Extramedullary T-lymphoblastic Crisis in a Myelodysplastic/Myeloproliferative Neoplasm with a t(12;22)/MN1::ETV6 Translocation.

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are not a single disease, but rather a heterogenous group of entities which are increasingly subclassified according to recurrent genetic abnormalities. Chromosomal translocations involving meningioma 1 (MN1) and ETS variant 6 (ETV6) genes are extremely rare, but recurrent in myeloid neoplasms. We describe the case of a patient with a myelodysplastic/myeloproliferative neoplasm with neutrophilia, who developed an extramedullary T-lymphoblastic crisis with the t(12;22)(p13;q12) translocation as the only cytogenetic abnormality. This case shares several clinical and molecular features with myeloid/lymphoid neoplasms with eosinophilia. The treatment of this patient was challenging, as the disease proved to be highly refractory to chemotherapy, with allogenic stem cell transplantation as the only curative option. This clinical presentation has not been reported in association with these genetic alterations and supports the concept of a hematopoietic neoplasm originating in an early uncommitted precursor cell. Additionally, it stresses the importance of molecular characterization in the classification and prognostic stratification of these entities.

Leukaemic Ascites and Peritoneal Myeloid Sarcoma: Rare but Not Impossible.

A myeloid sarcoma is an extramedullary tumour arising from infiltration by leukemic cells at an anatomic site other than the bone marrow. Most commonly it precedes acute myeloid leukaemia but occasionally occurs simultaneously. It may also be associated with myeloproliferative neoplasms, myelodysplastic syndrome and the blast phase of chronic myeloid leukaemia. The most common sites for extramedullary tumours are bone, periosteum, soft tissue, lymph node and skin. Although this disease can affect a wide range of body sites, there are very few reports of peritoneal myeloid sarcoma or cavity effusion. The authors present the case of a 68-year-old man with myelodysplasia-related acute myeloid leukaemia and peritoneal myeloid sarcoma with myeloid ascites. The definitive diagnosis is challenging, requires a high level of suspicion, and relies on the exclusion of all alternative diagnoses and especially on complementary tests such as flow cytometry and immunohistochemistry analysis of ascitic fluid in order to detect the immature myeloid cells. LEARNING POINTS: Myeloid sarcomas are extramedullary leukemic tumours that occur before or simultaneously with acute myeloid leukaemia, other myeloproliferative neoplasms or myelodysplastic syndrome.Myeloid sarcomas are most often seen in bone, soft tissue, lymph node and skin, but can present in most locations.Peritoneal myeloid sarcoma and leukemic ascites, although very rare, must be searched for when a patient with acute leukaemia presents with newly diagnosed ascites, through ascitic fluid flow cytometry and immunophenotypic analysis.

Disseminated cutaneous lesions in an HIV-positive patient-Is there more than meets the eye?

A patient living with HIV developed disseminated erythematous plaques and the biopsy was consistent with hematological neoplasm infiltration. Further evaluation revealed hepatosplenomegaly, anemia, thrombocytopenia, and leukocytosis, with 33% myeloblasts. Bone marrow assessment confirmed acute myelomonocytic leukemia, with NPM1 mutation. The patient was treated with a conventional induction regimen obtaining complete remission.

Screening a Targeted Panel of Genes by Next-Generation Sequencing Improves Risk Stratification in Real World Patients with Acute Myeloid Leukemia.

Although mutation profiling of defined genes is recommended for classification of acute myeloid leukemia (AML) patients, screening of targeted gene panels using next-generation sequencing (NGS) is not always routinely used as standard of care. The objective of this study was to prospectively assess whether extended molecular monitoring using NGS adds clinical value for risk assessment in real-world AML patients. We analyzed a cohort of 268 newly diagnosed AML patients. We compared the prognostic stratification of our study population according to the European LeukemiaNet recommendations, before and after the incorporation of the extended mutational profile information obtained by NGS. Without access to NGS data, 63 patients (23%) failed to be stratified into risk groups. After NGS data, only 27 patients (10%) failed risk stratification. Another 33 patients were re-classified as adverse-risk patients once the NGS data was incorporated. In total, access to NGS data refined risk assessment for 62 patients (23%). We further compared clinical outcomes with prognostic stratification, and observed unexpected outcomes associated with FLT3 mutations. In conclusion, this study demonstrates the prognostic utility of screening AML patients for multiple gene mutations by NGS and underscores the need for further studies to refine the current risk classification criteria.

Rare Association Between Idiopathic Multicentric Castleman Disease, Nephrotic Syndrome and Polyneuropathy in an Immunocompetent Patient.

Multicentric Castleman disease (MCD) represents a group of poorly understood lymphoproliferative disorders related to proinflammatory hypercytokinaemia. In immunocompetent patients the aetiology is still unknown, hence the designation of idiopathic MCD (iMCD). To successfully diagnose iMCD, diagnostic criteria must be fulfilled and a large array of alternative diagnoses excluded. Peripheral neuropathy and nephropathy are relatively common findings in cases associated with POEMS syndrome, but very rarely reported in iMCD. We present the case of a 64-year-old man with iMCD (HIV- and HHV-8-negative) with nephrotic syndrome and severe motor polyneuropathy. Alternative diagnoses were excluded. The patient was treated with intravenous glucocorticoid followed by rituximab. Complete clinical and laboratory remission was achieved and maintained at the 2-year follow-up. LEARNING POINTS: iMCD is a lymphoproliferative disease in immunocompetent patients with no known cause.To diagnose iMCD major and minor criteria must be fulfilled, and alternative diagnoses must be excluded.Nephrotic syndrome and motor polyneuropathy are rare in iMCD and all alternative diagnoses must be excluded before relating all of these.

Clonal Hypereosinophilia with ETV6 Rearrangement Evolving to T-Cell Lymphoblastic Lymphoma: A Case Report and Review of the Literature.

Hypereosinophilia, either clonal or reactive, has been described in association with multiple hematological malignancies. We describe a case of a patient presenting with hypereosinophilia that evolved into T-cell lymphoblastic lymphoma. Complete remission was achieved with chemotherapy; however, hypereosinophilia recurred 5 months later in association with myeloblastic bone marrow infiltration and without evidence of lymphoblastic lymphoma relapse. Cytogenetic analysis of the bone marrow showed a complex translocation involving chromosomes 7, 12, and 16. A rearrangement of ETV6 gene (12p13) was demonstrated by FISH studies, thus confirming the clonality of this population. The association of lymphoblastic lymphoma, eosinophilia, and myeloid hyperplasia has been described in disorders with FGFR1 rearrangements. We hypothesize that other clonal eosinophilic disorders lacking this rearrangement could behave in a similar fashion through different pathogenic mechanisms.