# Diseases of the salivary glands **DR LALIMA TIWARI** BDSC (UWA), DCLINDENT (ORALMED) (UWA), MRACDS (ORALMED), FOMAA **ORAL MEDICINE SPECIALIST** **CLINICAL SENIOR LECTURER** Presented by: **Dr. Lalima Tiwari** BDSC (UWA), DClinDent (OralMed) (UWA), MRACDS (OralMed), FOMAA - Oral Medicine Specialist - Clinical Senior Lecturer # Learning Outcomes Knowledge of diseases of the salivary glands including localized salivary gland disorders; iatrogenic salivary gland disorders and diseases with extra-oral manifestations that present with salivary gland disorders. 1. Discuss the clinical features, diagnosis and treatment of salivary gland aplasia. 2. Describe the aetiology, pathogenesis, the clinical and histopathologic features and the diagnosis and treatment of: - Mucocles - Sialolithiasis - Sialadenitis - Sjogren syndrome - Sialadenosis - Necrotizing sialometaplasia This section covers knowledge of diseases of the salivary glands, including localized salivary gland disorders, iatrogenic salivary gland disorders, and diseases with extra-oral manifestations that present with salivary gland disorders. #### Developmental and Inflammatory Disorders 1. Discuss the clinical features, diagnosis, and treatment of salivary gland aplasia. 2. Describe the aetiology, pathogenesis, clinical and histopathologic features, diagnosis, and treatment of: - Mucoceles - Sialolithiasis - Sialadenitis - Sjogren syndrome - Sialadenosis - Necrotizing sialometaplasia # Learning Outcomes Discuss the aetiology, pathogenesis, the clinical and histopathologic features and the diagnosis and treatment of the following salivary gland neoplasms: - Pleomorphic adenoma - Warthin’s tumour - Oncocytoma - Mucoepidermoid carcinoma - Acinic cell carcinoma - Adenoidcystic carcinoma - Polymorphous low grade adenocarcinoma Discuss the aetiology, clinical features, diagnosis and management of dry mouth. #### Salivary Gland Neoplasms Discuss the aetiology, pathogenesis, clinical and histopathologic features, diagnosis, and treatment of the following salivary gland neoplasms: - Pleomorphic adenoma - Warthin’s tumour - Oncocytoma - Mucoepidermoid carcinoma - Acinic cell carcinoma - Adenoid cystic carcinoma - Polymorphous low grade adenocarcinoma #### Xerostomia Discuss the aetiology, clinical features, diagnosis, and management of dry mouth. ```markdown Review of anatomy - Three paired major salivary glands - Parotid - Submandibular - Sublingual - 600 – 1000 minor salivary glands - Buccal, lingual, palatal, labial mucosa - Floor of mouth ``` <img src="https://i.imgur.com/8XzQZ9L.png" alt="Anatomical illustration of the head and neck showing salivary glands">  #### Major Salivary Glands The human anatomy includes three paired major salivary glands: - Parotid - Submandibular - Sublingual #### Minor Salivary Glands There are between 600 and 1000 minor salivary glands located throughout the oral cavity, including: - Buccal, lingual, palatal, and labial mucosa - Floor of mouth Anatomical illustration of the head and neck showing the location and structure of the major salivary glands, including the parotid, submandibular, and sublingual glands, with a focus on their placement relative to the facial structures and oral cavity. # Review of histology - Parotid gland: - Serous acini - Pyramidal – shaped cells with basophilic appearance - Submandibular and Sublingual glands - Mixed mucous and serous acini - Lobules of acini separated by fibrous connective tissue septa and adipose tissue - Ductal system consists of ducts: - Intercalated - secretory - Striated - secretory - Interlobular – excretory - Myoepithelial cells surround acini and intercalated ducts - Basal cells associated with striated and excretory ducts <img src="https://i.imgur.com/1ZqXJjS.png" alt="Microscopic images of salivary gland tissue (a, b, c)"/> <img src="https://i.imgur.com/7mQYJ9p.png" alt="Diagram of salivary gland ductal system showing serous acinar cells, mucous acinar cells, myoepithelial cells, intercalated duct, striated duct, excretory duct, and saliva flow"/>     #### Glandular Composition - **Parotid gland**: Comprised of serous acini with pyramidal-shaped cells that have a basophilic appearance. - **Submandibular and Sublingual glands**: Comprised of mixed mucous and serous acini. - **Structural Organization**: Lobules of acini are separated by fibrous connective tissue septa and adipose tissue. #### Ductal System The ductal system is organized into specific functional units: - **Intercalated ducts**: Secretory function. - **Striated ducts**: Secretory function. - **Interlobular ducts**: Excretory function. #### Cellular Components - **Myoepithelial cells**: Surround the acini and intercalated ducts to facilitate secretion. - **Basal cells**: Associated with the striated and excretory ducts. Microscopic image of salivary gland tissue showing serous acini with pyramidal-shaped cells and basophilic appearance, consistent with parotid gland histology. Microscopic image of salivary gland tissue illustrating mixed mucous and serous acini, representative of submandibular and sublingual glands. Microscopic image of salivary gland tissue displaying lobules of acini separated by fibrous connective tissue septa and adipose tissue. Diagram of the salivary gland ductal system showing serous and mucous acinar cells, myoepithelial cells, intercalated duct, striated duct, excretory duct, and saliva flow. # Review of salivary gland physiology ## In health - Major salivary glands account for 90% of saliva production - Minor salivary glands account for 10% of saliva production - Saliva flow rate has circadian variation with a peak in late afternoon - Unstimulated whole saliva flow rate: 0.2 – 0.5 ml/min - Stimulated whole saliva flow rate: 1.0 – 2.0 ml/min - 60% of unstimulated whole saliva produced by submandibular glands - Primary saliva produced by acinar cells → ion composition modified during transport through striated ducts → sodium, chloride reabsorbed → bicarbonate and potassium secreted in ductal cells → myoepithelial cells help move saliva through ducts → hypotonic saliva - Excretion controlled by autonomic parasympathetic, and sympathetic nerves ## Salivary Gland Anatomy and Physiology ### Higher Centers - **Salivary Nuclei** - Autonomic nervous system - Parasympathetic fibers → Acetylcholine - Sympathetic fibers → Noradrenalin ### Afferent Nerves - Masticatory afferents → Trigeminal nerve - Gustatory afferents → Facial, glossopharyngeal and vagal nerves ### Saliva Composition #### Primary saliva (mM) | Ion | Na⁺ | K⁺ | Cl⁻ | |-----------|-----|----|-----| | Value | 145 | 4 | 100 | #### Final saliva (mM) | Condition | Na⁺ | K⁺ | Cl⁻ | HCO₃⁻ | |----------------|-----|----|-----|-------| | Unstimulated saliva | 2 | 27 | 23 | 2 | | Stimulated saliva | 47 | 20 | 40 | 25 | ### Salivary Gland Structure #### Parotid acini - Serous cells only #### Submandibular acini - Mixed mucous and serous cells #### Ductal System - Striated duct - Intercalated duct - Excretory duct ### Cellular Components - Myoepithelial cell ### Ion Transport in Ducts - Lumen - Na⁺ - Cl⁻ - HCO₃⁻ - K⁺ ### Receptors - Muscarinic and adrenergic Receptors ### Excretion - The oral cavity --- <figure> <img src="https://i.imgur.com/8XqQ7jK.png" alt="Salivary gland physiology diagram showing nerve inputs, gland structure, ion transport, and ductal system."> </figure>    #### Saliva Production and Flow Rates - **Production Distribution**: - Major salivary glands account for 90% of saliva production. - Minor salivary glands account for 10% of saliva production. - 60% of unstimulated whole saliva is produced by the submandibular glands. - **Flow Rates**: - Unstimulated whole saliva: 0.2 – 0.5 ml/min. - Stimulated whole saliva: 1.0 – 2.0 ml/min. - Flow rates follow a circadian variation, peaking in the late afternoon. #### Mechanism of Secretion 1. **Primary Saliva**: Produced by acinar cells. 2. **Modification**: Ion composition is modified during transport through striated ducts. - Sodium and chloride are reabsorbed. - Bicarbonate and potassium are secreted by ductal cells. 3. **Transport**: Myoepithelial cells help move saliva through the ducts. 4. **Final Product**: Results in hypotonic saliva delivered to the oral cavity. #### Neural Control and Regulation Excretion is controlled by the autonomic nervous system via muscarinic and adrenergic receptors: - **Parasympathetic fibers**: Release Acetylcholine. - **Sympathetic fibers**: Release Noradrenalin. - **Afferent Pathways**: - Masticatory afferents: Trigeminal nerve. - Gustatory afferents: Facial, glossopharyngeal, and vagal nerves. #### Saliva Ion Composition (mM) | Saliva Type | Na⁺ | K⁺ | Cl⁻ | HCO₃⁻ | | :--- | :--- | :--- | :--- | :--- | | **Primary Saliva** | 145 | 4 | 100 | - | | **Final (Unstimulated)** | 2 | 27 | 23 | 2 | | **Final (Stimulated)** | 47 | 20 | 40 | 25 | A detailed diagram illustrating salivary gland physiology, showing nerve inputs from higher centers, gland structure including parotid and submandibular acini, ductal system, and ion transport processes. The diagram also includes tables for primary and final saliva composition, highlighting changes in ion concentrations during saliva modification. A table showing the ion composition of primary saliva in mM, with values for Na⁺ (145), K⁺ (4), and Cl⁻ (100), located in the upper left section of the diagram. A table displaying the ion composition of final saliva in mM for both unstimulated and stimulated conditions, including Na⁺, K⁺, Cl⁻, and HCO₃⁻ concentrations, positioned at the bottom left of the diagram. ```mermaid graph TD A[SALIVA FUNCTIONS] --> B[Antifungal] A --> C[Wound healing] A --> D[Buffer] A --> E[Teeth mineralisation] A --> F[Food digestion] A --> G[Coating & Lubrications] A --> H[Antiviral] A --> I[Antibacterial] ```  #### Functions of Saliva Saliva serves multiple critical roles in oral and systemic health: - **Protection and Defense**: - Antibacterial - Antiviral - Antifungal - **Oral Maintenance**: - Buffer (pH regulation) - Teeth mineralization - Coating and lubrication - Wound healing - **Digestion**: - Food digestion A flowchart diagram illustrating the various functions of saliva in the oral cavity. The central box labeled 'SALIVA FUNCTIONS' is connected by arrows to surrounding boxes representing specific functions: antibacterial, antifungal, wound healing, buffer, teeth mineralisation, food digestion, coating & lubrications, and antiviral. The diagram visually organizes these functions as key roles of saliva. # Salivary gland aplasia - Congenital absence of salivary glands - Rare - Unilateral or bilateral - Isolated or part of a hereditary syndrome - Syndromes of the ectodermal tissues - Ectodermal dysplasia - Mandibulofacial dysotosis - Hemifacial microsomia - Parotid gland aplasia estimated incidence of 1: 5000 live births - Related to earlier morphogenesis compared to other salivary glands Salivary gland aplasia refers to the congenital absence of salivary glands. It is a rare condition that can be unilateral or bilateral and may occur as an isolated finding or as part of a hereditary syndrome. #### Etiology and Incidence - Parotid gland aplasia has an estimated incidence of 1:5,000 live births. - The higher frequency of parotid involvement is related to its earlier morphogenesis compared to other salivary glands. #### Associated Syndromes of Ectodermal Tissues - Ectodermal dysplasia - Mandibulofacial dysostosis - Hemifacial microsomia ```markdown | Developmental anomalies | Clinical features (head and neck) | | :--- | :--- | | **1. Syndromes closely related to SG aplasia/hypoplasia** | | | Lacrimo-auriculo-dento-digital syndrome (LADD) or Levy-Hollister syndrome | Oral cavity: small and sharp lateral incisor, lateral upper incisor agenesis, and bifid uvula<br>Lacrimal glands: aplasia/hypoplasia, duct obstruction, and absence of lacrimal punctum<br>Other: cup-shaped ears, sensory, or mixed deafness. | | Oculo-auriculo-vertebral spectrum (OAVS) | Oral cavity: micrognathia, macrostomia, oral facial cleft, mandibular hypoplasia/deformity, and tongue anomaly;<br>Other: microtia, hemifacial macrosomia, facial palsy, branchial cyst, preauricular skin tag, and oral apraxia | | Ectrodactyly ectodermal dysplasia cleft lip/palate syndrome (ECC) | Oral cavity: dental abnormalities, lip, and palate cleft<br>Lacrimal glands: absence of lacrimal punctum<br>Other: deformed ears, conductive hearing loss | | **2. Syndromes that can be associated with SG aplasia/hypoplasia** | | | Down syndrome | Oral cavity: dental agenesis, hypo/hyper/microdontia, delayed eruption, open bite, taurodontism, gingivitis/periodontitis, cheilitis-stomatitis, ogival vault, protruding tongue, and maxillary processes hypoplasia<br>Head and neck: slanting palpebral fissures, epicanthic folds, brachycephaly, flat cranial base, and flattened nose bridge | | Klinefelter syndrome | Oral cavity: shovel-shaped incisor, taurodontism, and delayed eruption<br>Head and neck: brachycephaly | | Treacher-Collins syndrome | Oral cavity: mandibular/maxillary dysostosis, cleft palate | | **3. Developmental anomalies associated with SG aplasia/hypoplasia in non-syndromic patients** | | | Lacrimal glands | Secretion disorders | | Oral cavity | Hypo/oligo/anodontia, enamel hypoplasia, multiple caries, fissured tongue, lip, and palate cleft | | Head and neck | Cranial deformity, mandibular ramus agenesis | SG, salivary gland. Togni Lucrezia, Mascitti Marco, Santarelli Andrea, Contaldo Maria, Romano Antonio, Serpico Rosario, Rubini Corrado, TITLE=Unusual Conditions Impairing Saliva Secretion: Developmental Anomalies of Salivary Glands, JOURNAL=Frontiers in Physiology, VOLUME=10, YEAR=2019 ```  | Developmental Anomalies | Clinical Features (Head and Neck) | | :--- | :--- | | **1. Syndromes closely related to SG aplasia/hypoplasia** | | | Lacrimo-auriculo-dento-digital syndrome (LADD) or Levy-Hollister syndrome | **Oral cavity:** small and sharp lateral incisor, lateral upper incisor agenesis, and bifid uvula. **Lacrimal glands:** aplasia/hypoplasia, duct obstruction, and absence of lacrimal punctum. **Other:** cup-shaped ears, sensory, or mixed deafness. | | Oculo-auriculo-vertebral spectrum (OAVS) | **Oral cavity:** micrognathia, macrostomia, oral facial cleft, mandibular hypoplasia/deformity, and tongue anomaly. **Other:** microtia, hemifacial macrosomia, facial palsy, branchial cyst, preauricular skin tag, and oral apraxia. | | Ectrodactyly ectodermal dysplasia cleft lip/palate syndrome (ECC) | **Oral cavity:** dental abnormalities, lip, and palate cleft. **Lacrimal glands:** absence of lacrimal punctum. **Other:** deformed ears, conductive hearing loss. | | **2. Syndromes that can be associated with SG aplasia/hypoplasia** | | | Down syndrome | **Oral cavity:** dental agenesis, hypo/hyper/microdontia, delayed eruption, open bite, taurodontism, gingivitis/periodontitis, cheilitis-stomatitis, ogival vault, protruding tongue, and maxillary processes hypoplasia. **Head and neck:** slanting palpebral fissures, epicanthic folds, brachycephaly, flat cranial base, and flattened nose bridge. | | Klinefelter syndrome | **Oral cavity:** shovel-shaped incisor, taurodontism, and delayed eruption. **Head and neck:** brachycephaly. | | Treacher-Collins syndrome | **Oral cavity:** mandibular/maxillary dysostosis, cleft palate. | | **3. Developmental anomalies in non-syndromic patients** | | | Lacrimal glands | Secretion disorders. | | Oral cavity | Hypo/oligo/anodontia, enamel hypoplasia, multiple caries, fissured tongue, lip, and palate cleft. | | Head and neck | Cranial deformity, mandibular ramus agenesis. | *SG: salivary gland.