Submitting Author: Brooks, Sarah Ashley, MD
Institution: Medical University of South Carolina
Additional authors:Ana Maria Medina, MD, Michelle Hudspeth, MD, Natalie Mason, MD, Nicole Miller, DO, John Lazarchick, MD
Session: B Lymphoblastic Leukemia/Lymphoma

A male neonate was at an outside hospital born at 38 weeks gestational age. He was normal weight for his gestation and initially had Apgar scores of 7 and 9 at 1 and 5 minutes of life, respectively. At birth, he was noted to have a diffuse blueberry rash and massive hepatosplenomegaly on physical exam. A CBC showed markedly elevated white blood cell count at 450 K/Cumm with 100% blasts and thrombocytopenia with a platelet count of 32 K/Cumm. An abdominal x-ray showed nonspecific abdominal gaseous distention secondary to fluid or organomegaly. He was immediately transferred to our institution on day 1 of life for further treatment. He was intubated and underwent leukopheresis. The peripheral blood and cerebrospinal fluid were positive for blasts and are depicted in the images. The infant was given intrathecal chemotherapy, dexamethasone and pegaspargase; however due to hyperbilirubinemia the full course of treatment was not given. The patient’s clinical course continued to deteriorate becoming anuric with acute renal failure and placed on hemodialysis. Approximately one month after birth the patient was placed on palliative care and expired shortly after.

In utero, he had exposure to multiple medications until approximately 7 weeks gestation. The medication exposures include: pregabalin, venlafaxine, lorazepam, buprenrphine, bupropion, oxycodone, and diphenhydramine. His mother has a remote history of soft tissue sarcoma, but is otherwise healthy.

The peripheral smear shows an increased population of white blood cells predominantly composed of small to medium sized blasts characterized by homogenous chromatin, increased nuclear to cytoplasmic ratios, scant cytoplasm without granules, and occasional prominent nucleoli.

The cerebrospinal fluid cytology shows a cellular sample with many small and medium-sized blasts characterized by scant cytoplasm and homogenous chromatin. Red blood cells are seen in the background and the specimen may represent peripheral blood contamination

Flow cytometric analysis of the peripheral blood reveals approximately 95% of the white blood cell population as blasts expressing HLA-DR, dim CD15, dim CD19, CD38, and cytoplasmic CD79a, indicating precursor B-cell lineage. A subset of the cells also express CD10.

46,XY,del(3)(q12),dup(3)(q23q27),t(11;19)(q23;p13.3),add(17)(q25)[8]/46,idem,del(6)(q15q21)[2]/46,XY[7]

Cytogenetic analysis reveals a complex phenotype: deletion of 3q, a duplication of part of the other 3q, an 11;19 translocation, additional material on 17q, and deletion of 6q.

Fish confirms the presence of the rearrangement of the MLL gene and the presence of an extra copy of the chromosome 9 centromere

This is an interesting case due to the rare incidence of congenital acute lymphoblastic leukemia (ALL). ALL in infants is more often associated with a higher tumor burden at diagnosis, a rearrangement of the MLL gene, and very immature B-cell phenotype (pro-B-ALL) without CD10 expression.1 In our case the MLL gene was rearranged. Interestingly, by flow cytometric analysis, a subpopulation of the blasts expressed CD10. Infants with MLL translocations, particularly those <6 months of age, have a particularly poor prognosis.

References:

Van der Linden, M.H., Valsecchi, M.G. et al. Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol. Blood. 2009;114: 3764-3768.

Congenital B-cell Acute Lymphoblastic Leukemia with t(v;11q23) MLL rearranged

Congenital B-acute lymphoblastic leukemia with t(11;19)(q23;p13.3); MLL rearranged

Case 386