Can Submandibular Gland be Preserved During Neck Disscetion in Oral Cavity Squamous Cell Carcinoma?

Abstract

Submandibular gland is commonly removed as an integral part of level I neck dissection for oral cavity squamous cell carcinoma. However, it is unclear whether lymph nodes are present within the submandibular gland which may form the basis of lymphatic spread and gland removal. So, this study investigated the incidence of submandibular gland involvement in oral cavity squamous cell carcinoma to determine the possible feasibility of submandibular gland sparing neck dissection. The medical records of 83 patients diagnosed with oral cavity squamous cell carcinoma were reviewed retrospectively to determine frequency of intraglandular lymph nodes in submandibular gland [submandibular gland metastasis] and incidence and mechanism of submandibular gland involvement by oral cavity squamous cell carcinoma. The overall incidence of cervical metastasis was 56.4%, of whom majority had level I metastasis. Submandibular gland involvement via direct invasion from the anatomical proximity of T4a tumors or extra nodal extension from level 1b node was evident in 6 patients. Despite the high incidence of level I metastasis, lymphatic metastases to submandibular gland itself are unlikely based on absence of intraglandular lymph nodes. The results suggest the feasibility of preserving the submandibular gland in early-stage oral cavity carcinoma unless the tumor extends level 1b with extra nodal extension.

Introduction

Globally there has been increasing numbers of oral cancers with the highest rates observed in India, Sri Lanka, Pakistan, Bangladesh, Hungary and France. According to recent GLOBOCON 2021 data in India, lip and oral cavity cancers new cases are ranked as 2^nd with 10.3% incidence and 21.77% prevalence rate [1]. Tobacco chewing, smoking and alcohol are the major preventable attributing factors [2, 3] still responsible for the increasing trend of cases. The standard treatment for oral cavity squamous cell carcinoma (OCSCC) is surgery and adjuvant radiotherapy or chemoradiotherapy if indicated [4]. Neck dissection is an integral part of treatment, in addition to primary tumor surgery for tumor control even in clinically negative neck [5, 6]. Lesions of the oral cavity usually metastasize to levels I, II and III while levels IV and V are rarely involved [7, 8].

The first description of a systematic blocklike removal of the lymphatics of the neck for lymph node metastases was published by Crile in 1906 [9]. He actually attempted a complete removal of the cervical lymphatics, the sternocleidomastoid muscle (SCM), the internal jugular vein (IJV), and all of the fibro fatty and lymphatic tissue of the various triangles of the neck including submandibular gland. Thereafter various modification in neck dissection procedures were done focusing on functional improvement via preserving spinal accessory nerve (SAN), sternocleidomastoid muscle (SCM) & internal jugular vein (IJV) depending upon necessity leading to concept of functional neck dissection. However, submandibular gland (SMG) excision is still usually a standard process to clear all possible lymph nodes in level 1b in any type of neck dissection for oral SCC based on the fact that the SMG is located adjacent to the primary tumor and that there may be possible lymph nodes within the SMG. With the progression of anatomy research and surgical techniques, many authors have confirmed that there are no lymph nodes within the SMG [10–12].

Routine excision of the submandibular gland during level I dissection causes a significant decrease in unstimulated saliva production, leading to xerostomia [13]. Another cause of xerostomia is adjuvant radiotherapy, and it may not be possible to spare the submandibular glands from radiotherapy fields in advanced stage diseases [14]. However, as the submandibular gland does not contain intraglandular lymph nodes, removal of an uninvolved submandibular gland may not always be necessary, particularly in cases of early-stage oral cavity SCC, with the potential benefit of reducing post-operative xerostomia [4]. On the other hand, the oncological safety of preserving the submandibular gland remains a debatable question. Therefore, we aim to investigate the incidence and relevant factors associated with submandibular gland involvement in oral cavity SCC and to discuss the possibility of preserving the submandibular gland from a pathological point of view.

Methodology

We retrospectively reviewed data of oral cavity SCC who underwent surgery with curative intent in the Department of Head and neck oncology at Kidwai memorial institute of oncology (KMIO), Bengaluru, Karnataka, India between January 2021 to August 2021.

The Inclusion criteria was.

• (1) Biopsy proven SCC.

• (2) Complete imaging data (CT, MRI & PET CT) for primary tumors and cervical lymph node.

• (3) Complete data of operative procedure done.

• (4) Postoperative histopathological report available.

The Exclusion criteria was:

• (1) Prior surgery or radiotherapy in the Head and neck region.

• (2) Synchronous second primary or recurrent cancer.

• (3) Detailed medical records not available.

