Lesion. This Was Perhaps the First Explanation That Scar Tissue

Cysts and Cyst-like Lesions of the Salivary Glands 101

(b)

k k

(a) (c) Figure 4.7. This elderly woman shows left submandibular swelling (a). Her history includes numerous aspirations of fluid within a ranula of the left floor of mouth. Computerized tomograms of the neck show a fluid filled lesion of the submandibular region (b). A diagnosis of plunging ranula was made and the patient underwent left sublingual gland excision (c). Examination of the left floor of mouth did not show signs of ranula in this region. Scar tissue formation from her previous aspirations resulted in the development of a plunging ranula.

lesion. This was perhaps the first explanation that muscle and its hiatus or cleft, and herniations scar tissue formation in the mucosa of the floor of within the mylohyoid muscle, has been studied to mouth was responsible for the development of the explain the development of a plunging ranula. In cervical mass as it descended through the cleft of their study of 23 adult cadavers, Harrison, et al. the posterior extent of the mylohyoid muscle as identified a bilateral mylohyoid hiatus to exist in a path of least resistance (Figure 4.7) (Braun and ten of their 23 specimens (43%), with the hiatus Sotereanos 1982). The anatomy of the mylohyoid being unilateral in six (26%) and bilateral in four

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(17%) cadavers (Harrison et al. 2013). The median structure of the floor of mouth. He believes that anteroposterior dimension of the hiatus was 7 mm some of these lesions are unrelated to the sublin- with a range of 2–11 mm, and the median medi- gual gland, such that its removal is not indicated. olateral dimension was 14 mm with a range of Specifically, he cites the existence of mucoceles 7–20 mm. The authors identified sublingual gland arising from the mucus-secreting incisal gland in tissue in nine hernias and fat in six hernias. Other the anterior floor of mouth, single or multiple authors have demonstrated that approximately one retention cysts involving the openings of the ducts third of the population has discontinuities of the of Rivinus, and retention cysts at the Wharton mylohyoid muscle such that direct invasion of the duct orifice that can resemble the sublingual gland pseudocyst through these defects of the muscle associated ranula, but that would possibly not be permits extension into the neck (McClatchey, et al. cured with sublingual gland removal. Moreover, 1984). While the pathophysiology of the plunging the author states that sublingual gland excision is ranula is now well understood from an anatomic potentially associated with significant morbidity perspective, the literature continues to identify such as injury to the Wharton duct with resultant controversy with regard to the most appropriate salivary obstruction or salivary leakage, and lin- means to treat the ranula and plunging ranula gual nerve injury (Baurmash 1992). Zhao and his (Patel, et al. 2009; Harrison 2010; Lesperance, et al. group presented an objective assessment of com- 2013; Sigismund, et al. 2013). plications associated with surgical management If anything has been learned by reading the of ranulas treated with a variety of procedures scientific literature on the topic of cyst-like lesions (Zhao, et al. 2005). These included 9 marsupi- of the salivary glands, it is the common pathogen- alizations, 28 excisions of the ranula only, 356 esis of three clinical entities: the mucocele, the sublingual gland excisions, and 213 excisions of oral ranula, and the plunging ranula. Specifically, both the sublingual gland and ranula. A total of it is their lack of an epithelial lining, and their 569 sublingual gland excisions were performed in association with a salivary gland, whether major 571 patients undergoing 606 operations. Injury to k or minor, that these entities share in common. the Wharton duct occurred in 11 of 569 patients k If the offending sublingual salivary gland is not who underwent excision of the sublingual gland removed, the lesion has a statistical likelihood with or without excision of the ranula compared of recurrence (Catone, et al. 1969; Suresh, et al. to 0 of 37 patients who did not undergo sublingual 2012). This notwithstanding, while the diagnosis gland excision. Injury to the lingual nerve occurred of the conventional, non-plunging ranula remains in 21 of patients who underwent sublingual gland straightforward, its management has historically excision compared to 0 patients who did not been variable and controversial, ranging from undergo sublingual gland excision. Of particular incision and marsupialization to sublingual gland note is that recurrence of the ranula occurred in excision. Interestingly, most mucoceles are located 1.2% of patients who underwent excision of their in the lower lip and are treated with an excision sublingual glands compared to 60% of patients of the mucocele and associated etiologic minor who underwent marsupialization or excision of salivary gland tissue of the lower lip. Ironically, the ranula only. Baurmash laments that simple although the ranula of the floor of mouth is the marsupialization has fallen into disfavor because second most common type of mucocele, removal of the excessive number of failures associated with of the ranula and the associated salivary gland, this procedure (Baurmash 1992). The recurrence in this case the sublingual gland, has not been patterns have been confirmed by other authors, uniformly accepted as standard treatment of the as well (Yoshimura, et al. 1995). As such, he ranula as it is for the lower lip mucocele. To this recommends packing the cystic cavity with gauze end, there are several published papers adamantly for 7–10 days. In so doing, he reports that the recommending that more conservative procedures recurrence rate is reduced to 10–12% (Baurmash be performed as first line therapy (Baurmash 1992, 2007). McGurk points out that the disadvantage of 2007). One such procedure is marsupialization with this procedure is that the results are unpredictable packing (Baurmash 1992). The author contends and that the packing is uncomfortable for the that routine sublingual removal is inappropriate patient (McGurk 2007). He concludes by stating therapy for several reasons. The first is that the that reliable eradication of the ranula comes from term “ranula” is loosely applied to any cyst-like removal of the sublingual gland. Further work

