Mesenchymal Chondrosarcoma in Children and Young Adults: A Single Institution Retrospective Review

Abstract

Background. Mesenchymal chondrosarcoma is an aggressive, uncommon histologic entity arising in bone and soft tissues. We reviewed our institutional experience with this rare diagnosis. Methods. We conducted a retrospective chart review on patients with mesenchymal chondrosarcoma over a 24-year period. Clinicopathologic and radiographic features were reviewed. Results. Twelve patients were identified. Nine were females; median age was 14.5 years (1.2–19.7 years). The most common site was the head/neck (7/12). Disease was localized in 11/12 patients (one with lung nodules). Six with available tissue demonstrated NCOA2 rearrangement by FISH. Six underwent upfront surgical resection, and six received neoadjuvant therapy (2 chemotherapy alone and 4 chemotherapy and radiation). All patients received adjuvant chemotherapy (most commonly ifosfamide/doxorubicin) and/or radiation (median dose 59.4 Gy). At a median follow-up of 4.8 years, 5-year disease-free survival and overall survival were 68.2% (95% CI 39.8%, 96.6%) and 88.9% (95% CI 66.9%, 100%). Two patients had distant recurrences at 15 and 42 months, respectively. Conclusion. Aggressive surgical resection of mesenchymal chondrosarcoma with chemoradiotherapy yields excellent local control and may reduce likelihood of late recurrence. Characterization of downstream targets of the HEY1-NCOA2 fusion protein, xenograft models, and drug screening are needed to identify novel therapeutic strategies.

Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes

“…Based on the deletions reported in mesomelia‐synostoses syndrome, a candidate gene is NCOA2 , which encodes a transcriptional coactivator for nuclear hormone receptors (steroid, thyroid, retinoid, and vitamin D receptors) also known as TIF2. HEY1‐NCOA2 fusion proteins have been found in specimens of mesenchymal chondrosarcoma, an aggressive, uncommon histologic tumor arising in bone and soft tissues . A similar mechanism has been proposed for another skeletal disorder, the mesomelic dysplasia Savarirayan type (MIM#645274).…”

“…HEY1-NCOA2 fusion proteins have been found in specimens of mesenchymal chondrosarcoma, an aggressive, uncommon histologic tumor arising in bone and soft tissues. 39 A similar mechanism has been proposed for another skeletal disorder, the mesomelic dysplasia Savarirayan type (MIM#645274). Three unrelated cases with 2 Mb overlapping de novo 6p22.3 microdeletions spanning 4 genes with no previous association with skeletal anomalies were identified.…”

Chondrosarcoma of the Osseous Spine

“…34 In context, this finding is consistent with children tolerating higher doses of chemotherapy, which is used in instances of advanced disease in mesenchymal and dedifferentiated chondrosarcoma, that may be otherwise intolerable in older patients for therapeutic effect. 18,19,35 Although there was an observed trend, the decade of diagnosis was not found to be associated with a statistically significant improvement in survival in either univariate or multivariate analysis, or for chondrosarcoma variants. Contextually, this may suggest that advances in radiation therapy and chemotherapy regimens have not been as successful for chondrosarcoma as for other bone tumors.…”

Clinical outcomes for patients after surgery and radiation therapy for mesenchymal chondrosarcomas

“…While systemic therapy did not result in a statistically significant improvement in DFS (HR ¼ 3.1132; P ¼ 0.157) or OS (HR ¼ 0.668; P ¼ 0.776), this may reflect selection of patients with less favorable prognostic factors for treatment with chemotherapy, small cohort size, or limited effectiveness of the chemotherapy regimens employed. Bishop et al stated in their publication that mesenchymal chondrosarcomas are chemoresistant based on their observations using volumetric modeling that only one patient out of six evaluable patients had partial response to treatment [20]. Nakashima et al did not observe a specific gain with use of chemotherapy in their cohort either [3].…”