Myomatous erythrocytosis syndrome: a uterine fibroid associated with polycythaemia

Abstract

Myomatous erythrocytosis syndrome (MES) is a rare form of secondary erythrocytosis seen with myomas. Here, we present a case of a postmenopausal, nulliparous woman in her 50s incidentally found to have asymptomatic erythrocytosis on routine laboratory work. She was found to have an 18.5 cm myoma and after surgical resection, the patient’s haematological values returned to normal ranges after a few weeks. This established the diagnosis as MES. The aetiology of MES continues to remain unknown but is most likely caused by an autonomous production of erythropoietin from the myomatous tissue. This case highlights obtaining a detailed history and physical examination to differentiate between the different causes of erythrocytosis, considering MES as a rare cause of secondary erythrocytosis and to prevent unnecessary procedures such as phlebotomy as surgery is the mainstay of treatment.

Background

Myomas, or uterine fibroids, are common benign tumours that affect 20% of women of childbearing age.¹ Uterine myomas have been associated with polycythaemia for seven decades, now called myomatous erythrocytosis syndrome (MES), with the first case described in 1953.² MES has an estimated incidence rate of 0.02%–0.5% and is associated with an abnormal increase in red cell count (RCC), haemoglobin (Hb) and haematocrit (Hct).³ The diagnosis of MES is done retrospectively as it requires erythrocytosis, a myoma and also the restoration of normal haematological values (ie, RCC, Hb and Hct) after surgical resection.³

Case presentation

A postmenopausal, nulliparous, woman in her 50s with a medical history of hypertension, fatty liver disease, obesity and type 2 diabetes mellitus was found to have incidental erythrocytosis during routine blood work. The patient reported increased fatigue for the past few months and more frequent nocturia in which she attributed to her older age. She denied any abdominal distention or pain. The patient’s vitals were normal and her body mass index was 35.22 kg/m². On physical exam, the patient’s abdomen was soft and flat, no abdominal distention was seen, and no mass was palpated. Bulging of the upper vagina was seen, consistent with pressure from a possible mass, and mild uterine prolapse without a visible cervix was seen on speculum exam. On bimanual exam, a uterine fundus approximately 2 cm above the umbilicus was palpated. Her laboratory values revealed normal white cell count of 6.0 x 10ˆ9 cells/L, elevated RCC of 6.7 x10ˆ12 cells/L, elevated Hb of 195 g/L, elevated haematocrit of 63%, with normal mean corpuscular volume of 93 fL. Repeat blood work several weeks later revealed similar, persistent erythrocytosis. When compared with labs 6 months prior, the patient had a normal Hb of 150 g/L and a haematocrit of 46.6%.

Investigations

On further evaluation, the patient was found to have slightly elevated erythropoietin (EPO) at 20 mU/mL (normal 2.6–18.5 mU/mL) and normal carboxyhaemoglobin of 1.2% (normal <2%). The patient was negative for JAK2 V617F and JAK2 exon 12–15 mutations. On physical exam on a subsequent visit, the patient had no visible cervix with bulging of the upper vagina most suspicious of a uterine mass. CT of the abdomen and pelvis revealed an enlarged uterus with a mass occupying nearly all of the dorsal myometrium. The uterus measured 22×15×17 cm (figures 1–3). Imaging suggested a myoma, although a malignant process was not completely excluded.

Figure 1.

Enlarged uterus with pelvic mass occupying nearly all of the entire dorsal myometrium.

Figure 2.

Sagittal view of the pelvic mass.

Figure 3.

Transverse view of the pelvic mass.

Differential diagnosis

The patient denied a recent history of dehydration, supplementation with EPO, blood doping, tobacco use, residing in a high-altitude environment or carbon monoxide exposure. She denied a medical history of renal issues including cysts, obstructive sleep apnoea, chronic cardiopulmonary disease and a family history of erythrocytosis, blood disorders or cancers. Furthermore, she denied confusion, headache, facial plethora, aquagenic pruritus and visual disturbances concerning for polycythaemia vera (PV).

Treatment

The patient underwent an exploratory laparotomy resulting in a total hysterectomy with salpingo-oophorectomy and bilateral ureterolysis due to the ongoing pressure from the pelvic mass, overall without complications (figure 4). On gross exam, pathology revealed that the majority of the myometrium and cervix were occupied by a well-circumscribed ovoid mass measuring 18.5×14×14 cm and weighing 2.5 kg (figure 5). On microscopic exam, the cervix was negative for HPV-associated changes and dysplasia. The endometrium appeared inactive and the uterine serosa was unremarkable. The smooth muscle tumours did not demonstrate atypical features. The ovaries demonstrated physiological structures without evidence of endometriosis or neoplasm and all other structures were unremarkable. Thus, this was consistent with the final diagnosis of a uterine myoma.

Figure 4.

Pelvic mass in situ during surgery.

Figure 5.

