Musculoskeletal

Fibrous dysplasia and bone tumors: overview

Clinical Overview and When to Suspect Fibrous Dysplasia and Bone Tumors

— Monostotic (~70–80%): single bone, usually adolescents/young adults

— Polyostotic (~20–30%): multiple bones, often unilateral, more deformity

— McCune-Albright syndrome (MAS): polyostotic FD + café-au-lait macules (jagged "coast of Maine" borders) + endocrinopathies (precocious puberty, hyperthyroidism, GH excess, Cushing, FGF23-mediated hypophosphatemia)

— Mazabraud syndrome: FD + intramuscular myxomas

— Adolescent or young adult with painless bony expansion, limb deformity, or pathologic fracture

— Incidental "ground-glass" lesion on radiograph of femur, tibia, ribs, or skull base

— Recurrent fractures of proximal femur producing "shepherd's crook" deformity

— Craniofacial asymmetry, proptosis, hearing loss, or cranial neuropathy from skull base lesions

— Unexplained hypophosphatemia in a young patient (FGF23 from dysplastic bone)

— Benign: osteoid osteoma, osteoblastoma, osteochondroma, enchondroma, giant cell tumor (GCT), non-ossifying fibroma, aneurysmal bone cyst

— Malignant primary: osteosarcoma, Ewing sarcoma, chondrosarcoma, chordoma

— Metastatic (most common cause of bone lesion >40 yo): breast, prostate, lung, kidney, thyroid

Fibrous dysplasia (FD) is a benign, non-inherited skeletal disorder caused by postzygotic activating mutations in GNAS (encoding Gsα), leading to replacement of normal bone and marrow with fibro-osseous tissue.

When to suspect FD on Step 3:

Broader bone tumor framework (must distinguish from FD):

Board pearl: In a patient <30 with a lytic, well-defined "ground-glass" diaphyseal lesion and no aggressive features, think FD first. In a patient >40 with a destructive lesion, think metastasis until proven otherwise — order PSA, mammogram, CT chest/abdomen/pelvis, and SPEP before biopsy to avoid surprising a renal cell or myeloma lesion.

Presentation Patterns and Key History

— <5 yrs: Langerhans cell histiocytosis, metastatic neuroblastoma, leukemia

— 5–20 yrs: osteosarcoma (metaphysis), Ewing sarcoma (diaphysis), osteoid osteoma, non-ossifying fibroma, simple bone cyst, fibrous dysplasia

— 20–40 yrs: GCT (epiphysis, after physeal closure), enchondroma, chondroblastoma, FD still possible

— >40 yrs: metastasis, multiple myeloma, chondrosarcoma

— Often asymptomatic, found incidentally on radiograph for unrelated trauma

— Dull, activity-related bone pain that worsens with weight bearing (femur, tibia)

— Progressive deformity — bowing, leg-length discrepancy, facial asymmetry

— Pathologic fracture with minimal trauma

— MAS triad clues: girl with precocious puberty (vaginal bleeding before age 8), café-au-lait spots, and limp

— Night pain, rest pain, constitutional symptoms (weight loss, fevers, night sweats)

— Rapidly enlarging mass

— Pain unresponsive to NSAIDs (note: osteoid osteoma pain classically relieved by NSAIDs/aspirin)

— History of prior radiation, Paget disease, retinoblastoma (osteosarcoma risk)

— Multiple hereditary exostoses (osteochondromas) — AD, EXT1/EXT2

— Ollier disease/Maffucci syndrome (multiple enchondromas) — malignant transformation risk

— Li-Fraumeni, Rothmund-Thomson — osteosarcoma

— Prior cancer history → metastasis until proven otherwise

Age and tempo are pivotal triage tools for any bone lesion question on Step 3.

Fibrous dysplasia history clues:

Red-flag history suggesting malignancy (steer away from FD):

Family/personal history:

Key distinction: FD pain is mechanical and dull, often in the proximal femur, and is not relieved specifically by aspirin — that feature points to osteoid osteoma. Conversely, night pain awakening the patient should never be attributed to FD without ruling out malignancy with MRI and possibly biopsy.

Physical Exam Findings

— Limb-length discrepancy, angular deformity, antalgic gait — polyostotic FD

— Shepherd's crook deformity of proximal femur (varus bowing) — pathognomonic visual for polyostotic FD

— Craniofacial asymmetry, frontal bossing, proptosis, malocclusion — craniofacial FD ("leontiasis ossea")

— Palpable, non-tender bony expansion of rib, tibia, or mandible

— Café-au-lait macules with irregular "coast of Maine" borders, often respecting midline, ipsilateral to bone lesions

— Contrast with NF1's smooth "coast of California" borders and axillary freckling

— Look for acromegalic features (coarse facies, large hands) if GH excess

— Tanner staging — precocious puberty (peripheral, gonadotropin-independent, often from autonomous ovarian cysts in girls)

— Goiter, tachycardia, lid lag — hyperthyroidism

— Moon facies, striae — Cushing (usually infantile in MAS)

— Visual acuity, visual fields, fundoscopy — optic canal narrowing from craniofacial FD

