Submitting Author: Hosking, Paul Robert, MD
Institution: Columbia University, New York, NY
Additional authors:Bachir Alobeid, Govind Bagat, Daniela Hoehn
Session: T Lymphoblastic Leukemia/Lymphoma

The patient is a 2-year-old previously healthy boy who had a 2 week history of abdominal distension, intermittent abdominal pain and low grade fever.

CBC revealed a markedly increased WBC, anemia, and thrombocytopenia (WBC: 210.3, Hb: 7.5, Platelets: 51, differential showing 85% blasts. LDH was markedly elevated at 1800).

Peripheral blood flow cytometry and bone marrow aspiration/biopsy were diagnostic of T lymphoblastic leukemia.

Post-induction bone marrow examination was negative, demonstrating morphologic, flow cytometric, and cytogenetic remission. While receiving consolidation therapy, approximately 8 months after diagnosis, the patient began to have worsening thrombocytopenia and was admitted to the hospital. He had abdominal pain, emesis and abdominal distension, and was found to have acute pancreatitis. A bone marrow examination was performed at that time.

Following this biopsy, the patient developed skin nodules, and nodules in the liver, spleen, and pancreas. The patient received a bone marrow transplant, and by day 20, had developed sinus, opthalmic and possible dural aspergillosis, renal insufficiency, pancytopenia, adenovirus pneumonia, and anasarca.

The patient expired 26 days after the bone marrow transplant.

Initial diagnostic bone marrow examination: A bone marrow trephine biopsy fixed in Bouin’s solution. The bone marrow aspirate was evaluated by morphology, cytogenetic analysis and flow cytometry.

On hematoxylin and eosin stained slides, the bone marrow showed 100% cellularity with numerous blast forms, comprising 70% of total cells.

Giemsa-Wright stained aspirate smears revealed a predominant leukemic blast population, 60% of all marrow nucleated elements, which had lymphoblastic morphologic characteristics.

Bone marrow examination performed 8 months after diagnosis: On hematoxylin and eosin stained slides, there was an extensive histiocytic infiltrate with cytologic atypia. Special stains for microorganisms (AFB and GMS), CMV immunostain, and EBERish for EBV were all negative.

Giemsa-Wright stained aspirate smears revealed numerous atypical histiocytes, frequently exhibiting hemophagocytosis. Large and atypical clusters of histiocytes were noted with occasional multinucleation. The myeloid series showed a left shift. The erythroid series showed a hyperplasia with normoblastic morphology. No lymphoblast cells seen.

Initial diagnostic bone marrow examination:

Flow cytometric analysis detected a large population of precursor T-cells (70%) with the following aberrant immunophenotype: TdT-, CD34-, HLA-DR+, CD1a+/- (68% of gated cells), sCD3+, cCD3+, CD2+, CD5+, CD7+, CD117-/+ (on a small subset), CD4-, CD8-, TCR-, CD10-, CD25-, CD30-, CD56-, and CD52+.

Bone marrow examination performed 8 months after diagnosis:

On immunohistochemical analysis, the infiltrating histiocytes were CD163++, CD68(PGM1)+, CD1a-, CD14+, Factor 13a+, fascin+, and S100 negative. The Ki-67 proliferation index in the area of interest was not high.

Flow cytometric analysis detected no leukemic lymphoblasts.

Initial diagnostic bone marrow examination:

G-banding karyotype analysis demonstrated the following karyotype: 46,XY,del(9)(p13)[7]/46,XY[20]

FISH analysis using the TEL/AML1, MLL, BCR/ABL, and p16/CEP 9 probes showed deletion of p16 in 31.5% cells. This is consistent with del(9)(p13).

Bone marrow examination performed 8 months after diagnosis:

G-banding karyotype analysis demonstrated normal karyotype: 46,XY[20]

FISH analysis using p16/CEP 9 probe showed no evidence of p16 deletion.

Initial diagnostic bone marrow examination:

Clonal TCR-Beta gene rearrangement, negative for clonal IgH gene rearrangement.

Bone marrow examination performed 8 months after diagnosis:

Negative for clonal IgH gene rearrangement.

POLYCLONAL products, consistent with a polyclonal T-cell population in the sample.

Note: The peaks previously identified as clonal in the initial diagnostic sample, are not seen significantly above the polyclonal background in the current sample. However, in light of the intensity and- position within the polyclonal range- of the peaks in the original sample, the sensitivity for the detection of this clone is probably low.

This case may represent trans-differentiation from a T-cell lymphoblastic leukemia to a clonal disorder of histiocytic lineage.

Atypical histiocytic proliferation with JXG phenotype post T-cell lymphoblastic leukemia.

Atypical histiocytic proliferation with JXG phenotype, in a patient with a history of T-acute lymphoblastic leukemia

Case 124