Systemic cystic angiomatosis in pregnancy: A case presentation and review of the literature A. Bardeguez, MD, M. Chatterjee, MD, M. Tepedino, MD, and B. Sicuranza, MD Newark, New Jersey Systemic cystic angiomatosis is the involvement of multiple organ systems with a congenital vascular malformation. A combination of vascular anomalies, namely lymphangioma and hemangioma, can coexist. The liver, spleen, kidney, and colon are the most commonly affected organs. The clinical presentation varies and generally reflects the involved organ system. A case of systemic cystic angiomatosis involving the spleen, liver, and kidney is presented. The diagnosis and management during pregnancy is discussed. (AM J OBSTET GVNECOL 1990;163:42-5.)
Key words: Pregnancy, systemic, cystic, angiomatosis Lymphangiomatosis is a rare congenital malformation of the lymphatic system that generally is first seen during childhood and in young adults.' The term systemic cystic angiomatosis is used when the process involves multiple organ systems. The liver, spleen, kidney, and colon are the most commonly affected organs. Occasionally a combination of vascular anomalies, namely, lymphangioma and hemangioma, can coexist. Fink described the first case with spleen involvement in 1885. By 1979 fewer than 10 cases of systemic cystic angiomatosis that involved the spleen have been reported in the world literature. We present the first case of systemic cystic angiomatosis diagnosed with ultrasonography during pregnancy, a review of the literature, and our recommendation for management. Case report A 35-year-old white female, gravida 7, para 4, was first seen at 16 weeks' gestation with severe left upper quadrant pain of 3 months' duration associated with low-grade fever. Her medical history was significant for left nephrectomy in 1979 because of persistent hematuria. The pathologic findings were compatible with a cavernous hemangioma of the kidney. Physical examination on admission revealed a well developed female in moderate distress with a tender, mobile left upper quadrant mass with a lower edge that was palpable 12 cm below the left costal margin; the bowel sounds were normal. There was no evidence of lymphadenopathy. Fundal height was appropriate for 16 week's gestation and fetal heart rate was normal. From the Department of Obstetrics and Gynecology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School. Received for publication June 9, 1988; revised July 20, 1988; accepted December 29, 1989. Reprint requests: Arlene D. Bardeguez, MD, UMDNJ-New Jersey Medical School, Department of Obstetrics and Gynecology, 185 S. Orange Ave., E506, Newark, NJ 07103.
611 /19058
Initial laboratory data included the following: hematocrit 37%, platelet count 135,000, prothrombin time 9.2 (control 4.6), negative direct and indirect Coomb's test results, 0 positive blood type, and burr cells and decreased platelets on peripheral smear. Hemoglobin electrophoresis, hepatic and renal function studies, screening for collagen vascular disease, febrile agglutinins, carcinoembryogenic antigen, and 0:fetoprotein were all within normal limits. Bone marrow findings were consistent with normal cellularity. Abdominal ultrasonography confirmed an enlarged spleen with extensive cystic changes (Fig. 1). There was also an area of increased attenuation on the right aspect of the liver, suggestive of an intrahepatic lesion. Pelvic ultrasonographic examination confirmed a 16-week intrauterine pregnancy. The preoperative diagnosis was mild hypersplenism, probably a result of congenital cystic spleen. The patient underwent exploratory laparotomy at 18 weeks' gestation with general anesthesia. An enlarged spleen (615 gm) measuring 17 X 12 X 7 cm was found at surgery. The irregular external surface was characterized by multiple cysts that measured 0.5 to 7 cm in diameter and contained clear or hemorrhagic fluid. The histopathologic findings were compatible with mixed lymphangioma and hemangioma structures (Figs. 2A and 2B). The remainder of her pregnancy was uneventful. She had a normal spontaneous vaginal delivery of a male infant with Apgar scores of 9 and 10 at 1 and 5 minutes, respectively, and a birth weight of 3945 gm. Comment
Cystic lymphangiomatosis is a benign congenital vascular malformation frequently seen in infancy and childhood. Histologically it comprises cystic spaces of varying sizes lined by endothelium and surrounded by connective tissue. Any combination of capillary, venous, arterial, and lymphatic components can occur.' The pathogenesis of these lesions remains contro-
Systemic cystic angiomatosis in pregnancy
Volume 163 Number I. Part 1
43
Fig. 1. Ultrasonographic view of spleen illustrates hypersplenism and extensive cystic changes.