— Hearing (Weber/Rinne) — conductive loss from temporal bone involvement

— Distal pulses, sensation, motor in any limb with deformity or pain — assess for impending fracture

— Osteosarcoma: tender, warm, firm metaphyseal mass near knee with overlying venous distention

— Ewing: similar but often with low-grade fever and erythema mimicking osteomyelitis

— GCT: epiphyseal tenderness near knee/distal radius in skeletally mature patient

— Osteochondroma: hard, non-tender pedunculated mass continuous with cortex

General inspection:

Skin exam (critical in suspected MAS):

Endocrine exam (MAS):

Neurovascular and cranial nerve exam:

Tumor-specific exam pearls:

Step 3 management: In any child or adolescent presenting with café-au-lait macules plus precocious puberty, document a full skeletal survey, TSH, IGF-1, AM cortisol, LH/FSH/estradiol, and serum phosphorus at the index visit — MAS screening cannot wait for the next encounter.

Diagnostic Workup — Initial Labs and Imaging

— FD classic appearance: well-defined, central medullary "ground-glass" lesion in the diaphysis/metadiaphysis, endosteal scalloping, expansile remodeling, thin sclerotic ("rind") border, no periosteal reaction, no soft tissue mass

— Femoral neck shepherd's crook, tibial bowing, ribs (most common rib lesion in adults), and skull base thickening are characteristic

— Polyostotic disease tends to be unilateral

— Aggressive periosteal reaction: Codman triangle, sunburst, onion-skin (Ewing)

— Wide zone of transition, cortical destruction, soft tissue mass

— Permeative or moth-eaten lytic pattern

— CBC, CMP, calcium, phosphorus, alkaline phosphatase (ALP), 25-OH vitamin D, PTH

— ALP often mildly elevated in active FD; markedly elevated in Paget, osteosarcoma, healing fracture

— Low phosphorus + inappropriately normal/low 1,25-vitamin D + phosphaturia → FGF23-mediated hypophosphatemia of FD/MAS

— In adults >40: SPEP/UPEP with immunofixation, serum free light chains to exclude myeloma; PSA in men; consider TSH, ferritin

First-line imaging: plain radiograph of the symptomatic site, two orthogonal views.

Radiographic features signaling malignancy (NOT FD):

Initial laboratory panel for any bone lesion:

Endocrine screen if MAS suspected: TSH/free T4, IGF-1, AM cortisol with dexamethasone suppression if clinical signs, LH/FSH/estradiol or testosterone, prolactin.

Bone scan (Tc-99m MDP) for polyostotic mapping — FD lesions are markedly hot; useful before deciding on therapy and to screen the entire skeleton.

CCS pearl: When ordering imaging on CCS for a young patient with a long-bone lesion, sequence is: plain radiograph → CBC/CMP/Ca/Phos/ALP → MRI of the lesion → referral to orthopedic oncology before biopsy. Biopsy before MRI can obscure staging and is a documented exam trap.

Diagnostic Workup — Advanced and Confirmatory Studies

— Pain is disproportionate to plain film findings

— Soft tissue component, cortical breakthrough, or marrow edema suspected

— Preoperative planning, suspected malignancy, or spinal/pelvic lesions

— FD on MRI: low-to-intermediate T1, variable T2, heterogeneous enhancement; cystic change can mimic aggressive lesions

— Craniofacial FD — defines optic canal, foramen narrowing

— Characterizing matrix mineralization (ground-glass vs chondroid rings-and-arcs vs osteoid cloud-like)

— Guiding biopsy

— Many classic FD lesions do not require biopsy if imaging is diagnostic and lesion is asymptomatic/stable

— Biopsy if: atypical features, pain change, suspicion of malignant transformation (rare, <1%), or before surgical intervention in unclear cases

— Must be performed by the operating orthopedic oncology team through a planned, resectable tract — improper biopsy tract can convert a limb-salvage case to amputation

— FD histology: "Chinese letters" or "alphabet soup" — irregular curvilinear woven bone trabeculae without osteoblastic rimming, embedded in bland fibrous stroma

— GNAS mutation testing can confirm in ambiguous cases

— Osteosarcoma: malignant osteoid by atypical cells

— Ewing: small round blue cells, CD99+, t(11;22) EWSR1-FLI1

— GCT: multinucleated osteoclast-like giant cells in mononuclear stroma

— Chondrosarcoma: malignant cartilage with myxoid change

— Osteoid osteoma: central nidus <2 cm with surrounding sclerosis

MRI with and without contrast is the next step when:

CT is best for:

FDG-PET/CT and whole-body MRI: staging suspected malignancy; not routine for FD.

Biopsy — when and how:

Histology pattern recognition for comparison:

Board pearl: Absence of osteoblastic rimming distinguishes fibrous dysplasia from ossifying fibroma, which has plump rimming osteoblasts. This is a favorite USMLE pathology distinction and changes prognosis and surgical approach.

Risk Stratification and First-Line Management Logic

— Tier 1 — Asymptomatic, monostotic, no deformity/fracture risk:

Observation with annual clinical exam and serial radiographs; activity unrestricted; ensure calcium and vitamin D sufficiency.

