Current evidence on diagnosis and treatment of parotid gland lymphomas: a systematic review.

BACKGROUND AND PURPOSE: Parotid gland lymphoma (PGL) is a rare and challenging diagnosis. Different lymphomas can develop in the parotid gland, with the most common being the mucosa-associated lymphoid tissue (MALT) lymphoma, which originates directly from the glandular parenchyma. Other histologic subtypes arise from both intraglandular and extraglandular parotid lymph nodes. A consensus on diagnosis and treatment of PGL is still lacking, and published data is scarce and heterogeneous. METHODS: We performed a systematic review of the literature, including studies published after 2001, when the WHO classification of lymphoid tumours was introduced. RESULTS: Twenty retrospective studies were included in the analyses, eight of which focused exclusively on MALT lymphomas. Final analysis included 612 cases of PGL, with a 1.68:1 F/M ratio. MALT lymphoma was the most common histology, followed by follicular and diffuse large B-cell lymphoma. Most cases were low stages (IE/IIE acc. Ann Arbour, 76.5%) and only 10% of patients presented with symptoms, most commonly pain (4.8%) and B symptoms (2.2%). A high prevalence of associated autoimmune diseases was found, particularly Sjögren's syndrome, that affected up to 70% of patients with MALT lymphoma. In most cases diagnosis was achieved through parotidectomy (57.5%), or open biopsy (31.2%). Treatment strategies were either surgical, non-surgical or a combination of modalities. Surgery as a single-modality treatment was reported in about 20% of patients, supposing it might be a valuable option for selected patients. CONCLUSIONS: Our review showed that the diagnosis and treatment of PGLs is far from being standardized and needs further, more homogeneous reports to reach consensus.

Acinic cell carcinoma of the parotid gland: Timeo Danaos et dona ferentes? A multicenter retrospective analysis focusing on survival outcome.

OBJECTIVES: To analyze the demographic data, surgical and adjuvant treatment data and the survival outcomes in adult patients affected by acinic cell carcinoma of the parotid gland (AciCC). METHODS: A retrospective multicenter analysis of patients treated for AciCC of the parotid gland from 2000 to 2021 was performed. Exclusion criteria were pediatric (0-18 years) patients, the absence of follow-up and patients with secondary metastatic disease to the parotid gland. Multivariable logistic regression was used to determine factors associated with survival. RESULTS: The study included 81 adult patients with AciCC of the parotid gland. The median age was 46.3 years (SD 15.81, range 19-84 years), with a gender female prevalence (F = 48, M = 33). The mean follow-up was 77.7 months (min 4-max 361, SD 72.46). The 5 years overall survival (OS) was 97.5%. The 5 years disease-free survival (DFS) was 60%. No statistical differences have been found in prognosis for age (< 65 or ≥ 65 years), sex, surgery type (superficial vs profound parotid surgery), radicality (R0 vs R1 + Rclose), neck dissection, early pathologic T and N stages and adjuvant therapy (p > 0.05). CONCLUSION: This study did not find prognostic factor for poorest outcome. In contrast with the existing literature, our results showed how also high-grade tumours cannot be considered predictive of recurrence or aggressive behaviour.

Transcatheter Arterial Sclerosing Embolization for the Treatment of Giant Propranolol-Resistant Infantile Hemangiomas in the Parotid Region.

PURPOSE: To report the effectiveness and safety of transcatheter arterial sclerosing embolization (TASE) for the treatment of parotid infantile hemangiomas that did not respond appreciably to propranolol. MATERIALS AND METHODS: A total of 21 infants (12 male and 9 female) with large propranolol-resistant infantile hemangiomas in the parotid region were enrolled in this study. During TASE, the feeding arteries of the lesions were embolized using pingyangmycin-lipiodol emulsion and polyvinyl alcohol particles (300-500 µm) to reduce the blood flow rate. All children were followed up as outpatients at 2 weeks and monthly thereafter. The curative effect was evaluated at the 1- and 3-month follow-up visits. RESULTS: Nine lesions were located on the right side of the parotid gland, whereas 12 were located on the left side. The feeding arteries in all patients originated from branches of the external carotid artery. TASE was technically successful in all patients. The mean (± SD) maximal diameter of the hemangiomas significantly decreased from 6.50 cm ± 2.28 before treatment to 3.56 cm ± 1.84 at 1 month after TASE (P <. 05). Three months after TASE, the mean maximal diameter further significantly decreased to 1.94 cm ± 1.58 (P <. 05). During the follow-up period, 16 cases were rated as excellent and 5 as good; no recurrence or serious complications were noted. Minor side effects, such as slight pain, mild fever, and tissue swelling, were observed. CONCLUSIONS: TASE significantly decreased the size of the parotid hemangiomas with minor side effects during a short follow-up period.

