1. Case Presentation 31 year-old man with increased blast count
Mariko Yabe, MD, PhD
Hematopathology Fellow
University of Texas MD Anderson Cancer Center
January 22, 2016

2. Clinical History 31 year-old man Fever, chills, night sweat for 1 week
PMH
Crohn’s disease
(Treated with 6-Mercaptopurine,Mesalamine)
Physical exam
Jaundice
Splenomegaly

3. CBC
WBC 7.2 x 109/L (Meta 1, Neutro 54, Lymph 23, Mono 22)
Hgb 8.7 g/dL
MCV 94 fL
PLT 75 x 109/L
Chemistry
T-Bil 2.1 mg/dL (ref: )
ALP 240 IU/L (ref: )
LDH IU/L (ref: )
AST 67 IU/L (ref: 10-40)
ALT 87 IU/L (ref: 15-46)
B2M 3.8 mg/L (ref: )

4. BM aspirate
Giemsa (x 500)

5. BM diff Blasts 34 % (0-5) Progranulocytes 0 % (2-8)
Myelocytes % (5-20)
Metamyelocytes % (13-32)
Granulocytes % (7-30)
Eosinophils % (0-4)
Lymphocytes % (3-17)
Plasma cells % (0-2)
Monocytes % (0-5)
Pronormoblasts % (1-8)
Normoblasts % (7-32)
M:E Ratio (3-4)

6. BM core Bx
H&E (x 100)

7. CD3

8. CD4

9. CD8

10. TCRγ

11. βF1

12. Other Immunohistochemistry
TIA-1 Negative
Granzyme B Negative
EBER Negative

13. Flow cytometry
SSC
CD4
CD8
CD45

14. CD2
CD7
CD5
CD26
TCR γδ
CD56
CD57
TCR αβ

15. Cytogenetics Molecular
46,X,-Y,i(7)(q10),+8[6]/
46,X,-Y,i(7)(q10),+8,t(9;20)(q13;q11.2)[1]/
46,XY[13] v
Molecular
Monoclonal TCR gamma rearrangement detected

16. Proposed Diagnosis
Hepatosplenic T-cell Lymphoma

17. Discussion HSTCL can be a mimic of T lymphoblastic leukemia/lymphoma
Subset of HSTCL patients has underlying immune disorders
Prognostic factors

18. Discussion HSTCL can be a mimic of T lymphoblastic leukemia/lymphoma
Subset of HSTCL patients has underlying immune disorders
Prognostic factors

19. Hepatosplenic T-cell lymphoma
Rare and aggressive extranodal T-cell lymphoma, usually seen in adolescents and young adults
Virtually all cases show bone marrow involvement
Lymphoma cells typically show
CD2+/CD3+/CD4-/CD5-/CD7+/CD8-/CD56+/CD57-
TIA-1+/Granzyme B ±

20. Morphologic Spectrum Small 18% Intermediate 43% Large 14% Blastoid 25%
Yabe M, et al. Am J Surg pathol in press

21. Lymphoma cell/prolymphocyte-like morphology
T lymphoblastic leukemia/lymphoma
Lymphoma cell/prolymphocyte-like morphology
Blastoid Hepatosplenic T-cell lymphoma

22. Take-home messages (1)
Virtually all cases of hepatosplenic T-cell lymphoma show bone marrow involvement
Subset of cases has blastoid morphology
-> HSTCL could be misdiagnosed with
T lymphoblastic leukemia/lymphoma

23. Discussion HSTCL can be a mimic of T lymphoblastic leukemia/lymphoma
Subset of HSTCL patients has underlying immune disorders
Prognostic factors

24. HSTCL arising in patients with underlying immune disorders
Subset of patients (~20%) with HSTCL have a history of immune disorders
In our multi-institutional study
29 HSTCL patients (Jan 2000-Dec 2015)
7 patients had underlying immune disorders (24%)

25. 7 Patients at MD Anderson
Time to develop HSTCL
Case #
Gender
Age
Underlying
disease
From immune
disorder (years)
From drug
exposure (years) 1 M 21 CD 13 NA 2 49 UC 5 3 31 4 18 38 16 6 51 RA 7 F 72
Yabe M, et al. USCAP 2016

