Sublingual gland

Accepted Manuscript

Sublingual Gland Patrick J Bradley MBA FRCS PII: DOI: Reference:

S1043-1810(18)30036-8 10.1016/j.otot.2018.06.006 YOTOT 821

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Operative Techniques in Otolaryngology - Head and Neck Surgery

Please cite this article as: Patrick J Bradley MBA FRCS , Sublingual Gland , Operative Techniques in Otolaryngology - Head and Neck Surgery (2018), doi: 10.1016/j.otot.2018.06.006

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ACCEPTED MANUSCRIPT Sublingual Gland Patrick J Bradley, MBA FRCS

Corresponding Author

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Professor Patrick J. Bradley, MBA FRCS 10 Chartwell Grove Mapperley Plains Nottingham NG3 5RD

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United Kingdom [email protected]

Acknowledgment:

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Thanks to Dr Ahmed Zahoor, FRACS, Consultant ORL-HNS, Counties Manukau Health Auckland University Hospitals, New Zealand for the clinical pictures of ranulae.

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ACCEPTED MANUSCRIPT Abstract It is infrequent for surgery to be necessary for the sublingual salivary gland. As such the anatomy of the floor of mouth is not well taught or understood to medical graduates and head and neck surgeons. Three diseases or conditions require surgical management: the ranula, neoplasm and sialolithiasis. In the benign conditions, the lingual nerve and submandibular duct must be identified and preserved to avoid patient morbidity. Malignant salivary gland neoplasms are rare, and hence an inaccurate diagnosis frequently delayed commencement of

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correct treatment. Most cases present at an advanced stage of disease. Surgical excision with a “safe margin” is required, and thus removal of the lingual nerve and submandibular gland are sequelae of the treatment rather than a complication.

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120 words Introduction

The sublingual space is an anatomical area without a fascial lining and is located supero-medial to the mylohyoid muscle and lateral to the genioglossus and geniohyoid muscles in the floor of the oral cavity. The

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contents of the sublingual space include the sublingual gland (SLG); the submandibular duct; the deep portion

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of the submandibular gland; the lingual nerve; and the lingual artery and vein. Ranulas and salivary gland neoplasms, and occasionally sialolithiasis of the sublingual gland or retained stones in the proximal portion of

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the submandibular duct stump are indications for surgery.

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Anatomy

The SLG is located in a submucosal space in the antero-lateral aspect of the floor of the oral cavity. The SLG

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lacks a capsule or fascial sheath and rests in areolar tissue between the mucosa and the mylohyoid muscle. The sublingual space is V-shaped, with the apex pointing anteriorly. Its boundaries are the mucosa of the floor of the mouth superiorly, the mylohyoid muscle inferiorly and the medial surface of the mandible laterally, with the geniohyoid and genioglossus muscles medially. The SLG is shaped like a large tadpole. The head of the tadpole lies superficially in the anterior floor of the mouth, and the tail is variable in length but can runs posterior to contact the submandibular gland as it nudges over the posterior limit of the mylohyoid muscle - the two structures may on occasions be in continuity. The

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ACCEPTED MANUSCRIPT superficial portion of the head of the SLG is oval in form but in depth is wedge shaped lying on the genioglossus muscle medially and the mandible laterally, and extends down to the mylohyoid. The tail extends 1

along the sublingual gutter with the submandibular duct attached to its deep surface . The submandibular duct always lies directly beneath the SLG, attached to it by loose areolar tissue, and continues along the floor of the mouth to empty intraorally just lateral to the fraenulum of the tongue. In the region of the second 2

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molar teeth the lingual nerve runs beneath the submandibular duct then ascends within the tail of the SLG . The head of the SLG is distinct from its tail, with the head being firmly attached to the mucosa resulting in difficult to separate intact because of the multiple penetrating salivary ductules (15 – 30) which drain each of the discrete salivary gland units (ducts of Rivinus) [Figure 1 a and b]. The tail, when present (>65%), is a single discrete secretory unit, which drains by a single duct (Bartholin duct) not attached to the mucosa and can be

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easily dissected . The microanatomy of the SLG and its relationship with the submandibular duct has been 4

investigated and has shown that there are three major anatomical patterns; 1) small ducts from the head open directly onto the floor of the mouth (no tail), 2) small ducts from head, and separate duct from the tail

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which opens into the submandibular duct, and 3) small ducts from the head and a separate duct from the tail that opens independently into the floor of the mouth via a sublingual punctum.

