summary Chondroblastomas are rare, benign but locally destructive tumors of immature cartilage-forming cells (chondroblasts) that arise almost universally in the epiphysis of long bones. Patients typically present between the ages in 3rd decade of life with regional pain and/or a limp. Diagnosis is made with biopsy showing chondroblasts arranged in a "chickenwire" pattern with foci of chondroid matrix and scattered multinucleated osteoclast-type giant cells. Treatment is usually intralesional resection, local adjuvant therapy (i.e. cryoablation), +/- bone graft Epidemiology Demographics rare (~1% of osseous neoplasms) M:F = 2:1 predominantly occur in the immature skeleton 80% of patients under 25 years of age Anatomic location almost exclusively arise in the epiphysis of skeletally immature long bones common locations include the proximal humerus, proximal femur, distal femur, and proximal tibia can cross the physis into the metaphysis may also arise from an apophysis; from the patella, from the talus or calcaneous in the feet ("epiphyseal equivalents"), or from flat bones Etiology Pathophysiology bengin proliferation of immature cartilage cells (chondroblasts) that are locally destructive thought to arise from cartilaginous epiphyseal plate, but histogenesis is controversial chondroblasts produce areas of chondroid matrix, but hyaline cartilage is rarely produced Recurrent chondroblastomas can show cellular atypia, but this is usually not equivalent to malignant transformation Genetics no principally defining mutations mutations in histone H3.3 are described abnormalities on chromosomes 5 and 8 are common Associated conditions pulmonary metastasis <1% develop "benign" pulmonary metastasis similar to giant cell tumor in this regard treatment may be observation or surgical resection secondary Aneurysmal Bone Cyst (ABC) up to 1/3 of chondroblastomas have areas of secondary ABC Presentation Symptoms pain progressive pain at tumor site joint stiffness limp Physical examination local muscle atrophy tenderness over the affected bone decreased range of motion of the affected joint, possibly with an effusion Imaging Radiographs recommended views AP, lateral, and oblique of involved area chest radiographs evaluate for possible metastatic lesions findings lytic epiphyseal lesion a geographic, well-circumscribed, oval or round lytic lesion of the epiphysis with a thin sclerotic border that sharply demarcates the tumor from normal bone lesions may cross the physis into metaphysis matrix calcifications internal matrix calcifications that are often only apparent on CT scan (25%-45%) cortical remodeling cortical expasile remodeling may be present soft tissue extension soft tissue extension is rare, and there is usually a thin rim of calcification from the intact periosteum joint effusion metaphyseal periosteal reaction periosteal reaction at the metaphyseal region (there is no periosteum over the epiphysis) due to irritation from the tumor aggressive appearance a small subset have a more aggressive appearance due to secondary ABC formation, which can be seen in 15 to 32% of cases differential with radiographs includes other epiphyseal lesions CT CT of lesion/involved area indications not required, but can be useful if 3-dimensional anatomy is distorted or complex findings defines bony extent of lesion may show stippled calcifications of the cartilaginous matrix CT chest indications CT chest should be considered if chest radiographs show any signs of metastases MRI findings extensive edema of the bone marrow and/or soft tissues surrounding the lesion intermediate signal intensity on T1 variable, heterogenous signal intensity on T2 heterogenous enhancement with gadolinium fluid-fluid levels (indicates secondary aneurysmal bone cyst) Bone scan indications not required findings chondroblastomas demonstrate increased radionuclide uptake, especially in the uninvolved bone adjacent to the tumor Studies Histology findings polygonal mononuclear chondroblasts sheets of intermediate-sized round to polygonal mononuclear cells (chondroblasts) with well defined borders large, central nuclei with longitudinal grooves ("coffee bean" nuclei) are classic a fine network of pericellular "chicken wire" dystrophic calcification is characteristic chondroblasts are positive for vimentin, neuron-specific enolase, S100+, and Sox9 scarce mitotic figures recurrent lesions may show cellular atypia that shouldn't be confused with malignant transformation multinucleated osteoclast-type giant cells scattered multinucleated osteoclast-type giant cells are almost uniformly present among the chondroblasts amorphous chondroid matrix islands of amorphous chondroid matrix are typical mature hyaline cartilage is uncommon Differential Chondroblastoma almost exclusively occurs in the epiphysis and should be high on the differential for a young person with an epiphyseal lesion the differential for chondroblastomas chiefly includes other ephiphyseal or apophyseal lesions diagnosis must be confirmed with a biopsy Differential tables Chondrogenic Lesions BENIGN Radiographic Presentation Characteristic Histology Treatment Enchondroma Most common in patients 20 to 50 years old Well defined, lucent, central medullary lesions. Blue gray, lobulated hyaline cartilage, with scattered calcifications. Observation Periosteal chondroma Most common in patients 10 to 30 years old Well-demarcated, shallow cortical defect Similar to enchondroma (bland hyaline cartilage with small chondroid cells except for increased cellularity and more malignant looking cells. Marginal excision Solitary Osteochondroma Most common in patients 10 to 30 years old Pedunculated lesions on bone surface with continuity of cortex Similar to a normal physis with hyaline cartilage cap and well-defined perichondrium. Observation if asymptomatic Chondroblastoma Most common in patients 10 to 30 years old Lytic epiphyseal lesion Chicken wire" dystrophic calcification with sheets of polygonal mononuclear chondroblasts Intralesional curettage and bone grafting. Chondromyxoid fibroma Age at diagnosis typically ranges from 10-30 years Lobulated, eccentric lytic lesions with sclerotic borders Assortment of