The atypical chondrogenic tumor springerlink

The atypical chondrogenic tumorAtypical chondrogenic tumors (ACT) of the short and long tubular bones, formerly known as chondrosarcomas G1, behave aggressively locally but have a very low metastatic potential. Differentiation from benign enchondromas is complex from a clinical, radiological, and histopathological perspective.

Aim of the work

Epidemiology, diagnosis and therapy of ACTs with special emphasis on the differentiation between ACTs and enchondromas are presented.

Material and Methods

The following is a summary of the international literature on ACTs and enchondromas.


The incidence of enchondromas, and even more so of ACT, has increased over the years, indicating that diagnosis is becoming more frequent. In contrast to enchondromas, ACTs may be associated with pain and show radiographic signs of aggressive growth, such as deep endosteal scalloping. Biopsy alone to differentiate between enchondromas and ACT is often not helpful, as sampling error may result from punctate tie sampling. The definitive surgical treatment of ACT of the long and short tubular bones has changed over the last years from radical tumor removal to intralesional curettage. Waiting is possible for radiological suspicion of the presence of an enchondroma regular follow-up by magnetic resonance imaging (MRI).


ACT, in contrast to enchondromas, show radiological signs of aggressive growth. Nowadays, the preferred therapy consists of intralesional curettage. Diagnostics as well as therapy and follow-up of cartilaginous tumors should be performed at a specialized tumor center.



Atypical cartilagineous tumors (ACTs) of short and long bones, previously termed as chondrosarcoma G1, are of locally aggressive behavior, but have little metastatic potential. Differentiation between ACTs and enchondromas is complex on clinical, radiological and histopathological basis.


Epidemiology, diagnosis, and therapy of ACTs with specific focus on distinction from enchondroma.

Materials and Methods

Summary of international literature on ACTs and enchondromas.


The incidence of enchondromas, and even more the one of ACTs, has increased over the years, indicating more frequent application of diagnostics. Contrary to enchondroma, ACTs may be associated with pain and present with radiological signs indicative of aggressive growth, such as deep endosteal scalloping. Performing biopsy only to differentiate between suspected enchondroma and ACT may be unhelpful as the acquired tie specimen can lead to a "sampling error". Definite surgical therapy of ACTs of long and short bones has changed over the last years, shifting from radical tumor resection towards intralesional curettage. A primary watch-and-wait approach is possible in enchondroma using regular MRI check-ups.


Other than enchondroma, ACTs present with radiologic signs of aggressive growth. Nowadays, ACTs are preferably treated by intralesional curettage. Diagnosis, therapy and follow-up of cartilaginous tumors should be carried out at specialized tumor centers.


Atypical chondrogenic tumors (ACT) are bone tumors derived from cartilage matrix, formerly also referred to as chondrosarcomas G1 [17, 33]. Enchondromas, on the other hand, are considered purely benign lesions, which – unlike ACT – have a low local recurrence risk and a negligible tendency to malignant degeneration. However, differentiation between enchondromas and ACT is complex from a clinical as well as radiologic and histopathologic perspective.


In 2013, chondrosarcomas G1 of the long and short tubular bones were distinguished from true malignant chondrosarcomas G2 and G3, by name change to ACT, by the World Health Organization (WHO) [18, 33]. This change emphasizes that ACT should be classified as tumors of intermediate dignity because they are locally aggressive but rarely metastasize.

"The term "ACT" should be used only in the extremities"

The prevalence of ACT is 0.4% [35], compared with a prevalence of almost 2% (at the shoulder) to 3% (at the knee joint) for enchondromas [20, 35]. Both enchondromas and ACT occur in majority in long – as well as especially enchondromas – also in short long bones [37]. However, the term "ACT" should be used only in the extremities, whereas the histologically low-malignant chondrogenic tumors of the axial skeleton (e.g. B. pelvis, scapula) should be designated as "chondrosarcoma G1" and treated differently, d. h. by means of wide resection [36].

In the publication by van Praag et al. from 2018, a continuous increase in the incidence of enchondromas and, even more, ACT has been reported [31], and it can be amed that this phenomenon is strongly related to more frequent diagnostics such as radiographs, magnetic resonance imaging (MRI), or. is related to the stricter classification of chondrogenic tumors based on radiological criteria [33].


