A rare case of mucoepidermoid carcinoma ex pleomorphic adenoma of the lacrimal gland.

Carcinoma ex pleomorphic adenoma (CEPA) of the lacrimal gland is a rare malignant tumor that arises from a pre-existing pleomorphic adenoma. Lacrimal gland CEPA with mucoepidermoid histological subtype is exceedingly rare. Diagnosis can be aided by radiographic findings, though the gold standard is histopathological analysis following excisional biopsy. Management options include complete surgical excision with or without adjuvant radiation therapy based on tumor grade and invasiveness. We present a 76-year-old woman with 6 months of diplopia and unilateral proptosis. Her initial exam was remarkable for hypoglobus, proptosis, and limited elevation of the right eye. Computed tomography (CT) scan demonstrated a superior, well-circumscribed, extraconal orbital mass. An excisional biopsy was performed, and histopathological findings were consistent with mucoepidermoid carcinoma ex pleomorphic adenoma with positive margins in the tumor capsule. The patient received radiation therapy and remains markedly improved with no disease recurrence at 5 months post-operatively.

Mucoepidermoid Carcinoma of the Parotid: Very Close Margins and Adjuvant Radiotherapy.

BACKGROUND/AIMS: The importance of adjuvant radiotherapy in patients with close margin resections for mucoepidermoid carcinoma of the parotid gland remains unclear. METHODS: Patients who underwent parotidectomy for mucoepidermoid carcinoma with or without adjuvant radiotherapy at a single academic tertiary care center from 2000 to 2014 were identified. Included patients had negative but close (≤2 mm) surgical margins without other high-risk histopathological factors including advanced T-stage, positive nodal disease, lymphovascular or perineural invasion, or high-grade histology. RESULTS: Nineteen patients were identified, of whom 15 (79%) were observed postoperatively, while 4 (21%) underwent adjuvant radiotherapy. There were no significant differences in extent of parotidectomy, elective neck dissection, T staging, or tumor size between patients who were observed and those undergoing adjuvant radiation. There were no locoregional or distant recurrences in any patients at a mean follow up 74.3 months. Patients undergoing adjuvant radiation, however, had significantly more intermediate-grade as compared to low-grade histology (75% vs. 13%, difference 62%, 95% CI 4% to 100%). CONCLUSIONS: Patients with negative but close (≤2 mm) surgical margins without other high-risk histopathological factors have excellent long-term locoregional control with surgery alone. The effects of adjuvant radiotherapy for those who have intermediate-grade disease remain uncertain.

Multi-institutional retrospective study of mucoepidermoid carcinoma treated with carbon-ion radiotherapy.

This study aimed to evaluate the clinical outcomes of patients with mucoepidermoid carcinomas in the head and neck treated with carbon-ion radiotherapy. Data from 26 patients who underwent carbon-ion radiotherapy in four facilities were analyzed in this multi-institutional retrospective study: the Japan Carbon-ion Radiation Oncology Study Group. The median follow-up time was 34 months. One patient experienced local recurrence, and the 3-year local control rate was 95%. One patient developed lymph node recurrence and five developed distant metastases. The 3-year progression-free survival rate was 73%. Five patients died, two of mucoepidermoid carcinoma and three of intercurrent disease. The 3-year overall survival rate was 89%. Acute mucositis and dermatitis of grade 3 or higher were experienced by 19% and 8% of patients, respectively; these improved with conservative therapy. Late mucositis and osteonecrosis of jaw were observed in 12% and 23% of patients, respectively. The 3-year cumulative rate of any late adverse event of grade 3 or higher was 14%. None of the patients died of the acute or late adverse events. Carbon-ion radiotherapy was efficacious and safe for treating mucoepidermoid carcinoma in this multi-institutional retrospective study (registration no. UMIN000024473). We are currently undertaking a prospective multicenter study.

Persistent Pneumonia: Time to Take a Closer Look.

