a good 5-year prognosis and low rate of distant metastasis. Prognostic factors were nodal involvement, tumor size, and extraparenchymal extension.

Cutaneous Metastasis From Parotid Tumors: A Report of 2 Cases and Literature Review.

ABSTRACT: Cutaneous metastases from parotid tumors are uncommon and imply a poor prognosis. In this article, we report 2 new cutaneous metastasis cases from 2 different parotid malignancies and 42 additional cases from a literature review. Clinical manifestations, localization, and outcomes of skin metastasis from parotid tumors are described. Although infrequent, parotid neoplasms may develop skin metastasis many years after the initial diagnosis, mostly in the head and neck region. Therefore, long-term follow-up and periodic skin examination of these patients is mandatory. Dermatologists and surgeons must have a high index of suspicion when evaluating any skin lesion arising on these patients because cutaneous metastasis from parotid neoplasms generally implies a poor prognosis.

Clinical outcomes of bulky parotid gland cancers: need for self-examination and screening program for early diagnosis of parotid tumors.

BACKGROUND: Early detection and diagnosis of parotid gland cancer (PGC) are essential to improve clinical outcomes, because Tumor-Node-Metastasis stage at diagnosis is a very strong indicator of prognosis in PGC. Nevertheless, some patients still present with large parotid mass, maybe due to the unawareness or ignorance of their disease. In this study, we aimed to present the clinical outcomes of bulky PGC (defined by a 4 cm cutoff point for T3-4 versus T1-2 tumors), to emphasize the necessity of a self-examination tool for parotid gland tumor. METHODS: We retrospectively reviewed 60 consecutive cases with bulky (equal to and greater than 4 cm in the longest diameter, determined radiologically) malignant tumors arising from the parotid gland from 1995 to 2016. The clinical and pathological factors were analyzed to identify risk factors for poor outcomes using Cox proportional hazard models. In addition, we designed a self-examination tool for parotid gland tumors, similar to breast self-examination for breast cancer detection. RESULTS: Patients with bulky parotid cancer showed 48.9% 5-year and 24.5% 10-year overall survival rates and a 47.9% risk of high-grade malignancy. The common pathological diagnoses were carcinoma ex pleomorphic adenoma (18.3%), adenocarcinoma (16.7%), mucoepidermoid carcinoma (16.7%), salivary duct carcinoma (16.7%), and adenoid cystic carcinoma (11.7%). Survival analyses revealed that tumor size (hazard ratio, HR = 1.262 upon increase of 1 cm, 95% confidence interval, 95%CI 1.059-1.502), lymph node metastasis (HR = 2.999, 95%CI 1.048-8.583), and high tumor grade (HR = 4.148, 95%CI 1.215-14.154) were independent prognostic factors in multivariable analysis. Functional preservation of the facial nerve was possible only in less than half of patients. CONCLUSION: In bulky PGC, lymph node metastasis at diagnosis and high tumor grade indicated poor survival outcomes, and functional outcomes of the facial nerve were suboptimal. Thus, a public effort seems to be necessary to decrease these patients with bulky PGC, and to increase patients' self-awareness of their disease. As a way of early detection, we proposed a parotid self-examination tool to detect parotid gland tumors at an early stage, which is similar to breast self-examination.

Outcomes of carcinoma ex pleomorphic adenoma compared to de novo adenocarcinoma of major salivary glands.

BACKGROUND AND OBJECTIVES: Carcinoma ex pleomorphic adenoma (CXPA) is a rare disease of the major salivary glands that remains poorly characterized. Our objective was to compare the clinical outcomes of patients with CXPA of the major salivary glands to those with de novo adenocarcinomas. METHODS: Review of the NCDB between 2004 and 2016 to compare cases of CXPA and adenocarcinoma of major salivary glands. Demographics, clinical characteristics, and survival were analyzed. RESULTS: We identified 1181 patients with CXPA and 3326 patients with adenocarcinoma of major salivary glands. Adenocarcinomas presented with higher rates of nodal metastasis (54.7% vs. 30.4%, p < .001). Five-year survival of adenocarcinoma (55.8%) was worse than that of CXPA (68.5%, p < .001). When stratified by nodal status, there was no significant difference in 5-year survival between CXPA and adenocarcinoma node-negative (75.3% vs. 71.6%, respectively) and node-positive (40.4% vs. 36.1%, respectively) patients. CONCLUSIONS: CXPAs of the major salivary glands present at an earlier stage with lower rates of regional metastasis compared to adenocarcinomas. After controlling for lymph node metastases, the outcomes are quite similar.

