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Trauma and Injuries to the Salivary Glands 421

(e) (f) k k

(g) Figure 16.10. (Continued)

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TRAUMA TO DUCTS treated non-operatively, 9 (47%) healed without complications. Although seven patients (36.8%) Transection developed salivary fistulas and four (21.4%) devel- As has already been discussed previously in oped sialoceles, these were described as short the sections on fistulas and sialoceles related to term and resolved without the need for surgery parenchymal trauma, conservative management (Lewis and Knottenbelt 1991). Van Sickels (1981), is usually satisfactory except in those cases where divided the parotid duct anatomically into three the injury involves partial or complete transac- sites of injury, based on implications for treatment. tion of the duct. Under these circumstances most Site A is the intra-glandular portion of the duct papers have indicated that resolution is less cer- and ductal injuries in this location are treated as tain and takes longer with active management described previously for parenchymal trauma. Site frequently required. There are studies that support B represents the duct as it overlies the masseter conservative measures in duct injuries and in one muscle and site C is the duct’s course anterior to report, of 19 patients with duct injury confirmed the masseter muscle through the deep tissues of by methylene blue dye injection in a retrograde the cheek into the mouth. Injuries at both these fashion through the Stenson duct who were sites require exploration and direct repair of the

k k

(a) (b) Figure 16.11. (a) Lateral view of face of patient complaining of gustatory sweating (Frey syndrome). (b) Bottle of iodine solution that is painted on the face and then covered with corn starch. (c) While the patient eats an apple the corn starch is colored blue-black, indicative of gustatory sweating.

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Trauma and Injuries to the Salivary Glands 423

k k

(c) Figure 16.11. (Continued)

duct if possible. If repair is impossible, creating saline or a small (1 cc) amount of methylene blue a direct fistula into the mouth is the treatment of through the Stenson papilla. Van Sickels (2009) choice for site C injuries (Lazaridou, et al. 2012). cautions against injecting too much dye which can However, in most cases current management stain the tissues and increase the difficulty of the is directed toward primary repair and the clinician dissection. Identification of the proximal end may must therefore have a high level of suspicion for be technically difficult as it can retract into the injuries involving the region of the parotid duct. gland substance. Milking the gland to obtain sali- The classic anatomic surface markings of the vary flow is helpful in these circumstances and the duct are illustrated in Figure 16.12. However, an anesthesiologist must be cautioned preoperatively ultrasound study has shown that 92% of ducts against the use of anti-parasympathetic agents. If were below the classic anatomic surface markings, the proximal and distal ends of the duct are identi- although 93% of the ducts were within 1.5 cm fied and can be coapted, then microsurgical repair of the middle half of a line between the tragus and can be carried out (Hallock 1992) (Figure 16.14). the cheilion (Stringer, et al. 2012). In this study, The use of stents (usually indwelling the mean internal caliber of the duct was 0.6+/− catheters) for 10–14 days to prevent stenosis is 0.2 mm. Confirmatory evidence for transaction is advocated by some and appears a reasonable obtained by cannulating the distal portion of the hypothesis, although no long term studies of duct through the Stenson papilla and observing the these injuries with and without stenting has catheter in the wound (Figure 16.13) or by injecting been published. A technique of using a 4F Foley

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When the injury is too proximal, the wound is avulsive or the duct cannot be identified, the clinician can either create an intraoral fistula or ligate the proximal duct. A controlled fistula can be created by suturing the proximal duct through the buccinator into the oral cavity if enough length is present, or by placing a catheter or drain from the area of the wound into the mouth and leaving it to fistualize (Figure 16.15). Although tying off the proximal duct to cause eventual atrophy has been proposed (Van Sickels 1981), in the author’s experience this is unpredictable and, even with the use of pressure and antisialogogues, these patients can have considerable swelling and pain. Chemical denervation using botulinum toxin A may be used to achieve a good outcome in these circumstances (Arnaud, et al. 2006). In the case of the submandibular duct tran- section is usually iatrogenic as a result of surgery on the sublingual gland, sialolithotomy from Whar- ton duct, or resection of floor of mouth cancer. In this case sialodochoplasty with repositioning of the duct posteriorly is all that is required. A catheter has been used as a stent (Ord and Lee 1996), fol- lowing reposition of Wharton duct in floor of mouth k cancer; however, now the duct lumen is identified, k one blade of a sharp iris scissors is inserted and a vertical cut through one wall of the duct carried out. The duct is now “fish-tailed” and sutured to Figure 16.12. Surface markings of the parotid duct are a newly created hole in the with 6o shown by a line drawn from the tragus of the ear to bisect nylon sutures. Stenosis and stricture has not been a line drawn from the alar base to the commissure. The a problem with this technique. middle third of this line (arrow) is surface marking of the parotid duct. Stenosis of the Duct When ductal injuries are not surgically repaired embolectomy catheter for identification of the immediately complications, such as fistulas and transaction and then left in place as a stent is sialoceles, may arise and their management has described (Etoz, et al. 2006). When the proximal been discussed. If the duct has not been surgically and distal ends of the duct cannot be coapted due repaired by 72 h conservative or medical therapy to tissue loss, repair using a vein graft has been is recommended (Arnaud, et al. 2006). In the long reported (Heymans, et al. 1999). Steinberg and term stricture of the duct may occur, although Herréra (2005) recommended the use of sialog- most strictures are secondary to inflammatory raphy postoperatively to assess the result of duct or infective conditions. In cases of intra-ductal repair, stating this technique may not always be salivary gland obstruction 22.6% of 642 cases practical or possible in the acute setting. How- were due to strictures, which were more com- ever,wehaveusedsialographyintraoperatively mon in females (Ngu, et al. 2007) (Figure 16.16). (Figure 16.13). A further development in the repair When this occurs at the distal end of the Sten- of ductal injuries has been the utilization of the son duct, excision and diversion of the duct into sialendoscope in some centers, for both repair and the oral cavity may be feasible. When the main followup assessment (Koch, et al. 2013; Kopec,´ duct is involved with strictures, sialendoscopy et al. 2013). may be useful to dilate the strictures using saline