Primary pulmonary tumors are rare in pediatrics. When they are encountered, they are usually carcinoid tumors or mucoepidermoid carcinomas. We present a patient who presented to both his primary care physician and the pediatric emergency department with recurrent bouts of wheezing and pneumonia, none of which ever completely resolved despite appropriate treatment. The patient had multiple chest films, which demonstrated the persistence of what appeared to be a right-sided infiltrate/atelectasis. Ultimately, the patient underwent a diagnostic workup that included a computed tomography scan and bronchoscopy. These studies revealed the presence of a bronchial mucoepidermoid carcinoma. The patient was successfully treated with photoablation of the lesion through the involvement of multiple subspecialists, including pediatric pulmonology, pediatric surgery, pediatric otolaryngology, and pediatric oncology. We discuss the incidence and epidemiology of pediatric bronchial tumors in general and mucoepidermoid carcinoma in particular as well as diagnosis, treatment options, and prognosis. Emergency physicians must maintain a high index of suspicion for alternate diagnoses in patients whose disease fails to respond to traditionally accepted therapy.

Survival Impact of Elective Neck Dissection and Adjuvant Radiation in N0 High-Grade Mucoepidermoid Carcinoma.

OBJECTIVE: We aim to evaluate the role of elective neck dissection (END) and adjuvant radiation on survival in N0 high-grade mucoepidermoid carcinoma (MEC). STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. METHODS: All patients diagnosed with high-grade MEC with node-negative disease (N0) from 2004 to 2018 were included. Demographic, clinicopathologic, treatment, and outcomes were analyzed. Kaplan-Meier survival curves were used to evaluate 5-year disease-specific survival (DSS) and 5-year overall survival (OS). Multivariate Cox regression analysis was used to control for confounders. RESULTS: A total of 310 patients with high-grade MEC and N0 (clinical and pathologic) disease were identified. The parotid was the most common primary site (266, 86%). Of included patients, 133 (42.9%) were T3-T4 tumors and 212 (68%) received adjuvant radiation. END was performed on 223 (71.9%) of cases. END in T3-T4 high-grade MEC led to significant improvements in DSS (74.3% vs 34.0%, P < .01) and OS (55.2% vs 20.5%, P < .01) as compared to no END. Subanalysis shows that in patients who received neck dissections and were pathologic N0, adjuvant radiation had no impact on DSS (84.0% vs 72.1%, P = .45) and OS (52.1% vs 55.8%, P = .91). Benefits persisted when controlling for confounders using multivariate Cox proportional regression. CONCLUSION: Patients with T3-T4 high-grade MEC who underwent END and found to be pathologically node-negative (pN0) had significantly improved 5-year DSS and 5-year OS than patients who were cN0 and did not undergo END. Importantly, although 68% of patients received adjuvant radiation, we show no benefit of this treatment modality on outcomes in pN0 high-grade MEC.

The role of radiation therapy in pediatric mucoepidermoid carcinomas of the salivary glands.

OBJECTIVE: To investigate the role of radiation therapy in rare salivary gland pediatric mucoepidermoid carcinoma (MEC). STUDY DESIGN: A French multicenter retrospective study (level of evidence 4) of children/adolescents treated for MEC between 1980 and 2010 was conducted. RESULTS: Median age of the 38 patients was 14 years. Parotid subsite, low-grade, and early primary stage tumors were encountered in 81%, 82%, and 68% of cases, respectively. All except 1 patient were treated by tumoral surgical excision, and 53% by neck dissection (80% of high grades). Postoperative radiation therapy and chemotherapy were performed in 29% and 11% of cases. With a median 62-month follow-up, overall survival and local control rates were 95% and 84%, respectively. There was 1 nodal relapse. Lower grade and early stage tumors had better survival. Postoperative radiation therapy and chemotherapy were associated with similar local rates. Patients with or without prior cancer had similar outcomes. CONCLUSIONS: Pediatric salivary gland MEC carries a good prognosis. Low-intermediate grade, early-stage tumors should be treated with surgery alone. Neck dissection should be performed in high-grade tumors. Radiation therapy should be proposed for high grade and/or advanced primary stage MEC. For high-grade tumors without massive neck involvement, irradiation volumes may be limited to the primary area, given the risk of long-term side effects of radiation therapy in children. Pediatric MEC as second cancers retain a similar prognosis. Long-term follow-up is needed to assess late side effects and second cancers.