Successful tri-modality treatment of atypical carcinoma ex-pleomorphic adenoma with more than 50 nodal metastases.

Carcinoma ex-pleomorphic adenoma (CEPA), an extremely aggressive malignant tumor, bears a significant potential for locoregional recurrence and distant metastases. Management of the disease usually involves definitive surgery with postoperative radiotherapy administered for identified nodal metastases. Two cases of CEPA with many (>50) cervical lymph node metastases and other histopathological features were managed by tri-modality treatment scheme. No evidence of disease occurred during follow-up of at least 2 years. These cases may eventually establish the value of surgery with adjuvant radiochemotherapy in patients with CEPA and supernumerary nodal metastases.

Metastatic Pleomorphic Adenoma in the infratemporal fossa and neck following total parotidectomy after 30 years.

Metastasising pleomorphic adenoma is rare and may occur years after surgical excision of a pleomorphic adenoma (PA). We present a 61-year-old woman with a right infratemporal PA with metastases to the cervical lymph nodes after 30 years following a total parotidectomy. She was treated successfully with a resection of the tumour with combined neck and mandibulotomy approach along with postoperative radiotherapy given subsequently.

Diplopia: a unique presentation of recurrence of a salivary gland carcinoma.

A 79-year-old man with a history of radical excision of a left submandibular gland carcinoma ex-pleomorphic adenoma presented with a new 2 cm lump in his left submandibular region which proved to be recurrence on surgical excision. During work up for revision surgery he developed a right VI cranial nerve palsy, which was attributed to his microvascular status having had a history of three previous transient ischemic attacks (TIAs). 6 months later, his palsy had not resolved. MRI revealed new soft tissue by the cavernous segment of the internal carotid artery. The exact source of this was unclear as there was no evidence of local recurrence or nodal disease. A repeat MRI scan 16 months later revealed further growth of abnormal tissue in the cavernous sinus and the primary submandibular location, now involving multiple nerves including branches of cranial nerves IV, V, VI, VII and XII making surgical excision impossible.

The role of adjuvant radiotherapy in management of recurrent pleomorphic adenoma of the parotid gland: a systematic review.

PURPOSE: Recurrent pleomorphic adenoma poses a significant treatment challenge, considering its propensity for further recurrence and potential for malignant transformation. The role of adjuvant radiotherapy in its management is widely debated. The aim of this study was to determine whether adjuvant radiotherapy is more effective than surgical resection alone in patients with recurrent pleomorphic adenoma of the parotid gland, in terms of further recurrence, malignant transformation and treatment-related complications. METHODS: Using PRISMA guidelines, a systematic review comparing adjuvant radiotherapy with surgery alone in the treatment of recurrent pleomorphic adenoma was conducted. Pubmed, OVID, EBSCO, Embase, The Cochrane Library, SCOPUS and OpenGrey databases from 1988 to 2018 were searched. Quality analysis was carried out using the Newcastle-Ottawa Scale and narrative synthesis used to summarise results. RESULTS: Of 891 records screened, eight studies were included, assessing 366 participants. Two noted a benefit of adjuvant radiotherapy in reducing further recurrence. The remainder did not show significant benefit, although four showed a trend towards lower rates. Only one case of malignant transformation was identified in a patient not irradiated. Similar rates of facial nerve dysfunction were identified between groups. CONCLUSION: The available evidence suggests that adjuvant radiotherapy reduces recurrence rates in patients with recurrent pleomorphic adenoma and certain adverse prognostic factors. While it appears not to have significant adverse effects, given the lack of prospective evidence, we recommend careful use in patients at high risk of further recurrence and further research in the form of well-designed randomised controlled trials.