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Trauma and Injuries to the Salivary Glands 425

(a) (b)

k k

(c) (d) Figure 16.13. (a) Patient with cheek laceration that was primarily sutured now has developed due to missed duct injury. (b) Wound reopened for re-exploration. The duct is discovered to be transected. Vessel loop around distal end of duct. Lacrimal probe passed from intra-oral through the Stenson duct into the wound (short arrow). (c) After finding the proximal end of the duct by milking the gland the duct is approximated. The duct is cannulated and contrast dye injected for intra-operative sialogram. (d) Fluoroscopic image of intra-operative sialogram with repaired duct (arrow).

pressure, balloon dilatation, or the miniforceps five of these patients remained asymptomatic grasper, and even the insertion of a stent to the on followup (Salerno, et al. 2007). If this is un- duct lumen (Nahliel, et al. 2004). Simple balloon successful and the patient continues to have recur- angioplasty was successful in 7/9 patients and rent swelling and , denervation with

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426 Chapter 16

(a) (b)

k k

(c) (d) Figure 16.14. (a) A 38-year-old man with a laceration of the right cheek in the operating room in preparation for primary closure and exploration of Stenson duct due to the depth and anatomic location of the laceration. (b) Sterile milk was injected in the distal aspect of Stenson duct that permitted the identification of its laceration. (c) The proximal end of the lacerated Stenson duct is able to be cannulated with a lacrimal probe. (d) The proximal and distal ends of the Stenson duct are primarily closed with 6-0 Prolene sutures with an indwelling catheter in place. (e) The catheter is sutured to the oral mucosa and maintained in place for 2 weeks. (f) The cheek wound is primarily closed in anatomic layers. The location of the laceration is appreciated to exist along the middle third of the line denoting the surface marking of the Stenson duct. Source: Courtesy of Dr. J. Greg Anderson and Dr. Michael Foster, University of Tennessee Medical Center Department of Oral and Maxillofacial Surgery. Reproduced with permission of Dr. Anderson.

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Trauma and Injuries to the Salivary Glands 427

(e) (f) Figure 16.14. (Continued)

botulinum toxin or even parotidectomy may be dose to both the parotid and submandibular glands required. (Jellema, et al. 2005). These authors also found that In the submandibular gland the stricture can the stickiness of saliva post-radiation depended be excised and sialodochoplasty performed as mainly on the mean dose to the submandibular described earlier. glands. The exact pathogenesis and mechanism of injury to the saliva glands as a result of radiation k Radiation Injury therapy is also controversial with no universal k agreement as to cause. Based on animal studies EXTERNAL BEAM on the rat model, a mechanism of delayed serous cell death due to sublethal DNA damage, which Radiotherapy is commonly administered to patients results in death during a reproductive phase due to with head and neck cancer, however, the injurious highly redox-reactive metal ions, for example iron effect that this treatment modality has on the sali- vary glands leading to profound , which and copper associated with secretion granules has may be permanent, is well known. The serous cells been proposed (Nagler 2002, 2003). Another study found in the parotid gland are extremely sensitive showed significant increase in cytotoxic T-cells to apoptotic death following even moderate doses in irradiated submandibular glands, suggesting of radiation. Indeed, permanent loss of salivary cell mediated mechanisms may be responsible function is seen after doses approximately larger for the sialadenitis with subsequent acinar cell than 3500 cGy with little in the way of measurable destruction/atrophy (Teymoortash, et al. 2005). parotid saliva and 5% of patients will demonstrate The use of FDG-PET-CT to measure fractional loss a sialadenitis with gland swelling and raised amy- of parotid FDG uptake has been proposed as a lase within 12 h of their first treatment (Parsons means to predict post-radiation therapy parotid 1994). However, although it is known that damage toxicity (Cannon, et al. 2012). to the salivary glands will increase with radiation Obviously, once established, the effects of dose and volume of gland irradiated there is no radiation damage are difficult to treat or reverse so universal agreement over the dose required to much effort has been aimed at prevention. Impor- produce xerostomia. Someya, et al. (2003) found tant advances in delivery of radiation therapy using gradual recovery of function over time with doses 3-D conformal planning and intensity-modulated of 5000 cGy, while no significant recovery was seen radiation therapy (IMRT), combined with drugs in patients who had >5800 cGy (Figure 16.17). The such as growth factors, cholinergic agonists, and minor salivary/sublingual glands do not seem to cytoprotective agents (Amifostine) are currently play much of a role in the development of xerosto- the preferred modalities of prevention (Garden, mia, which seems to depend mainly on the mean et al. 2006).

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428 Chapter 16

(a) (b)

k k

(c) (d) Figure 16.15. (a) Gunshot wound entering at right parotid region with exit at left infraorbital region as indicated by suction tubing. (b) The parotid duct is identified and dissected from the wound to be cannulated as shown. (c) The duct is diverted intraorally via the cannula. Note powder burn at entrance wound. (d) Final repair. This case was treated by Dr. J. Caccamese, Department of Oral and Maxillofacial Surgery, University of Maryland.

