Benign fibrous histiocytoma

Benign fibrous histiocytoma (BFH) is a rare, benign mesenchymal neoplasm composed of a mixture of fibroblastic and histiocytic cells.[1][2] Although BFH is one of the most common mesenchymal tumors of the skin (where it is synonymous with dermatofibroma), involvement of the oral and maxillofacial region is uncommon.[1][2] BFH may arise in oral soft tissue or within the jawbones as an intraosseous lesion.[1][3] The histogenesis remains uncertain; despite the name, studies suggest the proliferative compartment is predominantly fibroblastic/mesenchymal rather than truly histiocytic.[4] Intraosseous jaw lesions typically present as radiolucent defects in the posterior mandible, and the overall biologic behavior is indolent, with most cases amenable to conservative surgical management.[3]

Current classification

• In the 2020 WHO Classification of Soft Tissue and Bone Tumors, deep fibrous histiocytoma is listed under "so-called fibrohistiocytic tumors" as an intermediate (rarely metastasizing) entity.[5][6]
• Cutaneous fibrous histiocytoma (dermatofibroma) and its variants (cellular, aneurysmal, atypical, epithelioid) are classified separately under the 2018 WHO Classification of Skin Tumors as benign fibrohistiocytic neoplasms.[7][8]

Accepted names and aliases

• Benign fibrous histiocytoma (BFH) — the most widely used term in the oral and maxillofacial literature.[1][3]
• Fibrous histiocytoma — abbreviated form used interchangeably.
• Dermatofibroma — synonym restricted to the cutaneous form.[7][9]
• Fibroxanthoma — older term applied to bone lesions with xanthomatous histiocytes; now largely replaced.[10]

Obsolete or confusing terms

• "Malignant fibrous histiocytoma" (MFH) was reclassified in the 2013 and 2020 WHO editions; the term should not be applied to benign lesions.[6][11]
• "Xanthofibroma" and "xanthoma of bone" appear in older literature for histiocyte-rich osseous variants and are no longer preferred.[10][12]

BFH of the oral and maxillofacial region is rare. A systematic review identified fewer than 60 published cases across all oral and maxillofacial subsites.[1]

• Age: Mean age approximately 35 years (±20 years) for all oral/maxillofacial BFH. Intraosseous jaw lesions cluster in the second through fourth decades (mean ~29 years).[1][3]
• Sex: Slight male predominance (~57% male).[1]
• Soft-tissue distribution: Buccal mucosa is the most common oral soft-tissue site (~20%), followed by the tongue, gingiva, and lip.[1]
• Intraosseous distribution: The posterior mandible accounts for approximately 86% of gnathic fibrohistiocytic lesions. Maxillary involvement is uncommon. Rare sites include the mandibular condyle.[3][13]

Soft-tissue lesions

• Present as a painless, slowly growing, firm nodule ranging from a few millimeters to several centimeters.[1][2]
• Approximately 87% are asymptomatic at presentation.[1]
• The overlying mucosa is usually intact; surface color may be normal or slightly altered.
• The most common clinical impression before biopsy is fibroma (~32% of cases).[1]

Intraosseous lesions

• Often discovered incidentally on routine dental radiographs.[3][13]
• When symptomatic, patients may report mild pain, swelling, or jaw expansion.[3]
• Tooth mobility or displacement is occasionally noted with larger lesions.
• Growth tempo is slow; the largest jaw series documented lesional stability over an average follow-up of 85 months.[3]
• No paresthesia or pathologic fracture has been consistently reported in gnathic BFH.

Red flags

• Rapid growth, pain, or paresthesia should raise concern for a higher-grade process (e.g., malignant fibrous tumor or metastatic disease) and warrants prompt biopsy.

Radiographic features of intraosseous BFH are variable, and no single pattern is pathognomonic. The largest jaw series (50 cases) and a systematic review provide the most comprehensive imaging data.[1][3]

Location and distribution

• Strong predilection for the posterior mandible (~86% of intraosseous cases), including the body, angle, and ramus.[3]
• Maxillary involvement is uncommon.
• Rare reports describe lesions in the mandibular condyle.[13]
• Soft-tissue BFH of the oral cavity does not produce a primary osseous radiographic finding; imaging is relevant only for intraosseous lesions.

