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© Springer Nature Switzerland AG 2021

R. Reti, D. Findlay (eds.)Oral Board Review for Oral and Maxillofacial

8. Oral Pathology

Naomi Ramer1  , Molly Cohen1, Trina Sengupta2, Chandni Desai3, John W. Hellstein4, Beomjune B. Kim5, Ryan J. Smart6, Waleed Zaid7 and Prashanth Konatham-Haribabu8

Mount Sinai Medical Center, Department of Pathology and Dentistry/Division of Oral and Maxillofacial Pathology, New York, NY, USA

Jamaica Hospital Medical Center, Department of Dentistry/Division of Oral and Maxillofacial Surgery, Jamaica, NY, USA

University of Iowa, Oral & Maxillofacial Pathology, Iowa City, IA, USA

University of Iowa Hospitals and College Dentistry, Oral Pathology, Radiology and Medicine, Iowa City, IA, USA

Cancer Treatment Centers of America, Head and Neck Surgery, Tulsa, OK, USA

University Medical Center/El Paso Children’s Hospital, Department of Oral Surgery, El Paso, TX, USA

LSUHSC – School of Dentistry, Oral and Maxillofaical Surgery Department, Baton Rouge General, Oral and Maxillofacial Surgery, Baton Rouge, LA, USA

AT Still University-Missouri School of Dentistry and Oral Health, St. Louis, MO, USA
Naomi Ramer

Dentigerous cystPeriapical cystRadicular cystResidual cystLateral periodontal cystGlandular odontogenic cystOdontogenic keratocystCalcifying odontogenic cyst (Gorlin cyst)Nevoid basal cell carcinoma syndromeSquamous cell carcinomaAmeloblastomaMyxomaFibro-osseous lesionsFibrous dysplasiaCemento-osseous dysplasiaCentral giant cell granulomaPeripheral giant cell granulomaMedication-related osteonecrosis of the jawsBisphosphonatesOsteoradionecrosisMelanomaSquamous cell carcinomaNeck dissectionPleomorphic adenomaMucoepidermoid carcinoma

Odontogenic Cysts

  • Cysts derived from the tissues involved in odontogenesis.

Dentigerous Cyst

  • Represents 1/3 of all odontogenic cysts.

  • Associated with the crown of an impacted or unerupted permanent tooth and rarely involves an unerupted deciduous tooth.

  • Caused by an accumulation of fluid between the reduced enamel epithelium and the crown of the tooth.

  • Has three variants:

    1. 1.

      Central – cyst surrounds the entire crown of the tooth (attached to the tooth at the CEJ). The most common variant.

    2. 2.

      Lateral – cyst grows lateral along the lateral aspect of the tooth.

    3. 3.

      Circumferential – cyst surrounds the tooth and gives the appearance that the tooth is within the cystic cavity.

  • Teeth most commonly involved (in descending order):

    • Mandibular third molar.

    • Maxillary cuspid.

    • Maxillary third molars.

    • Mandibular second premolars.

  • Can cause bony expansion, root displacement, and root resorption.

Radiographic Appearance

  • Well-delineated unilocular or multilocular radiolucency.

  • Root resorption may be evident.

  • Impacted tooth may be displaced a long distance from its original site.


  • Size and location of the cyst will dictate treatment.

  • Small lesions – enucleation.

  • Larger lesions – marsupialization (followed by enucleation after decompression).

  • Recurrence is uncommon.

Periapical Cyst (Radicular Cyst)

  • All ages, and all teeth, can be affected.

  • Most common cyst of the jaw bones.

  • Occurs most commonly in the maxilla.

  • Forms as a sequela of chronic inflammation in a preexisting periapical granuloma.

  • Cyst is usually located at the apex of a non-vital tooth.

Radiographic Appearance

  • Well-circumscribed unilocular radiolucency around the apex.

  • May cause root resorption or tooth displacement.


  • Endodontic therapy.

  • Extraction of tooth with apical curettage/enucleation.

