Parotid Gland Tumors Research Articles

Role of Cross-sectional Imaging in Evaluation of Parotid Gland Tumours: A Pictorial Review

Radiological evaluation of the parotid gland neoplasms is a major challenge for radiologists, due to the wide variety of imaging features and differential diagnosis. Though Ultrasonography (USG) combined with guided Fine Needle Aspiration Cytology (FNAC) is the primary diagnostic modality, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) play an important role in the evaluation of patients presenting with suspected neoplastic lesions of the parotid gland. Cross-sectional imaging data of seven patients were selected and reviewed in detail. CT and MRI imaging had been done on patients referred to Radiology Department for clinically suspected parotid tumours. All of them underwent surgical excision and histopathological examination postimaging. Benign tumours usually arise from superficial lobe and exhibit strong signal intensity on T2 weighted images with well-defined margins. Lobulated margins with T2 dark rim are characteristic of pleomorphic adenoma. Hyperdense lesion with cystic changes with occasional bilateralism favour Warthin’s tumour. Most of the malignant parotid tumours involve deep lobe and appear as low signal lesion on T2 weighted imaging with ill-defined margins. Locally aggressive features like subcutaneous/deep infiltration strongly suggests malignancy. Cross-sectional imaging feature of carcinoma ex pleomorphic adenoma is variable from focally aggressive to totally aggressive tumourigenesis. Few malignant tumours like high-grade Mucoepidermoid Carcinoma (MEC) and Adenoid Cystic Carcinoma (AdCC) can show tendency towards perineural spread. Although histopathological examination is required for definitive diagnosis, few pathology-specific imaging findings on cross-sectional imaging can help in localising and characterising the parotid lesions and categorising innocuous benign from sinister malignant lesions and thus narrow down the differential diagnosis.

Minimally Invasive Approach in the Treatment of Benign Parotid Gland Tumors

Minimally Invasive Approach in the Treatment of Benign Parotid Gland Tumors

Evaluating Online Patient Health Information on Parotidectomy - Is it Readable and of Good Quality?

Parotidectomy is considered the definitive management for benign and malignant parotid gland tumours. Complications and long-term outcomes of parotidectomy can pose a massive impact on patients’ quality of life. Although there are potential benefits of obtaining health information from the internet, it has its limitations on quality and accuracy of information. This research evaluates the readability and quality of online patient health information(PHI) on parotidectomy.

Clinico-pathological profile of parotid gland tumors at a tertiary care center in North India.

The objective of this study was to know the various types of parotid tumors and their clinical presentations, surgical management, and post-operative outcome. Data of 102 patients assessed from hospital records who underwent parotid surgery between the years 2013 and 2018 were obtained. Parameters included age, sex, socio-demographic profile, presenting complaints, examination findings, and cytopathology. Surgical techniques, post-operative complications such as a facial scar, retro-mandibular and pre-auricular depression, facial palsy, Frey's syndrome, and numbness over the ear lobule were analyzed. Out of a total of 102 patients, 54.0% of patients were male, and 45.1% were female. The mean age of patients was 33.30 ± 13.87 years ranging from 7 to 65 years. The most common clinical presentation was swelling in the parotid region (95.1%), and associated symptoms with swelling were pain (17.5%), facial palsy (4.9%), discharging sinus (4.9%), and ulcerative lesions (1%) at the time of presentation. Pleomorphic adenoma was the most common benign neoplasm (76.5%), followed by Warthin's tumors (2.9%). Mucoepidermoid carcinoma was the most common malignant neoplasm (3.9%). After parotid surgery, 35% of patients had a sensory impairment or hypoesthesia of the ear lobule, and 23.28% had temporary facial nerve weakness. 5.0% of patients had permanent facial weakness, and 2.06% of patients had weakness of the marginal mandibular nerve. Pleomorphic adenoma and mucoepidermoid carcinoma are the most common benign and malignant tumors, respectively, and parotidectomy is the treatment of choice, depending on the tumor location. Successful treatment depends on early diagnosis and histopathological and radiological investigations. Sensory impairment and temporary facial nerve paralysis are the most common post-operative complications, which are minimized by proper knowledge of anatomy and meticulous dissection of the facial nerve during parotid surgery.

