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A 50-Year-Old Woman With Uterine Myomatosis, Rapidly Progressive Dyspnea, and Lower Extremity Edema
[
Pulmonary, Critical Care, and Sleep Pearls
]
A 50-Year-Old Woman With Uterine Myomatosis, Rapidly Progressive Dyspnea, and Lower Extremity Edema José de Jesús Rodriguez-Andoney, MD; Luis Alfonso Castillejo-Adalid, MD; Eduardo Rivero-Sigarroa, MD; José Luis Hernandez-Oropeza, MD; Roberto Redding-Ochoa, MD; and Guillermo Dominguez-Cherit, MD
A 50-year-old woman with morbid obesity (BMI, 49 kg/m2) was admitted to the ED due to shortness of breath triggered by mild to moderate efforts over the previous 3 weeks that rapidly progressed to dyspnea at rest and became associated with oppressive chest pain and edema of the lower extremities. Four months prior to admission, she had been diagnosed with a uterine mass (18 21 cm2) suggestive of a leiomyoma, manifesting with abnormal vaginal bleeding and microcytic hypochromic anemia (Fig 1).
CASE PRESENTATION:
CHEST 2019; 156(3):e69-e72
Physical Examination Findings The patient’s vital signs were normal except for a heart rate of 104 beats/min. Jugular vein distention of 8 cm was observed, and cardiopulmonary auscultation was normal. Abdominal examination showed a nonstrangulated abdominal wall hernia, a diffusely palpable mass in the lower abdomen, and edema of the lower extremities (grade 3þ).
Diagnostic Studies The ECG revealed sinus tachycardia and her laboratory tests showed the following: hemoglobin, 10.2 g/dL (> 13 g/dL); mean corpuscular volume, 64.8 fL (83-98 fL); mean corpuscular hemoglobin, 27.8 pg (27-34 pg); creatinine, 0.79 mg/dL (0.6-1.2 mg/dL); BUN, 12.9 mg/dL (7-25 mg/dL); brain natriuretic peptide, 453 pg/mL (< 100 pg/mL); troponin I, 0.01 ng/mL (< 0.02 ng/mL); and arterial blood lactate, 4.2 mmol/L (< 2 mmol/L). AFFILIATIONS: From the Critical Care Medicine Department (Drs Rodriguez-Andoney, Rivero-Sigarroa, Hernandez-Oropeza, and Dominguez-Cherit), Pulmonary Hypertension Clinic (Drs RodriguezAndoney, Castillejo-Adalid, and Hernandez-Oropeza), the Pathology Department (Dr Redding-Ochoa), Instituto Nacional de Ciencias Médicas y Nutricion Salvador Zubiran, Mexico City, Mexico; and Tecnologico de Monterrey (Drs Dominguez-Cherit and Rivero-Sigarroa), Mexico City, Mexico.
chestjournal.org
Figure 1 – Abdominal CT scan showing the uterine mass.
An echocardiogram revealed a thrombus-like mass originating in the inferior vena cava (IVC) and protruding toward the right atrium, measuring 65 36 mm2, mobile, and nonadherent to the atrial wall. The CORRESPONDENCE TO: Guillermo Dominguez-Cherit, MD, Av Vasco de Quiroga 15, Col Seccion XIV, Tlalpan, Ciudad de Mexico, Mexico, 14080; e-mail: [email protected] Copyright Ó 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: https://doi.org/10.1016/j.chest.2019.05.018
e69
Figure 2 – A-C, CT scan showing the uterine mass (green asterisk) with no involvement of the inferior vena cava or heart, obtained 4 months prior to admission. D-F, CT scan showing the tumor occupying the inferior vena cava (yellow asterisk) and involvement of the right heart cavities (red asterisk), and the renal and left gonadal veins (white arrows).
mass also protruded toward the right ventricle and led to intermittent blood flow obstruction. A CT scan showed the previously diagnosed pelvic mass and a new intravascular lesion in the IVC, cephalically extending toward the right side of the heart as well as caudally toward the renal and left gonadal veins (Fig 2).