  • Endodontic therapy with apicoectomy.

Residual Cyst

  • All ages.

  • Cyst that has been left in the jaw bone after the associated tooth has been extracted.

  • More common in maxilla.

Radiographic Appearance

  • Well-defined radiolucency.


  • Simple excision .

Lateral Periodontal Cyst

  • Also has a polycystic variant known as the botryoid odontogenic cyst (appears in a grapelike cluster).

  • Most common in second–fourth decades.

  • Arises in the periodontal ligament along the lateral aspect of the root of a tooth.

  • Teeth are vital.

  • Intrabony counterpart of the gingival cyst of adults.

  • More common in males.

  • Mandible: Canine-premolar region.

  • Maxilla: Lateral incisor-canine region.

  • Asymptomatic.

Radiographic Appearance

  • Well-defined (unilocular or multilocular) radiolucency along the lateral surface of tooth root.

  • Multilocular appearance seen in botryoid variant.


  • Enucleation

Glandular Odontogenic Cyst

  • Large variation in the age of presentation, second to eighth decades of life (average fifth decade).

  • Rare cyst that can show clinically aggressive behavior (expansion, pain, and paresthesia).

  • Has a strong predilection for the anterior mandible and usually crosses the midline.

  • Can have histological features of a low-grade mucoepidermoid carcinoma.

Radiographic Appearance

  • Unilocular or multilocular well-defined radiolucency surrounded by a sclerotic border.

  • Larger cysts may cause bony expansion and cortical disruption.


  • Curettage.

  • Some surgeons advocate for marginal or en bloc resection due to high recurrence (30%) [1].

Odontogenic Keratocyst (OKC)

  • Most commonly in second–third decade.

  • Associated with the PTCH tumor suppressor gene.

  • Derived from the rests of dental lamina (rests of Serres).

  • Slight male predilection.

  • More common in the mandible – third molar/ramus area.

  • Maxilla: posterior region is the most common area for occurrence.

  • Aggressive growth potential with higher tendency to recur (most recurrences are within the first 5 years after original treatment).

  • Most are asymptomatic.

  • Commonly displace the inferior alveolar nerve (IAN).

  • Will resorb roots of teeth.

  • Histologically will see a cyst lined by a thin layer of parakeratotic stratified squamous epithelium, which is usually 6–8 layers thick (rete ridge formation is inconspicuous).

  • May be associated with nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome. Features include:

    • Multiple basal cell carcinomas.

    • Multiple OKCs.

    • Palmer and plantar pits.

    • Calcified falx cerebri.

    • Rib anomalies (bifid, missing, or partially developed).

    • Spina bifida.

    • Hypertelorism.

    • Enlarged head circumference due to frontal bossing.

    • Cleft lip and palate.

Radiographic Appearance

  • Unilocular or multilocular radiolucency.

  • Displacement or resorption of teeth may be noted.


  • Treatment depends on size, extent, and location of lesion.

  • Enucleation and curettage with peripheral Ostectomy. Large cysts may be decompressed prior to treatment.

  • Cryotherapy with liquid nitrogen offers penetration up to 1.5 mm into the bone. It is difficult to work with as the peripheral tissues are at risk of injury and need to be protected. Additionally, if the inferior alveolar nerve is exposed, there is a high rate of paresthesia with reasonable recovery. Fractures of the mandible are also a known risk.

  • Chemical cauterization with Carnoy’s solution (mixture of ethanol, chloroform, glacial acetic acid, and ferric chloride). It is known that chloroform is a carcinogen, thus its usage has been banned in North America, rendering the use of Carnoy solution as banned. There is a modified form without chloroform, but the recurrence rate is considerably higher as chloroform is essential for its successful use.

  • Some authors advocate for en bloc resection with 1 cm margins due to the high recurrence rate and the aggressive nature of the lesion.

Calcifying Odontogenic Cyst (Gorlin Cyst)

  • Age: second and third decade.