k k

Cysts and Cyst-like Lesions of the Salivary Glands 103

by this author has led to a recommendation for the development of scar tissue in the ﬂoor of conservative treatment of the oral ranula by partial mouth is such that the anatomy may be more excision of the sublingual gland (McGurk et al. obscured related to a recurrence after a marsupi- 2008). It is true that the sublingual gland excision alization and packing procedure. With this issue requires an anatomically precise approach such in mind, a sublingual gland excision should prob- that some surgeons may wish to defer the sublin- ably be performed from the outset (Figure 4.8). gual gland excision for recurrences. Unfortunately, While the anatomy of the ﬂoor of mouth might

(a) (b) k k

(c) (d) Figure 4.8. The excision of the sublingual gland and associated ranula from Figure 4.1. An incision is designed over the prominence of the sublingual gland and ranula, and lateral to the Wharton duct (a). Careful dissection allows for separation of the mucosa from the underlying pseudocystic membrane (b). The dissection continues to separate the sublingual gland from surrounding tissues, including the underlying Wharton duct and the lingual nerve beneath the Wharton duct (c). The specimen and ranula are able to be delivered en bloc (d). If the pseudocyst bursts intraoperatively, no compromise in cure exists as long as the sublingual gland is completely excised. The histopathology shows the non-epithelial lining (e) and the intimate association of the sublingual gland and mucus escape reaction (f). The remaining tissue bed shows the anatomic relationship of the preserved superficial Wharton duct and underlying lingual nerve (g). Wharton duct originates posteriorly in a medial position to the lingual nerve and terminates in a position lateral to the nerve. The sublingual vein can be visualized in the tissue bed lateral to the anterior aspect of Wharton duct (g). Healing is uneventful as noted in the one month postoperative image (h).

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104 Chapter 4

(e) (f)

k k

(g) (h) Figure 4.8. (Continued)

be considered foreign and intimidating to some are predictably treated for cure with excision of the surgeons, preservation of the lingual nerve and offending sublingual gland. While it is not essen- Wharton duct is not a difﬁcult task, and treatment tial to remove the non-epithelial lined pseudocyst of this pathologic process with sublingual excision with the sublingual gland, it is common for the should be a curative procedure. One pathologic tightly adherent pseudocyst to be delivered with and clinical similarity of the ranula and mucocele the sublingual gland specimen (Figure 4.10). As is their derivation from salivary gland tissue. As such, documentation of a plunging component to stated previously, there does not seem to be a the ranula serves a matter of medical completeness dispute amongst clinicians as to the best surgical rather than representing an implication for surgical therapy for the mucocele, with complete surgical treatment. excision of the etiologic minor salivary tissue along with the mucus escape reaction being highly accepted (Figure 4.9). As such, it is advisable to Submandibular Gland Mucocele apply the same approach to the ranula that only Clinical experience demonstrates that patients differs from the mucocele in the anatomic region occasionally present with a neck examination in which it occurs. With regard to the ranula and consistent with a diagnosis of plunging ranula, plunging ranula, even the most extensive lesions yet without signs of ranula on oral examination.

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Cysts and Cyst-like Lesions of the Salivary Glands 105

Cyst of Blandin and Nuhn Glands On rare occasions, the mucosa of the ventral sur- face of the tongue may become a source for the development of a mucous escape reaction. This process is referred to as a cyst of Blandin and Nuhn gland (Figure 4.12). This designation is a misnomer, as this process represents a mucous escape reaction, rather than a true cyst. In this sense, then, it represents a ranula of the tongue. Simple excision of the “cyst” and the associated gland of Blandin and Nuhn is the treatment of choice with recurrence being uncommon.

