Submitting Author: Li, Ying , MD, PhD
Institution: University of Florida
Additional authors:Samer Z Al-Quran, Christopher Carter, Matthew Simmons, Ahmed Basem, Brian Gray
Session: Acute leukemias of ambiguous lineage

10-year-old Caucasian female presented with left cervical lymphadenopathy for a year and a half. The patient was treated with antibiotics and the lymphadenopathy resolved in approximately one month. She then presented again with painless bilateral cervical lymphadenopathy for three months, which was non-responsive to antibiotics. Laboratory studies (including CBC) revealed no abnormality. Infectious workup for toxoplasmosis, CMV, Lyme and Bartonella was negative and EBV testing was negative. Chest x-ray revealed no evidence of mediastinal mass. Ultrasound and right anterior cervical lymph node fine needle aspiration was non-conclusive. A full-body CT scan, including neck, chest, abdomen and pelvis, performed at readmission revealed extensive bilateral cervical, axillary and inguinal lymphadenopathy. The patient underwent an open biopsy.

Left neck, lymph nodes: formalin fixation

The lymph nodes show effaced nodal architecture and diffuse infiltration of neoplastic lymphoid cells. The neoplastic lymphoid cells are intermediate to large in size with scant cytoplasm, round to convoluted nuclei, fine chromatin, indistinct nucleoli and frequent mitosis.

Bone marrow biopsy: formalin fixation:

The bone marrow biopsy from the left side reveals cellular marrow (95-100% cellularity) with multilineage hematopoiesis. Increased numbers of immature mononucleated cells are identified. Immunostains for CD7 and CD34 showed <10% CD34/CD7-positive blasts.

Lymph node flow cytometry:

Flow cytometry analysis revealed a large population of leukemic blasts (74%), expressing CD7, dim CD5, CD2, CD34, CD117, CD11b, CD33, CD71, TDT, variable HLA-DR and cytoplasmic CD3. The blasts are negative for CD1a, CD4, CD8, or myeloperoxidase.

Cytochemical stain of cells of lymph node): The tumor cells were negative for myeloperoxidase or non-specific esterase.

Bone marrow flow cytometry:

The blasts represent approximately 7-8% of the total nucleated marrow cells by flow cytometry analysis, and they show similar levels of CD7, CD34 and cytoplasmic CD3. However, 40-50% of the blasts were positive for myeloperoxidase.

45,XX,der(5)t(5;12)(q22;q13),-7,-12,der(13)t(7;13)(q11.2;q34),+der(?)t(?;7)(?;p?15)[9]/46,XX[11]

Rearrangements affecting both long and short arms of chromosome 7 have been implicated in various forms of T-cell neoplasias. Such chromosome 7 rearrangements generally result in alterations of the TRB gene locus at 7q35 and/or the TRG gene locus at 7p15p14.

Molecular studies (TCR gamma gene rearangement) failed to detect evidence of clonal T cells.

The blasts in the lymph node expressed CD7, CD2, CD5, CD34, CD117, CD11b, CD33, TDT, variable HLA-DR and cytoplasmic CD3, without significant reactivity for myeloperoxidase or non-specific esterase. The expression of cytoplasmic CD3 defines the T cell lineage. The expression of CD11b, CD33 and HLA-DR is usually associated with myeloid differentiation, but they are not specific enough to define myeloid lineage differentiation. Therefore the tumor cells in the lymph node specimen are most consistent with precursor T cell acute lymphoblastic lymphoma with aberrant expression of multiple myeloid antigens.

However, the blasts detected in the bone marrow specimen showed significant expression of myeloperoxidase. 40-50% blasts show coexpression of CD34+, Cytoplasmic CD3 and myeloperoxidase. The expression of myeloperoxidase is considered as one of the critical parameters for defining myeloid differentiation. Therefore, the tumor cells identified in the bone marrow specimen may be classified as ambiguous lineage (T/myeloid) because of coexpression of cytoplasmic CD3 and myeloperoxidase. The T/Myeloid differentiation is generally considered as a poor prognosis, but data are limited on their outcome. Patients with T/myeloid tumor have not been treated uniformly.

This case demonstrates that the extent and direction of tumor cell differentiation may vary at different tissue environments. From the clinical presentation, we can assume that the tumor first presented in lymph nodes and then migrated into bone marrow. If we performed the bone marrow biopsy a few days later, we might, without knowing the immunophenotype of tumor cells in the lymph node, come to the conclusion of acute myeloid leukemia of ambiguous lineage (T/myeloid). On the other hand, if we obtained the lymph node biopsy a few weeks earlier before the patient had bone marrow involvement, the case would be classified as precursor T cell lymphoblastic leukemia.

Precursor T-cell acute lymphoblast lymphoma with myeloid differentiation in the bone marrow specimen.

T lymphoblastic lymphoma in lymph node, with bone marrow involvement by mixed phenotype blast population (T/myeloid)

Case 402