  • Occurrence : less than 1% of odontogenic cysts [1].

  • Calcifying odontogenic cysts (COCs) behave in a benign fashion.

  • Most cases are within bone, 5–17% are found extraosseous [1].

  • Maxilla and mandible have equal distribution as it relates to occurrence.

Radiographic Appearance

  • Unilocular or Multilocular with radiopaque structures that represent calcification.

  • Displacement or resorption of adjacent teeth may be seen.

  • May be associated with an unerupted tooth.


  • Conservative surgical removal.

  • Low recurrence rate.

Odontogenic Tumors

  • Neoplasms derived from the tissues that are involved in odontogenesis (Table 8.1).

Table 8.1

Origin of odontogenic tumors

Odontogenic epithelium

Odontogenic mesenchyme



Central odontogenic fibroma

Ameloblastic fibroma

Calcifying odontogenic cyst (Gorlin Cyst)

Odontogenic myxoma

Ameloblastic fibro-odontoma

Calcifying epithelial odontogenic tumor

Cementifying fibroma

Ameloblastic fibrosarcoma

Adenomatoid odontogenic tumor



Squamous odontogenic tumor


Clear cell odontogenic tumor


Tumors Consisting of Odontogenic Epithelium


  • Most common epithelial odontogenic tumor.

  • Age: 30–70 years.

  • Most common in the mandible with a predilection for molar/ramus area.

  • Causes jaw expansion.

  • High rate of recurrence.

Radiographic Appearance

  • Unilocular or multilocular radiolucency.

  • Referred to as a “soap bubble” appearance when the loculations are large.

  • Referred to as a “honeycomb” appearance when the loculations are small.

  • Well-defined borders.

  • Root resorption of adjacent teeth may occur.

  • May simulate a dentigerous cyst when associated with an impacted tooth.

  • There are many histological subtypes (See Table 8.2).

Table 8.2

Ameloblastoma histological subtypes

Follicular pattern

Most common.

Islands of odontogenic epithelium

A single layer of columnar ameloblast-like cells surrounds the central core.

Central core resembles stellate reticulum.

Ameloblast-like cells nuclei exhibit reversed polarity from basement membrane and subnuclear vacuoles.

Plexiform pattern

Interconnecting elongated islands of Od. Epithelium.

Acanthomatous pattern

Squamous metaplasia in the center of the islands.

Granular cell type

Eosinophilic granular cells.

Desmoplastic type

Well-collagenized stroma.

May mimic a fibro-osseous lesion radiographically. More common anterior mandible/maxilla.

Unicystic Ameloblastoma

  • 13–21% of all cases of ameloblastoma [2].

  • Mimics a dentigerous cyst.

  • Most common in mandibular third molar region.

  • Younger age group than multicystic ameloblastomas.

  • Slow growing, paresthesia uncommon.

  • There are three histological variants (Table 8.3).

Table 8.3

Unicystic ameloblastoma subtypes


Epithelium fulfills criteria of ameloblastoma.

Intraluminal type

Nodules of ameloblastic cyst lining project into the lumen.

Mural type

Tumor islands present in the cystic wall.

Radiographic Appearance

  • Unilocular radiolucency.

Peripheral Ameloblastoma

  • Arises from rests of dental lamina, or from the basal cell layer of the surface epithelium.

  • Exophytic mass of the tooth-bearing area.

  • Normally does not invade the underlying bone.

  • Less aggressive than the intraosseous counterpart.

Malignant Ameloblastoma

  • Malignant (metastasizing) ameloblastoma: Metastasizes, but metastatic deposits are histologically benign.

  • Overall rate <1% of ameloblastomas [1].

  • Most metastases are to the lungs followed by the cervical lymph nodes.

  • Ameloblastic carcinoma: histologically malignant with hyperchromatism, increased nuclear-to-cytoplasmic ratio, and presence of high mitoses [1].