versial. Nevertheless some authors believe that these tumors develop as areas of localized lymphatic stasis because of a congenital blockage of the regional lymphatic drainage. There is a female preponderance of these tumors and 80% to 90% are detected before the end of the second year after birth.' If the lymphangioma is part of a generalized disorder with cystic involvement of many organs and tissues the term systemic cystic angiomatosis is used. Different organs have been involved including mesentery, liver, spleen, kidney, lung, mediastinum, pericardium, skeletal system, and somatic soft tissue. The clinical presentation varies depending on which organ system is involved." 2 Patients with splenic lymphangioma could be asymptomatic or symptomatic at the time of diagnosis. The most common symptom is left upper quadrant pain as a result of enlarging abdominal mass. Other signs and symptoms include nausea, vomiting, weight loss, hypertension, hypersplenism, and consumptive coagulopathy! This last complication is a result of platelet trapping within an angiomatous cyst. A dramatic resolution of the symptoms is generally observed after surgery. Our patient had involvement of three visceral organs-kidney, liver, and spleen. The clinical presentation at the time of admission was a result of the splenic involvement of the disease. The techniques currently in use of the evaluation of the spleen include arteriography, computerized tomography scan, scintigraphy, and ultrasonography. The radionuclide and computerized tomography scan can show splenomegaly with multiple focal defects. A "Swiss cheese" appearance on angiography has been
considered pathognomonic of splenic cystic lymphangiomatosis. Sonography is a simple and informative, noninvasive technique that can confirm the cystic nature of the lesion and identify involvement in other organs without the use of dyes or radiation. The differential diagnosis of cystic diseases of the spleen includes parasitic cysts, epithelial lined cysts, and malignancies. The preoperative workup in our patient was not suggestive of a malignancy, but the final diagnosis can be verified only after surgery.' One advantage of performing the surgery in a controlled situation is the prevention of splenic rupture later in pregnancy. This dangerous complication was first reported in a pregnant woman in 1803 by Saxtorph . Buchsbum reviewed 72 cases of splenic rupture during pregnancy and found that most of the affected patients were multiparous and 60% of the ruptures occurred during the third trimester or intrapartum. The presence of a malformed spleen carries a higher risk for spontaneous rupture. The maternal mortality in his series (15.4%) was a result of delay in diagnosis. The perinatal mortality was 70%, and in all cases of surviving infants the splenic rupture occurred before the third trimester. The postoperative complications of splenectomy are subphrenic abscess, thrombocytosis, and infection. Abscess formation is more common in patients undergoing splenectomy for trauma. The occurrence of thrombocytosis seems to be related to the underlying disease. Its incidence ranges between 7% to 70%. In general, patients with hypersplenism have a higher risk of this complication. Asplenic patients are also at risk of the development of overwhelming infections. This
44
Bardeguez et al.
July 1990 Am J Obslel Gyneco l
Fig. 2A. Histopathology of spleen illustrates multiple cystic changes on external surface.
Fig. 2B. Cysts are filled with clear or hemorrhagic fluid compatible with mixed lymphangioma and hemangioma of spleen .
increased predisposition to infection is a result of defective or decreased production of immunoglobulins, a delayed macrophage mobilization, and a defective phagocytosis of pathogenic bacteria. Therefore these patients must be followed up carefully and periodic immunizations should be given as necessary.
Our patient represents a case of symptomatic systemic cystic angiomatosis that was first seen during pregnancy. Sonographic evaluation confirmed the splenomegaly and revealed the cystic nature of that organ. A conservative approach was not advisable because the patient'S symptoms worsened during her stay
Systemic cystic angiomatosis in pregnancy
Volume 163 Number I, Part 1
in the hospital, a benign cause could not be confirmed without tissue pathology, and the possibility of splenic rupture at a more advanced gestational age. It is our belief that the maternal and fetal risks of an emergency splenectomy exceed those of a controlled secondtrimester laparotomy.
REFERENCES I. Asch MJ, Cohen AH, Moore TC. Hepatic and splenic Iymphangiomatosis with skeletal involvement: report of a case and review of the literature. Surgery 1974;76:334-9. 2. Dietz WH, Stuart MJ. Splenic consumptive coagulopathy in a patient with disseminated lymphangiomatosis. J Pediatr 1977;90:421-3.
