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Targeted NGS on sequential bone marrow biopsies aids in the evaluation of cytopenias and monocytosis and documents clonal evolution-a proof of principle study.
Nann, Dominik; Rau, Achim; Mahmutovic, Lejla; Steinhilber, Julia; Meca, Vanessa; Federmann, Birgit; Vogel, Wichard; Bonzheim, Irina; Quintanilla-Martinez, Leticia; Fend, Falko.
Affiliation
  • Nann D; Institute of Pathology and Neuropathology, University Hospital Tuebingen and Comprehensive Cancer Center, Tuebingen, Germany.
  • Rau A; Institute of Pathology and Neuropathology, University Hospital Tuebingen and Comprehensive Cancer Center, Tuebingen, Germany.
  • Mahmutovic L; Institute of Pathology and Neuropathology, University Hospital Tuebingen and Comprehensive Cancer Center, Tuebingen, Germany.
  • Steinhilber J; Institute of Pathology and Neuropathology, University Hospital Tuebingen and Comprehensive Cancer Center, Tuebingen, Germany.
  • Meca V; Institute of Pathology and Neuropathology, University Hospital Tuebingen and Comprehensive Cancer Center, Tuebingen, Germany.
  • Federmann B; Institute of Pathology and Neuropathology, University Hospital Tuebingen and Comprehensive Cancer Center, Tuebingen, Germany.
  • Vogel W; Department of Peptide-Based Immunotherapy and Clinical Collaboration Unit Translational Immunology, Department of Internal Medicine, University Hospital Tuebingen, Tuebingen, Germany.
  • Bonzheim I; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Tuebingen, Tuebingen, Germany.
  • Quintanilla-Martinez L; Cluster of Excellence iFIT (EXC2180) "Image-Guided and Functionally Instructed Tumor Therapies", Tuebingen, Germany.
  • Fend F; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tuebingen, Tuebingen, Germany.
Virchows Arch ; 483(6): 835-845, 2023 Dec.
Article in En | MEDLINE | ID: mdl-37610626
ABSTRACT
Differential diagnosis of clonal versus reactive cytopenia and monocytosis, respectively, frequently presents a diagnostic challenge. With the two recent classifications of myeloid disorders, mutational analysis has gained importance as a diagnostic tool. However, reports on its utility on trephine bone marrow biopsies (BMB) are sparse. The aim of our proof of principle study was to determine the suitability of targeted sequencing for the longitudinal evaluation of cytopenia and monocytosis and demonstration of clonal evolution on sequential BMB. Seventy-seven EDTA-decalcified BMB of 33 patients with peripheral cytopenia and/or monocytosis, including at least one follow-up biopsy/patient, were included. Initial morphological diagnoses were idiopathic cytopenia of undetermined significance (ICUS, 8 cases), MDS (without blast increase, 7 cases), MDS with increased blasts/excess blasts (MDS-IB/EB) (11 cases), and CMML (7 cases). Thirty-one genes relevant for myeloid disorders were examined using two custom AmpliSeq NGS panels. Mutations were found in the initial BMB of 5/8 cases of ICUS, thus changing the diagnosis to clonal cytopenia of unknown significance (CCUS), 5/7 MDS, 10/11 MDS-IB/EB, and 7/7 CMML. Clonal evolution was observed in 14/33 (42%) cases, mostly associated with disease progression. None of the wild-type patients acquired mutations during follow-up. NGS-based mutation profiling is a robust diagnostic tool for BMB and provides valuable additional information, especially for cases with no/minimal dysplasia, and for better risk stratification of MDS. Tracking variant allele frequency and appearance of mutations over time allows for observing clonal evolution or relapse.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bone Marrow / Myelodysplastic Syndromes Limits: Humans Language: En Journal: Virchows Arch Journal subject: BIOLOGIA MOLECULAR / PATOLOGIA Year: 2023 Document type: Article Affiliation country: Alemania

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bone Marrow / Myelodysplastic Syndromes Limits: Humans Language: En Journal: Virchows Arch Journal subject: BIOLOGIA MOLECULAR / PATOLOGIA Year: 2023 Document type: Article Affiliation country: Alemania