Synchronous mucoepidermoid carcinoma of sublingual gland and pleomorphic adenoma of palatal gland-a case report and literature review

Abstract

Background

The synchronous development of multiple, histologically distinct primary salivary gland tumors is exceedingly rare, especially with involvement of both major and minor glands. Although growing research has advanced epidemiological understanding, clinical management continues to be significantly impeded by underdiagnosis and misdiagnosis.

Case presentation

We present an 18-year-old female with two slow-growing, asymptomatic masses over a two-year period. The palatal mass showed gradual enlargement and mucosal protrusion. In contrast, the sublingual mass grew more rapidly, becoming fixed and immobile within the past year. Magnetic resonance imaging (MRI) revealed corresponding nodular soft-tissue masses with heterogeneous signals. The palatal lesion was irregular yet relatively well-defined; however, the sublingual mass displayed locally aggressive behavior with invasion of the mandibular lingual periosteum and floor-of-mouth muscles, resulting in ill-defined margins and submandibular duct dilation. Histopathologic correlation confirmed an intermediate-grade mucoepidermoid carcinoma of the sublingual gland and a pleomorphic adenoma of the palate.

Conclusions

The synchronous occurrence of benign and malignant salivary gland tumors is a rare clinical phenomenon that demands thorough evaluation to ensure diagnostic accuracy and a favorable prognosis. We report a unique case of synchronous mucoepidermoid carcinoma in the sublingual gland and pleomorphic adenoma in the palate, which, to our knowledge, is the first such documented instance. This report expands the documented spectrum of multiple primary salivary gland tumors and serves as a vital clinical reference, underscoring the need for heightened awareness when assessing concurrent lesions.

Background

Salivary gland neoplasms characteristically manifest as a solitary mass within a single salivary gland. The occurrence of multiple tumors is infrequent, and coexistence of benign and malignant tumors in different glands is particularly unusual [1–3]. Salivary gland tumors are a clinically diverse group of neoplasms, of which pleomorphic adenoma and mucoepidermoid carcinoma are the most frequent benign and malignant tumors, respectively [4–6]. In the sublingual gland and minor salivary glands, the majority of the tumors are malignant [7]. Although the parotid gland is the primary site for multiple salivary gland tumors (most often Warthin tumors), and concurrent tumors in the parotid and submandibular glands typically share the same histology (frequently pleomorphic adenoma), it is notably rare to find divergent pathological types coexisting across these different glands. To the best of our knowledge, the synchronous and combination of mucoepidermoid carcinoma in sublingual gland and pleomorphic adenoma in palatal gland has not been reported previously. This case constitutes the initial documentation of this combination of neoplasms. While recent clinical epidemiological investigations have deepened our understanding of multiple primary salivary gland tumors, significant challenges in their diagnosis and management persist, including issues such as underdiagnosis and misdiagnosis. This case report and literature review not only enrich the epidemiological data on multiple primary salivary gland tumors but also provide crucial diagnostic insights for clinicians, prompting critical diagnostic consideration.

Case presentation

One 18 years old female was referred to us for the chief complaint of two masses in the oral cavity for 2 years, without any numbness and pain symptoms. The sublingual gland mass was the first to be noticed, measuring approximately 1.0 cm × 1.0 cm, firm in consistency, and mobile vertically in the floor of the mouth. 2 days later, a palatal mass of similar size and firmness was identified. Neither mass was significantly raised or associated with swelling, pain, or numbness. As they did not impact daily life, no medical intervention was sought at that time. Both lesions were exhibited slow growth, although the sublingual gland mass progressed slightly faster and had been fixed for one year. Currently, both lesions are protruding from the mucosal surface with overlying mucosal congestion, and the patient reports a subjective sensation of a foreign body during speech and swallowing. Physical examination revealed the presence of two distinct lumps. The first was a firm lump measuring approximately 2.0 cm × 1.5 cm, located on the right soft palate. The second nodule measuring approximately 2.0 cm × 2.5 cm, located beneath the mucosa of the right floor of mouth. The mucosa covering the lesions is characterized by the absence of ulcers, but with dilatation of apparent blood capillaries (Fig. 1). On bimanual examination, the sublingual gland mass was fixed to the mandibular lingual periosteum and floor-of-mouth muscles.

Fig. 1.