* A table categorizing developmental anomalies related to salivary gland (SG) aplasia/hypoplasia, divided into three sections: syndromes closely related to SG aplasia/hypoplasia, syndromes associated with SG aplasia/hypoplasia, and developmental anomalies in non-syndromic patients. The table lists various syndromes and their corresponding clinical features in the oral cavity, lacrimal glands, and head and neck regions. # Salivary gland aplasia ## Clinical Features - Dependent on number of missing salivary glands - Variable degrees of xerostomia and oral dryness - Some can be asymptomatic - Erythematous oral mucosa - Glossitis - Cheilitis - Chronic erythematous candidiasis - Exfoliate lips - Increased risk of dental caries, teeth erosion, periodontal disease - Tongue papillary atrophy - Oral ulcers - Hoarseness - Dysphagia - Oropharyngeal symptoms - Absence of parotid papillae or submandibular orifices - Lack of saliva production upon palpation - Asymmetry The clinical presentation of salivary gland aplasia is dependent on the number of missing glands. While some patients can be asymptomatic, others experience variable degrees of xerostomia and oral dryness. #### Oral Mucosal and Dental Impact - Erythematous oral mucosa - Glossitis and tongue papillary atrophy - Cheilitis and exfoliative lips - Chronic erythematous candidiasis - Oral ulcers - Increased risk of dental caries, teeth erosion, and periodontal disease #### Functional and Physical Signs - Hoarseness and dysphagia - Oropharyngeal symptoms - Absence of parotid papillae or submandibular orifices - Lack of saliva production upon palpation - Facial asymmetry ```html <table border="1" cellpadding="5" cellspacing="0"> <tr> <td> <img src="https://i.imgur.com/3QZ6z8l.png" alt="Oral cavity view showing tongue and teeth"/> </td> <td> <p>Louis Mandel, An unusual pattern of dental damage with salivary gland aplasia,<br>The Journal of the American Dental Association, Volume 137, Issue 7, 2006,<br>Pages 984-989,</p> <img src="https://i.imgur.com/3QZ6z8l.png" alt="Image A showing dental damage"/> <img src="https://i.imgur.com/3QZ6z8l.png" alt="Image B showing dental damage"/> <img src="https://i.imgur.com/3QZ6z8l.png" alt="Image C showing dental damage"/> <img src="https://i.imgur.com/3QZ6z8l.png" alt="Image D showing dental damage"/> </td> </tr> </table> <p>Chadi, M.J., Saint Georges, G., Albert, F., Mainville, G., Nguyen, J.M. and Kauzman, A. (2017), Major salivary gland aplasia and hypoplasia in Down syndrome: review of the literature and report of a case. Clin Case Rep, 5: 939-944. <a href="https://doi.org/10.1002/ccr3.975">https://doi.org/10.1002/ccr3.975</a></p> ```   Clinical documentation and literature reviews highlight unusual patterns of dental damage associated with salivary gland aplasia and hypoplasia, particularly in cases involving systemic conditions such as Down syndrome. A detailed intraoral photograph showing the tongue and teeth, illustrating dental damage in a patient with salivary gland aplasia. The image highlights severe carious lesions on the posterior teeth, consistent with the case study described in the accompanying text. A series of four close-up photographs (labeled A-D) showing severe dental damage in a patient with salivary gland aplasia. The images display extensive carious lesions on the posterior teeth, with significant tooth decay and loss of dental structure, illustrating the unusual pattern of dental damage. # Salivary gland aplasia ## Diagnosis - History - Examination findings - Imaging - Ultrasonography - Computed tomography (CT) - Magnetic resonance imaging (MRI) ## Management - Saliva substitutes - Lifestyle changes - Increase water intake - Limit irritating foods - Low-sugar diet - Regular dental examinations - Fluoride based dental products #### Diagnostic Methods - **History:** Comprehensive patient medical and dental history. - **Examination findings:** Clinical assessment of oral dryness and ductal orifices. - **Imaging:** - Ultrasonography - Computed tomography (CT) - Magnetic resonance imaging (MRI) #### Management Strategies - **Symptom Relief:** Use of saliva substitutes. - **Lifestyle Changes:** - Increase water intake - Limit irritating foods - Maintain a low-sugar diet - **Preventative Care:** - Regular dental examinations - Use of fluoride-based dental products 2. Describe the aetiology, pathogenesis, the clinical and histopathologic features and the diagnosis and treatment of: - Mucocèles - Sialolithiasis - Sialadenitis - Sjogren syndrome - Sialadenosis - Necrotizing sialometaplasia This section covers the aetiology, pathogenesis, clinical and histopathologic features, diagnosis, and treatment of the following conditions: - Mucoceles - Sialolithiasis - Sialadenitis - Sjogren syndrome - Sialadenosis - Necrotizing sialometaplasia # Mucocles ## Introduction - Mucocles are cavities filled with mucus present as benign soft tissue mass in the oral cavity (mucous extravasation cyst) - When in the floor of mouth, they are called ranula (mucous retention cyst) ## Epidemiology - Very common - Young persons are more frequently affected #### Overview - **Mucoceles:** Cavities filled with mucus that present as benign soft tissue masses in the oral cavity (mucous extravasation cyst). - **Ranula:** A mucocele located specifically in the floor of the mouth (mucous retention cyst). #### Epidemiology - Very common occurrence. - Young persons are the most frequently affected demographic. # Mucocles ## Aetiopathogenesis - Mucocles are often associated with a history of trauma, resulting in the leakage of fluid from the ducts or acini into the surrounding tissue - Mucous Retention Cysts (Ranula) are caused by obstruction of a duct rather than trauma ## Clinical Presentation - Mucocles commonly present as soft, painless swellings ranging from deep blue to normal pink in colour - Mucocles can occur as a lump on the mucosa or vermilion of the lower lip but can present at other intraoral sites - Duration is variable and often dependent on how much inconvenience the lesion causes <img src="https://i.imgur.com/7ZJjK8l.jpg" alt="Image from Contemporary Oral Medicine 2019"/> Image from Contemporary Oral Medicine 2019  #### Aetiopathogenesis - **Mucoceles:** Often associated with a history of trauma, resulting in the leakage of fluid from the ducts or acini into the surrounding tissue. - **Mucous Retention Cysts (Ranula):** Typically caused by the obstruction of a duct rather than direct trauma. #### Clinical Presentation - Commonly present as soft, painless swellings. - Color ranges from deep blue to normal pink. - Frequent locations include the mucosa or vermilion of the lower lip, though they can occur at other intraoral sites. - Duration is variable and often depends on the level of inconvenience caused to the patient. A close-up clinical photograph showing a mucocle on the lower lip, illustrating a soft, painless swelling with a bluish hue. The image is sourced from Contemporary Oral Medicine 2019 and visually supports the text describing the clinical presentation of mucocles as soft, painless swellings ranging from deep blue to normal pink in color. ```markdown # Mucocèles ## Histopathologie - Si retiré intact - Cyste pseudocystique contenant du mucus, de nombreux histiocytes épithéliaux foamy (muciphages), neutrophiles et tissu granuleux - Si retiré rupturé - Fragments de tissu granuleux contenant des histiocytes épithéliaux foamy (muciphages) et des neutrophiles, on peut voir du matériel mucineux. Parenchyme de glande salivaire retiré montrant des changements obstructifs - Atrophie des acini, dilatation des canaux avec hyalinisation périductale, infiltration lymphoplasmocytaire interstitielle et fibrose interstitielle à stade tardif - On peut voir un canal salivaire nourricier rupturé avec métaplasie squameuse - Les lésions chroniques s'organisent en fibrose ressemblant à un polype fibroépithélial - Aucune couche épithéliale cystique, on peut voir une muqueuse orale superficielle avec atrophie variable dans les mucocèles superficiels --- **Image 1** Micrographie à faible puissance (H&E 1.8x) montrant un mucocèle entièrement excisé avec du mucus extravasé et la glande salivaire nourricière. **Image 2** Micrographie à puissance moyenne (H&E 5x) montrant des changements obstructifs dans la glande salivaire mineure cohérents avec une sialoadénite chronique, des macrophages épithéliaux peuvent être vus parmi le mucus. --- Lee N, Ng T. Mucocèle. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/oralcavitymucocèle.html. Consulté le 14 mars 2022. ```   #### Histopathology - **Intact Lesions:** - Pseudocystic cavity containing mucus. - Presence of numerous foamy epithelial histiocytes (muciphages), neutrophils, and granulation tissue. - No epithelial cystic lining; superficial oral mucosa may show variable atrophy in superficial mucoceles. - **Ruptured Lesions:** - Fragments of granulation tissue containing muciphages and neutrophils. - Visible mucinous material. - Associated salivary gland parenchyma may show obstructive changes, including acinar atrophy, ductal dilatation with periductal hyalinization, interstitial lymphoplasmacytic infiltration, and late-stage fibrosis. - **Additional Features:** - A ruptured feeder salivary duct with squamous metaplasia may be observed. - Chronic lesions may organize into fibrosis resembling a fibroepithelial polyp. Low power micrograph (H&E 1.8x) showing a fully excised mucocèle with extravasated mucin and the feeding minor salivary gland, illustrating a pseudocystic cavity with mucus and histiocytes. Medium power micrograph (H&E 5x) showing obstructive changes in the minor salivary gland consistent with chronic sialoadenitis, with epithelioid macrophages visible among the mucin. # Mucocèles ## Diagnosis - History - Clinical examination - Biopsy ## Management - Removal of the lesion by complete excision without rupture including removal of the associated minor salivary gland is curative. - Damage to the adjacent gland during removal may result in a new lesion developing and the patient should be warned of this as well as possibility of sensory nerve damage. - Cryotherapy where deliberate destruction of mucocèle and underlying associated salivary gland tissue is another curative alternative, however no specimen is available for histopathologic review, so an accurate clinical diagnosis is paramount. #### Diagnosis - Patient history - Clinical examination - Biopsy #### Management - **Surgical Excision:** Complete excision of the lesion without rupture, including the removal of the associated minor salivary gland, is curative. - **Complications:** Damage to adjacent glands during surgery may cause new lesions; patients should be warned of this and the risk of sensory nerve damage. - **Cryotherapy:** An alternative curative method involving the deliberate destruction of the mucocele and underlying gland tissue. Note: This method does not provide a specimen for histopathologic review, making accurate clinical diagnosis essential. # Sialolithiasis - Also known as salivary calculus or salivary stones ## Epidemiology - Very common disease of the salivary glands - More than 80% of sialoliths occur in the submandibular gland or its duct, 6% occur in the parotid gland and 2% occur in the sublingual gland or minor salivary glands. - Occur more frequently in men than women - Peak incidence between 30 years – 60 years Sialolithiasis refers to the formation of salivary calculus or salivary stones. #### Epidemiology - A very common disease of the salivary glands. - **Distribution:** - >80% occur in the submandibular gland or its duct (Wharton’s duct). - 6% occur in the parotid gland. - 2% occur in the sublingual or minor salivary glands. - **Demographics:** More frequent in men than women, with a peak incidence between 30 and 60 years of age. # Sialolithiasis ## Aetiopathogenesis - Aetiology remains unknown, but there are some factors contributing to stone formation such as irregularities in the duct system, inflammation or local irritants - It is thought that the more alkaline, viscous, mucous-rich saliva which contains a higher percentage of calcium phosphates, in addition to the long and sinuous position of Wharton’s duct, contributes to stasis, making the submandibular gland more prone to the development of sialoliths than the parotid gland ## Clinical Presentation - Recurrent swelling and pain in the involved gland, often associated with eating due to obstructions of the draining duct may be seen, although some can be asymptomatic - Most common cause of acute and chronic infections of salivary glands - Can vary considerably in size, but usually less than 1cm - Can occasionally be palpated – feel like hard small pebbles <img src="https://i.imgur.com/5ZzXJzr.png" alt="Sialolithiasis images: (a) clinical view of sialolith in duct, (b) radiograph, (c) gross specimen, (d) histological section" /> Image from Contemporary Oral Medicine 2019  #### Etiology and Pathogenesis - The exact etiology is unknown, but contributing factors include duct system irregularities, inflammation, or local irritants. - The submandibular gland is more prone to stones due to: - More alkaline, viscous, and mucous-rich saliva. - Higher percentage of calcium phosphates. - The long, sinuous path of Wharton’s duct, which contributes to stasis. #### Clinical Presentation - Recurrent swelling and pain in the involved gland, often exacerbated by eating (mealtime syndrome). - Some cases remain asymptomatic. - Sialoliths are the most common cause of acute and chronic salivary gland infections. - Size is usually less than 1 cm. - Palpable stones feel like hard, small pebbles. A composite image showing four views of sialolithiasis: (a) a clinical view of a sialolith in the duct, (b) a radiograph revealing the stone, (c) a gross specimen of the stone next to a ruler, and (d) a histological section showing the stone within glandular tissue. ```markdown # Sialolithiasis ## Histopathology - Varying degrees of acinar destruction, fibrosis and chronic inflammation, with lymphoid aggregates containing prominent germinal centers - Ducts may undergo squamous and mucous metaplasia - Lobular arrangement is maintained - May see microliths <img src="https://i.imgur.com/placeholder.png" alt="40 year old man with submandibular pain; chronic inflammation is well circumscribed, lacking infiltration into the surrounding tissue (4x)."