The significance of genetic mutations and their prognostic impact on patients with incidental finding of isolated del(20q) in bone marrow without morphologic evidence of a myeloid neoplasm.

Patients with a sole del(20q) chromosomal abnormality and without morphologic features of a myeloid neoplasm (MN) have shown variable clinical outcomes. To explore the potential risk stratification markers in this group of patients, we evaluated their genetic mutational landscape by a 35-gene MN-focused next-generation sequencing (NGS) panel and examined the association of mutations to progression of MNs. Our study included 56 patients over a 10-year period with isolated del(20q), of whom 23 (41.1%) harbored at least one mutation. With a median follow-up of 32.6 months (range: 0.1-159.1), 9 of 23 patients with mutation(s) progressed to MNs, while all 33 patients without mutations did not progress to MN. Kaplan-Meier survival analysis demonstrated the presence of mutation(s) as a significant risk factor for progression to MN (P < 0.0001). MN progression was strongly associated with the presence of non-DNMT3A/TET2/ASXL1 epigenetic modifiers and nonspliceosome mutations (P = 0.003). There was no significant difference among patients with and without MN progression with respect to the number of mutations, variant allele frequency, percentage of del(20q), and other clinical/laboratory variables. This study illustrates the underlying genetic heterogeneity and complexity of isolated del(20q), and underscores the prognostic value of NGS mutational analysis in these cases.

A Rare Case of Extramedullary Relapse of Multiple Myeloma Causing Bowel Obstruction.

Extramedullary myeloma, defined by presence of plasma cells outside the bone marrow, is a rare entity accounting for about 3-9% of all cases. It usually is aggressive with a median survival of <6 months. It is also associated with adverse prognostic factors including 17p deletions and high-risk gene profiles. While common extramedullary sites include bones, there have been several case reports of hematogenous extramedullary myeloma to the liver, lungs, pancreas, breast, skin, and soft tissues. Extramedullary myeloma to the mesentery is a rare entity with only a handful of cases reported. We present a case of 69-year-old man presenting with relapse of multiple myeloma to the mesentery, resulting in bowel obstruction to highlight the various presentations of myeloma.

Transient monosomy 7 in a chronic myelogenous leukemia patient during nilotinib therapy: a case report.

Tyrosine kinase inhibitor treated chronic myelogenous leukemia patients with monosomy 7 arising in Philadelphia chromosome negative (Ph-) cells tend to evolve into MDS/AML. However, monosomy 7 in Ph- cells can be a transient finding, and it is not an absolute indication of the emergence of a new myeloid malignancy.

Clinical course of patients with incidental finding of 20q- in the bone marrow without a morphologic evidence of myeloid neoplasm.

Deletion of the long arm of chromosome 20 (20q-) is a frequent finding in bone marrow karyotypes, mainly associated with myeloid neoplasms (MNs). Its clinical significance in the setting of normal bone marrow morphology is unclear. We described the clinical characteristics, cytogenetic findings, and outcome of 102 such patients seen at our institution from 2000-2014. Their median age was 66 years. The indication for bone marrow biopsy was either unexplained cytopenias (48%) or hematologic cancer staging/reevaluation (52%). In 88 (86%) patients, 20q- was an isolated finding. Thirty-nine (38%) patients previously received chemotherapy and 88 (86%) had cytopenias at the time of 20q- finding. After a median of 35 months, 12 (13%) patients developed MNs: 10 myelodysplastic syndromes, one acute myeloid leukemia and one myeloproliferative neoplasm. None of 14 patients with normal blood counts, but 7 of 35 (20%) with mild cytopenias, and 5 of 53 (9%) with moderate/severe cytopenias developed MNs. We did not find an association between the number of metaphases with 20q- and the development of MN. The incidental finding of 20q- in the bone marrow generally does not portend an early stage MN. Particularly, those without cytopenias at the time of diagnosis may have a good prognosis. Am. J. Hematol. 91:556-559, 2016. © 2016 Wiley Periodicals, Inc.

Increased Multinucleated Megakaryocytes as an Isolated Finding in Bone Marrow: A Rare Finding and Its Clinical Significance.

OBJECTIVES: Multinucleated megakaryocytes are a unique morphologic form of megakaryocytes characterized by multiple, distinctly separated nuclei. We investigated whether increased multinucleated megakaryocytes (≥25%) in otherwise normal-appearing bone marrow were associated with the development of a myelodysplastic syndrome (MDS). METHODS: We retrospectively reviewed the medical records and bone marrow biopsy specimens of patients evaluated at our institution from 2011 to 2015 that met all of the following criteria: (1) 25% or more multinucleated megakaryocytes, (2) no other dysplastic features, (3) absence of a myeloid neoplasm, and (4) absence of neoplastic karyotypic abnormalities. RESULTS: Nine cases of 19,885 bone marrow biopsy specimens were identified. The indications for bone marrow examination included plasma cell neoplasm, lymphoma, and cytopenia(s). All patients had anemia at the time the multinucleated megakaryocytes were found. No patients had thrombocytopenia or neoplastic karyotypic abnormalities. Follow-up was available for seven patients with a median of 27 months (range, 7-53 months). No patients developed progressive cytopenias or MDS. CONCLUSIONS: Multinucleated megakaryocytes (≥25%) as an isolated finding in the bone marrow are a rare phenomenon. These patients do not appear to be at increased risk of developing progressive cytopenia(s) or MDS. Caution should be taken to not overdiagnose these cases as MDS.