This picture of the patient’s oral cavity shows two separate masses. The PA of the palatine gland is marked by the red dotted line, and the MEC of the sublingual gland is marked by the yellow dotted line. PA: Pleomorphic adenoma. MEC: Mucoepidermoid carcinoma

MRI demonstrated nodular soft-tissue masses in the right soft palate and sublingual gland (Fig. 2), demonstrating heterogeneous T1 hypotintensity (Fig. 2A, C, D, E, F) and T2 hyperintensity with internal areas of increased signal on fat-suppressed sequences (Fig. 2B, G, H, I, J). The palatal lesion (1.5 cm × 1.8 cm × 1.5 cm) was irregular but relatively well-defined. In contrast, the sublingual mass (1.6 cm × 2.0 cm × 2.5 cm) showed aggressive features, including ill-defined borders, invasion of the mandibular lingual periosteum, and a 5 mm dilation of the submandibular duct (Fig. 2J).

Fig. 2.

MRI examination pictures show the lesions’ locations and their features in T1WI (A, C, D, E, F) and T2WI (B, G, H, I, J). The images (A-B) with blue border are the sagittal section, the images (C, E, G, I) with red border are the coronal section and the images (D, F, H, J) with yellow border are the transverse section. The red arrow indicates the tumor of the palatine gland, and the yellow arrow indicates the tumor of the sublingual gland. MRI: Magnetic resonance imaging, T1WI: T1 weighted imaging, T2WI: T2 weighted imaging. Scale bar: 5 cm

A preoperative incisional biopsy of the right sublingual gland neoplasm was diagnostic of intermediate-grade mucoepidermoid carcinoma. Given this fixation and the radiographic evidence of local invasion, under general anesthesia, an en bloc resection of the sublingual gland, submandibular gland, a segment of the mandible, and the involved muscles was performed to obtain sufficient oncologic margins. Negative margins were verified by intraoperative frozen section. Besides, the palatal gland mass was also managed with a regional resection and the intraoperative frozen section examination was confirmed to be pleomorphic adenoma. Simultaneously, a vascularized free osteocutaneous fibular flap was harvested to reconstruct the composite defects of mandible and the floor of mouth, and the palatal wound was closed with an adjacent soft tissue flap. Finally, postoperative histopathological examination reveals a well-encapsulated tumor in palatal gland. The tumor cells form gland-like structures and solid epithelial nests, with visible myxoid areas. The duct lumens are lined by glandular epithelial cells, surrounded by myoepithelial cells. Immunohistochemistry showing positivity for CK5/6, CK7, S-100, GFAP, calponin, and P63, with a Ki-67 proliferation index of 2%, supports the diagnosis of pleomorphic adenoma of palatal gland (Fig. 3). At low magnification, the tumor cells in sublingual gland are arranged in cords and sheets, exhibiting infiltrative growth, with the formation of small cystic spaces. On high-power field, the tumor cells are primarily composed of epidermoid cells and intermediate cells, with scattered mucus-secreting cells distributed among the tumor areas. Immunohistochemistry showing diffuse positivity for CK7, positivity for CK5/6 and P63, focal positivity for AB, and a Ki-67 index of 2%, supports the diagnosis of mucoepidermoid carcinoma of sublingual gland (Fig. 4). At the three-year follow-up, there was no evidence of tumor recurrence or metastasis.

Fig. 3.

The hematoxylin and eosin stain revealed a PA in palatine with tumor cells form glandular duct-like structures, solid epithelial nests, and visible mucus areas (A). Scale bar: 500 μm and (B). Scale bar: 100 μm). Immunohistochemical staining showed: (C) CK5/6 (+), (D) CK7 (+), (E) S-100 (+), (F) SMA (-), (G) GFAP (+), (H) β-catenin in cell cytoplasm and membrane (+), (I) calponin (+), (J) P63 (+), and (K) Ki67 rate = 2%, Scale bar: 200 μm

Fig. 4.

