Submitting Author: Torlakovic, Emina Emilia, MD, PhD
Institution: University Health Network/University of Toronto
Additional authors:Ken Craddock, Raheela F Siddiqui, Anna Porwit
Session: B Lymphoblastic Leukemia/Lymphoma

No previous history of hematological disease. Presentation with thrombocytopenia and circulating blasts. Male patient, 61-year old with bilateral axillary and extensive retroperitoneal adenopathy with mild splenomegaly. Clinical impression was lymphoma. However, because of the circulating blasts, the patient first underwent bone marrow biopsy. Lymph node biopsy was not performed. Labs: Hb 111 g/L, WBC 8.5 x x10e9/L, Plt 14 x 10e9/L, Blasts 31%.

Bone marrow aspirate and biopsy.

The tissue biopsy was fixed in IBF and decalcified with RDO for 1 h. Our minimum fixation time is 4 hours. Aspirate was processed as smears and samples were forwarded for flow cytometry, molecular, and cytogenetic analyses.

Aspirate smears showed sheets of blasts consistent with lymphoblasts. There were about 50% blasts.

Similarly, the bone marrow core biopsy showed hypercellular bone marrow with sheets of blasts and some residual evidence of hematopoiesis.

Flow cytometry detected two aberrant populations:

Population A (70% of gated blasts):

CD20 dim, CD38 bright, CD10+, cCD79a+ (moderate), TdT dim, and no definite evidence of surface Ig expression.

Population B (28% of gated population):

CD20 bright, Cd38+/-, CD10-, cCD79a+ bright, TdT-, surface Ig+ moderate

Immunohistochemistry:

Morphological blasts: CD20-, CD10+++, Pax-5+/+++, CD79a+, CD45-, TdT unclear

Morphological peri- to para-trabecular infiltrate: CD45+++, CD20+++, CD79a+++, TdT-, and most likely CD10-.

Results of G-banded karyotype:

All 10 metaphases showed abnormal clonal proliferation with t(8;22), t(14;18), and t(3;13)(q27;q14), +18, +i(1)(q10).

Results by interphase FISH:

Positive for MYC rearrangement, positive for IGH-BCL2 rearrangement; positive for BCL6 rearrangement.

Not performed.

The 2008 WHO Classification suggests that lymphoblastic lymphoma needs to be differentiated from the “blastic”/”blastoid” cases of double and triple hit lymphomas from the B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.

Our case illustrates that triple-hit lymphomas may have both, lymphoblastic morphology and immunophenotype (bright CD38, bright CD10, dim CD20, no surface Ig, and dim TdT but this we could not confirm by IHC). The presence of a smaller mature B-cell population that was detected by flow and also by IHC predominately in peri- and para-trabecular localization, suggests origin in follicular lymphoma, but origin in de novo double-hit mature B-cell process cannot be ruled out.

Triple-hit B-cell lymphoproliferative disorder with B-lymphoblastic features and an additional mature B-cell lymphoproliferative disorder suggestive of follicular lymphoma. Alternatively, the triple-hit lymphoblastic process progressed from de novo double-hit mature B-cell process.

Additional immunostains performed by the conference consensus group:

PAX5: Strongly positive
TdT: Negative
Ki-67/Mib-1: Positive in 80-90% of nuclei
BCL6: Suboptimal study, appears to be dimly positive

High-grade TdT-positive blastic B-cell leukemia/lymphoma with t(8;22), t(14;18), and t(3;13)(q27;q14); probable transformation of follicular lymphoma

Case 159