Treatment of Conventional or Unicystic Ameloblastoma with Extraluminal Invasion

  • Enucleation and Curettage – this procedure is not considered curative and should be used for palliative purposes such as when there is a major anesthetic or surgical risk for the patient. The particulation of an ameloblastoma with enucleation and peripheral ostectomy is known to liberate tumor cells within the soft tissue and cause debilitating recurrences. This type of treatment has recurrence rates approaching 70–85% (recurrence usually occurs within 5 years) [1].

  • Marginal or block resection – curative form of treatment with resection using 1.0–1.5 cm bony margins and one uninvolved anatomical margin [3, 4]. Maxillary lesions may be more aggressive since they are not contained by cortical bone.

Treatment for Other Types of Ameloblastoma

  • Unicystic ameloblastoma with intraluminal confinement – enucleation with long term follow up.

  • Peripheral ameloblastoma – treatment with local surgical excision with 2–3 mm margins. Recurrence to bone treated with further local excision.

  • Malignant ameloblastoma – En bloc resection of the primary tumor with wedge resection of the lung (71% cases travel to lung) and possibly chemotherapy [5]. Requires a multidisciplinary approach.

  • Ameloblastic carcinoma – resection with 2–3 cm bony lesions with neck dissection. Consideration for chemotherapy with platinum-based agents and radiotherapy.

Calcifying Epithelial Odontogenic Tumor (Pindborg Tumor)

  • Uncommon odontogenic tumor of the bone.

  • Commonly located in the mandibular premolar region.

  • Presents as a slow painless expansion.

  • Age: fourth–sixth decade.

  • No sex predilection.

Radiographic Features

  • Unilocular or multilocular radiolucency (Fig. 8.1).

  • Usually well-delineated lesion, but up to 20% have ill-defined borders [1].

  • May be associated with an impacted tooth.

  • CT scan may show an expanding mass.

  • Calcified structures (Liesegang ring calcifications) can be seen within the lesion. Amyloid-like material is found within the stroma.

Fig. 8.1

Calcifying epithelial odontogenic tumor, aka Pindborg tumor. Can be unilocular or multilocular radiolucent lesion. (Reprinted with permission from Neville et al. [1])


  • Conservative local resection with peripheral ostectomy has a recurrence rate around 15% [1, 6].

  • Some surgeons advocate for resection with 1–1.5 cm margins and an uninvolved anatomical barrier.

Adenomatoid Odontogenic Tumor/ Cyst

  • 2/3rds seen in teenage females.

  • Location : Anterior maxilla more commonly than anterior mandible.

  • 2/3rds seen in association with impacted canines.

  • Slow growing, usually asymptomatic.

Radiographic Findings

  • Unilocular, well circumscribed.

  • Snowflake-like calcifications.


  • Conservative enucleation, removed easily from its bed due to a thick fibrous capsule.

Tumors Consisting of Odontogenic Mesenchyme

Odontogenic Myxoma

  • Arises from odontogenic ectomesenchyme.

  • No sex predilection.

  • Occurs more commonly in the mandible than maxilla.

  • Young adults, 25–30 years of age [1].

  • Can cause expansion of the affected area and displace/resorb teeth.

  • Histologically will see a myxoid stroma containing spindle- and stellate-shaped cells.

Radiographic Appearance

  • Multilocular radiolucency is more common but soap bubble and honeycomb patterns do occur.


  • Curettage – used for palliation and small lesions.

  • Resection – curative form of treatment with resection using 1.0–1.5 cm bony margins and one uninvolved anatomical margin [7].

Cemento-Ossifying Fibroma (Cementifying or Ossifying Fibroma)

  • A distinct form of ossifying fibroma, which is confined to tooth-bearing area of jaws.

  • Third–fifth decade with a female predilection.

  • Occurs more commonly in the mandible.

  • Slow growing, painless, and may cause large expansion.

Radiographic Appearance

  • Well circumscribed, round radiolucent or radiopaque lesion.

  • Displacement of teeth.


  • Conservative enucleation for a small, well-demarcated lesion, as those lesions are usually encapsulated.