Parotid Gland Oncocytoma-A Case Report

Tumors of parotid glands are majority benign and commonest of them is Pleomorphic adenoma. Patients commonly presents with a painless swelling in face. Parotid Oncocytoma is a rare parotid tumor with incidence of 0.1-1.5% (rarest of salivary tumor type) of all parotid tumors, and it occurs in 6-8 decade of life. In this case report we will present a case of 75 years old male with painless swelling in parotid gland and diagnosis of Oncocytoma was made.

Deep learning-assisted diagnosis of parotid gland tumors by using contrast-enhanced CT imaging.

Imaging interpretation of the benignancy or malignancy of parotid gland tumors (PGTs) is a critical consideration prior to surgery in view of therapeutic and prognostic values of such discrimination. This study investigates the application of a deep learning-based method for preoperative stratification of PGTs. Using the 3D DenseNet-121 architecture and a dataset consisting of 117 volumetric arterial-phase contrast-enhanced CT scans, we developed a binary classifier for PGT distinction and tested it. We compared the discriminative performance of the model on the test set to that of 12 junior and 12 senior head and neck clinicians. Besides, potential clinical utility of the model was evaluated by measuring changes in unassisted and model-assisted performance of junior clinicians. The model finally reached the sensitivity, specificity, PPV, NPV, F1-score of 0.955 (95% CI 0.751-0.998), 0.667 (95% CI 0.241-0.940), 0.913 (95% CI 0.705-0.985), 0.800 (95% CI 0.299-0.989) and 0.933, respectively, comparable to that of practicing clinicians. Furthermore, there were statistically significant increases in junior clinicians' specificity, PPV, NPV and F1-score in differentiating benign from malignant PGTs when unassisted and model-assisted performance of junior clinicians were compared. Our results provide evidence that deep learning-based method may offer assistance for PGT's binary distinction.

Preliminary study of a novel radiation shield for jaw in dental radiography using the high-density polyethylene/bismuth oxide nanocomposite

Dental radiography has been linked in numerous studies to an elevated risk of brain cancer, meningioma cranial tumors, and parotid gland tumors. Unfortunately, not much attention has been given to this problem. This research aims to determine and quantify the radiation shielding properties of High-Density Polyethylene/Bismuth Oxide composite (HDPE-Bi2O3) including the linear attenuation coefficient (μ), mass attenuation coefficient (μ/ρ), half-value layer (HVL) and tenth-value layer (TVL) for photons at 59.5 keV. First, the MCNP code—which showed a reasonable degree of consistency with the XCOM data—was used to simulate the variables μ, μ/ρ, HVL, and TVL that were connected to different concentrations of the composite. Then, the nanocomposite containing of 60 wt% Bi2O3 was chosen and fabricated via the casting method. There were XRD, and FESEM tests performed. Two techniques using the CsI(Tl) scintillation detector and the Geiger counter were applied to measure the shielding quantities at 59.5 keV gamma-rays of the 241Am radioactive source. Finally, results of the measurements revealed a comparatively good agreement with the values from the MCNP and XCOM simulations, with a maximum 3% discrepancy. The artifact test at the presence of the composites shield using a dental radiographic system at 60 kV have not been influenced adversely. This composite at the optimal weight fraction and thickness has potential application to be used as a radiation shield for jaw in dental radiography.

Assessment of Parotid Gland Tumors by Means of Quantitative Multiparametric Ultrasound (mpUS)

The preoperative diagnostical differentiation of parotid gland tumor (PGT) is not always simple due to several different entities. B-mode-ultrasound (US) remains the imaging modality of choice, while histopathology serves as the gold standard for finalizing the diagnosis. We aimed to evaluate the use of multiparametric US (mpUS) in the assessment of PGT. We included 97 PGTs from 96 patients. A standardized mpUS protocol using B-mode-US, shear-wave elastography (SWE), and standardized contrast-enhanced ultrasound (CEUS) was performed prior to surgical intervention. SWE was assessed by real-time measurement conducting a minimum of five measurements, while quantitative CEUS parameters were assessed with a post-processing perfusion software. SWE allowed differentiation between benign PGT (Warthin's Tumor (WT) paired with lymph nodes (LN) and pleomorphic adenoma (PA)), and WT and LN were softer compared to PA. WT showed lower velocities than squamous cell carcinoma (SCC): the most common malignant PGT. CEUS parameters showed significant group differences between WT and PA, WT and malignant lesions, WT and SCC, WT paired with LN versus PA, and WT paired with LN versus SCC. MpUS seems to be beneficial in the assessment of PGT characterization, with benign PGT appearing to be softer in SWE than tumors with malignant tendencies. The quantitative CEUS parameter shows higher perfusion in WT than in PA, and malignant PGTs are less vascularized than WTs.