Elective neck management for high-grade salivary gland carcinoma.

PURPOSE: To determine whether patients with clinically node negative (cNo) high grade salivary gland carcinomas benefit from an elective neck dissection prior to postoperative radiotherapy (RT). MATERIAL/METHODS: Between October 1964 and October 2009, 59 previously untreated patients with cNo high-grade salivary gland carcinomas (squamous cell carcinomas were excluded) were treated with curative intent using elective neck dissection (END; n=41), or elective neck irradiation (ENI; n=18) at the University of Florida College of Medicine (Gainesville, FL). All patients underwent resection of the primary cancer followed by postoperative RT. The median follow-up period was 5.2years (range, 0.3-34years). RESULTS: Occult metastases were found in 18 (44%) of the 41 patients in the END group. There were 4 recurrences (10%) in the END group and 0 recurrence in the ENI group. Neck control rates at 5years were: END, 90%; ENI, 100%; and overall, 93% (p=0.1879). Cause-specific survival was 94% in the ENI group, 84% in the END group, and 86% for all patients (p=0.6998). There were 3 reported grade 3 or 4 toxicities. Two patients had a postoperative fistula and one patient had a grade 4 osteoradionecrosis that required a partial mandibulectomy. CONCLUSIONS: Patients with cNo high grade salivary gland carcinomas who are planned to undergo surgery and postoperative RT likely do not benefit from a planned neck dissection.

Relapsing high grade mucoepidermoid carcinoma. Long-lasting complete response following reirradiation and EGFR blockade.

BACKGROUND AND PURPOSE: The treatment strategy for inoperable recurrent mucoepidermoid carcinoma (MEC) is not well established. Here, we present a case of a relapsed high grade MEC of the salivary glands of the hard palate that was successfully treated with a reirradiation (re-RT) and cetuximab, an antibody against epidermal growth factor receptor (EGFR). CASE REPORT: Twelve years after resection and adjuvant radiotherapy for high grade MEC of the salivary glands, a patient presented with inoperable recurrent disease. She received another 59.4 Gy. In addition, 400 mg/m(2) cetuximab was administered in the first week, followed by six additional weekly courses at 250 mg/m(2). RESULTS: Treatment was well tolerated. The patient is doing well and continuous radiological complete response (CR) is documented for 25 months after completion of the combined treatment. CONCLUSION: Combined re-RT and targeted inhibition of EGFR with cetuximab may be a valuable therapeutic strategy in patients with recurrent localized high grade MEC who are not candidates for radical surgery.

Proton beam therapy for inoperable recurrence of bronchial high-grade mucoepidermoid carcinoma.

We report the case of a 17-year-old patient who received four courses of proton beam therapy for inoperable recurrent high-grade bronchial mucoepidermoid carcinoma of the chest wall and lymph nodes. The equivalent doses in conventional fractionation of 79.2-80.6 Gy were applied to the tumor from the first to third courses of proton beam therapy; the hemi-chest wall was also irradiated prophylactically in the third course. The irradiated tumor recurred marginally and liver metastasis developed, but tumor size within the irradiated field was suppressed. Proton beam therapy was also applied to the marginally recurrent tumor in the fourth course. The patient died of cancer about 5 years after the first course of proton beam therapy-about 9 years after the initial diagnosis and surgery. Repeated irradiation of the mediastinum and chest wall with photon radiotherapy is often limited by side-effects in the heart, esophagus and spinal cord. However, no severe late complications in critical organs were detected in this case. Only a Grade 2 skin reaction and lymphatic edema were observed. Therefore, high-dose proton beam therapy may be an option as a salvage therapy with less toxicity to normal tissues compared with photon radiotherapy and provide an alternative to repeated surgery.

PET/CT significance for planning radiotherapy of head and neck cancer.