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The sympathetic innervation to the SLG is from the para-vascular nerves along the facial artery; the parasympathetic supply comes from the submandibular ganglion via the lingual nerve (postganglionic fibers

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that arise from the chorda tympani nerve). The arterial supply is the sublingual artery (branch of the lingual artery) and the submental artery (branch of the facial artery). The venous drainage follows the artery. The

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Ranula

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lymphatics of the SLG drain into the submandibular lymph nodes.

The term “ranula” describes a blue, fluctuant, translucent dome shaped swelling on the floor of the mouth, a term derived from the Latin “rana” (frog). Ranulae are pseudocysts (not lined by epithelium) that arise from the mucus fluid of the SLG, and are extravasation mucocoeles that arise from a damaged duct or rupture 3

acinus following obstruction . Ranulae are clinically classified into three types: 1) oral or non-plunging ranulae confined to the floor of the mouth, also termed “simple ranulae”, [Figure 2] 2) cervical or plunging ranula extending from the floor of the mouth, between or through the mylohyoid muscle, manifesting as a mid-line

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ACCEPTED MANUSCRIPT or lateral neck swelling, without an oral component and 3) and those with an oral and a neck or mixed 5

component [Figure 3] . Anomalies of Bartholin duct are reported and it has been proposed that the duct is connected to the submandibular duct more posteriorly in plunging ranulas than in non-plunging ranulae

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The SLG is a spontaneous secretor that produces a continuous flow of mucus even in the absence of nervous stimulation and it has a great resistance to obstruction. In the case of ranulae, a balance is established

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between sublingual secretory activity and the attempts of the body to limit the extravasation by inflammatory fibrosis (foreign body reaction) and the removal of mucus by macrophages. This allows the water and inorganic component to drain away in the lymphatics. Granulation tissue forms fibrous tissue, which restricts the 3

extravasation and sometimes may seal the leak .

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The commonest and most consistent finding in plunging ranulae is a defect of the mylohyoid muscle – almost always in the anterior half of the mylohyoid-mandible attachment. The mass most commonly is centred on the submandibular triangle with the average size of 4 to 10 cm, but can extend superiorly as far as the skull base, 8

and inferiorly to the supraclavicular area, as well as posteriorly and across the midline .

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Ranulae both simple and plunging have been reported at all ages, with most plunging types presenting in the

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second and third decades of life. Bilateral ranulae while rare (< 5%), are well recognised supporting the anatomical weakness theory [Figure 4]. There is a marked preponderance of ranulae in peoples of Asian

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origin, accounting for more than 80% of the published literature. The aetiology of ranulae is unknown, but 9

they have been associated with congenital anatomical variations, trauma and disease .

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Differential Diagnosis

The presentation of a mass in the floor of the mouth should be investigated with the knowledge of its

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embryological development into inflammatory, developmental and neoplastic lesions. Thus mucus retention cysts and ranulae, the cystic group of dermoid, epidermoid and lymphoepithelial are developmental. The possible diagnosis of a thyroglossal cyst, and the neoplasms that include lipoma, salivary gland neoplasms, and 10

benign mesenchymal tumours should also be considered . The plunging ranula type, and more so patients who present without any intra-oral manifestation, tends to present as a painless, recurrent or progressive neck swelling. They present as a submandibular triangle lesion,

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ACCEPTED MANUSCRIPT may mimic a congenital lesion, lymphangioma, haemangioma, an abscess, or a simple cyst. Occasionally a midline submental lesion could be mistaken as a thyroglossal or dermoid cyst. A low threshold for performing fine-needle aspiration cytology (FNAC) will, in the majority of patients, clinch the correct diagnosis. The aspirate will reveal a mucoid content which is positive for amylase four times the normal value, and the protein content 50% that of serum

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Management of ranulae

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Various therapies for ranulae have been proposed and the rate of success ranges from 0% to 100% . The complete removal of the SLG is to be expected to cure both oral and plunging ranulae, since the gland is the source of the ranula

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. Removal of the ranula itself is essentially unnecessary because it consists of

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mucus contained by inflamed granulation tissue, which will eventually disappear. The premise for such a

surgical approach is that a ranula is an extravasation cyst arising from the SLG. They are not epithelial lined cysts, but pseudocysts with a connective tissue wall. If the walls are collapsed they will fuse and the cystic space be eliminated

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. Successful treatment depends upon either the removal of the unit of the SLG from 16

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which the extravasation occurs or the sealing of the leak from the gland .