/> <img src="https://i.imgur.com/placeholder.png" alt="40 year old man with submandibular pain; chronic inflammation with acinar"/> ```   #### Histopathology - **Glandular Changes:** Varying degrees of acinar destruction, fibrosis, and chronic inflammation. - **Lymphoid Response:** Presence of lymphoid aggregates containing prominent germinal centers. - **Ductal Changes:** Ducts may undergo squamous and mucous metaplasia. - **Architecture:** The lobular arrangement of the gland is generally maintained. - **Microliths:** Small calcifications may be visible within the tissue. Microscopic image of a 40-year-old man with submandibular pain, showing chronic inflammation that is well-circumscribed and lacks infiltration into surrounding tissue at 4x magnification. Microscopic image of a 40-year-old man with submandibular pain, showing chronic inflammation with acinar involvement, illustrating histopathological features of sialolithiasis. ```markdown # Sialolithiasis ## Diagnosis - Clinical examination may reveal swelling and absence of saliva secretion from the gland if it is blocked - Diagnostic imaging is used to identify presumed salivary calculi: intraoral occlusal radiograph, OPG or CBCT. However, 60-70% calcified sialoliths are not detected by conventional radiography and non-contrast computerized tomography is indicated. ## Management - Lesions associated with minor salivary glands can be excised with the associated gland. - When a sialolith can be palpated in the oral cavity, the sialolith often can be removed by an intraoral or sialoendoscopic approach and the affected gland can be left in situ, otherwise the associated gland is often removed - Salivary gland massage, irrigation, sour diet, sialologues to stimulate salivary flow in cases of small sialolith Kraaij, S., Karagozoglu, K., Forouzanfar, T. et al. Salivary stones: symptoms, aetiology, biochemical composition and treatment. *Br Dent J* **217**, E23 (2014). https://doi.org/10.1038/sj.bdj.2014.1054 ``` ```html <table border="1" cellpadding="5" cellspacing="0"> <tr> <td><img src="https://i.imgur.com/3Q3Q3Q3.jpg" alt="Three salivary stones"></td> </tr> <tr> <td><img src="https://i.imgur.com/4Q4Q4Q4.jpg" alt="Close-up of a sialolith in the oral cavity"></td> </tr> <tr> <td><img src="https://i.imgur.com/5Q5Q5Q5.jpg" alt="Intraoral radiograph showing a sialolith"></td> </tr> </table> ```    #### Diagnosis - **Clinical Examination:** May reveal swelling and absence of saliva secretion upon ductal blockage. - **Imaging:** - Intraoral occlusal radiographs, OPG, or CBCT. - Note: 60-70% of calcified sialoliths are not detected by conventional radiography; non-contrast CT is the preferred indicator. #### Management - **Minor Glands:** Excision of the stone along with the associated gland. - **Major Glands:** - Palpable stones may be removed via an intraoral or sialoendoscopic approach, sparing the gland. - If endoscopic removal is not possible, the associated gland may require removal. - **Conservative Measures:** For small sialoliths, management includes salivary gland massage, irrigation, a sour diet, and sialogogues to stimulate flow. Three sialoliths (salivary stones) are shown in a clinical photograph, illustrating their size and irregular shape. This image is used to visually represent the subject of sialolithiasis discussed in the text. A close-up intraoral photograph shows a sialolith located in the floor of the mouth, near the opening of the submandibular duct. This image visually supports the discussion on diagnosis and management of salivary stones. An intraoral radiograph (occlusal view) displays a sialolith as a radiopaque object within the submandibular gland region. This image illustrates the use of diagnostic imaging, as mentioned in the text, to identify salivary calculi. # Sialadenitis ## Introduction - Bacterial sialadenitis can be either acute or chronic. - Often occurs in elderly patients who suffer from salivary gland hypofunction. ## Aetiopathogenesis - Decreased saliva flow rate is the primary predisposing factor, and this allows retrograde microbial colonization of the duct, which may result in the development of acute or chronic suppurative infection. - It can be associated with obstruction of the salivary ducts by deposition of calculi, mucus plugs, tumour growth or by trauma. - *Staphylococcus aureus* is the most common pathogen isolated from purulent sialadenitis Sialadenitis is an inflammation of the salivary glands. Bacterial forms can be either acute or chronic and often affect elderly patients with salivary hypofunction. #### Etiology and Predisposing Factors - **Primary Factor:** Decreased saliva flow rate, allowing retrograde microbial colonization of the duct. - **Obstruction:** Can be caused by calculi (stones), mucus plugs, tumor growth, or trauma. - **Microbiology:** *Staphylococcus aureus* is the most common pathogen isolated in purulent cases. # Sialadenitis ## Clinical Presentation - Acute sialadenitis is characterized by a painful swelling of a single salivary gland, commonly the parotid gland. - A purulent discharge may be expressed from the salivary duct orifice. - Patient may present with redness of the overlying skin or even abscess formation within the inflamed gland tissue. - The infection may become life-threatening in immunocompromised individuals due to sepsis. - Chronic sialadenitis may develop following acute sialadenitis, characterized by repeated episodes of pain and inflammation. <img src="https://i.imgur.com/5JzFzQm.jpg" alt="Image showing facial swelling consistent with sialadenitis"/> Image from Contemporary Oral Medicine 2019  #### Clinical Presentation - **Acute Sialadenitis:** - Painful swelling of a single gland (commonly the parotid). - Purulent discharge may be expressed from the duct orifice. - Overlying skin may be red; abscess formation may occur. - Risk of sepsis in immunocompromised individuals. - **Chronic Sialadenitis:** - May follow acute episodes. - Characterized by repeated cycles of pain and inflammation. A clinical photograph showing facial swelling consistent with sialadenitis, specifically highlighting the parotid gland area. The image illustrates a painful swelling of a single salivary gland, which is a key feature of acute sialadenitis as described in the accompanying text. # Sialadenitis ## Histopathology - Diagnoses of both acute supplicative and viral sialadenitis are usually reached on clinical grounds, although rarely biopsied - Acute supplicative sialadenitis is associated with edema, hyperemia and acute inflammation - Viral sialadenitis shows diffuse interstitial edema, intense hyperemia and a dense lymphohistiocytic infiltrate Ely KA. Sialadenitis-infectious. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/salivaryglandssialadenitis.html. Accessed March 14th, 2022. #### Histopathology - **Acute Suppurative Sialadenitis:** Characterized by edema, hyperemia, and acute inflammatory cell infiltration. - **Viral Sialadenitis:** Shows diffuse interstitial edema, intense hyperemia, and a dense lymphohistiocytic infiltrate. *Note: Diagnosis is usually clinical; biopsies are rarely performed for these conditions.* # Sialadenitis ## Diagnosis - Diagnosis is based mainly on clinical presentation. - Patients with chronic sialadenitis should be evaluated with imaging for underlying pathology such as a calculus or stricture. ## Management - Management involves treating the infection and reversing predisposing factors. - Stimulation of salivary flow by application of warm compresses, administration of sialogogues and salivary gland massage can be employed. - Empiric antimicrobial therapy is initially directed – often amoxicillin-clavulanate. #### Diagnosis - Primarily based on clinical presentation. - Chronic cases should be evaluated with imaging (e.g., ultrasound or CT) to identify underlying pathology like calculi or ductal strictures. #### Management - **Infection Control:** Empiric antimicrobial therapy, often starting with amoxicillin-clavulanate. - **Flow Promotion:** - Application of warm compresses. - Administration of sialogogues. - Salivary gland massage. - **Predisposing Factors:** Addressing the underlying cause of decreased flow or obstruction. # Sjogren syndrome ## Introduction - Sjogren’s Syndrome is an autoimmune systemic rheumatic disease characterized by progressive focal lymphocytic cell infiltration and destruction of exocrine glands - It predominantly affects the salivary and lacrimal glands leading to dry eyes and subjective dry mouth ## Epidemiology - Commonly affects females (female: male ratio of 9:1) - Can occur at all ages, but median age of presentation is around 50 years ## Aetiopathogenesis - Not completely understood but multiple environmental factors interacting with an individual’s genetic susceptibility can trigger autoimmunity resulting in chronic inflammation of exocrine glands and eventual loss of physiologic function Sjogren’s Syndrome is an autoimmune systemic rheumatic disease characterized by progressive focal lymphocytic infiltration and destruction of exocrine glands. #### Epidemiology - Predominantly affects females (9:1 female-to-male ratio). - Median age of presentation is approximately 50 years, though it can occur at any age. #### Pathogenesis - Triggered by environmental factors interacting with genetic susceptibility. - Results in chronic inflammation of exocrine glands (primarily salivary and lacrimal) and eventual loss of physiological function. # Sjogren syndrome **Clinical Manifestations** - Slowly progressing autoimmune disease - Clinical manifestations are extremely variable - Ranging from organ-specific disease to systemic autoimmune disease and lymphoproliferative condition Dryness of eyes and mouth **Oral signs:** - Dry, erythematous, sticky oral mucosa - Fissured tongue - Accelerated dental caries, oral candidosis - Swelling of parotid glands (1/3 of patients) **Ocular signs** - May be red in appearance - Conjunctival inflammation Dryness can affect nose, upper respiratory tract, oropharynx, vaginal dryness <img src="https://i.imgur.com/9Z1zQvL.jpg" alt="Sjogren syndrome - image of a tennis player"> Britto-Zeron et al. 2016  #### Clinical Manifestations Sjogren’s Syndrome is a slowly progressing disease with highly variable manifestations, ranging from organ-specific to systemic involvement. - **Sicca Symptoms:** Dryness of the eyes (xerophthalmia) and mouth (xerostomia). - **Oral Signs:** - Dry, erythematous, sticky mucosa. - Fissured tongue. - Accelerated dental caries and oral candidosis. - Parotid gland swelling (observed in 1/3 of patients). - **Ocular Signs:** - Red appearance and conjunctival inflammation. - **Other Dryness:** Can affect the nose, respiratory tract, oropharynx, and vagina. A photograph of a female tennis player, likely used as a visual metaphor or example related to the clinical manifestations of Sjogren syndrome. The image is cited as 'Britto-Zeron et al. 2016' and appears to be a figure accompanying the text on dryness and systemic effects. Sjogren syndrome <table> <tr> <th>General Symptoms</th> <th>Cutaneous features</th> <th>Articular and Muscle Features</th> </tr> <tr> <td> <ul> <li>Fatigue (80%)</li> <li>Chronic pain</li> <li>Low – grade fever (5%)</li> <li>Weight loss</li> <li>Lymphadenopathy (15%)</li> </ul> </td> <td> <ul> <li>Cutaneous vasculitis (10%)</li> <li>Purpura</li> <li>Cutaneous ulcers</li> <li>Annular erythema (9%)</li> <li>Abnormally dry skin (23-68%)</li> </ul> </td> <td> <ul> <li>Arthralgia (60-70%)</li> <li>Non – erosive arthritis</li> <li>Subclinical synovitis (20-30%)</li> <li>Myalgias (20-40%)</li> </ul> </td> </tr> </table>  #### Systemic Features - **General Symptoms:** - Fatigue (80%) - Chronic pain - Low-grade fever (5%) - Weight loss and Lymphadenopathy (15%) - **Cutaneous Features:** - Abnormally dry skin (23-68%) - Cutaneous vasculitis (10%), purpura, and ulcers - Annular erythema (9%) - **Articular and Muscle Features:** - Arthralgia (60-70%) - Myalgias (20-40%) - Subclinical synovitis (20-30%) and non-erosive arthritis A photograph showing two legs with widespread red, purpuric lesions, indicative of cutaneous vasculitis, a common feature in Sjogren syndrome. The image illustrates the skin manifestations associated with the condition, as listed in the surrounding text. # Sjogren syndrome ## Pulmonary Complications (25%) - Chronic obstructive lung disease - Bronchiectasis - Interstitial lung diseases - Pleuritis ## Cardiovascular complications - Raynaud phenomenon (13% of patients) - Pericarditis - Pulmonary arterial hypertension - Dysautonomia - Cryoglobulinaemic vasculitis ## Nephro-urological complications - Renal tubular acidosis (9% of patients) - Glomerulonephritis (4% of patients) - Interstitial cystitis (in the absence of bacterial infection) - Osteomalacia - Recurrent renal colic due to renal stones - Hypokalaemic paralysis #### Internal Organ Complications - **Pulmonary (25%):** Chronic obstructive lung disease, bronchiectasis, interstitial lung diseases, and pleuritis. - **Cardiovascular:** Raynaud phenomenon (13%), pericarditis, pulmonary arterial hypertension, dysautonomia, and cryoglobulinaemic vasculitis. - **Nephro-urological:** - Renal tubular acidosis (9%) and glomerulonephritis (4%). - Interstitial cystitis, osteomalacia, and renal stones. - Hypokalaemic paralysis. # Sjogren syndrome ## Peripheral nervous system complications (10%) - Mixed polyneuropathy - Axon sensory polyneuropathy - Axon sensorimotor polyneuropathy - Trigeminal or other cranial neuropathies - Demyelinating polyradiculoneuropathy - Small-fibre neuropathy (painful paraesthesias) ## Central nervous system complications (2%) - White matter lesions (multiple sclerosis-like disease) - Neuromyelitis optica spectrum disorder - Recurrent aseptic meningitis ## Haematologic Features - Haemolytic anaemia - Unexplained leukopenia (lymphopenia and neutropoenia) - Unexplained thrombocytopenia**** (2%) - Evans syndrome - Unexplained monoclonal gammopathy - Thrombotic thrombocytopenic purpura - B cell lymphoma**** (5%) #### Neurological and Haematologic Complications - **Peripheral Nervous System (10%):** Mixed polyneuropathy, axon sensory/sensorimotor polyneuropathy, trigeminal or cranial neuropathies, and small-fibre neuropathy. - **Central Nervous System (2%):** White matter lesions (MS-like), neuromyelitis optica, and recurrent aseptic meningitis. - **Haematologic Features:** - Unexplained leukopenia, lymphopenia, or neutropenia. - Thrombocytopenia (2%) and Evans syndrome. - Monoclonal gammopathy. - **B-cell lymphoma (5%):** A significant long-term risk. # Sjogren syndrome ## Histopathology – labial salivary gland biopsy - The key requirements for an accurate histological evaluation are an adequate number of glands (3–5 in total) - Determination of an average focus score (the number of lymphocytic aggregates per 4 mm² of glandular surface analysed) - ≥1 foci/ 4mm² - Focal lymphocytic sialadenitis is the key histopathological feature of SS Brito-Zeron et al. 2016 Shiboski et al. 2016 #### Histopathology: Labial Salivary Gland Biopsy - **Requirements:** Accurate evaluation requires an adequate sample size (3–5 glands). - **Focus Score:** Defined as the number of lymphocytic aggregates (foci) per 4 mm² of glandular surface. - **Diagnostic Threshold:** A focus score of ≥1 foci/4 mm² is indicative of the disease. - **Key Feature:** Focal lymphocytic sialadenitis is the hallmark histopathological feature of Sjogren’s Syndrome. ```html <table border="1" cellpadding="5" cellspacing="0" style="border-collapse: collapse; width: 100%;"><tr><td style="text-align: center; vertical-align: middle;"><strong>Figure 4 Histopathological features of the salivary gland in SjS scenarios</strong></td></tr><tr><td style="text-align: center; vertical-align: middle;"><img src="https://i.imgur.com/3XJZQ3L.png" alt="Figure 4 Histopathological features of the salivary gland in SjS scenarios" /></td></tr><tr><td style="text-align: center; vertical-align: middle;"><strong>Nature Reviews | Disease Primers</strong><br>Images courtesy of L. A. Hernández, Hospital Clinic, Barcelona, Spain.