DIAGNOSIS AND MANAGEMENT

1. DIAGNOSIS AND MANAGEMENT SALIVARY GLAND PATHOLOGY

2. Salivary gland pathology, he guarantees you will see this in your practice. We will talk on benign as well as malignant disease and management.

3. There are 6 major salivary glands; there are 6 because they are paired. • The parotid gland is the largest of all the salivary glands. • It is intimately associated with the 7th cranial nerve, the nerve of facial expression. • It is interesting to note that CN 7 effects all 3 glands • The submandibular gland is in the floor of the mouth. It is not uncommonly associated with sialolith (or salivary stone) formation. • The sublingual gland is that gland that is in the floor of the mouth and is quite superficial. It is most commonly associated with the pathologic entity, the ranula.

4. Much more numerous than the major glands, they approach almost 1000 • All glands will secrete saliva. The composition of the saliva is different relative to the gland.

5. DISTRIBUTION OF MINOR SALIVARY GLANDS • Palate 60% • Tongue 10% • Lips 10% • Cheeks 10% • Retromolar 10% • We see that in most cases the palatal minor salivary glands are the most numerous. You will see most of the salivary gland formations that may be malignant, or benign, have a palatal presentation. • You can see the other glands are distributed in the tongue, lips, cheek, and retromolar area. • So in terms of location one will see a palatal presentation with minor salivary gland mass formation.

6. TONGUE GLANDS(LINGUAL) YOU WILL SEE THIS AGAIN • Inferior apical—glands of Blandin Nuhn • These are mucous secreting glands • Taste buds—vonEbner’s glands • These are serous secreting glands • THIS IS ON BOARDS • Posterior lubricating • Essentially as it relates to secretion, the types of secretion are mucous, serous, or mixed.

7. The basic cell located in all glands is the secretory cell referred to as the acinus (plural acini) • Now, in embryology the major glands preceed the formation of the minor glands. One will see the major glands starts earlier than the minor glands.

8. PAROTID GLAND • Mainly serous; largest of all major glands • Largest of all salivary glands • The duct is referred to as STENSEN’S DUCT, length of 6cm, diam. of 1-3mm • This in areas of trauma is the most common salivary gland duct to be cut from a laceration • If the duct is cut is must be repaired, if it is not it will form a sialocele • The duct is about 60 mm in length and has diameter of 1-3 mm • The duct has an excretory papilla right in the area of the maxillary first molar • 3 major structures pass through substance of gland • Facial nerve • Retromandibular vein • External carotid artery

9. Parotid Gland • Notes on those Structures: • The facial nerve is situated between the two lobes of the parotid gland. Those two lobes are the superficial and deep lobes. Of course, a risk of a partoidectomy is facial nerve paralysis. • The facial nerve can be affected secondary to a viral infection. Typically the patient’s face won’t move. This is referred to as Bell’s Palsy. • The retromadibular vein descends into the neck to become the external jugular vein. • Thickening in gland capsule is the stylomandibular ligament • The parotid gland is covered by fascia. The name of this fascia is the partidomasseteric fascia. • This fascia is also associated with the muscles of facial expression. Therefore, a face lift is associated with tightening of the fascia. • There is a thickening of the fascia referred to as the stylomandibular ligament (it forms a gland capsule around the parotid). We referred to that ligament when we talked about the ligaments associated with the TMJ. • 25 % of daily salivary production (serous salivary secretion)

10. PAROTID GLAND • Located on the face and is palpable between the mandibular ramus and mastoid process • Lateral surface covered by skin and dermis, thus vulnerable to injury with lacerations • This is vulnerable to injury with facial trauma • If the duct is injured it must be reapproximated • Described as having superficial and deep lobes, the plane between is defined by the facial nerve • When patients have a tumor of the parotid gland, most commonly it is benign

11. When you look at the parotid gland and duct. Typically superiorly to the duct are the vessels. • The retromandibular vein is right behind the tail of the parotid gland. • The duct is most vulnerable to injury in an area from the lateral canthus of the eye to the auricular cartilage. • So one would suspect injury if you have a laceration to the face.