The hematoxylin and eosin stain revealed a MEC in sublingual gland with tumor cells arranged in cords and clumps, invasive growth, small sac cavity formation and a small number of mucus cells are visible (A). Scale bar: 500 μm and (B). Scale bar: 100 μm). Immunohistochemical staining showed: (C) CK5/6 (+), (D) CK7 (+), (E) SMA (-), (F) GFAP (-), (G) β-catenin in cell cytoplasm and membrane (+), (H) calponin (-), (I) P63 (+), (J) AB individual cells (+), and (K) Ki67 rate = 2%, Scale bar: 200 μm. (Arrow in Figure B demonstrates small sac cavity formation, and arrows in Figure J indicates mucous cells)

Discussion and conclusions

Salivary gland tumors, which exhibit distinctive clinicopathological features, are common in the oral and maxillofacial region. Own to its diversity of histological types and the similarity of clinical characteristics, it makes diagnosis and treatment challenging for clinicians. According to epidemiological statistics, the majority of salivary gland tumors were of epithelial origin, with the majority being benign. The parotid gland was the most common site of occurrence, and the presentation was typically as a solitary mass. Pleomorphic adenoma was the most frequent benign tumor [8, 9]. In contrast, the vast majority of tumors arising in the sublingual glands were malignant, with adenoid cystic carcinoma being the most prevalent histopathological type, followed by Mucoepidermoid carcinoma (MEC) [10]. The probability of malignancy in a minor salivary gland mass ranges from 70% to 90%, with most cases located in the palate [11].

Multiple primary carcinomas or tumors refer to the occurrence of two or more primary malignant tumors in the same patient, either simultaneously or at different times. Based on the timing of onset, they are classified as synchronous carcinomas (within 6 months) or metachronous carcinomas (beyond 6 months). Differentiation from malignant tumor metastasis is generally required. The diagnosis of multiple primary tumors first necessitates clarification of the anatomical sites and timing of tumor occurrence. Second, each tumor must have a definitive histological diagnosis, and the pathological types may be identical or different. Multiple salivary gland tumors are regarded as rare clinical entities, which are predominantly of the same histological type, specifically Warthin tumor. The presence of synchronous salivary gland tumors of differing histological types is an occasional occurrence. The most common combination is that of Warthin tumor and pleomorphic adenoma. More infrequently, benign and malignant tumors may occur concurrently. The coexistence of pleomorphic adenoma in palatal gland and mucoepidermoid carcinoma in sublingual gland has not been previously documented. In our report, the patient first noticed a sublingual gland mass, followed by the discovery of a similarly firm mass in the right palate two days later. The diagnostic priority was to exclude metastasis, as the presentation was inconsistent with the typical pattern of salivary gland malignancy. The preliminary assessment suspected a malignant sublingual tumor (with adenoid cystic carcinoma, mucoepidermoid carcinoma, or carcinoma ex pleomorphic adenoma as possibilities) and a palatal tumor most likely to be a pleomorphic adenoma, though a lesion identical to the sublingual tumor could not be ruled out. In this case, the final pathological diagnosis confirmed an intermediate-grade mucoepidermoid carcinoma in the sublingual gland and a pleomorphic adenoma in the palatal gland. Therefore, we definitively diagnosed this as a case of synchronous multiple primary tumors of different histological types arising in different salivary glands.

In 1953, Tanaka published the first report on the case of synchronous bilateral multiple parotid gland tumors(Warthin tumor associated with mucoepidermoid carcinoma) [12]. Subsequent studies have documented the occurrence of synchronous benign and malignant salivary gland neoplasms in 33 papers (Table 1) [1, 2, 12–42]. According to prior studies, synchronous bilateral multiple parotid tumors were typically with a greater frequency among male patients, exhibiting a male-to-female ratio of 1.2:1. The median age of the cohort was 55 years, and the age of onset ranges from 35 to 85. From a histopathological perspective, the most commonly observed benign neoplasm was Warthin tumor (26/50 cases), followed by pleomorphic adenoma (16/50 cases). Additionally, there are other benign tumors, including canalicular adenoma, basal cell adenoma, sebaceous lymphadenoma, oncocytoma and myoepithelioma. The most frequently described malignant lesion was mucoepidermoid carcinoma (15/50 cases), with acinic cell carcinoma (9/50 cases) coming in second. The most prevalent histopathological combination of benign and malignant tumors is Warthin tumor and mucoepidermoid carcinoma (10/50 cases). Consequently, our study is a further complement to the above combination. This rare case provides a new kind of combination of multiple salivary tumors, which should raise the clinicians’ vigilance in the process of evaluation of multiple primary neoplasms involving different salivary glands.

Table 1.

