Case Presentation: A 59-year-old previously healthy man presented with subacute fatigue, back pain, and fevers. He developed gradual exertional intolerance in the preceding months which had progressively worsened prior to seeking medical attention. On the day of his presentation, he developed significant abdominal and atraumatic midline back pain. Vital signs at presentation were notable for a temperature of 100.6 °F. He did not have adenopathy or spinal tenderness on physical examination. Laboratory data on presentation revealed pancytopenia with a white blood cell count of 2120/µL, absolute neutrophil count of 320/µL, platelet count of 8000/µL and 1.4% nucleated red blood cells (NRBCs) on the automated differential. His reticulocyte percentage was 0.8%. He was admitted to the general medical service for further evaluation of his pancytopenia. Review of a peripheral smear confirmed NRBCs and many immature blood cells suggestive of a leukoerythroblastic anemia. An MRI of his cervical, thoracic and lumber spine was obtained which showed diffuse T1 hypointensity throughout the marrow and patchy T2 hyperintensities in the T11-L5 vertebral bodies, consistent with a marrow-replacing process. Given his presenting syndrome, marrow-replacing signal on MRI and leukoerythroblastosis, flow cytometry was obtained urgently which showed 5% circulating B-lymphoblasts. A bone marrow biopsy was performed and confirmed the diagnosis of B-cell acute lymphoblastic leukemia. He was subsequently transferred to the leukemia service of our hospital and initiated on treatment with cyclophosphamide, vincristine, doxorubicin, and dexamethasone. He has since received lymphodepleting therapy with methotrexate and cytarabine and has now completed Chimeric Antigen Receptor-T Cell (CAR-T) therapy for chemotherapy-refractory disease. He was discharged after experiencing a favorable response.
Discussion: Pancytopenia is frequently encountered by hospitalists and has a broad differential diagnosis with multiple potential causes including nutritional deficiencies, sequestration, infections, marrow failure syndromes, and malignancy. Along with assessing reticulocyte response, morphological examination of peripheral blood represents a key initial step in the work-up for pancytopenia. When evaluating the peripheral blood, the presence of NRBCs can be an important clue in identifying the underlying disease driving the pancytopenia. NRBCs are an immature form of red blood cells typically found only in the peripheral blood of a fetus or newborn infant.(1) When observed in an adult with pancytopenia, NRBCs can quickly shift the initially-broad differential towards malignant or myelophthisic etiologies, as marrow overcrowding can result in the disruption of the marrow-blood barrier, enabling progenitor cells to be released into peripheral blood.(2) In the absence of an elevated reticulocyte count, marrow infiltration and a malignant etiology should be promptly considered and evaluated.
Conclusions: Although often overlooked, NRBCs provide rapid information about the potential presence of a space-occupying lesion in the marrow and may indicate the need for a bone marrow biopsy.