Mucous Retention Cysts

The mucus retention cyst is less common than the mucus escape reaction. This entity is a true cyst Figure 4.9. The specimen from the excision of the muco- that is lined by epithelium. The exact classification cele seen in Figure 4.3. The minor salivary gland tissue of this lesion seems to be in question. Some prefer remains attached to the mucus escape reaction. to simply include it with the more common mucus escape reaction, whereas others describe it as a separate entity (Koudelka 1991). The pathogenesis Moreover, many of these patients will demonstrate seems to be related to partial obstruction of a duct, CT evidence of a fluid filled lesion originating from as opposed to complete severance of the salivary k the submandibular gland rather than from the duct that is seen in the mucus escape reaction. k sublingual gland. These rare cases are typically The increased pressure in the salivary duct causes diagnosed as submandibular gland mucoceles dilatation without rupture such that prolifera- (Ozturk, et al. 2005; Hze-Khoong, et al. 2012) tion of the ductal epithelium occurs. The Armed on clinical grounds and should be treated with Forces Institute of Pathology reviewed 178 cases excision of the offending submandibular gland of mucus retention cysts, accounting for 0.9% of and associated mucocele (Figure 4.11). A thorough all salivary gland pathology cases in their files analysis of the CT scans is thought to be able to (Koudelka 1991). One hundred and seventy-one distinguish the sublingual gland ranula from the cases (96%) occurred in the major salivary glands submandibular mucocele by identifying the tail-like with 156 (87.6%) occurring in the parotid gland extension of the ranula to the sublingual gland that (Figure 4.13), 14 cases (7.8%) occurring in the is absent in the submandibular gland mucocele submandibular gland, and only 1 case occur- (Anastassov, et al. 2000). This notwithstanding, ring in the sublingual gland. Only one case was the management of the submandibular gland specifically documented as occurring in the minor mucocele requires removal of the submandibular salivary glands. The mean age of patients is late gland and its associated mucocele. Excision of the 40s, with a nearly equal gender predilection. The sublingual gland en bloc with the submandibular clinical presentation of the mucus retention cyst is gland and mucocele may be performed when the that of a slowly enlarging, painless, fluctuant soft mucocele appears to be intimately associated the tissue swelling that may persist from months to sublingual gland (Ozturk, et al. 2005). The sur- years. These cysts vary in their size, and the color geon’s intraoperative discretion dictates whether of the overlying tissues depends on their depth the sublingual gland is indicated for removal when within the soft tissue. Superficial lesions are blue providing surgical treatment for the submandibular in color, whereas deep lesions take on the same gland mucocele. As with the mucocele and the color of the overlying tissue. Some pathologists ranula, appropriate surgical management of the have split the mucus retention cysts into separate submandibular mucocele represents a curative categories. Eversole has categorized these lesions procedure for this diagnosis. as mucus retention cysts, reactive oncocytoid cysts,

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106 Chapter 4

(a)

k k

(c) (b) Figure 4.10. The patient seen in Figure 4.7 underwent excision of her left sublingual gland for her plunging ranula. The specimen (a) includes the sublingual gland and associated mucus escape reaction. Her 2-year postoperative examination shows no mass in the submandibular region (b) and a normal oral examination without recurrence of the ranula (c).

and mucopapillary cysts (Eversole 1987). In his gland with the excision. Some mucus retention series of 121 mucus retention cysts, he found 70 cysts, however, may be removed without the inclu- mucus retention cysts, 41 reactive oncocytoid cysts, sion of the salivary gland, a distinct departure and 10 mucopapillary cysts. From a pathologic and from the recommendations associated with mucus surgical standpoint, perhaps the most striking escape reactions. piece of information in this report was the need to distinguish the mucopapillary cyst from the low-grade mucoepidermoid carcinoma. Parotid Cysts Associated with Human Treatment of mucus retention cysts is Immunodeficiency Virus Infection most commonly conservative surgical excision (Figure 4.13). Cysts within or closely associated Infection with the human immunodeﬁciency virus with a salivary gland should include that salivary has been shown to manifest in variety of ways.

k k

Cysts and Cyst-like Lesions of the Salivary Glands 107

(a) (c)

k k

(b) (d) Figure 4.11. A 48-year-old man with a swelling of the right submandibular region (a). Palpation of this swelling revealed a ballotable mass. A CT scan revealed a fluid filled lesion intimately associated with the right submandibular gland (b). A clinical diagnosis of submandibular gland mucocele was made and the patient underwent excision of his right sublingual gland and submandibular gland/mucocele (c). The presence of a submandibular gland mucocele was confirmed by histopathology (d). Hematoxylin and eosin, original magnification ×100.