Interrelationship between atrial natriuretic factor concentrations and acute volume expansion in pregnant and nonpregnant women Christos G. Hatjis, MD,.,c Alexander D. Kofinas, MD,. James P. Greelish, BA,. Melissa Swain, RN,. and James C. Rose, PhD·,b Winston-Salem, North Carolina, and Columbus, Ohio The secretion of atrial natriuretic factor by human atrial myocytes is stimulated by increased intraatrial pressure or atrial distention. To determine whether acute intravascular volume expansion affects atrial natriuretic factor concentrations during pregnancy, circulating atrial natriuretic factor levels were measured in pregnant women at term (before elective cesarean section) and nonpregnant control subjects before and dur:ng intravenous infusion of lactated Ringer's solution (approximately 30 ml/kg). Venous plasma concentrations of a-human atrial natriuretic factor were determined by a specific radioimmunoassay. A significant increase in a-human atrial natriuretic factor levels in nonpregnant subjects was seen. Pregnant women did not show a significant response to a similar stimulus. Finally, basal a-human atrial natriuretic factor levels in pregnant and nonpregnant women were not different. Volume expansion (long-term or short-term) in normal human pregnancy may not be sensed by atrial volume sensors, possibly because it is accommodated by an enlarged maternal vascular compartment. (AM J OBSTET GVNECOL 1990;
163:45-50.)
Key words: Maternal atrial natriuretic factor concentrations, nonpregnant women atrial natriuretic factor concentrations, volume expansion Atrial natriuretic factor (ANF) is a hormone secreted by specialized cells in atrial myocytes.' ANF demonstrates multiple circulatory and endocrine effects ranging from vasodilation and natriuresis to inhibition of aldosterone and renin production! Increased intraFrom the Departments of Obstetrics and Gynecology" and Physiology 1Pharmacology, b Bowman Gray School ofMedicine of Wake Forest University, and the Division of Perinatology, Riverside Methodist Hospitals.' This work was partially supported by the Bowman Gray School of Medicine United Way Venture Grant, Grant HD 17644 from the National Institutes of Health, United Cerebral Palsy Grant R-35687, and the March of Dimes Birth Defects Foundation. Received for publication January 12, 1990; accepted March 28,
1990.
Reprint requests: Christos G. Hatjis, MD, Director of Perinatology, Riverside Methodist Hospitals, 3535 Olentangy River Road, Columbus, OH 43214. 611121194
atrial pressure or atrial distention stimulates secretion of ANF. Physiologic or pathologic conditions of central hypervolemia that are secondary to intravascular volume expansion may result in increased secretion of ANF and high circulating levels of a-human ANF (ahANF).2 We have previously shown that during normal human pregnancy maternal ANF levels do not change with advancing gestation. 3 This lack of increase in the maternal plasma ANF concentrations occurs despite a presumed increment in plasma and blood volume during pregnancy. We therefore asked the question whether normal pregnant women at term can respond to an acute intravascular volume expansion with an increase in circulating maternal a-hANF levels and whether there is a difference between their response and that seen in nonpregnant control subjects.
45
Key words: Pregnancy, systemic, cystic, angiomatosis Lymphangiomatosis is a rare congenital malformation of the lymphatic system that generally is first seen during childhood and in young adults.' The term systemic cystic angiomatosis is used when the process involves multiple organ systems. The liver, spleen, kidney, and colon are the most commonly affected organs. Occasionally a combination of vascular anomalies, namely, lymphangioma and hemangioma, can coexist. Fink described the first case with spleen involvement in 1885. By 1979 fewer than 10 cases of systemic cystic angiomatosis that involved the spleen have been reported in the world literature. We present the first case of systemic cystic angiomatosis diagnosed with ultrasonography during pregnancy, a review of the literature, and our recommendation for management. Case report A 35-year-old white female, gravida 7, para 4, was first seen at 16 weeks' gestation with severe left upper quadrant pain of 3 months' duration associated with low-grade fever. Her medical history was significant for left nephrectomy in 1979 because of persistent hematuria. The pathologic findings were compatible with a cavernous hemangioma of the kidney. Physical examination on admission revealed a well developed female in moderate distress with a tender, mobile left upper quadrant mass with a lower edge that was palpable 12 cm below the left costal margin; the bowel sounds were normal. There was no evidence of lymphadenopathy. Fundal height was appropriate for 16 week's gestation and fetal heart rate was normal. From the Department of Obstetrics and Gynecology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School. Received for publication June 9, 1988; revised July 20, 1988; accepted December 29, 1989. Reprint requests: Arlene D. Bardeguez, MD, UMDNJ-New Jersey Medical School, Department of Obstetrics and Gynecology, 185 S. Orange Ave., E506, Newark, NJ 07103.
