Uncommon Coexistence of Pleomorphic Adenoma and Warthin’s Tumor in a Painfully Swollen Left Parotid Gland: A Surgical Case Report

Background

Only a small proportion of all tumors of the head and neck region occur in the salivary glands; however, up to 85% of these tumors are located within the parotid glands [1]. The benign epithelial lesions pleomorphic adenoma (PA) and Warthin’s tumor (WT), the latter named after A. Warthin who published 2 cases of papillary cystadenoma lymphomatosum in 1929, are the 2 most common benign neoplasms of the parotid gland [2,3]. They account for 71% (in case of PA, an annual incidence of approximately 2–3.5 cases/100 000 population is described) and 22%, respectively, of all benign salivary gland tumors and are classified due to their histological appearance as well as their distinct genetic profile in case of PA (characteristic PLAG1/HMGA2 transcription factor gene rearrangements) [3–6].

Although tumors of the salivary glands usually occur as solitary lesions, multiple parotid tumors have been reported in the literature [7–15]. Depending on the underlying patient population and therefore based on different incidences, multiple parotid tumors have been described with frequencies of 3.4% (Yu et al; cohort of 2055 patients, Peking) up to 5% (Ethunandan et al; cohort of 606 patients, Chichester) [11,13]. Terminologically and etiologically, a further characterization of the lesion(s) is made according to their time of development and appearance (synchronous/metachronous), according to their localization (bilateral/ipsilateral), as well as according to their distinct histological entity (identical/different) [16]. Here, we report the rare clinical case of a 54-year-old woman with a 6-month history of painful swelling of the left parotid gland due to synchronous benign pleomorphic adenoma and Warthin’s tumor.

Case Report

MEDICAL HISTORY AND CLINICAL PRESENTATION:

A 54-year-old female patient presented to the otorhinolaryngology clinic at the University Hospital (Goethe University, Frankfurt am Main, Germany) after reporting a history of a progressive and painful swelling of the left parotid gland for the last 6 months with a marked increase in size in recent weeks. The patient denied allergies or regular intake of medication. The extra-oral examination revealed a bulging, displaceable mass of the left parotid gland with a diameter of about 3 cm. The mass was located in the caudal part of the left parotid gland, and a small (<1 cm) inconspicuous lymph node was located in the immediate neighborhood. On palpation, the mass appeared solid, well-displaced, and not pressure-dolent. The overlying skin was intact and not pathologically altered. The ENT (ear, nose, and throat) status showed no signs of pathological affection; in particular, the function of the facial nerve was not affected. Despite a small inconspicuous lymph node in the left glandula parotidea, there were no pathologic lymph nodes or other lesions detected cervically. On the intra-oral examination, the oral mucosa was non-irritant except for minimal redness of the posterior pharyngeal wall, and the tonsils were small and regular. The dental status was unremarkable. An externally performed MRI scan of the neck showed a quasi-spherical mass, measuring 1.5×1.5×2 cm, with moderate contrast enhancement (T1 low-intensity and T2 high-intensity, compatible with a suspected diagnosis of WT) within the tail of the left parotid gland, as well as a small contrast-enhancing lesion in the middle part of the parotid gland (Figure 1) [17]. All other salivary glands showed no abnormalities in the MRI. At the second presentation in our clinic, the described mass was assessed by ultrasound, and a 1.4×1.2 cm homogeneous lesion was detected (Figure 2). After explaining conservative and surgical treatment options, the patient opted for a definite surgical procedure; accordingly, a lateral (superficial) parotidectomy was planned to remove the tumor, while sparing the facial nerve (VII). Intraoperatively, the multifocal occurrence of the lesion was acknowledged and 3 tissue fragments were sent from the operating room to pathology for histopathological evaluation. The specimens appeared beige-brownish on gross examination and originated intraparotidally from the left part of the parotid gland, the lower pole, and preauricularly from the left parotid gland.

On hematoxylin and eosin (H&E) staining, the tissue removed from the lower pole proved to be an encapsulated tumor with bilayered oncocytic epithelia based on a dense lymphoid stroma with germinal centers (Figure 3). The oncocytic epithelium did not show a distinct nuclear pleomorphism or marked hyperchromasia as signs of malignancy. Intermittently, cystic eosinophilic areas demarcated by an epithelial wall as well as granulomatous-appearing areas were found. Additively, small fragments of locoregional, lipomatous-altered, glandular tissue were removed. The histomorphological assessment of the preauricularly resected tissue fragment revealed resident glandular tissue adjacent to an encapsulated tumorous lesion (Figure 4). This specimen showed a multiform cellular pattern with both epithelial and mesenchymal differentiation of tumor cells; the tissue fraction contained predominantly densely packed myoepithelial cells adjacent to a myxoid stromal component. All the tumor cells showed no signs of dysplasia and no increased mitotic rate and no necrosis. There was no capsular rupture and no perineural infiltration. The intraparotideal tissue of the left side was a lymph node with reactive changes (not shown). Further molecular testing of both lesions to exclude mimickers was not performed. The pathology examination revealed the ipsilateral and simultaneous presence of a WT as well as a PA; therefore, the patient was diagnosed with ipsilateral, synchronous multiple parotid tumors with different histological characteristics. At the time of publication, the patient had neither clinical symptoms nor signs of recurrence. As a regular follow-up, a clinical and ultrasonographical examination once a year was recommended.