12. INNERVATION OF PAROTID GLAND • Innervation to the gland is provided by CN 7. You will see sensation is provided by the auriculotemporal nerve. The 7th cranial nerve has parasympathetic innervations. It is the parasympathetic innervation that is responsible for salivary secretion. • There is a ganglion that is associated with the parotid anatomy. The name of that parasympathetic ganglion is the otic ganglion.

13. SUBMANDIBULAR GLAND • 2nd largest of major saliv. glands • Mixed mucous/serous • Located in submandibular triangle, with the lingual & hypoglossal nn. in intimate contact; fed by lingual and facial arteries • The submandibular triangle is composed of the anterior and posterior bellies of the digastric muscle and the ramus and body of the mandible • Nerves in intimate contact with the submandibular gland: lingual nerve and hypoglossal nerve. • The lingual nerve is a branch of the 3rd division of the trigeminal nerve. The hypoglossal nerve is CN 12. • The third nerve, while not involved with the submandibular gland, must be bypassed when getting to the gland is the marginal mandibular branch of the 7th cranial nerve. • The two arteries associatd with the submandibular gland, and in its removal must be tied off, are the: lingual artery and the facial artery

14. Submandibular Gland • Duct: Wharton’s duct, length of 5cm and diam. Of 2-4mm • Slightly shorter than Stenson’s Duct (50 mm) • When one looks at a description of Wharton’s duct, you will see that they refer to it as having a torturous anatomy, meaning it has multiple turns and curves. The reason that is important is because one will see stasis of the submandibular salivary secretions. This stasis of secretions is why we see a higher prevalence of stones in the submandibular architecture. • 70% of daily salivary production • The submandibular gland is relative important because 70% of salivary production is produced by the two submandibular glands. • One would see more problematic xerostomia with removal of the submandibular gland than the parotid gland.

15. SUBMANDIBULAR GLAND • Fills major portion of the digastric or submandibular triangle • 2 portions: superficial lobe lying superficial to the mylohyoid and a deep lobe which wraps around the posterior border of the mylohyoid • The muscle that divides the submandibular gland into two lobes is the mylohyoid muscle • There is another salivary gland that sits above the submandibular gland and shares part of its excretory duct system, that is the sublingual gland • The mylohyoid muscle is important because if you get a ranula of the sublingual gland, it can penetrate the mylohyoid muscle. If it does we refer to that as a plunging ranula.

16. SUBMANDIBULAR AND SUBLINGUAL GLAND INNERVATION • They both have parasympathetic innervations. This is provided by the submandibular ganglion. In addition, you have innervation from the chorda tympani. This of course is responsible for taste, but it also, with food in your mouth, is part of the gustatory stimulus.

17. SUBLINGUAL GLAND • Smallest of major saliv. glands • Lies in the submucosal plane in the anterior floor of the mouth • Mainly mucous secreting • The acinar ducts called Bartholin’s ducts and coalesce to form the ducts of Rivinus • 3-4% of daily salivary production • With removal of the gland you only lose 3-4% of daily salivary production so xerostomia is not a primary clinical component of removal • The sublingual and submandibular glands have excretory ducts that coalesce. In removal of the sublingual gland you must make sure that you do not tie off the duct to the submandibular gland. If you do that you will then blow out the submandibular gland

18. EMBRYOLOGY • Parotid gland is first to make appearance at the 6th gestational week • Sumandibular gland first appears at end of the 6th gestational week • Sublingual gland develops at the 8th gestational week • Of the glands the parotid gland is the first to appear. Followed by the submandibular gland and then the sublingual gland.