— Tier 2 — Symptomatic FD (chronic bone pain) without impending fracture:

Pain control with acetaminophen/NSAIDs first; if persistent, bisphosphonates (IV pamidronate or zoledronic acid) are mainstay; consider denosumab in refractory cases.

— Tier 3 — Polyostotic / MAS:

Multidisciplinary team — orthopedics, endocrinology, ENT/ophthalmology if craniofacial; treat each endocrinopathy; screen for and correct hypophosphatemia with oral phosphate + calcitriol.

— Tier 4 — Impending or pathologic fracture, severe deformity, neurologic compromise:

Surgical intervention — internal fixation (intramedullary nail preferred over plates for proximal femur), osteotomy for deformity correction, decompression for optic nerve only if vision compromised.

— <1% lifetime risk; higher with prior radiation (which is contraindicated in FD)

— Signals: new severe pain, rapid growth, ALP spike — re-image and biopsy

— Benign latent (NOF, enchondroma): observe

— Benign active/aggressive (GCT, ABC): curettage ± adjuvant (phenol, cement, cryo)

— Malignant: neoadjuvant chemo → limb-salvage resection → adjuvant chemo (osteosarcoma, Ewing)

Stratify FD patients into management tiers:

Optic nerve management controversy: Prophylactic optic nerve decompression is NOT recommended in asymptomatic craniofacial FD — observe with serial visual fields/OCT; decompress only if documented progressive vision loss.

Malignant transformation:

Bone tumor general triage:

Step 3 management: For a 25-year-old with monostotic femoral FD and dull thigh pain, the correct next step is NSAID trial + DEXA + 25-OH vit D, not immediate bisphosphonate or surgery. Escalate to IV zoledronic acid only after NSAID failure documented over weeks.

Pharmacotherapy — First-Line Drug Regimen

— IV zoledronic acid 5 mg yearly (most common adult regimen) OR IV pamidronate 60 mg over 4 hours every 3–6 months

— Reduces bone pain in ~50–70% of patients, lowers bone turnover markers (CTX, P1NP, ALP)

— Does NOT reverse deformity or prevent fracture definitively — counsel realistically

— Pre-treatment: dental clearance, correct vitamin D >30 ng/mL, calcium intake 1000–1200 mg/day

— Monitor: serum creatinine, calcium, phosphate; acute-phase reaction (flu-like) in 30% after first dose — pretreat with acetaminophen

— Oral phosphate 1–3 g/day divided + calcitriol 0.25–0.5 mcg/day

— Monitor for nephrocalcinosis and secondary hyperparathyroidism

— Burosumab (anti-FGF23 monoclonal) emerging for FGF23-mediated hypophosphatemia

— Precocious puberty (girls): letrozole or tamoxifen; GnRH agonist if central component activates

— Hyperthyroidism: methimazole; definitive RAI or thyroidectomy often needed

— GH excess: pegvisomant or somatostatin analogs

— Cushing (infantile): often resolves spontaneously; ketoconazole or adrenalectomy if severe

Bisphosphonates are the cornerstone medical therapy for symptomatic FD.

Denosumab (RANKL inhibitor): off-label for FD refractory to bisphosphonates; rapid response but rebound hypercalcemia and vertebral fractures on discontinuation — must transition carefully, often back to bisphosphonate.

Hypophosphatemia treatment (MAS/FD):

Endocrine therapy in MAS:

Pain ladder: acetaminophen → NSAIDs (caution renal) → bisphosphonate → consider gabapentinoid for neuropathic component → avoid chronic opioids.

Board pearl: Always assess and correct vitamin D and calcium before starting any bisphosphonate or denosumab — failure to do so causes symptomatic hypocalcemia and is a classic Step 3 patient-safety distractor in vignette answer choices.

Procedures and Surgical Management

— Pathologic fracture (acute fixation)

— Impending fracture — Mirels score ≥9 or progressive cortical thinning in weight-bearing bone

— Progressive deformity affecting function (shepherd's crook, tibial bowing)

— Failed medical management of pain

— Neurologic compromise (spine, optic nerve with documented decline)

— Concern for malignant transformation

— Intramedullary nailing preferred over plate-and-screw constructs in long bones — better load sharing, resists deformity recurrence

— Avoid bone grafting with cancellous autograft — gets resorbed and replaced by dysplastic bone; cortical strut allograft or cement augmentation preferred

— Curettage alone has high recurrence in skeletally immature patients — combine with mechanical stabilization

— Radiation therapy is contraindicated — increases sarcomatous transformation risk

— Contouring/recontouring for cosmesis once growth slows

— Optic canal decompression only for documented vision loss

— Address malocclusion, airway, sinus drainage as needed

— Osteoid osteoma: CT-guided radiofrequency ablation of the nidus — first line

— GCT: intralesional curettage + adjuvant (phenol, liquid nitrogen, PMMA cement); denosumab for unresectable/recurrent

— Aneurysmal bone cyst: curettage + bone graft or selective arterial embolization

— Osteosarcoma/Ewing: neoadjuvant chemo → limb-salvage wide resection → adjuvant chemo

— Solitary bone metastasis with impending fracture: prophylactic intramedullary nailing + postop radiation

Indications for orthopedic surgery in FD:

Surgical principles:

Craniofacial FD surgery:

Procedures for other bone tumors (high-yield contrasts):

CCS pearl: In a 14-year-old with proximal femoral FD and a Mirels score of 10, the correct order set is NPO, type and screen, ortho consult, MRI hip, and admit for prophylactic intramedullary nailing — do not discharge home on crutches "to follow up in clinic," a frequent CCS trap.

