Aneurysmal bone cyst

Aneurysmal bone cyst (ABC) is a benign, locally aggressive neoplasm of bone characterized by blood-filled cystic spaces separated by fibrous septa.[1][2] Primary ABC is now recognized as a true neoplasm driven by USP6 gene rearrangements, most commonly via a promoter-swapping mechanism with CDH11 as the upstream fusion partner.[3][4] Secondary ABC-like changes, which lack USP6 rearrangements, arise within pre-existing bone lesions—most notably ossifying fibroma and fibrous dysplasia in the jaws—and represent a reactive morphologic pattern rather than a distinct neoplasm.[3][5] In the jaws, ABC is exceedingly rare, constituting approximately 0.047% of oral and maxillofacial biopsies, with only about 2% of all ABCs occurring in the craniofacial skeleton.[6][7] The signature imaging pattern is a well-demarcated, expansile, multilocular radiolucency with marked cortical expansion and frequent cortical disruption.[8] Treatment is primarily surgical, with a favorable prognosis in most cases.[9]

• The 2020 WHO Classification of Soft Tissue and Bone Tumours reclassified ABC from the intermediate (locally aggressive) category to the benign category within the osteoclastic giant cell–rich tumour group.[2][10]
• Primary ABC designates the true neoplasm harboring USP6 rearrangements; secondary ABC (or ABC-like change) describes morphologically similar cystic changes arising within other bone lesions and lacking USP6 rearrangements.[3]
• The solid variant (approximately 5% of ABCs) lacks prominent blood-filled cystic spaces but is otherwise morphologically and molecularly identical to conventional ABC.[11][12]
• Older literature may refer to ABC as a "pseudocyst" or group it with simple bone cyst under "jaw pseudocysts"; this terminology is outdated given the established neoplastic basis of primary ABC.[13]

• Age: Predominantly affects children and young adults; approximately 75–90% of cases occur in patients under 20 years. Mean age in jaw series ranges from 18.8 to 24.7 years.[6][9][14]
• Sex: No consistent sex predilection overall. Some jaw series report a slight female predominance, while others show near-equal distribution.[6][8][9][15]
• Frequency: ABC accounts for 1–2% of primary biopsied bone tumors across all skeletal sites. Gnathic involvement is extremely rare, estimated at 0.047% of oral and maxillofacial biopsies.[6][11]
• Anatomic distribution in the jaws:
  • Mandible: 76–95% of jaw cases[6][9][15]
  • Maxilla: 5–24%[9][15]
  • Strong predilection for the posterior mandible (body, angle, ramus)[8][9]

Presentation and symptoms

• Painless swelling is the most common presenting complaint, reported in 70–77% of jaw cases. A minority present with painful swelling (approximately 18–25%).[5][6][9][16]
• Growth may be rapid, prompting concern for malignancy.[7]
• Mucosal discoloration or a bluish hue overlying the lesion is occasionally noted.
• Tooth mobility and malocclusion may develop as the lesion enlarges.[17]

Examination findings

• Firm or fluctuant bony expansion, typically involving the buccal and sometimes lingual cortices.[8][9]
• Overlying mucosa is usually intact; ulceration is uncommon.
• Aspiration may yield frank blood, which is a useful clinical clue but is not pathognomonic.[18]

Tempo and complications

• ABCs can enlarge rapidly over weeks to months, occasionally reaching substantial size before diagnosis.[7]
• Cortical perforation is common (78% in one large series), which may lead to soft-tissue extension.[8]
• Pathologic fracture of the mandible is a recognized but uncommon complication.
• Paresthesia of the inferior alveolar nerve may occur with large mandibular lesions.

Location and distribution

• The posterior mandible (body, angle, ramus) is the most common jaw location, accounting for the majority of cases. Anterior mandibular and maxillary involvement is less frequent.[6][8][9]
• Lesions are typically centered within the medullary bone and expand outward.

Periphery and shape

• ABCs present as well-demarcated radiolucent lesions with a defined corticated or partially corticated border.[5][8]
• The majority display a multilocular (soap-bubble or honeycomb) pattern, reported in 59–77% of jaw cases. A unilocular pattern is seen in the remainder.[5][6][8][15]
• Margins are generally well defined (71% in one series), though ill-defined borders occur occasionally.[5]

Internal architecture

• The internal structure is predominantly radiolucent. Multilocular lesions contain bony septa of variable thickness that create compartments.[8][15]
• On CBCT, intracystic septa are more readily visualized than on conventional radiographs, and the internal compartments may vary in density depending on the age and composition of hemorrhagic contents.[7][15]
• The rare solid variant lacks the characteristic cystic spaces and appears as a more homogeneous soft-tissue density mass without fluid-fluid levels, making radiographic distinction from other solid bone tumors difficult.[19][20]