Efficacy of surgery combined with postoperative 125 I interstitial brachytherapy for treatment of acinic cell carcinoma of the parotid gland in children and adolescents.

BACKGROUND: Acinic cell carcinoma (AciCC) is rare in children; therefore, reaching a consensus on its management is challenging and radiotherapy is limited by concerns about long-term toxicity. The purpose of this study is to analyze the effectiveness and safety of surgery plus postoperative 125 I interstitial brachytherapy (IBT) for children and adolescents with AciCC of the parotid gland (PG) treated at a single institution. PROCEDURE: Sixteen patients ≤ 18 years old with AciCC of the PG treated with surgery plus 125 I IBT from 2007 to 2018 were included. Surgery was the primary treatment; ten patients underwent total gross excision and six subtotal gross excision. The matched peripheral dose was 60-120 Gy. Overall survival, disease-free survival (DFS), local control rate, distant metastasis, and radiation-associated toxicities were analyzed, and factors influencing outcomes were evaluated. RESULTS: During follow-up (1.8-12.6 years; mean, 6.3 years), lymph node metastasis was observed in one case, 2.6 years after 125 I IBT treatment. The five-year overall and DFS rates were 100% and 91.7%, respectively. On univariate analysis, tumor size ≥ 3 cm (100% vs 50%; P = 0.025) and extraglandular extension (100% vs 50%; P = 0.025) were significant prognostic indicators for DFS. No severe radiation-associated complications occurred. CONCLUSIONS: Children and adolescents with AciCC of the PG with high-risk features can be managed using surgery plus postoperative 125 I IBT with excellent local control. Radiation-related complications were minor. Patients with facial nerve involvement can have their facial nerves preserved. Residual tumors can be safely managed using adjuvant 125 I IBT.

Resected specimen size: A reliable predictor of severe Frey syndrome after parotidectomy.

BACKGROUND: Frey syndrome is a common complication after parotidectomy. This study aimed to investigate the potential predictors for developing severe Frey syndrome after parotidectomy and to identify patients who may benefit from additional preventive maneuvers. METHODS: A total of 485 patients received parotidectomy because of parotid tumors at the Otolaryngology Department of the National Cheng Kung University Hospital, from July 2009 to November 2015. Only 115 of 485 patients were included in this study and to fill in a questionnaire to determine the occurrence and severity of Frey syndrome. RESULTS: A total of 115 parotidectomies were identified. 84 (73%, 84/115) patients were aware of the discomfort and were thus considered symptomatic. 39 (34%, 39/115) patients considered the symptoms apparently affected their quality of life. MSI tests showed that 56 (49%, 56/115) patients had a positive MSI test. By combining the results from symptom questionnaire and MSI test, 23 patients (20%, 23/115) had a severe form of Frey syndrome. Among all clinicopathological variables, the resected specimen size was the only significant predictor of the severe Frey syndrome group (P = 0.04). Disease pathology, tumor size, and adjuvant radiotherapy did not correlate with the severe Frey syndrome. Using receiver operating curve analysis, the best cutoff value of the resected specimen size (in largest dimension) for predicting severe Frey syndrome was 40 mm(sensitivity: 71.7%, specificity: 42.0%; area under the curve = 0.6483). The odds ratio of severe Frey syndrome with every 10 mm increase in the largest diameter of resected specimen was 1.30 (95% confidence interval, 1.01-1.68; P = 0.04). CONCLUSIONS: Resected specimen size is the only significant predictor of developing severe Frey syndrome after parotidectomy. Preventive interventions may have to be considered in high-risk patients whose resected specimen size (in largest dimension) is greater than 40 mm.

Retrograde parotidectomy under local anesthesia for benign, malignant, and inflammatory lesions.

