13. Conclusion

Myeloid sarcoma is acknowledged as a separate disease entity for a significant period. It is an extremely rare hematological malignancy and is often associated with poor prognosis. Due to the scarcity of samples, there is no risk assessment study for MS. There are several unanswered questions for MS. Specifically, is there a bias for certain AML (such as CBF leukemia) to induce extramedullary infiltration. If yes, what is the primary mechanism(s) that drives the processes? Does MS represent alternate molecular landscapes, clonal evolution, from the original bone marrow disease? It can be argued that MS reflects a state of reduced immune surveillance in a patient at diagnosis or following hematopoietic stem cell transplantation. Consequently, this raises the possibility that MS may serve as a sanctuary site for leukemic relapse. The observation supports this implication that isolated MS ultimately gives rise to leukemia involving bone marrow.

MS is often challenging to identify and even more challenging to diagnose. Owing to its similarity with solid tumors, MS is often misdiagnosed, particularly as non-Hodgkin lymphoma. Accurate diagnosis of MS required an orchestrated approach involving whole body imaging (PET/CT, MRI), broad panels of immunohistochemical staining, and FISH assay for cytogenetic and chromosomal abnormalities. Also, bone marrow biopsy should be that part of the diagnosis. In fact, all isolated MS cases should be prophylactically treated for AML even if there is no detectable leukemia. Caution should be exercised when analyzing immunohistochemistry for MS. For example, CD43 and CD68, although, a reliable indicator of AML, should be correlated with CD33, myeloperoxidase staining for accurate MS diagnosis. Treatment should involve systemic chemotherapy as the first line of treatment with radiotherapy and allo-HCT as part of the consolidation therapy. Surgery should be employed for tumor resection, if possible.

We need more prospective studies with larger patient cohorts to understand the mechanism(s) of MS development. In addition, future studies should be directed to whole genome sequencing of MS samples to understand the different genetic abnormalities associated with MS and how they differ from the corresponding bone marrow disease. Genetic information will also help in better patient stratification. As evident from the whole-body PET/CT imaging, the incidence of MS is more prevalent than expected indicating that we most likely have underestimated the impact and implications of MS.
