A 55-year-old woman with secondary polycythemia from uterine leiomyoma
A 55-year-old female with history of diabetes, hypertension, sickle cell trait and history of fibroid uterus presented to her primary care physician for preoperative evaluation to undergo hysterectomy.
She had a fibroid uterus for a long period of time and developed increasing lower abdominal discomfort a few months before presentation. Her gynecologist recommended hysterectomy because the discomfort was thought to be related to the large fibroid, causing mass effect in the pelvis.
During preoperative blood tests, her PCP noted very high hemoglobin level of 20.5 g/dL — corresponding to a hematocrit of 61.7% — and sought a hematology consult.
The woman had normal appetite, and she denied weight loss, fevers, night sweats, shortness of breath, chest pain or prior bleeding episodes. She had no history of blood clots, deep vein thrombosis or pulmonary embolism, miscarriages, leg swelling, pruritus, tingling, numbness, stroke or transient ischemic attacks.
She did not have any other constitutional symptoms. Her family history was unremarkable. She smoked two to five cigarettes per day. Physical examination was unremarkable except for a vague lower abdominal mass arising from the pelvis. No hepatosplenomegaly or lymph node enlargements were noted. She had a pelvic ultrasound and MRI of the pelvis, which showed a 23 cm x 16 cm x 20 cm lesion consistent with fibroids (see Figures).
However, careful review of her blood work showed she had an elevation in hemoglobin of 16.4 gm/dL about 1 year before her current presentation, and hemoglobin of about 18 gm/dL about 4 months prior.
Our differential diagnosis included primary and secondary polycythemia. She had a normal white blood cell count of 3.8 K/uL and a platelet count of 203 K/uL. Elevated white count and platelet count may suggest possibility of primary polycythemia, although absence of these does not exclude the diagnosis.
Workup for polycythemia vera was negative [serum erythropoietin: 24.6 mIU/mL (normal, 3.7 mIU/L to 31.5 mIU/L); vitamin B12: 654 pg/mL (normal, 211 pg/mL-911 pg/mL); JAK2 mutation analysis negative]. She had low arterial oxygen saturation with normal PaO2.
Source: Images courtesy of M. Ghesani, MD reprinted with permission.
We sought a tentative diagnosis of secondary polycythemia, possibly caused by uterine fibroids. Her smoking history of two to five cigarettes a day was low on the differential but could be contributory. Smoking cessation counseling was offered.
Before planned hysterectomy, we recommended phlebotomy for a target hematocrit of about 55% or less to reduce the incidence of hematological complications. Her use of aspirin, which she started many years ago given her underlying diabetes and hypertension, was stopped 1 week before surgery. She underwent phlebotomies before surgery and underwent total abdominal hysterectomy at a hemoglobin level of 17.2 gm/dL and hematocrit of 54.2%.
Pathology revealed a 30 cm x 22 cm x 15 cm, well-circumscribed, pink-tan mass with spindle cell proliferation consistent with uterine leiomyoma. She had an uneventful perioperative course. Three weeks after surgery, her hemoglobin was 12.9 gm/dL and her serum erythropoietin level was 7.9 mIU/mL.
Secondary polycythemia can be caused by a variety of erythropoietin-producing renal lesions and cancers.
Renal cysts, hydronephrosis, renal cell carcinoma, hepatocellular cancers and uterine myomas are known to cause increased erythropoietin secretion, thereby causing secondary polycythemia.
However, hypoxemia secondary to chronic pulmonary disease, sleep apnea, morbid obesity, cardiac shunts and high altitude also can cause physiological rise of hemoglobin levels to improve oxygen delivery to the tissues. Androgen use is another common cause of secondary polycythemia.
Myomatous erythrocytosis syndrome encompasses the triad of erythrocytosis, uterine myoma and resolution of erythrocytosis after hysterectomy. Fibroid-associated erythrocytosis occurs with an incidence of about 0.2% to 0.5%.
Multiple theories have been proposed as a cause of polycythemia in fibroid uterus. These include intra-uterine shunting; compression of the ureters, resulting in inappropriate excessive production of erythropoietin by the kidneys; tissue hypoxemia in the myomata, causing increased polycythemia, increased erythropoietin production or erythropoietin-like substance from the myomatous tissue; or increased life span of the red blood cells.
In a study published in Human Pathology in 2005, Pollio and colleagues suggested that the increased erythropoietin-receptor expression in the large uterine myomas in combination with erythropoietin could be the pathogenetic mechanism in the production of the unusually large tumor size.
Imaging cannot reliably differentiate between benign uterine leiomyoma and leiomyoma sarcoma. Although rapid growth rate has been associated with potential malignancy, recent studies have not substantiated this concept. Generally, leiomyomas present as an enlarged uterus with mass effect. Ultrasound will demonstrate a well-defined focal mass that is hypoechoic to myometrium, with blood flowing centripetally from the periphery with degeneration. However, the echotexture may appear heterogeneous.
On CT scan, leiomyomas appear homogenous to the uterus but may appear heterogeneous with hemorrhage, cystic degeneration, calcification or necrosis. On T1 weighted MRI images, leiomyomas will appear isointense to myometrium, with areas of high signal corresponding to blood products, and they appear hypointense on T2 weighted images. Areas of cystic degeneration will appear hyperintense on MRI images.
Preoperatively, most authors employ phlebotomy before surgery to decrease the incidence of possible hematological complications, such as excessive bleeding or thrombosis, although it is unclear if the risk of hematological complications is increased in secondary polycythemia. This is contrary to polycythemia vera, in which the risk for thrombosis and bleeding are increased with higher perioperative hemoglobin levels. However, there are some occasional case reports in which venous thrombosis has been reported with secondary polycythemia.
In conclusion, uterine myomas are a rare but not uncommon cause of erythrocytosis and should be considered in the differential diagnosis of secondary polycythemia. Diagnosis of the myomatous erythrocytosis syndrome should still be considered with normal serum erythropoietin levels, especially with levels closer to the high end of the normal values.
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Munir Ghesani, MD, is an attending radiologist at St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center, an associate clinical professor of radiology at Columbia University College of Physicians and Surgeons, and a HemOnc Today section editor. He can be reached at Department of Radiology, Beth Israel Medical Center, First Avenue at 16th Street, New York, NY 10003; email: firstname.lastname@example.org.
Rangaswamy Chintapatla, MD, is a fellow in hematology and oncology at St. Luke’s-Roosevelt Hospital Center.
Robert Hang, MD, is a radiology resident at St. Luke’s-Roosevelt Hospital Center.
Disclosure: Ghesani, Chintapatla and Hang report no relevant financial disclosures.