Parotid gland tumors, staging, diagnostic and therapeutic approaches: A comparison between two countries

 Corresponding author: ERVIN DYRMISHI. Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. Parotid gland tumors, staging, diagnostic and therapeutic approaches: A comparison between two countries ERVIN DYRMISHI 1, * BIRKENA QIRJAZI 1, 2, XHEVAIR HOXHALLARI 1 and GILBERTO ACQUAVIVA 3 1 Otorhinolaryngology and Head-Neck Surgery Clinic, “Mother Teresa” University Hospital, Tirana, Albania. 2 Department of ENT-Ophthalmology, University of Medicine of Tirana, Albania; Otorhinolaryngology and Head-Neck Surgery Clinic, “Mother Teresa” University Hospital, Tirana, Albania. 3 Department of Otolaryngology,” San Camillo Forlanini” Hospital, Rome, Italy. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 125-136 Publication history: Received on 12 January 2025; revised on 03 March 2025; accepted on 05 March 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.21.3.0262 Abstract BACKGROUND: Epidemiological studies on parotid gland tumors are often limited to single institutions, lacking comprehensive statistical analysis. In Albania, the only study on the disease, conducted nine years ago, did not address correlations with risk factors, treatment, or post-surgical rehabilitation. Additionally, no studies compare the management of parotid tumors in different countries, which hinders the evaluation of various approaches. AIM: This study compares two multicenter experiences regarding the diagnosis, treatment, and follow-up of parotid gland tumors using consistent statistical data. METHODS: Data was collected from 2016 to 2023 at five healthcare institutions in Tirana, Albania, and Rome, Italy, including patient demographics, lesion characteristics, histology, and surgical procedures, adhering to European Association of Salivary Glands (ESGS) guidelines. RESULTS: The study included 100 patients from each country. The average age was 59.2 years for Italians and 63.9 years for Albanians. In Italy, 88% of lesions were benign, while 12% were malignant. In Albania, 63% were benign, and 37% were malignant, with 16% of malignant cases originating from benign tumors (e.g., pleomorphic adenoma). Common benign tumors in both groups were pleomorphic adenoma and Warthin's tumor, while malignant tumors included squamous cell carcinoma and adenocarcinoma. Surgical procedures mainly involved parotidectomy I-II for benign tumors and parotidectomy I-IV for malignant tumors. CONCLUSIONS: Early diagnosis and awareness of parotid gland tumors in Albania are crucial for improving treatment outcomes and minimizing complications. Efforts should focus on achieving tumor-free excision margins with minimal surgery. Keywords: Parotid; Salivary Glands; Tumor; Pleomorphic Adenoma; Warthin; Parotidectomy 1. Introduction Salivary gland tumors are rare entities, accounting for approximately 3-6% of all head and neck neoplasms, with an incidence rate ranging from 0.4 to 13.5 per 100,000 inhabitants per year1. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 125-136 126 Generally, parotid glands are affected in 70% of cases, submandibular glands in 10%, and sublingual glands in less than 1%. The remaining 20% are tumors of the small salivary glands, mostly originating in the upper aerodigestive tract, such as the palate and lips.1,2,3 The majority of parotid gland tumors are benign, while malignant forms are relatively rare. The risk of malignancy increases with the smaller size of the gland, so malignant lesions are more common in small salivary glands.2,3 Typically, patients are over 40 years old, and both genders are equally affected. Salivary glands have several histological subtypes. The 5th edition of WHO classification of Head and Neck tumors of 2022 listed 22 different primary neoplasms.2 Numerous studies on the epidemiology of salivary gland tumors highlight that prevalence, incidence, gender distribution, age, anatomical location, and survival rates vary significantly across different regions of the world.3 Many other studies report that the most common histological types of tumors affecting the parotid gland include pleomorphic adenoma, Warthin’s tumor, mucoepidermoid carcinoma, and adenoid cystic carcinoma.4 Ad-hoc investigations in countries like the United States and Japan have shown a notable increase in the incidence of parotid gland tumors compared to other salivary gland neoplasms.4 The study by Boci et al.5 analyzed the surgical variations and treatment outcomes of parotid gland tumors in patients who underwent parotidectomy between 2004 and 2015 at Tirana University Hospital Center (TUHC). This study found that