A 15-year-old boy is brought to the emergency department due to progressive shortness of breath. The patient has no chronic medical conditions. Temperature is 37.1 C (98.8 F), pulse is 130/min, and respirations are 32/min. Pulse oximetry is 94% on room air. Lung examination demonstrates diffusely diminished breath sounds. Clusters of enlarged cervical lymph nodes are palpable bilaterally. A large mediastinal mass is visualized on chest x-ray. The leukocyte count is elevated, and a peripheral blood smear shows abnormal white blood cells, as shown in the image below: Specialized staining shows the cells are positive for terminal deoxynucleotidyl transferase (TdT) and CD3; they are negative for CD19 and myeloperoxidase (MPO). Which of the following is the most likely diagnosis?

Question

A 15-year-old boy is brought to the emergency department due to progressive shortness of breath.  The patient has no chronic medical conditions.  Temperature is 37.1 C (98.8 F), pulse is 130/min, and respirations are 32/min.  Pulse oximetry is 94% on room air.  Lung examination demonstrates diffusely diminished breath sounds.  Clusters of enlarged cervical lymph nodes are palpable bilaterally.  A large mediastinal mass is visualized on chest x-ray.  The leukocyte count is elevated, and a peripheral blood smear shows abnormal white blood cells, as shown in the image below:  Specialized staining shows the cells are positive for terminal deoxynucleotidyl transferase (TdT) and CD3; they are negative for CD19 and myeloperoxidase (MPO).  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

11ec160b_3969_a97e_9249_137e23043507_MD0001_00 This patient's peripheral blood smear demonstrates blast cells characterized by large nuclei, scant cytoplasm, visible nucleoli, and immature (ie, fine) chromatin. These early hematologic precursors normally comprise a small percentage in the bone marrow but, with malignant transformation, can proliferate and be detected in peripheral blood (eg, acute leukemia). The presence of myeloperoxidase (MPO) helps determine whether blasts are lymphoid or myeloid in origin. Because MPO is an enzyme involved in microbial killing by myeloid derivatives (eg, neutrophils), it is absent in lymphoid cells. In addition, positive terminal deoxynucleotidyl transferase (TdT) indicates lymphoblasts; TdT is a DNA polymerase involved in V(D)J recombination, which generates antigen receptor diversity during early lymphoid maturation. Therefore, negative MPO and positive TdT confirm that these are lymphoblasts. Lymphoblasts are further differentiated by markers unique to B (eg, CD19) or T (eg, CD3) cells. This patient's CD3-positive lymphoblasts indicate T-lymphoblastic leukemia (T-ALL). Unlike B-lymphoblastic leukemia (B-ALL), which usually occurs in early childhood, T-ALL is most common in adolescence. Tumors classically develop in the thymus, the site of T-cell development, and often result in the formation of a mediastinal mass that compresses the airway, causing cough and dyspnea, or the nearby blood vessels, causing superior vena cava syndrome. (Choice A) Acute myeloid leukemia arises from myeloid precursors (myeloblasts), and cells therefore express MPO, not CD3 and TdT. (Choice B) B-ALL, the most common ALL subtype, expresses TdT. However, expression of B-cell surface markers (eg, CD19) would be expected. In addition, presentation usually involves signs of bone marrow failure (eg, pallor, bruising) in young children, not a mediastinal mass in an adolescent. (Choice C) Burkitt lymphoma, a malignancy derived from mature B cells, can present with disseminated disease involving the bone marrow. An enlarging mass can be seen, but it is usually in the abdomen or jaw, not the mediastinum. Cells express B-cell, not T-cell, markers. Because Burkitt lymphoma is composed of mature B cells, TdT is negative. (Choice D) Hodgkin lymphoma can present with a mediastinal mass and painless lymphadenopathy. Circulating blasts are not typical. Instead, Reed-Sternberg cells (large cells with multilobated nuclei and eosinophilic nucleoli) within lymph nodes are characteristic. Because they arise from mature germinal or post-germinal center B cells, TdT is negative. Educational objective: T-lymphoblastic leukemia (T-ALL) is characterized by circulating lymphoblasts that express terminal deoxynucleotidyl transferase (TdT) and CD3. T-ALL often presents in adolescents/young adults with a mediastinal mass.

A 15-Year-Old Boy Is Brought to the Emergency Department Due