The combination of positron emission tomography and computed tomography (PET/CT) offers metabolic mapping in addition to anatomic information of the primary lesion, nodal and distant metastases in patients with head and neck tumors, and may be therefore beneficial for radiotherapy planning. The aim of our study was to evaluate benefits of combined PET and CT imaging for staging and target volume delineation in this group of patients.Fifty three patients (40 men and 13 women) with confirmed advanced, inoperable or non-radically operated head and neck cancer were assessed based on the results of PET/CT as well as standard diagnostic examinations. All patients were subsequently treated with intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) of 6 MV X-rays. There was an agreement between the standard examinations results and results of PET/CT in 30 cases. In 23 cases there was disagreement either in tumor size, nodal involvement or presence of distant metastases. Results of the tumor size assessment differed significantly in 5 cases. There was no agreement found in nodal involvement in 10 cases. The cancer confirmed by standard examination was not found by PET/CT in 2 cases; 3 PET/CT positive findings were not confirmed by standard examinations. In 3 patients PET-CT revealed new distant metastatic disease. Based on PET/CT assessment we changed treatment strategy and applied potentially curative dose of radiotherapy to previously undiscovered regions in 9 patients. We decided to change the treatment intent in 3 cases and only palliative treatment was applied. Based on our experience and the literature review, PET/CT may be considerable contribution to the standard diagnostic procedures in approximately one third of cases.

Osteoradionecrosis of the mandible and mastoiditis after radiotherapy for parotid mucoepidermoid carcinoma.

Osteoradionecrosis of the mandible in conjunction with mastoiditis is an extremely rare occurrence following irradiation of salivary gland malignancy in the orofacial region. We report one such case of a patient who presented to us with trismus, jaw pain, and ear discharge. Imaging of the jaws revealed classical features of osteoradionecrosis and mastoiditis. This case is important because presenting features like trismus and dental infection led us to investigative procedures that revealed extensive bone involvement including mastoiditis. Trismus progressively increased over a period of 8 years. In this case, we would like to emphasize the importance of good oral hygiene in the postradiotherapy stage for head and neck cancer.

Mucoepidermoid carcinoma of the parotid gland in childhood survivor of acute lymphoblastic leukemia with need of radiotherapy for treatment and review of the literature.

Diagnosis of secondary malignancies began with the increasing survival in childhood cancer. Children treated for acute lymphoblastic leukemia (ALL) have an increased risk for developing mucoepidermoid carcinoma (MEC) of the parotid gland. The latent period ranges from 5 to 16 years. A 2 6/12-year-old girl was treated for pro-B ALL. Treatment included multidrug chemotherapy, prophylactic intrathecal methotrexate, and cranial radiotherapy. MEC of the left parotid gland was diagnosed at the age of 8 years, 3 years after completing treatment. She was treated with multiple surgery and radiotherapy. The authors aimed to emphasize the need for concern about second cancers of the parotid gland in children treated for ALL.

[Clinical analysis of 36 cases of esophageal mucoepidermoid carcinoma].

OBJECTIVE: To review the clinical characteristics, diagnosis, treatment and prognosis of esophageal mucoepidermoid carcinoma (MEC). METHODS: Clinical data of 36 patients with pathologically confirmed esophageal MEC who received surgical treatment in Cancer Hospital of Shantou University Medical College from Jan 1991 to Jun 2010 were retrospectively analyzed. The survival analysis was performed using Kaplan-Meier method. RESULTS: Of the 4253 patients diagnosed as esophageal cancer during the same time in our center, only 36 had esophageal MEC, accounted for 0.8%. This group included 27 men and 9 women ranging in age from 40 to 78 years (median 58 years). Esophageal MEC showed similar clinical symptoms, radiological and endoscopic features to esophageal squamous cell carcinoma (ESCC). Of the 20 cases who received preoperatively endoscopic biopsy, 18 were misdiagnosed as ESCC and 2 were misdiagnosed as esophageal adenosquamous carcinoma. The mean follow-up duration of this series was 38.8 months (3-142 months). 22 patients died of the disease during the follow-up period, 12 were still alive and 2 were lost of follow-up. The median survival time (MST) of the 36 patients was 29.0 months, and the 1-, 2-, 3-, and 5-year overall survival rates (OS) were 80.6%, 57.1%, 34.4%, 25.8%, respectively. CONCLUSIONS: Esophageal MEC is a rare disease and prone to be misdiagnosed by endoscopic biopsy. Surgical resection is the primary treatment but the prognosis is poor.