  • Large lesions require resection with 5 mm borders. No need to remove involved soft tissue as tumor is encapsulated.

Cementoblastoma (True Cementoma)

  • Solitary lesion found in continuity with a tooth root.

  • Teeth are normally vital.

  • Site: mandibular premolar or molar.

  • Age: most patients are less than 30 years old.

  • May have expansion and discomfort.

Radiographic Appearance

  • Well-defined dense radiopaque mass in continuity with the tooth root with a radiolucent halo around the lesion.

  • Periodontal ligament space surrounds the mass to distinguish from hypercementosis.


  • Excision, often with loss of involved tooth (low recurrence rate).

  • May also consider endodontic treatment with root resection.

Tumors Consisting of Odontogenic Epithelium and Odontogenic Mesenchyme

Ameloblastic Fibroma

  • First and second decade.

  • Slightly more common in males.

  • Posterior mandible more commonly involved.

  • Bony expansion.

Radiographic Appearance

  • Unilocular or multilocular radiolucency with well-defined borders.

  • Commonly associated with unerupted tooth.

  • Cortical expansion common.


  • Conservative surgical excision is recommended initially, with close follow up.

  • More aggressive excision for recurrent lesions.

  • Ameloblastic fibrosarcoma may develop in the setting of recurrent ameloblastic fibroma.

Ameloblastic Fibrosarcoma

  • Third decade of life.

  • Predilection for the mandible.

  • Rapid clinical growth, often with pain and swelling.

  • Malignant counterpart of ameloblastic fibroma.

  • May arise de novo or from pre-existing ameloblastic fibroma.

Radiographic Findings

  • Poorly defined destructive radiolucency.

  • Unilocular or Multilocular.

  • Expansile.


  • Radical surgical excision with 1–1.5 cm margins and uninvolved margin.

  • Lesions do not usually metastasize, but patients may die from uncontrolled local disease [8].

Ameloblastic Fibro-Odontoma (Ameloblastic Dentinoma)

  • Younger population than ameloblastic fibroma (average age of 9) [1].

  • Mandible is affected more commonly than maxilla

  • No longer considered a separate entity by the WHO but a developmental stage of odontoma.

Radiographic Appearance

  • Well-defined unilocular or multilocular lesion.

  • Contains calcifications and often an unerupted tooth.


  • Enucleation and curettage.

Odontoma (Compound and Complex)

  • The most common odontogenic tumor.

  • Compound odontomas are more common in anterior maxilla. Complex odontoma are found in the posterior region of either jaw.

Radiographic Appearance

  • Compound odontoma: appears as a small, tooth-like structure often surrounded by a radiolucent halo.

  • Complex odontoma: radiopaque mass also surrounded by a radiolucent rim.

  • Odontomas may be found associated with a tooth that has failed to erupt.


  • Excision .

Fibro-Osseous Lesions

  • Fibro-osseous lesions – disease processes characterized by normal bone being replaced by fibrous tissue containing a mineralized product.

Fibrous Dysplasia

  • Characterized by normal bone being replaced by fibrous tissue.

  • Associated with a GNAS gene mutation/deletion. The timing of the mutation during embryogenesis determines the extent of involvement.

  • Can involve one bone if mutation is late (monostotic) or multiple bones (polyostotic) if mutation is early on.

  • Monostotic disease:

    • Most common form of the disease.

    • Equal male and female predilection.

    • Usually diagnosed in the second decade of life.

    • Can involve the craniofacial bones, ribs, femur, and tibia.

    • Maxilla is affected more than the mandible.

    • Manifests as a slow, painful growth of the jaw. Adjacent teeth may be displaced by the expansile lesion.

    • Maxillary lesions can cause obliteration of the antrum if extensive enough and cause a functional issue. Maxillary lesions can extend to the zygoma, sphenoid, ethmoid, and frontal bone (craniofacial fibrous dysplasia).