Summary of the literature on synchronous benign and malignant salivary gland tumors

Case	Author	Year	Age	Gender	Location	Benign tumour	Malignant tumour
1	Kasthurirengan [42]	2023	61	M	Palatine gland	Canalicular adenoma	Polymorphous adenocarcinoma
2	Kaleem A[41]	2020	63	M	Parotid gland	Warthin tumor	Secretory carcinoma
3	Lu H[40]	2019	NA	F	Parotid gland	Pleomorphic adenoma	Lymphoepithelial carcinoma
4	Lu H[40]	2019	NA	M	Parotid gland	Warthin tumor	Acinic cell carcinoma
5	Lu H[40]	2019	NA	M	Parotid gland	Warthin tumor	Acinic cell carcinoma
6	Lu H[40]	2019	NA	F	Parotid gland	Basal cell adenoma	Mucoepidermoid carcinoma
7	Lu H[40]	2019	NA	F	Parotid gland	Basal cell adenoma	Basal cell adenocarcinoma
8	Lee H[39]	2018	49	M	Parotid gland	Pleomorphic adenoma	Oncocytic carcinoma
9	Ortega M[38]	2017	61	F	Upper lip	Canalicular adenoma	Polymorphous adenocarcinoma
10	Topal O[37]	2016	66	F	Parotid gland and submandibular gland	Pleomorphic adenoma	Lymphoepithelial carcinoma
11	Ochal-ChoinskaA[2]	2015	61	M	Parotid gland	Warthin tumor	Carcinoma ex pleomorphic adenoma
12	Jin J[36]	2011	ND	ND	ND	Pleomorphic adenoma	Lymphoepithelial carcinoma
13	Srivastava S[35]	2009	52	M	Parotid gland	Warthin tumor	Mucoepidermoid carcinoma
14	Roh JL[34]	2007	71	M	Parotid gland	Warthin tumor	Adenocarcinoma
15	Tanaka S[33]	2007	67	M	Parotid gland	Warthin tumor and pleomorphic adenoma	Salivary duct carcinoma
16	Ethunandan M[32]	2006	ND	ND	Parotid gland	Warthin tumor	Adenocarcinoma
17	Ethunandan M[32]	2006	ND	ND	Parotid gland	Warthin tumor	Acinic cell carcinoma
18	Bie´ n S[31]	2006	51	M	Parotid gland	Pleomorphic adenoma	Adenocarcinoma
19	Bie´ n S[31]	2006	66	M	Parotid gland	Pleomorphic adenoma	Adenocarcinoma
20	Bie´ n S[31]	2006	72	F	Parotid gland	Pleomorphic adenoma	Salivary duct carcinoma
21	Yu G-Y[30]	2004	ND	ND	ND	Warthin tumor	Squamous cell carcinoma
22	Zeegregts CJ[29]	2003	ND	ND	ND	Pleomorphic adenoma	Acinic cell carcinoma
23	Shukla M[28]	2003	68	F	Parotid gland	Sebaceous lymphadenoma	Squamous cell carcinoma
24	Fábio R[27]	2003	40	F	Tongue and submandibular gland	Pleomorphic adenoma	Mucoepidermoid carcinoma
25	Curry JL[26]	2002	67	F	Parotid gland	Pleomorphic adenoma	Salivary duct carcinoma
26	Curry JL[26]	2002	51	F	Parotid gland	Warthin tumor	Mucoepidermoid carcinoma
27	Mayorga M[25]	1999	78	F	Parotid gland	Sebaceus lymphadenoma	Acinic cell carcinoma
28	Misselevich I[24]	1997	44	F	Parotid gland	Pleomorphic adenoma	Acinic cell carcinoma
29	Seifert G[23]	1997	73	M	Parotid gland	Warthin tumor	Mucoepidermoid carcinoma
30	Hanada T[22]	1995	71	F	Parotid gland	Myoepithelioma	Adenoid cystic carcinoma
31	Gnepp DR[1]	1989	60	M	Parotid gland	Warthin tumor	Mucoepidermoid carcinoma
32	Gnepp DR[1]	1989	84	M	Parotid gland	Warthin tumor	Acinic cell carcinoma
33	Gnepp DR[1]	1989	56	M	Parotid gland	Warthin tumor	Acinic cell carcinoma
34	Gnepp DR[1]	1989	69	M	Parotid gland	Warthin tumor	Ductal adenocarcinoma
35	Gnepp DR[1]	1989	61	M	Parotid gland	Warthin tumor and pleomorphic adenoma	Mucoepidermoid carcinoma
36	Gnepp DR[1]	1989	66	M	Parotid gland	Warthin tumor	Adenoid cystic carcinoma
37	Janecka IP[21]	1983	45	F	Parotid gland	Pleomorphic adenoma	Mucoepidermoid carcinoma
38	Janecka IP[21]	1983	64	M	Parotid gland	Warthin tumor	Adenocarcinoma
39	Janecka IP[21]	1983	58	M	Parotid gland	Warthin tumor	Mucoepidermoid carcinoma
40	Volmer J[20]	1982	85	F	Parotid gland	Warthin tumor	Squamous cell carcinoma
41	Bab IA[19]	1979	Sixth decade	F	Parotid gland	Sebaceous cell adenoma	Adenoid cystic carcinoma
42	Bab IA[19]	1979	Sixth decade	F	Parotid gland	Oncocytoma	Carcinoma ex pleomorphic adenoma
43	Bird RJ[18]	1979	NA	NA	Parotid gland	Warthin tumor	Acinic cell carcinoma
44	Pontilena N[17]	1979	45	F	Parotid gland	Pleomorphic adenoma	Mucoepidermoid carcinoma
45	Gadient SE[16]	1975	60	M	Parotid gland	Warthin tumor	Mucoepidermoid carcinoma
46	Lumerman H[15]	1975	65	M	Parotid gland	Warthin tumor	Mucoepidermoid carcinoma
47	Iannaccone P[14]	1975	70	F	Parotid gland	Warthin tumor	Mucoepidermoid carcinoma
48	Turnbull[13]	1969	69	M	parotid and submandibular gland	Pleomorphic adenoma	Adenocarcinoma
49	Turnbull[13]	1969	36	F	parotid and submandibular gland	Warthin tumor	Carcinoma ex pleomorphic adenoma
50	Tanaka N[12]	1953	NA	NA	NA	Warthin tumor	Mucoepidermoid carcinoma