<br><br>Brito-Zerón, P. et al. (2016) Sjögren syndrome<br>Nat. Rev. Dis. Primers doi:10.1038/nrdp.2016.47</td></tr></table> ```  Histopathological analysis of salivary glands in Sjogren’s Syndrome scenarios typically demonstrates the characteristic focal lymphocytic sialadenitis required for classification and diagnosis. Figure 4 shows histopathological features of the salivary gland in Sjögren syndrome (SjS) scenarios, presenting four micrographs (a-d) of tissue sections stained with hematoxylin and eosin. The images illustrate progressive changes in glandular architecture, including lymphocytic infiltration and glandular destruction, with white circles highlighting specific areas of interest. # Sjogren syndrome - Diagnosis of Sjogren’s Syndrome is based on both clinical presentation and laboratory investigations - The 2016 American College of Rheumatology/European League Against Rheumatism provides a classification criterion on SS utilising a weighted sum of five items ## Management - 5-10% of Sjogren’s syndrome patients develop mucosa-associated lymphoid issue, often in parotid glands and thus require periodic review - Utilize products to relieve oral dryness (saliva stimulation, moisturizing agents) and reinforce caries prevention protocol Table 3. American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome: The classification of primary Sjögren's syndrome applies to any individual who meets the inclusion criteria, does not have any of the conditions listed as exclusion criteria, and has a score of ≥4 when the weights from the 5 criteria items below are summed. | Item | Weight/score | | :--- | :--- | | Labial salivary gland with focal lymphocytic sialadenitis and focus score of ≥1 foci/4 mm² | 3 | | Anti-SSA/Ro positive | 3 | | Ocular Staining Score ≥5 (or van Bijsterveld score ≥4) in at least 1 eye | 1 | | Schirmer's test ≤5 mm/5 minutes in at least 1 eye | 1 | | Unstimulated whole saliva flow rate ≤0.1 ml/minute | 1 |  #### Classification Criteria (ACR/EULAR 2016) Primary Sjogren’s Syndrome is classified if a patient scores ≥4 based on the following weighted items: | Item | Weight/Score | | :--- | :--- | | Labial salivary gland with focal lymphocytic sialadenitis (focus score ≥1/4 mm²) | 3 | | Anti-SSA/Ro positive | 3 | | Ocular Staining Score ≥5 (or van Bijsterveld score ≥4) in at least 1 eye | 1 | | Schirmer's test ≤5 mm/5 minutes in at least 1 eye | 1 | | Unstimulated whole saliva flow rate ≤0.1 ml/minute | 1 | #### Management and Monitoring - **Lymphoma Risk:** 5-10% of patients develop mucosa-associated lymphoid tissue (MALT) lymphoma, often in the parotid glands; periodic review is mandatory. - **Symptom Management:** Use of saliva stimulants and moisturizing agents. - **Prevention:** Reinforcement of strict caries prevention protocols. Table 3 presents the American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome, listing five items with corresponding weights. The table includes criteria such as labial salivary gland biopsy with focal lymphocytic sialadenitis (score 3), anti-SSA/Ro positivity (score 3), ocular staining score ≥5 (score 1), Schirmer's test ≤5 mm/5 minutes (score 1), and unstimulated whole saliva flow rate ≤0.1 ml/minute (score 1). A diagnosis requires a total score of ≥4. # Sialadenosis ## Introduction - It is an uncommon, benign, non-inflammatory, non-neoplastic, bilaterally symmetrical and painless enlargement of salivary glands. - It is also known as sialosis. ## Epidemiology - Usually begins between ages 20 – 60 years and may persist for more than 20 years. - More commonly affects the parotid glands. ## Aetiopathogenesis - A variety of causes are recognized, most associated with autonomic neuropathy. - This condition can be associated with endocrine disorders such as diabetes mellitus and hypothyroidism, alcohol abuse, nutritional disorders and medication induced-sialadenosis including psychotropic medications and antihypertensive drugs. Sialadenosis (or sialosis) is an uncommon, benign, non-inflammatory, and non-neoplastic enlargement of the salivary glands, typically presenting as bilaterally symmetrical and painless swelling. #### Epidemiology - Usually begins between ages 20 and 60 years. - Condition may persist for over 20 years. - Most commonly affects the parotid glands. #### Etiology - Often associated with autonomic neuropathy. - **Linked Conditions:** - Endocrine disorders (Diabetes mellitus, hypothyroidism). - Alcohol abuse and nutritional disorders. - Medication-induced (psychotropic or antihypertensive drugs). # Sialadenosis ## Clinical Features - Patients present with slowly progressing bilateral swelling of parotid glands. - They can be asymptomatic - Rarely patients may complain of reduced salivary flow ## Histopathology - Acinar enlargement - The diameter of the acinar cell tends to increase by two to three times that of normal. - The nuclei tend to be basally situated, and the cytoplasm tends to be packed with granules. - There is no correlation between the specific clinical type of sialosis and the histologic appearance. - Inflammatory cells tend to be absent. - The long-standing nature of the underlying disease may ultimately lead to acinar atrophy and replacement with fat <img src="https://i.imgur.com/4JjXeKQ.png" alt="Microscopic images of sialadenosis (A1, B1, A2 CK14, B2 CK14) and clinical photographs of patient with bilateral parotid gland swelling." />   #### Clinical Presentation - Slowly progressing bilateral swelling of the parotid glands. - Patients are often asymptomatic, though some may complain of reduced salivary flow. #### Histopathology - **Acinar Changes:** Significant acinar enlargement (2-3 times normal diameter). - **Cellular Features:** Basally situated nuclei and cytoplasm packed with granules. - **Inflammation:** Inflammatory cells are typically absent. - **Progression:** Long-standing disease may eventually lead to acinar atrophy and fatty replacement. - *Note: There is no correlation between specific clinical types and histologic appearance.* Microscopic images showing histopathological features of sialadenosis, including acinar enlargement with enlarged cells and granular cytoplasm, labeled as A1, B1, A2 CK14, and B2 CK14. Clinical photographs of a patient with bilateral parotid gland swelling, showing frontal and profile views with the eyes obscured for privacy. # Sialadenosis ## Diagnosis - Diagnosis is one of exclusion, based mainly on history and clinical examination. - Investigations may include: blood tests, ultrasound, sialography. - Biopsy is rarely needed. ## Management - No treatment is available. - If a likely cause is identified, then sialadenosis may resolve when underlying cause is managed. #### Diagnosis - Primarily a diagnosis of exclusion based on history and clinical examination. - **Investigations:** May include blood tests, ultrasound, or sialography. - **Biopsy:** Rarely required. #### Management - No specific treatment is available. - Sialadenosis may resolve if the underlying systemic cause (e.g., endocrine disorder or medication) is successfully managed. # Necrotizing sialometaplasia - Benign, inflammatory disorder of salivary glands ## Aetiopathogenesis - Aetiology unknown - Ischaemic necrosis of minor salivary gland tissue thought to be causative factor - Associated with smoking - Local trauma - Pressure from denture - Local anaesthetic injection - Local surgical procedures - Immune response to unknown allergen Necrotizing sialometaplasia is a benign, inflammatory disorder of the salivary glands. #### Etiology - The exact etiology is unknown, but ischemic necrosis of minor salivary gland tissue is the primary causative factor. - **Associated Triggers:** - Smoking - Local trauma or pressure from dentures - Local anesthetic injections or surgical procedures - Immune response to an unknown allergen # Necrotizing sialometaplasia ## Clinical Features - Posterior region of hard palate - Chronic ulcer on hard palate – punched out appearance - Can resemble malignancy ## Histopathology - Lobular arrangements of salivary tissue with squamous cell metaplasia of ductal system centrally - Islands of squamous cells can be close to salivary ducts with features of hyperplasia - Necrotic acini and inflammatory cells are present at periphery - Inflammatory infiltrate is diffuse and mixed with lymphocytes, plasma cells, neutrophils, occasional eosinophils, macrophages --- <img src="https://i.imgur.com/9WJzJzL.png" alt="Microscopic images of necrotizing sialometaplasia showing clinical appearance (a) and histopathological features (b)"/> Contemporary oral medicine, 2019 Tanakchi S, Aly FZ. Necrotizing sialometaplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/salivaryglandsnecrotizingsialo.html. Accessed March 14th, 2022.   #### Clinical Presentation - Most commonly located in the posterior region of the hard palate. - Presents as a chronic, "punched-out" ulcer. - Clinical appearance can resemble malignancy (e.g., squamous cell carcinoma). #### Histopathology - **Ductal Changes:** Lobular arrangement is preserved, but the central ductal system shows squamous cell metaplasia. - **Cellular Features:** Islands of squamous cells may show hyperplasia. - **Necrosis:** Necrotic acini and inflammatory cells are present at the periphery. - **Infiltrate:** Diffuse mixed inflammatory infiltrate consisting of lymphocytes, plasma cells, neutrophils, macrophages, and occasional eosinophils. Microscopic images of necrotizing sialometaplasia showing clinical appearance (a) and histopathological features (b). Image (a) displays a chronic ulcer on the hard palate with a punched-out appearance, while image (b) shows lobular arrangements of salivary tissue with squamous cell metaplasia and necrotic acini at the periphery. A histopathological image of necrotizing sialometaplasia showing a tissue section with lobular arrangements of salivary tissue, squamous cell metaplasia of the ductal system centrally, and necrotic acini with inflammatory cells at the periphery. # Necrotizing sialometaplasia ## Diagnosis - Clinical examination - Biopsy ## Management - Self-limiting - Resolves in 3 – 10 weeks - Symptomatic treatment: analgesics, 0.12% Chx - Surgical intervention not required #### Diagnosis - Clinical examination - Biopsy (essential to rule out malignancy) #### Management - **Natural Course:** The condition is self-limiting. - **Resolution:** Typically resolves spontaneously within 3 to 10 weeks. - **Symptomatic Treatment:** Analgesics and 0.12% Chlorhexidine (Chx) mouthwash. - **Intervention:** Surgical intervention is not required. # Learning Outcomes Discuss the aetiology, pathogenesis, the clinical and histopathologic features and the diagnosis and treatment of the following salivary gland neoplasms: - Pleomorphic adenoma - Warthin’s tumour - Oncocytoma - Mucoepidermoid carcinoma - Acinic cell carcinoma - Adenoidcystic carcinoma - Polymorphous low grade adenocarcinoma Discuss the aetiology, clinical features, diagnosis and management of dry mouth. #### Learning Outcomes Discuss the aetiology, pathogenesis, clinical and histopathologic features, diagnosis, and treatment of the following salivary gland neoplasms: - Pleomorphic adenoma - Warthin’s tumour - Oncocytoma - Mucoepidermoid carcinoma - Acinic cell carcinoma - Adenoid cystic carcinoma - Polymorphous low grade adenocarcinoma Discuss the aetiology, clinical features, diagnosis, and management of dry mouth. # Pleomorphic adenoma ## Introduction - Other names: Benign mixed tumour. - Most common benign neoplasm of the major and minor salivary glands (account for up to 80% of benign salivary gland tumours). - Malignant transformation may occur in long-standing lesions. ## Epidemiology - Wide age range – may be found in children and adults; but most common in the 3rd to 6th decades of life. - Female predominance (2:1). #### Introduction - **Other names:** Benign mixed tumour. - **Prevalence:** Most common benign neoplasm of the major and minor salivary glands, accounting for up to 80% of benign salivary gland tumours. - **Malignancy:** Malignant transformation may occur in long-standing lesions. #### Epidemiology - **Age:** Wide age range; found in children and adults, but most common in the 3rd to 6th decades of life. - **Gender:** Female predominance (2:1). # Pleomorphic adenoma ## Aetiopathogenesis - Aetiology unknown. - Incidence of pleomorphic adenomas have been reported to increase 15-20 years after exposure to radiation. ## Clinical Presentation - Slow-growing, painless submucosal mass. The tumour may remain undiagnosed for years. - May be fixed or mobile. - Signs and symptoms depend on site of involvement. It may also present with pain, facial nerve palsy, skin fixation and epistaxis. - In the major salivary glands, the most common site of occurrence is the superficial lobe of the parotid gland. Less commonly, it can occur in the submandibular and sublingual salivary glands. - In minor salivary glands, the most common sites of occurrence are the palate and upper lip; but can occur at any oral site as well as the nose, paranasal sinuses and larynx. - Rapid enlargement of a tumour nodule should raise suspicion of malignant transformation. #### Aetiopathogenesis - **Aetiology:** Unknown. - **Radiation:** Incidence has been reported to increase 15-20 years after exposure to radiation. #### Clinical Presentation - **Growth:** Slow-growing, painless submucosal mass; may remain undiagnosed for years. - **Mobility:** May be fixed or mobile. - **Symptoms:** Depend on the site of involvement; may include pain, facial nerve palsy, skin fixation, and epistaxis. - **Major Salivary Glands:** Most common site is the superficial lobe of the parotid gland. Less commonly occurs in submandibular and sublingual glands. - **Minor Salivary Glands:** Most common sites are the palate and upper lip, but can occur at any oral site, the nose, paranasal sinuses, and larynx. - **Warning Signs:** Rapid enlargement of a tumour nodule should raise suspicion of malignant transformation. # Pleomorphic adenoma ## Histopathology - Bosselated outer surface, often with tongue-like protrusions (pseudopods) - Typically has 3 components: - Epithelial (ductal) component forming the inner layer of cysts and tubules - Myoepithelial cells as the outer layer of cysts and tubules and scattered within the myxoid stroma - Cytology of myoepithelial cells can be plasmacytoid, spindled, epithelioid, clear or stellate shaped - Stromal component is typically myxoid, chondroid or myxochondroid - It can also be hyalinized or fibrotic - Metaplastic changes may be seen, e.g. adipose metaplasia, osseous metaplasia, squamous metaplasia (sometimes with keratinization), sebaceous metaplasia and mucinous metaplasia - Intravascular permeation has been reported in a small percentage of cases and does not increase the risk of recurrence or distant metastasis #### Histopathology - **Gross Features:** Bosselated outer surface, often with tongue-like protrusions (pseudopods). - **Primary Components:** - **Epithelial (ductal):** Forms the inner layer of cysts and tubules. - **Myoepithelial cells:** Forms the outer layer of cysts and tubules; also scattered within the myxoid stroma. Cytology can be plasmacytoid, spindled, epithelioid, clear, or stellate shaped. - **Stromal component:** Typically myxoid, chondroid, or myxochondroid; can also be hyalinized or fibrotic. - **Metaplastic Changes:** May include adipose, osseous, squamous (sometimes with keratinization), sebaceous, and mucinous metaplasia. - **Vascular Involvement:** Intravascular permeation has been reported in a small percentage of cases and does not increase the risk of recurrence or distant metastasis. ```html <table> <tr> <td><img src="https://i.imgur.com/1a.png" alt="Image a" /></td> <td><img src="https://i.imgur.com/1b.png" alt="Image b" /></td> </tr> <tr> <td><img src="https://i.imgur.com/1c.png" alt="Image c" /></td> <td><img src="https://i.imgur.com/1d.png" alt="Image d" /></td> </tr> </table> ``` Image from Contemporary oral medicine. 