A 7-year-old boy is brought to the office due to easy bruising and frequent epistaxis for 2 weeks. Temperature is 36.7 C (98 F), blood pressure is 106/60 mm Hg, pulse is 94/min, and respirations are 18/min. Examination shows pale lips with mucositis in the oropharynx. The neck is supple. The abdomen is soft, and pulses are 2+. Laboratory results are as follows:
| Hemoglobin | 8.2 g/L |
| Platelets | 40,000/mm3 |
| Leukocytes | 2,100/mm3 |
Findings from a bone marrow biopsy are shown in the image below:
Show Explanatory Sources
Which of the following is the most likely diagnosis?
Show Explanatory Sources
This patient with pancytopenia has bone marrow biopsy findings consistent with aplastic anemia, a form of acquired bone marrow failure caused by direct toxic injury or cytotoxic T-cell destruction of multipotent hematopoietic stem cells. Because these stem cells generate all mature blood cells for the body, their destruction dramatically reduces mature and immature blood cell populations in the bone marrow. Therefore, bone marrow biopsy typically reveals a profoundly hypocellular marrow with abundant lipid cells and small clusters of morphologically normal hematopoietic cells.
Although most cases of aplastic anemia are idiopathic, a minority are triggered by viruses (eg, Epstein-Barr, hepatitis), exposures (eg, toxic chemicals, radiation), or medications (eg, chemotherapy, antiseizure agents). Patients usually present with manifestations of pancytopenia such as pale lips (anemia), easy bruising/bleeding (thrombocytopenia), and infections (leukopenia) (eg, this patient's mucositis).
In contrast to many other causes of pancytopenia, extramedullary hematopoiesis (eg, splenomegaly) is usually absent because stem cells are damaged and unable to generate cells in any organ.
(Choice A) Acute lymphoblastic leukemia is the most common childhood malignancy. Although it can present with pancytopenia, most patients have lymphadenopathy and hepatosplenomegaly due to leukemic cell infiltration. In addition, bone marrow biopsy would show a hypercellular marrow with numerous lymphoblasts (immature lymphocytes).
(Choice C) Myelodysplastic syndrome is a clonal hematopoietic neoplasm that crowds out the bone marrow, leading to pancytopenia. Bone marrow biopsy usually shows a hypercellular marrow with abnormally differentiated cells (eg, hypogranular neutrophils, erythroid precursors with misshapen nuclei). Most cases occur in patients age ≥65.
(Choice D) Primary myelofibrosis is a myeloproliferative neoplasm that usually occurs in older adults. Patients may be cytopenic, but bone marrow biopsy would show marrow fibrosis; in addition, splenomegaly is usually prominent due to extramedullary hematopoiesis.
(Choice E) Parvovirus B19 infects erythrocyte precursors and can cause an aplastic crisis in patients with preexisting hematologic disease (eg, sickle cell anemia, hereditary spherocytosis). Leukocytes and thrombocytes are not generally affected.
Educational objective:
Aplastic anemia is a form of bone marrow failure caused by direct toxic injury or cytotoxic T-cell destruction of multipotent hematologic stem cells, which leads to pancytopenia. Bone marrow examination will show profound hypocellularity, an abundance of fat cells, and small clusters of morphologically normal hematologic cells.