Juxtaglomerular cell tumor in pregnancy

associated with placental mesenchymal dysplasia. Placenta 1997;18:701– 6. 3. Moscoso G, Jauniaux E, Hustin J. Placental vascular anomaly with diffuse mesenchymal stem villous hyperplasia: A new clinico-pathological entity? Pathol Res Pract 1991;187: 324 – 8. 4. Sander CM. Angiomatous malformation of placental chorionic stem vessels and pseudo-partial molar placentas: Report of five cases. Pediatr Pathol 1993;13:621–33. 5. Hojberg KE, Aagaard J, Henriques U, Sunde L. Placental vascular malformation with mesenchymal hyperplasia and a localized chorioangioma: A rarity simulating partial mole. Pathol Res Pract 1994;190:808 –13. 6. Lee GK, Chi JG, Cha KS. An unusual venous anomaly of the placenta. Am J Clin Pathol 1991;95:48 –51. 7. Alwaidh MH, Woodhall CR, Carty HT. Mesenchymal hamartoma of the liver: A case report. Pediatr Radiol 1997; 27:247–9. 8. Chen CP, Chern SR, Wang TY, Huang ZD, Huang MC, Chuang CY. Pregnancy with concomitant chorioangioma and placental vascular malformation with mesenchymal hyperplasia. Hum Reprod 1997;12:2553– 6. Juxtaglomerular Cell Tumor in Pregnancy thirds of those tumors occurred in young women in their reproductive years. The average age of the reported women with a tumor is 21 years. According to our MEDLINE search from 1966 to 2000 using the terms “juxtaglomerular cell tumor” and “renal tumor,” no cases have been reported as occurring during pregnancy. We present a case of juxtaglomerular cell tumor diagnosed in a 16-week pregnant woman. Natalie L. Henderson, MD, and R. Carrington Mason, DO, FACS Methodist Medical Center, Dallas, Texas BACKGROUND: Although rare, two thirds of juxtaglomerular cell tumors of the kidney occur in young women in their reproductive years. CASE: A primigravid woman with a 6-year history of chronic hypertension was evaluated for the sudden onset of uncontrolled hypertension, proteinuria, and hypokalemia at 16 weeks’ gestation. An abdominal sonogram revealed a left flank mass, and magnetic resonance imaging confirmed that the mass was of renal origin. The worsening hypertension was not controlled with labetolol, methyldopa, nifedipine, or hydralazine, and required a nitroglycerine drip. The patient had left nephrectomy and subsequently miscarried at 19 weeks’ gestation. Her blood pressure gradually decreased and normalized within 6 months. A pathologic examination of the renal mass confirmed that it was a juxtaglomerular cell tumor. CONCLUSION: This tumor should be considered in the differential diagnosis as a cause of severe hypertension in pregnancy. (Obstet Gynecol 2001;98:943–5. © 2001 by the American College of Obstetricians and Gynecologists.) Since Robertson et al1 and Kihara et al2 reported the first two cases of juxtaglomerular cell renal tumors in 1967 and 1968, respectively, more than 50 cases of juxtaglomerular cell tumors have been reported to date. In a review of the first 38 cases, McVicar et al3 found that two Address reprint requests to: Natalie L. Henderson, MD, 1441 North Beckley, Dallas, Texas 75203; E-mail: [email protected]. Received February 5, 2001. Received in revised form March 29, 2001. Accepted June 21, 2001. CASE A 32-year-old primigravida with a 6-year history of untreated chronic hypertension presented for her first prenatal visit during the sixth gestational week at a rural clinic. Her blood pressure was in the 150/100 mmHg range. She was treated initially with methyldopa, and subsequently nifedipine and hydralazine were added to her medical therapy when she continued to have blood pressures of 150 to 160/100 to 110 mmHg. No autoimmune studies or 24-hour urine testing was done during that time. Urinalysis was negative for proteinuria, and dipstick urine proteins remained trace to mild during initial prenatal care. A first-trimester ultrasound confirmed the gestational age. At 16 weeks’ gestation, severe headaches and blurry vision developed despite the high doses of antihypertensive medications. Blood pressure was in the 230/150 mmHg range. She was transferred to our institution for further evaluation of uncontrolled malignant hypertension when her blood pressure was not controlled adequately with these combined medications. Her medical history confirmed that chronic hypertension had been diagnosed 6 years previously. At that time, her blood pressure was considered borderline by her primary care physician, and treatment was not initiated. No records of those visits are available, but she stated that she visited her physician yearly. She denied any history of hematuria or proteinuria, use of nonsteroidal VOL. 98, NO. 5, PART 2, NOVEMBER 2001 © 2001 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc. 0029-7844/01/$20.00 PII S0029-7844(01)01547-2 943 anti-inflammatory drugs, exposure to toxic agents, or known history of vasculitis. She had a family history of hypertension, but no known renal disease. Upon initial presentation at our hospital, results of