Osteosarcoma of the mastoid process following radiation therapy of mucoepidermoid carcinoma of the parotid gland--a case report.

Radiation therapy is frequently used method in treatment of the head and neck malignancies. Osteosarcoma is a rare complication of radiation therapy and usually occurs after a long latent period. We report the case of 75-year-old female with osteosarcoma of the mastoid process. Twelve years before presentation she received radiation therapy after total parotidectomy and radical neck dissection in treatment of mucoepidermoid carcinoma of the parotid gland. Diagnostic procedures included contrast-enhanced CT and MRI of the head and neck and HRCT of the temporal bone. The final diagnosis of the low grade osteosarcoma was confirmed by biopsy. Diagnostic criteria were fulfilled and the lesion was classified as a radiation induced osteosarcoma.

Iodine-125 brachytherapy for the treatment of central mucoepidermoid carcinoma of the jaw in a pre-teen.

Central mucoepidermoid carcinoma (MEC) of the jaw is a rare malignant neoplasm, even rarer in teenagers. Radical surgical resection, such as en bloc resection or segmental resection, is the main treatment for MEC of the jaw. This surgical treatment results in a loss of integrity of the jaw. The successful application of iodine-125 brachytherapy for the treatment of intraosseous MEC of the mandible in an 11-year-old girl is reported here. No local recurrence or distant metastasis was observed during 6 years of follow-up. The integrity of the mandible was preserved and the development of the mandible was not significantly affected. Iodine-125 brachytherapy is a potential alternative treatment for central mucoepidermoid carcinoma of the jaw, especially in teenagers, and may preserve the continuity and function of the jaw.

Presentation and outcomes of patients with clinically T1-2, N0 parotid mucoepidermoid carcinoma: The roles of elective neck dissection and adjuvant radiotherapy.

OBJECTIVES: Examine the role of elective neck dissection (END) and adjuvant radiotherapy (RT) in early-stage clinically N0 parotid mucoepidermoid carcinoma (MEC). METHODS: The study is a retrospective analysis of the National Cancer Database, 2004-2016. The study population included adult patients with MEC who underwent parotidectomy. RESULTS: A total of 1233 patients were included. Histopathology demonstrated well, moderately, and poorly differentiated MEC 47.12%, 39.98%, and 12.90% of the time, respectively. END was performed in 78.67% of patients, resulting in nodal upstaging in 4.43% and identification of extracapsular extension (ECE) in 0.72%. RT was utilized in 67.33% of patients with advanced pathological features. Neither END nor RT improved overall survival separately (p < 0.05) or combined (adjusted HR: 1.19, 95%CI: 0.52, 2.70, p = 0.68). CONCLUSION: This study provides an epidemiological perspective regarding patients with clinically T1-2, N0 MEC. There was no observed survival advantage with END and RT.

Prolonged response to checkpoint inhibitor therapy in two metastatic mucoepidermoid salivary gland carcinoma cases: a research report.

Salivary gland tumors (SGTs) are heterogeneous tumors that range from benign masses to aggressive high-grade carcinomas with distant metastatic potential and limited response to chemotherapy. Mucoepidermoid carcinoma (MEC) accounts for 10% of SGTs and has a poor prognosis. In this research report, we describe two cases of metastatic high-grade MECs with prolonged response to immune checkpoint inhibitor pembrolizumab. Case 1 presented with a left neck mass, and biopsy of the parotid mass revealed MEC. The patient underwent surgical resection and adjuvant chemoradiation therapy for stage IVB disease. Post-treatment, she was found to have brain and spinal metastases and was placed on pembrolizumab. Case 2 presented with a left neck mass, and biopsy of the right parotid gland revealed MEC. Further staging demonstrated metastatic disease in the lungs, and he was placed on pembrolizumab. Both cases of MEC demonstrated prolonged extracranial responses to pembrolizumab. Although both cases reported little to no PD-L1 expression, these results demonstrate immunotherapy efficacy in advanced/metastatic MEC.