Ultrasound Diagnostics of Diseases of the Parotid Salivary Glands in the Practical Work of a Polyclinic Doctor: Pilot Results

Between January 2019 and May 2022 parotid salivary glands were examined in 130 patients who were directed for ultrasonographic evaluation to the Radiology Department of State Budget-Funded Healthcare Institution of the City of Moscow «City Polyclinic № 191 of Moscow Healthcare Department» or were self-motivated to screening in medical project «Zdorovaya Moskva». Of the 130 patients, 71 were directed to ultrasonographic evaluation with provisional diagnosis «Tumor of parotid salivary gland». The ultrasonographic features were compared with diagnostic patterns of parotid salivary glands in medical literature.

Management Strategies of Benign Parotid Tumors

Background: Parotid gland tumor is the most common salivary gland tumors. Benign tumors account for about 80% of parotid gland tumors. Surgical excision is the treatment of choice in most cases when treating benign parotid tumors. However, due to the special anatomical location of the parotid gland and the different pathology of the tumor, there are many complications after parotid gland tumor operation, which also seriously affects patients quality of life.

PCT: Pyramid convolutional transformer for parotid gland tumor segmentation in ultrasound images

Preoperative segmentation of parotid gland tumor regions using deep learning is of great significance for treatment decisions. However, there are still two major limitations: to the best of our knowledge, no networks are designed specifically for parotid gland tumor segmentation tasks; and neither convolutional neural network (CNN) nor Transformer can extract both global and local feature solely. To address these issues, we first propose a Pyramid Convolutional Transformer (PCT) architecture based on the shrinking pyramid framework and Fusion Attention Transformer CNN (FTC) block for parotid gland tumors segmentation. In this architecture, the shrinking pyramid framework can effectively capture parotid gland tumor image features with dense pixel by integrating multi-scale dependencies of images. And the FTC block is constructed to address complex and variable contour characteristics of parotid gland tumors, which combines Transformer with CNN for preferable extracting global and local features of images by dual branch structure. The experimental results suggest that proposed PCT achieved intersection-over-union (IoU) of 0.8434 and Dice similarity coefficient (Dice) of 0.9151 on parotid gland tumor segmentation (PGTSeg) dataset, and attained new state-of-the-art performance on multiple challenging benchmarks with IoU of 0.8521 on MoNuSeg and IoU of 0.9080 on ISIC 2018. Meanwhile, common backbones equipped with FTC block outperformed the baseline model. The code and models will be available at: https://github.com/Twoverz/PCT-Pyramid-Convolutional-Transformer.

Low intensity whole-body oxidative stress in patients with parotid gland tumors.

Recently, there has been a significant increase in the number of patients hospitalized and undergoing surgery due to parotid gland tumors. We have observed an increase in the total number of salivary gland tumors, and hence an increased number of malignant tumors. Etiological factors of salivary gland tumors are still unknown. Oxidative stress (OS) has been suggested to be an important indicator of carcinogenesis in some tumors. Therefore, the aim of our study was to assess the state of OS in patients with selected benign and malignant parotid gland tumors. After final postoperative histological diagnosis of the tumor, patients were divided into the following groups i.e. pleomorphic adenoma 35 patients, Warthins tumor (WT) - 17 patients, mucoepidermoid carcinoma - 9 patients and 45 controls. The final study group included 106 patients. We found an increase in plasma lipofuscin levels in patients with all investigated parotid gland tumors. Furthermore, the activity of Cu/Zn-SOD in Warthins tumor patients was statistically lower compared to the controls, pleomorphic adenoma or mucoepidermoid carcinoma.In conclusion, we sustain the hypothesis on the presence of a low intensity whole-body OS in patients with parotid gland tumors. Furthermore, LPS may be a useful marker of OS in patients with benign and malignant tumors. Moreover, pathological mechanisms connected with WT seem to be different compared to malignant neoplasms and other benign tumors. It seems that Cu/Zn-SOD, as an antioxidative enzyme, may play an important role in those mechanisms taking part in WT.

