Discussion
BMN is an exceedingly rare pathologic finding in children. In our review of 3,760 bone marrow studies, six patients (0.24%) were identified to have BMN, all in the setting of malignancy. Based on the rarity of this pathologic finding, and the strong association with malignancy, a high suspicion should be maintained in pediatric patients with BMN.
Several themes emerged in the presentation, evaluation, and outcomes in the review of our cohort. The common presenting symptom for all patients was pain which prompted further evaluation. A review of peripheral blood findings, similar to a previous study, showed anemia as the predominant cytopenia, with leukopenia and thrombocytopenia developing later.
In the evaluation of BMN, diagnostic radiological imaging can serve as a helpful resource. MRI has been widely used to detect bone abnormalities in multiple disease entities, including hematologic malignancies. Previously described BMN MRI findings include fluid-filled necrotic lesions, hyperintense lesions and other findings with similar appearance to periarticular avascular necrosis. While not typically part of the diagnostic workup, due to atypical presentations of patients in our cohort, MRIs were obtained in many patients demonstrating abnormal bone signal corresponding to areas of BMN. Patient 2, after undergoing two previous non-diagnostic bone marrow examinations at the bilateral ilia, underwent an MRI which demonstrated absence of necrosis at the humerus and tibia. This prompted a BM evaluation at these sites which yielded viable tissue and ultimately lead to the diagnosis of AML (Figure 1). In patients with BMN evidenced by biopsy, imaging provides the advantage of analyzing a larger area of bone and subsequently determining the best place to biopsy and obtain viable tissue.
In regards to outcomes, only one patient in our cohort (Patient 1) died. Patient 1 was an outlier as BMN was not identified on initial diagnostic bone marrow evaluation and only identified after receiving intensive multi-modal chemotherapy. The remainder of evaluable patients are in disease-free remissions of two years or more. Based on ours and other previous studies, inferior outcomes in the setting of BMN have not been realized in the pediatric population, making it an unlikely indicator of prognosis. This is in contrast to adults where BMN necrosis has been associated with poor outcomes
An additional finding upon review of patients that required repeat bone marrow evaluations revealed they had previously been treated with immunosuppressive therapy, including steroids and a tumor-necrosis-factor antagonist. Based on the small sample, it is unclear if this played a role in the development of BMN. Further studies are needed to assess a potential causal relationship between immunosuppressive medication in the setting of malignancy and BMN.
While this review encompassed more than 3,700 bone marrow evaluations, it is a single institutional review which limits the scope. Additionally, comprehensive chart review from one case was not completed due to an inability to access outside medical records.
BMN in the pediatric population is exceedingly rare and when encountered, a malignant etiology should be suspected. Diagnosis from bone marrow evaluations is challenging, and radiological imaging is a helpful modality for localizing non-necrotic areas of bone marrow. A more comprehensive multi-institutional review would allow for a greater understanding of this unique pathologic entity.
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FIGURE 1 Bone marrow aspirate (A) showing myeloblasts. Bone marrow biopsy (B) consistent with bone marrow necrosis in the patient with AML. Axial T2 (C) and T1 (D) post-contrast images demonstrate a lesion in the left iliac bone consistent with bone marrow necrosis (white arrow).