Special Populations — Elderly and Renal/Hepatic Impairment

— Default suspicion shifts from FD to metastasis or myeloma above age 40

— Workup pivots: CT chest/abdomen/pelvis, mammogram, PSA, SPEP/UPEP, serum free light chains, TSH, urinalysis (for RCC hematuria)

— Long-standing FD can persist into older adulthood but typically stable; new pain in an older FD patient = re-image and consider transformation to osteosarcoma or fibrosarcoma

— Paget: markedly elevated ALP, mosaic pattern on biopsy, cortical thickening with coarse trabeculae, often pelvis/skull/spine, >55 years

— FD: ground-glass medullary lesion, normal-to-mildly elevated ALP, younger onset

— Treatment overlap: both respond to bisphosphonates

— Bisphosphonates contraindicated if CrCl <35 mL/min (zoledronic acid); reduce/avoid pamidronate similarly

— Denosumab is not renally cleared — preferred in CKD but risk of severe hypocalcemia is higher; check calcium, phosphate, magnesium, vitamin D before and during therapy

— Oral phosphate in MAS hypophosphatemia → monitor for hyperphosphatemia, vascular calcification in CKD

— NSAIDs: avoid chronic use; favor acetaminophen for analgesia

— Bisphosphonates require no hepatic dose adjustment

— Acetaminophen: limit to ≤2 g/day in significant hepatic dysfunction

— Avoid hepatically cleared opioids in advanced cirrhosis; use morphine cautiously and adjust

— Reconcile sedating analgesics, antihypertensives

— Vitamin D, calcium, balance training, home safety eval — same secondary fracture prevention pillars as osteoporosis care

Elderly patients with newly discovered bone lesions:

Paget disease vs FD in older adults:

Renal impairment considerations:

Hepatic impairment:

Polypharmacy/fall risk:

Key distinction: A 70-year-old with a new lytic lesion + ALP elevation + back pain should trigger a myeloma and metastasis workup first, not an FD workup — even if a "ground-glass" appearance is described, pretest probability for primary FD at this age is very low.

Special Populations — Pregnancy and Pediatrics

— Most FD presents in childhood/adolescence; growth and skeletal maturation drive deformity progression

— MAS suspicion in any girl <8 with vaginal bleeding or breast development + café-au-lait — evaluate per algorithm above

— Letrozole preferred over historical agents (testolactone) for peripheral precocious puberty in MAS girls; reduces estrogen synthesis

— Bisphosphonates in children: used for severe pain/recurrent fracture; long-term skeletal effects monitored but generally safe with pediatric endocrine guidance

— Avoid radiation absolutely; minimize ionizing imaging — favor MRI for surveillance

— Multidisciplinary care: pediatric endocrinology, orthopedics, ophthalmology, ENT, audiology, dentistry, genetics, school accommodations

— Estrogen-driven activation can worsen FD lesions during pregnancy — increased pain and rarely accelerated growth, especially craniofacial

— Bisphosphonates are pregnancy category D / avoid — long skeletal half-life means even pre-pregnancy use raises theoretical fetal bone concerns; counsel women of childbearing age before starting zoledronic acid; advise contraception during therapy

— Denosumab contraindicated in pregnancy (fetal harm in animal studies)

— Acetaminophen safe; avoid NSAIDs in 3rd trimester (premature ductus closure)

— Mode of delivery dictated by obstetric, not FD, considerations unless pelvic deformity present

— Lactation: limited data on bisphosphonates — generally avoid

— Persistent night pain, limp, knee pain in a teenager → image promptly; do not dismiss as "growing pains"

— Pathologic fracture through "simple bone cyst" of proximal humerus is classic

— Ewing can mimic osteomyelitis with fever, ESR↑ — biopsy if antibiotics fail to resolve

Pediatric FD/MAS:

Pregnancy and FD:

Pediatric bone tumor red flags (parents often delay):

Step 3 management: A 28-year-old woman with monostotic FD on stable bisphosphonate therapy who wants to conceive should stop bisphosphonate, switch analgesia to acetaminophen, optimize vitamin D, and plan pregnancy with obstetrics and orthopedics co-managing — document the contraception/preconception discussion in the chart.

