Fine Needle Aspiration Biopsy with Flow Cytometry Is a Reliable Method for Defining Immunophenotype of Prognostic Value in T Lymphoblastic Lymphoma.

In contrast to T lymphoblastic leukemia (T-ALL), there is a little data on the incidence and prognostic value of immunologic subtypes of adult T lymphoblastic lymphoma (T-LBL) as the use of flow cytometry in the absence of leukemia may be problematic. Our aim was to define immunophenotype of T-LBL and T-ALL in 51 consecutive patients by use of the flow cytometry (FCM) of tissue aspirates if peripheral blood (PB) and bone marrow (BM) were uninvolved. We also evaluated prognostic value of immunophenotype and clinical features of adult patients treated on uniform ALL protocol.

Between 1997 and 2006, 51 adult patients with T-LBL/ALL were treated according to the GMALL (German Multicenter Study Group for Adult ALL) 05/93 and T-LBL/2004 protocols (D.Hoelzer et al., Blood 2002; 99:4379). Immunophenotype was determined by specimen immunohistochemical staining and by FCM of cellular suspension obtained from lymph nodes (n=22), skin tumors (n=2) or mediastinal mass (n=9) by fine needle aspiration biopsy (FNAB), as well as of BM (n=6), PB (n=7) and pleural fluid (n=5). Disease subtype was defined according to WHO 2008 classification. Pro-T: cCD3+, CD7+, CD2-, CD1a-, CD34+/-; pre-T: cCD3+, CD7+, CD2+, CD1a-, CD34+/-; cortical T: cCD3+, CD7+, CD2+, CD1a+, CD34-, CD4+, CD8+; medullary T: cCD3+, sCD3+, CD7+, CD2+, CD1a-, CD34-, CD4+ or CD8+. Recognition of pan-T-cell CD antigens (pTAg) expression included: CD1a, CD2, cCD3, sCD3, CD4, CD5, CD7, CD8 and CD10, CD16&CD56, CD56, CD13, CD15, CD33.

Patients (pts) characteristics: ALL (BM+ >20%): 37%, LBL: 63%, age < 35: 80%, males: 75%, median WBC: 22 G/L, Hb: 13.6 g/dl, plt: 267 G/L, mediastinal mass (MM): 92%, primary CNS+: 10%, PS 0-1: 60%, LDH > normal: 69% of pts. Immunophenotype: pro-T: 20%, pre-T: 12%, cortical: 51%, medullary: 12%, blastic plasmacytoid dendritic cell neoplasm with skin manifestation: 6% of pts. Number of pTAg present: 0-3: 39%, and 4-7: 61% of pts. Most frequently expressed pTAg were: CD7: 86%, CD5: 78%, CD2: 69%, CD1a: 47%, and CD56: 59%. Myeloid markers: CD13/33/15 were expressed in 14%/23%/10% of pts. Complete and partial remission (mostly residual MM) rate was 75% and 21%. With a median follow up for surviving patients of 62 months, 5 yr overall (OS) and disease-free (DFS) survival (95%C.I.) was 45% (31%; 59%) and 46% (32%, 60%), respectively. 5 yr OS for pts with CD2 and more than 3 pTAg present was 61% and 63% compared to 7% and 19% for pts without CD2 and 3 or less pTAg, (p=0.004 and 0.025) respectively. CD1a expression was favorable but of unconfirmed significance (p=0.09). On Cox's analysis of clinical features, only PS and LDH were predictive for OS and DFS and only expression of CD2 among immunophenotypic variants was significant for OS (p=0.004) and DFS (p=0.004).

Combined use of fine needle aspiration biopsy and flow cytometry is a reliable method for defining immunologic subtype of lymphoblastic lymphoma. In a prospective evaluation of 51 consecutive T-LBL/ALL patients treated on GMALL protocols, expression of CD2 antigen – mostly consistent with cortical and pre-T subtypes, and presence of more than 3 pTAg along with PS less than 2 and normal LDH were predictive for favorable outcome.

No relevant conflicts of interest to declare.