Since enchondromas and ACT do not cause any specific symptoms, they are usually diagnosed as incidental findings in the course of a radiological workup due to other complaints (e.g., adenocarpal syndrome). B. degenerative joint changes) are discovered. Exceptions may be pathologic fractures, which often occur in the short tubular bones of the hand skeleton, and large cartilaginous tumors of the long tubular bones, in which patients occasionally report pain [15]. Pain is reported in this case u. a. attributed to erosive processes of the cortical bone with more or less pronounced scalloping. Nevertheless, "pain" should not be evaluated as a specific criterion, as this may even be more frequent in patients with enchondromas than in ACT due to other pain-causing pathologies [14].

The history is followed by clinical examination, which includes u. a. local prere pain, swelling and mobility of adjacent joints should be interrogated [15]. Afterwards, if not already done, an X-ray examination of the affected region in 2 planes should be ordered, which gives first essential clues to the dignity of the cartilaginous lesion (Tab. 1). If a cartilaginous tumor has been diagnosed on the radiograph, further MRI or computed tomography (CT) should be performed [30, 40]. A distinctive radiologic sign of cartilaginous lesions is "scalloping," focal erosion of the cortex (Tab. 1; Fig. 1; 2 and 3; [5, 14]).

Tab. 1 Possible radiological differentiation between enchondromas, atypical chondrogenic tumors (ACT), and chondrosarcomas G2/3 of the long bones. (Adapted from [13, 15, 21, 24, 33])

The atypical chondrogenic tumor springerlink

Atypical chondrogenic tumor (ACT) of the right proximal humerus in a 53-year-old female patient. In a.-p.-Radiograph of cartilaginous lesion of proximal humeral metaphysis with deep endosteal scalloping of the greater tuberosity (a). In magnetic resonance imaging (MRI) typical signaling in the T1 (b) and T2-weighted (c) sequence. In the axial image focal cortex destruction in the area of the sulcus bicipitalis with small extraosseous tumor component detectable (Arrow, d). R right

Enchondroma of the right distal femur in a 50-year-old female patient, discovered as an incidental finding during workup of a twisted knee trauma. In the a.-p.- and lateral radiograph solitary lesion of the distal femoral diaphysis with cartilaginous matrix and weak transition zone (a). In addition, superficial endosteal scalloping of the ventral matrix is visible (Arrow, b). Histologically lobulated, cell-poor tumor with partially calcified chondrogenic matrix (c, d Section of c)

Atypical chondrogenic tumor (ACT) of the proximal left tibia of a 17-year-old female patient. On the a.-p.- (a) and lateral (b) Radiographs elongated cartilaginous lesion with endosteal scalloping of the medial cortex. In coronary computed tomography (CT) scan, deep endosteal scalloping without cortex destruction (Arrow, c). On magnetic resonance imaging (MRI), confirmation of the cartilaginous etiology of the sharply circumscribed lesion with lobulated contour. Typical hyperintense signal in the fatty suppression T2-weighted coronary sequence (d) as well as hypointense signal in the T1-weighted axial sequence (e) as well as septal nodular contrast enhancement (f); neither soft tie component nor periosteal reaction visible. Condition 2 months after surgery with curettage and composite osteosynthesis, patient symptom-free (g,h). In histology, low-to-moderate cellular chondrogenic tumor with inclusion of preexistent bone nodules (indicative of infiltrative growth pattern). Calcifications detectable only focally (i, j Section of i)

Novel imaging techniques such as dynamic MRI examination, positron emission tomography-computed tomography (PET-CT), and computerized texture analysis are used in an attempt to differentiate between benign and malignant cartilaginous lesions [9]. However, the value of PET-CT and bone scintigraphy in differentiating between enchondromas and ACT is controversial [2, 33] and of questionable significance. In bone scintigraphy, ACT resp. Chondrosarcomas G1 increased 99 technetium and 201 thallium [21]. However, on the one hand, other reasons of tracer uptake must always be excluded (z. B. local overload reactions) [15]; on the other hand, the sensitivity of 99 technetium in particular is low [21]. In 18 F-FDG( 18 fluorodeoxyglucose) PET-CT it is possible to distinguish between ACT and higher grade chondrosarcomas, but this is hardly possible between enchondromas and ACT due to similar metabolic activity [2].

Biopsy alone for differentiation of suspicious enchondromas or. ACT is often not helpful, as it can lead to "sampling-error"; while parts of the tumor may be more or less well differentiated, the pathologist only gets selected regions for evaluation. Furthermore, the histologic similarities of enchondromas and ACT make it necessary to correlate histopathologic diagnosis with imaging [33].

