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
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
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: 0.0-1.0) ALP 240 IU/L (ref: 58-237) LDH 3163 IU/L (ref: 313-618) AST 67 IU/L (ref: 10-40) ALT 87 IU/L (ref: 15-46) B2M 3.8 mg/L (ref: 0.7-1.8)
BM aspirate Giemsa (x 500)
BM diff Blasts 34 % (0-5) Progranulocytes 0 % (2-8) Myelocytes 11 % (5-20) Metamyelocytes 9 % (13-32) Granulocytes 11 % (7-30) Eosinophils 2 % (0-4) Lymphocytes 7 % (3-17) Plasma cells 2 % (0-2) Monocytes 2 % (0-5) Pronormoblasts 1 % (1-8) Normoblasts 22 % (7-32) M:E Ratio 1.4 (3-4)
BM core Bx H&E (x 100)
CD3
CD4
CD8
TCRγ
βF1
Other Immunohistochemistry TIA-1 Negative Granzyme B Negative EBER Negative
Flow cytometry SSC CD4 CD8 CD45
CD2 CD7 CD5 CD26 TCR γδ CD56 CD57 TCR αβ
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
Proposed Diagnosis Hepatosplenic T-cell Lymphoma
Discussion HSTCL can be a mimic of T lymphoblastic leukemia/lymphoma Subset of HSTCL patients has underlying immune disorders Prognostic factors
Discussion HSTCL can be a mimic of T lymphoblastic leukemia/lymphoma Subset of HSTCL patients has underlying immune disorders Prognostic factors
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 ±
Morphologic Spectrum Small 18% Intermediate 43% Large 14% Blastoid 25% Yabe M, et al. Am J Surg pathol. 2016 in press
Lymphoma cell/prolymphocyte-like morphology T lymphoblastic leukemia/lymphoma Lymphoma cell/prolymphocyte-like morphology Blastoid Hepatosplenic T-cell lymphoma
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
Discussion HSTCL can be a mimic of T lymphoblastic leukemia/lymphoma Subset of HSTCL patients has underlying immune disorders Prognostic factors
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%)
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
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
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
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
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
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
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
Discussion HSTCL can be a mimic of T lymphoblastic leukemia/lymphoma Subset of HSTCL patients has underlying immune disorders Prognostic factors
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.
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. 2016 in press
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
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