Differentiated chondrosarcoma, variants of transformation of the sarcomatous component of the tumor
Authors: Kozlova E. V. , Bulycheva I. V. , Fedorova A. V. , Sushentsov E. A. , Kovaleva O. V. , Kushlinskii N. E. 
Published: April 2023

Introduction. It is generally accepted that dedifferentiated  chondrosarcomas are a result of transformation of low-grade (grade I and II) malignant chondrosarcomas into sarcoma with marked signs of cellular and tissue anaplasia with more aggressive clinical progression. Morphological examination of dedifferentiated  chondrosarcomas allows to detect presence of pre-existent low-grade malignant chondrosarcoma tissue. Dedifferentiated chondrosarcomas comprise about 10 % of all chondrosarcomas. Most frequently, this tumor is located in the femur, pelvic bones, and humerus. A common clinical complication of dedifferentiated chondrosarcomas is pathological fracture. This disease is characterized by more aggressive progression with unfavorable prognosis compared to conventional types of chondrosarcomas.

Aim. To study in detail  the  data  of laboratory,  clinical, radiological and morphological examinations of patients with different chondrosarcoma types for refinement of the algorithm of dedifferentiated chondrosarcoma examination and diagnosis.

Materials and methods. Between 2008 and 2022, data of 160 patients  with chondrosarcomas of varying locations and differentiation were analyzed. Diagnosis of “cartilaginous tumor” was made in all patients after clinical and radiological exams, as well as preoperative biopsy. Diagnosis of “dedifferentiated chondrosarcoma” was made in 30 patients. Radiological exam included several methods (X-ray, X-ray computed tomography, and magnetic resonance imaging) and modes of patient  examination.  Morphological diagnosis included routine  techniques  of histological analysis with gentle decalcification and subsequent immunohistochemical (PD-L1, PU-1, CD8, CD20, Ki67, CD34) and genetic analyses (IDH1/IDH2).

Results. Among 160 patients, preoperative biopsy verified the diagnosis of “dedifferentiated chondrosarcoma” only in 6 patients. In 4 patients, the possibility of chondrosarcoma transformation into poorly differentiated sarcoma of non-cartilaginous structure was suspected. At the stage of postoperative material examination, diagnosis of “dedifferentiated chondrosarcoma” was confirmed in 4 patients with suspicion of more malignant tumor transformation and newly made in 20 more patients.  Female patients were a little more common (19/11).  Mean patient  age was 59 years. Pathological fracture at the preoperative stage was observed in 6 patients. In almost one third of the cases (36 %), decreased differentiation of chondrosarcoma compared to preoperative biopsy was observed. It is important for management of these patients that in approximately 13 % of chondrosarcoma cases, recurrence with decreased tumor differentiation is observed.

Conclusion. Radical surgical resection remains the standard treatment of chondrosarcoma as the effectiveness of radio- and chemotherapy is limited though it remains important in dedifferentiated type of the disease. These circumstances lead to the use of tumor immunotherapy targeted at the search for potential use of the immune response for recognition and killing of various malignant cells including dedifferentiated chondrosarcoma. Consequently, a promising research direction is determination of the significance of tumor-associated macrophages, as well as tumor-infiltrating lymphocytes as antitumor factors and biomarkers affecting clinical and morphological characteristics of oncological diseases.