Managing malignant sublingual gland tumors: a single institution experience with 23 patients

Abstract

Background

Due to the relative rarity of malignant sublingual gland tumors, diagnosing and treating them clinically pose challenges. Hence, there’s a need to explore the pathological types, characteristics, treatment methods, and prognosis of primary malignant tumors of the sublingual gland to improve our understanding and management of these rare yet highly malignant conditions.

Methods

This study reviewed cases of primary malignant sublingual gland tumors, analyzing their characteristics. The treatment methods included surgical excision, with additional radiotherapy, or brachytherapy for advanced stages or positive surgical margins. The study also summarized different treatment approaches, including lymph node dissection and soft tissue reconstruction using free flaps such as the anterolateral thigh flap and forearm flap.

Results

We have gathered 23 cases of sublingual gland malignancies treated at the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, from January 2013 to May 2024. The most common pathological types were adenoid cystic carcinoma and mucoepidermoid carcinoma, with rare cases of mucosa-associated lymphoid tissue (MALT) lymphoma and nonspecific salivary gland clear cell carcinoma. Early diagnosis and surgical intervention were crucial for a favorable prognosis. Marginal mandibulectomy was necessary for cases involving the mandible. Patients with positive preoperative lymph node detection required cervical lymph node dissection. Extensive tissue defects in the floor of the mouth were effectively reconstructed with free flaps to prevent oral-mandibular fistula.

Conclusion

Surgical excision remains the preferred treatment for malignant sublingual gland tumors. Early diagnosis and comprehensive surgical management are essential for improving prognosis. The study’s limitations include a small sample size and short follow-up duration, necessitating further research with larger clinical samples to confirm these findings.

Background

Malignant salivary gland tumors are prevalent malignancies within the oral and maxillofacial region, predominantly occurring in the parotid gland, submandibular gland, and minor salivary glands. The incidence of malignancy varies across these glands, with 15–32% in the parotid gland, 41–45% in the submandibular gland, and 70–90% in the sublingual gland [1]. While tumors in the sublingual gland are relatively rare, they are predominantly malignant, unlike those in the parotid and submandibular glands, which are often benign [2]. Early-stage malignant sublingual gland tumors typically manifest as painless masses, making them difficult to detect. By the time symptoms such as pain and numbness arise, the tumors are often in advanced stages [3]. Effective diagnosis and treatment plans tailored to the pathological types and stages of malignant sublingual gland tumors are crucial for patient prognosis. However, due to their low incidence, clinicians have limited experience with these tumors, leading to challenges in diagnosis and treatment [4]. Upon reviewing the literature on malignant sublingual gland tumors, we found that due to the rarity of this condition, previous studies have generally involved small patient samples. Moreover, due to the small sample size, previous study usually focused on one or a few aspects (such as pathological types or prognosis) of this disease. Literature reports indicate that malignant sublingual gland tumors are predominantly adenoid cystic carcinoma (ACC), with the cribriform subtype being the most common, followed by mucoepidermoid carcinoma (MC). The literature suggests that the treatment for ACC typically requires surgery combined with postoperative radiotherapy (PORT) [5, 6]. This study retrospectively analyzes the clinical data of 23 cases of malignant sublingual gland tumors treated at the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, from January 2013 to May 2024, making it one of the larger studies on this topic. To provide a comprehensive understanding of the characteristics, we elucidated the clinical characteristics, treatment methods, and outcomes of patients with sublingual gland malignancies, providing valuable insights for their clinical diagnosis and treatment. We believe that these findings will serve as an important reference for understanding the treatment and prognosis of various types of malignant sublingual gland tumors in clinical practice.

Methods

Study design and population

This retrospective study was approved by the Ethics Review Committee of the School and Hospital of Stomatology, Wuhan University (WDKQ2024-B26). Given its retrospective nature, informed consent was not required. The study included 23 patients diagnosed with malignant sublingual gland tumors who were admitted to and underwent surgical treatment at the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, between January 2013 and May 2024. Pathological confirmation of all cases as malignant tumors originating from the sublingual gland was performed by the Oral Histopathology Department, School and Hospital of Stomatology, Wuhan University. The schematic representation in Fig. 1 illustrates the methodology employed for case identification and selection. The clinical manifestations, staging, pathological types, and treatment methods of the 23 patients were retrospectively analyzed. The characteristics of these individuals are presented in Table 1.

