Case 246

Submitting Author: Chabot-Richards, Devon S., MD
Institution: University of New Mexico
Additional authors:David R. Czuchlewski, Stuart Winter
Session: Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1

HISTORY

A 9-year-old male with a previous history of aortic coarctation (surgically repaired at age 4) presented to the urgent care clinic with rapidly enlarging bilateral cervical lymphadenopathy. Chest CT showed a small mediastinal mass as well as bilateral renal masses. The white blood cell count was 17.4 x 109/L, with 8% circulating blasts, a mild left shift (3% metamyelocytes, 1% myelocytes), neutrophilia (10.6 x 109/L), monocytosis (1.6 x 109/L), mild eosinophilia (0.5 x 109/L) and minimal basophilia (0.2 x 109/L). Red blood cell indices and platelets were within normal range (hemoglobin 14.0 g/dL and platelets 272 x 109/L). Biopsies of a right cervical lymph node and bone marrow were performed.

DETAILS

Blasts (35%) were present in a diffuse and interstitial pattern admixed with background myeloid and erythroid precursors and morphologically normal megakaryocytes. Bone marrow eosinophilia was not present. The blasts were intermediate to large in size with fine chromatin, discrete nucleoli, and scant cytoplasm. The lymph node showed complete architectural effacement by the blasts

IMMUNOHISTOCHEMISTRY AND FLOW CYTOMETRY

Flow cytometric analysis of both the lymph node and bone marrow showed an identical blast immunophenotype in both locations: expression of dim surface CD3, cytoplasmic CD3, CD2, CD5, CD7, partial coexpression of CD4/CD8, CD10, and dim CD45. The blasts did not express CD34, CD117, CD19, CD20, CD33, CD56, CD13, HLA-DR, or CD1a. Immunohistochemical stains showed the nodal infiltrate to be positive for CD3, CD99, and TdT. Cytochemical myeloperoxidase stain was negative.

CYTOGENETIC FINDINGS

Conventional cytogenetics revealed an abnormal karyotype: 47,XY,add(5)(q31),del(5)(q13q33),+mar[2], 46,XY[18] Because of the presence of additional chromosomal material at 5q31, the site of PDGFRB, additional FISH testing with a PDGFRB break apart probe was performed. This analysis showed separation of the fusion signal, indicating rearrangement of the PDGFRB locus.

MOLECULAR FINDINGS

NA

INTERESTING FEATURES

PDGFRB rearrangements have previously been associated with a diverse group of myeloid neoplasms with eosinophilia, most often with the appearance of chronic myelomonocytic leukemia and chronic eosinophilic leukemia. Historically, they were not identified in lymphoblastic neoplasms, however, recent case reports have described this finding in lymphoblastic lymphomas with accompanying myeloid neoplasms. In our case, the peripheral blood findings were not definitively diagnostic of a myeloid neoplasm. However, in light of these case reports, the mild to moderate neutrophilia, monocytosis, eosinophilia, and basophilia may suggest some myeloproliferative component. Our patient’s peripheral counts returned to normal after treatment directed at the lymphoblastic leukemia. The 2008 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues describes the entity of Myeloid Neoplasms with PDGFRB rearrangement, however, lymphoid malignancies with this finding are not addressed. Cases such as this indicate that this category may need to be expanded to include lymphoblastic neoplasms.

PROPOSED DIAGNOSIS

T lymphoblastic leukemia with abnormality of PDGFRB

CONSENSUS DIAGNOSIS

Myeloid and lymphoid neoplasm with PDGFRB rearrangement, presenting with T lymphoblastic leukemia/lymphoma