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Surgical success in the past, by performing partial or incomplete excision of the SLG is achieved by sealing of the source of extravasation by post-operative fibrosis, induced by the trauma of surgery or by the method of 17

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Salivary Neoplasms

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marsupialisation with packing the cavity which is still recommended for the simple ranulas < 2 cm. in size .

Salivary gland neoplasms of the SLG are rare and comprise between 0.5% and 1% of all epithelial salivary

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tumours [Figure 5]. Although rare, mesenchymal and haemato-lymphoid neoplasms have also been reported, usually as case reports. However in clinical practice, the dominant benign neoplasm is the pleomorphic adenoma, and of the malignant lesions adenoid cystic and mucoepidermoid carcinoma make up >90% of this 18

group . The majority of patients are aged between 30 and 60 years, without gender predilection. The majority of patients present with an asymptomatic non-ulcerative swelling located in the floor of the mouth which gradually increases in size. Symptoms suggestive of possible malignancy include pain, swelling in the neck,

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ACCEPTED MANUSCRIPT numbness of the tongue, limited tongue movement, fixity of the mass and oral bleeding associated with 19

mucosal ulceration . All lesions must have the radiologic evaluation as to disease extent, followed by pathologic diagnosis confirmed by aspiration cytology, core needle biopsy or even open biopsy. The malignant sublingual salivary glands are staged for disease according to the TNM staging system similar for the parotid 18

and submandibular salivary gland neoplasms .

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Prognostic determinants of patient’s outcome are similar to those of the other major salivary gland sites. Local presenting factors such as; pain, advanced stage, limited tongue movement, paralysis of the lingual nerve, and positive cervical lymph nodes confer an increased risk of loco-regional recurrence, distant metastasis and mortality at 5 years. The histopathological examination of the excised specimen of a salivary gland neoplasm is

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essential to identify the recognised adverse pathologic prognostic factor;, tumour grade, perineural and /or perivascular invasion, and evaluation the excised margin for close or involved tumour. When these adverse factors are reported then the application of post-operative radiotherapy is indicated to minimise the risk of 20

local recurrence .

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Surgical Approaches Excision of Sublingual Gland:

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Surgery on the floor of the mouth can be exacting as a result of limitations in access. A general anaesthetic with nasal intubation is essential. Identification of the submandibular duct using a probe, stent, and more 1

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recently sialendoscopy is required. The presence of a stent provides a palpable landmark during surgery to aid with dissection and mobilisation of the duct, thus minimising iatrogenic injury and hence post-operative

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duct stenosis and possibly submandibular sialadenitis. The key to stress free surgery is attention to minimising 1

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bleeding .

Infiltration of the surgical field with a lignocaine and epinephrine solution prior to surgery is recommended. Making the mucosal incision should be planned as the tissue is exceedingly thin, friable and very mobile. Raising a flap, usually with scissors, may result in a perforation or tear, resulting in poor wound healing. By using several transfixion sutures, passing across the dorsum of the tongue, and by using a retractor, the floor of mouth mucosa can be stabilised, improving access, and hence facilitating dissection. A curvilinear incision should be sited medially on thicker mucosa overlying the lateral aspect of the tongue which is distant from

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ACCEPTED MANUSCRIPT important submucosal anatomy and local pathology. This incision is best suited to cases where the distal submandibular duct and the sublingual gland are excised because of persistent symptoms, usually pain and/or 21

SLG sialadenitis, following elective removal of the submandibular gland for sialadenitis/sialolithiasis . The use of bipolar cautery aids with minimising bleeding. The incision can be extended anteriorly to incorporate a cuff of mucosa around the sublingual papilla to allow for submandibular duct manipulation if

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considered necessary. Dissection proceeds submucosally from medial to lateral, identifying the submandibular duct and once identified, the SLG can be dissected in a lateral direction from the mylohyoid muscle. The duct is retracted laterally and traced posteriorly identifying the lingual nerve [Figure 6 a and b]. The sublingual artery and vein are identified and ligated on the postero-medial aspect of the sublingual gland proximal to the lingual

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nerve. Should a Bartholin duct be identified, which is separate from the submandibular duct, it should be ligated and divided to prevent local saliva accumulation from the submandibular gland resulting in a 7

“recurrence” of a ranula . The SLG is excised under direct vision, and haemostasis is obtained. Attention should be paid posteriorly, as the SLG may be continuous with the oral portion of the submandibular gland, 1

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and requires ligation and division, avoiding trauma to the submandibular duct . The incision and the sublingual papilla are repositioned and the wound closed with 3/0 or 4/0 resorbable interrupted vicryl sutures.