the average age of patients with parotid gland disorders requiring surgery was 41 years and identified pleomorphic adenoma as the most prevalent pathology affecting the parotid gland5. However specific details regarding surgical techniques and variations were not provided there. Our study aims to investigate whether there is a similar trend in the increasing rate of parotid gland tumors within our population. Additionally, it seeks to evaluate the incidence, follow-up outcomes, and surgical approaches to the treatment of parotid gland tumors in Albania. To analyze this data properly, it is crucial to compare and identify differences in the diagnostic and treatment protocols for these tumors with those of neighboring countries, such as Italy and Greece. To date, no such comparative study has been conducted It is worth reminding that two major systems are commonly used for analyzing parotid tumors, whether benign or malignant: the TNM system and the ESGS classification. The ESGS Classification divides the parotid gland into five anatomical levels for describing the location of the tumor and helping to identify the most appropriate surgical approach. • Level I: Superior lateral parotid gland (superficial portion). • Level II: Inferior lateral parotid gland. • Level III: Deep inferior parotid gland. • Level IV: Superior deep parotid gland. • Level V: Accessory parotid tissue or glands. Meanwhile, TNM staging follows the AJCC (American Joint Committee on Cancer) guidelines. The TNM system stages the tumors based on size, regional lymph node involvement, and distant metastasis; it is more focused on the oncologic management of the patient. This article provides a comprehensive analysis of parotid gland tumors, focusing on their epidemiology, staging, diagnostic approaches, and surgical treatment, with a comparative assessment of cases from Italian and Albanian medical centers over 7 years. This comparison will provide valuable insights and facilitate the adoption of new techniques to improve treatment outcomes for parotid gland tumors in our countries. 2. Materials and methods This retrospective study, aimed to analyze data from patients treated for suspected primary neoplastic lesions of the parotid gland, across several medical centers in Italy and Albania, from January 2016 to December 2023. Data was World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 125-136 127 collected from the TUHC and the Departments of Otolaryngology and Head and Neck Surgery at four major health institutions in Central Italy. Each center contributed data on patients who underwent surgery for parotid tumors during the specified period. Information collected included patient demographics, histology of the tumors (classified as benign or malignant), fineneedle aspiration cytology (FNAC) reports, types of surgical procedures performed, postoperative complications, and histopathological findings of the excised masses. All data were sourced directly from the clinical databases and medical records of the participating hospitals. Throughout the data collection and presentation process, strict measures were implemented to ensure the protection of sensitive patient information and maintain confidentiality. Exclusion criteria for the study included secondary neoplasms of the parotid gland arising from primary tumors located in other anatomical sites. The study included a total of 250 patients, all suspected of having malignancy in the parotid gland. Based on histological evaluation, only patients with confirmed parotid gland tumors were included in further analysis. Therefore, the Italian and Albanian samples consisted solely of 200 patients who met this criterion. The subjects were categorized based on gender, incidence by decade, laterality, tumor size, histology, and the type of surgical procedures used, under the new classification proposed by the European Salivary Gland Society (ESGS). The staging of the tumors was also part of the initial evaluation of the subjects, but it was not analyzed in depth in this study. 2.1. Statistical Analysis Data from 200 selected cases was collected and analyzed using the Excel-incorporated Tool-Pack (Microsoft Corp., Redmond, WA, USA) to estimate descriptive statistics. Levene’s and T-test statistical methods were used and calculated to compare results. All estimates are within the standards of professional ethics and are part of routine hospital procedures. 