April 2017 Case Cedars-Sinai Skip to content Close Select your preferred language English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog English English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog Translation is unavailable for Internet Explorer Cedars-Sinai Home 1-800-CEDARS-1 1-800-CEDARS-1 Close Find a Doctor Locations Programs & Services Health Library Patient & Visitors Community My CS-Link Education clear Go Close Academics Academics Faculty Development Community Engagement Calendar Research Research Areas Research Labs Departments & Institutes Find Clinical Trials Research Cores Research Administration Basic Science Research Clinical & Translational Research Center (CTRC) Technology & Innovations News & Breakthroughs Education Graduate Medical Education Continuing Medical Education Graduate School of Biomedical Sciences Professional Training Programs Medical Students Campus Life Office of the Dean Simulation Center Medical Library Program in the History of Medicine About Us All Education Programs Departments & Institutes Faculty Directory Anatomic and Clinical Pathology Residency Back to Anatomic and Clinical Pathology Residency Application Information Explore the Residency Training Curriculum Autopsy Pathology Rotation Bone and Soft Tissue Head and Neck Pathology Rotation Breast Pathology Rotation Cardiovascular Pathology Rotation Clinical Chemistry Rotation Coagulation Rotation Cytopathology Rotation Dermatopathology Rotation Forensic Pathology Rotation Frozen Section Rotation Gastrointestinal and Liver Pathology Genitourinary Pathology Rotation Genomic Pathology Rotation Gynecologic Pathology Rotation Hematopathology Rotation Laboratory Management Rotation Microbiology Rotation Neuropathology Rotation Pulmonary and Mediastinal Pathology Rotation Renal Pathology Rotation Transfusion Medicine Rotation Surgical Pathology Pathology Physician Scientist Training Program Residents Graduates Case of the Month Archive Publications Leadership Frequently Asked Questions April 2017 Case Authors Cyrus Oster, MD (Fellow) and Mark Ewalt, MD (Attending) Subject Hematopathology Clinical History A 73-year-old female with a history of uterine adenocarcinoma treated with surgery and XRT in 2007 presents with slowly progressive macrocytic anemia and thrombocytopenia. Serum B12 and iron levels at the time of consultation were normal. A bone marrow biopsy was subsequently performed. Additional Studies A myeloid malignancies panel was performed by next generation sequencing (NGS) which demonstrated an SF3B1 K700E mutation with a variant allele fraction of 31.3%. Diagnosis Systemic mastocytosis with associated clonal hematological non-mast cell lineage disease (SM-AHNMD) Discussion Mastocytosis is a neoplastic clonal proliferation of mast cells which can occur in one or more organ systems. A diagnosis of systemic mastocytosis is rendered when the major criterion and one minor criterion or at least three minor criteria are observed as defined by the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2016). The major criterion for diagnosis is the presence of clusters of atypical mast cells with at least 15 mast cells forming aggregates. Minor criteria include greater than 25% of mast cells having spindle-shaped or otherwise abnormal morphology, greater than 25% of mast cells being immature or atypical, detection of KIT mutation, aberrant express of CD2 and/or CD25 in addition to normal mast cell marker expression and serum tryptase above 20 ng/mL in the absence of a clonal myeloid disorder. The atypical mast cell findings in this case are consistent with a diagnosis of systemic mastocytosis. The diagnosis of systemic mastocytosis with associated clonal hematological non-mast cell lineage disease (SM-AHNMD) is made when a clonal hematological non-mast cell lineage disorder is present that meets WHO criteria for a distinct entity. In this case the presence of anemia, significant dyserythropoiesis and ring sideroblasts seen in greater than 15% of marrow erythroid precursors is consistent with a diagnosis of myelodysplastic syndrome with ring sideroblasts (MDS-RS), formerly refractory anemia with ring sideroblasts (RARS). This was further supported by the SF3B1 mutation detected by NGS. Somatic mutations of SF3B1 are commonly associated MDS-RS and recent studies show that this mutation portends a favorable prognosis regardless of morphological classification. References 1. Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., Thiele, J., Vardiman, J.W. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC. 4th Ed. 2008 2. Malcovati, L., Karimi, M., Papaemmanuil, E., Ambaglio,I., SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblast. Blood. 2015 126:233-241; doi: https://doi.org/10.1182/blood-2015-03-633537 3. Alpermann, T., Jeromin, S., Haferlach, C., Kern, W., Schnittger, S., Haferlach, T. MDS and AML With ≥15% Ring Sideroblasts Share Overlapping Features In Cytogenetics But Demonstrate Different Patterns and Incidences Of SF3B1 mutations. Blood. 2013 122:2776 Have Questions or Need Help If you have questions or would like to learn more about the Anatomic and Clinical Pathology Residency Program at Cedars-Sinai, please call or send a message to Academic Program Coordinator, LeeTanya Marion-Murray. Department of Pathology and Laboratory Medicine 8700 Beverly Blvd., Room 8709 Los Angeles, CA 90048-1804 310-423-6941 send a message Please ensure Javascript is enabled for purposes of website accessibility