2019     #### Microscopic Illustrations Visual documentation of Pleomorphic Adenoma features (Contemporary Oral Medicine, 2019) demonstrating the diverse epithelial and stromal arrangements characteristic of the "mixed" tumour. Clinical photograph showing a lesion in the oral cavity, with visible tissue and teeth, labeled as image a. Clinical photograph showing a surgical procedure with a tumor being excised, labeled as image b. Histopathological image of a tissue sample stained with hematoxylin and eosin, showing cellular architecture, labeled as image c. Microscopic view of a tissue section showing cellular details and staining patterns, labeled as image d. # Pleomorphic adenoma ## Diagnosis - History. - Clinical examination. - Investigations may include: - Imaging – e.g. ultrasound, CT, MRI. - Biopsy - Small incisional biopsies or fine needle aspirates can complicate diagnosis as they may not be representative of the entire lesion. ## Management - Excision of the tumour with clear margins. - Prognosis is excellent after surgical resection in most cases. - Recurrence is related to many factors, including incomplete encapsulation, extracapsular tumour extension, and intraoperative tumour rupture and spillage. - Malignant transformation into Carcinoma ex pleomorphic adenoma occurs in up to 7% of cases. #### Diagnosis - **History and Clinical Examination** - **Investigations:** - Imaging: Ultrasound, CT, MRI. - Biopsy: Small incisional biopsies or fine needle aspirates (FNA) can complicate diagnosis as they may not be representative of the entire lesion. #### Management and Prognosis - **Treatment:** Excision of the tumour with clear margins. - **Prognosis:** Excellent after surgical resection in most cases. - **Recurrence Factors:** Related to incomplete encapsulation, extracapsular tumour extension, and intraoperative tumour rupture/spillage. - **Malignant Transformation:** Progression into Carcinoma ex pleomorphic adenoma occurs in up to 7% of cases. # Warthin’s tumour ## Introduction - Other names: Adenolymphoma, papillary cystadenoma lymphomatosum, cystadenolymphoma. - Warthin tumour is a benign salivary gland tumour composed of oncocytic epithelial cells lining ductal, papillary and cystic structures in a lymphoid stroma. - It is the second most common salivary gland neoplasm. - Malignant transformation has been reported. ## Epidemiology - Accounts for up to 15% of all salivary gland tumours. - Most commonly diagnosed in the 6th to 7th decade of life. - Slight male predominance. #### Introduction - **Other names:** Adenolymphoma, papillary cystadenoma lymphomatosum, cystadenolymphoma. - **Definition:** A benign salivary gland tumour composed of oncocytic epithelial cells lining ductal, papillary, and cystic structures within a lymphoid stroma. - **Prevalence:** Second most common salivary gland neoplasm, accounting for up to 15% of all salivary gland tumours. - **Malignancy:** Malignant transformation has been reported. #### Epidemiology - **Age:** Most commonly diagnosed in the 6th to 7th decade of life. - **Gender:** Slight male predominance. # Warthin’s tumour ## Aetiopathogenesis - Smoking - Reported since 1980's - Numerous studies have noted associations - Demonstrate that smoking habit has 4 – 8-fold greater risk of developing WT than non-smokers - Kotwall C. 1992 - Case-control study between 1980 – 1989 - WT (28) V PA (69) - Defined positive smoking hx as 10 pack-year - 8 times risk of developing WT than non-smokers #### Risk Factors: Smoking - **Association:** Reported since the 1980s; numerous studies note a strong correlation. - **Risk Level:** Smoking habit carries a 4 to 8-fold greater risk of developing Warthin's tumour (WT) compared to non-smokers. - **Research (Kotwall C. 1992):** - Case-control study (1980–1989) comparing WT (28 cases) vs. Pleomorphic Adenoma (69 cases). - Positive smoking history defined as 10 pack-years. - Found an 8 times higher risk for WT in smokers. # Warthin’s tumour ## Aetiopathogenesis - Autoimmune diseases - Gallo et al. 1997: retrospective analysis of 140 WT patients c.f 380 patients with PA over 25-year period - WT patients had higher incidence of autoimmune disorders (23% v 3%; p<0.001) - Significant smoking hx (87% v 38%; p<0.001) - Support hypothesis of immune pathogenesis of WT - Possible role of smoking facilitating immune reactions #### Risk Factors: Autoimmune Diseases - **Research (Gallo et al. 1997):** - Retrospective analysis of 140 WT patients vs. 380 Pleomorphic Adenoma (PA) patients over 25 years. - WT patients showed a significantly higher incidence of autoimmune disorders (23% vs. 3%; p<0.001). - Significant smoking history in WT group (87% vs. 38%; p<0.001). - **Pathogenesis Hypothesis:** Supports an immune-mediated pathogenesis; smoking may facilitate these immune reactions. # Warthin’s tumour ## Aetiopathogenesis - EBV infection - Santucci et al. 1993: - First reported detection of EBV genome in Warthin’s tumour - Frequently noted in neoplastic cells of multiple/bilateral Warthin's tumour (86.7%) - Occasionally noted in solitary Warthin’s tumour (16.7%) - Suggested strong association between EBV infection of cells and development of multiple/bilateral lesions #### Risk Factors: EBV Infection - **Research (Santucci et al. 1993):** - First reported detection of the EBV genome in Warthin’s tumour. - Frequently noted in neoplastic cells of multiple or bilateral WT (86.7%). - Occasionally noted in solitary WT (16.7%). - **Significance:** Suggests a strong association between EBV infection of cells and the development of multiple or bilateral lesions. # Warthin’s tumour ## Pathogenesis - Controversial and not completely understood - neoplastic process vs metaplastic with secondary lymphoid reaction - Accepted theory: - Neoplasm arising from heterotopic salivary ducts - Present within pre-existing intra-parotid or para-parotid lymphoid tissue - Supported by IHC - luminal and basal epithelial cells of Warthin’s tumour similar to striated duct cells and basal cells of excretory duct of salivary gland - Ellis & Auclair 1996 - Nitrous Oxide associated with development of WT - role in pathogenesis in Warthin’s yet to be established #### Pathogenesis - **Nature of Process:** Controversial; debated as a neoplastic process versus a metaplastic process with secondary lymphoid reaction. - **Accepted Theory:** - Neoplasm arising from heterotopic salivary ducts located within pre-existing intra-parotid or para-parotid lymphoid tissue. - **Immunohistochemistry (IHC) Support:** Luminal and basal epithelial cells of WT are similar to striated duct cells and basal cells of the excretory duct (Ellis & Auclair 1996). - **Other Factors:** Nitrous Oxide has been associated with WT development, though its specific role in pathogenesis is not yet established. Warthin’s tumour Clinical Presentation - Painless, discrete, slow-growing lump. - Almost exclusively involves the parotid glands, and often presents as a mass/swelling in the upper neck or angle of the mandible. - There may be multifocal lesions. - Unilateral or bilateral involvement. - May present with facial nerve palsy if there is facial nerve involvement. <img src="..."/> <img src="..."/>   #### Clinical Presentation - **Symptoms:** Painless, discrete, slow-growing lump. - **Location:** Almost exclusively involves the parotid glands; often presents as a mass/swelling in the upper neck or angle of the mandible. - **Distribution:** May be unilateral or bilateral; multifocal lesions may occur. - **Complications:** May present with facial nerve palsy if the nerve is involved. A photograph showing a patient with a visible swelling in the upper neck region, consistent with a parotid gland mass, illustrating the clinical presentation of Warthin's tumour. A close-up photograph of a patient's neck and ear area, highlighting a palpable mass in the parotid region, which is characteristic of Warthin's tumour. Warthin’s tumour Histopathology - Papillary – cystic structures - Lined by oncocytic epithelial cells - Lymphoid stroma with germinal centres - Epithelial component: - inner columnar - outer cuboidal cells - Granulomatous reaction with Langham's type giant cells may occur <img src="https://pathpedia.com/warthins" alt="Microscopic image of Warthin's tumour showing papillary-cystic structures lined by oncocytic epithelial cells with lymphoid stroma and germinal centres." /> WHO 4th edition ; Images from: pathpedia.com/warthins  #### Histopathology - **Architecture:** Papillary-cystic structures. - **Stroma:** Lymphoid stroma with germinal centres. - **Epithelial Component:** Lined by oncocytic epithelial cells arranged in two layers: - Inner columnar cells. - Outer cuboidal cells. - **Secondary Features:** Granulomatous reaction with Langhans-type giant cells may occur. Microscopic image of Warthin's tumour showing papillary-cystic structures lined by oncocytic epithelial cells with lymphoid stroma and germinal centres, as described in the adjacent text. # Warthin's tumour ## Histopathology - Papillary – cystic structures - Lined by oncocytic epithelial cells - Lymphoid stroma with germinal centres - Epithelial component: - inner columnar - outer cuboidal cells - Granulomatous reaction with Langham's type giant cells may occur <img src="https://i.imgur.com/6ZjKjJl.png" alt="Microscopic image of Warthin's tumour showing papillary-cystic structures lined by oncocytic epithelial cells with lymphoid stroma and germinal centres." /> WHO 4th edition ; Images from: pathpedia.com/warthins  #### Histopathology (Continued) - **Key Features:** - Papillary-cystic structures. - Oncocytic epithelial cell lining. - Lymphoid stroma with germinal centres. - **Cellular Detail:** - Inner columnar epithelial cells. - Outer cuboidal epithelial cells. - Potential for granulomatous reaction with Langhans-type giant cells. Microscopic image of Warthin's tumour showing papillary-cystic structures lined by oncocytic epithelial cells with lymphoid stroma and germinal centres, as described in the adjacent text. # Warthin's tumour **Histopathology** - Papillary – cystic structures - Lined by oncocytic epithelial cells - Lymphoid stroma with germinal centres - Epithelial component: - inner columnar - outer cuboidal cells - Granulomatous reaction with Langham's type giant cells may occur <img src="https://pathpedia.com/warthins" alt="Microscopic image of Warthin's tumour showing papillary-cystic structures lined by oncocytic epithelial cells with lymphoid stroma and germinal centres. Arrows point to the epithelial component." /> WHO 4th edition ; Images from: pathpedia.com/warthins  #### Histopathology Summary - **Structural Patterns:** Papillary-cystic formations. - **Cellular Lining:** Oncocytic epithelial cells (inner columnar and outer cuboidal). - **Background:** Lymphoid stroma containing germinal centres. - **Inflammatory Response:** Possible granulomatous reaction with Langhans-type giant cells. Microscopic image of Warthin's tumour showing papillary-cystic structures lined by oncocytic epithelial cells with lymphoid stroma and germinal centres. Arrows point to the epithelial component, highlighting inner columnar and outer cuboidal cells. # Warthin’s Tumour ## Diagnosis NCCN Guidelines; Guidelines for diagnosis and management of salivary gland tumours; AHNS; 2019 - Clinical Evaluation - History and physical examination including H+N examination - Known risk factors for salivary gland tumours? - Smoking history - Role of Imaging - Imaging of clinically benign, superficial parotid tumours is unclear - Warthin’s tumour appear hypermetabolic on PET scan #### Clinical Evaluation and Imaging - **Clinical Evaluation:** - History and physical examination, including Head and Neck (H&N) exam. - Assessment of risk factors, specifically smoking history. - **Role of Imaging:** - The necessity of imaging for clinically benign, superficial parotid tumours is unclear. - Warthin’s tumours appear hypermetabolic on PET scans. # Warthin’s tumour ## Management - Surgical management – complete excision + adequate margin - Superficial parotidectomy - Facial nerve damage - Freys syndrome - haematoma - Low recurrence rate - Malignant transformation rare (0.3%) - Few reported cases - Conservative management - Observation – controversial #### Management and Outcomes - **Surgical Management:** Complete excision with an adequate margin. - **Superficial Parotidectomy Risks:** Facial nerve damage, Frey's syndrome, haematoma. - **Prognosis:** - Low recurrence rate. - Malignant transformation is rare (approximately 0.3%). - **Conservative Management:** Observation is considered controversial. # Oncocytoma ## Introduction - Other names: Oncocytic adenoma, oxyphilic adenoma. - Oncocytoma is an uncommon benign salivary gland neoplasm predominantly composed of large eosinophilic epithelial cells called oncocyes. ## Epidemiology - Uncommon (up to 2% of all salivary gland neoplasms). - Most common in 6th to 8th decades of life. - No gender predilection. #### Introduction - **Other names:** Oncocytic adenoma, oxyphilic adenoma. - **Definition:** An uncommon benign salivary gland neoplasm predominantly composed of large eosinophilic epithelial cells called oncocytes. #### Epidemiology - **Prevalence:** Uncommon (up to 2% of all salivary gland neoplasms). - **Age:** Most common in the 6th to 8th decades of life. - **Gender:** No gender predilection. # Oncocytoma ## Histopathology - Eosinophilic or clear cell (glycogen) with sheets, trabeculae, acini or follicular patterns of monotonous large polygonal cells with well defined cell borders, deeply eosinophilic, granular cytoplasm, small round nuclei - Vascular stroma, may have clear cell change, background of oncocytic nodular hyperplasia, psammoma bodies, tyrosine rich crystals - No mitotic figures, no elastosis #### Histopathology - **Cellular Morphology:** Monotonous large polygonal cells with well-defined cell borders, deeply eosinophilic granular cytoplasm (or clear cell/glycogen change), and small round nuclei. - **Growth Patterns:** Sheets, trabeculae, acini, or follicular patterns. - **Stroma and Inclusions:** - Vascular stroma. - Background of oncocytic nodular hyperplasia. - Psammoma bodies and tyrosine-rich crystals may be present. - **Exclusions:** No mitotic figures and no elastosis.  