What is the diagnosis?
e70 Pulmonary, Critical Care, and Sleep Pearls
[
156#3 CHEST SEPTEMBER 2019
]
Diagnosis: Intravascular leiomyomatosis Discussion Intravascular leiomyomatosis (IVL) is a variant of uterine leiomyomatosis characterized by the abnormal intravascular proliferation of histologically benign smooth muscle cells with a potentially deadly behavior. Extension to the IVC or into the heart is extremely rare, with only 200 reported cases. The average age of presentation is between 40 and 50 years. Asian subjects are more frequently affected, and up to 50% of patients have a history of hysterectomy or myomectomy. IVL has been posited to originate in smooth muscle cells within the uterine vessel walls. These lesions are highly angiogenic and have great invasive potential. Some authors have suggested that IVL develops from a polypoid protrusion of uterine leiomyoma histology within the vascular lumen that becomes endothelialized but without compromising the vascular wall. IVL lesions originating in the uterus disseminate through the IVC, most frequently via the iliac veins (55%), by invading the gonadal vein (26.3%), or through both vascular pathways (5.3%). The tumor’s most distal portion in the IVC reaches the right heart cavities and even the pulmonary circulation leading to systemic venous congestion, impeding venous return, which, in turn, decreases cardiac output. Clinical manifestations depend on the size and degree of tumor extension, whereby the patient is asymptomatic (13% of all cases) in early stages and develops rightsided heart failure once the heart is involved. The most frequent clinical manifestations are dyspnea (37%), edema of the lower extremities (20%), abnormal vaginal bleeding with pelvic pain (18%), and chest pain (12%). Rarely, its presentation may include abdominal distention, palpitations, and sudden death. IVL should be suspected in women during their fertile years and/or with a history of uterine myomatosis and cardiovascular symptoms with no evident diagnosis. An echocardiogram is useful to confirm invasion and tumor extension into the right heart cavities and to exclude other causes of heart failure. An angio-CT scan or MRI can determine the degree of intravascular extension and help plan a surgical approach. The differential diagnoses include atrial myxoma, intransit thrombi, and malignant neoplasms with IVC invasion such as renal cell carcinoma, hepatocellular
chestjournal.org
carcinoma, lymphomas, and adrenal cancer. The definitive diagnosis is established histopathologically and must exclude other uterine entities such as cotyledonoid dissecting leiomyoma, invasive vascular leiomyoma, adenomyomatosis, and leiomyosarcoma. Definitive treatment is radical tumor resection. Two equally effective strategies have been proposed: (1) resection of the intravascular and intracardiac tumor as well as a radical hysterectomy in one surgical event; and (2) resection in two stages. The two-stage procedure would comprise initial resection of the intracardiac tumor and of the IVL in the superior segment of the IVC, followed by IVL resection in the inferior segment of the IVC and radical hysterectomy during a second surgical procedure. Bilateral salpingo-oophorectomy must be performed due to the tumor’s sensitivity to estrogen. The choice of surgical strategy depends on the patient’s condition and clinical stability, the center’s experience, and the degree of IVL extension. Following surgery, aromatase inhibitors or gonadotropin-releasing hormone agonists should be started to inhibit estrogen-mediated growth, but their effect on the decrease in recurrence is controversial; patients with IVL and cardiac extension on antiestrogen therapy have reported recurrence rates between 20% and 50%. Mortality is < 1% if surgical intervention is elective and timely, and the patient is clinically stable.
Clinical Course Twelve hours following admission, the patient became hypotensive with signs of poor tissue perfusion. She required endotracheal intubation, IV resuscitation with crystalloids, and the infusion of norepinephrine (0.6 mg/ kg per minute). The patient underwent surgery with an initial en bloc resection of the abdominal tumor followed by cavoatrial tumor removal. Following removal of the extracorporeal circulation pump, she remained hemodynamically unstable and in heart failure despite the use of inotropic drugs and progressed to refractory cardiac arrest. The diagnosis of intravascular leiomyomatosis was confirmed by histopathologic examination (Fig 3).
