Myeloid/Lymphoid Neoplasm with FGFR1::ZMYM2 Rearrangement Presenting as T-Cell Acute Lymphoblastic Lymphoma with Concurrent Myeloproliferative Neoplasm: A Case Report.
This case report describes a 23-year-old woman with FGFR1::ZMYM2-rearranged T-lymphoblastic lymphoma and concurrent myeloproliferative neoplasm who received a pediatric ALL regimen, progressed to AML with sequentially identified CSF3R and PTEN variants, and died approximately 10 months after diagnosis without completing allogeneic transplantation.
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This case report describes a 23-year-old woman with FGFR1::ZMYM2-rearranged T-lymphoblastic lymphoma and concurrent myeloproliferative neoplasm who received a pediatric ALL regimen, progressed to AML with sequentially identified CSF3R and PTEN variants, and died approximately 10 months after diagnosis without completing allogeneic transplantation.
Research significance
The case supports prompt molecular diagnosis and early transplant evaluation in suspected MLN-FGFR1; it raises, but does not establish, the hypothesis that sequential CSF3R and PTEN alterations may mark or contribute to progression and that pediatric ALL-directed chemotherapy alone is insufficient for durable disease control.
Source abstract
Background: Myeloid/lymphoid neoplasms with FGFR1 rearrangement (MLN-FGFR1), also known as 8p11 myeloproliferative syndrome, are rare and aggressive hematologic malignancies arising from pluripotent stem cells. The FGFR1::ZMYM2 fusion resulting from t(8;13)(p11.2;q12) characteristically co presents as T-lymphoblastic lymphoma in lymph nodes alongside a myeloproliferative neoplasm in the bone marrow. The disease is resistant to tyrosine kinase inhibitors and conventional chemotherapy, and carries a median survival of less than 12 months without allogeneic hematopoietic stem cell transplantation (allo-HSCT). Case Presentation: We report a 23-year-old female who presented with progressive cervical lymphadenopathy and hyperleukocytosis (WBC 186.6 K/μL). Excisional lymph node biopsy demonstrated T-cell acute lymphoblastic lymphoma (T-ALL) with eosinophilic infiltration; immunohistochemistry confirmed lymphoblasts positive for CD1a, CD2, CD3, CD4, CD5, CD7, CD8, and TdT. Concurrent bone marrow biopsy showed a myeloproliferative neoplasm without excess blasts. Chromosomal analysis confirmed t(8;13)(p11.2;q12) with FGFR1::ZMYM2 rearrangement, and NGS identified a concurrent CSF3R variant (Q741*). She received induction chemotherapy per the PEDS AALL1231 protocol (Arm A) followed by consolidation, with a course complicated by hyperleukocytosis, venous thromboembolism, E. coli bacteremia, and severe mucositis requiring PICU admission. Despite initial response, the disease progressed to acute myeloid leukemia (AML) with acquisition of a PTEN variant; the patient was offered but did not complete allo-HSCT and died of refractory AML approximately 10 months after diagnosis. Conclusions: This case highlights the aggressive clinical course and diagnostic challenges of MLN-FGFR1, a rare stem cell-derived myeloid/lymphoid neoplasm. To our knowledge, this appears to be the first reported case documenting sequential CSF3R and PTEN variant acquisition with complete follow-up through fatal AML transformation, and the first to describe treatment with a pediatric ALL induction protocol (PEDS AALL1231) in this setting. The characteristic histomorphologic pattern of eosinophil-rich T-ALL in lymph nodes with concurrent myeloproliferative neoplasm in bone marrow should prompt immediate molecular workup. Allo-HSCT must be pursued urgently at diagnosis, as complications rapidly narrow the transplant window and the disease is uniformly fatal without it.