3. Results Of the 200 patients included in the study (100 from Italy and 100 from Albania), there were notable differences in gender distribution between the two samples. In the Italian sample, 55 (55%) patients were male and 45 (45%) were female, indicating a slight male predominance with a female-to-male (F:M) ratio of 1:1.3. Conversely, in the Albanian sample, 64 (64%) patients were male and 36 (36%) were female, demonstrating a more pronounced male predominance with an F:M ratio of 1:1.8. The average age of patients was 59.2 years (57.9, SD 16,7) in the Italian cohort (age range: 8–94 years) and 63.9 years (64.3 SD 13.3) in the Albanian cohort (age range: 23–89 years). It was noted that the mean age difference was not statistically significant (t=.015, df =198, p<0.05) Table 1 Age/Incidence Descriptive Statistic Descriptive Statistics N Minimum Maximum Mean Std. Deviation Italian 100 8 94 57.86 16.727 Albanian 100 23 89 64.33 13.317 Valid N (listwise) 100 World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 125-136 128 Table 2 Age difference/Incidence descriptive analysis Independent Samples Test Levene's Test for Equality of Variances t-test for Equality of Means F Sig. t df Sig. (2tailed) Mean Difference Std. Error Difference 95% Confidence Interval of the Difference Lower Upper Age Equal variances assumed 6.06 0.015 -3.026 198 0.003 -6.47 2.138 -10.686 -2.254 Equal variances not assumed -3.026 188.528 0.003 -6.47 2.138 -10.688 -2.252 As illustrated in Figure 1 and 2, the peak incidence of parotid tumors in both samples occurred during the sixth and seventh decades of life. Notably, the Italian sample exhibited a higher incidence of diagnosis at relatively younger ages compared to the Albanian sample. Figure 1 Evaluation of Albanian incidence according to decades of age World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 125-136 129 Figure 2 Evaluation of Italian incidence according to decades of age In the Italian cohort, the right side was affected in 56% of cases, while the left side was involved in 44%. Conversely, in the Albanian cohort, 59% of cases involved the left side, and 41% affected the right side. The average size of neoplasms (measured as the largest diameter) was 2.4 cm ± in the Italian sample and 3.8 cm ± in the Albanian sample. As shown in Figure 3 and 4, most tumors in the Italian cohort measured 2–3 cm at the time of diagnosis. In contrast, the majority of tumors in the Albanian cohort were larger, measuring 3–4 cm, followed by 4–5 cm. Figure 3 Evaluation of Albanian incidence according to neoplasm dimensions World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 125-136 130 Figure 4 Evaluation of Italian incidence according to neoplasm dimensions In terms of histology, 88% of tumors in the Italian sample were benign, and only 12% were malignant. In the Albanian sample, however, 63% of tumors were benign, while 37% were malignant. Of the malignant cases in the Albanian group, 16% had developed from an initially benign lesion (e.g., pleomorphic adenoma). Figure 5 Evaluation of Italian incidence according to tumour histological type The most common benign tumors in the Italian cohort were Warthin’s tumor and pleomorphic adenoma. Among malignant tumors, the most frequent histotypes were mucoepidermoid carcinoma, squamous cell carcinoma and adenocarcinoma in that order as stated in Figure 5. In the Albanian sample, the most frequent benign tumors were pleomorphic adenoma and Warthin’s tumor, while the most common malignant tumors were adenocarcinoma, squamous cell carcinoma, and myoepithelial carcinoma as reflected in Figure 6. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 125-136 131 Figure 6 Evaluation of Albanian incidence according to tumour histological type In the Italian sample, the average age of patients with benign lesions was 56.9 years, compared to 64.24 years for malignant cases. In the Albanian sample, the average age was 60.8 years for benign lesions and 70.2 years for malignant cases. The age difference for malignant cases was not statistically significant (t = 1.307, df = 47, p < 0.05) (Table3,4). Similarly, the age difference for benign cases was not statistically significant (t = 0.176, df = 149, p < 0.05)(Table5,6) Table 3 Age/Malignancy descriptive analysis Group Statistics Nationality N Mean Std. Deviation Std. Error Mean Age Italian 12 64.25 22.046 6.364 Albanian 37 70.22 9.903 1.628 Table 4 Age difference/ Malignancy descriptive analysis Independent Samples Test Levene's Test for Equality of Variances t-test for Equality of Means F Sig. t df Sig. (2tailed) Mean Difference Std. Error Difference 95% Confidence Interval of the Difference Lower Upper Age Equal variances assumed 8.205 0.006 - 1.307 47 0.198 -5.966 4.565 -15.151 3.218 Equal variances not assumed - 0.908 12.47 0.381 -5.966 6.569 -20.219 8.287 World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 