chondroid, myxoid, and fibrous tissue with stellate cells in a pseudolobulated architecture Intralesional curretage and bone grafting (or PMMA) MALIGNANT Chondrosarcoma Occurs in older adults (40 to 75 years) Lytic lesions with characteristic "rings and arcs" or "popcorn calcification" Bland hyaline cartilage appearance with varying amount of cellularity based on grade Wide surgical excision Mesenchymal chondrosarcoma Occurs in younger patients (20 to 40 years) than conventional chondrosarcoma Moth-eaten or permeative lytic lesion with variable matrix calcification High-grade biphasic chondrosarcoma characterized by poorly differentiated small round blue cells and islands of hyaline cartilage Wide surgical excision May respond to chemotherapy and radiation Secondary chondrosarcoma Usually found in significantly younger patients (3rd and 4th decades) than primary conventional chondrosarcoma From osteochondroma: cartilage cap >2cm on MRI or CT with intralesional lysis of calcifications and cortical destruction Same as conventional chondrosarcoma Wide surgical excision Clear cell chondrosarcoma Occurs in younger patients (20 to 40 years) than conventional chondrosarcomas Well-defined osteolytic lesion in the epi-metaphyseal region Low-grade malignant chondrogenic neoplasm characterized by lobules of clear cells Wide surgical excision Differential Diagnosis for Epiphyseal Lesion Key Differentiating Findings Chondroblastoma (this topic) Typically skeletally immature, insidious and progressive pain, may see mineralization of cartilaginous matrix; extensive peritumoral edema on MRI Giant Cell Tumor Typically skeletally mature (age 20-40) with closed physes; originates from metaphysis but can extend into the epiphysis; pathologic fracture common Clear Cell Chondrosarcoma More common in 3rd to 5th decades of life; typically larger on presentation (>4cm); less peritumor edema on MRI than chondroblastoma; malignant Brodie abscess Typically sketally immature; often metaphyseal; signs and symptoms of infection are frequently absent; "penumbra" on MRI is characteristic Intraosseous Ganglion Typically occur in middle-age; periosteal reaction should be absent; cystic on MRI with less peri-lesional edema than chondroblastoma Eosinophilic Granuloma Variable radiographic appearance Brown Tumor Typically age >50; chronic renal disease / hyperparathyroidism Aneurysmal Bone Cyst Typically age <20; multicystic bone lesion with fluid-fluid levels on MRI; Osteoblastoma Typically 2nd and 3rd decades; rarely epiphyseal; commonly painful; may see matrix mineralization; extensive peritumoral edema on MRI Osteoid Osteoma Children and adolescents; typically diaphyseal, rarely epiphyseal; nocturnal pain relieved by NSAIDs; nidus on CT; peritumoral edema on MRI Other Metastatic disease, multiple myeloma, lymphoma Treatment Nonoperative observation alone indications rarely indicated as there are no medical therapies for chondroblastoma and chondroblastomas do not heal spontaneously Operative intralesional curettage and bone grafting with local adjuvant indications standard of care for most lesions chondroblastomas do not heal spontaneously techniques local adjuvant therapy should be given to prevent local recurrence modalities include phenol hydrogen peroxide argon beam coagulation cryotherapy radiofrequency ablation indications can be considered as a first-line treatment as there is good success with similar recurrence rate as intralesional curettage MRI hallmarks of success include necrosis beyond tumor margin and resolution of perilesional edema wide excision indications some tumors, such as those in the ribs, may best be treated with en bloc resection endoprosthetic reconstruction or amputation indications reserved for destructive, aggressive recurrences (rare) surgical resection of pulmonary metastases indications solitary or oligometastases those with numerous metastases can be treated with denosumab with good long-term outcomes Technique Intralesional curettage and bone grafting approach the entire tumor should be excised by intralesional excision through a cortical window it is common to extend local resection with high-speed burr into healthy bone for complete excision the physis should be spared if possible technique bone graft bone graft should be used to fill the cavitary defect after curettage dependent on location, structural osteochondral graft may be needed for weight bearing surfaces local adjuvant treatment local adjuvant treatment should be used to decrease risk of recurrence examples include cryotherapy, phenol, and hydrogen peroxide Complications Local recurrence incidence local recurrence rate is 10-15% after treatment this includes both surgical and RFA techniques purely epiphyseal lesions recur at a significantly higher rate than epiphyseal-metaphyseal, apophyseal, and metaphysical only lesions etiology recurrence is primarily thought to occur from inadequate resection rather than a completely new lesion in the same area of complete excision treatment surveillance radiographs should be performed for 5 years to monitor for local recurrence repeat surgical intervention is warranted Limb length discrepancy etiology physis may be damaged by the tumor or by treatment treatment consider contralateral epiphysiodesis versus limb lengthening depending on the patient Degenerative joint disease incidence hip replacement and knee replacement often required in affected joint in adult ages Metastatic lung disease incidence occurs in <1% of cases treatment treated with surgical resection usually has indolent course Prognosis Survival generally considered a benign, curable disease if treated surgically or via RFA as it does not spontaneously resolve Malignant transformation incidence exceedingly rare, several case reports have been published presents later in life, median age 52 years can metastasize to lungs, bone, soft tissues of the axial and appendicular skeleton, brain histology shares some histological characteristics with chondroblastoma-like osteosarcoma, but there is no osteoid produced permeative growth pattern and significant cellular atypia are characteristic findings treatment wide surgical resection is standard of care