| Chondroblastoma | |
|---|---|
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| Micrograph of a chondroblastoma.H&E stain. | |
| Specialty | Oncology  |
Chondroblastoma is a rare,benign, locally aggressive bone tumor that typically affects theepiphyses orapophyses oflong bones.[1][2] It is thought to arise from an outgrowth of immaturecartilage cells (chondroblasts) fromsecondary ossification centers, originating from theepiphyseal plate or some remnant of it.[2][3]
Chondroblastoma is very uncommon, accounting less than 1% of allbone tumors. (The chances of having this condition are roughly one in a million.)[1][3] It affects mostly children and young adults with most patients being less than 20 years of age.[1][4] Chondroblastoma shows a predilection towards the male sex, with a ratio of male to female patients of 2:1.[1][4][5] The most commonly affected site is thefemur, followed by thehumerus andtibia.[1][3][4][6] Less commonly affected sites include thetalus andcalcaneus of thefoot andflat bones.[1][6]
The most common symptom is mild to severe pain that is gradually progressive in the affected region and may be initially attributed to a minor injury orsports-related injury.[1][3][5][6] Pain may be present for several weeks, months, or years.[1][5] Other symptoms in order of most common to least commonly observed includeswelling, alimp (when affected bone is in the lower extremity),joint stiffness, and a soft tissue mass.[1][6]
Physical findings include localized tenderness and a decreased range of motion in the involved bone and nearbyjoint,muscle atrophy, a palpable mass, soft tissue swelling, andjoint effusion in the affected area.[1][5][6] Less commonly,pathological fractures can be found, especially in cases involving the foot.[1] In cases involving thetemporal bone,tinnitus,dizziness, andhearing loss have been reported.[6]
In a publication by Turcotte et al. it was found that the average duration of symptoms for patients with chondroblastoma was about 20 months, ranging from 5 weeks to 16 years.[5][6]
Currently, the genetic or environmental factors that predispose an individual for chondroblastoma are not well known or understood.[1] Chondroblastoma affects males more often than females at a ratio of 2:1 in most clinical reports.[1][3][4][5][6] Furthermore, it is most often observed in young patients that are skeletally immature, with most cases diagnosed in the second decade of life.[2][5] Approximately 92% of patients presenting with chondroblastoma are younger than 30 years. There is no indication of a racial predilection for chondroblastoma.[5]
The etiology of chondroblastoma is uncertain, as there is no specific characteristic abnormality orchromosomal breaking point observed, despitecytogenetic abnormalities being highly specific for some tumors.[1][5]
Romeoet al has noted that chondroblastoma arising in long bones mainly affects the epiphyses, while in other locations it is close toossification centers. Additionally, rare prevalence of chondroblastoma inintra-membranous ossification suggests a close relationship with growth plate cartilage. In chondroblastoma, growth signaling molecules may be present due to the pre-pubertal signaling network as well as cartilage growth.Sex hormones are thought to be linked to this process because of the spatial relationship of chondroblastoma with the growth plate and its typical occurrence before growth plate fusion.[2] BothIndian Hedgehog/parathyroid hormone-related protein (IHh/PtHrP) andfibroblast growth factor (FGF) signaling pathways, important for development of the epiphyseal growth plate, are active in chondroblastoma leading to greaterproliferation among the cells in the proliferating/pre-hypertrophic zone (cellular-rich area) versus the hypertrophic/calcifying zone (matrix-rich area). These findings suggest that chondroblastoma is derived from amesenchymal cell undergoingchondrogenesis via active growth-plate signaling pathways (seeEndochondral ossification).[1][2]
