1. 18th Meeting of the European Association for Hematopathology
BMWS #314
Birgit FEDERMANN
Institute of Pathology and Neuropathology
Comprehensive Cancer Center
and University Hospital Tübingen 1

2. Clinical History
21-year old female with a history of of Crohn´s disease and severe EBV infection 4 years previously presented with fever up to 40C° and deterioration of general condition for 2 weeks
In CT scan hepatosplenomegaly
Months before, an immunosuppressive therapy with Azathioprine had been started 2

3. Peripheral Blood at onset 2008
Leukocytes 590/µl Hb 7.7 g/dl Platelets /µl LDH 438 U/l Ferritin 120 µg/dl Triglycerides 378 mg/dl Fibrinogen 131 mg/dl Reactivation of EBV and CMV infection (Serology and PCR) 3

4. Bone Marrow - Cytology 4

5. Bone Marrow - HE 5

6. Bone Marrow Giemsa ASDCL6

7. Bone Marrow – CD68 7

8. Bone Marrow
CD3
CD20 8

9. Liver – HE 9

10. Immunophenotype Immunohistochemistry Flow Cytometry
Few reactive CD20+ B-cells
Large nodules of CD3+ T-cells
Increase of CD8+ cytotoxic T-cells
Increase of CD68+ macrophages
Negativity for EBV-in-situ-hybridization
Flow Cytometry
NK-cells 1% decerased
CD4/CD8 ratio decreased 10

11. Interesting Features
Acquired form of hemophagocytic lymphohistiocytosis (HLH) in a patient with immunosuppression because of Crohn´s disease and Azathioprine therapy
Diagnostic criteria completely fullfiled
fever, splenomegaly, cytopenia, hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis in bone marrow, no evidence of malignancy, low or lacking activity of NK cells, increased Ferritin and soluble IL-2 receptor 11

12. Interesting Features
Impaired function of NK-cells and cytotoxic T-cells
virus infections with EBV and CMV
immune defect due to the chronic inflammatory bowel disease and the immune suppressive therapy
Important to start promptly with an adequate suppression of the hyperstimulated immune system and to treat a virus infection 12

13. Proposed Diagnosis
Acquired non-neoplastic Hemophagocytic Lymphohistiocytosis, associated with reactivation of EBV- and CMV-infection and immunosuppressive therapy 13