Microscopic images of oncocytoma and oncocytic carcinoma, showing various histological features such as nests of granular eosinophilic cells, vascular stroma, and clear cell patterns. The figure includes multiple panels labeled A, B, C, and D, each depicting different aspects of the pathology, with inset images providing detailed views of specific cellular structures. # Oncocytoma ## Diagnosis - History. - Clinical examination. - Investigations may include: - Imaging – e.g. ultrasound, CT, MRI. - Cytology. - Technetium 99-m pertechnetate scintigraphy – Oncocytomas present as hot lesions. ## Management - Surgical excision. - Recurrences are rare, though additional oncocytomas may arise in the residual salivary gland. #### Diagnosis - **Clinical Assessment:** History and physical examination. - **Investigations:** - Imaging: Ultrasound, CT, MRI. - Cytology. - **Scintigraphy:** Technetium 99-m pertechnetate scintigraphy; oncocytomas present as "hot" lesions. #### Management - **Treatment:** Surgical excision. - **Prognosis:** Recurrences are rare, though additional oncocytomas may arise in the residual salivary gland tissue. # Mucoepidermoid carcinoma ## Introduction - Other names: Mucoepidermoid tumour. - Mucoepidermoid carcinoma (MEC) is a salivary gland malignancy composed of mucinous, intermediate (clear-cell) and squamoid/epidermoid tumour cells forming cystic and solid patterns. - It is the most common malignant salivary gland tumour in children and young adults. ## Epidemiology - Wide age range, with peak incidence in the second decade of life. ## Aetiopathogenesis - MECs may develop secondary to radiation or chemotherapy during childhood (median latency period of 8 years). #### Introduction - **Other names:** Mucoepidermoid tumour. - **Definition:** A salivary gland malignancy composed of mucinous, intermediate (clear-cell), and squamoid/epidermoid tumour cells forming cystic and solid patterns. - **Prevalence:** Most common malignant salivary gland tumour in children and young adults. #### Epidemiology and Aetiology - **Age:** Wide age range, with a peak incidence in the second decade of life. - **Risk Factors:** May develop secondary to radiation or chemotherapy during childhood (median latency period of 8 years). # Mucoepidermoid carcinoma ## Clinical Presentation - Clinical presentation varies depending on tumour site, size and grade. - Generally presents as a slow-growing mass. - Cystic intraoral MEC can resemble a mucocoele. - Mucinous MEC may fluctuate in size due to cyst rupture. - Most commonly occurs in the parotid gland, followed by the palate, submandibular gland, and other intraoral minor salivary glands. Rarely, they can present as primary intraosseous (central) MECs. <img src="https://i.imgur.com/8ZJzFzL.jpg" alt="Clinical presentation of Mucoepidermoid carcinoma: intraoral lesion">  #### Clinical Presentation - **General Features:** Varies by site, size, and grade; generally presents as a slow-growing mass. - **Specific Presentations:** - Cystic intraoral MEC can resemble a mucocele. - Mucinous MEC may fluctuate in size due to cyst rupture. - **Common Sites:** Parotid gland (most common), followed by the palate, submandibular gland, and other intraoral minor salivary glands. - **Rare Sites:** Primary intraosseous (central) MECs. Clinical presentation of mucoepidermoid carcinoma: an intraoral lesion showing a pinkish, raised mass on the floor of the mouth near the mandibular teeth, illustrating a slow-growing mass as described in the text. ```html <table> <tr> <td> <img src="https://i.imgur.com/1.png" alt="Microscopic image of parotid gland tissue showing mucoepidermoid carcinoma occupying the inferior half of the gland." /> </td> <td> <p>Mucoepidermoid carcinoma. Sections show parotid parenchyma with a mucoepidermoid carcinoma, occupying predominantly the inferior half of the gland (a).</p> </td> </tr> <tr> <td> <img src="https://i.imgur.com/2.png" alt="Microscopic image showing numerous mucin-filled cysts of varying shape and size and cribriform structures set within dense desmoplastic stroma." /> </td> <td> <p>The tumor is composed of numerous <strong>mucin-filled cysts</strong> of varying shape and size and cribriform structures set within <strong>dense desmoplastic stroma</strong> (b).</p> </td> </tr> <tr> <td> <img src="https://i.imgur.com/3.png" alt="Microscopic image showing cystic spaces lined by a combination of mucocytes, intermediate cells, and epidermoid cells." /> </td> <td> <p>The cystic spaces are lined by a combination of <strong>mucocytes</strong>, <strong>intermediate cells</strong>, and <strong>epidermoid cells</strong> (c).</p> </td> </tr> <tr> <td> <img src="https://i.imgur.com/4.png" alt="Microscopic image showing mucous cells with pale cytoplasm and peripherally displaced nuclei, and epidermoid cells with central, mildly pleomorphic nuclei and abundant cytoplasm." /> </td> <td> <p>The mucous cells contain pale cytoplasm and peripherally displaced nuclei. The epi-dermoid cells are polygonal with central, mildly pleomorphic nuclei and abundant cytoplasm, but no defi-nite keratinization (d).</p> </td> </tr> <tr> <td> <img src="https://i.imgur.com/5.png" alt="Microscopic image showing extensive sclerosis and a prominent peritumoral inflammatory infiltrate composed of lymphocytes and plasma cells, with small lymphoid aggregates containing reactive germinal centers." /> </td> <td> <p>In the surrounding stroma, there is extensive sclerosis and a prominent peritumoral <strong>inflammatory infiltrate</strong> composed of <strong>lymphocytes</strong> and <strong>plasma cells</strong>, with small lymphoid aggregates containing reactive germinal centers (e)</p> </td> </tr> </table> ```  #### Histopathology - **Architecture:** Numerous mucin-filled cysts of varying shapes and sizes and cribriform structures set within a dense desmoplastic stroma. - **Cell Types:** Cystic spaces are lined by a combination of: - **Mucocytes:** Pale cytoplasm and peripherally displaced nuclei. - **Intermediate cells.** - **Epidermoid cells:** Polygonal with central, mildly pleomorphic nuclei and abundant cytoplasm (no definite keratinization). - **Stroma:** Extensive sclerosis and a prominent peritumoral inflammatory infiltrate (lymphocytes, plasma cells, and lymphoid aggregates with reactive germinal centers). The image displays a series of five microscopic images (a-e) showing a mucoepidermoid carcinoma in the parotid gland. Figure (a) shows the tumor occupying the inferior half of the gland. Figure (b) reveals mucin-filled cysts and cribriform structures within dense desmoplastic stroma. Figure (c) illustrates the cystic spaces lined by a combination of mucocytes, intermediate cells, and epidermoid cells. Figure (d) depicts mucous cells with pale cytoplasm and peripherally displaced nuclei, and epidermoid cells with central, mildly pleomorphic nuclei and abundant cytoplasm. Figure (e) shows extensive sclerosis and a prominent peritumoral inflammatory infiltrate composed of lymphocytes and plasma cells, with small lymphoid aggregates containing reactive germinal centers. # Mucoepidermoid carcinoma ## Diagnosis - History. - Clinical examination. - Investigations may include: - Imaging – e.g. ultrasound, CT, MRI. - Cytology. - Biopsy. ## Management - Surgical excision with clear margins. - Radiotherapy may be appropriate for local control in some cases. - Low- and intermediate-grade MECs are generally less aggressive. - 10-year survival rates range from 90% (low-grade MEC), 70% (intermediate-grade MEC) and 25% (high-grade MEC). #### Diagnosis and Management - **Diagnosis:** History, clinical examination, imaging (ultrasound, CT, MRI), cytology, and biopsy. - **Management:** - Surgical excision with clear margins. - Radiotherapy may be used for local control in specific cases. - **Prognosis:** - Low- and intermediate-grade MECs are generally less aggressive. - **10-year survival rates:** - Low-grade: 90% - Intermediate-grade: 70% - High-grade: 25% # Acinic cell carcinoma ## Introduction - Other names: Acinic cell adenocarcinoma, acinar cell carcinoma. - Acinic cell carcinoma is a malignant salivary gland neoplasm composed of cancer cells with acinar features. - Second most common salivary gland malignancy in children. ## Epidemiology - Occurs over a wide age range (including children), but most are found in patients aged 50 years and above. - Female predominance (1.5:1). ## Aetiopathogenesis - Aetiology unknown. - Risk factors include previous radiation exposure. #### Introduction - **Other names:** Acinic cell adenocarcinoma, acinar cell carcinoma. - **Definition:** A malignant salivary gland neoplasm composed of cancer cells with acinar features. - **Prevalence:** Second most common salivary gland malignancy in children. #### Epidemiology and Aetiology - **Age:** Wide range (including children); most patients are aged 50 years and above. - **Gender:** Female predominance (1.5:1). - **Aetiology:** Unknown; previous radiation exposure is a known risk factor. # Acinic cell carcinoma ## Clinical Presentation - Slow-growing, solitary, unfixed masses. - Over 90% occur in the parotid glands. They can also occur in the intraoral minor salivary glands. - Some may be multinodular and/or fixed to the skin. - Pain may be a symptom in a third of patients. - Facial paralysis may develop if there is neural involvement. <img src="image.png" alt="Clinical image of acinic cell carcinoma"/> Bavle RM, Makarla S, Nadaf A, et al Solid blue dot tumour: minor salivary gland acinic cell carcinoma Case Reports 2014;**2014**:bcr2013200885.  #### Clinical Presentation - **Mass Characteristics:** Slow-growing, solitary, unfixed masses; some may be multinodular or fixed to the skin. - **Location:** Over 90% occur in the parotid glands; can also occur in intraoral minor salivary glands. - **Symptoms:** - Pain occurs in approximately one-third of patients. - Facial paralysis may develop if there is neural involvement. Clinical photograph showing a solid blue dot tumor in the intraoral region, consistent with a minor salivary gland acinic cell carcinoma. The image depicts a reddish, elevated mass on the buccal mucosa, with a gloved hand retractor holding the area for examination. This visual is presented in the context of describing the clinical presentation of acinic cell carcinoma. ```markdown # Acinic cell carcinoma ## Histopathology - Multiple cell types are noted - Cell types include serous acinar, intercalated ductal, vacuolated, nonspecific glandular and clear cells - Acinar cells are large and polyhedral, with basophilic granular cytoplasm and eccentric nuclei - Cytoplasmic diastase resistant positive periodic acid-Schiff (PAS) reaction may be focal - Variety of morphologic patterns, including solid, microcystic, papillary cystic and follicular - Prominent lymphoid infiltrate may be present (tumour associated lymphoid proliferation varies from randomly scattered, patchy collections of lymphocytes to diffuse, dense infiltrates with well formed follicles throughout the tumour) - Mitosis, necrosis and significant pleomorphism usually absent <img src="https://i.imgur.com/7JZJZJZ.png" alt="Parotid gland excision, acinic cell carcinoma. Well circumscribed tumor with microcystic to solid growth pattern (H&E)."> Lahouti AH, Rao RA. Acinic cell carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/salivaryglandsaciniccell.html. Accessed March 15th, 2022. ```  #### Histopathology - **Cellular Diversity:** Multiple cell types including serous acinar, intercalated ductal, vacuolated, nonspecific glandular, and clear cells. - **Acinar Cell Features:** Large and polyhedral with basophilic granular cytoplasm and eccentric nuclei. Focal diastase-resistant PAS positive reaction may be present. - **Morphologic Patterns:** Solid, microcystic, papillary cystic, and follicular. - **Stroma:** Prominent lymphoid infiltrate (tumour-associated lymphoid proliferation) ranging from patchy collections to dense infiltrates with follicles. - **Exclusions:** Mitosis, necrosis, and significant pleomorphism are usually absent. Microscopic image of a parotid gland excision showing acinic cell carcinoma with a well-circumscribed tumor exhibiting a microcystic to solid growth pattern, stained with H&E. The image displays a dense population of neoplastic cells with basophilic granular cytoplasm and eccentric nuclei, consistent with the histopathological features of acinic cell carcinoma. # Acinic cell carcinoma ## Diagnosis - History. - Clinical examination. - Investigations may include: - Imaging – e.g. ultrasound, CT, MRI. - Cytology. - Biopsy – wide variation in histomorphology. ## Management - Surgical excision. - Radiotherapy may be indicated in some cases. - Recurrence rates of up to 35% have been reported. - The tumour can metastasise to regional lymph nodes and the lungs. - Good survival rate of approximately 90% over 10 years. #### Diagnosis and Management - **Diagnosis:** History, clinical examination, imaging, cytology, and biopsy (noting wide variation in histomorphology). - **Management:** - Surgical excision. - Radiotherapy may be indicated in some cases. - **Prognosis:** - Recurrence rates up to 35%. - Metastasis can occur to regional lymph nodes and lungs. - Good 10-year survival rate of approximately 90%. # Adenoidcystic carcinoma ## Introduction - Adenoid cystic carcinoma (ACC) is a slow-growing but relentless salivary gland malignancy. - Composed of epithelial and myoepithelial neoplastic cells that form various patterns (manifest as a variety of tubular and cribriform structures with variably solid components). - Accounts for < 10% of all salivary gland neoplasms. ## Epidemiology - Annual incidence: 2 cases per 100 000 population. - Median age: 57 years. - Female predominance (1.5:1). - No