Contrast-Enhanced Ultrasound in the Differentiation between the Most Common Benign Parotid Gland Tumors: A Systematic Review and Meta-Analysis.

Recently, contrast-enhanced ultrasound (CEUS) has become a promising tool in distinguishing benign from malignant parotid gland tumors. However, its usefulness in differentiating various benign parotid tumors has not been determined so far. This study aimed to systematically review the literature to determine the utility of CEUS in the preoperative differentiation between pleomorphic adenomas (PAs) and Warthin's tumors (WTs) of the parotid gland. PubMed, Embase, and Cochrane were searched for English-language articles published until 21 July 2022. Fifteen studies were included. On CEUS examination, a significantly greater percentage of PAs displayed heterogeneous enhancement texture compared to WTs. Contrarily, the enhanced lesion size, the enhancement margin, and the presence of the enhancement rim did not differ significantly between the entities. Significantly longer normalized mean transit time (nMTT) and time to peak (TTP) were observed in PAs. Contrarily, the mean values of area under the curve (AUC) and time from peak to one half (TPH) were significantly higher for WTs. Due to the considerable overlap among the qualitative CEUS characteristics of PAs and WTs, the reproducible, investigator-independent quantitative CEUS measurements have a greater potential to distinguish PAs from WTs, which might influence the selection of an appropriate management strategy.

Solitary fibrous tumor of parotid gland: a case report and short review of literature.

This case report represents a solitary fibrous tumor, which is a very rare neoplasm in the parotid gland. 80-year-old Caucasian female patient with palpable, immobile, painless, slow growing, semi-rigid-elastic neoplasm in the left parotid gland, that was existing for four months. There were no signs of inflammation and facial paralysis. The tumor was initially interpreted as a salivary gland neoplasm of uncertain origin. Fine needle aspiration was performed 2 times; however, the precise diagnosis was challenging. The tumor was excised, regional lymphadenectomy was performed. Morphological and immunophenotypical findings were consistent with solitary fibrous tumor of parotid gland. Currently, the patient is under regular follow-up period at 9 months with no evidence of metastasis or recurrence. Although very rare, solitary fibrous tumor (SFT) should be suspected in cases of slow growing, solid, well-defined nodules of the parotid gland. The SFT of the parotid gland are usually benign tumors, however there is a low risk of recurrency and malignant behavior with metastatic potential. Complete resection of the tumor should be performed since it is crucial for management without any recurrence.

Radiomic Analysis of Multi-parametric MR Images (MRI) for Classification of Parotid Tumors.

Characterization of parotid tumors before surgery using multi-parametric magnetic resonance imaging (MRI) scans can support clinical decision making about the best-suited therapeutic strategy for each patient. This study aims to differentiate benign from malignant parotid tumors through radiomics analysis of multi-parametric MR images, incorporating T2-w images with ADC-map and parametric maps generated from Dynamic Contrast Enhanced MRI (DCE-MRI). MRI scans of 31 patients with histopathologically-confirmed parotid gland tumors (23 benign, 8 malignant) were included in this retrospective study. For DCE-MRI, semi-quantitative analysis, Tofts pharmacokinetic (PK) modeling, and five-parameter sigmoid modeling were performed and parametric maps were generated. For each patient, borders of the tumors were delineated on whole tumor slices of T2-w image, ADC-map, and the late-enhancement dynamic series of DCE-MRI, creating regions-of-interest (ROIs). Radiomic analysis was performed for the specified ROIs. Among the DCE-MRI-derived parametric maps, wash-in rate (WIR) and PK-derived Ktrans parameters surpassed the accuracy of other parameters based on support vector machine (SVM) classifier. Radiomics analysis of ADC-map outperformed the T2-w and DCE-MRI techniques using the simpler classifier, suggestive of its inherently high sensitivity and specificity. Radiomics analysis of the combination of T2-w image, ADC-map, and DCE-MRI parametric maps resulted in accuracy of 100% with both classifiers with fewer numbers of selected texture features than individual images. In conclusion, radiomics analysis is a reliable quantitative approach for discrimination of parotid tumors and can be employed as a computer-aided approach for pre-operative diagnosis and treatment planning of the patients.

