32.1 Odontogenic and Non-Odontogenic Cysts

Odontogenic Cysts: Classification & Pathogenesis

A cyst is defined as an abnormal, closed pathological cavity containing fluid, semi-fluid, or gas, which is frequently, but not invariably, lined by epithelium (true cyst vs pseudocyst). Cysts of the jaws occur with greater frequency than in any other bone because of the abundant embryonic epithelial remnants left behind following odontogenesis (the epithelial rests of Malassez, reduced enamel epithelium, and remnants of the dental lamina).

                                    Cysts of the Jaws
                                            │
            ┌───────────────────────────────┴───────────────────────────────┐
            ▼                                                               ▼
     Odontogenic Cysts                                             Non-Odontogenic Cysts
            │                                                               │
    ┌───────┴───────┐                                              Nasopalatine Duct Cyst
    ▼               ▼                                              • Heart-shaped radiolucency
Inflammatory   Developmental                                       • Vital central incisors
• Radicular    • Dentigerous (crown of unerupted tooth)            • Midline anterior maxilla
• Residual     • Odontogenic Keratocyst (aggressive, 25-60% rec)
• Paradental   • Lateral Periodontal

1. Inflammatory Odontogenic Cysts

Radicular (Periapical) Cyst

• Epidemiology: The most common cyst of the jaws, accounting for approximately 55% to 70% of all diagnosed odontogenic cysts. Most frequently diagnosed in the 3rd to 5th decades, with a predilection for the anterior maxilla.
• Pathogenesis:
  1. Untreated dental caries or trauma precipitates pulpal necrosis.
  2. Bacterial endotoxins and antigens exit the apical foramen, generating chronic periapical periodontitis.
  3. Inflammatory cytokines (interleukins IL-1, IL-6, TNF-α, epidermal growth factor) stimulate normally quiescent epithelial rests of Malassez (remnants of Hertwig's epithelial root sheath within the periodontal ligament).
  4. Proliferating epithelial islands outgrow their central blood supply, undergoing liquefactive necrosis to form a lumen, or form a microcavity that expands via an osmotic gradient created by breakdown products and cellular debris.
• Diagnostic Hallmark: The associated tooth is NON-VITAL (gives zero response to thermal cold testing and electric pulp testing). A non-vital tooth is mandatory for the diagnosis of a radicular cyst.
• Radiographic Features: A round or pyriform, well-defined, unilocular radiolucency centered precisely at the apex of a non-vital tooth. The border is sharply demarcated by a thin, radiopaque, corticated sclerotic margin (which may be lost if secondarily infected).
• Histopathology:
  • Lined by a non-keratinised stratified squamous epithelium of variable thickness, demonstrating inflammatory hyperplasia with prominent arcading or anastomosing rete ridges.
  • Fibrous capsule packed with chronic inflammatory cells (plasma cells with Russell bodies, lymphocytes, macrophages).
  • Cholesterol clefts: Slit-like empty spaces left by dissolved cholesterol crystals, surrounded by multinucleated foreign body giant cells and haemosiderin.
  • Rushton bodies: Curved, linear, or hairpin-shaped eosinophilic, amorphous hyaline calcifications embedded within the epithelial lining (found in ~10% of radicular cysts).

Residual Cyst

• A radicular cyst that remains in the jawbone after extraction of the causative non-vital tooth. Radiographically appears as a well-circumscribed unilocular radiolucency in an edentulous alveolar space.

2. Developmental Odontogenic Cysts

Dentigerous (Follicular) Cyst

• Epidemiology: The second most common odontogenic cyst (~20% of all jaw cysts).
• Pathogenesis: Arises from fluid accumulation between the inner and outer enamel epithelium of the reduced enamel epithelium (REE) and the crown of an unerupted, impacted tooth. Fluid accumulates under hydrostatic and osmotic pressure. Crucially, the cyst attachment is strictly attached to the cementoenamel junction (CEJ) of the tooth.
• Predilection: Teeth with the highest impaction rates: mandibular third molars (75%), followed by maxillary permanent canines and mandibular second premolars.
• Radiographic Features: A well-circumscribed, symmetrical, unilocular radiolucency surrounding the crown of an unerupted tooth, with its corticated sclerotic margin attached precisely at the CEJ. (A pericoronal follicular space >3 to 4 mm on a dental pantomogram is highly suspicious for a developing dentigerous cyst).
• Vitality: The impacted tooth itself is vital (unexposed pulp); adjacent teeth are vital unless compressed.
• Histopathology: Lined by a thin, regular, non-keratinised stratified squamous epithelium (typically 2 to 4 cell layers thick), resembling reduced enamel epithelium without rete ridges. Mucous metaplasia may occur.
• Complications: Untreated dentigerous cysts can undergo metaplastic transformation into an ameloblastoma (unicystic ameloblastoma), squamous cell carcinoma, or mucoepidermoid carcinoma.