19. SALIVA • 500-1500 cc/day or about 1ml/min however salivary flow decreases after age 20; max. rate is 1 mL/min/gram of glandular tissue • You produce up to 1.5 liters of saliva a day. • Salivary production peaks in early adulthood and decreases after that • Remember, with radiation you decrease the rate of salivary flow • Anytime you have an increase in xerostomia you have an increase of cervical caries • FUNCTIONS: • a) Lubrication for food bolus, removal of food debris (concept of xerostomia and caries) • b) Antimicrobial: sIgA, lactoferrin, lactoperoxidase, mucins, histatins • All of these function keep the bacterial count down • How many bacterial species are there in the mouth? • 264

20. SALIVARY FUNCTIONS CON’T • DIGESTIVE: amylase, lipase, proteases, gustin, mucins • REMINERALIZATION: Ca++, phosphate,statherin,secreted saliv. Fl • Saliva is important because that is where the fluoride we take systemically is secreted • TASTE: for a substance to be tasted, it must be in aqueous solution; fluid seal for suckling and sucking • One thing saliva is most important for is taste. One of the primary complaints of patients who undergo head and neck radiation, is that they can’t taste their food. • In addition, in the pediatric or infant population xerostomia is particularly problematic because they cannot suckle • MUCOSAL INTEGRITY • Finally, it is important for mucosal integrity. You will see significant abrasions in patients who have xerostomia

21. You will see in addition that patients who have xerostomia have a propensity to have fungal infections in their mouth. The most common fungus is Candidia.

22. You can see that in terms of flow rate the parotid gland when stimulated gives just a little bit more flow than the submn gland. • You also can see that there are things within the saliva, inorganic and organic analytes. It is interesting to note that you can see stuff like sodium, potassium, chloride, and bicarb in saliva. • The largest amount of substance that one sees in saliva is proteinaceous.

23. HYPERSECRETION ASSOCIATIONS • INFLAMMATORY: Stomatitis, Rabies • Rabies give a significcant amount of hypersecretion • ENDOCRINE: Pregnancy, Graves disease • Pregnant patients have a relatively increased salivary flow, as do patients with Grave’s disease (hyperthryoidism) • NEUROPSYCHIATRIC: Epilepsy, Cerebral palsy, Hysteria • He’s not sure if you have a relative increase in secretions or a problem with maintaining saliva within the mouth with Cerebral Palsy. CP has a problem with muscle coordination. • One thing parents will ask him to do with CP patients is to take out the submandibular gland. He refuses to do that because we can use medication to decrease salivary flow instead. This is also seen with Down’s Syndrome. • Hysteria will cause an increased salivary flow. The treatment for hysteria is antipsychotic medication and that causes xerostomia. • DRUGS: Mercury, Iodine, Pilocarpine

24. XEROSTOMIA • This is more of a problem • LOCAL: Irradiation, chronic sialoadenitis, interruption of chorda tympani, surgery • These include head and neck radiation, chronic sialoadenitis (inflammation of the gland), patients who have interruption of the chorda tympani • One may see that with surgery in the submandibular triangle and the mastoid process for mastoiditis. • SYSTEMIC: Sjogren’s, diabetes, dehydration,debilitation, mental stress, infection, anemia • There are systemic diseases that may be associated with xerostomia. The one that comes to mind is Sjogren’s syndrome. These also include Diabetes, dehydration, debilitation (poorly fit, homeless), mental stress. He has infection listed, the concept there being infection with temperature elevation. And the last one is anemia.

25. Xerostomia • DRUGS:diuretics, antihypertensives, antiemetics, antispasmodics, anticonvulsants, psychotropics • We now see though that there are a lot of cases that are produced by pharmacology. When thing you should ask if a patient complains of dry mouth is if they are diuretic therapy. The diuretic that produces xerostomia is purocimide (Lazis) • The most common antiemetic medication that causes xerostomia is the scopolamine patches. • One of the biggest areas of patient medication that you will see has to do with the control of GURD. • The antispasmodics he is referring to is Reglen, it increases peristalasis. • Antipsychotics not uncommonly are phenothiazines, the most common being thorazine

26. IRRADIATION • 50% of function lost after only 1000cGy (1 week of radiation) and conventional radiotherapy is 6-7K cGY. This radiation dose causes 80% salivary dysfunction. • Most of the time if you need radiation to the head and neck you will get about 7000 Rads. This typically lasts about 6 weeks. You usually get 1000 Rads/week. • 50% of salivary gland function is lost after only 1000 cGy. So if you complete the whole radiation dose you lose about 80% of your salivary gland function. • Damage is to the acinar parenchyma • Radiation actually damages the secretory cells • So what would you do if you had a patient who had undergone radiation for SCC of the oral cavity and he is complaining of dry mouth, you tell that patient he needs to carry water with him at all times. In addition, there are also saliva substitutes. There are multiple different types of the market. There has been an attempt to add fluoride to saliva substitutes. This didn’t work. It was trying to prevent cervical caries, but the patient ended up getting fluorosis from too much fluoride in the body.