OBJECTIVE: To report the patient selection, surgical technique, and outcomes of parotidectomy using local anesthesia under monitored anesthesia care (MAC). METHODS: A retrospective chart review was performed for patients undergoing parotidectomy under local anesthesia at an academic head and neck surgery center. RESULTS: Six patients deemed high risk for general anesthesia (GA) due to medical comorbidities or with a strong preference to avoid GA underwent parotidectomy using local anesthesia and MAC. Parotidectomy was performed for several indications, including benign tumors, malignant tumors, and chronic sialadenitis. Mean age of patients was 78.0 ±â€¯7.9 years, and all had an American Society of Anesthesia score ≥ 2 and Charlson comorbidity index ≥4. Mean operative time was 102.8 ±â€¯38.3 min, comparable to that of parotidectomy under general anesthesia. No major complications occurred. Minor complications included three cases of temporary postoperative facial nerve weakness limited to 1-2 lower division branches. At most recent follow up (10 to 48 months), all patients were medically stable and disease free. CONCLUSION: In carefully selected patients, parotidectomy under local anesthesia is a viable treatment alternative that can be offered to patients. Successful outcomes require preoperative counseling, meticulous technique, and close collaboration with anesthesia colleagues.

Chronic atypical first bite syndrome and primary squamous cell carcinoma of the parotid.

BACKGROUND: First bite syndrome is a well-recognized complication of parapharyngeal space surgery. There are no reported cases of protracted first bite syndrome and subsequent diagnosis of a primary squamous cell carcinoma (SCC) of the parotid. METHODS: We present the case of a 73-year-old man with no surgical history and 9 years of first bite syndrome who was ultimately diagnosed with a primary SCC of the parotid. Diagnostic workup, including MRI and biopsy, along with oncologic treatment, were performed. RESULTS: Surgical treatment confirmed malignancy and also resulted in complete resolution of the first bite syndrome. CONCLUSION: First bite syndrome without prior surgery may warrant further diagnostic workup with imaging to evaluate for salivary gland pathology. When no radiographic mass lesion is detected but the patient displays protracted symptoms unresponsive to conservative therapy, one should maintain an index of suspicion for malignancy, especially in the presence of symptom escalation.

Three-Dimensional Printed Plate-Guided 125I Brachytherapy for Malignant Parotid Tumors.

PURPOSE: The treatment of malignant parotid tumors with 125I brachytherapy is rarely reported. This study evaluated the efficacy and dose and response of 125I brachytherapy in patients with malignant tumors. MATERIALS AND METHODS: From July 2014 through August 2017, 39 patients with malignant parotid tumors were treated with 125I brachytherapy. Thirty-five patients were treated with conservative surgical resection before brachytherapy. Four patients were treated with brachytherapy alone. Clinical outcomes and side effects were evaluated. Clinical factors were investigated to determine correlations with local control (LC) and side effects. RESULTS: Mean follow-up was 25 months (range, 7 to 47 months). The LC rate was 87.2% and the overall survival rate was 97.4%. High tumor grade and large tumor showed a propensity for local recurrence. Acute skin toxicity occurred in 87.2% of patients and grade 3 and 4 radioepidermitis was found in 20.5% of patients. In total, 89.7% of patients with facial nerve dysfunction recovered within 12 months. CONCLUSIONS: 125I brachytherapy was a feasible treatment option for patients with malignant parotid tumors. Although side effects were minimal, strict follow-up was necessary for patients treated with a high dose.

Mandibular growth in survivors of pediatric parotid gland carcinoma treated with interstitial brachytherapy.

BACKGROUND: The aim of the study was to present long-term results of mandibular growth in pediatric parotid gland carcinoma survivors treated with interstitial brachytherapy. PROCEDURE: Twenty-five survivors of pediatric parotid gland carcinoma treated with iodine-125 seed interstitial brachytherapy were included for quantitative analysis, including three dimensional (3D) cephalometry and measurement of mandibular volume. RESULTS: 3D cephalometry showed that the median fore-and-aft increments of the lengths of the condyle, the ramus, and the body of the mandible were 1.23, 0.19, and 1.66 mm for the affected side, respectively, and were 1.37, 1.95, and 3.42 mm for the unaffected side, respectively. The difference in increments of the ramus was statistically significant between the affected side and the unaffected side (P = 0.003; P < 0.05). Moreover, mandibular volume measurements showed that the median fore-and-aft increments of the volumes of the condyle, the ramus, and the body of the mandible were 290.62, 220.14, and 1706.40 mm3 for the affected side, respectively, and were 269.15, 370.40, and 1469.86 mm3 for the unaffected side, respectively. The difference in increments was statistically significant between the affected side and the unaffected side for the ramus (P = 0.005; P < 0.05) and the body (P = 0.043; P < .05). CONCLUSION: Mandibular growth was affected by interstitial brachytherapy, especially for the ramus, in pediatric parotid gland carcinoma survivors treated with interstitial brachytherapy. Nevertheless, the impact was mild in these survivors.