Complications and Adverse Outcomes

— Pathologic fractures — most common in proximal femur; recurrent in polyostotic disease

— Progressive deformity — shepherd's crook, tibial bowing, leg-length discrepancy, facial asymmetry

— Chronic bone pain — under-recognized, drives functional decline

— Spinal involvement — vertebral fracture, scoliosis, rarely cord compression

— Aneurysmal bone cyst can develop within FD lesions and accelerate growth/pain

— Optic neuropathy (vision loss)

— Conductive or sensorineural hearing loss

— Sinus obstruction, mucocele

— Trigeminal/facial nerve compression

— Malocclusion, dental displacement

— Cosmetic deformity and psychosocial burden

— Precocious puberty → short adult stature from premature epiphyseal closure

— Hyperthyroidism with cardiac sequelae

— Acromegaly, Cushing syndrome

— Renal phosphate wasting → osteomalacia overlay worsening FD

— Hepatobiliary, cardiac, and gastrointestinal manifestations of GNAS mosaicism

— Bisphosphonate: acute-phase reaction, hypocalcemia, osteonecrosis of the jaw (ONJ), atypical femoral fractures (rare but reported in long FD courses), renal toxicity, uveitis (rare)

— Denosumab: hypocalcemia, ONJ, rebound vertebral fractures on discontinuation

— Surgical: infection, nonunion, hardware failure, recurrence of deformity through dysplastic bone

— Repeated imaging: cumulative radiation, especially pediatric — favor MRI/US when possible

— Osteosarcoma > fibrosarcoma > MFH

— Risk factors: polyostotic disease, MAS, prior radiation

— Presents as new pain, swelling, cortical destruction, soft tissue mass, ALP spike

Skeletal complications of FD:

Craniofacial complications:

Endocrine complications in MAS:

Treatment-related complications:

Malignant transformation (<1%):

Board pearl: Any new soft-tissue mass or rapid pain escalation in a known FD lesion warrants urgent MRI and orthopedic oncology referral — assume sarcoma until biopsy proves otherwise; never attribute new symptoms to "FD flare" without imaging.

When to Escalate Care — ICU, Consult, or Inpatient Triage

— Acute pathologic fracture requiring fixation

— Severe symptomatic hypocalcemia (post-bisphosphonate/denosumab) — tetany, QT prolongation, seizures

— Severe symptomatic hypophosphatemia (<1.0 mg/dL) — respiratory muscle weakness, rhabdomyolysis, hemolysis

— Spinal cord or cauda equina compression from vertebral lesion → emergent MRI, neurosurgery, dexamethasone

— Acute vision change from craniofacial FD → neuro-ophthalmology, CT/MRI orbits, optic canal decompression evaluation

— Suspected malignant transformation requiring expedited workup/biopsy

— Hypercalcemia of malignancy (in metastatic disease) — IV fluids, calcitonin, zoledronic acid

— Hemodynamic instability from massive long-bone fracture (fat embolism syndrome — hypoxia, petechiae, altered mental status)

— Thyroid storm in MAS with hyperthyroidism + intercurrent illness

— Acute adrenal crisis in MAS Cushing post-adrenalectomy

— Tumor lysis syndrome (rare; more relevant in Ewing/high-grade sarcomas during chemo)

— Orthopedic oncology before any biopsy of a bone lesion of uncertain nature

— Endocrinology for MAS, hypophosphatemia, or bisphosphonate planning

— Neurosurgery for spinal lesions

— Radiation oncology — but NOT for FD treatment (contraindicated); for palliation of bone metastases

— Medical oncology for primary malignant bone tumors and metastatic disease

— Genetics (for hereditary syndromes like multiple exostoses, Li-Fraumeni)

— Stable monostotic FD with controlled pain

— Routine bisphosphonate infusion (day infusion)

— Surveillance imaging

Inpatient admission triggers in FD/bone tumors:

ICU triage:

Required consults:

Outpatient appropriate (do not admit):

CCS pearl: A patient with new lower-extremity weakness, urinary retention, and a known thoracic vertebral FD lesion requires immediate MRI total spine, IV dexamethasone 10 mg, neurosurgery consult, and admission to a monitored bed — this is cord compression until proven otherwise, and delay in CCS will dock you on outcome.

Key Differentials — Same-Category Causes (Other Fibro-Osseous and Benign Bone Lesions)

— Mandible/maxilla typically; well-circumscribed

— Histology: woven bone WITH osteoblastic rimming (vs FD without rimming)

— More aggressive surgical resection because not self-limiting

— Children/adolescents; eccentric, cortical-based, well-defined lytic lesion in metaphysis of long bones (distal femur, tibia)

— Asymptomatic, regress spontaneously — leave alone (Jaffe lesion)

— Proximal humerus or femur in children

— "Fallen fragment sign" after pathologic fracture

— Observation, aspiration/steroid injection, or curettage

— Expansile, eccentric, fluid-fluid levels on MRI

— Can be primary or secondary (within FD, GCT, osteosarcoma)

— Curettage, embolization, or denosumab

— Tibial diaphysis, anterior cortical, in young children

— Distinguish from adamantinoma (low-grade malignant, same location, older patients) — sometimes coexist; biopsy if any doubt

— Lytic lesion mimicking FD; check calcium, PTH, vitamin D, phosphate

— Treat underlying hyperparathyroidism — lesion resolves

— Epiphyseal, after physeal closure (young adults)

— Distal femur, proximal tibia, distal radius

— "Soap bubble," locally aggressive, can metastasize to lung (benign metastasizing)

— Hand short tubular bones; central with rings-and-arcs chondroid calcifications

— Ollier disease (multiple) and Maffucci (+ hemangiomas) raise chondrosarcoma transformation risk

Ossifying fibroma:

Non-ossifying fibroma (NOF) / fibrous cortical defect:

Simple (unicameral) bone cyst:

Aneurysmal bone cyst (ABC):

Osteofibrous dysplasia (Campanacci):

Paget disease: older adult, mosaic histology, marked ALP↑, cortical thickening — covered above.

