1. A 58 year-old man with bilateral lung transplant three years ago for severe COPD presents with pleural effusion and pleural-based lung nodules. A whole body pan scan (including brain) showed no masses or other lesions. An FNA of a lung mass was worked up with a battery of immunostains and showed GFAP reactivity.

2. Dr. Bonfiglio

9. Anaplastic Carcinoma Pleomorphic Sarcoma Large Cell Anaplastic Lymphoma Anaplastic Neural tumor –Glioblastoma Multiforme

10. Glial and other neural tumors Pleomorphic Adenomas Cartilage tumors Chordomas Soft Tissue myoepitheliomas

11. Morphology- –Consistent with anaplastic glial malignancy Immunostains –GFAP +

12. # 1. Glioblastoma

13. Glioblastoma Multiforme From Where ?

14. What is the rest of the Story ?

15. Metastatic Glioblastoma Multiforme Probably Transplant Transmitted

16.  Panelist I – “Malignant – favor PD carcinoma (look at rest of immunostain results)”  Panelist II – “ Post-transplant lymphoproliferative disorder ”  Panelist III – “ Some kind of GFAP + adenoca (? lung, ?breast, ?em, ?choroid glioma, ? colon)”

17.  25% - “Glioma NOS, GBM”  22% – “ACA”  11% – “Lymphoma, PTLD”  Misc – Transplant rejection, Atypical carcinoid, CA ex-PA, Mesothelioma, Malignant nerve sheath tumor, “I do not know”, Other

24. Pleural Effusion –Metastatic PD Carcinoma

25. Patient had bilateral lung tranplant for severe IPF Explanted organs were from a donor with h/o GBM  Lung FNA  Metastatic GBM (donor-acquired)  Positive: GFAP, CD56  Negative: CK7, CK20, TTF-1, HMB-45

26.  Donor-acquired solid organ malignancy is a rare complication of organ transplantation  This highlights the potential problems of using donors with GBM in an effort to increase the availability of solid tumor organs for transplantation  Of the 24,000 solid organ transplants performed yearly,1000 are lung transplants  Lack of supply, increasing demand for transplants and the significant shortage of donor organs > 1/3rd of all patients awaiting solid organs, die on the waiting list  Of those considered, only 7% to 22% of potential multiorgan donors are deemed suitable for lung transplantation Basic Facts Armanios MY et al., Neuro Onc 2004

27.  To bridge this discrepancy, patients with low-grade skin cancer (basal or squamous cell), in situ malignancies, and primary brain tumors have been included  Mortality:  Infections and graft rejection (majority)  EBV–associated PTLD and non-melanoma skin cancers, recipient derived, related to immune- suppressive therapy (minority)  Risk of donor-derived malignancies? Basic Facts Armanios MY et al., Neuro Onc 2004

28.  UNOS Data (published 2000):  14,705 cadaveric donors  257 h/o cancer (157 CNS tumors)  No documented donor-derived cancers recorded (45-mo mean f/u) Basic Facts Armanios MY et al., Neuro Onc 2004

29.  UNOS Data (published 2002):  397 donors with h/o CNS tumors (1220 organs)  No donor-derived cancers after 36 mo f/u Basic Facts Armanios MY et al., Neuro Onc 2004  Published Literature (since 1987)  10 case reports of donor-derived CNS cancers  7 GBMs, 1 meningioma, 1 NHL, 1 MB

33.  Donor-derived cancers are extremely rare  Extra cranial metastases can occur with PCNS cancers  Clinical history and immunolabeling is critical