The highly heterogeneous nature of the tumor makes classification particularly difficult especially considering the origins of chondroblastoma.[2] There are two opposing views on the nature of chondroblastoma, one favoring anosseous origin and the other favoring acartilaginous origin. The work of Aigneret al suggests that chondroblastoma should be reclassified as a bone-forming neoplasm versus a cartilaginous neoplasm due to the presence ofosteoid matrix,type I collagen, and absence of true cartilage matrix (collagen II).[2][5] However, Edelet al found thatcollagen II, a marker for maturechondrocytes, was expressed in chondroblastoma, supporting the chondroid nature of theneoplasm. The results of Romeo and colleagues favor the view of Edelet al of chondroblastoma being cartilaginous in nature but recognize that any definitive determinations regarding the origin of this neoplasm are not possible because of theplasticity of mesenchymal cells when set into different microenvironments and static approaches used in literature. Romeoet al have observed chondroblastoma neoplasms to be composed of mesenchymal cells that have completed normal chondrogenesis along with the production of osteoid and collagen I that could be the result oftransdifferentiation of chondrocytes towardsosteoblasts.[2]
A variety of imaging studies can be used to diagnose chondroblastoma, withradiographs being the most common.[1][5] Laboratory studies are not considered useful.[5] Classical chondroblastoma (appearing on long bones) appears as a well-defined eccentric oval or round lytic lesion that usually involves the adjacentbone cortex withoutperiosteal reaction. Asclerotic margin can be seen in some cases. For long bone chondroblastomas the tumor is typically contained to the epiphysis or apophysis but may extend through the epiphyseal plate.[1][6] Chondroblastomas are usually located in themedullary portion of bones and can, in some cases, include themetaphysis.[1][6] However, true metaphyseal chondroblastomas are rare and are typically the result of an extension from a neighboring epiphyseal legion.[1][6] Most lesions are less than 4 cm. A mottled appearance on the radiograph is not atypical and indicates areas ofcalcification which is commonly associated with skeletally immature patients. Additionally, one-third of all cases involveaneurysmal bone cysts which are thought to be the result of stress,trauma orhemorrhage.[1] In cases involving older patients or flat bones, typical radiographic presentation is not as common and may mimic aggressive processes.[1][6]
Other imaging techniques involvecomputed tomography (CT),magnetic resonance imaging (MRI), andbone scans, which may be helpful in determining the anatomical boundaries, associatededema, or biological activity of the chondroblastoma, respectively.[1][5] MRI studies may show extensive oedema around the lesion and show variable T2 signal intensity.[7]
Chondroid differentiation is a common feature of chondroblastoma.[1][4][6] A typicalhistological appearance consists of a combination of oval mononuclear and multi-nucleatedosteoclast-type giant cells.[1][3][4] However this is not a prerequisite for diagnosis, as cells withepithelioid characteristics have been observed in lesions of theskull andfacial bones.[4] A "chicken-wire" appearance is characteristic of chondroblastoma cells and is the result ofdystrophic calcification that may surround individual cells.[1][5] Although, calcification may not be present and is not a prerequisite for diagnosis.[1][3][4]Mitotic figures can be observed in chondroblastoma tissue but are not considered atypical in nature, and therefore, should not be viewed as a sign of a more seriouspathology.[1][4] There is no correlation between mitotic activity and location of the lesion.[4] Furthermore, the presence of atypical cells is rare and is not associated withmalignant chondroblastoma.[1][6]
Chondromyxoid fibromas can share characteristics with chondroblastomas with regards to histologic and radiographic findings. However they more commonly originate from the metaphysis, lack calcification and have a different histologic organization pattern.[5] Other differential diagnoses for chondroblastoma consist ofgiant cell tumors,bone cysts,eosinophilic granulomas,clear cell chondrosarcomas, andenchondromas (this list is not exhaustive).[1][5]
Chondroblastoma has not been known to spontaneously heal and the standard treatment is surgicalcurettage of the lesion withbone grafting.[1] To prevent recurrence or complications it is important to excise the entire tumor following strictoncologic criteria.[1][5] However, in skeletally immature patients intraoperativefluoroscopy may be helpful to avoid destruction of the epiphyseal plate. In patients who are near the end of skeletal growth, complete curettage of the growth plate is an option.[1] In addition to curettage, electric or chemicalcauterization (viaphenol) can be used as well ascryotherapy and wide or marginalresection. Depending on the size of the subsequent defect,autograft orallograft bone grafts are the preferred filling materials.[1][5] Other options include substitutingpolymethylmethacrylate (PMMA) or fat implantation in place of the bone graft.[1][3][5] The work of Ramappaet al suggests that packing with PMMA may be a more optimal choice because theheat of polymerization of the cement is thought to kill any remaining lesion.[1][3]
