Clinical Pathological Conference

1. Clinical Pathological Conference Shrujal Baxi, M.D. Chief Resident Department of Medicine November 9, 2007

2. Chief Complaint An 83 year-old man presents with three days of intermittent chest pain

3. History of Present Illness • Six months prior to admission when he noted decreased exercise tolerance and was found to have a normocytic anemiathought to be Myelodysplastic syndrome, but no work up done at that time • About five months prior to admission, pt noted a nonproductive, chronic cough that was worse in evenings and relieved with prn albuterol therapy • One month prior to admission, the patient again started experiencing increasing shortness of breath. • 5-10lb weight loss over last few months, night sweats, subjective fevers

4. History of Present Illness On day of admission, pt presented with three days of intermittent chest pain that was substernal and radiated to his left arm and shoulder. It was sharp and stabbing in nature and worse with inspiration. The episodes would last hours and were variably relieved with sublingual nitroglycerin.

5. Past Medical History: Hypertension ≥ 20 years Diabetes ≥ 10 years Hypercholesterolemia ≥ 10 years Past Surgical History: Appendectomy Medications: (outpatient) Glyburide Ramipril Atenolol Erythropoietin and iron albuterol prn

6. Allergies:none Family History: Brother died at 55 of MI. No family history of malignancy, inflammatory conditions Social History: Born in the United States, patient fought in East Asia during World War II. He has no recent travel. 50 pack year tobacco history, quit 35 years ago. No alcohol use. No illicit drug use. Pt lives with wife in upstate New York. Pt worked in construction prior to retiring at the age of 69. ROS:otherwise noncontributory

7. Physical Exam General: Well developed male with evidence of respiratory distress who appears younger than stated age Vital Signs: BP 105/68 HR 120, regular, RR 20, Temp 98.2, SpO2 92% room air HEENT: Oropharynx clear and dry Lymph Nodes: No cervical, axillary or inguinal lymphadenopathy Neck: Supple, jugular venous distention difficult to assess

8. Physical Exam Pulmonary: Decreased breath sounds at bases, 1/3 up bilaterally. Dull to percussion Heart: Decreased heart sounds, tachycardic, regular rhythm, pulsus paradoxus of 22 Abdominal: Soft, nontender, nondistended, normal bowel sounds, with liver span of 14cm and dullness in Traube’s space Extremities: No peripheral edema, 2+ peripheral pulses Skin: No rashes, no purpura, no petechia

9. Admission Labs

10. Admission Labs

11. EKG

13. Upon Admission A prompt cardiac evaluation revealed a moderate to large pericardial effusion with right atrial collapse with a question of a right atrial mass. Pt was admitted to CCU for further evaluation. A diagnostic procedure was performed…

14. T1 T2 STIR

15. PATHOLOGY Dr. Hui Tsou Clinical Assistant Professor Department of Pathology  

18. Final Diagnosis • Diffuse Large B-Cell Lymphoma (DLBCL) with primary cardiac involvement - CD45+, CD20+ - CD3-, CD15-, CD30-, CD10-

19. Primary Cardiac Tumors • Prevalence-.002-.025% at autopsy • 75% benign in nature • Systemic embolization is presenting symptom in 25-50% of cases • Metastatic tumors 10-40X more likely than primary tumor

20. Primary Cardiac Tumors Benign (75% of all cases) • Myxoma • Rhabdomyoma • Fibroma • Teratoma Malignant (25% of all cases) • Sarcoma (majority) • Angiosarcoma • Rhabdomyosarcoma • Lymphoma • Histiocytoma • Malignant (25 of all cases) Sarcoma Angiosarcoma Rhabdomyosarcoma Fibrosarcoma Leiomyosarcoma Other Lymphoma Histiocytoma

21. Primary Cardiac Lymphoma (PCL) • Defined as presence of Non-Hodgkin’s Lymphoma confined to the heart or pericardium • PCL represents <2.0% of 1° cardiac tumors and 0.5% of extranodal lymphomas • More common in immunocompromised • Increased incidence due to AIDS and improved imaging techniques

22. Lymphoma • Now the 5th most common cancer diagnosed in both men and women • Represent 4% of all cancers • Approximately 63,000 cases diagnosed annually • Age at diagnosis is 60 with more than 50% over the age of 65 • 5 year survival is 63% and 10 year survival is 49%

23. Pathophysiology

24. Pathophysiology Assignment of Human B-Cell Lymphomas to Their Normal B-Cell Counterparts Kuppers R et al. N Engl J Med 1999;341:1520-1529

25. Pathophysiology

26. PCL • Common presentations of this uncommon diagnosis are based on location of tumor • Right-sided heart failure • Precordial chest pain • Pericardial effusion • Superior vena cava syndrome • Arrhythmia • CHF • Constitutional Symptoms

27. Pathogenesis of Disease Tumor Mass from replicating atypical lymphoma cells Environmental Factors Release of Cytokines (TNF, IL-6) Mutation to Oncogene of Lymphoid Cell Tissue invasion of right atrium and septal wall Night Sweats Weight Loss Pericardial Effusion Atrial Fibrillation Anemia of Chronic Disease Pleural effusions cough dyspnea chest pain fatigue

28. Diagnostic Studies • Labs:  LDH,  IL-2,  ESR • ECG: AV block, RBBB, Inverted T waves, Low voltage • CXR: Pleural Effusion and/or Cardiomegaly • Echocardiography: • Hypoechoic masses in the R atrium with pericardial effusion • TTE: difficulty visualizing pulmonary vessels, SVC, R atrium

29. Diagnostic Studies • CT • Appears hypodense or isodense relative to adjacent myocardium • + Contrast: heterogenous enhancement • MRI • T1 images: Hypointense and Dark • T2 images: Hyperintense and Bright • + Gadolinium: Heterogenous enhancement • Useful in making diagnosis and assessing response to RX • Nuclear medicine techniques • Gallium 67 • Technetium-99m hexakis-2-methoxyisobutyl isonitrile • Thallium-201

30. Diagnostic Studies Tissue is the Issue… • Pericardial fluid • Diagnostic in 67 % of cases • Tissue biopsy • Mediastinoscopy • Thoracoscopic biopsy • TEE guided biopsy • Endomyocardial transvenous biopsy • Exploratory thoracotomy

31. Treatment • Treatment for DLBCL is the chemotherapy regimen of R-CHOP • R=Rituximab • C=Cyclophosphamide • H=Adriamycin • O=Vincristine • P=Prednisone • Alternative regimens include: • COP • CHOP • Bone Marrow Transplant

32. Follow-Up • Upon admission, pt had pleural and pericardial drains placed • While work-up continuing, patient developed rapid afib controlled with low-dose b-blocker • Due to concern of significant atrial wall involvement of disease, first 2 cycles of R-CHOP given in CCU setting with continuous cardiac monitoring • Patient is currently disease free after receiving a complete course of R-CHOP

33. Thank you… • Dr. Srichai-Parsia • Dr. Kahn • Dr. Hui Tsou • Dr. Blaser • Dr. Grieco • Dr. Ballard • Dr. Mark Fisch