Odontogenic Keratocyst (OKC / Keratocystic Odontogenic Tumour)

• Etiology: Arises directly from remnants of the dental lamina (rests of Serres). Formerly reclassified by the WHO as a benign neoplasm ("keratocystic odontogenic tumour" in 2005) due to its clonal nature and destructive behaviour, it was re-categorised as a cyst in 2017 while emphasizing its aggressive biological behaviour and high recurrence rate (25% to 60%).
• Pathogenesis: Inactivation or loss-of-function mutation in the PTCH1 (Patched 1) tumour suppressor gene on chromosome 9q22, leading to constitutive activation of the Sonic Hedgehog (SHH) signaling pathway, driving autonomous epithelial cell proliferation.
• Anatomical Site: Approximately 70–75% occur in the mandible, with a predilection for the mandibular body, angle, and ascending ramus.
• Clinical Dynamics: OKCs have a remarkable tendency to grow anteroposteriorly within the medullary/cancellous space of the bone without causing marked expansion of the cortical plates until they reach an enormous size. Consequently, they are frequently discovered as incidental radiographic findings or only after cortical perforation and secondary infection.
• Radiographic Features: A well-demarcated, sharply corticated radiolucency, either unilocular with characteristic scalloped borders (scalloping between tooth roots) or multilocular. Root resorption of adjacent teeth is less frequent than in ameloblastoma (OKCs tend to displace teeth rather than resorb roots).

                                Pathognomonic Histology of the OKC
                                                │
      ┌──────────────────┬──────────────────────┴──────────────────────┬──────────────────┐
      ▼                  ▼                                             ▼                  ▼
Uniform Lining     Corrugated         Palisaded Basal Layer        Satellite / Daughter
Thickness          Parakeratin        • Tall columnar cells        Microcysts
• Strictly 6–8     Surface            • Hyperchromatic nuclei      • Located within the
  cell layers      • Wavy, sloughing  • Reversal of polarity       fibrous capsule
• Absence of rete  • Cheesy lumen     • "Tombstone" or "picket     • Source of recurrence
  pegs (flat base)   keratin            fence" appearance          after enucleation

• Histopathological Triad of OKC:
  1. A remarkably uniform epithelial lining, strictly 6 to 8 cells in thickness, with an entirely flat interface lacking rete pegs.
  2. A thin, wavy, corrugated parakeratinised surface layer, sloughing abundant thick, cheesy parakeratin flakes into the cyst lumen.
  3. A prominent, palisaded basal layer composed of tall columnar or cuboidal cells with hyperchromatic nuclei displaying reversed polarity (nuclei positioned away from the basement membrane), resembling a "picket fence" or "tombstones".
  4. The underlying thin, friable connective tissue capsule frequently contains satellite microcysts (daughter cysts) and detached epithelial rests.
• High Recurrence Rate (25–60%): Caused by: (a) thin, friable capsule that fragments easily during enucleation; (b) leaving behind microscopic satellite daughter cysts in the bone wall; and (c) new cysts arising from persistent dental lamina remnants.
• Surgical Management Protocols in the UK:
  • Enucleation alone carries an unacceptable recurrence rate of up to 50%.
  • Standard protocol: Thorough enucleation accompanied by chemical cauterization using Carnoy's solution (or modified Carnoy's solution without chloroform) applied to the bony cavity for 3 minutes, or liquid nitrogen cryotherapy, or mechanical peripheral ostectomy (burring 1–2 mm of the peripheral bony margin) to eradicate daughter cysts.
  • Large extensive lesions: Initial decompression / marsupialization to shrink the cyst and thicken the lining, followed by secondary enucleation.

Gorlin-Goltz Syndrome (Nevoid Basal Cell Carcinoma Syndrome / NBCCS)

An autosomal dominant disorder with high penetrance, caused by germline mutations in the PTCH1 gene on chromosome 9q22. Candidates must recognize the classic clinical tetrad:

1. Multiple Odontogenic Keratocysts of the jaws (often appearing in the first and second decades of life).
2. Multiple Basal Cell Carcinomas (BCCs) of the skin developing at an early age on sun-exposed and non-exposed skin.
3. Skeletal Abnormalities: Bifid ribs (most common), fused or splayed ribs, kyphoscoliosis, and frontal bossing.
4. Intracranial Calcification: Ectopic, heavy, lamellar calcification of the falx cerebri (seen on anteroposterior or lateral skull radiographs).
5. Additional features: Palmar and plantar epidermal pits (punctate pits on hands and soles), hypertelorism, and ovarian fibromas.

3. Non-Odontogenic Cysts

Nasopalatine Duct (Incisive Canal) Cyst

• Epidemiology: The most common non-odontogenic cyst of the oral cavity (~10% of all maxillary cysts).
• Pathogenesis: Develops from proliferation of embryonic epithelial remnants of the primitive paired nasopalatine ducts within the incisive canal.
• Clinical Presentation: Painless swelling in the midline of the anterior hard palate palatal to the maxillary central incisors, occasionally discharging salty fluid into the mouth.
• Radiographic Features: A classic, well-demarcated, corticated, heart-shaped or oval unilocular radiolucency located strictly in the midline between and above the apices of the permanent maxillary central incisors. (The heart shape is caused by superimposition of the anterior nasal spine).
• Crucial Diagnostic Test: The adjacent maxillary central incisors (11 and 21) are VITAL. Pulp testing is mandatory; finding vital incisors definitively rules out a periapical radicular cyst and prevents unnecessary endodontic treatment!
• Histology: Lined by stratified squamous, pseudostratified ciliated columnar (respiratory), or cuboidal epithelium. The fibrous wall characteristically contains prominent thick-walled blood vessels and muscular nerve trunks (branches of the nasopalatine nerve and sphenopalatine vessels) alongside mucous glands.

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