Relevant clinical data related to primary tumor, cervical lymph node size & site esp. submandibular triangle & preoperative imaging were analyzed and staged as per AJCC 8th edition. Operative procedure details related to neck dissection focusing mainly on submandibular triangle lymph node clearance- number, size, fixity to submandibular gland or mandible noted. All patients underwent upfront surgery involving neck dissection (including the resection of submandibular glands in all case). Based on post-operative histopathological report, total number of lymph nodes, pathological positive nodes with or without extra nodal extension [ENE] at submandibular triangle and intra-submandibular gland metastasis were assessed.

Results

A total of 83 OCSCC patients’ data could be retrieved as per inclusion criteria for retrospective analysis. [Table 1], of which 47 were females and 36 were males, with a mean age of 54.27 years (range: 26–79 years). Primary sites were buccal mucosa [51 cases,61.44%], tongue [12 cases, 14.45%], floor of mouth [2 cases, 2.40%], lower alveolus [8 cases, 9.6%], lower lip [2 cases, 2.40%] and retromolar trigone [8 cases, 9.6%], being former as majority.

Table 1.

Patient’s characteristics: [Total number–83]

Male	36
Female	47
Mean age	54.27
Primary site
Buccal Mucosa	51
Tongue	12
Lower lip	2
Retromolar trigone	8
Floor of mouth	2
Lower alveolus	8
Tumor stage–according to Ajcc 8th
cT1	5
cT2	17
cT3	2
cT4a	59
Nodal stage – according to Ajcc 8th
cN0	22
cN1	41
cN2	13
cN3	7
c Ene negative	77
c Ene positive	6
Clinical radiological prominent nodal level
No lymph node found clinically	20
Level 1a	1
Level 1b	41
Level II	18
Level III	3
Level IV	0
Level V	0

The majority patients were of stage T4 [59 cases,71.08%] and N1[41 cases,49.39%], followed by T2 [17 cases, 20.48%], T1 [5 cases, 6.02%%], and T3 [2 cases, 2.40%] and N0 [22 cases,26.50%], N2 [13 cases, 15.66%], N3 [7 cases,8.43%] as per AJCC 8th edition classification. All N3 cases were having clinical signs of extra nodal extension in form of either fixity to underlying structure or ulceration over skin surface. Out of 83 patients, 20 were N0 and 63 were N + as per clinical assessment and in N + necks prominent lymph node level largest being level 1b -submandibular triangle [41 cases,65.07%] followed by level II [18 cases, 28.57%], III [ 3 cases, 4.76%]. There was no clinical regional metastasis to level IV and V found in this study.

All patients underwent upfront surgery including neck dissection followed by adjuvant treatment if needed based on histopathology report. Out of 83 patients, in 76 ipsilateral and 7 bilateral neck were addressed, though majority being modified radical neck dissection [67 cases, 80.70%] on ipsilateral and selective neck dissection level I to III [4 cases,57.14%] on contralateral side. [Table 2].

Table 2.

Neck Dissection Details: [Total Number–83]

Type of neck disscetion done
SOHND	5
ESOHND	8
MRND	67
RND	3
Contralateral neck disscetion
Not done	76
Done	7
SOHND	4
ESOHND	1
MRND	2

According to Postoperative histopathological report [Table 3] in ipsilateral neck dissection cases, there were 36 node negative and 47 node-positive cases. In node positive cases majority were N2 [ 21 cases, 44.68%] followed by N3[ 17 cases,36.17%] and N1[ 9 cases,14.28]. In this study we found that majority of patients were having pathologically T4 [56 cases,67.46%] primary site disease followed by T2 [18 cases, 28.57%], T3 [7 cases, 8.43%], and T1 [2 cases, 2.40%]. Out of all ipsilateral 83 neck dissection specimen Submandibular gland [SMG] metastasis was confirmed in 6 cases, including 2 cases of direct invasion and 4 cases of level I extra nodal extension through the capsule. All 6 cases were stage T4aN3b. Submandibular gland involvement was related to the invasion of the primary lesion or extra nodal extension and the difference is statistically significant [P < 0.05].

Table 3.

Post operative histopathological characteristics: [Total number–83]

Pathological tumor stage–according to ajcc 8th
PT1	2
PT2	18
PT3	7
PT4	56
Nodal stage–according to AJCC 8th
PN0	36
PN1	9
PN2	21
PN3	17
P ENE- No	59
P ENE	24
Submandibular gland free	77
Submandibular gland involved	6

Discussion

For oral cavity squamous cell carcinoma [OCSCC], the recommended treatment option is resection of the primary tumor with ipsilateral or bilateral neck dissection, depending upon tumor size, site, depth of invasion, laterality and cervical lymphadenopathy. Cervical Lymph node metastasis is one of the most important factors that affects the prognosis of oral cancer. so, along with primary tumor resection, nodal metastasis must be addressed through neck dissection to improve the cure rate. At present neck dissection have evolved to limit to the neck dissection with region of the risk of lymph node metastasis and to preserve non lymphatic structures to the greatest extent as possible, such as the spinal accessory nerve [SAN], internal jugular vein [IJV], and sternocleidomastoid muscle [SCM], to reduce the risk of postoperative complications as recent advances in our understanding of the pattern of neck metastasis and surgical techniques improved.