Symptoms related to the head and neck have glands with or without hypofunction and xeros- historically been encountered in this disease. It has tomia (Owotade et al. 2005). In early lesions the been reported that 41% of patients with acquired submandibular and sublingual glands are often immunodeﬁciency syndrome (AIDS) initially pre- initially affected and enlarged. As the disease pro- sented with signs or symptoms of head and neck gresses, however, parotid gland swelling is more disease (Marcussen and Sooy 1985). Salivary gland commonly noted. As many as 5–10% of patients diseases include the enlargement of major salivary with HIV-1 infection have been reported to have

k k

108 Chapter 4

parotid swelling with the incidence increasing to approximately 20% in AIDS patients (Owotade, et al. 2005). Ryan and his group were the ﬁrst to describe salivary gland involvement in HIV disease as intrasalivary gland lymphadenopathy (Ryan, et al. 1985). Shortly thereafter, parotid gland cysts were reported, and were noted to resemble the benign lymphoepithelial lesion (BLL) histologically (Colebunders, et al. 1988). The BLL is a benign sialadenopathy associated with Sjogren syndrome with pathognomonic epimyoepithelial islands. It is felt to represent an autoimmune reaction in Sjogren syndrome, but the BLL is felt to be of unknown pathogenesis in HIV (Sperling, et al. 1990). It remains unclear whether lymphoepithelial cysts within parotid glands in HIV/AIDS Figure 4.12. A cyst of Blandin and Nuhn of the ventral sur- patients develop from pre-existing salivary gland face of the tongue. Simple excision of the cyst and associ- inclusions in intra-parotid lymph nodes or from a ated minor salivary gland tissue is curative for this mucus lymphoepithelial lesion of the parenchyma of the escape phenomenon. salivary gland.

k k

(a) (b)

(c) (d) Figure 4.13. A mucous retention cyst of the parotid gland as noted on MRI (T1 images–a;T2images–b).Thepatient underwent a superficial parotidectomy due to the concern for a cystic neoplasm. Histopathology showed a parotid cyst lined by columnar epithelium in one section of the cyst (c) and squamoid epithelium in another section (d).

k k

Cysts and Cyst-like Lesions of the Salivary Glands 109

k (a) (b) k

(c) (d) Figure 4.14. A 50-year-old HIV positive male presented in 1994 with obvious right parotid swelling (a,b). This time period pre-dated the development of HAART. Examination of the bilateral parotid gland regions revealed a large mass of the right parotid gland, and a smaller mass of the left parotid gland. Computerized tomograms (c) confirmed the findings of the physical examination. A clinical diagnosis of bilateral lymphoepithelial cysts was made. The patient requested removal of these cysts. A standard incision was made (d). This permitted unroofing of the large cyst in the right parotid gland (e) andthe smaller cysts in the left parotid gland (f). The specimen from the right parotid gland (g) and the left parotid gland (h) showed typical gross signs of lymphoepithelial cysts. The resultant right parotid tissue bed is noted (i). Six months postoperatively, the patient showed well healed surgical sites without signs of recurrent lymphoepithelial cysts (figures j, k, l, and m).

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110 Chapter 4

(e) (f) k k

(g) (h) Figure 4.14. (Continued)

Treatment of lymphoepithelial cysts of the an early experience with 50 patients with lym- parotid gland in HIV/AIDS patients is a function phoepithelial cysts of the bilateral parotid glands of the size of the cysts, the patient’s concern for (Shaha, et al. 1993). Their initial approach involved cosmetics, and compliance with medical ther- superficial parotidectomy with identification and apy. Following their original description, these preservation of the facial nerve. They subsequently cysts were managed in a variety of ways includ- performed excision of the cyst only. Ferraro and his ing periodic aspirations, simple excision of the group recommended against superficial parotidec- cysts, and nerve sparing superficial parotidectomy due to possible recurrence in the deep tomy (Figure 4.14). Shaha and his group reported lobe at a later date (Ferraro, et al. 1993). They

k k

Cysts and Cyst-like Lesions of the Salivary Glands 111

k (i) (j) k

(k) Figure 4.14. (Continued)

k k

112 Chapter 4

k (l) (m) k Figure 4.14. (Continued)

indicated that aspiration is usually ineffective as therapy will result in these cysts subsiding without a long term solution because of the high rates of the need for surgery (Figure 4.15). recurrence, in addition to the inability to obtain a tissue diagnosis of the cyst wall. Their solution to recurrence of the cyst was a second enucleation Branchial Cleft Cysts procedure. Improved and evolving pharmacologic ther- Patients with first branchial anomalies usually apy of HIV/AIDS has changed the management present with a unilateral painless swelling of the of these cysts. Highly active antiretroviral therapy parotid gland. Bilateral swelling is rare. Work has (HAART) uses combinations of drugs to maxi- classified these cysts as types I and II (Work 1977). mize viral suppression and minimize selection of Type I branchial defects are duplication anomalies drug-resistant strains. Most commonly, HAART of the membranous external auditory canal. These consists of a backbone of 2-nucleoside analogue defects are composed of ectoderm only. They are reverse transcriptase inhibitors in combination located within the preauricular soft tissues and with either a protease inhibitor or a non-nucleoside parotid gland and present as sinus tracts or areas reverse transcriptase inhibitor. Gland enlargement of localized swelling near the anterior tragus. Com- has been shown to be significantly and positively plete surgical removal is curative. Type II branchial associated with viral load in a linear fashion anomalies are less common than type I anomalies. (Mulligan, et al. 2000). Compliance with HAART, This defect is a duplication anomaly consisting therefore, has led to the observation that this of an anomalous membranous and cartilaginous