Brown tumor of hyperparathyroidism:

Giant cell tumor:

Enchondroma:

Key distinction: FD has no osteoblastic rimming; ossifying fibroma does. This single histologic detail has driven boards questions for decades — memorize it.

Key Differentials — Other-Category Causes (Malignant and Metabolic Mimics)

— Osteosarcoma: adolescents, distal femur/proximal tibia metaphysis, sunburst periosteal reaction, Codman triangle, ALP↑↑; risk in Paget, prior radiation, retinoblastoma, Li-Fraumeni

— Ewing sarcoma: 5–25 yo, diaphyseal, onion-skin periosteal reaction, fever/ESR↑ mimicking osteomyelitis, t(11;22), CD99+

— Chondrosarcoma: older adults, pelvis/proximal femur, chondroid matrix with cortical destruction

— Chordoma: midline (sacrum, clivus), notochord remnant, brachyury+

— Adamantinoma: tibial diaphysis, low-grade, overlaps osteofibrous dysplasia

— Lytic: lung, kidney, thyroid, GI, melanoma, multiple myeloma

— Blastic: prostate, breast (mixed), carcinoid, small cell lung

— Workup: CT C/A/P, mammogram, PSA, SPEP/free light chains, TSH, urinalysis; bone scan/PET; biopsy if primary unknown

— Punched-out lytic lesions, no rim of sclerosis (vs FD's sclerotic rind)

— Anemia, hypercalcemia, renal failure, monoclonal protein

— Bone scan often cold — use skeletal survey or whole-body MRI/PET

— Skull "punched-out" lesion in children; can mimic FD

— CD1a+, S100+, Birbeck granules on EM

— Often self-resolving; curettage or steroid injection

— Osteomyelitis (Brodie abscess can mimic osteoid osteoma)

— Brown tumor (hyperparathyroidism)

— Renal osteodystrophy

— Hypophosphatemic osteomalacia (FGF23-mediated mesenchymal tumors — TIO — overlap with MAS hypophosphatemia)

— Sickle cell bone infarct in young Black patient with sickle disease

Primary malignant bone tumors:

Metastatic bone disease (most common cause of bone lesion >40 yo):

Multiple myeloma:

Langerhans cell histiocytosis (eosinophilic granuloma):

Metabolic and infectious mimics:

Board pearl: Punched-out lytic skull lesions = think myeloma in adults and LCH in children, NOT FD; FD skull involvement is expansile, sclerotic, ground-glass thickening, not punched-out.

Secondary Prevention and Long-Term Plan

— Calcium 1000–1200 mg/day (dietary preferred) and vitamin D to maintain 25-OH >30 ng/mL

— Weight-bearing exercise as tolerated; physical therapy for gait, balance, deformity-specific strengthening

— Smoking cessation, moderate alcohol — both impair bone healing

— Fall prevention assessment, especially with deformity or leg-length discrepancy

— Continue bisphosphonates at intervals guided by pain and bone turnover markers (CTX, P1NP, ALP); typical IV zoledronic acid yearly, reassess at 3–5 years

— Consider drug holiday after symptom control to limit ONJ/atypical femoral fracture risk

— Avoid concurrent corticosteroids when possible (increase fracture and ONJ risk)

— Maintain endocrinopathy treatment in MAS — coordinated long-term plan

— Comprehensive dental exam before initiating bisphosphonate/denosumab, address extractions/implants first

— Maintain oral hygiene; avoid invasive dental work during therapy when feasible

— Inform all providers, including dentists, of bisphosphonate history (even years prior)

— Asymptomatic monostotic FD: clinical exam + radiograph every 6–12 months initially, lengthen if stable

— Polyostotic/MAS: low-dose CT or MRI of high-risk sites, vision/hearing screening annually

— Any new symptom triggers re-imaging to exclude transformation

— Analgesic taper plan, avoid chronic opioids

— DVT prophylaxis per orthopedic protocol

— Calcium/vitamin D

— Bisphosphonate plan

— Weight-bearing instructions and PT referral

— Clear follow-up date with orthopedics within 2 weeks

Bone health optimization for every FD patient:

Pharmacologic maintenance:

Dental and ONJ prevention:

Surveillance imaging:

Discharge medication checklist after fracture/surgery:

Step 3 management: For a polyostotic FD patient leaving the hospital after femoral nailing, ensure the discharge order set includes DEXA baseline, 25-OH vit D, calcium, dental referral, endocrinology follow-up within 4 weeks, and an outpatient zoledronic acid infusion appointment — fragmented follow-up is the most common board-tested transition-of-care failure.