Cystatin C - a fast and reliable biomarker for glomerular filtration rate in head and neck cancer patients.

PURPOSE: Determination of renal function is a prerequisite for planning therapy in cancer patients. Limitations of creatinine as marker for the glomerular filtration rate (GFR) led to the proposal of cystatin C as a more accurate biomarker especially in mild renal insufficiency or in patients with low muscle mass. We compared the accuracy of cystatin C- and creatinine-based equations to estimate GFR in head and neck cancer (HNC) patients receiving platinum-based radiochemotherapy. PATIENTS AND METHODS: The study population consisted of 52 HNC patients (GFR range, 37-105 mL/min/1.73 m(2) complemented by 17 patients with known renal insufficiency (GFR range, 10-60 mL/min/1.73 m(2)). Intraclass correlation coefficients were calculated between the reference method (51)Cr-EDTA clearance and estimated GFR by creatinine clearance and equations based on creatinine (Cockroft-Gault, modification of diet in renal disease (MDRD), Wright) or cystatin C (Larsson, Dade-Behring, Hoek). In addition, sensitivity and specificity to discriminate GFR > 60 mL/min/1.73 m(2) were evaluated by receiver operating characteristic curve (ROC). RESULTS: The highest correlation coefficients were found for the cystatin C-based estimates in comparison with creatinine-based estimates or creatinine clearance, even though Bland-Altman plots revealed GFR overestimation for all equations tested. The cystatin C-based Hoek formula exhibited the highest overall precision and accuracy. GFR of < 60 mL/min/1.73 m(2) was assumed as a cut-off for chemotherapy. ROC analyses revealed the highest AUC to predict a GFR > 60 mL/min/1.73 m(2) for the creatinine-based Wright formula, closely followed by the MDRD formula and cystatin C-based equations of Larsson, Dade-Behring, and Hoek. CONCLUSION: Cystatin C-based GFR estimates showed the overall strongest correlation to the reference method. Thus, we recommend cystatin C for GFR estimation in HNC patients as an alternative method to the estimated creatinine clearance in clinical practice.

Three-dimensional conformal postoperative radiotherapy in patients with parotid tumors: 10 years' experience at the European Institute of Oncology.

AIMS AND BACKGROUND: Salivary gland malignancies are rare. The aim of our study was to investigate radiotherapy-related toxicity and clinical outcome in patients treated at our division with postoperative radiotherapy (pRT) for parotid tumors. METHODS AND STUDY DESIGN: Forty-three consecutive patients (32 with primary parotid tumors, 9 with parotid metastases and 2 with recurrent benign diseases) were retrospectively analyzed. RESULTS: The median follow-up was 28 months. Twenty and 5 patients had a follow-up longer than 2 and 5 years, respectively. Thirty-seven patients were alive and most of them (78%) were free from disease. The local and distant control rates were higher in patients with primary parotid tumors (94% and 87.5%) than in patients with parotid metastases (87.5% and 75%). Grade 3 radiotherapy-related acute toxicity of skin and mucosa was recorded in 20.9% and 28% of patients, respectively. Two patients (4.7%) had grade 4 skin toxicity. Late toxicity data were available for 33 (77%) patients. None of the patients developed severe (grade 3 and 4) late toxicity of soft tissues, skin or temporomandibular joints. CONCLUSIONS: Postoperative radiotherapy is a feasible treatment that was found to be effective mainly in patients with primary parotid tumors. Toxicity was acceptable but could probably be further reduced using more advanced radiotherapy techniques. Longer follow-up is required to achieve definitive results.

Diagnosis and management of mucoepidermoid carcinoma of the lacrimal duct.

Primary tumors of the lacrimal sac are rare, and mucoepidermoid carcinomas of the lacrimal sac have only been reported 13 times in the literature. We reported an intermediate-grade mucoepidermoid carcinoma that was managed with wide local excision, medial maxillectomy, and external beam radiotherapy, and the patient has remained disease-free for 7 years. Orbital exenteration had generally been recommended for these tumors, but newer, more conservative resections along with radiation therapy may be equally effective.