A 6-year-old boy is brought to the clinic due to recurrent nosebleeds over the last couple of weeks. The patient has no chronic medical conditions and takes no medications. Vital signs are normal. On physical examination, there is conjunctival pallor. The nares have dried, crusted blood with no active bleeding. The oropharynx is clear. Neck examination shows enlarged, palpable lymph nodes bilaterally. Cardiopulmonary examination is unremarkable. The abdomen is soft and nontender, with the liver measuring 4 cm below the costal margin. There are scattered petechiae along the trunk. Complete blood count is as follows: Flow cytometry of the peripheral blood demonstrates a distinct population of cells that express terminal deoxynucleotidyl transferase (TdT), CD10, and CD19. Myeloperoxidase (MPO) is negative. Which of the following is the most likely diagnosis?

Question

A 6-year-old boy is brought to the clinic due to recurrent nosebleeds over the last couple of weeks.  The patient has no chronic medical conditions and takes no medications.  Vital signs are normal.  On physical examination, there is conjunctival pallor.  The nares have dried, crusted blood with no active bleeding.  The oropharynx is clear.  Neck examination shows enlarged, palpable lymph nodes bilaterally.  Cardiopulmonary examination is unremarkable.  The abdomen is soft and nontender, with the liver measuring 4 cm below the costal margin.  There are scattered petechiae along the trunk.  Complete blood count is as follows:  Flow cytometry of the peripheral blood demonstrates a distinct population of cells that express terminal deoxynucleotidyl transferase (TdT), CD10, and CD19.  Myeloperoxidase (MPO) is negative.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec160b_3968_70fb_9249_7b438ac9fda4_MD0001_00 This child with marked leukocytosis has lymphadenopathy, hepatomegaly, and signs of bone marrow failure (eg, pallor from anemia, bleeding/petechiae from thrombocytopenia). These findings are concerning for acute leukemia, which occurs due to clonal expansion of hematopoietic progenitor cells (ie, blast cells). Blasts may be either lymphoid or myeloid in origin. Immunophenotyping (eg, flow cytometry) is used to characterize blast cells and classify acute leukemia. This patient's cells are lymphoid in origin. Lymphoid cells typically lack myeloperoxidase (MPO), an enzyme involved in microbial killing by myeloid derivatives (eg, neutrophils). Immature lymphocytes (lymphoblasts) can be differentiated from mature lymphocytes by the presence of terminal deoxynucleotidyl transferase (TdT); TdT is a DNA polymerase involved in V(D)J recombination, which generates antigen receptor diversity during early lymphoid maturation. Therefore, this patient has acute lymphoblastic leukemia (ALL). ALL can be subdivided into B-lymphoblastic leukemia (B-ALL) or T-lymphoblastic leukemia (T-ALL) based on the following markers: This patient's cells express both CD10 and CD19, findings consistent with B-ALL. (Choice A) Acute promyelocytic leukemia (APML), a type of acute myeloid leukemia, can also present with bone marrow failure. However, APML would not express TdT, CD19, and CD10. Blast features that indicate a myeloid lineage include the expression of MPO and presence of Auer rods (needle-like cytoplasmic structures representing fused granules). (Choice C) Burkitt lymphoma can present with lymphadenopathy and disseminated disease, including bone marrow failure. Although the malignant cells express B-cell markers (eg, CD19), they do not express TdT because the cell of origin is a mature, not a progenitor, B cell. (Choice D) Mature T-cell leukemia is derived from mature or postthymic T cells, and immunophenotyping would reveal the presence of T-cell markers (eg, CD3) and the absence of TdT. Moreover, this is an uncommon neoplasm typically seen in adults, not young children. (Choice E) Immunophenotyping of cells in T-ALL, which typically presents in adolescents with a mediastinal mass, would show expression of TdT but would also express T-cell, not B-cell, markers. Educational objective: Acute lymphoblastic leukemia typically presents with signs/symptoms of bone marrow failure (eg, bleeding due to thrombocytopenia). Immunophenotyping by flow cytometry establishes the specific subtype; B-lymphoblastic leukemia shows expression of terminal deoxynucleotidyl transferase (TdT) (marker expressed in lymphoblasts) and B-cell markers (eg, CD10, CD19).

A 6-Year-Old Boy Is Brought to the Clinic Due to Recurrent