It has been shown with conventional radiation 2005). Jen, et al. (2005) compared 108 patients therapy that the ability to spare the contralateral treated with conventional RT to 72 treated with 3-D major salivary glands or to spare the parotid by conformal radiation therapy, finding that 3-D con- positioning of the portals can significantly increase formal radiation therapy delivered a higher dose to salivary flow and reduce xerostomia (Beer, et al. the tumor with better local control in T4 patients 2002; Malouf, et al. 2003). The sophistication and improved survival with significantly better of 3-D conformal planning and IMRT allows the parotid function. IMRT has also been used to spare radiotherapist to give more radiation to the tumor the submandibular glands to prevent radiation target with increased sparing of normal tissue. In induced xerostomia (Saarilahti, et al. 2006). The one study only 12% of patients developed xeros- ability to use 3-D conformal RT and IMRT to spare tomia following IMRT for head and neck cancer the opposite parotid by excluding the contralateral and there were no locoregional recurrences with a level II nodes from the field was not shown to be median follow up of 24 months (Saarilahti, et al. associated with any loco-regional recurrence and

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Trauma and Injuries to the Salivary Glands 429

(a) (b)

k k

(c) Figure 16.16. (a) Patient with soft tissue scarring from penetrating wounds caused by a road traffic accident 10 years previously. She now has a 7-year history of parotid and cheek swelling. (b and c) Sialogram shows stricture of duct with proximal dilatation of Stenson duct and secondary ducts and a large cystic swelling distal to the structure.

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430 Chapter 16

(Anne, et al. 2007). Another approach has been to use pilocarpine, which has been used to treat xeros- tomia during radiotherapy as a chemopreventive agent. A randomized, double blind, placebo con- trolled trial of pilocarpine on 60 patients, only 39 of whom were evaluable, indicated that pilocarpine used with radiotherapy could lead to significant diminishment in subsequent xerostomia (Haddad and Karimi 2002). Another randomized trial with 66 patients also concluded that patients with stim- ulated glands from pilocarpine during radiation had less decrease in salivary flow, which reduced radiation side-effects (Nyarady, et al. 2006). How- ever, the RTOG study 97–09, which was a phase III trial with 245 patients, showed that although there was a significantly increased unstimulated salivary flow in the pilocarpine group, there was no difference in parotid stimulated salivary flow in the amelioration of mucositis or quality of life between the two groups (Scarantino, et al. 2006). Figure 16.17. Marked skin reaction over parotid region Other novel approaches to the problem have been following 65 Gy external beam radiation given postopera- the use of gene therapy, which has yielded promis- tively. ing results in animal models (Thula, et al. 2005; Cotrim, et al. 2006). Future directions may lie k no recurrence occurred in the spared area (Bussels, in the use of stem cells to regenerate damaged k et al. 2004). salivary glands (Stiubea-Cohen, et al. 2013). Several studies have shown that IMRT is supe- Finally, a surgical approach to prevention rior to 3-D conformal radiotherapy in regards to late of xerostomia has been the transfer of the sub- toxicity from xerostomia (Kouloulias, et al. 2013; mandibular glands into the submental triangle Lambrecht, et al. 2013). In both these studies there out of the radiation field prior to the commence- was no difference in tumor control. ment of radiation therapy. In a phase II trial of A number of drugs have been investigated for patients who had primary surgery for oropha- preventing radiation damage. A phase III prospec- ryngeal cancer followed by adjuvant RT, with tive randomized trial of Amifostine (Ethyol) with or without submandibular gland transfer, 24 of 315 patients showed significant reduction in grade 51 patients were evaluated for swallowing. The 2 or greater xerostomia and chronic xerostomia cohort with preservation of one gland (13 patients) with no effect on locoregional control, disease free had significantly increased saliva and swallowing survival or overall survival. In this study, how- function (Rieger, et al. 2005). Similar results are ever, 53% of patients experience nausea and/or vomiting (Brizel, et al. 2000). A followup study to reported in a small series of patients undergoing review results of this study after 2 years, found the chemoradiation (Al-Qahtani, et al. 2006). Regard- significant decrease in grade 2 or greater xerosto- ing long term results in 26 patients followed for 2 mia had been maintained as well as an increase in years, normal amounts of saliva were reported in the proportion of patients with meaningful unstim- 83% (Seikaly, et al. 2004) A further study by the ulated saliva and reduced mouth dryness. There same group showed this surgical technique of sub- was no compromise of locoregional control, pro- mandibular gland transfer to be reproducible in a gression free, or disease free survival (Wasseman, multicenter setting with 74% of patients prevented et al. 2005). In this study, the Amifostine was given from XRT-induced acute xerostomia (Jha, et al., intravenously, and a recent phase II study has 2012). In a Chinese study of 38 patients, 92.3% shown a similar radioprotective benefit for Amifos- of patients had no or minimal xerostomia 2 years tine given subcutaneously as a simpler alternative post radiation therapy (Zhang, et al. 2012).

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Trauma and Injuries to the Salivary Glands 431

RADIOACTIVE IODINE to an oxidation injury indicated by an increase in prostaglandin levels (Wolfram, et al. 2004). Radioactive iodine is used in the treatment of A randomized placebo controlled study using thyroid cancer but is also concentrated in the vitamin E found a significant protective effect salivary glands particularly the parotid and may against radiation induced dysfunction in salivary cause sialadenitis, which is immediate or begins glands. In this trial, salivary function was assessed a few months after treatment (Mandel and Man- using salivary gland scintigraphy and, although the del 2003). In a prospective study of 76 patients control group had significantly reduced salivary receiving radioactive iodine, 20 (26%) developed secretion following the radioactive iodine, the salivary gland toxicity, 11 developed toxicity within group receiving Vitamin E had no reduced function 48 h, and 9 not until 3 months post-therapy. A (Fallahi, et al. 2013). total of 16 patients had chronic toxicity typically Current management is symptomatic as for xerostomia at 12 months (Hyer, et al. 2007). In sialadenitis and xerostomia from other causes. seeking to quantitate salivary gland dysfunction Animal studies using the rabbit model indicate using scintigraphy in 50 patients, 46 and 42% were that Amifostine can significantly reduce radioio- found to have decreased maximum secretion and dine induced parenchymal damage (Kutta, et al. uptake ratio, respectively (Raza, et al. 2006). The 2005). The use of sialendoscopic treatment in this damage was seen more in the parotid and was condition for patients with partial duct stenosis dependent on the radioiodine dose. The damage has also been reported (Kim, et al. 2007). In one and symptoms may be permanent (Mandel and series of sialendoscopy with dilation and irrigation, Mandel 1999). The damage is most likely related 54% of patients reported complete resolution of

Penetrating parotid gland injury k k Parenchymal injury with Parenchymal injury only Facial nerve transection Stenson duct injury

Approximation of duct Able to reapproximate segments without tension? without tension?