Discussion

PA and WT are common tumors of the parotid gland. Their synchronous and ipsilateral occurrence is a rare phenomenon in which clinical examination and various imaging techniques can be misleading. Our case report reflects the importance of a timely and accurate diagnosis with histopathology that can ultimately rule out the presence of malignant transformation.

The simultaneous detection of a PA and a WT was described in 1974 for the first time [18]. Table 1 gives a literature overview of published cases and clinical information on unilateral synchronous PA and WT of the parotid gland within the last 30 years (1993–2023). Table 2 summarizes statistical surveys in which the explicit combination of PA and WT is depicted. Overall, the literature provides different information on the localization and frequency of multiple salivary gland tumors in general. Depending on the cohort, a preferred occurrence of multiple parotid tumors has been reported both ipsilaterally (67%, Ethunandan et al analyzed 650 tumors of 606 patients of 617 parotidectomies removed with oncological indication in Chichester, United Kingdom), as well as bilaterally (58%, Yu et al screened 2055 patients with parotid tumors and determined 69 multiple primary tumors of the parotid gland at the University School of Stomatology, Peking, China). In either case the vast majority of multiple neoplasms of the parotid gland are identical in histology, namely WT [11,13]. However, simultaneous occurrence of multiple parotid tumors of different entities is rare and clinical experience on this subject is largely based on single case reports [7–10,18]. In such cases the tumors are, considering their high prevalence, ordinarily a combination of WT and PA [11,13,18].

Although clinical diagnosis by imaging methods such as MRI and ultrasound is usually successful in locating and assessing the malignant potential of singular/bilateral lesions of the parotid glands, the difficulty of correct preoperative radiological assessment of multiple ipsilateral parotid tumors is well known [7,19]. A definitive diagnosis is usually made only during histological tissue examination, as in the present case [7,11]. It should be emphasized that even a correct preoperative determination of a single tumor entity by means of fine-needle aspiration cytology (FNAC) can be misleading in patients with multiple tumors with different histology, as the second intact tumor entity in situ cannot be taken into account by the pathologist [7,8]. In our case, non-invasive imaging (MRI) but no FNAC or other histological confirmation was performed prior to surgery, because even in benign tumors of the salivary glands, the masses including their capsule should be completely removed to avoid recurrences. Despite the advantage of early histological confirmation of a malignant finding, carryover of single tumor cells could occur due to the FNAC procedure. Furthermore, even with a benign FNAC finding, malignancy cannot be ruled out with absolute certainty due to the small sample size. Therefore, the further procedure of surgical resection would not necessarily change depending on the result of the FNAC. Finally, previous sampling could cause scarring, which potentially complicates subsequent surgery [20,21]. In 2018, Heine et al reported 2 cases of synchronous unilateral PA and WT. Instead of using FNAC, they employed elastography (Virtual Touch Imaging Quantification, VTIQ) as an additional diagnostic tool. In this way, the physical stiffness, which can be used as a potential marker for malignancy, was successfully assessed and interpreted prior to surgery [22].

In the course of multiple parotid tumors, a possible combination of a benign neoplasm with a malignant lesion, in most of the cases a Warthin tumor and mucoepidermoid carcinoma, should be considered [22,23]. Ochal-Choinska et al provided a comprehensive literature overview of known cases of simultaneous, unilateral parotid gland tumors of benign and malignant histology [24]. Whether multiple parotid tumors are more frequently associated with 2 benign entities (Ethunandan et al) or with a combination of a benign tumor entity and a malignant tumor entity (Seifert et al, Yu et al, Zeebregts et al, Schilling et al) has not yet been clearly established [11,13,14,16,25].

In the constellation of multiple parotid tumors, each case remains an individual course until the final histopathological diagnosis postoperatively. Thus, 3 synchronously occurring tumor entities with individual malignancy potential, namely a PA, a WT and a salivary duct carcinoma, have already been described within the parotid gland and successfully treated by surgery and postoperative radiotherapy [26]. In our case of a WT and a PA, the therapeutic approach of choice was a complete surgical tumor resection. This is the first-line therapy in singular WTs/Pas and is also the treatment of choice in ipsi-lateral multiple parotid tumors with benign histology [5,8,18].

Conclusions

Our case report shows the rare phenomenon of synchronous occurrence of different tumor entities in the parotid gland. Our report further supports that the combination of PA and WT is the most common association. Since radiological imaging techniques and fine-needle aspiration do not allow for distinct diagnosis of underlying biological entities in these patients, a timely and accurate histomorphological analysis of all separate tumor specimens is important to determine treatment options and to exclude malignant transformation.