Submitting Author: Hu, Shimin, MD, PhD
Institution: University of Texas MD Anderson Cancer Center
Additional authors:Shimin Hu, Ken H. Young, L. Jeffrey Medeiros, C. Cameron Yin
Session: Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1

The patient is a 45-year-old woman who presented with bilateral cervical lymphadenopathy in September 2008. A lymph node biopsy showed T-lymphoblastic lymphoma (T-LBL) with foci of myeloid differentiation. The bone marrow was not involved. She was treated with hyper-CVAD and achieved complete remission. The patient was subsequently started on maintenance therapy with oral 6-MP and methotrexate and monthly vincristine and prednisolone. The patient remained free of disease until December 2011 when she developed recurrent generalized lymphadenopathy, splenomegaly and intrapulmonary nodules, which was proved to be recurrent disease. The patient was started on FLAG chemotherapy. She came to our institution for stem cell transplant in May 2012.

Upon presentation at our institution, her WBC was 20.0 K/uL, hemoglobin 13.2 g/dL, platelet count 147 K/uL, with a differential count of neutrophils 69%, lymphocytes 21%, monocytes 2% and eosinophils 8%. Her lactate dehydrogenase level was 942 IU/L, and b2-microglobulin was 3.6 mg/L. Bilateral bone marrow aspiration and biopsy revealed hypercellular (80-90%) bone marrow with eosinophilia (10%). Biospy of a pelvic lymph node showed recurrent T-LBL. The patient was transplanted with a matched unrelated donor in May 2012, and has remained free of disease with last follow-up in September 2012.

Lymph node, left cervical, excisional biopsy (11/24/08): The lymph node was extensively infiltrated by malignant lymphoma. The neoplasm had a diffuse and starry sky pattern. The neoplastic cells varied from small to intermediate-sized and have blastic chromatin. Eosinophils were present. Mitotic figures were easily identified. Foci of myeloid differentiation was also present.

Bone marrow biopsies and smears, bilateral (03/30/12): The bilateral bone marrow was hypercellular (80-90%) with left-shifted granulocytic hyperplasia and eosinophilia. There was no significant increase in blasts.

Lymph node, left pelvis, needle biopsy (04/09/12): The core needle biopsy demonstrated atypical lymphoid infiltrate of predominantly intermediate-sized cells with fine chromatin.

Lymph node, left cervical, excisional biopsy (11/24/08): Immunohistochemical stains showed that the neoplastic cells were positive for CD3, CD10, BCL-2 and TdT, and negative for PAX-5, CD20, CD21, CD30, and EBV. A stain for Ki-67 was positive in >70% of the cells. The myeloid component was positive for lysozyme, CD68, and myeloperoxidase.

Bone marrow biopsies, smears, and peripheral blood (03/30/12): Flow cytometric analysis was negative for T-lymphoblastic leukemia/lymphoma.

Lymph node, left pelvis, needle biopsy (04/09/12): Flow cytometric analysis revealed an aberrant T cell population (90% of total cells) that was positive for CD1a, CD2, cytoplasmic CD3, CD4, CD5, CD7, CD8, CD26, CD52, CD56 (partial), and TdT, and negative for surface CD3, CD10, CD16, CD19, CD20, CD30, CD34, CD57, CD94, CD117, MPO, T-cell receptor alpha/beta and gamma/delta, and immunoglobulin kappa and lambda light chains.

Conventional cytogenetic analysis of the bone marrow collected on 03/30/12 showed:

46,XX,t(8;13)(p11.2;q12)[15]/47,idem,del(2)(q31q35),+mar[1]/46,XX,t(3;15)(q12;q26.3),del(4)(q13.1q33)[1]/46,XX[3].

No monoclonal T-cell receptor beta or gamma chain gene rearrangement was detected by PCR from the bone marrow specimen collected on 3/30/2012.

1. Lymph node biopsy showed T-LBL with eosinophilia and minor myeloid component.

2. Bone marrow was hypercellular with eosinophilia but was not involved by T-LBL by morphology, flow cytometry immunophenotypig and T-cell receptor gene rearrangement studies. However, cytogenetic analysis showed the presence of t(8;13)Ip11.2;q12).

Neoplasms associated with t(8;13)(p11;q12)/ZMYM2-FGFR1 commonly resemble T-lymphoblastic lymphoma but often exhibit evidence of myeloid differentiation. These patients can present with eosinophilia or have an associated myeloproliferative/myelodysplastic neoplasm, either at initial diagnosis or subsequently. A subset of these patients can evolve into acute myeloid leukemia. These neoplasms are also known in the literature by the commonly used term 8p11 myeloproliferative syndrome. The WHO classification uses the term myeloid and lymphoid neoplasm with fibroblastic growth factor receptor 1 (FGFR1) abnormalities.

T-lymphoblastic lymphoma with eosinophilia and t(8;13)(p11.2;q12)

Myeloid and lymphoid neoplasm with t(8;13)(p11.2;q12), presenting with T lymphoblastic lymphoma and myeloproliferative neoplasm with eosinophilia

Case 317