Debridement and Yes No Yes No Closure of wound

Primary closure Superficial parotidectomy Primary Proximal Distal injury closure of injury Stenson duct Yes

Ligate duct Reconstruction with Able to reapproximate implantation in oral without tension cavity No

Delayed sialocele or Interpositional nerve graft or salivary fistula development nerve expander or alloplastic conduit

Aspiration of saliva Compression dressings Anticholinergic medications Botox

Figure 16.18. Algorithm for management of penetrating trauma to the parotid gland.

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432 Chapter 16

Blunt trauma to parotid gland

Salivary gland Facial nerve injury injury

Delayed sialocele or salivary Partial weakness Paralysis fistula development

Nerve conduction Aspiration of saliva Observation study Compression dressings Anticholinergic medications Botox

Yes Recovery

No

Consider surgical Figure 16.19. Algorithm for management of exploration blunt trauma to the parotid gland. k k symptoms, 36% partial improvement, and 10% no extending to the mediastinum, parotid duct ligation improvement at a mean follow up of 18 months was used for cure (Han and Isaacson 2004). (Prendes, et al. 2012). Summary Barotrauma See Figures 16.18 and 16.19 for algorithms for man- Air can be forced in a retrograde fashion into agement of trauma. the parotid duct by a rise in intraoral pressure and cause parotid emphysema or pneumoparotid. • Most parenchymal penetrating injuries of the This condition may occur in glass blowers and parotid gland will resolve with conservative musicians who play woodwind or brass instru- treatment. ments. It is usually a benign condition but can • Parotid fistulae and sialocele due to parenchy- cause recurrent sialadenitis or even progress to mal injury will also resolve with conservative subcutaneous emphysema. The condition has also therapy. been reported in conjunction with the use of an air • Chemical denervation of the gland with syringe during routine dentistry (Takenoshite, et al. Botulinum A toxin injected subcutaneously 1991), secondary to coughing with chronic obstruc- appears a safe way of treating fistulas and tive airways disease (Cook and Layton 1993), and sialoceles. self-induced in children and adults (Goguen, et al. • It is important to recognize the possibility of 1995; Gudlaugsson, et al. 1998). The condition can duct injury early as immediate repair is indi- be diagnosed by palpation of emphysema in the cated. parotid and the escape of frothy saliva from the • Microneural repair of facial nerve injuries duct. Sialography, and CT scans have been used for primarily without tension is the ideal man- diagnosis (Gudlaugsson, et al. 1998; Maehara, et al. agement for a transected facial nerve or its 2005). In one case with subcutaneous emphysema branches.

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Trauma and Injuries to the Salivary Glands 433