k k

Cysts and Cyst-like Lesions of the Salivary Glands 113

(a) (b) k k

(c) (d) Figure 4.15. A 35-year-old HIV positive man presented in 2005 with a complaint of bilateral parotid swellings. He admitted to non-compliance with his HAART. His CD4/CD8 was 0.69 at the time of initial consultation. Physical examination revealed an obvious right parotid swelling and a subtle mass of the left parotid gland (a and b). Computerized tomograms (c and d) confirmed these findings. A fine needle aspiration biopsy was performed that yielded thick white fluid. A diagnosisof lymphoepithelial cysts was made. The patient resumed his HAART and was the cysts regressed as noted on an examination 4 months later (e and f). His CD4/CD8 was 1.12 at this time.

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114 Chapter 4

k k (e) (f) Figure 4.15. (Continued)

external auditory canal. Unlike type I cysts, type epithelium and therefore are more accurately II cysts are composed of ectoderm and mesoderm. referred to as cyst-like lesions owing to ﬂuid They commonly present in the upper neck and ﬁlled soft tissue lining. are located posterior or inferior to the angle of the • The ranula and mucocele are examples of mandible and can extend into the external auditory mucous escape reactions that are not lined by canal or middle ear cavity. Sinus tracts are common epithelium. and abscess formation may also occur. Complete • Severance of a salivary duct due to trauma with surgical excision during an asymptomatic period resultant pooling of mucous into surrounding is the treatment of choice. The reader is directed tissues is the pathophysiology of the mucous to Chapter 17 for a more detailed discussion and escape reaction. illustration of these pathologic processes. • Excision of the salivary gland with or without the associated mucous escape reaction repre- Summary sents curative therapy for this process. • The mucous escape reaction is most com- • Cysts of the salivary glands may be asso- monly seen in the minor salivary glands. ciated with neoplasms or they may occur • Mucous retention cysts are lined by epithe- independently. lium, but are very rare. • While these lesions are collectively referred • When mucous retention cysts do occur, they to as cysts, many are not actually lined by seem to be most common in the major salivary

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Cysts and Cyst-like Lesions of the Salivary Glands 115