ethnic predilection. #### Introduction - **Definition:** A slow-growing but relentless salivary gland malignancy composed of epithelial and myoepithelial neoplastic cells. - **Architecture:** Forms various patterns including tubular and cribriform structures with variably solid components. - **Prevalence:** Accounts for less than 10% of all salivary gland neoplasms. #### Epidemiology - **Incidence:** Annual incidence of 2 cases per 100,000 population. - **Age:** Median age of 57 years. - **Gender:** Female predominance (1.5:1). - **Ethnicity:** No ethnic predilection. # Adenoidcystic carcinoma ## Aetiopathogenesis - Aetiology unknown. ## Clinical Presentation - Mass/swelling. - Perineural invasion – neurological signs or symptoms such as numbness, paraesthesia, pain or facial/tongue weakness may be present. - Occurs most frequently in the major salivary glands; however over 30% of cases occur in minor glands of the oral cavity, sinonasal tract or other sites. - Lymph node involvement is uncommon. - Distant metastasis reported in over 50% of cases (lungs, bone, liver, brain). <img src="https://i.imgur.com/5Vj7KzL.jpg" alt="Image of adenoidcystic carcinoma lesion in oral cavity"/>  #### Aetiology and Clinical Presentation - **Aetiology:** Unknown. - **Symptoms:** - Mass/swelling. - **Perineural Invasion:** Neurological signs such as numbness, paraesthesia, pain, or facial/tongue weakness. - **Location:** Most frequent in major salivary glands; over 30% occur in minor glands (oral cavity, sinonasal tract). - **Metastasis:** - Lymph node involvement is uncommon. - Distant metastasis reported in over 50% of cases (lungs, bone, liver, brain). A close-up photo of an adenoid cystic carcinoma lesion in the oral cavity, showing a pinkish mass with visible blood vessels on the mucosal surface. # Adenoidcystic carcinoma ## Histopathology - Biphasic salivary gland tumor, composed of ductal and myoepithelial cells - Myoepithelial cells have dark angulated nuclei and scanty cytoplasm, giving a basaloid appearance - Tubular, cribriform and solid architecture - Tubular pattern contains simple tubules composed of inner ductal and outer myoepithelial cells - Cribriform pattern is composed of predominantly myoepithelial cells with myxoid or hyalinized globules - Scattered ductal elements may be seen within the cribriform area - Solid pattern is solid nests composed of sheets of basaloid cells - Perineural invasion is frequent - High grade transformation can be seen in a small number of cases, defined as comedo type tumor necrosis, frequent mitoses (often > 10 per 10 high power fields) and marked nuclear atypia; high grade transformation is associated with high risk of lymph node metastasis, distant metastasis and disease related death #### Histopathology - **Cell Types:** Biphasic tumor composed of ductal cells (cuboidal, eosinophilic cytoplasm) and myoepithelial cells (dark angulated nuclei, scanty cytoplasm, basaloid appearance). - **Architectural Patterns:** - **Tubular:** Simple tubules with inner ductal and outer myoepithelial cells. - **Cribriform:** Predominantly myoepithelial cells with myxoid or hyalinized globules; scattered ductal elements. - **Solid:** Nests and sheets of basaloid cells. - **Invasion:** Perineural invasion is frequent. - **High-Grade Transformation:** Characterized by comedo-type necrosis, frequent mitoses (>10 per 10 HPF), and marked nuclear atypia. Associated with higher risk of metastasis and death. ```html <table border="1" cellpadding="5" cellspacing="0" style="border-collapse: collapse; width: 100%;"><tr><td style="width: 49%;"><img src="https://i.imgur.com/9zKzZzZ.jpg" alt="Tubular pattern micrograph"/><p>Tubular pattern is composed of inner ductal and outer myoepithelial cells. The ductal cells are cuboidal with eosinophilic cytoplasm. The myoepithelial cells are angulated and basaloid.</p></td><td style="width: 49%;"><img src="https://i.imgur.com/9zKzZzZ.jpg" alt="Cribriform pattern micrograph"/><p>Cribriform pattern is composed predominantly of myoepithelial cells admixed with hyalinized or myxoid globules. Scattered ductal elements (arrows) may also been present.</p></td></tr><tr><td colspan="2" style="text-align: center;"><img src="https://i.imgur.com/9zKzZzZ.jpg" alt="Tumor cells forming solid sheets and nests micrograph"/><p>Tumor cells forming solid sheets and nests.</p></td></tr></table> ```    #### Histopathologic Patterns - **Tubular Pattern:** Composed of inner ductal and outer myoepithelial cells. - **Cribriform Pattern:** Composed predominantly of myoepithelial cells admixed with hyalinized or myxoid globules. - **Solid Pattern:** Tumour cells forming solid sheets and nests. Micrograph showing a tubular pattern composed of inner ductal and outer myoepithelial cells, with cuboidal ductal cells having eosinophilic cytoplasm and angulated myoepithelial cells. Micrograph depicting a cribriform pattern with myoepithelial cells mixed with hyalinized or myxoid globules, and scattered ductal elements indicated by arrows. Micrograph illustrating tumor cells forming solid sheets and nests, with a dense cellular arrangement and pink stroma. # Adenoidcystic carcinoma ## Diagnosis - History. - Clinical examination. - Investigations may include: - Imaging – e.g. ultrasound, CT, MRI. - Cytology. - Biopsy. ## Management - Surgery – wide excision with clear margins. - Radiotherapy can help to improve local control in microscopic residual disease. - Local recurrence rate highly variable. - In recurrent or metastatic disease, treatment success with radiotherapy +/- chemotherapy is limited. - 10-year survival rate is 50-70%. #### Diagnosis and Management - **Diagnosis:** History, clinical examination, imaging, cytology, and biopsy. - **Management:** - Surgery: Wide excision with clear margins. - Radiotherapy: Improves local control in cases of microscopic residual disease. - **Prognosis:** - Local recurrence rate is highly variable. - Limited success with radiotherapy/chemotherapy for recurrent or metastatic disease. - **10-year survival rate:** 50-70%. # Polymorphous low grade adenocarcinoma ## Introduction - Other names: Polymorphous low-grade adenocarcinoma, terminal duct carcinoma, lobular carcinoma, cribriform adenocarcinoma of tongue/minor salivary glands. - Polymorphous adenocarcinoma (PAC) is a malignant salivary gland tumour characterised by cytological uniformity, histomorphological diversity, and an infiltrative growth pattern. - It is the second most common intraoral malignant salivary gland neoplasm. ## Epidemiology - Wide age range from young adult to elderly, but most commonly diagnosed in patients over 50 years of age. - Female predominance (2:1). ## Aetiopathogenesis - Aetiology unknown. #### Introduction - **Other names:** Terminal duct carcinoma, lobular carcinoma, cribriform adenocarcinoma of tongue/minor salivary glands. - **Definition:** A malignant salivary gland tumour (PAC) characterised by cytological uniformity, histomorphological diversity, and an infiltrative growth pattern. - **Prevalence:** Second most common intraoral malignant salivary gland neoplasm. #### Epidemiology and Aetiology - **Age:** Wide range; most commonly diagnosed in patients over 50 years of age. - **Gender:** Female predominance (2:1). - **Aetiology:** Unknown. # Polymorphous low grade adenocarcinoma ## Clinical Presentation - Painless mass of variable duration (weeks to years). - There may be clinical signs of bleeding, telangiectasia and ulceration of the overlying mucosa. - Most common site of involvement is the palate (hard palate > soft palate), followed by lips, buccal mucosa, alveolar mucosa and other intraoral sites. Other less common sites include the major salivary and lacrimal glands, nasopharynx and nasal cavity. - Aggressive clinical behaviour. - May invade adjacent soft tissue and infiltrate adjacent bone. There is often perineural involvement. - Nodal metastasis in up to 15% of cases <img src="https://i.imgur.com/8WjXkZt.jpg" alt="Image of oral lesion">  #### Clinical Presentation - **Symptoms:** Painless mass of variable duration (weeks to years); may show bleeding, telangiectasia, or ulceration. - **Location:** Most common site is the palate (hard > soft), followed by lips, buccal mucosa, and alveolar mucosa. Less common in major glands, nasopharynx, and nasal cavity. - **Behaviour:** Aggressive; may invade soft tissue and bone. - **Invasion:** Frequent perineural involvement. - **Metastasis:** Nodal metastasis in up to 15% of cases. A close-up photograph of an oral lesion on the hard palate, showing a reddish, raised mass adjacent to teeth, illustrating the clinical presentation of polymorphous low grade adenocarcinoma. # Polymorphous low grade adenocarcinoma ## Histopathology - Cytologic uniformity: the tumor is composed entirely of one type of tumor cells characterized by monotonous pale nuclei with marked chromatin clearing resembling that of papillary thyroid carcinoma - Architectural diversity: showing highly variable architectural patterns of different proportions, including single filing arrangement, trabecular, tubular, reticular, papillary, solid and cribriform pattern - Targetoid arrangement and streaming of tumor cells and nests around nerves and vessels are common <img src="https://i.imgur.com/1QX0s2V.png" alt="Microscopic images of Polymorphous low grade adenocarcinoma (A, B, C)"/> Head Neck Pathol. 2019 Jun; 13(2): 131–139.  #### Histopathology - **Cytologic Uniformity:** Monotonous tumor cells with pale nuclei and marked chromatin clearing (resembling papillary thyroid carcinoma). - **Architectural Diversity:** Highly variable patterns including: - Single filing arrangement - Trabecular, tubular, and reticular - Papillary, solid, and cribriform - **Growth Features:** Targetoid arrangement and streaming of tumor cells/nests around nerves and vessels are common. Microscopic images of polymorphous low grade adenocarcinoma showing cytologic uniformity with monotonous pale nuclei and architectural diversity including various patterns such as single filing, trabecular, tubular, reticular, papillary, solid, and cribriform arrangements. The images illustrate targetoid arrangement and streaming of tumor cells around nerves and vessels. # Polymorphous low grade adenocarcinoma ## Diagnosis - History. - Clinical examination. - Investigations may include: - Imaging – e.g. ultrasound, CT, MRI. - Cytology. - Biopsy - Diagnostic difficulties, especially with small biopsy samples. - PAC neoplastic cells may appear deceptively bland. ## Management - Surgical excision with clear margins. - Radiotherapy may also be appropriate in some cases. - Overall survival is generally good. - Local recurrence rates of up to 33% are reported, and about half occur within 5 years of initial diagnosis. #### Diagnosis and Management - **Diagnosis:** History, clinical examination, imaging, and cytology. - **Biopsy Challenges:** Difficulties with small samples; neoplastic cells may appear deceptively bland. - **Management:** - Surgical excision with clear margins. - Radiotherapy may be appropriate in select cases. - **Prognosis:** - Overall survival is generally good. - Local recurrence rates up to 33% are reported; approximately half occur within 5 years. Discuss the aetiology, clinical features, diagnosis and management of dry mouth. This section discusses the aetiology, clinical features, diagnosis, and management of dry mouth. # Xerostomia vs Salivary gland hypofunction - Salivary gland hypofunction: decreased saliva flow rate - Hyposalivation: pathological low saliva flow rate - Unstimulated whole saliva flow rate ≤ 0.1ml/min - Stimulated whole saliva flow rate ≤ 0.5-0.7 ml/min - Xerostomia: subjective feeling of oral dryness #### Terminology and Diagnostic Thresholds - **Salivary gland hypofunction**: Decreased saliva flow rate. - **Hyposalivation**: Pathological low saliva flow rate. - Unstimulated whole saliva flow rate: ≤ 0.1 ml/min - Stimulated whole saliva flow rate: ≤ 0.5–0.7 ml/min - **Xerostomia**: The subjective feeling of oral dryness. # Why should dentists care about a dry mouth? - Negative impact on quality of life - Functional limitation - Physical pain - Physical disability - Psychological discomfort - Taste changes - Difficulty chewing - Difficulty swallowing - Dental diseases <img src="https://i.imgur.com/7XZJz9l.jpg" alt="Oral cavity showing signs of dry mouth, including redness, white patches, and visible lesions."> <img src="https://i.imgur.com/9mX8n9r.jpg" alt="Close-up of tongue showing dryness and cracks, and teeth showing brown staining and decay.">    #### Clinical Significance in Dentistry Dry mouth has a significant negative impact on quality of life, including: - **Functional limitations**: Difficulty chewing and swallowing. - **Physical symptoms**: Physical pain and taste changes. - **Psychological impact**: Physical disability and psychological discomfort. - **Oral health risks**: Increased susceptibility to dental diseases. Close-up photo of an oral cavity showing signs of dry mouth, including redness, white patches, and visible lesions, illustrating the negative impact on quality of life. Photo of a dry, cracked tongue, demonstrating physical discomfort and functional limitations associated with dry mouth. Photo of teeth with brown staining and decay, highlighting dental diseases as a consequence of dry mouth. ```mermaid graph LR A[History] --> B[Examination] B --> C["Underlying cause/ Investigations"] C --> D[Diagnosis] D --> E[Management Plan] ```  #### Clinical Pathway 1. History 2. Examination 3. Underlying cause / Investigations 4. Diagnosis 5. Management Plan A flowchart diagram illustrating a clinical approach to managing a patient with dry mouth. The process starts with 'History', followed by 'Examination', then 'Underlying cause/Investigations', leading to 'Diagnosis', and finally a 'Management Plan'. The diagram uses blue rectangular boxes connected by arrows to show the sequence of steps. # History - Subjective symptoms - Complain of xerostomia throughout their oral cavity or localised to a part of their oral cavity - Carry bottles of water or other fluids - Glass of water beside bed - Change in saliva consistency - Assessment of xerostomia – Fox et al. 1987 - Does the amount of saliva in your mouth seem to be too little, too much, or do you not notice it? - Do you have any difficulty in swallowing? - Does your mouth feel dry when eating a meal? - Do you sip liquids to aid in swallowing dry food? - Medical history & Medications - Behaviours - Water intake? - Caffeine intake? - Alcohol/smoking #### Patient History and Subjective Assessment - **Subjective symptoms** - Complaints of xerostomia throughout the oral cavity or localized to specific parts. - Behavioral indicators: Carrying water bottles or keeping a glass of water beside the bed. - Noted changes in saliva consistency. - **Xerostomia Assessment (Fox et al. 1987)** - Does the amount of saliva in your mouth seem to be too little, too much, or do you not notice it? - Do you have any difficulty in swallowing? - Does your mouth feel dry when eating a meal? - Do you sip liquids to aid in swallowing dry food? - **Medical and Lifestyle Factors** - Review of medical history and current medications. - Assessment of behaviors: Water intake, caffeine intake, alcohol consumption, and smoking. <table> <thead> <tr> <th colspan="4">Examination</th> </tr> <tr> <th colspan="4">The Challacombe Scale of clinical oral dryness</th> </tr> </thead> <tbody> <tr> <td>1</td> <td><img src="mirror_sticking_to_buccal_mucosa.png" alt="Mirror sticks to buccal mucosa"></td> <td>Mirror sticks to buccal mucosa</td> <td rowspan="3">An additive score of 1 - 3 indicates mild dryness. May not need treatment or management. Sugar-free chewing gum for 15 mins, twice daily and attention to hydration is needed. Many drugs will cause mild dryness. Routine checkup monitoring required.