Bothradiotherapy andchemotherapy are not commonly used. Radiotherapy has been implemented in chondroblastoma cases that are at increased risk of being more aggressive and are suspected ofmalignant transformation.[1][5] Furthermore,radiofrequency ablation has been used, but is typically most successful for small chondroblastoma lesions (approximately 1.5 cm).[1] Treatment with radiofrequency ablation is highly dependent on size and location due to the increased risk of larger, weight-bearing lesions being at an increased risk forarticular collapse and recurrence.[1][5] Overall, the success and method of treatment is highly dependent upon the location and size of the chondroblastoma.[1][4][5]
Although not specific to one mode of management, lesion size, patient sex, or follow-up, the recurrence rate for chondroblastoma is relatively high, and has been shown in select studies to be dependent upon the anatomical location, method of treatment, and biological aggressiveness of the initial lesion.[1][3][5] The rate of recurrence is highly variable, ranging between 5% and 40%, as study results are generally inconclusive.[1] However, local recurrence for long bone lesions is around 10%, with chondroblastoma in flat bones having higher recurrence and more complications. Recurrences are more common in cases involving an open epiphyseal plate where they can be attributed to inadequate curettage to avoid damage.[1][5] Lesions of the proximal femur are particularly problematic because of difficulties accessing thefemoral head for completeexcision.[1] Chondroblastoma may recur in the soft tissue surrounding the initial lesion, especially in the case of incomplete curettage.[1] Recurrences have been shown to occur between 5 months and 7 years after initial treatment and are generally treated with repeat curettage and excision of affected soft-tissue.[1][5] No histological differences have been seen between recurrent and non-recurrent chondroblastomas.[1][4][6]
Rarely, more aggressive chondroblastomas canmetastasize.[1] The most common location for metastases is thelung, with some cases also involving secondary bone sites, soft tissue, skin, or theliver.[1][5] The prevalence of metastatic chondroblastoma, however, is quite low and is believed to be less than 0.5%. There is no relationship established between metastasis and previous surgery, non-surgical treatment, anatomical location, or patient age. Survival of patients with metastatic lesions is better when the metastases are surgically resectable, as chemotherapy has been shown to have little to no benefit.[1] Prognosis is bleak for patients with malignant chondroblastomas that are resistant to surgery, radiation, and chemotherapy.[5] However, patients with resectable metastases have survived for several years following diagnosis.[1]
While recurrence is the most common complication of chondroblastoma other issues includepost-surgery infection,degenerative joint disease, pathological fractures, failure of bone grafts, pre-matureepiphyseal closure, functional impairment, and malignant transformation.[1][5] Complications are less common in patients presenting with chondroblastoma in accessible areas.[1] Overall, patients with more classical chondroblastoma (appearing in long bones, typical presentation) have better prognoses than patients with atypical chondroblastoma (flat bones, skull, etc.).[1][3][4][5][6]
Chondroblastoma was first described in 1927 as a cartilage-containing giant cell tumor by Kolodny but later characterized by Codman in 1931.[1][4] Codman believed chondroblastoma to be an "epiphyseal chondromatous giant cell tumor" in the proximalhumerus.[1][3] This view was changed later by a comprehensive review completed by Jaffe and Lichtenstein in 1942 of similar tumors in other locations than the proximal humerus.[1][4] They re-defined the tumor as a benign chondroblastoma of the bone that is separate from giant cell tumors.[1][5] However, chondroblastoma of the proximal humerus is still sometimes referred to as Codman's Tumor.[1][3][4]