1. Case Study 42 Henry Armah, M.D., M.Phil.

2. Question 1 Clinical history: 80-year-old male with past medical history of malignant non-Hodgkin’s lymphoma, diffuse large B-cell type, of the left flank soft tissue and abdominal wall post chemotherapy 10 months prior. He also had past medical history significant for status post pacemaker placement, colorectal carcinoma, aortic valve replacement, diabetes mellitus, chronic obstructive pulmonary disease and coronary artery disease. He presented with confusion and unsteady gait. MRI was not done because the patient had a pacemaker. Describe the abnormal findings of this cranial CT scan with contrast?

3. Ax CT+C

4. Answer Bilateral thalamic and mesial temporal contrast enhancing masses.

5. Question 2 What are your differential diagnoses based on the patients’ age, past medical history, and the radiological findings?

6. Answer 1. Malignant Lymphoma 2. High-grade Glioma 3. Metastatic carcinoma 4. Abscess

7. Question 3 The neurosurgeon performs a CT-guided stereotactic biopsy of the mass, and requested an intraoperative consultation. Describe the microscopic findings on this touch preparation slide? Click here to view slide.here

8. Answer Blood and scattered atypical cells.

9. Question 4 What is your intraoperative diagnosis? (A: Category such as Defer, Reactive/Non-neoplastic, or Neoplastic; B: More specific diagnosis or statement)

10. Answer A. Defer B. Atypical cells with hemorrhage

11. Question 5 The permanent section has returned from histology. Describe the microscopic findings on this H&E slide? Click here to view slide.here

12. Answer Fragments of brain tissue extensively and diffusely infiltrated by angiocentric dense atypical lymphoid infiltrates. The majority of the lymphoid cells are large with moderate pleomorphism and occasional mitosis. The interface between the diffuse lymphoid infiltrate and the adjacent brain parenchyma show reactive gliosis.

13. Question 6 What additional studies would you need to confirm the final diagnosis in this case?

14. Answer 1. CD20 (L26) 2. CD5 3. CD10 4. BCL-2 5. MUM-1 6. Ki-67 (MIB-1) 7. CD3 8. Cyclin D1 9. CD21 10. EBER (EBV Insitu Hybridization)

15. Question 7 What do you see on this CD20 (L26) immunostain slide? Click here to view slide.here

16. Answer CD20 (L26) is strongly and diffusely positive in the neoplastic lymphoid cells.

17. Question 8 What do you see on this CD5 immunostain slide? Click here to view slide.here

18. Answer CD5 is strongly and diffusely positive in the neoplastic lymphoid cells.

19. Question 9 What do you see on this CD10 immunostain slide? Click here to view slide.here

20. Answer CD10 is strongly and diffusely positive in the neoplastic lymphoid cells.

21. Question 10 What do you see on this BCL-2 immunostain slide? Click here to view slide.here

22. Answer BCL-2 is strongly and diffusely positive in tumor cells.

23. Question 11 What do you see on this MUM-1 immunostain slide? Click here to view slide.here

24. Answer MUM-1 is strongly and diffusely positive in tumor cells.

25. Question 12 What do you see on this Ki-67 (MIB-1) immunostain slide? Click here to view slide.here

26. Answer Ki-67 (MIB-1) is positive in the nuclei of greater than 90% of the neoplastic lymphoid cells.

27. Question 13 What do you see on this CD3 immunostain slide? Click here to view slide.here

28. Answer CD3 is negative in the neoplastic lymphoid cells, but highlights scattered reactive T-lymphocytes at the interface between the lesion and the adjacent brain parenchyma.

29. Question 14 What do you see on this Cyclin D1 immunostain slide? Click here to view slide.here

30. Answer Cyclin D1 is negative in the neoplastic lymphoid cells, but highlights rare admixed lesional cells most probably infiltrating reactive lymphocytes.

31. Question 15 What do you see on this CD21 immunostain slide? Click here to view slide.here

32. Answer CD21 is negative in the neoplastic lymphoid cells.

33. Question 16 What do you see on this EBER (EBV Insitu Hybridization) slide? Click here to view slide.here

34. Answer EBER (EBV Insitu Hybridization) is negative in the neoplastic lymphoid cells.

35. Question 13 What is your final diagnosis in this case?

36. Answer Malignant Non-Hodgkin’s Lymphoma, Diffuse Large B- Cell Type