    • Lesions tend to stabilize after skeletal maturation and even regress in a few cases.

  • Polyostotic disease is usually associated with syndromes that have cutaneous and endocrine abnormalities.

    • Jaffe-Lichtenstein syndrome – polyostotic fibrous dysplasia with café au lait pigmentation.

    • McCune-Albright syndrome – polyostotic fibrous dysplasia with café au lait pigmentation and endocrinopathies (precocious puberty, hyperparathyroidism, hyperthyroidism, and hypercortisolism).

    • Mazabraud syndrome – polyostotic fibrous dysplasia with intramuscular myxomas.

Radiographic Appearance

  • Lesion appears with “ground glass” opacity and poorly defined margins. Periapical radiographs often demonstrate an ill-defined lamina dura (Fig. 8.2)

Fig. 8.2

Occlusal radiograph demonstrating ground glass appearance and expansion of the mandible seen in fibrous dysplasia. (Reprinted with permission from Neville et al. [1])


  • Conservative management is the treatment of choice.

  • Patients with minimal cosmetic and functional issues may not require surgical treatment.

  • Surgical contouring, shaving, and debulking may be performed for the purpose of severe cosmetic deformity and functional problems. Combined orthodontic treatment and orthognathic surgery may be needed should a malocclusion ensue

  • High concern for blood loss after surgery, consider blood banking prior to surgery.

  • Complete surgical removal should be considered for aggressive lesions or lesions refractory to repeated debulking.

  • Radiation is contraindicated due to the risk of post irradiation sarcoma development.

  • Bisphosphonates may help to relieve bone pain (must consider the risk of MRONJ should subsequent surgery be needed).

Cemento-Osseous Dysplasia (COD)

  • Common in Black females, fourth–fifth decade of life.

  • Teeth are vital.

  • Radiographic and clinical findings can lead to a presumptive diagnosis (black female with multiquadrant or lower anterior teeth involvement).

  • Pathological entity in which bone is replaced by a cementum-like material.

  • Three variants:

    1. 1.
      Focal COD:

      • Involves a single site.

      • Shows a female predilection and occurs from the third to sixth decade of life.

      • Mostly involves the posterior mandible in region of first or second molar.

      • Radiographic appearance ranges from radiolucent, to mixed, to completely radiopaque.

    2. 2.
      Periapical COD:

      • Predilection for the anterior mandible periapical region.

      • Predilection for female patients (mostly in females of African descent).

      • Tend to be asymptomatic.

      • Early lesions tend to be radiolucent and mimic periapical granulomas or cysts.

      • Lesions tend to mature and become a mixed radiopacity and ultimately become radiodense with a thin radiolucent rim.

    3. 3.
      Florid COD (Fig. 8.3):

      • Shows multifocal involvement (can involve all four quadrants).

      • Predilection for African American females.

      • Lesions are often asymptomatic and found on routine radiographic screening.

      • May develop swelling if simple bone cysts occur in long-standing lesions.

Fig. 8.3

Patient with multiquadrant cemento-osseous dysplasia (florid osseous dysplasia) . (Courtesy of Dr. Damian Findlay)


  • Teeth are vital.

  • Radiographic and clinical findings can lead to a presumptive diagnosis (Black female with multi-quadrant or lower anterior teeth involvement).


  • Lesions are not neoplastic and, therefore, surgical removal is usually not necessary

  • Sclerotic lesions are hypovascular, which makes them prone to necrosis/infection from minor traumatic insults (e.g., extractions/implant placement).

  • Patients with COD should have regular dental prophylaxis and follow up to prevent dental disease leading to tooth loss (periodontitis/caries).

  • Patients with evidence of osteomyelitis should undergo debridement with saucerization.

Central Giant Cell (CGC) Tumor

  • Intraosseous lesion that may exhibit nonaggressive (most cases) or aggressive behavior.

  • Nonaggressive lesions grow slowly, expand bone, are painless, and do not resorb roots or cortical bone.