26. No underlying immune disorders
Review of the literature identified additional 60 patients with HSTCL arising in immune disorders
Underlying
immune disorders
No underlying immune disorders
n= 67
n= 22
p value
Age, median (range)
31.5
7-79
32.5
4 - 82
0.8362
Gender
Male 56
84% 13
59%
Female 11
16% 9
41%
0.0359
Underlying immune disorders
Crohn's disease 40
Ulcerative colitis 7
Rheumatoid arthritis 6
Post renal transplant 5
Post liver transplant 2
Post allogeneic stem cell transplant 1
Churg Strauss syndrome
Sjogren syndrome
Systemic lupus erythematosus
Psoriasis
Hodgkin lymphoma, treated
ALPS, Evans syndrome
Yabe M, et al. USCAP 2016

27. Medication of Patients with Underlying Immune Disorders who Developed HSTCL
Immunosupressive/cytotoxic drugs %
Azathioprine
46%
6-Mercaptopurine
33%
Cyclosporine
13%
Methotrexate 8%
Tumor necrosis factor-α inhibitors
Infliximab
44%
Adalimumab
Etanercept 2%
Miscellaneous
Steroids
67%
Mesalazine or Sulfasalazine
39%
Yabe M, et al. USCAP 2016

28. 90% 49% 41% 2% 8% Neither Summary of Medication
immunosuppressive drugs
TNF-α inhibitors
90%
49%
41% 2% 8%
Neither
-> More than 50% patients didn’t receive TNF-α inhibitors

29. Comparison of Cytogenetic Analysis i(7q) significantly increased
Underlying
immune disorders
No underlying
p value
i(7q)
19/26
73%
6/19
32%
0.0076
Trisomy 8
9/26
35%
7/19
37%
1.0000
i(7q) significantly increased
No increase in trisomy 8
Yabe M, et al. USCAP 2016

30. Comparison of Immunophenotype
Underlying
immune disorders
No underlying
P-value
Immunophenotype (% positive cases)
CD2
28/28
100%
20/22
91%
0.1886
CD3
32/32
21/22
95%
0.4074
CD4
3/31
10%
0/22 0%
0.2576
CD5
2/27 7%
1/22 5%
1.0000
CD7
25/27
93%
22/22
0.4949
CD8
7/29
24%
4/28
18%
0.5045
CD56
26/28
14/22
64%
0.0145
CD57
0/15
1/17 6%
TIA-1
12/17
71%
20/21
0.0712
Granzyme B
2/13
15%
9/20
45%
0.1322
EBER
1/16
0/19
0.4571
Yabe M, et al. USCAP 2016

31. Take-home messages (2)
Subset of the patients have underlying immune disorders, most frequently Crohn’s disease
These patients show prominent male predominance, frequent expression of CD56, and often carry i(7q)
Despite the underlying immune disorders, EBER is negative in most of the cases

32. Discussion HSTCL can be a mimic of T lymphoblastic leukemia/lymphoma
Subset of HSTCL patients has underlying immune disorders
Prognostic factors

33. Clinical course of this 31 year-old patient
After the diagnosis of HSTCL, he received Hyper-CVAD.
A day #21 bone marrow aspiration showed persistent HSTCL.
He received additional 2 courses of Hyper-CVAD (total 3 courses)
Despite the chemotherapy, his splenomegaly and hepatomegaly was not controlled, and the clinical course was also complicated with multiple infections.
He died 11 weeks after the diagnosis of HSTCL.

34. Adverse prognostic factors
Outcomes (n= 27) OS
Adverse prognostic factors
Elevated serum bilirubin
Expression of αβ TCR
Presence of trisomy 8
Yabe M, et al. Am J Surg Pathol in press

35. Take-home messages (3)
Prognosis is poor, but some patients achieve long-term survival
Adverse prognostic factors are
Elevated serum bilirubin
Expression of αβ TCR
Presence of trisomy 8
Long term survival could be achieved with allogeneic Stem Cell Transplant

36. Thank you