In the recent 5th edition of the WHO classification of soft tissue and bone tumors, small cell osteosarcoma was merged under COS as a histopathologic variant [5]. Before that, it was considered as a stand-alone subtype of osteosarcoma for a long time. It is a rare variant, comprising about 1.5% of all osteosarcomas, first described by Sim et al. [11] as a distinct entity osteosarcoma with small cells simulating Ewing’s sarcoma.

The documented cases of SCCO were reported in several sites of the skeleton, such as pelvis and humerus [7]. However, to the extent of our knowledge, in gnathic sites (maxillary and mandibular jaws), there are only 6 reported cases in the English language literature (Table 1), whereas 5 cases were reported in the mandible and only one in the maxilla. We report the seventh case of gnathic sites affecting the mandible of a 62-year-old female. The reported median age of diagnosis was 26.7 affecting both sexes almost equally [6, 12,13,14,15,16].

To date, there is no specific molecular genetic alteration for SCOS. However, in some documented cases, there were many patients who had either Ewing sarcoma breakpoint region 1 (EWSR1) or BCOR that encodes the BCL-6 corepressor protein rearrangements reported [17,18,19,20]. Interestingly, Noguera et al. reported one case of translocation (11; 22) [21]. In addition, by genomic sequencing of the breakpoint between EWSR1 and CREB3L1, Debelenko et al. confirmed the chimeric fusion gene transcripts [22].

All the documented cases of SCOS shared the same histopathological criteria which are sheets of small round cells with indistinct cellular outlines separated by dense fibrous tissue. The tumor cells usually have scant eosinophilic cytoplasm with nuclei that are generally small to medium and round to oval in shape. The presence of osteoid in the stroma is considered a cornerstone for SCOS differentiation from other small round cell tumors. In our case, the diagnosis was challenging because the malignant stroma had minimal osteoid deposition arranged in a lacelike fashion.

SCOS stain positively to considerable number of IHC markers such as CD99, vimentin, osteocalcin, osteonectin, and cytokeratin [5, 16, 23]. These markers also stain several round cell tumors. The special AT-rich sequence-binding protein 2 (SATB2) is an important transcription factor for osteoblastogenesis and is considered a highly sensitive marker for osteoblast lineage differentiation. In our case, it was used to rule out the other undifferentiated round cell sarcomas such as Ewing and the so-called Ewing-like sarcoma, and rhabdomyosarcoma (these previous tumors usually occur in the pediatric age) [7,  18]. Moreover, the positive staining helped us to exclude other round cell tumors that share various degrees of similarity with SCOS like non-Hodgkin lymphoma, metastatic small cell melanoma, poorly differentiated synovial sarcoma, small cell carcinoma, neuroblastoma, and mesenchymal chondrosarcoma [7].

Surgical resection with clear margins was done for the patient, and this is considered the treatment of choice [5]. Aggressive lesions with local invasion needed adjuvant therapy like chemotherapy and radiotherapy [15]. Follow-up of our patient did not show any evidence of recurrence until writing this manuscript. It is worth mentioning that, in three of the documented cases, the recurrence was not recorded [12, 14, 16], two of the documented cases showed no evidence of recurrence [13, 23], and one case showed local recurrence in the orbit after 1 year and a half [15]. The use of SATB2 could be a possible strength point in this study, as it is considered a highly sensitive marker for osteoblast lineage differentiation. However, the absence of diagnostic molecular genetic testing and short follow-up period could be the limitation.