Carcinoma ex Pleomorphic Adenoma: A Case Series and Literature Review

Abstract Introduction Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor that can lead to severe complications and carries a risk of distant metastasis. This study aims to provide a comprehensive overview of CXPA through a case series and a review of the literature. Methods This was a single-center retrospective case series. The patients were included from November 2018 to December 2024. All confirmed cases of CXPA that were diagnosed and managed with complete clinical data were included in this study. Cases with incomplete data were excluded. Results Six patients were included, with ages ranging from 45 to 88 years (mean ± SD: 64 ± 15.36; median: 62). Most were male (66.7%), with an even distribution of occupations. All presented with preauricular swelling lasting 2 to 10 years, and three had left-sided tumors. Fine needle aspiration identified 33.3% as benign and 16.7% as malignant. Ultrasound examination showed solid tumors in four cases, three of which were well-defined. Three (50%) underwent total parotidectomy, and three (50%) underwent superficial parotidectomy. Histopathological examination revealed adenocarcinoma ex pleomorphic adenoma in 50% and squamous cell carcinoma ex pleomorphic adenoma in 16.7%. Tumor sizes ranged from 3.5 to 6 cm (mean: 4.73 ± 1.24 cm). Capsular invasion was present in all cases, with lymph node involvement in 33.3%, lympho-vascular invasion in 16.7%, and perineural invasion in 50%. Adjuvant therapy included radiotherapy or chemoradiotherapy. Conclusion Although CXPA is very rare, it is a serious condition; surgical approach with or without adjuvant therapy may result in preferable outcomes. Introduction Salivary gland tumors are uncommon neoplasms of the head and neck region. Among them, pleomorphic adenoma is the most prevalent benign type, accounting for approximately 70% of all salivary gland tumors [1]. The parotid gland is the most frequent site of occurrence for salivary gland tumors, followed by the submandibular gland and the minor salivary glands [2]. If left untreated, pleomorphic adenoma carries a risk of malignant transformation, with the risk reaching up to 9.5% after 15 years and continuing to increase over time [3]. Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor that develops from a pre-existing benign pleomorphic adenoma, accounting for approximately 5% of all head and neck malignancies [4]. CXPA constitutes approximately 3.6% of all salivary gland neoplasms, 6.2% of all mixed tumors, and 11.6% of all malignant salivary gland neoplasms. This malignancy predominantly occurs between the sixth and eighth decades of life and shows a slight female predominance [5]. Historical data reveal geographical variation in the incidence of this tumor relative to primary parotid malignancies, with reported rates of 12–13% in the United States, 14% in Switzerland, and up to 25% in the United Kingdom [1]. CXPA has also been referred to by other names, including carcinoma ex mixed tumor, carcinoma ex adenoma, and carcinoma ex benign pleomorphic adenoma [5]. The risk of malignant transformation is heightened by patient-related factors such as advanced age and a history of smoking, as well as disease-related factors, including larger tumor size and higher histological grade [1]. As a rare and complex disease, the clinical and pathological understanding of CXPA continues to evolve with ongoing research and advancements in diagnostic techniques [1]. This study aims to provide a comprehensive overview of CXPA by analyzing six cases, with a focus on clinical presentation, diagnostic approaches, treatment outcomes, and a review of the literature. The references have been evaluated for credibility using the most up-to-date criteria [6]. Methods Study design This single-center case series included consecutive patients diagnosed with CXPA who were treated between November 2018 and December 2024. Data collection After de-identification, the necessary data were retrospectively obtained from patient records in the Head and Neck clinic database. Extracted variables included patient demographics, occupation, clinical presentation, ultrasound (U/S) findings, treatment approach, outcomes, histopathological findings, and follow-up information. The follow-up period ranged from 1 to 5 years. Eligibility criteria All confirmed cases of CXPA that were diagnosed and managed with complete clinical data were included in this study. Cases with incomplete data were excluded. Intervention All patients underwent a thorough preoperative assessment, including a detailed clinical examination with an emphasis on facial nerve function, as well as imaging to assess lesion size, location, extent, and potential local invasion. Surgical procedures were performed under general anesthesia with