125-136 132 3.1. Benign Table 5 Age/benign descriptive analysis Group Statistics Nationality N Mean Std. Deviation Std. Error Mean Age Italian 88 56.99 15.828 1.687 Albanian 63 60.87 13.907 1.752 Table 6 Age difference/ benign descriptive analysis Independent Samples Test Levene's Test for Equality of Variances t-test for Equality of Means F Sig. t df Sig. (2tailed) Mean Difference Std. Error Difference 95% Confidence Interval of the Difference Lower Upper Age Equal variances assumed 1.847 0.176 - 1.563 149 0.12 -3.884 2.485 -8.795 1.026 Equal variances not assumed - 1.597 142.798 0.113 -3.884 2.432 -8.693 0.924 Overall, 15 different primary histological tumor types were identified in the Italian sample. 3.1.1. Benign Tumors The most prevalent benign tumors in this sample were Warthin’s tumor (40%) and pleomorphic adenoma (33%). Less common benign forms included: • Cystic lesions (4%) • Monomorphic adenoma (2%) • Oncocytoma (2%) • Neurofibroma (1%) 3.1.2. Malignant Tumors The most frequent malignant histotypes were: • Mucoepidermoid carcinoma (6%) • Squamous cell carcinoma (3%) Other less common malignant tumors included: • Carcinoma ex pleomorphic adenoma (2% of Carcinoma lesions%) • Adenocarcinoma (2%) In the Albanian sample, 12 histological types were identified. The most common benign forms were pleomorphic adenoma (37%) and Warthin’s tumor (15%), followed cystic adenoma (2%), and others. World Journal of Biology Pharmacy and Health Sciences, 2025, 21(03), 125-136 133 On the other hand, malignant lesions were primarily represented by adenocarcinoma (27%), with 16% developing from a pre-existing benign condition (e.g., pleomorphic adenoma). Squamous cell carcinoma (6%) and myoepithelial carcinoma (4%) were also observed. Further details are presented in Graphic 6. The general diagnostic protocol used in Italian hospital centers involved a clinical and ultrasound assessment, followed by a preoperative evaluation through ultrasound-guided fine-needle aspiration (US-FNA) and radiological imaging (CT and/or MRI) to determine the most appropriate surgical approach. In contrast, the diagnostic workup for Albanian patients was based on clinical evaluation, followed by CT and/or MRI imaging, and concluded with a histopathological examination of the excised mass after surgery. In both groups, the surgical approach was determined based on the size and location of the tumor within the gland. The procedures included superficial parotidectomy, partial superficial parotidectomy, deep lobe parotidectomy, superficial parotidectomy extended to the deep inferior lobe, extracapsular dissection, and total parotidectomy with either preservation or resection of the facial nerve in cases of malignant tumor infiltration. For malignant lesions, surgical treatment was planned after clinical evaluation of the primary tumor (T) and cervical lymph nodes (N). The primary approach consisted of total parotidectomy, with or without facial nerve preservation, and, when necessary, extension to extra glandular structures and adequate neck dissection. The study also analyzed the collected data according to the 2016 ESGS classification. 3.1.3. Italian Sample Table 7 indicates that the most common tumor size range was 2–2.99 cm, accounting for 37% of cases. Across all size categories, the most frequently performed surgical procedure was superficial parotidectomy (also referred to as parotidectomy I-II, according to the ESGS classification). Table 8 outlines the histological characteristics of the tumors, showing that Warthin's tumor was the most common type, representing 40% of all lesions. The primary treatment for this tumor was parotidectomy I-II, performed in 75% of cases with this type of tumor. The second most common procedure was total parotidectomy, classified as parotidectomy I-IV (13% of cases), followed by deep inferior lobe parotidectomy, also known as parotidectomy III-IV (3%). Table 7 Types of ESGS according to tumor dimensions in Italy Table 8 Types of ESGS according to histology in Italy Pleomorphic adenoma, accounting for 33% of all tumors, was treated with parotidectomy I-II in 77 % of cases, parotidectomy I-IV in 6% of cases, and parotidectomy I-II-III in another 9% of adenomas. Malignant tumors, representing 12% of all cases, were primarily managed with total parotidectomy (46.2%). In some patients, a portion of the gland was preserved, with surgical approaches including superficial parotidectomy (27.9%) or parotidectomy I-II-III (15.3%). In another 11.7% of cases, facial nerve sacrifice was necessary, requiring total facial resection parotidectomy, classified as parotidectomy I-IV (VII). Additionally, some