</td> </tr> <tr> <td>2</td> <td><img src="mirror_sticking_to_tongue.png" alt="Mirror sticks to tongue"></td> <td>Mirror sticks to tongue</td> </tr> <tr> <td>3</td> <td><img src="frothy_saliva.png" alt="Saliva frothy"></td> <td>Saliva frothy</td> </tr> </tbody> </table>  #### The Challacombe Scale: Mild Dryness An additive score of **1 - 3** indicates mild dryness. - **Clinical Signs**: 1. Mirror sticks to buccal mucosa 2. Mirror sticks to tongue 3. Saliva appears frothy - **Management**: - May not require intensive treatment. - Use sugar-free chewing gum for 15 minutes, twice daily. - Maintain proper hydration. - Monitor during routine checkups, as many drugs cause mild dryness. A table detailing the Challacombe Scale of clinical oral dryness, which includes three levels of severity. Level 1 shows a mirror sticking to the buccal mucosa, Level 2 shows a mirror sticking to the tongue, and Level 3 shows frothy saliva. The table explains that an additive score of 1-3 indicates mild dryness, requiring sugar-free chewing gum and hydration, with routine checkups needed. ```html <table> <tr> <th>4</th> <td><img src="https://i.imgur.com/1.png" alt="No saliva pooling in floor of mouth"/></td> <td>No saliva pooling in floor of mouth</td> </tr> <tr> <th>5</th> <td><img src="https://i.imgur.com/2.png" alt="Tongue shows generalised shortened papillae (mild depapillation)"/></td> <td>Tongue shows generalised shortened papillae (mild depapillation)</td> </tr> <tr> <th>6</th> <td><img src="https://i.imgur.com/3.png" alt="Altered gingival architecture (ie. smooth)"/></td> <td>Altered gingival architecture (ie. smooth)</td> </tr> </table> An additive score of 4 - 6 indicates moderate dryness. Sugar-free chewing gum or simple sialogogues may be required. Needs to be investigated further if reasons for dryness are not clear. Saliva substitutes and topical fluoride may be helpful. Monitor at regular intervals especially for early decay and symptom change. ```    #### The Challacombe Scale: Moderate Dryness An additive score of **4 - 6** indicates moderate dryness. - **Clinical Signs**: 4. No saliva pooling in the floor of the mouth 5. Tongue shows generalized shortened papillae (mild depapillation) 6. Altered gingival architecture (e.g., smooth appearance) - **Management**: - Sugar-free chewing gum or simple sialogogues may be required. - Further investigation is needed if the cause is unclear. - Saliva substitutes and topical fluoride may be helpful. - Regular monitoring for early decay and symptom changes. Close-up photo showing no saliva pooling in the floor of the mouth, corresponding to score 4 in a dryness assessment scale. Photo of the tongue displaying generalized shortened papillae, indicating mild depapillation, associated with score 5. Photo showing altered gingival architecture with a smooth appearance, corresponding to score 6 in the dryness assessment. ```markdown | 4 | No saliva pooling in floor of mouth | An additive score of 4 - 6 indicates moderate dryness. Sugar-free chewing gum or simple sialogogues may be required. Needs to be investigated further if reasons for dryness are not clear. Saliva substitutes and topical fluoride may be helpful. Monitor at regular intervals especially for early decay and symptom change. | | --- | --- | --- | | 5 | Tongue shows generalised shortened papillae (mild depapillation) | | | 6 | Altered gingival architecture (ie. smooth) | | | 7 | Glassy appearance of oral mucosa, especially palate | An additive score of 7 - 10 indicates severe dryness. Saliva substitutes and topical fluoride usually needed. Cause of hyposalivation needs to be ascertained and Sjögrens Syndrome excluded. Refer for investigation and diagnosis. Patients then need to be monitored for changing symptoms and signs, with possible further specialist input if worsening. | | 8 | Tongue lobulated / fissured | | | 9 | Cervical caries (more than two teeth) | | | 10 | Debris on palate or sticking to teeth | | ```  #### The Challacombe Scale: Severe Dryness An additive score of **7 - 10** indicates severe dryness. - **Clinical Signs**: 7. Glassy appearance of oral mucosa, especially the palate 8. Tongue is lobulated or fissured 9. Cervical caries (affecting more than two teeth) 10. Debris on the palate or sticking to teeth - **Management**: - Saliva substitutes and topical fluoride are usually necessary. - The cause of hyposalivation must be determined; Sjögren’s Syndrome should be excluded. - Refer for specialist investigation and diagnosis. - Continuous monitoring for worsening signs and symptoms. The image displays a table with a structured layout, presenting a scoring system for assessing oral dryness. The table is organized into rows, each corresponding to a numerical score from 4 to 10, with associated clinical signs such as 'No saliva pooling in floor of mouth' and 'Glassy appearance of oral mucosa, especially palate'. Each row includes a photograph illustrating the described condition, a textual description of the sign, and a corresponding clinical recommendation based on the score. The table uses a purple background and white text, with the left column containing the score numbers and the right column providing detailed guidance on management and monitoring. # Underlying Causes Salivary gland hypofunction & Xerostomia  #### Etiology of Salivary Gland Hypofunction and Xerostomia Identification of the underlying cause is essential for the management of salivary gland hypofunction and the subjective feeling of xerostomia. A light blue rectangular box with a thin blue border, containing the text 'Salivary gland hypofunction & Xerostomia' in black font. This figure is centered on the slide under the heading 'Underlying Causes' and appears to be a title or topic indicator for the content. # Underlying Causes ```html <table border="1" cellpadding="5" cellspacing="0" style="border-collapse: collapse; width: 100%;"> <tr> <td colspan="3" style="text-align: center; font-size: 2.5em; font-weight: bold;">Underlying Causes</td> </tr> <tr> <td rowspan="2" style="vertical-align: top; padding: 10px; text-align: center; background-color: #f2f2f2; border: 2px solid #808080; font-weight: bold;">Consequences<br>of Cancer<br>therapy</td> <td rowspan="2" style="vertical-align: top; padding: 10px; text-align: center; background-color: #f2f2f2; border: 2px solid #808080; font-weight: bold;">Medications</td> <td rowspan="2" style="vertical-align: top; padding: 10px; text-align: center; background-color: #f2f2f2; border: 2px solid #808080; font-weight: bold;">Infectious</td> </tr> <tr> <td style="vertical-align: top; padding: 10px; text-align: center; background-color: #f2f2f2; border: 2px solid #808080; font-weight: bold;">Developmental</td> <td style="vertical-align: top; padding: 10px; text-align: center; background-color: #f2f2f2; border: 2px solid #808080; font-weight: bold;">Autoimmune/Chronic<br>inflammatory</td> <td style="vertical-align: top; padding: 10px; text-align: center; background-color: #f2f2f2; border: 2px solid #808080; font-weight: bold;">Endocrine</td> <td style="vertical-align: top; padding: 10px; text-align: center; background-color: #f2f2f2; border: 2px solid #808080; font-weight: bold;">Neurological/Psychiatric</td> </tr> <tr> <td style="padding: 10px; text-align: left;">• Radiatior therapy<br>• Chemotherapy<br>• Graft vs Host disease</td> <td style="padding: 10px; text-align: left;">• Anticholinergic<br>• Antihypertensive<br>• Cytotoxic<br>• Opioids and benzodiazepine</td> <td style="padding: 10px; text-align: left;">• HIV<br>• Hepatitis C</td> <td style="padding: 10px; text-align: left;">• Salivary gland<br>aplasia/agenesis</td> <td style="padding: 10px; text-align: left;">• Sjogren’s Syndrome<br>• Rheumatoid Arthritis<br>• SLE<br>• Primary biliary cirrhosis<br>• Sarcoidosis</td> <td style="padding: 10px; text-align: left;">• Diabetes mellitus<br>• Hypothyroidism</td> <td style="padding: 10px; text-align: left;">• Anxiety<br>• Depression<br>• Parkinson’s disease</td> </tr> <tr> <td colspan="7" style="text-align: center; padding: 10px; font-weight: bold; background-color: #add8e6;">Salivary gland hypofunction & Xerostomia</td> </tr> <tr> <td rowspan="2" style="vertical-align: top; padding: 10px; text-align: center; background-color: #f2f2f2; border: 2px solid #808080; font-weight: bold;">Metabolic</td> <td rowspan="2" style="vertical-align: top; padding: 10px; text-align: center; background-color: #f2f2f2; border: 2px solid #808080; font-weight: bold;">Infectious</td> <td rowspan="2" style="vertical-align: top; padding: 10px; text-align: center; background-color: #f2f2f2; border: 2px solid #808080; font-weight: bold;">Neurological/Psychiatric</td> </tr> <tr> <td style="padding: 10px; text-align: left;">• Dehydration<br>• Chronic renal failure<br>• Bulimia<br>• Anaemia<br>• Alcohol abuse</td> </tr> </table> ```   #### Categorization of Underlying Causes - **Consequences of Cancer Therapy** - Radiation therapy - Chemotherapy - Graft vs. Host disease - **Medications** - Anticholinergics - Antihypertensives - Cytotoxic drugs - Opioids and benzodiazepines - **Infectious Diseases** - HIV - Hepatitis C - **Developmental Disorders** - Salivary gland aplasia or agenesis - **Autoimmune and Chronic Inflammatory Conditions** - Sjögren’s Syndrome - Rheumatoid Arthritis - Systemic Lupus Erythematosus (SLE) - Primary biliary cirrhosis - Sarcoidosis - **Endocrine Disorders** - Diabetes mellitus - Hypothyroidism - **Neurological and Psychiatric Factors** - Anxiety - Depression - Parkinson’s disease - **Metabolic and Other Factors** - Dehydration - Chronic renal failure - Bulimia - Anaemia - Alcohol abuse A flowchart diagram illustrating the underlying causes of salivary gland hypofunction and xerostomia. The diagram shows various contributing factors such as cancer therapy, medications, infections, developmental conditions, autoimmune diseases, endocrine disorders, and neurological/psychiatric conditions, all leading to the central outcome of salivary gland hypofunction and xerostomia. Arrows indicate the pathways from each cause to the final condition. A table titled 'Underlying Causes' that categorizes various factors contributing to salivary gland hypofunction and xerostomia. The table is organized into columns for consequences of cancer therapy, medications, infectious causes, developmental conditions, autoimmune/chronic inflammatory diseases, endocrine disorders, and neurological/psychiatric conditions, with specific examples listed under each category. # Investigations - Unstimulated or stimulated whole saliva test - Serology: SS-A, SS-B, ds-DNA, fasting glucose/HBA1C, Thyroid function test - Ultrasound - CT/MRI imaging - Salivary gland biopsy - Ophthalmology – Schirmer’s test #### Diagnostic Investigations - **Saliva Testing**: Unstimulated or stimulated whole saliva flow rate tests. - **Serology**: Testing for SS-A, SS-B, ds-DNA, fasting glucose/HbA1c, and thyroid function. - **Imaging**: Ultrasound, CT, or MRI imaging. - **Biopsy**: Salivary gland biopsy. - **Ophthalmology**: Schirmer’s test to assess tear production. # Management ## Salivary Stimulation - Chewing gum – sugar free, caries prevention - Pharmacology - Pilocarpine - Electro-stimulating devices - Saliwell device - Augments salivary reflex, stimulate motor neural pathways of submandibular and sublingual salivary glands <img src="https://i.imgur.com/8zQvXqL.png" alt="Saliwell device"> <img src="https://i.imgur.com/8zQvXqL.png" alt="Extra Peppermint gum">   #### Salivary Stimulation Techniques - **Mechanical Stimulation**: Chewing sugar-free gum to aid in caries prevention. - **Pharmacological Intervention**: Use of sialogogues such as Pilocarpine. - **Electro-stimulation**: Devices like the Saliwell device, which augment the salivary reflex and stimulate motor neural pathways of the submandibular and sublingual glands. A photo of the Saliwell device, an electro-stimulating device used for salivary stimulation, shown with a blue and white design. A photo of Extra Peppermint gum packaging, a sugar-free chewing gum recommended for caries prevention and salivary stimulation. # Management Managing oral mucosa and dental complications - Antifungal therapy - Reduce exposure to irritants: alcohol, smoking, hot or spicy food - Ensure adequate fit of denture - Caries prevention protocol - Oral hygiene - Fluoride use - Dietary modifications <img src="https://i.imgur.com/6XjJz8L.png" alt="Colgate NeutraFluor 5000 toothpaste and Espure Organic Xylitol package">  #### Management of Complications - **Mucosal Care** - Antifungal therapy for secondary infections. - Reduction of irritants: Avoid alcohol, smoking, and hot or spicy foods. - Ensure proper fit and hygiene of dentures. - **Caries Prevention Protocol** - Strict oral hygiene maintenance. - Regular use of topical fluorides (e.g., high-fluoride toothpaste). - Dietary modifications to reduce sugar intake (e.g., use of Xylitol). A product photo showing two dental care items: a tube of Colgate NeutraFluor 5000 toothpaste and a bag of Espure Organic Xylitol, both related to caries prevention as mentioned in the surrounding text. You survived! Questions Lalima.Tiwari@uwa.edu.au Congratulations on completing the module. #### Academic Inquiries If you have any questions regarding the material covered in this presentation, please direct your correspondence to: - **Email:** Lalima.Tiwari@uwa.edu.au [^1]: Original PDF page 1: [[L15 Non neoplastic and neoplastic salivary gland diseases_slides.pdf#page=1|L15 Non neoplastic and neoplastic salivary gland diseases slides, p.1]] [^2]: Original PDF page 2: [[L15 Non neoplastic and neoplastic salivary gland diseases_slides.pdf#page=2|L15 Non neoplastic and neoplastic salivary gland diseases slides, p.2]] [^3]: Original PDF page 3: [[L15 Non neoplastic and neoplastic salivary gland diseases_slides.pdf#page=3|L15 Non neoplastic and neoplastic salivary gland diseases slides, p.3]] [^4]: Original PDF page 4: [[L15 Non neoplastic and neoplastic salivary gland diseases_slides.pdf#page=4|L15 Non neoplastic and neoplastic salivary gland diseases slides, p.4]] [^5]: Original PDF page 5: [[L15 Non 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