Follow-Up, Monitoring Parameters, and Counseling

— Monostotic stable FD: annual visit with focused exam, ALP, radiograph of index lesion

— Symptomatic/polyostotic FD on bisphosphonates: every 3–6 months — pain assessment, ALP, calcium, phosphorus, creatinine, vitamin D, CTX

— MAS: coordinated visits — endocrinology q3–6 mo (growth, puberty staging, thyroid, IGF-1, cortisol), ophthalmology annually for craniofacial involvement, audiology, dentistry

— Pediatric: growth curves, school performance, psychosocial screening

— Before each infusion: serum creatinine, calcium, vitamin D, dental status

— During: watch acute-phase reaction

— Longitudinal: bone turnover markers (CTX, P1NP) — declining toward normal is goal; rebound signals need for redose

— Long-term: ONJ screening, femoral imaging for atypical fracture if thigh/groin pain emerges

— Physical therapy individualized to deformity; aquatic therapy useful with weight-bearing limits

— Orthotics for leg-length discrepancy ≥2 cm

— Vocational counseling — avoid high-impact occupations if extensive lower-extremity FD

— Pediatric: adapted PE, individualized education plan if hearing/vision involved

— Realistic expectation: bisphosphonates reduce pain, not deformity

— Lifelong condition — FD does not "go away" but most lesions stabilize after skeletal maturity

— Pregnancy planning: medication washout, increased deformity risk during pregnancy

— Genetic counseling: FD/MAS is sporadic, not heritable — reassuring point for patients planning families

— Patient advocacy: refer to FD/MAS Alliance, MAGIC Foundation

Outpatient cadence:

Monitoring parameters during bisphosphonate therapy:

Functional and rehab counseling:

Patient counseling pearls:

CCS pearl: Document on the chart and CCS notes: "Counseled patient that FD is not inherited; reproductive risk to offspring is not increased." This counseling line is a frequent ethics/communication item and reassures patients who fear passing on the disease.

Ethical, Legal, and Patient Safety Considerations

— Adolescent with MAS and precocious puberty: consent and assent — engage the minor in age-appropriate discussion of letrozole/GnRH agonist therapy; involve guardian for legal consent; document both

— Surgical biopsy of suspected sarcoma vs FD: consent must include the possibility of upstaging to malignancy, need for re-excision, and the risk that an improperly placed biopsy tract converts a limb-salvage case to amputation — this is a documented malpractice scenario

— Bisphosphonate in a woman of childbearing potential: explicit pregnancy/contraception discussion required and documented

— Multiple unexplained fractures in a child raise non-accidental trauma concerns; differentiate from polyostotic FD, osteogenesis imperfecta — but if the workup is incomplete, social work and child protective services consult is required while imaging proceeds

— Document objective findings and avoid premature exoneration or accusation

— GNAS testing is somatic mosaic — counsel that negative blood test does not exclude FD; affected tissue testing may be needed

— No prenatal testing applicable for FD/MAS; genetic counseling is for reassurance, not screening

— Handoff between pediatric and adult endocrinology often loses MAS patients to follow-up — formal transition clinic with written care plan

— After surgical fixation, ensure bone health medications, dental clearance, PT referral, and ortho follow-up are reconciled before discharge — incomplete reconciliation is a top patient-safety event

— Avoid radiation therapy in FD — clearly document this contraindication in the chart to prevent future inadvertent referral

— IV bisphosphonate infusions and denosumab can pose insurance barriers; identify financial counseling early

— Rural patients may face delayed orthopedic oncology referral — telehealth and tertiary-center partnerships mitigate

Informed consent edge cases:

Mandatory reporting and child welfare:

Genetic testing ethics:

Transition-of-care safety (Step 3 favorite):

Health equity and access:

Board pearl: On a vignette where a young patient with suspected sarcoma is referred for biopsy at a community hospital, the safest, board-correct answer is "refer to a sarcoma center for biopsy by the operating surgical oncology team" — never proceed with local open biopsy.

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: When a stem says "ground-glass femoral lesion in an adolescent with café-au-lait macules and vaginal bleeding," the diagnosis is McCune-Albright syndrome — order skeletal survey, TSH, IGF-1, AM cortisol, LH/FSH/estradiol, calcium, phosphate, 25-OH vitamin D.

GNAS-activating mutation (postzygotic somatic mosaic) → fibrous dysplasia ± MAS ± endocrinopathies

McCune-Albright triad: polyostotic FD + café-au-lait (coast of Maine) + endocrinopathy (precocious puberty most common)

Mazabraud syndrome: FD + intramuscular myxomas

"Ground-glass" diaphyseal lesion with sclerotic rim → FD

"Shepherd's crook" deformity of proximal femur → polyostotic FD

"Chinese letters" / "alphabet soup" woven bone without osteoblastic rimming → FD histology

Osteoblastic rimming present → ossifying fibroma (not FD)

Codman triangle, sunburst → osteosarcoma

Onion-skin periosteal reaction → Ewing sarcoma

CD99+, t(11;22) EWSR1-FLI1 → Ewing

Soap-bubble epiphyseal lesion in young adult → giant cell tumor

Nidus <2 cm with surrounding sclerosis, pain relieved by NSAIDs → osteoid osteoma → CT-guided RFA

Multiple enchondromas → Ollier; + soft tissue hemangiomas → Maffucci → ↑ chondrosarcoma risk