Partial parotidectomy under local anesthesia for benign parotid tumors - An experience of 50 cases.

PURPOSE: Benign parotid tumors are adequately treated with partial parotidectomy, which is often performed under general anesthesia (GA). We have reported our preliminary results on the feasibility to perform parotidectomy under local anesthesia (LA). We hereby present our accumulated experience of partial parotidectomy under LA to further consolidate its feasibility, efficacy and safety in a larger series. MATERIALS AND METHODS: Case series review was carried out using our own center patients' database. 50 patients with parotid tumors were treated with partial parotidectomy under LA, using a retrograde nerve dissection approach from January 2006 to October 2016. The inclusion criteria encompassed mobile parotid nodules primarily operated after non-suspicious fine-needle aspiration cytology. Their demographics, complications and outcomes were evaluated. RESULTS: No procedure required conversion to GA. There were 48 benign tumors and 2 lymphomas based on the histopathologic examination. The commonest pathologies were pleomorphic adenoma (40%), Warthin's tumor (38%) and cyst (8%). The mean tumor size was 2.68 ±â€¯1.5 cm and the mean operative time was 91.5 ±â€¯34.7 min. Forty-two operations were done as day cases. Ten (20%) patients suffered from transient ear lobe numbness and two (4%) patients had sialocele. Transient facial palsy occurred in 2(4%) patients while another patient (2%) had persistent House-Brackmann grade II facial palsy. No tumor recurrence was noted during follow-up period. CONCLUSIONS: Partial parotidectomy adopting a retrograde nerve dissection under LA is feasible and minimally invasive in treating benign parotid tumors. It can avoid the adverse effects of general anesthesia and promote day surgery or minimize hospital stay.

Complete remission and long-term survival of a patient with melanoma metastases treated with high-dose fever-inducing Viscum album extract: A case report.

INTRODUCTION: Metastatic malignant cutaneous melanoma (MCM)-a highly immunogenic cancer-typically has a poor prognosis. Viscum album extracts (VAEs) have strong immune-stimulating, apoptogenic, and cytotoxic effects. CASE PRESENTATION: A 66-year-old MCM patient with newly diagnosed lymph node metastases opted for sole VAE treatment. VAEs were initially applied subcutaneously, and then later in exceptionally high, fever-inducing doses, both intravenously and intralesionally. The metastases shrunk over the following months, and after 2 years, all lesions had completely remitted (regional and hilar lymph nodes). The patient has been tumor free for 3.5 years at the time of publication (and for 5 years since initiation of intensified VAE treatment). Besides fever and flu-like symptoms, no side effects occurred. DISCUSSION: We presume that VAE triggered an increased release of tumor-associated antigens, enhanced immunologic recognition, and increased immune response against the tumor tissue and induced tumor remission.

Parotidectomy under sedation and locoregional anesthesia with monitoring of brain activity.

BACKGROUND: Parotidectomy is usually performed while the patient is under general anesthesia, however, sedation with locoregional anesthesia could be an alternative. METHODS: Fifteen adult patients with parotid tumors of the superficial lobe were included in this study. Anesthetic procedure consisted of sedation associated with cervical plexus and auriculotemporal nerve block. Sedation was managed based on the bispectral index. RESULTS: Superficial parotidectomies were performed in 13 patients, and combined partial resections were performed in 2 patients. The mean operative time was 118.2 ± 16.4 minutes. Conversion to general anesthesia was necessary in only 1 patient. Ten surgeries were performed on an outpatient basis. Definitive facial paralysis occurred in 1 patient. All patients reported total satisfaction with the procedure. CONCLUSION: In selected cases, parotidectomy under sedation plus locoregional anesthesia is feasible and safe. The careful selection of patients and the close collaboration with an anesthesiologist is the key to a successful procedure. © 2016 Wiley Periodicals, Inc. Head Neck 39: 744-747, 2017.