[Diagnosis and treatment of basal cell adenoma of parotid gland].

Objective:To investigate the clinical features, diagnosis and treatment experience of basal cell adenoma (BCA).Method:The clinical data of 7 patients with basal cell adenoma of the parotid gland from the Second Affiliated Hospital of Medical University of Anhui from March 2012 to June 2016 were retrospectively analyzed. Combined with literature review, the experience of diagnosis and treatment was discussed.Result:Seven BCA were mostly diagnosed as pleomorphic adenoma and adenomatous lymphoma before operation using parotid ultrasound, fine needle aspiration cytology and parotid enhanced CT, and no patients was diagnosed as BCA prior to the operation. Four cases were diagnosed as BCA, 1 case was diagnosed as adenoma, 1 case was diagnosed as low-grade malignant tumor, and 1 case was not able to identify benign or malignant tumor by intraoperative fast frozen pathological examination. There were no obvious complications after the operation, and only 2 cases of mild facial paralysis returned to normal in 1 month, and no recurrence was found in the follow-up 18-69 months. Conclusion:Basal cell adenoma of the parotid gland is a rare benign tumor of parotid gland, the lack of specific clinical manifestations and signs, preoperative ultrasonography, fine needle aspiration cytology and parotid gland enhanced CT scan can not confirm the diagnosis, although they have some limitations, they are of great value in the localization, qualitative and differential diagnosis of BCA in the parotid gland. The diagnosis mainly depends on intraoperative, postoperative pathology and immunohistochemical examination. The treatment is mainly surgical excision, and the prognosis is better.

Coexistence of Lymphoepithelial Carcinoma of the Parotid Gland and Submandibular Gland Pleomorphic Adenoma.

Lymphoepithelial carcinoma is a variant of undifferentiated carcinoma with characteristic dense lymphoid stroma in which nasopharynx is site of predilection. Racial and geographic association and Epstein-Barr virus positivity in endemic areas are other characteristics of this rare neoplasm. Lymphoepithelial carcinoma accounts for only 0.4% of malignant salivary gland tumors. The authors present a patient with Epstein-Barr virus positive lymphoepithelial carcinoma of the parotid gland in a nonendemic region. Besides this, synchronous pleomorphic adenoma in the contralateral submandibular gland caused a challenge in making initial therapeutic decision.

Parapharyngeal space primary tumours. / Tumores primarios del espacio parafaríngeo.

INTRODUCTION AND OBJECTIVES: The aim of this study is to present our experience with the diagnostic and therapeutic approaches for parapharyngeal space tumours. PATIENTS AND METHOD: This study is a retrospective review of 90 patients diagnosed with tumours of the parapharyngeal space and treated surgically between 1984 and 2015. Patients whose tumours were not primary but invaded the parapharyngeal space expanding from another region, tumours originating in the deep lobe of the parotid gland and head and neck metastasis were excluded from this study. RESULTS: 74% percent of the parapharyngeal space neoplasms were benign and 26% were malignant. Pleomorphic adenoma was the most common neoplasm (27%), followed by paragangliomas (25%), miscellaneous malignant tumours (16%), neurogenic tumours (12%), miscellaneous benign tumours (10%), and malignant salivary gland tumours (10%). The transcervical approach was used in 56 cases, cervical-transparotid approach in 15 cases, type A infratemporal fossa approach in 13 cases, transmandibular approach in 4 cases and transoral approach in 2 cases. The most common complications were those deriving from nervous injuries. CONCLUSIONS: Most parapharyngeal space tumours can be removed surgically with a low rate of complications and recurrence. The transcervical approach is the most frequently used.

Invasive myoepithelial carcinoma ex pleomorphic adenoma of the major salivary gland: two case reports.