The submandibular gland [SMG] is located in the submandibular triangle along with lymph nodes, which is usually removed as part of the traditional radical neck dissection as first described by Crile in 1906. [9]. After that removal of the submandibular gland [SMG] has been introduced as a standard component of radical, modified radical and selective neck dissections while performing level I dissection. [4] Rouviere divided lymph nodes of submandibular triangle [15] which was further subdivided into six subgroups: preglandular, prevascular, retrovascular, retroglandular, intraglandular and deep by DiNardo. [12] The pre-vascular and retrovascular groups were suggested to be the most and the least commonly involved level Ib nodes respectively. [12, 19] However Sinha and Ng demonstrated an absence of intraglandular lymph nodes in the submandibular gland. [16].

Three potential mechanisms have been postulated for malignant spread to the Sub mandibular gland (1) Hematogenous, which is rare as mentioned by literature review by Vessecchia et al. [17] who identified more than 100 cases of metastasis to the submandibular gland from primary tumors at distant sites like breast, lungs and genitourinary system. (2) Lymphatic and (3) Direct extension from either a primary tumor or by extension from an involved level I lymph node.

Junquera et al. [20] evaluated submandibular gland involvement in patients with primary cancer of the floor of mouth, and documented the peri-glandular (preglandular and retroglandular) metastasis rate as 31.7 per cent, while no submandibular gland involvement was detected. Lim et al. analyzed the tumors emerging from the tongue and floor of mouth and concluded that the overall incidence of perivascular (prevascular and retrovascular) lymph node involvement and recurrences in this area after dissection was very low. [19] So this rarity of submandibular gland metastasis is related to the absence of abundant lymphatic vascular structure and Intra glandular lymphatic network as oppose to the parotid gland. However, excision of the SMG is frequently practiced in oncology patients because of its proximity to the primary lesion and adjacent lymph nodes. [18]

In OCSCC, invasion of the submandibular gland caused by level Ib periglandular nodal metastasis is observed in 0.3 to 1.7% of cases [21]. In the retrospective review by Ebrahim et al., only 8% of 107 neck dissection cases had level Ib involvement, among which only 1 had direct invasion of the submandibular gland. [22] Naidu TK et al. reported that only 2 out of 69 patients with OCSCC had submandibular gland metastasis, which resulted from the direct invasion of the primary tumors. [23] Cheng et al. analyzed 7 cases of submandibular gland metastasis, where 5 cases were caused by direct invasion of primary lesions, 1 case by level Ib nodal invasion, and 1 case by intraglandular nodal involvement. [24]

Liu et al. investigated Submandibular gland from 210 corpses and did not detect any visible lymph nodes in it. [25] In a prospective study by Dhiwakar et al., submandibular glands from 30 samples of neck dissection were sliced into specimens with a thickness of 3 mm, in which no intraglandular nodes or metastatic tumors were detected. [26] so it was supposed that intraglandular nodes might only collect lymph produced by submandibular gland or a very small region, which was based on 2 considerations: 1. For submandibular glands in the submandibular triangle, extracapsular lymphadenitis is much more common than intraglandular lymphadenitis; and 2. Metastasis of oral and maxillofacial cancer to submandibular glands is very rare.

In our study’s submandibular gland metastasis cases, all primary tumors were staged T4 and all regional nodal stages were N3b. No metastasis to submandibular gland was seen in stages T1-T3 or N0-N2.

In the 83 submandibular gland samples we studied, no apparent intraglandular nodes were present. Therefore, the probability of submandibular gland involvement caused by nodal metastasis is low, almost negligible. Due to the low probability of submandibular glandular metastasis in oral cancer, submandibular gland preservation can be considered as oncological safe.

Conclusion

The pathological findings of the present study would suggest that intraglandular lymphatic metastasis of SMG are extremely unlikely which can support the feasibility of preserving the submandibular gland mainly in early-stage oral cavity SCC. However, limitations of our study are the retrospective nature, limited number of included patients, advanced stage patients and absence of patients with submandibular gland sparing neck dissections for comparison. Further study with long-term prospective follow up of large sample size is needed to prove the oncological safety of this approach of sparing submandibular gland in OCSCC on a clinical basis.

Abbreviations

SCC

Squamous Cell Carcinoma

IGLN

Intra Glandular Lymph Node

ENE

Extra Nodal Extension

SND

Selective Neck Dissection

SOHND

Supra Omohyoid Neck Dissection

MRND

Modified Radical Neck Dissection

RND

Radical Neck Dissection

Declarations

Conflict of interest

There is no conflict of interest among authors.