Salivary Duct Carcinoma of the Parotid: Outcomes with a Contemporary Multidisciplinary Treatment Approach.

OBJECTIVE: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy for which an optimal treatment algorithm is lacking. We endeavored to assess the current treatment outcomes for SDC with a multimodality treatment approach combining surgery with adjuvant radiotherapy ± concurrent chemotherapy. STUDY DESIGN: Case series with chart review. SETTING: A National Cancer Institute-designated comprehensive cancer center. SUBJECTS AND METHODS: The clinical record of 17 patients with salivary duct carcinoma were analyzed to assess locoregional control, recurrence-free survival, and overall survival. RESULTS: All SDC cases (n = 17) were managed with surgical resection, followed by adjuvant radiotherapy (47.1%) or concurrent chemotherapy and radiotherapy (52.9%). Median patient follow up was 37 months. An aggressive disease course was generally observed, with 3-year recurrence-free survival and overall survival of 34.4% and 35.5%, respectively. The majority of recurrences were distant. Intensification with adjuvant concurrent chemotherapy was not associated with improved outcomes on univariate survival analysis. CONCLUSION: For salivary duct carcinoma, a multimodality treatment approach is associated with acceptable locoregional control rates but poor distant control and overall survival. Novel systemic therapies may be needed to optimize clinical outcomes.

(125)I interstitial brachytherapy for the treatment of myoepithelial carcinoma of the oral and maxillofacial region.

PURPOSE: This study evaluated the treatment of myoepithelial carcinoma (MC) of the oral and maxillofacial region with radioactive iodine ((125)I) seed implantation. METHODS AND MATERIALS: Twenty-seven patients with MC in the oral and maxillofacial region were treated with (125)I seed implantation between March 2006 and October 2012. Thirteen of the 27 patients (8/8 patients with primary disease and 5/19 patients with recurrent disease) were treated on an adjuvant setting after resections, and the other 14 patients were treated by brachytherapy after a recurrence precluding a surgical resection for salvage. The sites of the MC were the parotid for 18 patients, oral cavity for 2 patients, and base of skull for 7 patients. Recurrence-free survival (RFS), overall survival (OS) rates, and side effects were retrospectively reviewed. RESULTS: Patients were followed for 6-105 months (median 37 months). The 3- and 5-year RFS rates were 51.9% and 46.1%, respectively. The 3- and 5-year OS rates were 68.6% and 51.5%, respectively. The OS and RFS were significantly better among the 8 patients treated upfront in comparison with the 19 patients treated for salvage at relapse. The OS was worst for the 7 patients with base of skull region disease. No severe complications were observed during followup. CONCLUSIONS: This study showed (125)I brachytherapy is a feasible and effective modality for the treatment of MC. These findings should be interpreted cautiously due to the small number of patients and the relatively short followup.

Potential use of acupuncture in the treatment of first bite syndrome.

OBJECTIVES: First bite syndrome (FBS) is an early postoperative pain syndrome characterized by the sudden onset of pain in the parotid region at the first bite of each meal. The etiology is not certain, hence a standardized therapy does not exist. METHODS: A 50-year old woman referred to us complaining of a swelling in the right parotid region. Fine-needle aspiration biopsy (FNAB) was diagnostic for pleomorphus adenoma of the deep lobe of the parotid gland. A 50-year old man presented with a mass in the right side of the neck, FNAB was diagnostic for parapharyngeal space neurinoma. The first patient was submitted to total parotidectomy with facial nerve preservation, the second to extracapsular dissection of the tumor. A week after surgery both patients developed FBS. A qualitative/quantitative description of pain was obtained by means of a self-coded questionnaire. The score ranges from 8 to 44, corresponding to the lowest and the highest discomfort possible, respectively. Acupuncture was used to treat these 2 patients. The treatment protocol comprised 6 sessions, one per week, lasting 30 minutes each. RESULTS: Our questionnaire was administered before and after treatment and the score dropped from 33 to 25 in the female, from 30 to 15 in the male patient. CONCLUSION: FBS is a complication of upper cervical surgery with a high morbidity rate. We describe the first two cases of FBS that were successfully treated with acupuncture in our ENT department. We believe that this procedure may represent a valid therapeutic alternative in the future.