Prospective Assessment of Risk Factors Influencing Facial Nerve Paresis in Patients after Surgery for Parotid Gland Tumors.

Background and objectives: Facial weakness is the most important complication of parotid gland tumor surgery. The aims of this study are as follows: (1) assessment of the prevalence of postparotidectomy facial nerve dysfunction; (2) clinical and electrophysiological assessment of the facial nerve function before parotidectomy and at 1 and 6 months postoperatively; (3) assessment of the association of postoperative facial palsy with selected risk factors; and (4) assessment of the correlation between the results of clinical and neurophysiological assessments of facial nerve function. Materials and Methods: This study comprised 50 patients (aged 24-75 years) who underwent parotidectomy at the Department of Otolaryngology and Laryngological Oncology in Zabrze, Poland between 2015 and 2017. The evaluation included neurological, clinical and electrophysiological assessments of the facial nerve prior to surgery and at 1 and 6 months postoperatively. Results: No facial palsy was found preoperatively or 6 months postoperatively. Facial nerve dysfunction was found in 74% of patients 1 month postoperatively. In most cases (54%), paresis was mild or moderate (House-Brackmann grades II and III). The results of electrophysiological tests before parotidectomy were either normal or showed some mild abnormalities. We found a statistically significant correlation between the clinical assessment of the facial nerve function (based on the House-Brackmann scale) one month postoperatively and the latency of the CMAP response from the orbicularis oculi and orbicularis oris muscles. In all three studies, a statistically significant correlation was found between the amplitude of the compound muscle action potential (CMAP) of the orbicularis oris muscle and the degree of facial nerve weakness. Conclusions: The factors that may influence the risk of postoperative facial nerve paralysis (prolonged surgical time and the size and location of the tumor other than in the superficial lobe only) may indirectly suggest that surgery-related difficulties and/or surgeon experience could be crucial to surgery safety.

An attention base U-net for parotid tumor autosegmentation.

A parotid neoplasm is an uncommon condition that only accounts for less than 3% of all head and neck cancers, and they make up less than 0.3% of all new cancers diagnosed annually. Due to their nonspecific imaging features and heterogeneous nature, accurate preoperative diagnosis remains a challenge. Automatic parotid tumor segmentation may help physicians evaluate these tumors. Two hundred eighty-five patients diagnosed with benign or malignant parotid tumors were enrolled in this study. Parotid and tumor tissues were segmented by 3 radiologists on T1-weighted (T1w), T2-weighted (T2w) and T1-weighted contrast-enhanced (T1wC) MR images. These images were randomly divided into two datasets, including a training dataset (90%) and an validation dataset (10%). A 10-fold cross-validation was performed to assess the performance. An attention base U-net for parotid tumor autosegmentation was created on the MRI T1w, T2 and T1wC images. The results were evaluated in a separate dataset, and the mean Dice similarity coefficient (DICE) for both parotids was 0.88. The mean DICE for left and right tumors was 0.85 and 0.86, respectively. These results indicate that the performance of this model corresponds with the radiologist's manual segmentation. In conclusion, an attention base U-net for parotid tumor autosegmentation may assist physicians to evaluate parotid gland tumors.

Comparative analysis of benign and malignant parotid gland tumors: A retrospective study of 992 patients

ObjectiveWe analyzed and compared the clinical characteristics of benign and malignant parotid gland tumors. Patients and methodsA total of 992 patients who underwent surgical treatment for parotid gland tumors from January 2010 to December 2020 were included in this study. This study population was subdivided into benign (n = 812, 81.9 %) and malignant parotid gland tumors (n = 180, 18.1 %). ResultsPleomorphic adenoma is the most common benign tumor and mucoepidermoid carcinoma is the most common malignant tumor. The patients with malignant parotid gland tumors were older than the patients with benign lesions. The duration of symptoms was longer in patients with benign parotid gland tumors compared to those with malignant lesions. The size of the malignant tumors was larger than that of the benign lesions. Preoperative fine-needle aspiration cytology had a diagnostic sensitivity of 50.3 %, diagnostic specificity of 98.7 %, a positive predictive value of 89.5 %, a negative predictive value of 89.9 %, and accuracy of 89.9 % for diagnosing malignant parotid gland tumors. For benign parotid gland tumors, superficial parotidectomy was most frequently performed, and for malignant parotid gland tumors, total parotidectomy was most frequently performed. Facial palsy was observed in 19.4 % of the patients with malignant parotid gland tumors compared to 5.4 % of those with benign tumors. ConclusionThe clinical features of benign and malignant parotid gland tumors showed differences in age, symptoms, duration of symptoms, size and site of the parotid tumors, surgical procedures, and postoperative facial nerve palsy.