Fig. 1

Flow diagram of case search and inclusion and exclusion criteria

Results

General information

Among the 23 patients, 9 were male (39.1%) and 14 were female (60.9%), resulting in a male-to-female ratio of 0.64:1. Ages ranged from 31 to 76 years, with an average age of 57.5 years. Two patients (8.7%) were under 40 years old, 10 patients (43.5%) were between 40 and 60 years old, and 11 patients (47.8%) were over 60 years old.

Clinical manifestations

Of the 23 patients, 12 presented with a mass in the sublingual area accompanied by tenderness. Three had tenderness and tongue numbness, one had tongue numbness alone, and the remaining 7 presented with a painless mass in the sublingual area.

Clinical staging

According to the 8th edition of the AJCC Cancer Staging Manual, the distribution of clinical stages among the 23 patients was as follows: 1 patient in stage I, 14 in stage II, 6 in stage III, 2 in stage IV.

Pathological types

Based on the World Health Organization (WHO) histological classification of salivary gland tumors, the pathological types among the 23 patients were as follows: 17 patients (73.9%) had adenoid cystic carcinoma(ACC), the most common type, 7 patients were diagnosed with the cribriform-tubular pattern, while 3 exhibited the cribriform pattern (Fig. 2A). The remaining 6 cases included 3 mucoepidermoid carcinomas (MC). All three cases of mucoepidermoid carcinoma (MC) were classified as well-differentiated (Fig. 2B), 1 nonspecific salivary clear cell carcinoma (Fig. 2C), 1 mucosa-associated lymphoid tissue (MALT) lymphoma (Fig. 2D), and 1 biphasic carcinoma (epithelial-myoepithelial carcinoma combined with adenoid cystic carcinoma) (Fig. 2E, F).

Table 1 Demographics and clinical characteristics of patients with malignant sublingual tumors in the salivary gland

Fig. 2

Images of representative cases diagnosed as various pathological types of primary malignant sublingual gland tumors. A, Adenoid cystic carcinoma. B, Mucoepidermoid carcinomas. C, Nonspecific salivary clear cell carcinoma. D, Mucosa-associated lymphoid tissue (MALT) lymphoma. E-F, Biphasic carcinoma (epithelial-myoepithelial carcinoma combined with adenoid cystic carcinoma)

Imaging characteristics

High-density lesion or soft tissue mass are typically observed in the floor of the mouth and sublingual area. Both CT and MRI are useful for diagnosing primary malignant sublingual gland tumors, offering representative imaging manifestations as follows. Patient #5: CT Plain Scan: A roughly irregular soft tissue mass measuring approximately 5.5 cm x 3.1 cm x 3.1 cm is visible in the left submandibular region. The mass has indistinct borders and an uneven texture (Fig. 3A). Enhanced CT scan shows evident heterogeneous enhancement in the bilateral temporal, parapharyngeal, and submandibular gap structures (Fig. 3B). Patient #22: MRI Scan: A soft tissue mass measuring approximately 2.1 cm x 5.3 cm x 4.3 cm is visible on the right side of the floor of the mouth. The mass has clear borders and an uneven texture. It shows uneven high signal on T1WI, T2WI, and T2WI/STIR sequences. There is uneven enhancement on T1WI/WFI (Fig. 3C, D). For tumors with a large size, the tumors may extend through the submandibular region. Soft Tissue Window (CT scan): A soft tissue mass measuring approximately 3.2 cm x 6.0 cm x 3.9 cm is visible extending from the right floor of the mouth to the right submandibular region. The mass has unclear borders and exhibits moderate uneven enhancement on the enhanced scan. There is grid-like vascular enhancement at the lesion’s edge, causing compression and downward displacement of the right inferior genioglossus muscle (Fig. 3E-H).

Fig. 3

Imaging features of primary malignant sublingual gland tumors. A, B: CT plain and enhanced scan images of primary malignant sublingual gland tumors. C, D: MRI scan images of primary malignant sublingual gland tumors. E-H: CT scan images of large tumors extending through the submandibular region