611 /19058
Initial laboratory data included the following: hematocrit 37%, platelet count 135,000, prothrombin time 9.2 (control 4.6), negative direct and indirect Coomb's test results, 0 positive blood type, and burr cells and decreased platelets on peripheral smear. Hemoglobin electrophoresis, hepatic and renal function studies, screening for collagen vascular disease, febrile agglutinins, carcinoembryogenic antigen, and 0:fetoprotein were all within normal limits. Bone marrow findings were consistent with normal cellularity. Abdominal ultrasonography confirmed an enlarged spleen with extensive cystic changes (Fig. 1). There was also an area of increased attenuation on the right aspect of the liver, suggestive of an intrahepatic lesion. Pelvic ultrasonographic examination confirmed a 16-week intrauterine pregnancy. The preoperative diagnosis was mild hypersplenism, probably a result of congenital cystic spleen. The patient underwent exploratory laparotomy at 18 weeks' gestation with general anesthesia. An enlarged spleen (615 gm) measuring 17 X 12 X 7 cm was found at surgery. The irregular external surface was characterized by multiple cysts that measured 0.5 to 7 cm in diameter and contained clear or hemorrhagic fluid. The histopathologic findings were compatible with mixed lymphangioma and hemangioma structures (Figs. 2A and 2B). The remainder of her pregnancy was uneventful. She had a normal spontaneous vaginal delivery of a male infant with Apgar scores of 9 and 10 at 1 and 5 minutes, respectively, and a birth weight of 3945 gm. Comment
Cystic lymphangiomatosis is a benign congenital vascular malformation frequently seen in infancy and childhood. Histologically it comprises cystic spaces of varying sizes lined by endothelium and surrounded by connective tissue. Any combination of capillary, venous, arterial, and lymphatic components can occur.' The pathogenesis of these lesions remains contro-
Systemic cystic angiomatosis in pregnancy
Volume 163 Number I. Part 1
43
Fig. 1. Ultrasonographic view of spleen illustrates hypersplenism and extensive cystic changes.
versial. Nevertheless some authors believe that these tumors develop as areas of localized lymphatic stasis because of a congenital blockage of the regional lymphatic drainage. There is a female preponderance of these tumors and 80% to 90% are detected before the end of the second year after birth.' If the lymphangioma is part of a generalized disorder with cystic involvement of many organs and tissues the term systemic cystic angiomatosis is used. Different organs have been involved including mesentery, liver, spleen, kidney, lung, mediastinum, pericardium, skeletal system, and somatic soft tissue. The clinical presentation varies depending on which organ system is involved." 2 Patients with splenic lymphangioma could be asymptomatic or symptomatic at the time of diagnosis. The most common symptom is left upper quadrant pain as a result of enlarging abdominal mass. Other signs and symptoms include nausea, vomiting, weight loss, hypertension, hypersplenism, and consumptive coagulopathy! This last complication is a result of platelet trapping within an angiomatous cyst. A dramatic resolution of the symptoms is generally observed after surgery. Our patient had involvement of three visceral organs-kidney, liver, and spleen. The clinical presentation at the time of admission was a result of the splenic involvement of the disease. The techniques currently in use of the evaluation of the spleen include arteriography, computerized tomography scan, scintigraphy, and ultrasonography. The radionuclide and computerized tomography scan can show splenomegaly with multiple focal defects. A "Swiss cheese" appearance on angiography has been
considered pathognomonic of splenic cystic lymphangiomatosis. Sonography is a simple and informative, noninvasive technique that can confirm the cystic nature of the lesion and identify involvement in other organs without the use of dyes or radiation. The differential diagnosis of cystic diseases of the spleen includes parasitic cysts, epithelial lined cysts, and malignancies. The preoperative workup in our patient was not suggestive of a malignancy, but the final diagnosis can be verified only after surgery.' One advantage of performing the surgery in a controlled situation is the prevention of splenic rupture later in pregnancy. This dangerous complication was first reported in a pregnant woman in 1803 by Saxtorph . Buchsbum reviewed 72 cases of splenic rupture during pregnancy and found that most of the affected patients were multiparous and 60% of the ruptures occurred during the third trimester or intrapartum. The presence of a malformed spleen carries a higher risk for spontaneous rupture. The maternal mortality in his series (15.4%) was a result of delay in diagnosis. The perinatal mortality was 70%, and in all cases of surviving infants the splenic rupture occurred before the third trimester. The postoperative complications of splenectomy are subphrenic abscess, thrombocytosis, and infection. Abscess formation is more common in patients undergoing splenectomy for trauma. The occurrence of thrombocytosis seems to be related to the underlying disease. Its incidence ranges between 7% to 70%. In general, patients with hypersplenism have a higher risk of this complication. Asplenic patients are also at risk of the development of overwhelming infections. This
44
Bardeguez et al.
