Match each patient's clinical and histopathologic presentation with the corresponding defining cytogenetic abnormality and characteristic therapeutic approach.
- A 52-year-old woman presents with early satiety and left upper quadrant fullness. Complete blood count shows a leukocyte count of 75,000/mm3 with absolute basophilia and an elevated lactate dehydrogenase.t(9;22) translocation creating a constitutively active tyrosine kinase; initial therapy targets this specific aberrant kinase.
- A 38-year-old man presents with epistaxis, widespread ecchymoses, and gingival bleeding. Coagulation studies reveal elevated D-dimer, prolonged prothrombin time, and decreased fibrinogen. Smear shows abnormal cells with numerous cytoplasmic needle-like inclusions.t(15;17) translocation leading to blocked differentiation; immediate initiation of an oral vitamin A derivative is indicated.
- A 10-year-old boy of East African descent is evaluated for a rapidly expanding, non-tender jaw mass. Histology of the mass reveals a high mitotic index with scattered macrophages containing apoptotic debris.t(8;14) translocation resulting in c-MYC oncogene overexpression; requires prompt initiation of intensive, high-dose combination chemotherapy.
- A 62-year-old woman is evaluated for waxing and waning painless cervical and axillary lymphadenopathy. Excisional biopsy demonstrates a nodular proliferation of small cleaved cells lacking macrophages.t(14;18) translocation causing overexpression of an anti-apoptotic protein; therapy often incorporates a monoclonal antibody targeting CD20.
Answer
Patient 1 (CML) matches with the t(9;22) translocation. Patient 2 (APL) matches with the t(15;17) translocation. Patient 3 (Burkitt Lymphoma) matches with the t(8;14) translocation. Patient 4 (Follicular Lymphoma) matches with the t(14;18) translocation.
Each hematologic malignancy has a defining genetic lesion that dictates its clinical behavior and treatment. CML is driven by the BCR-ABL1 fusion from t(9;22) and is treated with tyrosine kinase inhibitors. APL is driven by the PML-RARA fusion from t(15;17), causing a differentiation block that is reversed by ATRA. Burkitt lymphoma relies on c-MYC overexpression from t(8;14), causing rapid proliferation requiring aggressive chemotherapy. Follicular lymphoma is driven by BCL2 overexpression from t(14;18), preventing apoptosis and presenting as an indolent disease often managed with anti-CD20 therapy.
Step-by-Step Solution
Key Concept
Molecular cytogenetics and associated targeted therapies in hematologic malignancies.
Estimated Time:1m 30s