Cortical involvement and extent

• Cortical expansion is a hallmark feature, present in approximately 91% of jaw ABCs, typically producing a "blow-out" or ballooning configuration.[8]
• Loss of cortical integrity (perforation or discontinuity) is common, reported in 78% of cases in the largest radiologic series. This feature may simulate an aggressive or malignant process.[8]
• Expansion is characteristically omnidirectional (buccal, lingual, and sometimes superior/inferior), distinguishing ABC from many odontogenic lesions that tend to expand preferentially in one direction.[7][8]
• On CBCT, thin residual cortical shells and areas of cortical breach with soft-tissue extension are well delineated, aiding surgical planning.[7]

Effects on teeth and adjacent structures

• Tooth displacement is common in tooth-bearing areas, with teeth pushed away from the expanding lesion.
• Root resorption is reported but is not a consistent feature; when present, it may be extensive.[13][17]
• Displacement of the inferior alveolar canal may be seen in mandibular lesions.[13]
• Developing tooth germs may be displaced in pediatric patients.

Growth pattern

• ABCs exhibit an expansile growth pattern with centrifugal enlargement, remodeling and thinning the surrounding cortex rather than infiltrating bone in a permeative fashion.[1][8]
• Rapid growth can produce a periosteal reaction, though this is more commonly described in long-bone ABCs than in jaw lesions.

Recognized variants

• Unilocular ABC: A minority of jaw cases present as a well-defined unilocular radiolucency, which may mimic a dentigerous cyst, odontogenic keratocyst, or simple bone cyst.[5][15]
• Solid variant: Appears as an expansile, predominantly solid mass without the characteristic cystic compartments or fluid-fluid levels; extremely rare in the jaws.[11][19]

MRI

• MRI is the most informative cross-sectional modality for ABC characterization. The hallmark finding is fluid-fluid levels within cystic compartments, representing layering of blood products of different ages and densities.[7][15][21]
• Fluid-fluid levels are highly suggestive but not pathognomonic for ABC; they may also be seen in telangiectatic osteosarcoma and, less commonly, in giant cell tumor with secondary cystic change.[1][20]
• Cystic compartments typically show low-to-intermediate signal on T1-weighted images and high signal on T2-weighted images; dependent layers of sedimented blood products produce the characteristic double-density appearance.[21][22]
• Thin fibrous septa enhance following gadolinium administration; the cystic spaces themselves do not enhance.[22]
• A thin, low-signal peripheral rim on all sequences corresponds to the residual cortical shell or periosteal new bone.[7]

Medical CT

• CT demonstrates an expansile, lytic lesion with internal septa and thinned or disrupted cortex.[15][20]
• Fluid-fluid levels may be visible on CT when the patient has been supine long enough for sedimentation, though they are better appreciated on MRI.[20]
• CT is useful for evaluating cortical integrity, the extent of soft-tissue extension, and the relationship to critical structures such as the inferior alveolar canal and maxillary sinus.[15]

The differential diagnosis of a well-demarcated, expansile, multilocular radiolucency in the jaws of a young patient centers on lesions that share the combination of osteolysis, expansion, and internal septation. Aspiration yielding frank blood narrows the differential but does not exclude other vascular or hemorrhagic lesions.

The highest-risk diagnostic pitfall is misidentification of telangiectatic osteosarcoma as ABC, since both share fluid-fluid levels and expansile lytic morphology. When imaging features are ambiguous, incisional biopsy with careful histopathologic evaluation—and USP6 FISH or next-generation sequencing when needed—is essential to exclude malignancy before definitive treatment.[20][24]

Conventional (cystic) ABC

• Blood-filled cystic spaces separated by fibrous septa containing bland spindle cells (fibroblasts/myofibroblasts), scattered osteoclast-like multinucleated giant cells, and reactive osteoid or woven bone formation.[22][24][25]
• The spindle cells are cytologically bland without significant atypia; mitotic figures may be frequent but atypical mitoses are absent.[22]
• Hemosiderin deposits are common within the septa.[16]
• So-called "lacy" or "blue" osteoid within the septa is a characteristic but not universal finding.[12][24]

Solid variant

• Composed of a spindle cell proliferation with scattered giant cells and woven bone but lacking prominent blood-filled cystic spaces.[11][24]
• Accounts for approximately 5% of ABCs.[12]
• Morphologically overlaps with giant cell granuloma and giant cell tumor, making histopathologic distinction challenging without molecular confirmation.[19][26]

Radiologic-pathologic correlation

• The multilocular radiographic pattern corresponds to the multiple blood-filled compartments separated by fibrous septa.
• Fluid-fluid levels on MRI reflect layering of unclotted blood and serum within these compartments.
• Cortical expansion and perforation correlate with the locally aggressive, expansile growth of the lesion.