BACKGROUND: Myoepithelial carcinoma (MEC) is a rare salivary gland tumor. Its long-term prognosis remains unknown because of the paucity of reported cases with long-term follow-up. Although some case series exist, the clinical features of MEC vary considerably depending on the site of origin. Therefore, accumulation of these rare cases is important. CASE PRESENTATION: Case 1: An 89-year-old man presented with a 10-year history of a mass originating from the right parotid gland and involving the neck. The mass grew rapidly for 3 months, reaching approximately 8 cm. There was no facial paralysis. MEC ex pleomorphic adenoma (PA) was suspected. Superficial parotid gland resection was performed in 2013; the tumor grade was pT3N0M0, and the resection margins were free of carcinoma. Because of several high-risk factors for metastasis (i.e., invasive carcinoma ex PA, high MIB1 index, and mutant p53 protein positivity), radiotherapy and chemotherapy were recommended as adjuvant therapy. Although the patient refused adjuvant therapy, he was recurrence-free at 36 months after surgery. Case 2: A 54-year-old woman presented with a >10-year history of a right submandibular mass, which grew rapidly for 1 year, reaching approximately 6 cm. Preoperative diagnosis was PA of the right submandibular gland. Submandibular gland resection was performed in 2013. Pathological analysis revealed invasive MEC ex PA, pT3N0M0; in addition, the carcinoma portion had an extra capsule and had invaded the platysma muscle close to the margin. An MIB1 index of 40 % and mutant p53 protein positivity indicated a high risk for metastasis. Additional resection and right neck dissection revealed no residual carcinoma. The patient refused adjuvant chemotherapy. One year after surgery, metastasis to the right pulmonary hilar node and both lungs were detected. Chemotherapy prevented recurrent growth of the lesion and extended survival. The patient was alive with cancer 30 months after the first surgery. CONCLUSIONS: High expression of the Ki67 labeling index might reflect prognosis of these cases. Chemotherapy for distant metastasis was effective, as expected. Further accumulation of cases and long follow-up data are needed to elucidate the pathophysiology and prognosis of MEC ex PA.

[The treatment of subglottic pleomorphic adenoma using the hypothermia plasma ablation: two cases report].

Subglottic pleomorphic adenoma is a rare disease . Surgery is the main curative treatment. To review some clinical cases and to summarize the characteristics and treatment experience of this disease,it is expected that we can provide more clinical thought and therapeutic strategy for subglottic pleomorphic adenoma.

[Predictors of malignancy in the management of parotid tumors: about 76 cases]. / Les facteurs prédictifs de malignité dans la prise en charge des tumeurs parotidiennes: à propos de 76 cas.

Salivary gland tumor pathology is complex and poses a diagnostic and therapeutic problem. A good analysis of predictive factors for malignancy in parotid tumors seems currently necessary for better therapeutic planning. The aim of this study was to investigate the predictive factors for malignancy in parotid tumors through a retrospective study of 76 cases of parotid tumor treated in a service of Otorhinolaryngology and Cervico Facial Surgery of Avicenne military hospital of Marrakech between January 2000 and December 2012. The study involved 40 women and 36 men. The average age was 44 years for benign tumours whereas it was 50 years for malignant tumours. The median of consultation time was 24 months for benign tumors and 16 month for malignant tumours. Swelling in the area of the parotid was always a patient detecting sign. Malignancy is clinically suspected based on pain, facial paralysis, surface structure and deeper structure fixity and on the presence of adenopathy. MRI has become the methodology of choice for evaluating parotid tumors due to its good diagnostic value in the assessment of benignity and malignancy. Fine needle aspiration biopsy has no value unless it is positive. Explorative parotidectomy with extemporaneous anatomopathological examination remains the key to positive diagnosis. Parotid benign tumors represent the most frequent entity (80%) and pleomorphic adenoma remains the predominant histologic type (61%). With regard to malignant tumors, they are rare, mainly dominated by mucoepidermoid carcinomas (6,5%). Surgical treatment is the first choice and it is often associated with lymph node dissection and radiation therapy for malignant tumors. Facial paralysis is the most common complication of parotid surgery.