Development and validation of CT-based radiomics nomogram for the classification of benign parotid gland tumors.

Accurate preoperative diagnosis of parotid tumor is essential for the formulation of optimal individualized surgical plans. The study aims to investigate the diagnostic performance of radiomics nomogram based on contrast-enhanced computed tomography (CT) images in the differentiation of the two most common benign parotid gland tumors. One hundred and ten patients with parotid gland tumors including 76 with pleomorphic adenoma (PA) and 34 with adenolymphoma (AL) confirmed by histopathology were included in this study. Radiomics features were extracted from contrast-enhanced CT images of venous phase. A radiomics model was established and a radiomics score (Rad-score) was calculated. Clinical factors including clinical data and CT features were assessed to build a clinical factor model. Finally, a nomogram incorporating the Rad-score and independent clinical factors was constructed. Receiver operator characteristics (ROC) curve was generated and the area under the ROC curve (AUC) was calculated to quantify the discriminative performance of each model on both the training and validation cohorts. Decision curve analysis (DCA) was conducted to evaluate the clinical usefulness of each model. The radiomics model showed good discrimination in the training cohort [AUC, 0.89; 95% confidence interval (CI), 0.80-0.98] and validation cohort (AUC, 0.89; 95% CI, 0.77-1.00). The radiomics nomogram showed excellent discrimination in the training cohort (AUC, 0.98; 95% CI, 0.96-1.00) and validation cohort (AUC, 0.95; 95% CI, 0.88-1.00) and displayed better discrimination efficacy compared with the clinical factor model (AUC, 0.93; 95% CI, 0.88-0.99) in the training cohort (p<0.05). The DCA demonstrated that the combined radiomics nomogram provided superior clinical usefulness than clinical factor model and radiomics model. The CT-based radiomics nomogram combining Rad-score and clinical factors exhibits excellent predictive capability for differentiating parotid PA from AL, which might hold promise in assisting radiologists and clinicians in the exact differential diagnosis and formulation of appropriate treatment strategy.

Cytokeratin 13 (CK13) expression in cancer: a tissue microarray study on 10,439 tumors.

Cytokeratin 13 (CK13) is a type I acidic low molecular weight cytokeratin, which is mainly expressed in urothelium and in the squamous epithelium of various sites of origin. Loss of CK13 has been implicated in the development and progression of squamous epithelial neoplasms. To comprehensively determine CK13 expression in normal and neoplastic tissues, a tissue microarray containing 10,439 samples from 131 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. CK13 immunostaining was detectable in 42 (32.1%) of the 131 tumor categories including 24 (18.3%) tumor types with at least one strongly positive case. The highest rate of positive staining was found in various urothelial neoplasms (52.1-92.3%) including Brenner tumor of the ovary (86.8%) and in squamous cell carcinomas from various sites of origin (39.1-77.6%), Warthin tumors of parotid glands (66.7%), adenosquamous carcinomas of the cervix (33.3%), thymomas (16.0%), and endometroid carcinomas of the ovary (15.3%). Twenty other epithelial or germ cell neoplasms showed - a usually weak - CK13 positivity in less than 15% of the cases. In bladder cancer, reduced CK13 expression was linked to high grade and advanced stage (p < 0.0001 each). In squamous cell carcinoma of the cervix, reduced CK13 immunostaining was related to high grade (p=0.0295) and shortened recurrence-free (p=0.0094) and overall survival (p=0.0274). In a combined analysis of 1,151 squamous cell carcinomas from 11 different sites of origin, reduced CK13 staining was linked to high grade (p=0.0050). Our data provide a comprehensive overview on CK13 expression in normal and neoplastic human tissues. CK13 expression predominates in urothelial neoplasms and in squamous cell carcinomas of different organs, and a loss of CK13 expression is associated with aggressive disease in these tumors.