glands, particularly the parotid gland. Simple Harrison JD, Kim A, Al-Ali S, Morton RP. 2013. Postmortem excision is the treatment of choice. investigation of mylohyoid hiatus and hernia: aetiological • As many as 5–10% of patients with HIV-1 factors of plunging ranula. Clin Anat 26:693–699. infection have been reported to have parotid Hze-Khoong EP, Xu L, Shen S, Yin X, Wang L, Zhang C. swelling with the incidence increasing to 2012. Submandibular gland mucocele associated with a approximately 20% in AIDS patients. Lym- mixed ranula. Oral Surg Oral Med Oral Pathol Oral Radiol phoepithelial cysts account for the majority of 113:e6–e9. Koudelka BM. 1991. Obstructive Disorders. In: Ellis GL, these swellings. Auclair PL, Gnepp DR (eds), Surgical Pathology of the Salivary Glands. Philadelphia, WB Saunders, Ch. 3, pp. 26–38. References Lesperance MM. 2013. When do ranulas require a cervical approach? Laryngoscope 123:1826–1827. Anastassov GE, Haiavy J, Solodnik P, Lee H, Lumerman Marcussen DC, Sooy CD. 1985. Otolaryngologic and head H. 2000. Submandibular gland mucocele: diagnosis and and neck manifestations of acquired immunodeficiency management. Oral Surg Oral Med Oral Pathol Oral Radiol syndrome (AIDS). Laryngoscope 95:401–405. Endod 89:159–163. McClatchey KD, Appelblatt NH, Zarbo RJ, Merrel DM. 1984. Baurmash HD. 1992. Marsupialization for treatment of oral Plunging ranula. Oral Surg 57:408–412. ranula: A second look at the procedure. J Oral Maxillofac McGurk M. 2007. Management of the ranula. JOralMax- Surg 50:1274–1279. illofac Surg 65:115–116. Baurmash HD. 2007. A case against sublingual gland McGurk M, Eyeson J, Thomas B, Harrison JD. 2008. Conser- removal as primary treatment of ranulas. J Oral Maxillo- vative treatment of oral ranula by excision with minimal fac Surg 65:117–121. excision of the sublingual gland: histological support for Bhaskar SN, Bolden TE, Weinmann JP. 1956a. Pathogenesis a traumatic etiology. J Oral Maxillofac Surg 66:2050–2057. of mucoceles. J Dent Res 35:863–874. Mulligan R, Navazesh M, Komaroff E, et al. 2000. Salivary Bhaskar SN, Bolden TE, Weinmann JP. 1956b. Experimental gland disease in human immunodeficiency virus-positive obstructive adenitis in the mouse. J Dent Res. 35:852–862. women from the WIHS study. Oral Surg Oral Med Oral k k Braun TW, Sotereanos GC. 1982. Cervical ranula due to an Pathol Oral Radiol Endod 89:702–709. ectopic sublingual gland. JMaxFacSurg10:56–58. Owotade FJ, Fatusi OA, Adebiyi KE, et al. 2005. Clinical Cataldo E, Mosadomi A. 1970. Mucoceles of the oral mucous experience with parotid gland enlargement in HIV infec- membrane. Arch Otolaryngol 91:360–365. tion: a report of five cases in Nigeria. JContempDent Catone GA. 1995. Sublingual gland mucous escape. Pseudo- Pract 15:136–145. cysts of the oral-cervical region. In: Carlson ER (ed.), The Ozturk K, Yaman H, Arbag H, Koroglu D, Toy H. 2005. Comprehensive Management of Salivary Gland Pathology. Submandibular gland mucocele: report of two cases. Philadelphia, WB Saunders Co., pp. 431–477. Oral Surg Oral Med Oral Pathol Oral Radiol Endod Catone GA, Merrill RG, Henny FA. 1969. Sublingual gland 100:732–735. mucus-escape phenomenon – treatment by excision of Patel MR, Deal AM, Shockley WW. 2009. Oral and plunging sublingual gland. JOralSurg27:774–786. ranulas: What is the most effective treatment? Laryngo- Colebunders R, Francis H, Mann JM, et al. 1988. Parotid scope 119:1501–1509. swelling during human immunodeficiency virus infec- Ryan JR, Ioachim HL, Marmer J, et al. 1985. Acquired tion. Arch Otolaryngol Head Neck Surg 114:330–332. immune deficiency syndrome – Related lymphadeno- Dardick I. 1996. Mucocele and sialocysts. In: Color pathics presenting in the salivary gland lymph nodes. Atlas/Text of Salivary Gland Tumor Pathology.New Arch Otolaryngol Head Neck Surg 111:554–556. York, Igaku-Shoin Medical Publishers, Inc., Ch. 14, pp. Shaha AR, DiMaio, Webber C, et al. 1993. Benign lymphoep- 131–141. ithelial lesions of the parotid. Am J Surg 166:403–406. Eversole LR. 1987. Oral sialocysts. Arch Otolaryngol Head Sperling NM, Lin P, Lucente FE. 1990. Cystic parotid masses Neck Surg 113:51–56. in HIV infection. Head & Neck 12:137–341. Ferraro FJ, Rush BF, Ruark D, Oleske J. 1993. Enucle- Sigismund PE, Bozzato A, Schumann M, Koch M, Iro H, ation of parotid lymphoepithelial cyst in patients who Zenk J. 2013. Management of ranula: 9 years’ clini- are human immunodeficiency virus positive. Surg Gyn cal experience in pediatric and adult patients. JOral Obstet 177:525–527. Maxillofac Surg 71:538–544. Harrison JD. 2010. Modern management and pathophysiol- Suresh BV, Vora SK. 2012. Huge plunging ranula. J Maxillo- ogy of ranula: literature review. Head Neck 32:1310–1320. fac Oral Surg 11:487–490.

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Thoma KH. 1950. Cysts and tumors of the salivary and Work WP. 1977. Cysts and congenital lesions of the parotid mucous glands. In: Oral Pathology. A Histological, gland. Otlaryngol Clin North Am 10:339–343. Roentgenological, and Clinical Study of the Diseases of the Yoshimura Y, Obara S, Kondoh T, Naitoh S. 1995. A compar- Teeth, Jaws, and Mouth.3rdedn.St.Louis,C.V.Mosby ison of three methods used for treatment of ranula. JOral Co., pp. 1260–1265. Maxillofac Surg 53:280–282. van den Akker HP, Bays RA, Becker AE. 1978. Plunging or Zhao YF, Jia J, Jia Y. 2005. Complications associated with cervical ranula. Review of the literature and report of 4 surgical management of ranulas. J Oral Maxillofac Surg cases. J. Max Fac Surg 6:286–293. 63:51–54.