"The sole biopsy for differentiation of suspicious enchondromas resp. ACT is often not helpful"

Finally, the decision to biopsy or not before definitive restoration of enchondromas (Fig. 2) resp. ACT (Fig. 3) u. a. depends on whether other differential diagnoses could be considered based on imaging or whether malignancy signs are detectable, indicating higher grade chondrosarcoma (G2/3) [33]. Radiologic signs of malignancy are u. a. Osteolysis, periosteal edema zones, absence of entrapped fat islands, permeative or moth-eaten bone destruction, and cortex destruction and an extraosseous soft tie component [24, 33, 43].

In histopathology, enchondromas represent cell-poor, lobulated tumors with hyaline matrix surrounded by a thin layer of reactive bone [16]. Cytologically inconspicuous chondrocytes are embedded in the matrix, which may be arranged in cell nests [16]. In places, the matrix may show calcifications (Fig. 2; [16]). In contrast, ACT are more cell-rich. Show low atypical chondrocytes. In addition, entrapment (inclusion) of preexistent bone bellicles is typical of ACT, indicating an infiltrative growth pattern (Fig. 3; [16]).

However, the tendency today is not to perform a biopsy before definitive surgery either for enchondromas – suspected on the basis of imaging – or for ACT, but to curettage the lesion directly, because the recurrence rate does not seem to be significantly higher after curettage, regardless of the final histopathologic result [4]. However, it must be remembered that definitive histology alone u. U. also not definitive between enchondromas. ACT can differentiate. Enchondromas. ACT can differentiate. Thus, depending on the localization, there are differences in the radiological. Histopathologic appearance. Enchondromas of the phalanges may show signs of aggressive growth in both radiology and histology, especially if a pathologic fracture is present. It is probably due to this fact that there is no clear description of ACT in the short tubular bones (fingers, toes) in the literature [3, 23]. At the same time, it should be noted that higher-grade chondrosarcomas (G2/3) are very rarely localized in short tubular bones [41].


Watch-and-wait approach

If all radiologic criteria indicate the presence of an enchondroma, clinical radiologic follow-up is sufficient. This is especially true for cartilaginous lesions of the short tubular bones, provided there is no discomfort and no risk of fracture. Cartilaginous lesions of the long tubular bones or the. of the axial skeleton should be followed up by MRI and referred to a tumor center [22]. Primary wait-and-see may be warranted even for lesions that can be classified as ACT, depending on the situation, provided there is no radiologic progression during the course, such as an increase in size> 6 mm within one year [8, 27, 28, 32].


Surgical treatment of ACT has been transformed over the years by the realization that these tumors are only locally aggressive and virtually never metastasize distantly: Wide resections are largely avoided today and curettage with or without the use of local adjuvants is preferred [10, 34]. Very low local recurrence rates of less than 10% have been achieved with this methodology [10, 34, 38].

Localization-dependent decision

Short tubular bones

Higher-grade chondrosarcomas of short tubular bones are generally rare [3, 23], and the distinction between ACT and chondrosarcomas is – as mentioned – not clearly defined. If enchondromas/ACT of the short tubular bones are treated surgically, this is usually in the context of pathological fractures or when there is a risk of fracture. After curettage, stabilization or. Filling of the medullary cavity with autologous or homologous cancellous bone as well as resorbable bone substitute (z. B. tricalcium phosphate), whereby in the case of autologous iliac crest cancellous bone, the not inconsiderable morbidity of the donor site must be taken into account.

Long tubular bone

In large ACT of the long bones, prophylactic stabilization, e.g., after curettage of the tumor site, may be necessary because of the postoperative risk of fracture [10]. B. with plate osteosynthesis, become necessary [28]. Due to higher complication rates. Potential clinical-functional disadvantages after osteosynthesis resp. Composite osteosynthesis, however, individual consideration is required in this regard [26, 27]. Nevertheless, the complication rate is much lower after intralesional surgery than after wide resection, with significantly better postoperative functionality [34].


On the trunk, low-malignant chondrogenic tumors generally behave more aggressively than on the axial skeleton, which is why they are classified as "chondrosarcoma G1" on the one hand, as mentioned at the beginning, and are more likely to be treated with wide resection margins on the other [12, 19].


