Myomatous erythrocytosis syndrome

Overview

Myomatous Erythrocytosis Syndrome is a rare paraneoplastic condition in which a benign uterine tumor, typically a leiomyoma (commonly referred to as a fibroid), leads to secondary erythrocytosis—an abnormal increase in red blood cell (RBC) mass. This unusual association is caused by excessive production of erythropoietin (EPO), a hormone that stimulates RBC production, secreted ectopically by the fibroid tissue.

The condition is uncommon and primarily affects women of reproductive age or perimenopausal women, the same demographic that frequently develops uterine fibroids. Recognition of this syndrome is important because the erythrocytosis often resolves completely after surgical removal of the fibroid. Misdiagnosis can lead to unnecessary treatment for primary polycythemia, such as polycythemia vera, a hematologic malignancy.

Causes

The cause of Myomatous Erythrocytosis Syndrome is the abnormal secretion of erythropoietin (EPO) by uterine leiomyomas. Although leiomyomas are generally benign smooth muscle tumors, in rare cases they produce biologically active EPO, leading to increased red blood cell production by the bone marrow.

Pathophysiological Mechanism

• Ectopic erythropoietin production: The fibroid tissue synthesizes and secretes EPO, mimicking the physiological response of the kidneys to hypoxia.

• Autonomous stimulation: The excessive EPO acts on bone marrow erythroid progenitors, leading to elevated hematocrit and hemoglobin levels.

This paraneoplastic phenomenon is rare and usually reversible upon removal of the fibroid, indicating that the fibroid is the sole source of the abnormal erythropoietin.

Symptoms

Symptoms of Myomatous Erythrocytosis Syndrome arise from both the uterine fibroid and the effects of elevated red blood cell mass. The presentation can vary depending on the size of the tumor and the degree of erythrocytosis.

Symptoms Related to Uterine Fibroids

• Pelvic pain or pressure

• Menorrhagia (heavy menstrual bleeding)

• Increased abdominal girth or palpable mass

• Urinary frequency or constipation due to mass effect

Symptoms Related to Erythrocytosis

• Headache

• Dizziness or lightheadedness

• Visual disturbances

• Facial flushing or ruddy complexion

• Fatigue

• Increased risk of thromboembolic events (e.g., deep vein thrombosis, stroke)

In many cases, the diagnosis is made after incidental findings of elevated hemoglobin or hematocrit on routine blood work during evaluation for fibroid-related symptoms.

Diagnosis

Diagnosis of Myomatous Erythrocytosis Syndrome involves identifying both a uterine fibroid and unexplained erythrocytosis, followed by ruling out other causes of elevated red blood cell mass. A key diagnostic clue is the normalization of red blood cell parameters after fibroid removal.

Diagnostic Evaluation

• Complete blood count (CBC): Elevated hemoglobin and hematocrit levels

• Serum erythropoietin level: Often elevated, though levels may be normal in some cases

• Imaging studies:

  • Pelvic ultrasound or MRI to detect and characterize uterine fibroids

  • Abdominal imaging to rule out renal tumors or cysts that could produce EPO

• Bone marrow biopsy: Typically normal, used to exclude polycythemia vera if clinically indicated

• JAK2 mutation testing: Negative in secondary erythrocytosis, helps rule out polycythemia vera

Confirmatory Test

• Resolution of erythrocytosis following surgical removal (myomectomy or hysterectomy) confirms the diagnosis

Histological examination of the fibroid may also demonstrate EPO expression through immunohistochemistry, further supporting the diagnosis.

Treatment

The definitive treatment for Myomatous Erythrocytosis Syndrome is surgical removal of the fibroid. Management is focused on eliminating the source of ectopic EPO production and reducing the risk of complications from erythrocytosis.

Primary Treatment

• Myomectomy: Surgical removal of the fibroid, preserving the uterus, preferred in women desiring fertility

• Hysterectomy: Complete removal of the uterus, often curative in women who do not plan future pregnancies

Supportive Measures

• Phlebotomy: Temporary measure to reduce hematocrit in symptomatic or high-risk patients before surgery

• Anticoagulation: Considered if the patient is at risk for thrombosis due to significantly elevated hematocrit

Postoperative Monitoring

• Follow-up CBC to confirm normalization of hemoglobin and hematocrit

• No long-term hematologic therapy needed once fibroid is removed

Medical management of fibroids (e.g., GnRH analogs) may help control symptoms but is not a definitive solution for erythrocytosis.

Prognosis

The prognosis for Myomatous Erythrocytosis Syndrome is excellent when properly diagnosed and treated. Surgical removal of the fibroid results in complete resolution of erythrocytosis in nearly all cases, with no recurrence as long as new EPO-secreting fibroids do not develop.

Favorable Prognostic Factors

• Timely diagnosis and surgical intervention

• Absence of thrombotic complications before treatment

• No underlying hematologic or neoplastic disease

Potential Complications (if untreated)

• Thromboembolic events (stroke, pulmonary embolism, DVT)

• Hypertension or cardiovascular strain due to increased blood viscosity

• Misdiagnosis leading to unnecessary treatments for primary polycythemia

With appropriate management, most women experience full recovery with no long-term hematologic abnormalities. Awareness of this rare syndrome is essential to avoid misdiagnosis and to provide a curative approach through surgery.