An 8-year-old boy comes to the office due to a mass in the right mandible. His family first noticed it a few months ago, and it has grown rapidly. He has had no fevers, chills, cough, or weight loss. The patient and his family recently immigrated to the United States from East Africa. He has no known medical problems. Temperature is 37 C (98.6 F). Physical examination shows a large tumor on the right mandible with palpable regional lymphadenopathy. A biopsy of the lesion is performed. Histopathologic examination shows a diffuse infiltrate of lymphoid cells with numerous mitotic figures; interspersed macrophages with clear cytoplasm are also seen. These lymphoid cells most likely have a chromosomal translocation that directly alters which of the following processes?

Question

An 8-year-old boy comes to the office due to a mass in the right mandible.  His family first noticed it a few months ago, and it has grown rapidly.  He has had no fevers, chills, cough, or weight loss.  The patient and his family recently immigrated to the United States from East Africa.  He has no known medical problems.  Temperature is 37 C (98.6 F).  Physical examination shows a large tumor on the right mandible with palpable regional lymphadenopathy.  A biopsy of the lesion is performed.  Histopathologic examination shows a diffuse infiltrate of lymphoid cells with numerous mitotic figures; interspersed macrophages with clear cytoplasm are also seen.  These lymphoid cells most likely have a chromosomal translocation that directly alters which of the following processes?

Quizplus · Accepted Answer

This patient likely has the endemic African form of Burkitt lymphoma, which primarily affects children and typically presents as a maxillary or mandibular mass. This type of lymphoma is strongly associated with Epstein-Barr virus (EBV) infection. On histopathologic examination, Burkitt lymphoma consists of monomorphic, intermediate-sized lymphoid cells with round nuclei, multiple nucleoli, and basophilic cytoplasm. A high mitotic index and high cell death rate are typically seen. Benign macrophages that phagocytize the resulting cellular debris ("tingible body macrophages") are distributed throughout the malignant tissue. The clear cytoplasm of the macrophages contributes to the characteristic "starry sky" appearance of Burkitt lymphoma. Most Burkitt lymphomas demonstrate a translocation between the c-Myc oncogene on the long arm of chromosome 8 and the Ig heavy chain region on chromosome 14 [t(8;14)]; this results in Myc overexpression due to the highly active immunoglobulin promoter in B cells. The product of c-Myc is a nuclear phosphoprotein that functions as a transcription activator, stimulating cell growth and proliferation. (Choice A) Follicular lymphoma is often characterized by a translocation between the long arm of chromosome 18 near the BCL2 gene and the Ig heavy chain gene on chromosome 14 [t(14;18)]. This translocation leads to overexpression of the apoptosis inhibitor protein Bcl-2. (Choice B) Mutations of DNA repair enzymes (eg, BRCA1, BRCA2) are associated with breast cancer, ovarian cancer, Lynch syndrome, xeroderma pigmentosum, Fanconi anemia, and many other diseases. (Choice C) Translocation between the cyclin D1 locus on chromosome 11 and the Ig heavy chain locus on chromosome 14 [t(11;14)] is characteristic of mantle cell lymphoma. This abnormality results in increased production of cyclin D1, a promoter of G1 to S-phase transition during the cell cycle. (Choice E) Translocation of the ABL gene from chromosome 9 to 22 [t(9;22)] results in the Philadelphia chromosome, a typical finding in chronic myeloid leukemia. BCR-ABL, the resulting fusion gene, encodes a protein with increased tyrosine kinase activity that inhibits apoptosis while promoting mitogenesis. Educational objective: Burkitt lymphoma is characterized by aggressive rapid growth and a "starry sky" microscopic appearance. Translocation between the c-Myc oncogene on the long arm of chromosome 8 with the Ig heavy chain region on chromosome 14 leads to overexpression of Myc, a nuclear phosphoprotein that functions as a transcription activator.

An 8-Year-Old Boy Comes to the Office Due to a Mass