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A 72-year-old woman with metastatic, well-differentiated, small intestinal neuroendocrine tumor (NET) presented for routine follow-up in September 2020 with worsening fatigue and flushing. She was initially diagnosed with metastatic involvement of the liver, bone, and intra-abdominal lymph nodes in 2015 and received 3 treatments with peptide receptor radionuclide therapy (PRRT) in 2017. After 2 years of disease stability she was retreated with PRRT in November 2019 because of radiographic progression of disease and worsening symptoms. A third dose of PRRT was given in March 2020; a fourth was deferred owing to persistent thrombocytopenia after treatment. Gallium 68 dotatate positron emission tomography–computed tomography in July 2020 revealed stable disease (Figure, A).
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C. Neuroendocrine tumor infiltration of bone marrow
Hematopathologic analysis revealed a mildly hypocellular marrow (10%-20% cellularity) with erythroid predominant trilineage hematopoiesis. No overt morphologic dysplasia or blasts were recognized; however, multiple aggregates of tumor cells that stained strongly positive by immunohistochemistry for synaptophysin and chromogranin were noted, which confirmed metastatic involvement of the NET in the bone marrow. Reports of bone marrow metastases from well-differentiated NETs are rare; we found only 5 cases in the literature since 2009.1 Patients with solid tumor metastases to bone marrow typically present with thrombocytopenia, anemia, and elevated red cell distribution width and carry a poor prognosis.2 For this patient, extensive bone involvement from her NET may have predisposed her to develop bone marrow infiltration; this association, however, has not been described in patients with NET and diffuse bone metastases.
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Corresponding Author: Satya Das, MD, MSCI, Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, 777 Preston Research Bldg, 2220 Pierce Ave, Nashville, TN 37232 (firstname.lastname@example.org).
Published Online: April 29, 2021. doi:10.1001/jamaoncol.2021.0183
Conflict of Interest Disclosures: Dr Das reported being a previous member of the Ipsen Speakers’ Bureau outside the submitted work. Dr Berlin reported being on the data safety monitoring boards of AstraZeneca, Novocure, Pancreatic Cancer Action Network Investigational Drug Steering Committee, and National Cancer Institute; being on the advisory boards of AstraZeneca, QED, Bayer, EMD Serono, Ipsen, Rafael, Clovis, FivePrime, Seagen, LSK, and Eisai; and receiving clinical trial support to his institution from Novartis (Array), AbbVie, Immunomedics, Taiho, Genentech/Roche, Bayer, Lilly, Incyte, Five Prime Therapeutics, Loxo, EMD Serono, Boston Biomedical, PsiOxus, Macrogenics, Boston Biomedical, Symphogen, Pfizer, I-Mab, WuXi, Dragonfly, and the National Cancer Institute. Dr Savona reported receiving grants from Astex, Takeda, Incyte, and TG Therapeutics; personal fees from BMS, AbbVie, Geron, Karyopharm, Ryvu, Sierra Oncology, Taiho, and TG Therapeutics and Karyopharm equity outside the submitted work.
Additional Contributions: We thank the patient for granting permission to publish this information. Mary Ann Thompson Arildsen, MD, PhD (Vanderbilt University Medical Center), provided the bone marrow biopsy photomicrographs. She was not compensated for her contribution.
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