Multiple osteochondromas (AD, EXT1/2) → ↑ chondrosarcoma risk

Punched-out lytic skull lesions, no rim → multiple myeloma (adult) or LCH (child)

Blastic bone metastases → prostate, breast

Lytic bone metastases → kidney, thyroid, lung, GI, melanoma, myeloma

Brown tumor → hyperparathyroidism (check Ca, PTH)

FGF23-mediated hypophosphatemia in FD/MAS → oral phosphate + calcitriol; burosumab emerging

Bisphosphonate = first-line medical therapy for symptomatic FD; denosumab if refractory (watch rebound)

Radiation contraindicated in FD (sarcomatous transformation)

Café-au-lait borders: "coast of Maine" jagged (MAS) vs "coast of California" smooth (NF1)

Precocious puberty in MAS = peripheral/gonadotropin-independent (autonomous ovarian cyst)

MAS girls treated with letrozole for peripheral precocious puberty

Board Question Stem Patterns

"A 16-year-old has dull right thigh pain after football practice. Radiograph shows a well-defined, expansile ground-glass medullary lesion with a sclerotic rim in the proximal femoral diaphysis, no periosteal reaction."

→ Answer: Fibrous dysplasia. Next step: MRI for characterization and orthopedic referral; observe if asymptomatic.

"A 6-year-old girl has vaginal bleeding, breast development, and a large irregular café-au-lait macule on her back with jagged borders. Hip radiograph shows shepherd's crook deformity."

→ Answer: MAS. Next: TSH, IGF-1, AM cortisol, estradiol, LH/FSH, calcium, phosphate, 25-OH vit D, letrozole for precocious puberty.

"Biopsy shows curvilinear woven bone trabeculae in fibrous stroma without osteoblastic rimming."

→ Fibrous dysplasia. (With rimming = ossifying fibroma.)

"Persistent thigh pain in polyostotic FD despite NSAIDs and acetaminophen."

→ IV zoledronic acid after vitamin D repletion and dental clearance.

"15-year-old with night pain in the tibia relieved by aspirin; radiograph shows a 1-cm lucent nidus with surrounding sclerosis."

→ Osteoid osteoma; treat with CT-guided radiofrequency ablation.

"68-year-old man with back pain, anemia, hypercalcemia, creatinine 2.4, lytic skull lesions."

→ Multiple myeloma. SPEP/UPEP, free light chains, marrow biopsy.

"Polyostotic FD with new lower-extremity weakness and urinary retention."

→ MRI total spine, IV dexamethasone, neurosurgery consult, admit.

"28-year-old on annual zoledronic acid wants to conceive."

→ Stop bisphosphonate, switch to acetaminophen, optimize vit D, counsel on increased FD activity in pregnancy.

"Long-standing FD patient with new severe rest pain and ALP doubling; new soft-tissue mass on MRI."

→ Suspect sarcomatous transformation; refer to sarcoma center for biopsy.

Stem 1 — Classic FD:

Stem 2 — McCune-Albright:

Stem 3 — FD vs ossifying fibroma:

Stem 4 — Treatment of symptomatic FD:

Stem 5 — Osteoid osteoma trap:

Stem 6 — Metastatic mimicker:

Stem 7 — Cord compression:

Stem 8 — Pregnancy planning:

Stem 9 — Malignant transformation:

CCS pearl: Whenever a stem mentions night pain, rest pain, weight loss, or rapid mass enlargement, the answer pivots away from FD toward malignancy — biopsy at a sarcoma center is almost always the safest next step.

One-Line Recap

Fibrous dysplasia is a sporadic GNAS-mutation–driven fibro-osseous disorder presenting as a ground-glass medullary lesion managed with bone health optimization, bisphosphonates for symptomatic disease, and surgery for fracture or deformity — while age, lesion location, periosteal reaction, and systemic features anchor the broader bone tumor differential.

Board pearl: If you remember nothing else — ground-glass + no osteoblastic rimming + GNAS = fibrous dysplasia, and night pain or rapid growth ≠ FD until sarcoma is excluded.

Recognize FD: ground-glass medullary lesion + sclerotic rim, "Chinese letters" without osteoblastic rimming, GNAS mutation; polyostotic forms + café-au-lait (coast of Maine) + endocrinopathy = McCune-Albright.

Manage FD: vitamin D/calcium replete first → NSAIDs → IV zoledronic acid (or pamidronate) for persistent pain → denosumab if refractory; never radiate (sarcoma risk); surgery for fracture, impending fracture (Mirels ≥9), progressive deformity, or documented optic nerve compromise — intramedullary nail preferred, cortical strut > cancellous graft.

Differentiate aggressively by age: <30 think FD/osteosarcoma/Ewing/GCT/osteoid osteoma; >40 think metastasis, myeloma, chondrosarcoma — order SPEP/free light chains, PSA, mammogram, CT C/A/P before biopsy; all suspected sarcoma biopsies go to a sarcoma center by the operating surgical team.

Transitions and safety: pre-bisphosphonate dental clearance and vitamin D repletion, contraception counseling in women of childbearing potential, structured pediatric-to-adult MAS transition, document that FD is sporadic/non-heritable, and treat any new pain or mass in known FD as transformation until imaging and pathology say otherwise.