• At present, the use of tissue glues for nerve Cannon B, Schwartz DL, Dong L. 2012. Metabolic imaging of repair does not appear to improve results. postradiotherapy xerostomia. Int J Radiol Oncol Biol Phys • Most cases of Frey syndrome following 1;83(5):1609–1616. parotidectomy are subclinical. Canosa A, Cohen MA. 1999. Post-traumatic parotid • Botulinum toxin is useful in the treatment of sialocele: report of two cases. J Oral Maxillofac Surg Frey syndrome. 57(6):742–745. • A variety of barrier techniques to prevent Frey Cant PJ, Campbell JA. 1991. Management of traumatic parotid sialoceleles and fistulas: a prospective study. syndrome have been described with the use Aust N Z J Surg 61(10):742–723. of the SAMAS layer appearing to give good Capaccio P, Cuccarini V, Benicchio V, et al. 2007. Treat- results. ment of iatrogenic submandibular sialocele with • IMRT and 3-D conformal planning show great botulinum toxin. Case report. Br J Oral Maxillofac promise in preventing radiation damage to the Surg 45(5):415–417. salivary glands. CaptierG,CanovasF,BonnelR,SeignarbieuxF.2005.Orga- • Amifostine and pilocarpine used during radia- nization and microscopic anatomy of the adult human tion may act as radioprotectants. facial nerve: anatomical and histological basis for surgery. Plast Reconstr Surg 115:1457–1465. Cesteleyn L, Helman J, King S, Van de Vyvere G. 2002. References Temperoparietal fascia flaps and superficial muscu- loaponeurotic system placation in parotid surgery Al-Qahtani K, Hier MP, Sultanum K, Black MJ. 2006. reduces Frey’s syndrome. J Oral Maxillofac Surg 60(11): The role of submandibular salivary gland transfer in 1284–1297. preventing xerostomia in the chemoradiotherapy patient. Cholankeril JV, Scioscia PA. 1993. Post-traumatic sialoce- Oral Surg Oral Med Oral Pathol Oral Radiol Endod les and mucoceles of the salivary glands Clin Imaging 101(6):753–756. 17(1):41–45. Ananthakrishnan N, Parkash S. 1982. Parotid fistuas: a Chow TL, Kwok SP. 2003. Use of botulinum type A in a k review. Br J Surg 69:641–644. case of persistent parotid sialocele. Hong Kong Med J k Anne PR, Machtay M, Rosenthal DI, et al. 2007. A phase II 9(4):293–294. trial of subcutaneous amifostine and radiation therapy in Cook JN, Layton SA. 1993 Bilateral parotid swelling asso- patients with head and neck cancer. Int J Radiat Oncol ciated with chronic obstructive pulmonary disease. A Biol Phys 67(2):445–452. case of pneumoparotid. Oral Surg Oral Med Oral Pathol Arnaud S, Batifol D, Goudot P, Yachouh J. 2006. Nonsur- 76(2):157–158. gical management of traumatic injuries of the parotid Cotrim AP, Mineshiba F, Sugito T, et al. 2006. Salivary gland gland using type a botulinum toxin. Plast Reconstr Surg gene therapy 2006. Dent Clin North Amer 50(2):157–173. 117(7):2426–2430. Dulguerov P, Marchal F, Gusin C. 1999. Frey syndrome Beer KT Zehnder D, Lussi A, Greiner RH. 2002. Sparing before Frey: the correct history. Laryngoscope 109(9): of contralateral major salivary glands has a significant 1471–1473. effect on oral health in patients treated with radical Eckardt A, Kuettner C. 2003. Treatment of gustatory sweat- radiotherapy of head and neck tumors. Strahlenther ing (Frey’s syndrome) with botulinum toxin A. Head Neck Onkol 178(12):722–726. 25(8):624–628. Berini-Aytes L, Gay-Escoda C. 1992. Morbidity associated Etoz A, Tuncel U, Ozcan M. 2006. Parotid duct repair by use with removal of the submandibular gland. JCraniomax- of an embolectomy catheter with a microvascular clamp. illofac Surg 20(5):216–219. Plast Reconstr Surg 117(10):330–331. Bonanno PC, Palaia D, Rosenberg M, Casson P. 2000. Pro- Fallahi B, Beiki D, Abedi SM, Saghari M, Fard-Esfahani A, phylaxis against Frey’s syndrome in parotid surgery. Ann Akhzari F, Mokarami B, Eftekhari M. 2013. Does vita- Plast Surg 44(5):498–501. min E protect salivary glands from I-131 radiation dam- Breuer T, Ferrazzini A, Grossenberger R. 2006. Botulinum age in patients with thyroid cancer? Nuc Med Commun toxin A as a treatment of traumatic salivary gland fistulas. 34(8):777–786. (In German). HNO 54(4):385–390. Farrag TY, Lehar M. Verhaegen P, et al. 2007. Effect Brizel DM, Wasserman TH, Henke M, et al. 2000. Phase III of platelet rich plasma and fibrin sealant on facial randomized trial of Amifostine as a radioprotector in head nerve regeneration in a rat model. Laryngoscope and neck cancer. JClinOncol18(19):3339–3345. 117(1):157–165. Bussels B, Maes A, Hermans R, et al. 2004. Recurrences after Faussat JM, Ghiassi B, Princ G. 1993. Rhinnorrhea of parotid conformal parotid sparing radiotherapy for head and neck origin. Apropos of a case. Rev Stomatol Chir Maxillofac cancer. Radiother Oncol 72(2):119–127. 94(6):363–365.