27. DIAGNOSTIC METHODS • Sialography: refers to the contrast study of a particular gland • Means you put contrast into the duct and then you see hwo quickly it is flushed out • One problem with this is there is a lot of salivary gland infection produced from the study. This is because you are putting contrast in a gland/duct that already isn’t working. How do you expect that to get out? • There is oil and water-soluble contrast used for this. The most common is the water-soluble contrast. • This is not really used that often anymore. • Radiosialography: the study of salivary gl. employing radioisotopes. Useful for studying the dynamic activity of a given gl. Has a flow phase, a concentration phase and a washout phase-also called salivary scintigraphy • This is when a radioisotope is put into the veins that allows you to look at the dynamic activity of a given gland. It has three phases, a flow phase, a concentration phase, and a wash out phase. This is when you are trying to see if it would be better to take the gland out or leave it in

28. DIAGNOSTIC METHODS CON’T • SIALOCHEMISTRY: The spit test associated with Cystic Fibrosis to evaluate levels of NaCl • This is most commonly employed at facilities like Children’s Mercy for diagnosis of things like Cystic Fibrosis. These patients have many pulmonary infections. • The spit test associated with Cystic Fibrosis to evaluate levels of NaCl • Cystic fibrosis is associated with exocrine gland dysfunction • To get a positive diagnosis one expects to see elevations of sodium chloride in salivary secretions. • This is run on infants at birth to rule out a diagnosis of CF

29. Diagnostic Methods Continued • These are the most common things we utilize to diagnose pathology in the gland. • CAT SCAN/ MRI • CAT SCAN: Anytime you think there may be an obstructive process (stones) this is the study of choice • Gold standard for looking at obstructive phenomena • It can be used if you are expecting stones (sialoliths), a mass/tumor, a ranula, etc • MRI: If you suspect tumor formation • To look for extensions within the gland • ULTRASOUND: Anytime you think there may be fluid accumulation • Ranulas often have an ultrasound component to their diagnosis

30. Diagnostic Methods Con’t • FINE NEEDLE ASPIRATION BIOPSY (to check for malignancy: Usually for parotid gland masses to see whether the mass is malignant of benign • To check for malignancy • This allows us to look into a gland without opening it up • This is the standard to let us know whether a tumor is benign of malignant • This is more or less a core biopsy – you will stick a needle within the mass and it will take a core of material out of the mass and will leave a small punctuate hole. • You usually make two or three passes to make sure you have a good sample • OPEN BIOPSY: Usually associated when you want a diagnosis of for example Sjogren’s syndrome. This of course needs a parotid gland and a minor salivary gland biopsy.

31. SIALOENDOSCOPY • This is the new toy on the block, they are now going to non-invasive surgery • He thinks this looks like • You pass the canula through the duct (this is difficult). You put the dialator in, then through the dialator you put another small tube. This tube puts out a sonic frequency like a scaler. When activated it shoots out a pulse of electricity and obliterates the stone. • Now that the stone is in small pieces these pieces can come out of the gland through the duct and into the mouth.

