21/09/2025
A powerful reminder of the diagnostic principle: ''always rule out reversible causes before jumping to invasive or aggressive treatments.''
Vitamin B12 deficiency can mimic hematologic malignancies, including acute lymphoma and myelodysplastic syndromes. Here's how:
Clinical Presentation: The patient had symptoms like fatigue, weight loss, and night sweats—classic red flags for lymphoma.
Lab Findings: Pancytopenia, macrocytic anemia (MCV 105), and elevated LDH levels suggested bone marrow dysfunction.
Peripheral Smear: Showed dysplastic features, but no blasts—raising suspicion without confirming malignancy.
Imaging: Enlarged lymph nodes and spleen added to the concern for lymphoma.
Underlying Cause: Pernicious anemia led to severe B12 deficiency, which explained all the hematologic abnormalities.
Why This Matters
Bone Marrow Biopsy Could Mislead: B12 deficiency can cause hypercellular marrow with blastic changes, mimicking leukemia or MDS.
Reversibility: With B12 supplementation, the patient’s blood counts normalized and symptoms resolved—no chemo, no biopsy, no unnecessary stress.
Before diagnosing acute leukemia or lymphoma, especially in patients with macrocytic anemia and pancytopenia, check B12 levels. It’s a simple test that can prevent a cascade of unnecessary procedures.
This case is a textbook example of why medicine demands both vigilance and humility.
Vitamin B12 deficiency disrupts hematopoiesis—your body's process of making blood cells—in profound and multifaceted ways. Here's a structured breakdown of how it happens:
Role of Vitamin B12 in Hematopoiesis
Vitamin B12 (cobalamin) is essential for:
DNA synthesis: It’s a cofactor for enzymes involved in converting homocysteine to methionine, which is crucial for DNA methylation and replication.
Cell division: Rapidly dividing cells, like those in the bone marrow, are especially vulnerable to B12 deficiency.
Neurological function: Though not directly part of hematopoiesis, B12 also maintains myelin integrity.
Hematologic Effects of B12 Deficiency
When B12 is deficient, hematopoiesis falters in several key ways:
1. Ineffective Erythropoiesis
Macrocytic anemia: Red blood cells become large (high MCV) due to impaired DNA synthesis and delayed nuclear maturation.
Megaloblastic changes: Bone marrow shows megaloblasts—immature, oversized precursor cells with nuclear-cytoplasmic asynchrony.
Pancytopenia: All three cell lines (RBCs, WBCs, platelets) may be reduced due to ineffective hematopoiesis.
2. Bone Marrow Hypercellularity
Despite low peripheral counts, the marrow may appear hypercellular with increased precursor cells trying (and failing) to mature properly.
This paradox can mimic myelodysplastic syndromes or acute leukemia on biopsy.
3. Dysplastic Features
Neutrophils: May show hypersegmentation.
RBCs: Anisopoikilocytosis, teardrop cells, and pencil cells may appear on smear.
These abnormalities can be mistaken for malignancy if B12 deficiency isn’t considered.
4. Elevated LDH and Bilirubin
Due to intramedullary hemolysis (destruction of immature cells in the marrow), LDH and indirect bilirubin rise—another mimic of aggressive hematologic disease.
Reversibility with Treatment
once B12 is replenished:
Blood counts normalize within weeks to months.
Bone marrow morphology returns to baseline.
Symptoms like fatigue, pallor, and neurologic deficits improve—often dramatically.
This is why clinicians emphasize: always exclude reversible causes like B12 deficiency before diagnosing hematologic malignancie.
University of Rochester Medical Center
Always Exclude the Reversibles: Vitamin B12 Deficiency.
Vitamin B12 deficiency should be ruled out in all suspected diagnosis of myelodysplastic syndrome and acute myeloid leukemia in clinically relevant settings.