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Chapter 5 Sialolithiasis

Outline and subsequent formation of a sialolith. In addition, the development of edema within a salivary Introduction duct can exacerbate existing obstruction when a Pathophysiology of Sialolithiasis small sialolith is present. As such, sialadenitis and Clinical Features of Sialolithiasis sialolithiasis should be considered together. Which Multiple Sialoliths Bilateral Sialoliths of these pathologic processes is the instigating Differential Diagnosis and causative factor, however, is unknown (Williams Diagnosis of Sialolithiasis 1999). This chapter will therefore discuss sialolithi- Treatment of Sialolithiasis asis and review some important concepts of Submandibular Sialolithiasis sialadenitis previously discussed in Chapter 3. Parotid Sialolithiasis Treatment of Multiple Sialoliths and Bilateral (Multiple Gland) Sialoliths Pathophysiology of Sialolithiasis Miscellaneous Sialolithiasis k Summary Sialolithiasis results from the deposition of calcium k References salts within the ductal system of salivary glands. The salivary stones are comprised primarily of Introduction calcium phosphate with traces of magnesium and ammonia with an organic matrix consisting Sialolithiasis is a relatively common disorder of the of carbohydrates and amino acids. Historically, salivary glands characterized by the development it has been taught that salivary stones develop of calculi. Sialolithiasis is thought to affect approx- around a central nidus of any number of ele- imately 1% of the population based on autopsy ments, including desquamated epithelial cells, studies (Williams 1999). It has been estimated to foreign bodies, microorganisms, and mucous plugs represent more than 50% of major salivary gland (Bodner 1993). Progression occurs once the nidus disease and is the most common cause of acute becomes lodged within the salivary ductal system. and chronic salivary gland infections (Escudier Stagnation of saliva enhances the development 1998). Sialadenitis (see Chapter 3) and sialolithia- of the sialolith and occurs secondary to either sis are disorders of the salivary glands that go hand the nidus itself, or due to the tortuosity of the in hand. Some consider sialolithiasis to be both ductal system. The nidus subsequently becomes a consequence and cause of sialadenitis (Berry bathed in a solution supersaturated with respect to 1995). For example, in some cases, the presence calcium and phosphate and slowly calciﬁes. This of a sialolith may cause obstruction such that the pathophysiologic mechanism has been empirically salivary gland is predisposed to retrograde infec- accepted for decades, while a paucity of evidence tion. In other cases, the presence of sialadenitis exists on the speciﬁc cause of sialolith formation. may result in a change in the characteristics of the Kasaboglu, et al. (2004) analyzed the chemical saliva thereby favoring the deposition of calcium composition and micromorphology of sialoliths

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using X-ray diffraction analysis (EDX) and scan- Table 5.1. Composition of normal adult saliva ning electron microscopy (SEM) (Kasaboglu, et al. 2004). In their reported six cases, X-ray diffraction Submandibular Gland Parotid Gland analysis determined that the sialoliths were comprised completely of multiple and polymorphous Calcium 3.6 mEq/L 2.0 mEq/L hydroxyapatite crystals. In their SEM evaluation, Phosphate 4.5 mEq/L 6.0 mEq/L no foreign body or organic material, and no signs Bicarbonate 18 mEq/L 20 mEq/L of microorganism-dependent core formation was Sodium 21 mEq/L 23 mEq/L detected. Potassium 17 mEq/L 20 mEq/L There are several reasons for sialolithiasis Chloride 20 mEq/L 23 mEq/L being observed most commonly in the sub- Magnesium 0.3 mEq/L 0.2 mEq/L mandibular system. First, the submandibular Urea 7.0 mEq/L 15 mEq/L gland lies inferior to the Wharton duct such that Proteins 150 mg/dL 250 mg/dL the flow of saliva must travel against the forces of Amino acids <1mg/dL 1.5mg/dL gravity. The physical characteristics of the Wharton Fatty acids <1mg/dL 1mg/dL duct, specifically its length and two acute bends, Glucose <1mg/dL <1mg/dL also theoretically predispose the ductal system to the development of sialolithiasis. The relatively long duct increases the transit time of saliva in the ductal system. The first bend occurs as the gland, although possessing salivary stagnation, gland courses posterior to the mylohyoid muscle, does not result in an increase in stone formation and the second occurs just proximal to the exit (Williams 1999). In completely obstructed glands, of the duct superiorly into the anterior floor of the calcium secretory granules in the acini become mouth. While the anatomic nature of the Wharton depleted and the saliva is less likely to produce duct has been considered to be etiologic in the stones. Baurmash has stated that salivary stasis k genesis of sialoliths in this system, the angle of and salivary viscosity, rather than the calcium k the genu of the duct has been investigated as to content of the salivary secretion determine the whether it represents a significant contributory development of sialoliths (Baurmash 2004). factor (Drage, et al. 2002). Specifically, these researchers retrospectively studied this issue using sialograms in 23 patients with sialadenitis, 61 Clinical Features of Sialolithiasis patients with sialolithiasis, and a control group of 18 patients. There were no statistical differences in Approximately 85% of sialoliths occur in the sub- the angle of the genu in three groups suggesting mandibular gland, 10% in the parotid gland, 5% that the difference in the angle of the genu of the in the sublingual gland, and the incidence of this submandibular duct in the sagittal plane is not of pathology is extremely rare in the minor salivary etiologic significance in the formation of sialoliths. glands (Miloro 1998). When involved, minor sali- The authors indicated that the length of the duct vary gland sialoliths occur in the buccal mucosa or might be of significance in the formation of stones; upper lip, forming an indurated nodule that may however, that parameter was not investigated in mimic a neoplastic process. Sialolithiasis occurs their study. One final issue related to submandibu- more often in males, with a peak age of occurrence lar sialolithiasis is the alkaline nature of the saliva, between 20 and 50 years of age (Lustmann, et al. its viscosity, and relatively high content of calcium 1990). Sialolithiasis in children comprises only 3% salts, specifically phosphates, carbonates, and of cases (Liu and Rawal 2013) with the youngest oxalates that make the submandibular saliva more documented age being 2 years of age (Kim, et al. prone to sialolithiasis than the other major glands 2013). (see Table 5.1). All of these features contribute The left submandibular gland is more often to salivary stasis, crystallization of precipitated affected than the right gland, and bilateral involve- calcium salts with calculus formation, obstruction ment in the absence of another systemic disorder to salivary flow, and infection. Interestingly, partial is rare. In fact, stone formation is not highly obstruction appears to be of great importance in the associated with systemic abnormalities of calcium development of sialoliths. A completely obstructed metabolism (King, et al. 1990). Gout is the only