32. SIALOENDOSCOPY • In 1991, Katz introduced a flexible mini-endoscope into the ductal system of the major salivary glands • The picture is a picture of the duct. You can’t get this all the way down in there

34. History/Examination Notes • Intermittent/persistent • An intermittent swelling that comes up and the gland almost always means there is an obstruction in the duct • A persistent swelling not uncommonly is associated with some type of tumor formation • Unilateral/bilateral • This is important because look at things that have bilaterality: • Alcoholism – you see a sialodenosis • HIV infection – gives you salivary gland hypertrophy • Sjogren’s Syndrome • Mumps – on occasion present with bilaterality • Unilateral enlargements: • Tumors • Tuberculosis • Infection

35. History/Examination Notes • Pain • This is usually found with obstructive disease • When talking about pain you have to think in terms of if there is a mucopurulent exudates. The salivary glands are not created equal. If you have a parotid gland infection the suspected bacterial entity would be a staphylococcal entity. On the other hand the submandibular gland has a tendency to be associated with a streptococcal type entity. • This is important because it determines what type of antibiotic to use. For the submandibular gland if you suspect an infection you would use a beta-lactam antibiotic (including the penicillins and the cephalosporins). Penicillin is really not that effective on staphylococcal infections. • Now we have the player MRSA. If you have a purulent exudates, you have to culture. • Sialorrhea/xerostomia • You want to know if there are areas of increase or decrease of salivary flow. • Facial paralysis • This is a dreaded complication. • If you have facial paralysis you will think in terms of two entities: a viral infection associated with the 7th cranial nerve (Bell’s Palsy) and the malignant transformation (a cancer of the salivary gland can cause facial paralysis)

36. SALIVARY GLAND DISEASES: CLASSIFICATION • 1. Nonneoplastic a) Infectious b) Noninfectious • 2. Neoplastic a) Benign b) Malignant

37. NONNEOPLASTIC-INFECTIOUS • Acute sialodenitis: acute inflamma. of gl. that causes erythema, pain, tenderness, swelling, & purulent discharge • Chronic recurrent sialodenitis • Granulomatous sialodenitis (TB/HIV) • Parotid abscess/acute parotitis • Viral parotitis-MUMPS caused by the paramyxovirus. Target organs are: parotid, testes, pancreas, brain, cochlea • Actinomycosis

38. NonNeoplastic-Infectious Notes • When the gland is inflamed we put the word –itis on the back of it. It can be acute or chronic. • An acute sialodenitis example would be a parotid abscess referred to as paratitis. The distinction here is mumps. Mumps is a paramyxovirus (you will see this again). We want to be sure we treat mumps, or prevent it if you get the vaccine, because hitting the target organs can cause infertility and hearing loss. • It has been proven that it is not true that infant vaccines cause autism. • Chronic recurrent sialodenitis is most commonly associated with obstructive phenomena, like thick spit or recurrent salivary gland stone formation. • Granulomatous sidalodenitis – in this disease you have giant cells and macrophages in the gland architecture. TB and HIV are associated with process like this in the gland. • Bacterial infection associated with salivary glands is the uncommon actinomycosis. Remember if a patient has an acute infection involving the gland and you suspect it might be actinomycoses then the purulent exudates will contain sulfur granules. • Actinomycosis is very difficult to eradicate. It will take usually a pick line (a purcutaneous intravenous catheter) left in the body for 6 weeks through which the patient has an infusion of antibiotics daily.

39. The girl has an asymmetry and the enlargement if red – this is by definition a sialodenitis • On a child you get a mumps titer, a WBC count, and some studies, most commonly a CT. If on the CT it looks like there is fluid in there, then you would get an ultrasound.

40. NONNEOPLASTICNONINFECTIOUS • SIALOLITHIASIS: Preferentially affects the SBM gl (80%). Calculi composed of hydroxyapatite. 65% of parotid calculi are lucent & 65% of SBM are opaque • BRANCHIAL APPARATUS ANOM. May form cysts or sinus tracts • BENIGN LYMPHO- EPITHELIAL LESION-Assd. HIV and lymphoma in 10%