NA No Available, ND No Data, F Female, M Male

As indicated in previous reports, the treatment and the prognosis of synchronous multiple tumours of both benign and malignant types are comparable to those of conventional malignant tumors of the same histopathological type. Surgery is regarded as the gold standard for the treatment of oral and maxillofacial tumors. In the case of benign salivary gland tumors and malignant tumors with intermediate-grade malignancy, the most effective approach remains a complete resection of tumor with adequate free surgical margins. In cases involving high-risk malignant tumors, more aggressive treatment strategies may be necessary. Therefore, a multifaceted treatment approach, encompassing radical surgery, facial nerve reconstruction, adjuvant radiotherapy, and other comprehensive treatment modalities, should be considered based on the tumor’s size, nature, and location. In this case, based on the clinical presentation, specialized examination, MRI findings, and the epidemiological features of sublingual and palatal gland tumors, a preliminary diagnosis was made of a malignant sublingual tumor (mucoepidermoid carcinoma or adenoid cystic carcinoma) and a benign palatal tumor (pleomorphic adenoma). However, the possibility that both were malignant (mucoepidermoid carcinoma or adenoid cystic carcinoma) could not be entirely excluded. While preoperative biopsy is generally not recommended for salivary gland tumors, with intraoperative frozen section being the preferred method, an exception was made in this instance. Given its suspected malignancy and extensive involvement of anatomical structures-where the definitive pathology would directly dictate the surgical approach-an incisional biopsy of the sublingual mass was performed preoperatively. The confirmation of an intermediate-grade mucoepidermoid carcinoma then guided the formulation of the definitive surgical plan.

This case of synchronous multiple primary salivary gland tumors not only augments epidemiological knowledge but also provides crucial diagnostic insights for clinicians and pathologists, thereby helping to prevent diagnostic oversights and errors.

Authors’ contributions

Kai Kang and Yahong Wu mainly drafted the manuscript; Wenjuan Liu refined the manuscript; Kang Liu and Tong Sha initiated the project and collected the medical records; all authors have read and approved the final manuscript.

Funding

Not applicable.

Data availability

All data generated or analysed during this study are included in this published article.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent were obtained from patient for publication of this case report and any accompanying images. All authors have approved the manuscript for submission.

Competing interests

The authors declare no competing interests.