What could be the cause of a teenage boy's elevated neutrophil and monocyte counts that temporarily normalized with a short course of dexamethasone (corticosteroid)?

Chronic Myelomonocytic Leukemia (CMML) or Myelodysplastic Syndrome (MDS)

The most likely diagnosis in this teenage boy with persistent neutrophilia (mid-40s) and monocytosis (low-50s) that temporarily normalized with dexamethasone is a myeloproliferative or myelodysplastic disorder, most concerning for chronic myelomonocytic leukemia (CMML) or myelodysplastic syndrome (MDS). The transient response to corticosteroids does not exclude these diagnoses and may reflect temporary suppression of the malignant clone.

Why This Pattern is Concerning

• Persistent elevation of both neutrophils and monocytes in a teenager is highly abnormal and mandates immediate exclusion of malignancy or bone marrow failure, particularly when fever and bicytopenia are absent 1

• The temporary normalization with dexamethasone is misleading because corticosteroids are known to increase neutrophil counts through demargination and prolonged neutrophil survival, not by correcting underlying bone marrow disorders 2, 3, 4

• Dexamethasone causes neutrophilia by delaying apoptosis through continuous stimulation of new protein synthesis, with peak neutrophil counts occurring 4-6 hours after administration 2, 4

• The fact that counts returned to abnormal levels after stopping dexamethasone strongly suggests an underlying bone marrow disorder rather than a reactive or inflammatory process 4

Critical Diagnostic Steps Required Immediately

A peripheral blood smear is absolutely critical to identify blasts, atypical cells, dysplastic features, or other abnormalities that would indicate a hematologic malignancy 1, 5

Bone marrow examination is mandatory in this case because:

• Persistent unexplained cytopenias or cytoses with abnormal counts beyond isolated thrombocytopenia require bone marrow evaluation 6, 5
• Age considerations aside, systemic abnormalities in multiple cell lines necessitate bone marrow aspirate and biopsy with flow cytometry and cytogenetic testing 5
• The American Society of Hematology recommends bone marrow examination when abnormalities exist beyond isolated thrombocytopenia in the blood count 5

Differential Diagnosis to Consider

Most Likely: Myeloproliferative/Myelodysplastic Disorders

• Chronic myelomonocytic leukemia (CMML) characteristically presents with persistent monocytosis (>1,000/μL) and can have associated neutrophilia 6
• Myelodysplastic syndromes can impair megakaryocyte function and cause abnormal cell counts across multiple lineages 5
• Juvenile myelomonocytic leukemia (JMML) should be considered in younger patients with monocytosis and neutrophilia

Less Likely but Must Exclude:

• Chronic infections (HIV, HCV, tuberculosis) can cause persistent monocytosis, though less likely to cause simultaneous neutrophilia 6, 5
• Autoimmune disorders rarely present with isolated neutrophilia and monocytosis without other systemic features 6
• Drug-induced changes are typically transient and resolve after drug discontinuation 5

Why Corticosteroid Response is Not Reassuring

• Corticosteroids increase neutrophil counts in both healthy individuals and those with underlying disorders by promoting neutrophil survival and demargination from vessel walls 2, 3

• Dexamethasone-induced neutrophilia requires continuous presence of the drug and reverses promptly upon discontinuation, which matches this patient's pattern 4

• The temporary normalization does not indicate resolution of an underlying bone marrow disorder; rather, it reflects pharmacologic manipulation of cell trafficking and survival 3, 4

• Corticosteroids decrease adhesion molecule expression (CD11b, CD18, CD62L) on neutrophils and monocytes, which affects cell distribution but does not correct clonal disorders 7

Common Pitfalls to Avoid

• Do not assume that response to corticosteroids indicates a benign or inflammatory condition in the setting of persistent unexplained cytoses 1, 5

• Do not delay bone marrow examination waiting for additional blood tests or observing for spontaneous resolution, as this delays diagnosis of potentially life-threatening conditions 1, 5

• Do not mistake corticosteroid-induced changes in cell counts for disease resolution, as the underlying pathology persists despite temporary normalization 4, 7

• Do not overlook the need for comprehensive bone marrow evaluation including aspirate, biopsy, flow cytometry, and cytogenetics when myeloproliferative or myelodysplastic disorders are suspected 5

Immediate Management Algorithm

1. Obtain peripheral blood smear immediately to evaluate for blasts, dysplasia, and abnormal cell morphology 1, 5

2. If smear shows any atypical features, proceed directly to bone marrow examination with aspirate, biopsy, flow cytometry, and cytogenetic analysis 5

3. Test for secondary causes including HIV, HCV, and comprehensive metabolic panel, though these are less likely given the clinical picture 6, 5

4. Refer urgently to pediatric hematology-oncology for definitive diagnosis and management, as myeloproliferative and myelodysplastic disorders require specialized care 6

5. Do not repeat corticosteroid trials as this will not provide diagnostic information and may delay appropriate workup 4, 7