Treatment

All 23 patients underwent extended resection of the malignant sublingual gland tumor (Table 2). Among them, 11 patients (47.8%) underwent neck lymph node dissection, 10 patients (10/17) with ACC and 1 patient with MC (1/3) underwent lymph node dissection. 10 patients had I-III level lymph node dissection, while one patient underwent I-V level lymph node dissection, with 3 showing lymph node metastasis in postoperative pathology (all of them are diagnosed as adenoid cystic carcinoma). The incidence of neck metastasis in patients with ACC and MC in present study are 30% (3/10) and 0% (0/1) respectively. The defects after tumor resection in 11 patients were directly sutured without a flap (Fig. 4A-D). Twelve patients underwent simultaneous soft tissue flap reconstruction, with 10 receiving free flap reconstruction (5 anterolateral thigh flaps and 5 forearm flaps) and 2 receiving pedicled flap reconstruction (1 submental island flap and 1 platysma flap); all flaps survived (Fig. 4E-H). Six patients underwent simultaneous marginal mandibulectomy. Among the 18 patients followed up postoperatively, 7 received adjuvant therapy (5 radiotherapy, 1 chemotherapy, and 1 implantation of I¹²⁵ radioactive seeds) (Fig. 5). There were no complications noted after surgery.

Fig. 4

Surgical procedure of patients with primary malignant sublingual gland tumors. A-D, A 65 years old female patient with adenoid cystic carcinoma underwent surgery, and the defect after tumor resection in 11 patients were directly sutured without the use of flap. E-H, A 55 years old male patient with mucoepidermoid carcinomas underwent repair of post-tumor resection defects using anterolateral thigh flap

Table 2 The summary of the treatment of 23 patients with primary malignant sublingual gland tumors

Fig. 5

A 66 years old female patient with adenoid cystic carcinoma underwent implantation of I¹²⁵ radioactive seeds after surgery. A, The CT image of the tumor (red arrow) before surgery. B, The CT image post-surgery. C, The virtual design of implantation of I¹²⁵ radioactive seeds. The CT image before (D) and 3 months after (E) implantation of I¹²⁵ radioactive seeds

Prognosis

Among the 23 patients, 5 were lost to follow-up. The remaining 18 had follow-up periods ranging from 1 to 108 months. Among these 18 patients, 1 died from non-tumor related causes (coronary heart disease), 1 (with adenoid cystic carcinoma) experienced local recurrence within six months postoperatively and underwent lesion extensive resection and anterolateral thigh flap reconstruction at another hospital, and the remaining 16 patients had no recurrence or metastasis during the follow-up period.

Discussion

Preoperative diagnosis and treatment

Early-stage malignant sublingual gland tumors often present as painless masses and are relatively hidden, making them difficult to detect and prone to misdiagnosis or delayed diagnosis. Adenoid cystic carcinoma, the most common type, is characterized by perineural invasion. When these tumors invade the lingual nerve, patients experience numbness in the tongue and floor of the mouth, which aids in clinical diagnosis; but by then, the tumors are often in advanced stages [1]. In this study, three patients diagnosed with epithelial-myoepithelial carcinoma combined with adenoid cystic carcinoma, MALT lymphoma, and nonspecific salivary clear cell carcinoma showed no significant preoperative clinical symptoms. Preoperative imaging, such as CT, is useful for determining tumor involvement with the adjacent structures like the mandible, while MRI provides better visualization of surrounding soft tissues. Intraoperative frozen section or postoperative pathology is the primary diagnostic method for sublingual gland tumors and is widely used for intraoperative and postoperative confirmation [4].

The current diagnostic criteria for malignant sublingual gland tumors include: (a) History and physical examination revealing a primary tumor in the sublingual area; (b) CT or MRI indicating a tumor originating from the sublingual gland within the boundaries of the mylohyoid muscle to the lingual frenulum; (c) Surgical findings of a tumor occupying the sublingual area, replacing part or all of the gland; (d) Histopathological examination confirming tumor origin in the sublingual gland or replacement of sublingual gland parenchyma, excluding tumors originating from minor salivary glands in the floor of the mouth and squamous cell carcinoma; (e) Intraoperative frozen section examination to confirm diagnosis and determine surgical margins [1]. All patients in this study met these diagnostic criteria for malignant sublingual gland tumors.