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Ranula surgery

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When performing ranula surgery, a technique of performing a preparatory procedure of decompressing the oral component, reducing the tension and size, ensures that the ranula can be manipulated during surgery 16

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exploration, reducing the risk of rupture and mucus spillage . This decompression procedure by aspiration should be performed some 3 – 5 days prior to the planned surgery. Saliva is bacteriostatic and the risk of

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infection is minimal. By performing this manoeuvre it is possible with oral (simple) ranula that the offending discrete unit of the sublingual gland can be excised completely. It is not advisable to aspirate at surgery because this produces a persistent leak of saliva from the puncture point throughout the procedure unless the puncture point is ligated. The cyst should not be evacuated completely; otherwise the “capsule” cannot be identified. A vertical or a modified L-shaped incision over the dome of the ranula is adequate, which achieves excellent exposure

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. Separation of the mucosal flap where the ducts of Rivinus are located tether the gland

to the mucosa, and care with mobilisation must be taken to avoid tearing the mucosa, which happens

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ACCEPTED MANUSCRIPT frequently. Manipulation of the cyst requires careful and deliberate local dissection at the margin of the capsule. When the cyst has been freed from the local structures, it will become apparent that it is firmly attached to part of the SLG. At the point of attachment a portion of the gland is excised in continuity of the 16

ranula using cutting diathermy to allow delivery . When excising a plunging ranula exploration of the SLG should be performed, and during surgery the ranula

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can be mobilised. During mobilisation the tract that has herniated through the mylohyoid muscle is identified, or the cyst can extend along the deep lobe of the submandibular gland between the mylohyoid and hyoglossus muscles. If this tract is identified, ligation should be attempted. This “closed cyst” can be aspirated

transcutaneously and a pressure bandage may be applied for a number of days which may aid with rapid

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healing. If this communication tract cannot be ligated, then the cyst sac should have a drain inserted (Penrose) into the cavity intra-orally for several days until the oral wound has healed by a combination of primary or 12

secondary intention . Oral feeding should be withheld for several days to avoid fluids trickling into the sac and that can cause infection.

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Salivary neoplastic surgery

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Should the biopsy of the SLG prove a benign pleomorphic adenoma and the lesion is small and easily mobile then a trans-oral excision may be undertaken, but with the intent to excise the lesion entirely with a “safe18

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margin” and to include the biopsy or incision tract , others recommend that such a tumour mass be excised 23

with the sublingual gland . The local excision may involve excision of a portion of the mylohyoid muscle,

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portion of the submandibular duct, and avoiding injury to the lingual nerve. This surgical approach is more difficult in dentate patients and not infrequently the submandibular duct requires a sialodochoplasty 1

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procedure .

As malignant SLG tumours are most frequently diagnosed at an advanced stage, a radical surgical approach is the preferred primary treatment. This requires a wide exposure, aiming at achieving complete safe margin excision of the primary disease and regional metastasis, relief of presenting symptoms, preservation of local oral function and cosmesis, and initiating any rehabilitation that may be anticipated or result from such 18

treatment .

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ACCEPTED MANUSCRIPT Approaches to excision of these tumors have been described and include the “pull-through technique”, the “visor approach” or a “subcutaneous mandibulotomy approach” but the functional result from a 24

mandibulotomy is better than the pull-through . It has been recommended that a neck dissection should be performed (depending on the presence or absence of lymph node metastasis), with excision of the SLG and surrounding tissues (floor of mouth and lateral aspect of the tongue) with a marginal mandibulectomy (as the periosteum is the lateral border of the SLG). A segmental mandibulectomy is indicated when the tumour

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invades the mandible. The lingual nerve when sacrificed should have frozen section confirmation of being disease free at the proximal stump of resection margin.

With many cases that present with advanced stage disease (T3/T4), the presence of lymph node metastasis is

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reported surprisingly low. Because the neck needs to be opened for access, excision of the submandibular gland, and isolation of donor blood vessels for “plumbing-in” the free flap for reconstruction, it has been recommended that as a minimum in such cases that a selective neck dissection (Levels Ia, Ib, IIa and III) should be undertaken25. A more comprehensive neck dissection must be undertaken should there be clinical or imaged

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evidence of cervical nodal disease.