physical and neurologic examinations were normal, except for severely elevated blood pressure. Fundoscopic examination was not recorded. Her hemoglobin was 13.6 g/dL, and a platelet count was 100,000 ⫻ 109/L. Results of coagulation studies were normal. Her potassium level was 3.0 mEq/L, serum urea nitrogen 8.0 mg/dL, creatinine 0.4 mg/dL, bilirubin 0.7 mg/dL, 24hour urine protein excretion 2.1 g, and creatinine clearance 129 mL/minute. Vanillylmandelic acid and catecholamine levels were normal. The plasma renin level was 37.6 ng/mL per hour (normal supine 0.2–2.3 ng/mL per hour). An aldosterone level was 89 ng/dL (normal less that 16 ng/dL). Her elevated liver enzymes were aspartate aminotransferase 153 U/L, alanine aminotransferase 166 U/L, and alkaline phosphatase 67 U/L. Antinuclear antibodies, antithrombin III, complement levels, thyroid functions, and Russell viper venom testing were normal. There was no cardiac enlargement or pulmonary or thoracic abnormalities on chest x-ray. An electrocardiogram was normal. Obstetric ultrasound revealed normal sized fetus at 15 weeks estimated gestational age weighing 137 g, which was consistent with her last menstrual period. A renal ultrasound showed the left kidney to measure 12.2 cm with a solid 3.6-cm mass in the upper pole. The right kidney was found to be unremarkable. Initially we were uncertain whether the mass was renal or adrenal in origin. Magnetic resonance imaging confirmed that the left-sided mass was an intrinsic renal mass. Shortly after arrival at our hospital, dizziness and altered mental status developed. Her blood pressure increased to 180/110 mmHg, and she was transferred to the intensive care unit. A nitroglycerine drip was started, which brought the blood pressure down to 140/90 mmHg. Her platelet count decreased to 70,000 (109/L), and schistocytes were present on the peripheral smear. Dexamethasone was started for the thrombocytopenia. The nitroglycerine drip was tapered over the next 2 days. She had a left radical nephrectomy without complication on hospital day 3. A 3.6 ⫻ 3.5 ⫻ 3.4-cm mass was found in the superior pole of the left kidney. Frozen section taken during surgery suggested a juxtaglomerular cell tumor. Two units of packed red blood cells were transfused intraoperatively. Her blood pressure remained elevated immediately after surgery. She received a large amount of crystalloid parenterally during surgery, which led to significant third spacing of these fluids. Diuresis ensued, but blood pressure remained 944 Henderson and Mason Juxtaglomerular Cell Tumor difficult to control postoperatively although her serum renin and aldosterone levels were within normal limits. Her diastolic blood pressure was maintained in the 90 – 100 mmHg range postoperatively with methyldopa, nifedipine, and hydralazine. She had a routine postoperative course and was discharged home from the hospital on postoperative day 4. During the antepartum follow-up, serum alpha-fetoprotein level was elevated. An obstetric ultrasound showed a small omphalocele or omphalomesenteric cyst of the fetus. She presented during the 19th week of gestation with intrauterine fetal death. She began to contract and subsequently delivered a macerated, 66-g fetus. This size is consistent with 16 weeks’ gestation, indicating probable growth retardation. No spina bifida, cleft lip or palate, or other external congenital anomalies were noted. There was no evidence of intrauterine infection. The patient declined a karyotype or autopsy of the fetus. Placental pathology showed only changes consistent with fetal demise. The patient’s blood pressure decreased gradually after delivery. She was weaned off of the blood pressure medications over several months. She is now in good health and does not require antihypertensive medications. To date, she has not attempted another pregnancy. COMMENT Juxtaglomerular cell tumor of the kidney is a rare type of renal tumor. Because these tumors tend to occur mainly in young women of reproductive age, it is important that early diagnosis and treatment be initiated in pregnant women with chronic hypertension and a possible juxtaglomerular cell tumor. Our patient had several of the typical features of that tumor, including a 6-year history of chronic hypertension before an acute exacerbation of hypertension. She presented with headaches and progressively uncontrolled hypertension at 16 weeks’ gestation. Renin and aldosterone levels were high, and she had hypokalemia. As was found in 50% of juxtaglomerular cell tumor cases, her blood pressure did not resolve with removal of the tumor. These findings are consistent with those of McVicar et al3 in 38 adult women who had symptoms for an average of 6 years before diagnosis. Unlike the cases reviewed by McVicar et al, this patient was older than the average patient (32-years-old versus 21 years.) Calcium-channel and beta blockers were used but did not control her hypertension. In case