the patient positioned supine and the head turned contralaterally to the lesion side. A standard Blair (lazy-S) incision was utilized, beginning anterior to the tragus, extending around the earlobe, and continuing into a natural skin crease in the upper neck to ensure optimal surgical access and cosmetic appearance. Following subplatysmal flap elevation, dissection was carried out to identify the main trunk of the facial nerve, typically located at the stylomastoid foramen, just inferior and medial to the tympanomastoid suture. In cases of partial parotidectomy, only the superficial lobe of the gland was excised, preserving the facial nerve and its branches. In total parotidectomy, both superficial and deep lobes were removed, with caution to maintain all major branches of the facial nerve. Dissection proceeded using fine instruments and bipolar cautery under loupe magnification to enhance visualization and minimize nerve trauma. Hemostasis was achieved using bipolar coagulation and ligation of feeding vessels. Redivac drains were placed in the surgical bed and secured with sutures to facilitate postoperative drainage and reduce the risk of hematoma or seroma formation. Skin closure was performed in layers using absorbable sutures for the deep plane and non-absorbable or subcuticular sutures for the skin to optimize healing and reduce scar formation. Post-intervention considerations Postoperatively, patients received protocol-based analgesia and prophylactic antibiotics. The diagnosis was confirmed through histopathological examination of the surgical specimens. Statistical analysis Data entry and coding were performed using Microsoft Excel 2019. Descriptive statistical analysis of qualitative data was conducted using the Statistical Package for the Social Sciences (SPSS) Version 25. Results were presented as means, frequencies, and percentages. Results This study included 6 patients, whose raw data are presented in Tables 1 & 2. Ages ranged from 45 to 88 years, with a median age of 62 and a mean age of 64 ± 15.36 years. Most of the patients were males (66.67%), with occupations evenly distributed (33.33% housewives, 33.33% unemployed, and 33.33% workers). Family history was unremarkable in all patients. Smoking was reported in only 1 patient. All the patients presented with preauricular swelling, with duration of symptoms ranging from 2 to 10 years. The left parotid gland was affected in 3 (50%) patients. Upon fine needle aspiration (FNA), 2 (33.33%) of the tumors were benign, while only 1 (16.67%) tumor was malignant with certainty. On U/S, 4 of the tumors were solid, 3 of which were well-defined. Lymph nodes were suspicious for involvement in 2 (33.33%) patients. three patients (50%) underwent total parotidectomy, while the other 3 (50%) underwent superficial parotidectomy. Histopathology revealed adenocarcinoma ex pleomorphic adenoma in 3 (50%) patients, and squamous cell carcinoma ex pleomorphic adenoma in 1 (16.67%) patient. Tumor sizes ranged from 3.5 to 6 cm (mean: 4.73 ± 1.24). Lymph node involvement was seen in 2 (33.33%) patients. Capsular invasion was observed in all patients, lympho-vascular invasion in 1 (16.67%) patient, and perineural invasion in 3 (50%) patients. Adjuvant therapy included radiotherapy and chemoradiotherapy (Table 3). No cases of recurrence were reported, and one patient passed away from old age. Table 1. Demographics and preoperative findings of the enrolled patients. Case no. Age Sex Occupation Family history Smoking Chief complaint Duration (years) Site FNAC findings Consistency (U/S) Size in cm (U/S) Suspecious lymph nodes (U/S) 1 67 F Housewife Unremarkable No Pre-auricular swelling 7 LPG SUMP Solid, well-defined 5.1 Not seen 2 88 M Jobless Unremarkable No Pre-auricular swelling 3 LPG AUS Complex 6.9 Seen 3 49 M Worker Unremarkable Yes Pre-auricular swelling 6 RPG Benign Solid, well-defined 1.7 Not seen 4 57 F Housewife Unremarkable No Pre-auricular swelling 4 RPG Benign Solid, well-defined 2.9 Not seen 5 45 M Worker Unremarkable No Pre-auricular swelling 2 LPG N/A N/A N/A N/A 6 78 M Jobless Unremarkable No Pre-auricular swelling & facial palsy 10 RPG Malignant Solid, irregular 3.6 Seen F: Female, M: Male, LPG: Left parotid gland, RPG: Right parotid gland, SUMP: Salivary gland Neoplasm of Uncertain Malignant Potential, AUS: Atypia of Undetermined Significance, U/S: Ultrasonography Table 2. Treatment and outcome of the enrolled patients. Surgical approach HPE Tumor stage Tumor size (CM) LN involvement Invasion Adjuvant therapy Outcome Follow-up (years) Capsular Lympho-vascular Perineural Total Parotidectomy Adenocarcinoma ex pleomorphic adenoma pT3 5.5 N/A FI Not seen Not seen N/A No recurrence 4 Superficial parotidectomy, suprahyoid lymph nodes dissection & excision of sublingual gland Adenocarcinoma ex pleomorphic adenoma pT4a N1