Clinical Pearls 1. IVL extending to the IVC or into the heart is an extremely rare entity (200 reported cases), characterized by anomalous intravascular proliferation of
e71
Figure 3 – A, Transverse cut of the uterine tumor. B, Subserosal uterine vessels (black arrows) seen as tortuous and dilated, and with tumoral intravascular involvement (black asterisk). C, The neoplasia is observed according to microscopy (right side of image) with a positive immunohistochemical reaction to smooth muscle actin and an integral vascular wall (blue asterisk). D, Intracardiac tumor (68 35 mm) of solid consistency and smooth edges. E, Hematoxylin and eosin microscopy revealed fusiform cell fascicles without atypia. F, The immunohistochemistry for smooth muscle actin was positive.
smooth muscle cells with benign histologic characteristics but with potentially deadly clinical behavior. 2. IVL should be suspected in any woman with a history of uterine leiomyomatosis and symptoms of right-sided heart failure without an obvious initial diagnosis, associated with the extension of a tumor into the IVC and right heart cavities. 3. The definitive treatment of IVL is the radical resection of the tumor and adjuvant antiestrogen therapy with aromatase inhibitors or gonadotropin-releasing hormone agonists due to the tumor’s sensitivity to estrogen. 4. Tumor recurrence despite use antiestrogen therapy is high, with recurrence rates between 20% and 50%.
Acknowledgments Financial/nonfinancial disclosures: None declared.
e72 Pulmonary, Critical Care, and Sleep Pearls
Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Suggested Readings Roques F, Sanchez B, Bucher B, Larivière J. Role of pre-operative assessment in the surgical management of leiomyoma extended to the right heart chambers: a compendium of information from isolated reports. Eur J Cardiothorac Surg. 2001;19(4):522-524. Kocica MJ, Vranes MR, Kostic D, et al. Intravenous leiomyomatosis with extension to the heart: rare or underestimated. J Thorac Cardiovasc Surg. 2005;130(6):1724-1726. Du J, Zhao X, Guo D, Li H, Sun B. Intravenous leiomyomatosis of the uterus: a clinicopathologic study of 18 cases, with emphasis on early diagnosis and appropriate treatment strategies. Hum Pathol. 2011;42(9):1240-1246. Zhang G, Yu X, Shi H, Fan Q, Lang J, Liu B. Clinical characteristics and prognostic features of intravenous leiomyomatosis with inferior vena cava or intracardiac extension. J Vasc Surg Venous Lymphat Disord. 2017;5(4):485-492. Chiang CS, Chen PL, Kuo TT, Chen IM, Wu NY, Chang HH. One-stage surgery for removal of intravascular leiomyomatosis extending to right ventricle. Medicine (Baltimore). 2018;97(11):e0051.
[
156#3 CHEST SEPTEMBER 2019
]
Pulmonary, Critical Care, and Sleep Pearls
]
A 50-Year-Old Woman With Uterine Myomatosis, Rapidly Progressive Dyspnea, and Lower Extremity Edema José de Jesús Rodriguez-Andoney, MD; Luis Alfonso Castillejo-Adalid, MD; Eduardo Rivero-Sigarroa, MD; José Luis Hernandez-Oropeza, MD; Roberto Redding-Ochoa, MD; and Guillermo Dominguez-Cherit, MD
A 50-year-old woman with morbid obesity (BMI, 49 kg/m2) was admitted to the ED due to shortness of breath triggered by mild to moderate efforts over the previous 3 weeks that rapidly progressed to dyspnea at rest and became associated with oppressive chest pain and edema of the lower extremities. Four months prior to admission, she had been diagnosed with a uterine mass (18 21 cm2) suggestive of a leiomyoma, manifesting with abnormal vaginal bleeding and microcytic hypochromic anemia (Fig 1).
CASE PRESENTATION:
CHEST 2019; 156(3):e69-e72
Physical Examination Findings The patient’s vital signs were normal except for a heart rate of 104 beats/min. Jugular vein distention of 8 cm was observed, and cardiopulmonary auscultation was normal. Abdominal examination showed a nonstrangulated abdominal wall hernia, a diffusely palpable mass in the lower abdomen, and edema of the lower extremities (grade 3þ).
Diagnostic Studies The ECG revealed sinus tachycardia and her laboratory tests showed the following: hemoglobin, 10.2 g/dL (> 13 g/dL); mean corpuscular volume, 64.8 fL (83-98 fL); mean corpuscular hemoglobin, 27.8 pg (27-34 pg); creatinine, 0.79 mg/dL (0.6-1.2 mg/dL); BUN, 12.9 mg/dL (7-25 mg/dL); brain natriuretic peptide, 453 pg/mL (< 100 pg/mL); troponin I, 0.01 ng/mL (< 0.02 ng/mL); and arterial blood lactate, 4.2 mmol/L (< 2 mmol/L). AFFILIATIONS: From the Critical Care Medicine Department (Drs Rodriguez-Andoney, Rivero-Sigarroa, Hernandez-Oropeza, and Dominguez-Cherit), Pulmonary Hypertension Clinic (Drs RodriguezAndoney, Castillejo-Adalid, and Hernandez-Oropeza), the Pathology Department (Dr Redding-Ochoa), Instituto Nacional de Ciencias Médicas y Nutricion Salvador Zubiran, Mexico City, Mexico; and Tecnologico de Monterrey (Drs Dominguez-Cherit and Rivero-Sigarroa), Mexico City, Mexico.
chestjournal.org
Figure 1 – Abdominal CT scan showing the uterine mass.
