4.3 Bone Pathology, Jaw Disorders & Salivary Gland Diseases

Bone Pathology, Jaw Disorders & Salivary Gland Diseases

Pathologies affecting the maxillofacial skeleton and salivary glands comprise a diverse group of neoplastic, metabolic, reactive, and autoimmune disorders. Mastery of clinical diagnostic criteria, histopathological features, and molecular etiologies is required for the LDS Part 1 examination.

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Benign Fibro-Osseous Lesions of the Jaws

Fibro-osseous lesions share a common histological footprint: normal architecture is replaced by cellular fibrous tissue containing varying amounts of mineralised material (woven bone, lamellar bone, or cementum-like spherules).

    Fibrous Dysplasia vs. Ossifying Fibroma Differentiation:
    Fibrous Dysplasia ──► GNAS Mutation + Poorly Demarcated "Ground-Glass" + NO Osteoblastic Rimming
    Ossifying Fibroma ──► True Neoplasm + Encapsulated / Well-Demarcated + PROMINENT Osteoblastic Rimming

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Metabolic & Osteonecrotic Jaw Pathologies

Paget's Disease of Bone (Osteitis Deformans)

• Pathophysiology: Uncoordinated, dysregulated bone remodeling characterized by intense osteoclastic resorption followed by chaotic, disorganized osteoblastic deposition.
• Clinical Features: Occurs in patients >50 years; progressive enlargement of the skull and maxilla ("leontiasis ossea"), spacing of teeth, poorly fitting dentures.
• Biochemical & Radiographic Findings: Serum alkaline phosphatase (ALP) is markedly elevated, while serum calcium and phosphate levels remain normal. Radiographs show cotton-wool radiopacities and extensive hypercementosis of tooth roots.
• Histopathology: Bone exhibits a pathognomonic mosaic or jigsaw puzzle pattern of basophilic reversal lines caused by repeated phases of destruction and repair.

       Paget's Disease Histopathology & Biochemistry:
       Histology: Mosaic / "Jigsaw Puzzle" Pattern of Reversal Lines
       Biochemistry: Markedly Elevated Serum Alkaline Phosphatase (ALP)
       Radiography: "Cotton-Wool" Sclerosis + Generalized Hypercementosis

Medication-Related Osteonecrosis of the Jaw (MRONJ)

Official Diagnostic Criteria

Diagnosis of MRONJ requires ALL three of the following parameters:

1. Current or previous treatment with antiresorptive agents (bisphosphonates like zoledronic acid/alendronate, RANKL inhibitors like denosumab) or antiangiogenic targeted therapies.
2. Exposed necrotic bone in the maxillofacial region or bone that can be probed through an intraoral or extraoral fistula persisting for more than 8 weeks.
3. No history of radiation therapy to the jaws or obvious metastatic disease of the jaws.

Staging & Pathogenesis

• Stage 0: Non-exposed bone variant; unexplainable pain, dull bone ache, loosening of teeth, radiographic bone loss without bone exposure.
• Stage 1: Exposed necrotic bone or fistula probing to bone; asymptomatic with no evidence of infection/soft tissue inflammation.
• Stage 2: Exposed necrotic bone or fistula; symptomatic with infection, erythema, purulent discharge, and pain.
• Stage 3: Exposed necrotic bone extending beyond alveolar bone (e.g., inferior border of mandible, maxillary sinus, pathologic fracture, extraoral fistula).
• Pathogenesis: Severe osteoclast inhibition prevents physiological bone microdamage repair, combined with local microvascular anti-angiogenic suppression, mucosal trauma (e.g., tooth extraction), and secondary bacterial colonisation (Actinomyces).

Osteoradionecrosis (ORN)

Definite diagnosis requires necrotic exposed bone in an area previously irradiated for head and neck malignancy that fails to heal over 3 months, in the absence of tumour recurrence.

• Marx Triad Pathogenesis: Radiation induces Hypoxia, Hypovascularity, and Hypocellularity, leading to chronic tissue breakdown and unhealing aseptic necrosis. High-risk threshold: radiation doses exceeding 60 Gy.