Pathological types and characteristics

In salivary gland tumors, the proportion of malignant tumors in the parotid gland, submandibular gland, and sublingual gland is 15–32%, 41–45%, and 70–90%, respectively. Primary malignant tumors of the sublingual gland are rare and most commonly occur in patients aged 30–60 years, with a higher incidence in females [1]. Adenoid cystic carcinoma and mucoepidermoid carcinoma are the most common pathological types of malignant sublingual gland tumors. In this study, 17 cases were adenoid cystic carcinoma, consistent with other reports. The typical pathological feature of adenoid cystic carcinoma is the arrangement of cancer cells in cord-like structures that interconnect, forming round, oval, or irregular epithelial clusters containing mucus, hyaline collagen fibers, and hyaline-like connective tissue [7]. Three cases were mucoepidermoid carcinoma, which has a lower malignancy, fewer lymphatic metastases, and a better prognosis. Postoperative radiotherapy can reduce the recurrence rate and improve survival [8]. One case was a sublingual gland MALT lymphoma, a type of extranodal marginal zone B-cell lymphoma. MALT lymphoma has the second-highest incidence rate among non-Hodgkin lymphomas (7–8%), following diffuse large B-cell and follicular lymphomas. It is also the most common indolent lymphoma in the Chinese population. MALT lymphoma most frequently occurs in the stomach, head-neck, lungs, skin, and intestines, with the parotid gland, palatal glands, and submandibular gland being the most common sites in the head and neck region. The proportion of occurrences in the sublingual gland is only 5%, and related reports are very rare [9]. Historically, localized therapy for early-stage MALT lymphoma has consistently achieved favorable outcomes, leading to a decreased consideration of chemotherapy and immunotherapy as initial treatment options for these patients. Recent advancements in our understanding of MALT lymphoma biology have expanded the potential for systemic therapies, now extending to localized disease. Given the indolent nature of MALT lymphoma and the high remission rates associated with chemotherapy, contemporary treatment strategies focus on minimizing side effects by investigating “chemotherapy-sparing” options, such as immune-modulating antibiotics like clarithromycin. In light of the evolving research landscape, the inclusion of MALT lymphoma patients in well-designed clinical trials is highly recommended. These trials are essential for establishing the efficacy of chemoimmunotherapy and assessing the role of systemic therapy in localized disease, ultimately paving the way for the development of more precise and effective treatment options tailored to MALT lymphoma patients [10, 11]. One case was nonspecific salivary gland clear cell carcinoma, including adenogenic, odontogenic, and metastatic types, commonly found in the kidneys and ovaries, and rarely in the head and neck region. In the head and neck region, it most commonly occurs in the soft palate, lips, and minor salivary glands, with very rare occurrences in the sublingual gland [12]. One case was a biphasic carcinoma: epithelial-myoepithelial carcinoma and adenoid cystic carcinoma, characterized by the presence of two or more histological features in the malignant tumor cells, which is relatively rare among oral malignant tumors.

Pathological types and prognosis

Different pathological types of primary malignant sublingual gland tumors exhibit significantly different prognoses. Studies have reported that the 3-, 5-, and 10-year survival rates of mucoepidermoid carcinoma are higher than those of adenoid cystic carcinoma [13]. The lower survival rate of adenoid cystic carcinoma is primarily due to its tendency for distant metastasis, with the lungs being the most common site. The incidence of distant metastasis for adenoid cystic carcinoma ranges from 5.5 to 33.3% [14, 15].

Treatment methods and efficacy

The primary treatment for malignant sublingual gland tumors is thorough resection of the primary lesion. The surgical method depends on the tumor size, depth of invasion, stage, and histological type of the primary tumor [16, 17]. Selecting the appropriate surgical method is crucial for improving treatment outcomes and reducing postoperative recurrence and metastasis.

Early malignant tumors with a diameter of less than 2 cm and confined to the floor of the mouth can be managed with lesion extensive resection. The ipsilateral submandibular gland must be removed due to the communication between the sublingual gland duct and the submandibular gland duct. For malignant tumors larger than 2 cm in diameter, more extensive resection is necessary, particularly for the highly invasive adenoid cystic carcinoma. When adenoid cystic carcinoma is diagnosed intraoperatively, it is generally recommended to resect the lingual nerve and send it for intraoperative frozen section examination. If the result is positive, the nerve should be further excised until a safe margin is achieved. If a negative margin cannot be achieved, postoperative radiotherapy is required. The hypoglossal nerve, which controls tongue movement and affects functions such as breathing, speech, and swallowing, should not be resected unless clinical symptoms such as tongue numbness or movement disorders are present.

Patients with malignant sublingual gland tumors have a low likelihood of lymph node metastasis. For patients with positive cervical lymph nodes detected preoperatively, cervical lymph node dissection is required. Since the treatment guideline recommends a prophylactic neck dissection for high-grade or T3-4 major salivary gland tumors [17, 18]. For late-stage or highly malignant tumors, lesion extensive resection of the primary lesion combined with cervical lymph node dissection and postoperative radiotherapy (or with chemotherapy) is recommended [3]. In this study, 11 patients underwent cervical lymph node dissection, with 3 cases of postoperative lymph node metastasis. And the areas of lymph node metastasis postoperatively corresponded to the regions of enlarged cervical lymph nodes preoperatively. For patients with nerve invasion (positive margins) or cervical lymph node metastasis, postoperative radiotherapy or interstitial implantation of I¹²⁵ radioactive seeds is recommended [4].

