Yale University School of Medicine New Haven, CT, United States
Robert Lam, MD1, Nicholas Tarangelo, MD1, Masayasu Horibe, PhD2, Alyssa Grimshaw, MSLIS1, Samir Haffar, MD3, Fateh Bazerbachi, MD4, Darrick Li, MD, PhD5 1Yale University School of Medicine, New Haven, CT; 2Keio University School of Medicine, Chiyoda, Tokyo, Japan; 3Syrian Private University, Damascus, Dimashq, Syria; 4St. Cloud Hospital, St. Cloud, MN; 5Yale School of Medicine, New Haven, CT
Introduction: Microangiopathic hemolytic anemia (MAHA) is a rare paraneoplastic syndrome in patients with metastatic signet ring cell carcinoma. We conducted a systematic review to characterize the clinical presentation, evaluation, and outcomes of patients with signet ring cell carcinoma of gastrointestinal origin with evidence of MAHA.
Methods: We performed a systematic search of Cochrane Library, Embase, Google Scholar, Japan Medical Abstracts Society, Medline, Pubmed, Scopus, and Web of Science databases for studies that reported cases of signet cell carcinoma and MAHA on March 2nd, 2021. Risk of bias was assessed using Murad’s framework. Descriptive analyses including median (IQR) and proportions were performed.
Results: A total of 52 patients (median age 49, 65% males) with signet ring cell carcinoma (50 gastric, 2 colonic origin) and MAHA were identified among 33 publications. All patients had symptoms at time of evaluation, including back pain (27%), bone pain (25%), and dyspnea (21%). Laboratory studies were consistent with a consumptive, hemolytic process, specifically low hemoglobin (median 7.7g/dL, IQR 7g/dL), low platelets (median 44.5x103/µl, IQR 25.6x103/µl), high total bilirubin (median 2.0 mg/dL, IQR 2.0 mg/dL), and high LDH (median 809 IU/L, IQR 1045.5 IU/L). Peripheral blood smear often featured schistocytes (51%) and leukoeyrthroblasts (37%). MAHA was classified as disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura (TTP) in 88% and 12% patients respectively. Endoscopic diagnosis of signet ring cell cancer obtained in 75% of patients most commonly visualized ulcerations (50%) and diffuse infiltration (17%). All patients had stage IV disease at the time of evaluation. Metastases were most often identified to the bone (77%), followed by bone marrow (62%) and lymph nodes (48%). CT scan was preferred for staging and commonly showed evidence of bone lesions (45%) and lymphadenopathy (32%). Half of the patients did not receive any treatment. Patients who received chemotherapy (40%) had 5-FU or cisplatin-based regimens. Median survival was only 4 weeks (IQR 6.6 weeks), with 92% of patients dying over median follow up time of 4 weeks (IQR 8 weeks).
Discussion: MAHA is a rare, late-stage complication of signet ring cell gastrointestinal carcinomas with poor overall prognosis. Bony metastatic disease, including marrow infiltration, is common. Endoscopy, bone marrow biopsy, and CT imaging are useful diagnostic studies to identify the primary cancer.
Robert Lam indicated no relevant financial relationships.
Nicholas Tarangelo indicated no relevant financial relationships.
Masayasu Horibe indicated no relevant financial relationships.
Alyssa Grimshaw indicated no relevant financial relationships.
Samir Haffar indicated no relevant financial relationships.
Fateh Bazerbachi indicated no relevant financial relationships.
Darrick Li indicated no relevant financial relationships.
Robert Lam, MD1, Nicholas Tarangelo, MD1, Masayasu Horibe, PhD2, Alyssa Grimshaw, MSLIS1, Samir Haffar, MD3, Fateh Bazerbachi, MD4, Darrick Li, MD, PhD5. P2023 - Microangiopathic Hemolytic Anemia (MAHA) Is a Late and Fatal Complication of Metastatic Signet Ring Cell Gastrointestinal Carcinoma: A Systematic Review, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.