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Ferraro G, Altieri A, Grella E, D’Andrea F. 2005. Botulinum severe dry mouth in nasopharyngeal cancer patients: a toxin: 28 patients affected by Frey’s syndrome treated dosimetric and clinical comparison with conventional with intradermal injections. Plast Reconstr Surg radiotherapy. Radiother Oncol 75(2):204–209. 115(1):344–345. Jha N, Harris J, Seikaly H, Jacobs JR, McEwan AJ, Rob- Frey L. 1923. Le Syndrome du nerf auriculo-temporal. Rev bins KT, Grecula J, Sharma AK, Ang KK. 2012. A phase Neurol 2:97. II study of submandibular gland transfer prior to radi- Filho WQ, Dedivitis RA, Rapoport A, Guimaraes AV. ation for prevention of radiation-induced xerostomia in 2004. Sternocleidomastoid muscle flap in preventing head-and-neck cancer (RTOG 0244). Int J Radiol Oncol Frey’s syndrome following parotidectomy. World J Surg Biol Phys 1;84(2):437–442. 28(4):361–364. Junior EDP, Valmaseda-Castellon E, Gay-Escoda C. 2004. Garden AS, Lewin JS, Chambers MS. 2006. How to reduce Facial nerve repair with epineural suture and anastomo- radiation-related toxicity in patients with cancer of the sis using fibrin adhesive: An experimental study in the head and neck. Curr Oncol Rep 8(2):140–145. rabbit. J Oral Maxillofac Surg 62(12):1524–1529. Gardetto A, Kovacs P, Piegger J, et al. 2002. Direct coapta- Kerawala CJ, McAloney N, Stassen LF. 2002 Prospective ran- tion of extensive facial nerve defects after removal of the domized trial of the benefits of a sternocleidomastoid flap superficial part of the parotid gland: an anatomic study. after superficial parotidectomy. Br J Oral Maxillofac Surg Head Neck 24(12):1047–1053. 40(6):468–472. Goguen LA, April MM, Karmody CS, Carter BL. 1995. Kim JW, Han GS, Lee SH, et al. 2007. Sialendoscopic treat- Self-induced . Arch Otolaryngol Head ment for radioiodine induced sialadenitis. Laryngoscope Neck Surg 121(12):1426–1429. 117(1):133–136. Govindaraj S, Cohen M, Genden EM, et al. 2001. The use Koch M, Bozzato IH, Zenk J. 2013. Sialendoscopy-assisted of acellular dermis in the prevention of Frey’s syndrome. microsurgical repair of traumatic transection of Stenson’s Laryngoscope 111(11 Pt 1):1993–1998. duct. Laryngoscope 123(12):3074–3077. Gudlaugsson O, Geirsson AJ, Benediktsdottir K. 1998. Pneu- Kope´c T, Wierzbicka M, Szyfter W, 2013. Stenson’s moparotitis: a new diagnostic technique and a case report. duct injuries: the role of sialendoscopy and adjuvant Ann Otol Rhinol Laryngol 107(4):356–358. botulinum toxin injection. Wideochir Inne Tech Malo Guntinas-Lichius O, Straesser A, Streppel M. 2007. k Inwazyine 8:112–116. k Quality of life after facial nerve repair. Laryngoscope Kouloulias V, Thalassinou S, Platoni K, Zygogianni A, Kou- 117(3):421–426. varis J, Antypas C, Efstathopoulos E, Nikolaos K. 2013. Guntinas-Lichius O, Streppel M, Stennert E. 2006. Postoper- The treatment outcome and radiation-induced toxicity for ative functional evaluation of different reanimation tech- patients with head and neck carcinoma in the IMRT era: niques for facial nerve repair. Am J Surg 191(1):61–67. a systematic review with dosimetric and clinical parame- Haddad P, Karimi M. 2002. A randomized, double-blind, Biomed Res Int placebo-controlled trial of concomitant pilocarpine ters. 2013:401261. with head and neck irradiation for prevention of Kutta H, Kampen U, Sagowski C, et al. 2005. Amifostine is radiation-induced xerostomia. Radiother Oncol 64(1): a potent radioprotector of salivary glands in radioiodine 29–32. therapy. Structural and ultrastructural findings. Strahlen- Hallock GG. 1992. Microsurgical repair of the parotid duct. ther Onkol 181(4):237–245. Microsurgery 13(5):243–246. Kyrmizakis DE, Pangalos A, Papadakis CE, et al. 2004. The Han S, Isaacson G. 2004. Recurrent pneumparotid: use of botulinum toxin type A in the treatment of Frey cause and treatment. Otolaryngol Head Neck Surg and crocodile tears syndromes. J Oral Maxillofac Surg 131(5):758–761. 62(7):840–844. Heymans O, Nelissen X, Medot M, Fissette J. 1999. Micro- Laage-Hellman J-E. 1957. Gustatory sweating and flush- surgical repair of Stenson’s duct using an interposition ing after conservative parotidectomy. Acta Otolaryngol vein graft. J Reconstr Microsurg 15(2):105–107. (Stokh) 48:234. Hyer S, Kong A, Pratt B, Harmer C. 2007. Salivary gland Lambrecht M, Nevens D, Nuyts S. 2013. Intensity-modulated toxicity after radioiodine therapy for thyroid cancer. Clin radiotherapy vs parotid-sparing 3D conformal radio- Oncol (R Coll Radiol) 19(1):83–86. therapy. Effect on outcome and toxicity in locally Jellema AP, Doornaert P, Slotman BJ, et al. 2005. Does radi- advanced head and neck cancer. Strahlenther Onkol ation dose to the salivary glands and oral cavity predict 189(3):223–229. patient-rated xerostomia and sticky saliva in head and Landau R, Stewart M. 1985. Conservative management of neck cancer patients treated with curative radiotherapy? post-traumatic parotid fistulas and sialoceles: A prospec- Radiother Oncol 77(2):164–171. tive study. Br J Surg 72:42. Jen YM, Shih R, Lin YS, et al. 2005 Parotid gland-sparing Lazaridou M, LLiopoulos C, Antoniades K, Tilaveridis I, three-dimensional conformal radiotherapy results in less Dimitrakopoulos I, Lazaridis N. 2012. Salivary gland

