A Literal Investigation Into the Existence of Leiomyomatous Erythrocytosis and Secretion of Erythropoietin-Like Substances: A Systematic Review

Uterine leiomyomas, or fibroids, are a very frequent benign tumor in women of reproductive age. Erythrocytosis is an increase in the number of red blood cells, leading to polycythemia. Erythrocytosis as a paraneoplastic condition associated with leiomyomas is an area not well studied. This study aimed to investigate the production of erythropoietin-like substances in uterine leiomyomas and their association with secondary erythrocytosis, as well as to identify additional symptoms and complications beyond those traditionally associated with leiomyomas. A literature search was conducted using PubMed and EBSCO for articles published between 2009 and 2023. Eligible studies included case reports and clinical studies involving patients aged ≥25 years diagnosed with uterine leiomyoma complicated by polycythemia. Hematologic criteria for polycythemia and pathological evidence of erythropoietin or erythroid activity within the tumor were analyzed. Study selection and eligibility assessment were performed independently by two reviewers. Thirteen studies met the inclusion criteria, comprising 1 clinical study, 1 case series, and 11 case reports. Among the case reports, 11 described single cases, while one included 3 cases, and the clinical study involved 114 participants. All included cases demonstrated polycythemia in association with uterine leiomyoma, with a positive correlation observed between tumor size and erythrocytosis. Hematologic findings consistently showed elevated hemoglobin, hematocrit, erythropoietin levels, and increased red blood cell counts. Histopathological analyses, based on specimens obtained via tumor resection, hysterectomy, or salpingectomy, supported the presence of erythropoietin production within the leiomyomas. These findings are consistent with myomatous erythrocytosis syndrome (MES), a rare but well-documented condition. MES is not a common paraneoplastic syndrome of leiomyoma, but it is still an occurrence that has to be taken note of to avoid unnecessary testing. Future research should prioritize prospective studies systematically screening women with leiomyomata for erythrocytosis and the time of diagnosis; matched case-control studies comparing EPO expression and hematologic profiles between women with MES and those with leiomyoma alone; molecular studies characterizing the mechanisms of EPO-independent erythrocytosis in leiomyoma; and the development of clinical guidelines for the evaluation and management of MES-affected women.