Periphery and shape

• Borders range from well-defined with a corticated rim to partly irregular without peripheral sclerosis.[3][13]
  • Some lesions show a well-corticated, sclerotic margin similar to other benign fibrous bone lesions.[14]
  • Others demonstrate partly irregular margins without sclerosis, which can mimic more aggressive processes.[13]
• Shape is variable: round, ovoid, or irregular.

Internal architecture

• Radiolucent appearance is the rule; no intrinsic mineralization is expected, consistent with the fibrous nature of the lesion.[15]
• Locularity:
  • Multilocular pattern reported in approximately 56% of intraosseous cases in the systematic review.[1]
  • Unilocular radiolucencies account for the remainder.
• A distinctive mottled, honeycomb-type pattern with punctate lucencies has been described as a recognizable radiographic signature in the largest jaw series. This pattern differs from the coarse septation of ameloblastoma or the soap-bubble appearance of odontogenic myxoma.[3]
• Internal septa, when present, tend to be fine and delicate rather than coarse.

Effects on teeth and adjacent structures

• Tooth displacement may occur with larger lesions.
• Root resorption has been reported but is not a consistent feature.
• Involvement of the inferior alveolar canal is possible when lesions occupy the posterior mandibular body.

Growth pattern, cortical involvement, and extent

• Slow, expansile growth is typical.[2][3]
• Cortical thinning and mild expansion of the buccal or lingual plate may be seen, particularly on cross-sectional imaging.[16][17]
• Cortical perforation is uncommon and, when present, should prompt consideration of a more aggressive entity.
• CBCT is more accurate than panoramic radiography for assessing cortical integrity, expansion, and the relationship to adjacent vital structures.[16][17]

Variants and atypical presentations

• A mandibular angle lesion may mimic a Stafne bone cavity on panoramic radiography; cross-sectional imaging reveals the intraosseous nature of the lesion.[18]
• Histiocyte-rich (xanthomatous) variants may not differ radiographically from conventional BFH.[3]

MRI features

• On MRI, BFH of bone typically demonstrates isointense signal on T1-weighted images (relative to skeletal muscle) and intermediate to high signal on T2-weighted images.[14][19]
• Contrast enhancement is variable; peripheral or heterogeneous gadolinium enhancement has been described.[19][20]
• MRI is useful for delineating soft-tissue extension and distinguishing solid from cystic components when the lesion is large or when cortical perforation is suspected.

CT features

• CT shows a lytic lesion with well-defined geographic margins and variable marginal sclerosis.[14]
• No intrinsic mineralization is present.
• CT is superior to conventional radiography for assessing cortical breakthrough and the extent of medullary involvement.[14][21]

Nuclear medicine

• Bone scintigraphy may show moderately increased uptake, a nonspecific finding that does not reliably distinguish BFH from other fibrous or giant-cell–containing bone lesions.[14]

Intraosseous BFH of the jaws enters the differential of radiolucent, uni- or multilocular posterior mandibular lesions. Because the radiographic appearance is nonspecific, clinical context, patient age, and histopathologic confirmation are essential.[3][22]

The highest-risk diagnostic pitfall is misinterpreting BFH as ameloblastoma or a malignant spindle-cell neoplasm, leading to unnecessarily aggressive resection. Biopsy with immunohistochemistry (CD68, vimentin, SMA) is required for definitive diagnosis, as imaging alone cannot reliably distinguish these entities.[3][22]

Microscopic features

• Storiform (mat-like) arrangement of bland spindle cells is the hallmark pattern, present in approximately 47% of oral/maxillofacial cases as the dominant architecture.[1][2]
• A biphasic population of fibroblastic and histiocytic cells is identified in roughly 40% of cases.[1]
• Variable admixed components include:
  • Foamy (xanthomatous) histiocytes — dominant in ~16% of jaw lesions ("histiocyte-rich" variant).[3]
  • Multinucleate giant cells and osteoclast-like giant cells.[31]
  • Hemosiderin deposits and chronic inflammatory cells.[31][32]
• Cytologic atypia and mitotic figures are absent or minimal; their absence is the principal feature separating BFH from sarcomas.[2]
• Margins are typically ill-defined in soft-tissue lesions; intraosseous lesions may be better circumscribed.[31][32]