Molecular findings

• Approximately 70% of primary ABCs harbor USP6 rearrangements, most commonly CDH11::USP6 resulting from t(16;17), with a growing list of alternative fusion partners including PAFAH1B1, COL1A1, RUNX2, CTNNB1, FAT1, and others.[3][4][25][27]
• The rearrangement causes overexpression of intact USP6 protein via a promoter-swapping mechanism; it is restricted to the neoplastic spindle cells.[3][4]
• USP6 rearrangements are absent in secondary ABC-like changes and in morphologic mimics including telangiectatic osteosarcoma and giant cell tumor.[3][25]
• FISH for USP6 break-apart is the preferred molecular test; next-generation sequencing–based RNA fusion panels offer higher sensitivity, particularly in decalcified specimens.[19][24][27]
• Notably, giant cell lesions of the jaw (central giant cell granuloma) harbor KRAS, FGFR1, or TRPV4 mutations rather than USP6 rearrangements, providing a molecular distinction from ABC.[25]

Workup and referral

• Referral to oral and maxillofacial surgery is appropriate for all suspected jaw ABCs.
• Incisional biopsy is the standard for definitive diagnosis; aspiration yielding blood is supportive but not diagnostic.[18][20]
• Cross-sectional imaging (CBCT or medical CT; MRI when available) should be obtained before biopsy to assess extent, cortical integrity, and relationship to vital structures.[7][15]

Surgical treatment

• Curettage (with or without adjuvants) is the most widely used treatment for jaw ABCs and is appropriate for smaller, well-contained lesions.[9][15]
  • Recurrence after curettage alone ranges from 15–22% in meta-analytic data across all skeletal sites.[28]
  • Adjuvant measures (high-speed burr, cryotherapy, chemical cauterization) may reduce recurrence.[28][29]
• Excision or en bloc resection is preferred for large lesions, recurrent disease, or cases with extensive cortical destruction, particularly when curettage would leave inadequate structural bone.[5][9][15]
  • In the largest jaw series (120 cases), 90% were treated by excision and curettage, with a recurrence rate below 10%.[9]
  • Resection with immediate autologous bone graft reconstruction is recommended for large mandibular defects.[15]

Nonsurgical and adjunctive options

• Denosumab (anti-RANKL monoclonal antibody) has shown efficacy in promoting calcification, size reduction, and devascularization of ABCs, particularly in surgically challenging locations such as the spine and skull base. Its use in jaw ABCs is limited to case-level evidence, and it remains an off-label application.[30][31][32]
• Doxycycline injection (percutaneous sclerotherapy) has demonstrated excellent healing rates (98%) with low recurrence (11%) in a systematic review of ABCs across all sites, though jaw-specific data are sparse.[28]
• Preoperative selective arterial embolization may reduce intraoperative hemorrhage and has been shown to improve recurrence rates when combined with curettage.[28]

Recurrence and prognosis

• Overall recurrence rate in jaw ABCs is less than 10% with adequate surgical treatment.[9]
• Younger age (under 13 years) and incomplete excision are associated with higher recurrence risk.[14][33]
• Recurrence typically occurs within the first 1–2 years after surgery; long-term follow-up with clinical and radiographic surveillance is recommended.[9][15]
• Malignant transformation of ABC is not a recognized phenomenon; however, secondary ABC arising within a pre-existing neoplasm (e.g., ossifying fibroma, fibrous dysplasia) requires treatment directed at the underlying lesion.[5][6]

Secondary ABC in the jaws

• A substantial proportion of jaw ABCs are secondary, arising within pre-existing lesions. In one series, 76.5% of jaw ABCs were secondary, with ossifying fibroma as the most common associated lesion (11 of 13 secondary cases). Other series report association with ossifying fibroma in approximately 12% and fibrous dysplasia in 4% of cases.[5][6]
• When secondary ABC is suspected, thorough histopathologic sampling of the solid component is essential to identify the underlying neoplasm, as management and prognosis depend on the primary lesion.[3][5]

Molecular distinction from gnathic giant cell lesions

• USP6 rearrangements, which define primary ABC, do not occur in giant cell lesions of the jaw (central giant cell granuloma), which instead harbor MAP kinase pathway mutations (KRAS, FGFR1, TRPV4). This molecular distinction is clinically relevant when histopathology is ambiguous, particularly in the solid variant of ABC.[25]

Pediatric considerations

• In children, rapid growth of jaw ABC may mimic malignancy and cause significant anxiety. Younger patients have a higher recurrence risk after curettage, and conservative surgical approaches aimed at preserving developing dentition and growth centers must be balanced against the need for adequate margins.[14][33]
• Denosumab use in pediatric patients carries a risk of rebound hypercalcemia after discontinuation, requiring careful monitoring and consideration of bisphosphonate bridging.[32][34]