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Figure 5.1. A single sialolith noted within the right submandibular gland. Isolated stones are most common in the submandibular system.

k k Figure 5.3. This lateral cephalometric radiograph shows a single stone located within the Stensen duct.

Figure 5.2. This panoramic radiograph close-up shows two sialoliths within the left submandibular gland.

systemic disease known to predispose to salivary stone formation. These stones are primarily made up of uric acid. Multiple occurrences of sialolith formation independent of systemic illness in the same gland, however, are common. While salivary stones are single in 70–80% of cases (Figure 5.1), Figure 5.4. This panoramic radiograph shows an oval two calculi occur in 20% of cases, and more sialolith of the left submandibular gland. than two calculi occur in 5% of cases (Williams 1999; Miloro and Goldberg 2002) (Figure 5.2). duct. When present for long periods of time, Sialolithiasis of the parotid gland is rare. When these stones may become quite large (Figure 5.5). stones occur in the parotid gland, they are smaller Bilateral salivary stones are quite rare; however, than submandibular gland stones, and more often they have been observed (Lutcavage and Schaberg multiple (Figure 5.3). With regard to location, sub- 1991) (Figure 5.6). mandibular stones are located in the duct 75–85% Sialolithiasis most commonly presents with of the time, while parotid stones are located in the painful swelling, although painless swelling or hilum or gland parenchyma in at least half of cases pain only are occasionally reported as symptoms. (Williams 1999). Submandibular stones located Lustmann’s study showed swelling to be present in within the gland are oval in shape (Figure 5.4) 94% of their 245 cases of sialolithiasis, while pain and elongated in shape when they occur in the occurred in 65.2%, pus secretion in 15.5%, and

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(a)

Figure 5.6. This axial section of computerized tomograms show the presence of bilateral sialoliths of the submandibular glands.

MULTIPLE SIALOLITHS k It has long been believed that multiple stones k of the salivary glands represent an uncommon occurrence. With the increasing sophistication and resolution of imaging studies and the increasing use of sialoendoscopy; however, it has become apparent that multiple sialoliths are uncommon but not rare as once believed (Ardekian, et al. (b) 2014). In their study of 530 consecutive cases of Figure 5.5. This very large sialolith is associated with the sialolithiasis, Ardekian, et al. (2014) identified mul- right submandibular gland as seen on panoramic radio- tiple calculi in 37 of 530 (7%) of these cases. The graph (a). Due to its size, it might be confused with an mean number of sialoliths per patient was 3.4 with osteoma of the mandible such that computerized tomo- 16 sialoliths being the largest number present in grams help to identify its presence within the submandibu- one patient in this series. The submandibular gland lar gland (b). was affected in 33 cases (90%), and the parotid gland was affected in the remaining 4 cases (10%). Preoperative imaging identified a solitary sialolith an absence of symptoms in 2.4% of their patients in 3 of the 37 cases (8%) of multiple sialoliths (Lustmann, et al. 1990). When symptoms do occur, where additional sialoliths were discovered by their magnitude seems to vary according to the sialoendoscopy. In other words, 92% of the cases gland involved and the location and size of the of multiple sialoliths were correctly identified by sialolith. A small sialolith may be asymptomatic preoperative imaging. Of the multiple submandibu- and serendipitously discovered during routine lar sialoliths, 40% were located in the proximal dental radiographic examination. Once the stone aspect of the duct and 60% were located distally. increases in size, salivary flow will be impaired, The multiple parotid sialoliths were located in the and spasmodic pain occurs during eating. Purulent duct and were typically smaller than those located infection may accompany sialolithiasis. in the submandibular system.