Medical Student SYB December 17, 2008 Matt Kulzer MSIV

Case Overview History ◦14yo male with history of Ataxia-Telangiectasia ◦Presented yesterday with 3 wk h/o chest pain, headache, low grade fever, and fatigue Physical Exam ◦T 38.1, HR 106, RR 20, SpO 2 99% on RA ◦Remainder WNL Labs ◦Omitted

Additional Information/Findings WBC 249,000 Anemia/thrombocytopenia Smear ◦Preponderance of blasts CXR - Soft tissue density projecting along the right heart border on the AP view. It appears to be contiguous with the heart border, and there is no evidence of a posterior mediastinal mass on the lateral view. This could represent a mediastinal mass rather than prominent ascending aorta. The former is more likely given high WBC and concern for leukemia. Recommend comparison to any outside chest radiographs before proceeding to additional cross-sectional imaging studies. CT ◦Heterogeneous anterior mediastinal mass measuring 4.2 x 6 cm in shortest and long axis. This anterior mediastinal mass abutting the right atrium, right ventricle, SVC, and descending aorta. ◦Two adjacent nodular opacities within the posterior basal segment of the right lower lobe, that are concerning for leukemic infiltrates or metastatic lesions versus infectious process (in a patient with history of fever). ◦Marked splenomegaly.

Ataxia Telangiectasia AR hereditary ataxic disorder Patients develop: ◦progressive cerebellar ataxia ◦abnormal eye movement ◦other neurologic disorders (gross motor dysfxn, LMN weakness, speech/swallowing dysfnx) ◦oculocutaneous telangiectasias ◦immune deficiency ◦leukemias/lymphomas

Mechanism of DNA damage susceptibility in AT Interaction between cancer susceptibility genes and DNA repair. ATM (ataxia-telangiectasia mutated) senses a double-strand break in DNA, induced by agents such as ionizing radiation. ATM and CHEK2 phosphorylate BRCA1, promoting its migration to the break site. The Fanconi's anemia protein complex (proteins A, C, E, F, G) triggers the ubiquitination and co-localization of the Fanconi protein D2 with BRCA1 at the break site. BRCA2 carries RAD51, an enzyme involved in DNA recombination repair, to the same site. BRCA1, BRCA2, and RAD51 repair the DNA break by an error- free recombination mechanism. RAD51 is a component of cell cycle check points. (Redrawn from Venkitaraman AR: A growing network of cancer-susceptibility genes. N Engl J Med 348:1917, 2003 and taken from Robbins and Cotran Pathologic Basis of Disease 7E on December 16, 2008.)

Mediastinal Masses: Approach Identify the lesion Location ◦AP ◦LATERAL!!!! Know the differentials based on location/age of pt

Mediastinal Masses: Anatomy

Mediastinal Masses: Anterior Anterior Mediastinal Masses DDx: Thymic Masses ◦Lymphoma* ◦Thymoma* ◦Thymic ca ◦Thymolipoma ◦Thymic cyst ◦Thymic hyperplasia Thyroid Masses ◦Thyroid goiter* ◦Thyroid cyst ◦Thyroid adenoma ◦Thyroid ca Germ Cell Tumors ◦Teratoma/teratocarcinoma* ◦Seminoma ◦Mixed Germ cell tumors * indicates most common Or, simplified: The 4 T’s: ◦Thymoma ◦Thyroid lesions ◦Teratoma ◦T-cell lymphoma

Mediastinal Masses: Middle Middle Mediastinal Masses DDx: ◦Goiter ◦Lymphadenopathy ◦Mets*(lung ca most common) ◦Lymphoma/leukemia* ◦Granulomatous infection ◦Sarcoidosis ◦Inhalational lung disease (i.e., silicosis, berylliosis, coal workers’ pneumoconiosis) ◦Castleman’s disease ◦Aortic abnormalities: aneurysm*, dissection*, traumatic rupture ◦Bronchopulmonary foregut cysts ◦Tracheal tumor ◦Esophageal abnormalities: neoplasm, achalasia ◦Hiatal hernia* (with air/fluid level) ◦Cardiac tumor ◦Left ventricle aneurysm/pseudoaneurysm ◦Pulmonary artery aneurysm ◦Neurogenic tumor of vagus nerve * indicates most common Or Simplified: ◦Thoracic aortic aneurysms ◦Hematomas ◦Neoplasms ◦Adenopathy ◦Esophageal lesions ◦Diaphragmatic hernias ◦Duplication cysts

Mediastinal Masses: Posterior Posterior Mediastinal Masses DDx: ◦Neurogenic tumors* (peripheral nerve, sympathetic ganglion, parasympathetic involvement) ◦Primary or metastatic bone tumor of thoracic spine ◦Osteomyelitis or paraspinal abscess of thoracic spine ◦Extramedullary hematopoesis * indicates most common Or simply: ◦90% Neurogenic  Young: neuroblastoma  Adult: neurofibromas, schwannomas, ganglioneuromas ◦Others:  Hernias  Other neoplasms  Hematomas  Extramedullary hematopoesis

References Kumar, et al (2005). Molecular Basis of Cancer, Robbins and Cotran Pathologic Basis of Disease 7E. Philadelphia: Elsevier Mettler, FA (2005). Mediastinal Masses, Essentials of Radiology. Philadelphia: Elsevier Puneet, et al (2008). Ataxia-telangiectasia, Up To Date. Retrieved from ontent/topic.do?topicKey=ped_neur/9337&selectedTit le=1~150&source=search_result ontent/topic.do?topicKey=ped_neur/9337&selectedTit le=1~150&source=search_result Torrigan, DA and Wallace, TM (2006). Mediastinal Masses. Pretorius, ES and Solomon, JA (Eds.), Radiology Secrets Second Ed.). Philadelphia: Elsevier.