studies by McVicar et al3 and Kashiwabara et al4 nifedipine and beta-blockade agents were used successfully to control hypertension before surgery. Our patient required a nitroglycerine drip to decrease her pressures to OBSTETRICS & GYNECOLOGY tolerable levels before surgery. That treatment had been used in nonpregnant individuals.5 In our patient, the severity of the hypertension was exacerbated by the pregnancy. Renin levels in pregnancy are normally 5–10 times higher than in nonpregnant individuals (a maximum normal level of 23 ng/mL per hour). Aldosterone levels in pregnancy are normally elevated to the 10 –20 ng/dL range.6 This patient’s aldosterone level was 89 ng/dL. Moreover, she had increasing hypertension during the early second trimester, when diastolic pressure is generally lower than at other times during pregnancy.6 Selective renin sampling of the renal veins was not done because the tumor was accurately localized radiographically. If this patient had progressed to the third trimester of pregnancy, severe preeclampsia and HELLP (hemolysis, elevated liver enzyme, low platelets) syndrome likely would have been suspected because of the hypertension, proteinuria, hemolysis, elevated liver enzymes, and low platelets. Because this patient was in the early second trimester, HELLP syndrome was not a likely diagnosis, and another etiology was sought. Because the patient miscarried and blood pressure returned to normal, it is likely that the pregnancy exacerbated the severity of the hypertension associated with the renal tumor. Karyotyping was not done, so a genetic abnormality of the fetus might also have been the cause of the miscarriage. Juxtaglomerular cell tumors can exist during pregnancy and contribute to an unfavorable outcome. It is important to recognize this rare cause of hypertension in pregnancy, especially if renin and aldosterone levels are extraordinarily high. Preclinical Phase of Polycythemia Vera in Pregnancy During this pregnancy, phlebotomies, low molecular weight heparin, and low-dose aspirin treatments resulted in the delivery of a healthy baby. Damien Subtil, MD, Philippe Deruelle, MD, Nathalie Trillot, MD, and Brigitte Jude, PhD Hôpital Jeanne de Flandre and Hôpital Cardiologique, Centre Hospitalier Régional et Universitaire de Lille, Lille Cedex, France BACKGROUND: In some cases, complications of pregnancy are related to thrombophilia. We describe a preclinical phase of polycythemia vera. CASE: A woman, who experienced perinatal deaths in her first two pregnancies, was diagnosed with polycythemia vera during antenatal counseling for a third pregnancy. Address reprint requests to: Damien Subtil, MD, Hôpital Jeanne de Flandre, Clinique de Gynécologie, Obstétrique et Néonatalogie, CHRU de Lille, 1 rue Eugéne Avinée, Lille Cedex 59037, France; E-mail: [email protected]. REFERENCES 1. Robertson PW, Klidjian A, Harding LK, Walters G, Lee MR, Robb-Smith AHT. Hypertension due to a renin-secreting renal tumor. Am J Med 1967;43:963–7. 2. Kihara I, Kitamura S, Hoshimo T, Seida H, Watanabe T. A hitherto unreported vascular tumor of the kidney: A proposal of juxtaglomerular cell tumor. ACTA Pathol Jpn 1968;18:197–206. 3. McVicar M, Carmen C, Chandra M, Abbi RJ, Teichberg S. Hypertension secondary to renin-secreting juxtaglomerular cell tumor: Case report and review of 38 cases. Pediatr Nephrol 1993;7:404 –12. 4. Kashiwabara H, Inaba M, Itabashi A, Ishii J, Katayama S. A case of renin-producing juxtaglomerular tumor: Effect of ACE inhibitor or angiotensin II receptor antagonist. Blood Pressure 1997;6:147–53. 5. Aurell M, Rudin A, Tissel LE, Kindblom LG, Sandberg G. Captopril effect on hypertension in patient with renin-producing tumor. Lancet 1979;2:149 –50. 6. Gabbe SG, Niebyl JR, Simpson JL. Obstetrics: Normal and problem pregnancies. 3rd ed. New York: Churchill Livingston, 1996. Received February 6, 2001. Received in revised form April 3, 2001. Accepted June 21, 2001. CONCLUSION: Polycythemia vera is a rare condition in women of childbearing age and can exist in a preclinical phase for many years. During pregnancy, it can cause severe but preventable thrombotic complications of placental origin. (Obstet Gynecol 2001;98:945–7. © 2001 by the American College of Obstetricians and Gynecologists.) Severe complications of pregnancy can be of thrombophilic origin, and inherited coagulation defects have been shown to increase the risk of pregnancy failure.1 Polycythemia vera is a rare and chronic myeloproliferative disorder characterized by clonal proliferation of bone marrow progenitors. It is rarely associated with pregnancy. With an annual incidence estimated between six and 16 cases per million inhabitants, it affects men more frequently than women (sex ratio 1.2/1) and generally occurs after the sixth decade of life.2 VOL. 98, NO. 5, PART 2, NOVEMBER 2001 © 2001 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc. 0029-7844/01/$20.00 PII S0029-7844(01)01564-2 945