July 1990 Am J Obslel Gyneco l
Fig. 2A. Histopathology of spleen illustrates multiple cystic changes on external surface.
Fig. 2B. Cysts are filled with clear or hemorrhagic fluid compatible with mixed lymphangioma and hemangioma of spleen .
increased predisposition to infection is a result of defective or decreased production of immunoglobulins, a delayed macrophage mobilization, and a defective phagocytosis of pathogenic bacteria. Therefore these patients must be followed up carefully and periodic immunizations should be given as necessary.
Our patient represents a case of symptomatic systemic cystic angiomatosis that was first seen during pregnancy. Sonographic evaluation confirmed the splenomegaly and revealed the cystic nature of that organ. A conservative approach was not advisable because the patient'S symptoms worsened during her stay
Systemic cystic angiomatosis in pregnancy
Volume 163 Number I, Part 1
in the hospital, a benign cause could not be confirmed without tissue pathology, and the possibility of splenic rupture at a more advanced gestational age. It is our belief that the maternal and fetal risks of an emergency splenectomy exceed those of a controlled secondtrimester laparotomy.
REFERENCES I. Asch MJ, Cohen AH, Moore TC. Hepatic and splenic Iymphangiomatosis with skeletal involvement: report of a case and review of the literature. Surgery 1974;76:334-9. 2. Dietz WH, Stuart MJ. Splenic consumptive coagulopathy in a patient with disseminated lymphangiomatosis. J Pediatr 1977;90:421-3.
Interrelationship between atrial natriuretic factor concentrations and acute volume expansion in pregnant and nonpregnant women Christos G. Hatjis, MD,.,c Alexander D. Kofinas, MD,. James P. Greelish, BA,. Melissa Swain, RN,. and James C. Rose, PhD·,b Winston-Salem, North Carolina, and Columbus, Ohio The secretion of atrial natriuretic factor by human atrial myocytes is stimulated by increased intraatrial pressure or atrial distention. To determine whether acute intravascular volume expansion affects atrial natriuretic factor concentrations during pregnancy, circulating atrial natriuretic factor levels were measured in pregnant women at term (before elective cesarean section) and nonpregnant control subjects before and dur:ng intravenous infusion of lactated Ringer's solution (approximately 30 ml/kg). Venous plasma concentrations of a-human atrial natriuretic factor were determined by a specific radioimmunoassay. A significant increase in a-human atrial natriuretic factor levels in nonpregnant subjects was seen. Pregnant women did not show a significant response to a similar stimulus. Finally, basal a-human atrial natriuretic factor levels in pregnant and nonpregnant women were not different. Volume expansion (long-term or short-term) in normal human pregnancy may not be sensed by atrial volume sensors, possibly because it is accommodated by an enlarged maternal vascular compartment. (AM J OBSTET GVNECOL 1990;
163:45-50.)
Key words: Maternal atrial natriuretic factor concentrations, nonpregnant women atrial natriuretic factor concentrations, volume expansion Atrial natriuretic factor (ANF) is a hormone secreted by specialized cells in atrial myocytes.' ANF demonstrates multiple circulatory and endocrine effects ranging from vasodilation and natriuresis to inhibition of aldosterone and renin production! Increased intraFrom the Departments of Obstetrics and Gynecology" and Physiology 1Pharmacology, b Bowman Gray School ofMedicine of Wake Forest University, and the Division of Perinatology, Riverside Methodist Hospitals.' This work was partially supported by the Bowman Gray School of Medicine United Way Venture Grant, Grant HD 17644 from the National Institutes of Health, United Cerebral Palsy Grant R-35687, and the March of Dimes Birth Defects Foundation. Received for publication January 12, 1990; accepted March 28,
1990.
Reprint requests: Christos G. Hatjis, MD, Director of Perinatology, Riverside Methodist Hospitals, 3535 Olentangy River Road, Columbus, OH 43214. 611121194
atrial pressure or atrial distention stimulates secretion of ANF. Physiologic or pathologic conditions of central hypervolemia that are secondary to intravascular volume expansion may result in increased secretion of ANF and high circulating levels of a-human ANF (ahANF).2 We have previously shown that during normal human pregnancy maternal ANF levels do not change with advancing gestation. 3 This lack of increase in the maternal plasma ANF concentrations occurs despite a presumed increment in plasma and blood volume during pregnancy. We therefore asked the question whether normal pregnant women at term can respond to an acute intravascular volume expansion with an increase in circulating maternal a-hANF levels and whether there is a difference between their response and that seen in nonpregnant control subjects.
45