  • Aggressive lesions will be symptomatic, occur in younger patients with rapid growth.

  • Diagnosis for the aggressive subtype requires possessing one major or three minor criteria:

    • Major: (1) Greater than 5 cm (2) Recurrence after treatment.

    • Minor: (1) Rapid growth (2) Clinical displacement or loosening of tooth (3) Cortical thinning or perforation (4) Radiographic evidence of tooth resorption or displacement.

  • Unknown origin – widely assumed to be trauma induced (but little supporting evidence).

  • Female predilection (2×).

  • The majority of cases are seen before the third decade of life, with a peak between the ages of 5 and 15.

  • Most cases involve the mandible (usually anterior mandible).

  • Nonaggressive lesions are usually discovered on routine radiographic examination or as a result of painless expansion.

  • Aggressive lesions tend to be aggressive resulting in pain, expansion, paresthesia, root resorption, and tooth displacement.

  • Histologically similar to brown tumors of hyperparathyroidism. Parathyroid hormone assay for primary hyperparathyroidism levels (with hypercalcemia) or for secondary hyperparathyroidism (with hypocalcemia) not routinely required as earlier concerning signs should be evident. Alkaline phosphatase elevation not necessarily needs to be assayed as it is normally elevated in growing children. CGCs demonstrate multinucleated giant cells within a spindle mononuclear cell stroma histologically.

Radiographic Features

  • Well-delineated unilocular or multilocular radiolucency (Fig. 8.4).

  • Displace teeth.

  • Resorb interradicular bone.

Fig. 8.4

Central giant cell tumor. Multilocular radiolucency of anterior mandible . (Image courtesy of Dr. Robert Reti)


  • Enucleation and curettage with peripheral ostectomy, recurrence rate 20% (more frequently in large lesions).

  • En bloc resection with 1 cm margins for recurrent lesions.

  • Conservative treatment for large lesions:

    • Intralesional corticosteroid injections – 1:1 mixture of local anesthetic and triamcinolone 10 mg/mL weekly for 6 weeks. 2 cc for every 1 cc of lesion visible on an orthopantogram; has a high recurrence rate.

    • Submucosal or nasal (less absorption predictability) calcitonin: 100 units calcitonin/day for 6 months. If nausea occurs, may reduce to 50 units/day. No radiographic changes are seen for approximately 9 months and requires 18–21 months for treatment. May also be used to debulk tumor for smaller area of resection if complete resolution is not achieved.

    • Subcutaneous Interferon alpha-2a. Side effects of fever, fatigue, and flu symptoms. Usually used in conjunction with curettage and postoperative treatment for 6 months to prevent recurrence.

    • Imatinib – tyrosine kinase inhibitor.

    • Bisphosphonates.

    • Newer treatment protocols with Rank-L inhibitor Denosumab® is showing to be effective as part of care.

Peripheral Giant Cell Granuloma

  • Soft tissue equivalent of central giant cell granuloma.

  • Caused by trauma or irritation.

  • Common tumor of the oral cavity. Part of 3Ps (1) Pyogenic Granuloma (2) Peripheral Ossifying Fibroma (3) Peripheral Giant Cell Granuloma.

  • Normally smaller than 2 cm with a sessile or pedunculated base.

  • Blue/purple in color.

  • Female predilection.

  • Common age 30–60.

  • Treatment is excision down to the bone.

Medication-Related Osteonecrosis of the Jaw (MRONJ)

  • The medications implicated in MRONJ are antiresorptive medications and antiangiogenic medications.

  • Bisphosphonates and RANK ligand inhibitors are antiresorptive medications. These medications work by diminishing or altering osteoclasts, the cells responsible for bone resorption. RANK ligand inhibitors prevent osteoclast differentiation while bisphosphonates inhibit osteoclast function and increase osteoclast apoptosis. These medications tend to concentrate in areas of bone repair and remodeling possibly explaining their affinity for the jaws and the selectivity of osteonecrosis in this area.