Small defects can be repaired by use of local mucosa, supplemented by buccal, lingual, naso-labial flap, or

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island platysma flap, more major defects and when a marginal mandibulotomy has been performed than the use

Complications

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of a free flap such as a RFFF or an ALT can be used with the aim of preventing ankyloglossia [Figure 7] 19,20.

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Recurrence: the most common cause of recurrence is incomplete excision of the primary disease , or 7

potentially if the Bartholin duct has not been ligated . Recurrence of ranulas depends on the treatment 27

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including surgery performed and large retrospective series describe some 12 different procedures , the rate varies between the different procedures but consistently the procedure that removes the SLG alone or in 5, 12 - 14

combination with another procedure achieves almost no recurrences

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local recurrence rate is reportedly 15 – 30%, but when it occurs, death results from local disease or distant 18

metastasis .

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ACCEPTED MANUSCRIPT Lingual nerve: Lingual nerve injury during surgery is not unreported, and the consequences of such disability and possibly litigation should be minimised by explanation of the risks by the pre-operative “informed consent 28

process” . Injury may result in neurogenic complaints such as dysaesthesia and allodynia. Pain with trigger 4

points may be temporary or permanent . The lingual nerve lies deep to the SLG, and the lateral side of the tongue. Damage can result from the uncontrolled use of the electrocautery or over manipulation. Temporary

resolution

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paraesthesia can last between 2 and 6 months, and has been reported to last for 2 years with spontaneous

The submandibular duct – If the duct is transected, then the proximal portion of the duct should be replanted into the floor of the mouth. If the segment is too short, the duct should be ligated. Subsequent gland 1

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symptoms are minimal and subside with atrophy of the gland . Stenosis of the duct may result in sialadenitis (due to back pressure or saliva stagnation) and possibly sialolithiasis affecting the submandibular gland in the long term. Subsequent submandibular excision has been reported following duct damage during ranula 11

surgery .

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Haematoma – Haematoma is usually associated with poor control of haemorrhage during surgery. Care needs to be taken when excising the SLG as the sublingual artery lies posterior and deep to the gland, the cut artery

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will retract into the mylohyoid muscle and cause persistent oozing. This results in a poor surgical field, and it’s

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associated with residual SLG being left behind.

Infection – The collection of saliva, ingested food or fluid into the submandibular space has resulted in patients

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being readmitted for drainage of the collection, and antibiotic treatment. The insertion of a drain through the neck, in the few cases that have a large submandibular space cavity, at completion of the oral cavity surgery 11

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may avoid such a complication . Dehiscence of the wound; Not infrequent after ranula surgery, the mucosa is flimsy and frequently torn, but all remaining mucosa should be approximated loosely with interrupted absorbable sutures, to allow free drainage. Secondary healing of the floor of the mouth usually results in 5 – 7 days without any significant permanent ankyloglossia

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Conclusion

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ACCEPTED MANUSCRIPT Surgery of the sublingual salivary gland is seldom necessary, but when indicated, an accurate diagnosis is required and imaging of the region is required to ensure that all events can be anticipated and planned for. An understanding of the pathology being treated, minimising recurrence and avoiding morbidity is essential prior to commencing surgery. In surgery for benign conditions and disease, such as ranula and sialadenitis, identification, avoidance, and minimal trauma to the lingual nerve and submandibular duct will aid with preserving or restoring patients’ recovery and maintaining good quality of life. In patients with malignant

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neoplasms, the surgery is based on surgical oncologic principles with “safe-margin” excision, which is most likely to necessitate excision of the lingual nerve and submandibular gland, as well as necessitation of tissuereplacement procedure to maintain oral functions.

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Words 3,471.

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Figures:

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Figure 1 a and b– Drawing of the sublingual gland

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ACCEPTED MANUSCRIPT Figure 2 – Colour picture of Oral Ranula

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Figure 3 – Colour picture of “Mixed Ranula”

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Figure 4 – Colour picture Bilateral Ranulas “Plunging”

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Figure 5 – Colour picture SLG Adenoid Cystic Carcinoma

Figure 6 a and b – Drawing of elevated posterior end of SLG to illustrate Submandibular Duct, Lingual Nerve as well as Sublingual artery and vein

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Figure 7 – Drawing of the repaired floor of mouth mucosal defect.

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