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Giant Cell & Hereditary Jaw Lesions

Central Giant Cell Granuloma (CGCG)

• Histopathology: Non-neoplastic proliferation of multinucleated osteoclast-like giant cells unevenly distributed within a vascular stroma of spindle-shaped mesenchymal cells. Demonstrates extravasated red blood cells, hemosiderin deposition, and reactive woven bone trabeculae.
• Clinical Note: Must rule out Hyperparathyroidism (Brown tumor of hyperparathyroidism exhibits identical histology; evaluate serum calcium, phosphate, and parathyroid hormone [PTH] levels).

Cherubism

• Genetics: Autosomal dominant disorder with high penetrance caused by mutations in the SH3BP2 gene (chromosome 4p16).
• Clinical Presentation: Appears in early childhood (2–5 years) with painless, bilateral swelling of the mandibular angles and maxilla, causing upward gaze of eyes ("cherubic" appearance).
• Histopathology: Multinucleated giant cells embedded in a fibrous stroma containing pathognomonic perivascular eosinophilic collagen cuffing around capillaries. Lesions typically regress spontaneously after puberty.

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Non-Neoplastic Salivary Gland Diseases

Sialolithiasis

Salivary calculi (stones) occur predominantly in the submandibular gland system (80–85%) within Wharton's duct.

• Predisposing Factors: Wharton's duct has a long, tortuous, upward-sloping anatomical course; submandibular saliva is higher in calcium and phosphate, more alkaline, and richer in mucin proteins compared to parotid saliva.
• Clinical Symptoms: Mealtime syndrome — acute, painful swelling of the submandibular gland triggered by eating due to ductal obstruction.

Sjögren's Syndrome

Systemic autoimmune exocrinopathy characterized by lymphocytic destruction of salivary and lacrimal glands.

• Primary vs. Secondary: Primary Sjögren's (dry eyes [keratoconjunctivitis sicca] + dry mouth [xerostomia]); Secondary Sjögren's (sicca complex combined with a connective tissue disease like Rheumatoid Arthritis or Systemic Lupus Erythematosus).
• Serology: Positive autoantibodies anti-Ro (SS-A) and anti-La (SS-B), positive Rheumatoid Factor (RF), and ANA.
• Minor Salivary Gland Biopsy Criteria: Labial salivary gland biopsy demonstrating focal lymphocytic sialadenitis with a Focus Score ≥1 per 4 mm² of tissue (a focus is defined as an aggregate of ≥50 lymphocytes, predominantly CD4+ T-cells, adjacent to acini).
• Malignancy Risk: Patients with Sjögren's syndrome carry a 44-fold increased risk of developing non-Hodgkin B-cell lymphoma, specifically MALT Lymphoma (Mucosa-Associated Lymphoid Tissue lymphoma) in the parotid gland.

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Salivary Gland Neoplasms

Salivary gland tumours follow the general rule: the smaller the salivary gland, the higher the probability of malignancy (Parotid: 20% malignant; Submandibular: 50% malignant; Sublingual/Minor glands: 80% malignant).

   Salivary Tumour Malignancy Rule:
   Parotid Gland ──────► 80% Benign / 20% Malignant
   Submandibular Gland ─► 50% Benign / 50% Malignant
   Minor / Sublingual ──► 20% Benign / 80% Malignant

Benign Salivary Neoplasms

Pleomorphic Adenoma (Benign Mixed Tumour)

• Frequency: The most common salivary gland tumour overall (~70% of parotid tumours).
• Histopathology: Characterized by remarkable architectural diversity. Consists of a mixture of epithelial and myoepithelial cells embedded in a variable chondromyxoid, mucinous, or hyaline stroma.
• Surgical Consideration: Possesses an incomplete fibrous pseudocapsule with microscopic tongue-like projections (pseudopods). Simple enucleation results in high recurrence rates; managed by partial parotidectomy. Risk of malignant transformation into Carcinoma ex Pleomorphic Adenoma (~5% of long-standing cases).

Warthin's Tumour (Papillary Cystadenoma Lymphomatosum)

• Etiology & Location: Monomorphic benign tumour almost exclusively occurring in the tail of the parotid gland. Strongly linked to cigarette smoking (8-fold risk increase).
• Histopathology: Cystic spaces lined by a double layer of oncocytic epithelial cells (tall granular eosinophilic luminal cells and small basal cells) exhibiting papillary projections, surrounded by a dense lymphoid stroma with germinal centres.

Malignant Salivary Neoplasms