Case 235

Submitting Author: Gomez-Gelvez, Juan Camilo, MD
Institution: Henry Ford Health System
Additional authors:Kedar Inamdar, MD, PhD, Kristin Hunt-Karner, MD
Session: B Lymphoblastic Leukemia/Lymphoma

HISTORY

A 25-year-old female patient presented to the emergency department complaining of three days of bilateral lower extremity swelling and non-tender patchy areas of erythema with irregular borders, measuring approximately 3 cm each. Initial laboratory tests showed leukocytosis (WBC: 273.9 K/uL) with 85% blasts in the peripheral blood. D-dimer was >20,000 FEU and LDH was 563 IU/L. Fibrinogen, PT, PTT and INR were within normal limits. Negative Doppler ruled out the presence of deep vein thrombosis.

The patient underwent bone marrow biopsy at that time, and a diagnosis of B lymphoblastic leukemia/lymphoma was made (see below). The patient received treatment with hyper-CVAD and allogeneic non-related peripheral stem cell transplant and went into complete remission. However, 17 months after her initial diagnosis she presented with a mass on her left upper chest at the level of the second and third ribs which was diagnosed on biopsy as relapsed B lymphoblastic leukemia/lymphoma requiring additional chemotherapy with clofarabine. This occurred approximately six months ago and unfortunately the patient has been lost to follow-up since that time.

DETAILS

Right posterior iliac bone marrow biopsy fixed in Bouin’s and decalcified with hydrogen chloride solution.

The aspirate smears show large numbers of medium sized blast cells with scant agranular cytoplasm and large, round but occasionally irregular nuclei with inconspicuous nucleoli. A subset of the blasts has cytoplasmic vacuolization. Non-specific esterase (NSE) and Sudan Black Blue (SBB) stains are both negative in the blast population. Aspirate smears contained 80% lymphoblasts. Hematopoiesis was severely decreased (M:E Ratio: 3.5: 1.0) without evidence of dysplasia.

Decalcified biopsy and clot sections showed a markedly hypercellular bone marrow (overall cellularity >95%) that is nearly completely effaced by sheets of immature cells. A mature lymphoid aggregate was also present. Of note, the bony trabeculae appear markedly osteopenic for the patient's age.

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Flow cytometry showed the following immunophenotype for the blasts: positive for CD19 and HLA-DR with dim expression of CD15 and a subset positive for CD34. The blasts are negative for CD10, CD79a, TdT and all of the T-cell and myeloid lineage markers examined.

CYTOGENETIC FINDINGS

Fluorescent in-situ hybridization (FISH) found evidence of a “deletion or rearrangement” of 11q23 (MLL) in 123 out 200 interphase cells analyzed (61.5%) (One fusion signal and one 5’ MLL signal was present with absence of the second 3’ MLL signal).

FISH tests performed with probes 8q22(ETO), 15q22(PML), inc(16) or t(16;16)(CBFB), 17q21(RARA) and 21q22(AML1) were within normal limits.

Conventional karyotyping grew only 13 cells adequate for analysis and the MLL abnormality was not detected (46,XX [13]).

MOLECULAR FINDINGS

Not performed

INTERESTING FEATURES

This case represents a classic example of B-ALL with the MLL gene rearrangement in terms of the immunophenotype, although the age at presentation is older than usual and argues against a mutation in utero for this particular patient. After reviewing the pattern on flow cytometry including CD19+/CD10 neg/CD15+, an MLL rearrangement was suspected and later confirmed. When this pattern is seen, one should think of and investigate for the MLL gene rearrangement.

PROPOSED DIAGNOSIS

B lymphoblastic leukemia/lymphoma with MLL gene rearrangement.

CONSENSUS DIAGNOSIS

B-acute lymphoblastic leukemia with MLL gene rearrangement