PDGFRB-rearranged T-lymphoblastic leukemia/lymphoma occurring with myeloid neoplasms: the missing link supporting a stem cell origin

Abstract

The 2008 WHO classification scheme of hematolymphoid neoplasms recognizes a category of myeloid and lymphoid neoplasms (MLNs) with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1.1 The postulated cell of origin for PDGFRA or FGFR1-rearranged diseases is a pluripotent progenitor capable of giving rise to myeloid neoplasms (myeloproliferative neoplasms and acute leukemias) and to lymphoblastic leukemia/lymphoma. Historically, PDGFRB translocations have not been associated with malignancies of the lymphoid lineage. Myeloid neoplasms with abnormalities of PDGFRB have been described to have hematologic features of chronic myelomonocytic leukemia (CMML), sometimes with eosinophilia, or as various other myeloproliferative and/or myelodysplastic neoplasms.2 In recognition of this distinction, the classification scheme designates specific categories of "MLNs" with PDGFRA and FGFR1 rearrangement, but omits the word "lymphoid" from the PDGFRBassociated entity.1 To call attention to the rare occurrence of lymphoid and mixed MLNs with abnormalities of PDGFRB, we present the clinical and pathological details of 2 cases. Case 1: MLN, eosinophilia, and RABEP1-PDGFRB fusion.A 64-year old man with splenomegaly and diffuse lymphadenopathy (supraclavicular, axillary, mediastinal, paraaortic, retroperitoneal, pelvic) was diagnosed with T-lymphoblastic lymphoma (T-LBL) on a left cervical lymph node (LN) biopsy. A complete blood count (CBC) showed anemia, thrombocytopenia and mild eosinophilia, but no blasts (Table 1). A staging bone marrow (BM) biopsy was abnormal, demonstrating features of a myeloid neoplasm with mixed myeloproliferative/myelodysplastic features but was not involved by T-LBL (Figure 1). He was treated with a vincristine/prednisone-based induction protocol for T-LBL. Following identification of a t(5;17)(q33;p13) in BM and confirmation of PDGFRB rearrangement in the LN and BM samples, imatinib 400 mg/day was added, but stopped after 18 days due to drug intolerance. Based on prior literature, fluorescence in situ hybridization (FISH) studies were subsequently performed that confirmed RABEP1 as the partner gene (Figure 1).

Systematic use of fluorescence in‐situ hybridisation and clinicopathological features in the screening of PDGFRB rearrangements of patients with myeloid/lymphoid neoplasms

“…PDGFRB rearrangements in myeloid and lymphoid neoplasms are rare, and disease characteristics have been determined from individual case reports or very small case series 7,10,11,25,26 . To date, only a few studies with >10 cases of PDGFRB ‐rearranged myeloid neoplasms have been published, and the studies were mainly focused on evaluating the response to imatinib or their molecular profiles 3–5,27,28 .…”

“…To date, only a few studies with >10 cases of PDGFRB ‐rearranged myeloid neoplasms have been published, and the studies were mainly focused on evaluating the response to imatinib or their molecular profiles 3–5,27,28 . PDGFRB rearrangements in B‐ALL are even more rare, and have only appeared in case reports 7–11,26 …”

“…It is noteworthy that, in recent years, some patients with B‐cell acute lymphoblastic leukaemia/lymphoma (B‐ALL) with PDGFRB rearrangement presented with de‐novo disease, without an underlying chronic myeloid neoplasm either prior to or after chemotherapy for B‐ALL. These B‐ALL cases are better classified as Philadelphia chromosome‐like (Ph‐like) B‐ALL, under the ABL‐class fusion kinase category 7 …”

Sustained Response to Imatinib in a Pediatric Patient with Concurrent Myeloproliferative Disease and Lymphoblastic Lymphoma Associated with a <b><i>CCDC88C-PDGFRB</i></b> Fusion Gene

“…The first description was of a concurrent acute myeloid leukemia and T-lymphoblastic lymphoma that was treated with chemotherapy and stem cell transplantation [4]. Two additional adult cases were reported, which were also treated with chemotherapy and stem cell transplantation [6]. The treatment with imatinib was started only after the identification of the PDGFRB rearrangement (one with RABEP1-PDGFRB and one with C6orf-204-PDGFRB ) in both the lymph node and BM samples and was successful in one patient.…”

The Diagnostic Work-Up of Hypereosinophilia

“…PDGFRB has been found rearranged to a large number of other partner genes [56][57][58][59][60] and such fusions are considered as uncommon variants. However, fusions that are typically associated with Ph-like B-lymphoblastic leukemia, such as EBF1-PDGFRB, SSBP2-PDGFRB, TNIP1-PDGFRB, ZEB2-PDGFRB, and ATF7IP-PDGFRB [61][62][63], are excluded from this category.…”