41. NonNeoplastic, Noninfectious • Sialolithiasis – the submandibular gland is preferentially affected. • Can you have a salivary gland stone of a minor gland? Yes • Typically composed of hydroxyapetite. There is another substance (this is why we submit are stones for study), you might also see uric stones (uric acid). The primary disease that has high levels of uric acid is Gout. The primary entity of that is a sore big toe. The treatment for that has some significant side effects and is very expensive. • Most salivary gland stones located in the submandibular gland will most likely be radiodense. Parotid gland stones, not uncommonly, are radiolucent. So you may have to use more than one type of study to look into a gland. • Other entities that can cause swelling associated with salivary glands include: • The brachial cleft cyst • This can occur anywhere from the external auditory meatus down to the neck • Not uncommonly, they can be fairly difficult to remove and on occasion require resection of the hyoid bone. • Benign Lymphoepithelial Lesion • Typically a patient is worked up for HIV infection with this. • 10% of the time you can have carcinomatous change and it can turn into a lymphoma • That’s why these must be followed

42. SIALOLITHS • This is what salivary gland stones look like • They usually have little protrusions or spikes • If the patient tells you they have a history of intermittent swelling when they think about food or smell food that is a common sign that they have an obstructive phenomena

43. PLAIN FILMS TO VISUALIZE SIALOLITHS • Periapical • Occlusal • Panelipse • “Puffed cheek” lateral oblique • You blow your check out and then they take a lateral flat plate of your face looking for stones

44. SIALOLITHS WHY SO MANY Submandibular gland STONES? • Submandibular glands have many more stones than the parotid gland because its architecture helps form them. There are two big kinks in the gland. • Parotid secretions are more [ ] exc. for the Ca ion, which is 2x more abundant in SBM gl. Also, SBM gl. saliva is of an alkaline pH, which further supports stone formation. • The calcium ions get together than form concretions. As the secretions become more concentrated more calciium ions settle out in the concretions and evenutally form a nodule that becomes a stone • There is also an alkaline pH. So acidity decreases stone formation and alkalinity increases stone formation. • Wharton’s duct is longest duct and has 2 sharp curves (stasis and slow flow) • The two curves in this duct ultimately give you some stasis and that is when you start to see big stones

45. SIALOLITH • A hair follicle found in Stenson’s duct after removal • Note the material on the follicle

46. SIALOENDOSCOPY • Sialolith located in orifice of Wharton’s duct • Sialolith located in orifice of Wharton’s duct • On the left are the “little graspers” that you use to try to pull the stone out • On the right is an actual stone in a gland

47. Top left – they have probes that go from 4 ott (the size of a hair) up to a 4 (size of a pencil lead), you dialate the area up Lithotripsy fragment

48. MUCOCOELES- mucous extravasation reaction • Most common site= lower lip, then buccal mucosa • Most of the time these affect the lower lip. You rarely see these on the upper lip. • Results from rupture of a saliv. gl. duct with spillage of mucin • Dome –shaped mucosal swelling • TX: EXCISIONAL BX (biopsy) • When you open into the lip, right underneath the mucosa is a grape-like cluster of the minor salivary glands. So when you make this incision you will take out multiple glands to remove the mucocele. The only way to remove a mucocele is to cut it out. Repetitive puncture will not make it go away, ultimately it will make it fibrose.

49. RANULA • Is a mucocoele of the floor of the mouth. “Rana” in Latin is a frog’s belly • Usually arises from the sublingual gland • Appears as a dome-shaped swelling immediately under the tongue • May be simple or plunging • These present intraorally except on occasion they may present on the neck, this is called a plunging ranula • It will penetrate the mylohyoid muscle

50. Ranula • Do not regress, surgery is indicated • The treatment of choice for an intraoral presentation is removal of the sublingual gland, typically tranorally (through the mouth). • If it goes through the mylohyoid muscle, you typically take out the sublingual gland and the submandibular gland. • The problem with taking out ranulas is that you get lost once you get in the floor of the mouth. You have to make an incision somewhere. You will stick a probe through the orifice of the submandibular and sublingual duct and through that orifice you will dilate the duct up. You will leave the probe in the duct, make the incision, and try to get the Jell-O out. • Immediately in the floor of the mouth are the sublingual artery, the duct, and the lingual nerve. It is difficult to remove this ball while leaving these structures intact. • Ranulas do not typically go away on their own, they must be removed. • Not uncommonly you will see these on children.