For those with adhesion to the cortical bone of the mandible or invasion of the periosteum, marginal mandibulectomy is required. Reconstructing the floor of the mouth after marginal mandibulectomy is a major challenge for clinicians. Currently, free flaps (anterolateral thigh flap and forearm flap) and pedicled flaps (platysma flap and submental island flap) are used to ensure the postoperative function of the tongue and the floor of the mouth [19]. In this study, 5 cases were reconstructed with anterolateral thigh flaps, 5 cases with forearm flaps, 1 case with platysma flap, and 1 case with submental island flap. One patient, due to tumor invasion of surrounding soft tissue, underwent I¹²⁵ seed implantation post resection. For patients diagnosed with malignant sublingual gland tumors, due to anatomical factors, such as the obstruction of the mandible, brachytherapy sources can be precisely placed at the tumor site, minimizing radiation exposure to the mandible while enabling high-dose localized radiation therapy for sublingual gland tumors. This precision reduces the risk of delivering an insufficient radiation dose to the entire tumor due to patient movement, and it lowers the risk of damage to surrounding healthy tissues and the occurrence of mandibular osteomyelitis. Consequently, this increases the likelihood of effectively treating the tumor while preserving organ function [20]. However, brachytherapy is primarily used in the tumor bed or surgical area after tumor resection and is not suitable for the radiotherapy of cervical lymph nodes, which are better managed with standard external radiation therapy. In our hospital, both brachytherapy and standard external radiation therapy are viable options for patients diagnosed with sublingual salivary gland malignancies. Brachytherapy is generally employed for the primary tumor site when lymph nodes do not require treatment, while standard external radiation therapy is used when there is cervical lymph node metastasis.

The choice of flap for floor of the mouth reconstruction depends on the extent of the defect. For extensive floor of the mouth tissue defects or marginal mandibulectomy patients, the anterolateral thigh free flap is preferred due to its sufficient size and vascular pedicle length matching cervical vessels, facilitating microvascular anastomosis. For smaller defects, the forearm flap or the thinned anterolateral thigh flap can be used. The forearm flap is thinner, providing better repair results for cases not involving muscle defects. With advances in medical technology, the clinical application of thinning techniques for the anterolateral thigh flap has expanded its use, reduced forearm and thigh trauma and improving the aesthetic appearance of exposed forearm areas. Choosing the appropriate recipient vessels is key to the success of free flap transplantation. Common recipient arteries include the superior thyroid artery and facial artery, and recipient veins include the anterior facial vein, external jugular vein, and internal jugular vein branches. For patients unsuitable for free flap transplantation due to their overall condition, adjacent pedicled flaps such as platysma flap, submental island flap or facial artery myomucosal flap can be used for floor of the mouth reconstruction, minimizing trauma [21, 22].For patients with mandibular bone destruction, a segmental mandibulectomy is necessary. To restore mandibular continuity and minimize aesthetic impact, reconstruction of the mandibular defect can be achieved using a deep circumflex iliac artery free flap or fibular free flap [5].

Conclusion

Surgical excision remains the primary treatment modality for malignant sublingual gland tumors. Early diagnosis and prompt surgical intervention are essential to ensure a favorable prognosis. The surgical approach should include a complete resection of the anterior floor of the mouth. In cases where there is adhesion to the cortical bone or invasion of the periosteum of the mandible, marginal mandibulectomy becomes necessary. Patients with negative lymph node findings preoperatively do not necessitate cervical lymph node dissection, while those with positive lymph nodes require this procedure. For extensive tissue defects in the floor of the mouth, simultaneous soft tissue reconstruction is critical to prevent the formation of oral-mandibular fistulas. Commonly utilized free flaps for this purpose include the anterolateral thigh flap and the forearm flap. Radiotherapy, chemotherapy, or brachytherapy (I¹²⁵ radioactive seed implantation) is generally recommended for patients with advanced clinical stages, high malignancy, or positive surgical margins. The limitations of this study include a small sample size and a relatively short follow-up duration. Additionally, the surgical treatment regimens for patients across different clinical stages did not demonstrate significant differences in survival outcomes. Future research should focus on larger clinical studies to further clarify these issues.