  • Oral bisphosphonates are most commonly used for the treatment of osteoporosis and osteopenia. They are less commonly used for Paget’s disease of bone and osteogenesis imperfecta.

  • Intravenous bisphosphonates for the treatment of osteoporosis are also available as once yearly zoledronic acid and four times yearly ibandronate infusions. Intravenous bisphosphonates are also used for the management of bone metastases of solid tumors, especially breast, prostate, and lung cancers as well as the lytic lesions of multiple myeloma. The RANK ligand inhibitor denosumab is also used to treat osteoporosis and manage bone metastasis (See Tables 8.4 and 8.5 for a list of medications associated with MRONJ).

Table 8.4





Alendronate (Fosamax®)



Risendronate (Actonel®)



Ibandronate (Boniva®)


Oral or IV

Zolendronate (Reclast®)



Zolendronate (Zometa®)

Bone metastases


Pamidronate (Aredia®)

Bone metastases


Table 8.5

RANK ligand inhibitors




Denosumab (Prolia®)



Denosumab (Xgeva®)

Bone metastases


  • Antiangiogenic medications prevent the formation of new blood vessels and are used as a cancer treatment. They include the classes of drugs known as tyrosine kinase inhibitors and monoclonal antibodies inhibiting vascular endothelial growth factor. There is currently little research on the association between osteonecrosis and these medications, but reports indicate that a low risk exists.

  • The 2014 AAOMS position paper on MRONJ requires three characteristics to be present to distinguish MRONJ from other conditions [9]:

    1. 1.

      Current or previous treatment with anti-resorptive or antiangiogenic agents.

    2. 2.

      Exposed bone present for more than 8 weeks that can be probed through an intraoral or extraoral fistula in the maxilla or mandible.

    3. 3.

      No history of radiation therapy or obvious metastatic disease to the jaws.


Radiographic Appearance

  • Radiographic changes are often seen before clinical evidence of necrosis and include increased radiopacity in the areas of increased bone remodeling such as tooth-bearing alveolar ridges.

  • Periosteal hyperplasia is occasionally seen.

  • In severe cases, a moth-eaten radiolucency with central sequestra is seen.

MRONJ Staging System [10]

  • Stage 0 – Non-exposed bone variant:

    • Patients present with no necrotic bone but have other non-specific symptoms such as bone pain and unexplainable tooth pain.

    • Patients may have loose teeth with no evidence of periodontal disease and fistulae unassociated with pulpal necrosis.

    • Radiographic bone changes (usually areas of increased radiopacity) that cannot be attributed to another source may be seen.

  • Stage 1 – Exposed and necrotic bone or fistulae that probe to bone in asymptomatic patients with no evidence of infection.

  • Stage 2 – Exposed and necrotic bone or fistulae that probe to bone in symptomatic patients with evidence of infection.

  • Stage 3 – Exposed and necrotic bone or fistulae that probe to bone in symptomatic patients with evidence of infection and one or more of the following:

    • Exposed necrotic bone extending beyond the alveolus.

    • Pathologic fracture.

    • Extra-oral fistula.

    • Oral antral/oral nasal communication.

    • Osteolysis extending to the inferior border of the mandible or sinus floor.

Preventative Management

  • Patients should be evaluated for both acute and potential sources of oral infection prior to beginning bisphosphonate therapy. Patients with dentures should be evaluated for areas of trauma, as well. Sources of infection should be eliminated and bisphosphonate treatment initiation should be delayed until there is adequate osseous healing (takes about 1 month if conditions permit). Excellent oral hygiene should be stressed.

  • For patients taking bisphosphonates for osteoporosis for 4 years or more or for those who are taking bisphosphonates along with systemic corticosteroids or antiangiogenic agents, a drug holiday should be considered beginning 2 months prior to dentoalveolar surgery and continuing until osseous healing is complete. A drug holiday is not necessary for osteoporosis patients on bisphosphonates for less than 4 years.

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Jul 23, 2021 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Pathology
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