Adjuvants can be applied after curettage of the ACT with the aim of minimizing the local recurrence risk due to remaining tumor cells after scraping out the tumor cavity (intralesional resection). In addition, like polymethylmethacrylate (PMMA, bone cement), they can be used simultaneously for defect filling. In the case of PMMA, the heat generated in the exothermic reaction during cement curing results in the destruction of possible residual marginal tumor cells. In addition, there is the advantage of better detection of recurrences in the marginal area between the bone cement plug and the healthy bone in further imaging follow-up. In addition to nonresorbable PMMA, tumor cavities can also be filled with resorbable bone substitutes based on (tri-)calcium sulfate and hydroxyapatite, although here, compared with PMMA, both the thermal effect and the improved delineation of recurrences in follow-up are omitted. Autologous cancellous bone-. Bone chip plastics (z. B. iliac crest) should be reserved for special indications today. Spongiosaplasties may be used in cases such as ACT close to the growth plate, in which the use of adjuvants is contraindicated due to cytotoxic and/or thermal effects. Bone spandex, in turn, can be used to splint pathological fractures of (short) long bones. Allografts (z. B. intramedullary strut grafts) have the great advantage over autografts of the lack of collection morbidity; at the same time, their limited availability is a major limitation [34].

In addition to PMMA, the most commonly used adjuvant includes phenol [34, 39], which is used to wet the walls of the tumor cavity at a concentration of 50-90% for a few minutes. However, because of the high toxicity of phenol (also high risk to the operator from inhalation), this adjuvant should no longer be used. A less expensive and less toxic alternative is hydrogen peroxide, the effectiveness of which has been confirmed in giant cell tumors of the bone [25]. Liquid nitrogen, which must be instilled into the tumor cavity at least 2 times in a row to achieve good cytotoxic effects, can also be used as an adjuvant [7, 34].

Radio frequency ablation

Radiofrequency ablation (RFA), which is used especially for osteoid osteomas, has rarely been used for the treatment of ACT [11]. In a recent 2019 study, it was shown that after biopsy with RFA as well as secondary planned curettage 3 months after the primary procedure, the tumor had been completely destroyed by RFA in over 70% of patients [11]. From today's point of view, this procedure should nevertheless be considered experimental for cartilaginous tumors.

Follow-up and staging

In general, annual follow-up of curetted ACT of the long bones by MRI should be performed, although the interval can be extended after one year should the initial follow-up MRI be unremarkable [39]. In addition, once after diagnosis of ACT of the long bones, a staging examination by chest CT is recommended by the authors.



If a patient is diagnosed with multiple enchondromas at a young age, this should raise suspicion of the presence of an enchondromatosis. Because 2 similar syndromes-Ollier's disease and Maffucci's syndrome-as well as metachondromatosis are characterized by the occurrence of multiple enchondromas [36]. Ollier's disease and Maffucci's syndrome differ in that the latter syndrome has additional vascular lesions such as spindle cell hemangiomas. In metachondromatosis, patients present with both enchondromas and osteochondromas caused by a PTPN11-Mutation [36, 42]. Maffucci syndrome and Ollier's disease, on the other hand, are caused by IDH1/IDH2-Mutations [29]. patients a follow-up. If there are complaints, further clarification should be made.

Malignant degeneration

According to a study by Altay et al. with 627 cases, the risk of degeneration in benign cartilaginous lesions in the direction of ACT is just under 4 % and in the direction of chondrosarcoma G2/3 is less than 1 % [1]. The amption that ACT will progress to higher grade chondrosarcomas without surgical therapy can be refuted by the fact that despite the increasing incidence of ACT (which is probably due to the forced diagnosis), the incidence of chondrosarcomas G2/3 did not show such an increase during the same period [6, 33].

Conclusion for practice

Diagnosis and therapy of cartilaginous tumors are multidisciplinary.

Pain without alternative cause is clinical evidence of atypical chondrogenic tumor (ACT).

Deep endosteal scalloping, increase in size during progression, focal cortex breakthrough at sites with physiologically thin cortex (z. B. Sulcus bicipitalis) are ACT-typical radiological signs.

Pathological fractures can occur in cartilaginous lesions of short tubular bones.

Only localizations in extremities are called "ACT"; histologically identical tumors of the trunk are to be classified as "chondrosarcomas G1" and treated differently.

A "sampling error" is common in the biopsy of enchondromas or. ACT possible due to lack of representativeness of focal sampling for the entire lesion.

Therapy for ACT is shifting away from radical tumor resection toward intralesional curettage, optionally using local adjuvants.


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