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trauma: a review of diagnosis and treatment. Craniomax- of conservative management in 51 cases. Ann Surg illofac Trauma Reconstr 5(4):189–196. 209(1):105–111. Lewis G, Knottenbelt JD. 1991. Parotid duct injury: Is imme- Parsons JT. 1994. The effect of radiation on normal tissues of diate surgical repair necessary? Injury 22:407. the head and neck. In: Million RR, Cassisi NJ (eds), Man- LewkowiczAA,HassonO,NablieliO.2002.Traumatic agement of Head and Neck Cancer: A Multidisciplinary injuries to the parotid gland and duct. J Oral Maxillofac Approach. Philadelphia, JB Lippincott Co., pp. 247–250. Surg 60(6):676–680. Piza-Katzer H, Balough B, Muzika-Herczeg E, Gardetto A. Maehara M Ikeda K, Ohmura N, et al. 2005. Multislice 2004. Secondary end to end repair of extensive facial computed tomography of pneumoparotid: a case report. nerve defects: surgical technique and postoperative Radiat Med 23(2):147–150. functional results. Head Neck 26(9):770–777. Malik TH, Kelly G, Ahmed A, et al. 2005 A comparison of Prendes BL, Orloff LA, Eisele DW. 2012. Therapeutic sialen- surgical techniques used in dynamic reanimation of the doscopy for the management of radioiodine sialadenitis. paralyzed face. Otol Neurotol 26(2):284–291. Laryngoscope 138(1):15–19. Malouf JG, Aragon C, Henson BS, et al. 2003. Influence of Ragona RM, Blotta P, Pastore A, et al. 1999. Management parotid-sparing radiotherapy on xerostomia in head and of parotid sialocele with botulinum toxin. Laryngoscope neck cancer patients. Cancer Detect Prev 27(4):305–310. 109(8):1344–1346. Mandel SJ, Mandel L. 1999. Persistent sialadenitis after Raza H, Khan AU, Hameed A, Khan A. 2006. Quantitative radioactive iodine therapy: report of two cases. JOral evaluation of salivary gland dysfunction after radioiodine Maxillofac Surg 57(6):738–741. therapy using salivary gland scintigraphy. Nucl Med Com- Mandel SJ, Mandel L. 2003. 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JSupportOncol4(5):252–258. tures: nature and incidence in benign salivary obstruc- Scher N, Poe DS. 1988. Post-traumatic prandial rhinorrhea, tion. Dentomaxillofac Radiol 36(2):63–67. J Oral Maxillofac Surg 46(1):63–64. Nolte D, Gollmitzer I, Loeffelbein DJ, et al. 2004. Botulinum Seikaly H, Jha N, Harris JR, et al. 2004. Long term outcomes toxin for treatment of gustatory sweating. A prospective of submandibular gland transfer for prevention of post randomized study. (In German). Mund Kiefer Gesichtschir radiation xerostomia. Arch Otolaryngol Head Neck Surg 8(6):369–375. 130(8):956–961. Nyarady Z, Nemeth A, Ban A, et al. 2006. A randomized Singh B, Shaha A. 1995. Traumatic submandibular salivary study to assess the effectiveness of orally administered gland fistula. J Oral Maxillofac Surg 53(3):338–339. pilocarpine during and after radiotherapy of head and Someya M, Sakata, Nagakura H, et al. 2003. The changes in neck cancer. 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Stiubea-Cohen R, David R, Neumann Y, Palmon A, Vargas H, Galati LT, Parnes SM. 2000. A pilot study evalu- Aframian D. 2013. Toward salivary gland stem cell ating the treatment of post parotidectomy sialoceles with regeneration. Compend Contin Educ Dent 34(Spec botulinum toxin type A. Arch Otolaryngol Head Neck Surg No:14–17):18. 126(3):421–424. Stringer MD, Miralili SA, Meredith SJ, Muirhead JC. Wasseman TH, Brizel DM, Henke M, et al. 2005. Influence 2012. Redefining the surface anatomy of the parotid of intravenous amifostine on xerostomia, tumor control, duct: an invivo ultrasound study. Plast Reconstr Surg and survival after radiotherapy for head-and-neck cancer: 130(5):1032–1037. a 2-year follow up of a prospective, randomized phase III Takenoshite Y, Kawano Y, Oka M. 1991. Pneumoparotis an trial. Int J Radiat Oncol Biol Phys 15(4):985–990. unusual occurrence of parotid gland swelling during den- Wolfram RM, Palumbo B, Chehne F, et al. 2004. tal treatment. Report of a case with a review of the litera- Prostaglandins in saliva indicate oxidation injury after ture. J Craniomaxillofca Surg 19(8):362–365. radioiodine therapy. Rev Esp Med Nucl 23(30):183–188. Teague A, Akhtar S, Phillips J. 1998. Frey’s syndrome fol- Ya Z, Gao Z, Wang J. 2007. Primary clinical study on using lowing submandibular gland excision: an unusual post end to end neurorrhaphy following rapid nerve expansion operative complication. ORL J Otorhinolaryngol Relat Spec to repair facial nerve defect (In Chinese). Zhongguo Xiu 60(6):346–348. Fu Chong Jian Wai Ke Za Zhi 21(1):23–25. Teymoortash A, Simolka, Schrader C, et al. 2005. Lympho- Zhang Y, Guo CB, Zhang L, Wang Y, Peng X, Mao XC, Yu cyte subsets in irradiation-induced sialadenitis of the sub- GY. 2012. Prevention of radiation-induced xerostomia mandibular gland. Histopathology 47(5):493–500. by submandibular gland transfer. Head Neck 34(7): Thula TT, Schultz G, Tran-Soy-Tay R, Batich C. 2005. 937–942. Effects of EGF and bFGF on irradiated parotid glands. Zumeng Y, Zhi G, Gang Z, et al. 2006. Modified superfi- Ann Biomed Eng 33(5):685–695. cial parotidectomy: preserving both the greater auricular Van Sickels JE. 1981. Parotid duct injuries. Oral Surg Oral nerve and the parotid gland fascia. Otolaryngol Head Neck Med Oral Pathol Oral Radiol Endod 52(4):364–367. Surg 135:458–462. Van Sickels JE. 2009. Management of parotid gland and duct injuries. Oral and Maxillofac Clin North Am 21(2):243–246. k k

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Chapter 17 Miscellaneous Pathologic Processes of the Salivary Glands

Outline Hereditary and Congenital Introduction Conditions Hereditary and Congenital Conditions Aplasia APLASIA Duct Atresia Aberrant Glands Aplasia of one or all of the major salivary glands Polycystic Disease of the Salivary Glands is a rare condition, which may present with First Branchial Cleft Cysts, Fistulas, and Sinuses severe xerostomia, rampant caries, , Cystic Fibrosis pharyngitis, and laryngitis. In addition “dental Saliva chipping” (Mandel 2006) and recurrent herpes Saliva as a Diagnostic Fluid labialis (Heath, et al. 2006) has been described as a presenting sign of . It is said Saliva in the Management of Xerophthalmia k to be more common in males (Frydrych and Koong k Ischemic/degenerative Changes 2014). MRI may be used to confirm the clinical Necrotizing Sialometaplasia Age Changes in Salivary Glands diagnosis of salivary gland aplasia (Mohan, et al. 2013). Küttner Tumor The condition may occur as part of a recog- Summary nized syndrome, including Down syndrome (Odeh, References et al. 2013), associated with other congenital anomalies, or as an isolated phenomena. In one series of 21 Treacher Collins patients, 19% had apla- Introduction sia and 29% dysplasia diagnosed on ultrasound and salivary gland function tests (Østerhus, et al. 2012). This chapter will review a heterogenous group Aplasia of the lacrimal and salivary glands (ALSG) of salivary diseases that are not covered in other presenting with irritable eyes and xerostomia is an autosomal dominant condition, which appears sections of this book. Hereditary and developmen- to be related to mutations in FGF10 (Entesarium, tal conditions of the glands are rare such that the et al. 2007). In lacrimo-auriculo-dento-digital syn- most common branchial arch anomalies will be drome (LADD) agenesis of salivary glands as well emphasized. Under the heading of saliva, most as lacrimal glands can be seen and is an autosomal clinical emphasis will be given to the treatment dominant condition with variable expressivity of drooling. This condition is not uncommon and (Inan, et al. 2006). A case of submandibular there are a wide variety of treatment approaches agenesis with parotid gland hypoplasia in asso- which will be discussed. ciation with ectodermal dysplasia is reported

Salivary Gland Pathology: Diagnosis and Management, Second Edition. Edited by Eric R. Carlson and Robert A. Ord. © 2016 John Wiley & Sons, Inc. Published 2016 by John Wiley & Sons, Inc.