Disección extracapsular para la remoción quirúrgica de adenoma pleomorfo de parótida / Extracapsular dissection for parotid pleomorphic adenoma removal

Existe una gran controversia acerca de la extensión del margen requerido para la remoción del adenoma pleomorfo en la glándula parótida. Si bien el tratamiento del adenoma pleomorfo más aceptado mundialmente es la parotidectomía superficial con disección del nervio facial, en la literatura se describe un amplio espectro de tratamientos, que van desde parotidectomía total hasta la disección extracapsular. La disección extracapsular consiste en la disección del tumor por fuera de la cápsula, sin la necesidad de un margen amplio ni de la identificación previa del nervio facial. El objetivo de este trabajo es presentar las ventajas, desventajas, indicaciones y limitaciones de la disección extracapsular para la remoción del adenoma pleomorfo de la glándula parótida.

Osteoradionecrosis of the temporal bone: a case series.

OBJECTIVE: To study osteoradionecrosis (ORN) of the temporal bone. STUDY DESIGN: Retrospective case review. SETTING: Academic medical center. PATIENTS: Patients were included who had previously undergone radiation to the head and neck and then developed exposed necrotic bone within the ear canal that persisted at least 3 months. INTERVENTIONS: Patients were treated with a variety of modalities, including conservative therapy with antibiotic ear drops and in-office debridements, hyperbaric oxygen therapy, and surgery. MAIN OUTCOME MEASURES: To describe the presentation and management of patients with temporal bone osteoradionecrosis. RESULTS: Thirty-three patients with temporal bone osteoradionecrosis were included. The most common site of primary tumor was the parotid gland (n = 11), followed by the nasopharynx (n = 7). The time to development of ORN varied between 1 and 22 years, with mean of 7.9 years. The mean radiation dose was 62.6 Gy to the primary tumor, 53.1 Gy to the affected temporal bone, and 65.2 Gy to the affected tympanic bone. The most common symptoms of ORN were otorrhea (n = 15), hearing loss (n = 13), and otalgia (n = 12). Fifteen patients had bacterial superinfection, most commonly Staphylococcus aureus (n = 9). Conservative therapy was successful at managing symptoms but not in eradicating exposed bone in most patients. Surgery was used for recalcitrant pain, infection, cholesteatoma, cranial neuropathies, and intracranial complications. CONCLUSION: Osteoradionecrosis is a rare complication of radiation to the temporal bone. Management should be aimed at relief of symptoms, eradication of superinfection, and treatment of other commonly present radiation effects like cholesteatoma and hearing loss.

Postoperative [¹²5I] seed brachytherapy in the treatment of acinic cell carcinoma of the parotid gland: with associated risk factors.

BACKGROUND: This retrospective study was undertaken to analyze data from patients receiving iodine-125 ([(125)I]) seed brachytherapy postoperatively for the treatment of acinic cell carcinoma (ACC) of the parotid gland along with the following risk factors: residual tumor, recurrent tumor, facial nerve invasion, positive resection margins, advanced tumor stage, or tumor spillage. PATIENTS AND METHODS: Twenty-nine patients with ACC (17 females, 12 males; age range, 13-73 years; median age, 37.3 years) were included. Median follow-up was 58.2 months (range, 14-122 months). Patients received [(125)I] seed brachytherapy (median actuarial D90, 177 Gy) 3-41 days (median, 14 days) following surgery. Radioactivity was 18.5-33.3 MBq per seed, and the prescription dose was 80-120 Gy. RESULTS: The 3-, 5-, and 10-year rates of local control were 93.1, 88.7, and 88.7 %, respectively; overall survival was 96.6, 92, and 92 %; disease-free survival was 93.1, 88.4, and 88.4 %; and freedom from distant metastasis was 96.6, 91.2, and 91.2 %. Lymph node metastases were absent in all patients, although two patients died with distant metastases. Facial nerve recovery was quick, and no severe radiotherapy-related complications were noted. Recurrence history, local recurrence, and distant metastasis significantly affected overall survival. CONCLUSION: Postoperative [(125)I] seed brachytherapy is effective in treating ACC and has minor complications. Patients with a history of recurrence showed poor prognosis and were more likely to experience disease recurrence and develop metastases.