Large pelvic mass measuring 18.5×14×14 cm.

Outcome and follow-up

The patient’s haematological values returned to normal ranges 3 months after the surgery and continued to stay normal on subsequent follow-up appointments consistent with the diagnosis of MES. Furthermore, the patient has not experienced any recurrence of signs or symptoms to date.

Discussion

Women by the age of 50 have a 70%–80% lifetime risk of developing a myoma, which can be asymptomatic or present with abnormal uterine bleeding, pelvic pain and pressure or reproductive dysfunction.¹ Typically, nulliparous women, such as our patient, are at an increased risk for endometrial hyperplasia due to the increased exposure of unopposed oestrogen leading an increased risk for myomas. Our patient’s medical history of obesity, hypertension and type 2 diabetes likely increased her risk for developing a myoma as well. While it is common for myomas to persist after menopause, they usually shrink and become far less symptomatic. However, this contrasts with what has been seen with documented myomas presenting with MES and what was seen in our patient. In all 56 cases of previously reported MES cases aged 48.7±12.3 years, regardless of parity or menopausal status, there is no difference seen in incidence of MES.^{3 4} This suggests an autonomous process irrelated to the normal menstrual cyclicity and concomitant steroid levels. As more cases become known, perhaps these trends may change.

The pathophysiology and epidemiology of MES continue to remain uncertain.¹ What is seen is the aforementioned autonomous expression of EPO without negative feedback. EPO is a glycoprotein hormone primarily produced by the kidneys. EPO induces erythropoiesis and promotes the proliferation and differentiation of erythroid precursors in the bone marrow. The production of EPO in patients with MES has been seen to originate from the myoma and play a large role in the angiogenesis of the tumour, leading to their unusually large size.⁵ Unfortunately, immunostaining for EPO on the tissue was not done, but previous cases of MES show strong positive staining for EPO of the myoma. As a potential mechanism, Menzies described compression of the urinary tract by the myoma resulting in elevated renal parenchyma pressure causing EPO stimulation. This is why the surgeon along with the total hysterectomy with bilateral salpingo-oophorectomy (THBSO), performed the ureterolysis. Another mechanism suggested was compression of the renal vessels leading to renal hypoperfusion and EPO secretion.⁶ Of note, JAK2-STAT5 pathways are activated when EPO binds to its receptor. Mutations in these genes, JAK2 V617F or JAK2 exon 12–15, lead to the classic PV. However, none of the reported MES cases have had these mutations including our patient.³ The proposed role of EPO highlights the potential for targeted molecular therapy. A less invasive and effective therapy such as an EPO inhibitor or EPO-R antagonist delivered locally to the uterus has been proposed as a successful treatment for MES.³

The definitive treatment for MES is surgical. In all previous recorded cases, all patients underwent myomectomy or hysterectomy with concomitant resolution of their MES.³ Phlebotomy may be performed in symptomatic patients mainly due to hyperviscosity for relief of symptoms including headache, dizziness, mental slowing, fatigue, visual changes, dyspnoea and palpitations. There is insufficient evidence to recommend prophylactic aspirin as is with PV. Despite the patient’s age and her risk factors contributing to the formation of the myoma, THBSO was effective in treating her MES. THBSO was pursued due to her postmenopausal status, similar to previous reported cases of postmenopausal women, as it tends to be more minimally invasive and is generally considered to be lower risk compared with myomectomy. Our patient experienced complete resolution of secondary erythrocytosis within a few weeks.

Patient’s perspective.

The first time I found out was just on normal routine bloodwork that my PCP obtained. I had literally no idea that this was going on. I had no pain, no bleeding, and I was postmenopausal. I had some fatigue, but thought it was normal due to getting older. I also started to have to use the bathroom more often to urinate in the middle of the night. Again, I thought it was because I was getting older just like mom who would often have to urinate in the middle of the night because she had a small bladder. I didn’t feel any swelling of my belly at all. I was referred to hematology after repeat blood tests showed my hemoglobin still elevated. I was happy with how I was treated and how the hematologist worked quickly. In about 3 weeks, we found out what was the issue. Even before my abnormal labs, I was really worried because my father died from lymphoma in his 40s, so I was waiting for someone to tell me the big ‘C’ word (cancer) for a long time. However, from the hematologist to the gynecologic oncologist, they put my mind to ease that the fibroid was benign, and they worked quickly and concisely to resect the fibroid. I have healed well from the scars and am so happy that I have had no further issues.

Learning points.

• A detailed history and physical examination are essential to develop a comprehensive differential diagnosis for primary and secondary erythrocytosis.

• Timely and accurate diagnosis of myomatous erythrocytosis syndrome can prevent the patient from undergoing unnecessary treatments such as phlebotomy.

• Surgery is the mainstay of treatment where indicated and has been shown to result in a full recovery of erythrocytosis within a few weeks postsurgery.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).