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(Singh and Warnakulasuriya 2004). In addition ABERRANT GLANDS aplasia in association with hypoplasia of the thy- roid (D’Ascanio, et al. 2006), accessory parotid Accessory glands are ectopic in position but pos- tissue (Antoniades, et al. 2006) and cleft and sess a duct that usually opens into another main (Reija, et al. 2013) is described. duct, for example the accessory parotid gland In a comprehensive review of the literature whereas aberrant glands have no duct system. in 2010 (Pham Dang, et al.), 35 cases of bilateral Some of these aberrant glands can form fistulas major gland aplasia were identified. These authors and secrete while the patient is eating others do also document 10 cases of unilateral submandibular not secrete but form choristomas. The commonest agenesis, 10 cases of aplasia of the salivary glands sites for these aberrant glands is the lateral neck, with absent lacrimal puncta with no family history, pharynx, and middle ear (Enoz and Suoglu 2006), and 2 familial forms of this condition have also presumably from their proximity to the first two been studied. branchial arches during development. These aber- Management of these cases is symptomatic rant glands may be involved in neoplastic change and directed towards the xerostomia and other oral and may account for the central salivary tumors of health care issues. the jaws (usually the ). A case of ectopic parotid in conjunction with CHARGE syndrome (coloboma of the eye, heart DUCT ATRESIA defects, atresia of the nasal choanae, retardation of growth, genital abnormalities, and ear abnormal- Duct atresia is rare and in a 2001 review (Hof- ities/deafness) has been reported (Ormitti, et al. frichter, et al. 2001) only eight previous case of 2013). submandibular duct atresia were found with six unilateral and two bilateral. The condition usu- ally presents in babies or infants as a “” POLYCYSTIC DISEASE OF THE SALIVARY (Aronovitch and Edwards 2014) and is thought k GLANDS k to be due to failure of the duct to penetrate the oral mucosa during development, known This is a rare disease, which may be a hereditary as an imperforate Wharton duct (Figure 17.1). condition as familial cases have been reported The diagnosis can be made by the presence of (Smyth, et al. 1993). It is thought to be due to a dilated Wharton duct(s) on CT scan. Manage- developmental abnormality of the intercalated duct ment is by sialodochoplasty to create a new duct system. Seifert, et al. (1981) reviewed 5739 cases of orifice. and found 360 cases of cystic

(a) (b) Figure 17.1. A 3-month-old baby with swelling of the floor of mouth (a) for whom a clinical diagnosis of congenital ranula was made. Intraoperative exploration identified a significantly dilated Wharton duct (b) with no opening of the duct to the oral mucosa. An imperforate duct was therefore diagnosed and a sialodochoplasty was performed for correction. Source: John Caccamese, Reproduced with permission of John Caccamese.

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Miscellaneous Pathologic Processes of the Salivary Glands 439

(a) (b)

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(c) (d) Figure 17.2. (a and b) Middle-aged woman with right parotid swelling for “many” years. Patient is concerned regarding her appearance as she has no symptoms. (c, d, e, and f) MRI films show multiple cysts within the gland. At the time of surgery multiple microliths were seen.

disease, of which 2 patients were classified with male patient is reported (Garcia, et al. 1998). Histo- dysgenetic polycystic parotid disease. Although logically, the gland is replaced with multiple cysts it is usually bilateral, unilateral cases have been that may contain spheroliths or microliths. There described (Seifert, et al. 1981) (Figure 17.2). It is is a marked absence of inflammatory change. said to be always seen in females, however, a case Parotidectomy may be carried out for esthetic of the condition in the submandibular glands in a reasons.

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(e) (f) Figure 17.2. (Continued)

FIRST BRANCHIAL CLEFT CYSTS, k k FISTULAS, AND SINUSES Anomalies of the first brachial arch are intimately associated with the parotid gland and the periau- ricular structures. They are less common than sec- ond branchial arch anomalies. In a survey of 183 patients with branchial cleft cysts and fistulas, 148 patients (80.8%) had branchial cysts of which 35 (23.6%) arose from the first arch and 35 (23.6%) had fistulas of which 11 (31.4%) arose from the first arch (Agaton-Bonilla and Gay-Escoda 1996). The usual figure for the incidence of first branchial arch anomalies is 10% (Olsen, et al. 1980). Figure 17.3. A 20-year-old girl with recurrent localized Although Work (1972) classified type I cystic infection of the parotid and a periparotid sinus. lesions containing only squamous epithelium and type II lesions that contained squamous epithelium with adnexal skin structures plus cartilage, the found 20 (51%) sinuses, 11 (28%) fistulas, and 8 presence of infection may make it impossible to (21%) cysts. Similarly, in the series of 10 patients classify these lesions using these criteria. Olsen, by Solares, et al. (2003), 5 (50%) were sinuses, 3 et al. (1980) simplified this classification divid- (30%) fistulas, and 2 (20%) cysts. ing the type II anomaly into cysts, fistulas, and Presentation is usually with recurrent infec- sinuses. Cysts are tracts with no opening, sinuses tion, with discharge of pus or an abscess in the are a tract with a single opening usually from the anterior neck, a chronic purulent discharge from external auditory canal, and fistulas are tracts with the ear or an infected swelling of the parotid region two openings usually from the external auditory (Figure 17.3). The usual age of presentation is meatus to the anterior neck above the hyoid bone. between birth and twenty years with most cases In their series of 39 cases, Triglia, et al. (1998), diagnosed at age of 2-and-a-half years.

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