Immunohistochemistry

• CD68 and vimentin: positive in virtually all tested cases.[1][3]
• CD163: strongly positive in the largest jaw series.[3]
• Smooth muscle actin (SMA): variable positivity.[3][31]
• S-100, cytokeratin, CD34: negative, helping exclude neural tumors, carcinomas, and dermatofibrosarcoma protuberans.[13][33]
• Desmin: negative or only focally positive.[31]

Radiologic-pathologic correlation

• The mottled, honeycomb radiographic pattern corresponds histologically to fibrous tissue admixed with clusters of xanthomatous histiocytes interspersed among residual bony trabeculae.[3]
• Multilocular radiolucencies reflect irregular replacement of medullary bone by the fibrohistiocytic proliferation.

Variants of note

• Cellular fibrous histiocytoma: more monomorphic spindle-cell proliferation with higher mitotic rate; carries ~25% local recurrence risk in cutaneous sites.[7][34]
• Aneurysmal fibrous histiocytoma: blood-filled spaces without endothelial lining; classified as intermediate grade when occurring as the angiomatoid variant.[33][35]
• Deep (subcutaneous/soft-tissue) fibrous histiocytoma: well-circumscribed, storiform pattern with hemangiopericytoma-like vasculature; rare metastatic potential (~5% in consultation series, likely overestimated).[31]

Workup and referral

• Incidental radiolucent jaw lesions with features suggestive of BFH warrant referral for biopsy to exclude ameloblastoma, odontogenic keratocyst, or malignant spindle-cell neoplasms.[3][22]
• Serum calcium and parathyroid hormone should be checked when brown tumor of hyperparathyroidism is in the differential.[12]

Treatment

• Intraosseous jaw lesions: Conservative management — curettage or enucleation — is the standard approach. In the largest jaw series, 92% of cases were treated conservatively with excellent outcomes.[3]
• Oral soft-tissue lesions: Local surgical excision with adequate margins is the treatment of choice.[1][2]
• Radical resection is not indicated for typical BFH and should be reserved for cases with histologic features of a higher-grade process.

Recurrence

• Overall recurrence rate in the oral/maxillofacial region is approximately 8%.[1]
• In the largest intraosseous jaw series, only 2 of 50 cases recurred (both at 24 months), with no malignant transformation over a mean follow-up of 85 months.[3]
• Recurrence is generally attributed to incomplete excision rather than intrinsic aggressiveness.[2][31]

Prognosis

• Prognosis is excellent. No malignant transformation has been documented in gnathic BFH.[3]
• Deep soft-tissue BFH carries a slightly higher recurrence rate (~22%) and rare metastatic potential, but this subtype is exceptional in the jaws.[31]

Surveillance

• Clinical and radiographic follow-up at 6- to 12-month intervals for the first 2 years after treatment is reasonable, given the low but nonzero recurrence risk.[3]
• Long-term stability without progression has been documented over follow-up periods averaging 7 years.[3]

Relationship to non-ossifying fibroma

Intraosseous BFH of bone is histologically identical to non-ossifying fibroma (NOF), the common self-limiting metaphyseal lesion of children and adolescents.[10][12] The distinction is clinical: BFH occurs in adults, is symptomatic (or incidentally discovered in atypical locations such as the jaws), and does not spontaneously regress.[10][12] This overlap has led some authors to consider gnathic fibrohistiocytic lesions a heterogeneous group encompassing both reactive and neoplastic processes.[3]

Rare aggressive behavior

Although exceedingly uncommon, PRKCD gene fusions (e.g., KIRREL1::PRKCD, LAMTOR1::PRKCD) have been identified in rare cases of "benign" fibrous histiocytoma with recurrence and metastasis.[36] Complex chromosomal abnormalities may serve as indicators of aggressive potential. These molecular findings have not been reported in gnathic BFH but underscore the importance of adequate excision and follow-up, particularly for deep or recurrent lesions.