Kai Zong Teo¹, Dale Wright^2,4, Ali Moghimi^1,3

¹Department of Histopathology, The Children’s Hospital at Westmead, Sydney, NSW, Australia 

²Department of Cytogenetics, The Children’s Hospital at Westmead, Sydney, NSW, Australia

³Faculty of Medicine and Health, The Children's Hospital at Westmead Clinical School, University of Sydney, Sydney, NSW, Australia.

⁴Specialty of Genomic Medicine, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

Introduction:  Small cell osteosarcoma (SCOS) is a rare variant of osteosarcoma that mimics other round cell tumours of bone, particularly Ewing sarcoma (ES).[1-2] NKX2.2 immunohistochemistry has greatly improved distinction between SCOS and ES.[3]  

Aims: We present a previously undescribed finding of SCOS with positive NKX2.2 immunohistochemical staining. 

Case description: A 14-year-old boy was investigated for an FDG-avid mass in the left humeral diaphysis showing cortical erosion and muscle involvement. Core biopsy showed uniform round to oval, and occasional larger pleomorphic tumour cells, with necrosis, scattered mitotic and apoptotic nuclei, laciform woven bone, and cartilage formation. The tumour showed strong nuclear staining for SATB2 and p53, and NKX2.2 nuclear staining in many cells. No gene rearrangement of EWSR or FUS was identified on FISH or RNA sequencing. Chromosome microarray revealed a highly complex copy-number profile with near doubling of tumour genomic material more typical of osteosarcoma.

Discussion: The positive NKX2.2 expression is likely an incidental upregulation of transcription factors secondary to the complex tumour mutation profile. It is of unknown clinical significance and did not alter patient management. However importantly, it demonstrates a novel finding which if unknown to the reporting pathologist may lead misdiagnosis in particularly limited biopsies resulting in suboptimal management of disease.

References
1. Baumhoer D, Rosenberg AE, Cates JMM, et al. Osteosarcoma [Internet]. World Health Organization. World Health Organization; 2020 [cited 2024 Aug 7]. Available from: https://tumourclassification.iarc.who.int/chaptercontent/33/153 
 2. Righi A, Gambarotti M, Longo S, et al. Small cell osteosarcoma: clinicopathologic, immunohistochemical, and molecular analysis of 36 cases. Am J Surg Pathol. 2015 May;39(5):691-9. doi: 10.1097/PAS.0000000000000412. PMID: 25723116.
 3. Hiemcke-Jiwa LS, Sumathi VP, Baumhoer D, et al. Small cell osteosarcoma versus fusion-driven round cell sarcomas of bone: retrospective clinical, radiological, pathological, and (epi)genetic comparison with clinical implications. Virchows Arch. 2024 Mar;484(3):451-463. doi: 10.1007/s00428-024-03747-2. Epub 2024 Feb 9. PMID: 38332052; PMCID: PMC11021258.
  

This abstract is my (Kai Zong Teo) own original work with corrections and suggestions from Ali Moghimi and Dale Wright.