An echocardiogram revealed a thrombus-like mass originating in the inferior vena cava (IVC) and protruding toward the right atrium, measuring 65 36 mm2, mobile, and nonadherent to the atrial wall. The CORRESPONDENCE TO: Guillermo Dominguez-Cherit, MD, Av Vasco de Quiroga 15, Col Seccion XIV, Tlalpan, Ciudad de Mexico, Mexico, 14080; e-mail: [email protected] Copyright Ó 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved. DOI: https://doi.org/10.1016/j.chest.2019.05.018
e69
Figure 2 – A-C, CT scan showing the uterine mass (green asterisk) with no involvement of the inferior vena cava or heart, obtained 4 months prior to admission. D-F, CT scan showing the tumor occupying the inferior vena cava (yellow asterisk) and involvement of the right heart cavities (red asterisk), and the renal and left gonadal veins (white arrows).
mass also protruded toward the right ventricle and led to intermittent blood flow obstruction. A CT scan showed the previously diagnosed pelvic mass and a new intravascular lesion in the IVC, cephalically extending toward the right side of the heart as well as caudally toward the renal and left gonadal veins (Fig 2).
What is the diagnosis?
e70 Pulmonary, Critical Care, and Sleep Pearls
[
156#3 CHEST SEPTEMBER 2019
]
Diagnosis: Intravascular leiomyomatosis Discussion Intravascular leiomyomatosis (IVL) is a variant of uterine leiomyomatosis characterized by the abnormal intravascular proliferation of histologically benign smooth muscle cells with a potentially deadly behavior. Extension to the IVC or into the heart is extremely rare, with only 200 reported cases. The average age of presentation is between 40 and 50 years. Asian subjects are more frequently affected, and up to 50% of patients have a history of hysterectomy or myomectomy. IVL has been posited to originate in smooth muscle cells within the uterine vessel walls. These lesions are highly angiogenic and have great invasive potential. Some authors have suggested that IVL develops from a polypoid protrusion of uterine leiomyoma histology within the vascular lumen that becomes endothelialized but without compromising the vascular wall. IVL lesions originating in the uterus disseminate through the IVC, most frequently via the iliac veins (55%), by invading the gonadal vein (26.3%), or through both vascular pathways (5.3%). The tumor’s most distal portion in the IVC reaches the right heart cavities and even the pulmonary circulation leading to systemic venous congestion, impeding venous return, which, in turn, decreases cardiac output. Clinical manifestations depend on the size and degree of tumor extension, whereby the patient is asymptomatic (13% of all cases) in early stages and develops rightsided heart failure once the heart is involved. The most frequent clinical manifestations are dyspnea (37%), edema of the lower extremities (20%), abnormal vaginal bleeding with pelvic pain (18%), and chest pain (12%). Rarely, its presentation may include abdominal distention, palpitations, and sudden death. IVL should be suspected in women during their fertile years and/or with a history of uterine myomatosis and cardiovascular symptoms with no evident diagnosis. An echocardiogram is useful to confirm invasion and tumor extension into the right heart cavities and to exclude other causes of heart failure. An angio-CT scan or MRI can determine the degree of intravascular extension and help plan a surgical approach. The differential diagnoses include atrial myxoma, intransit thrombi, and malignant neoplasms with IVC invasion such as renal cell carcinoma, hepatocellular
chestjournal.org
carcinoma, lymphomas, and adrenal cancer. The definitive diagnosis is established histopathologically and must exclude other uterine entities such as cotyledonoid dissecting leiomyoma, invasive vascular leiomyoma, adenomyomatosis, and leiomyosarcoma. Definitive treatment is radical tumor resection. Two equally effective strategies have been proposed: (1) resection of the intravascular and intracardiac tumor as well as a radical hysterectomy in one surgical event; and (2) resection in two stages. The two-stage procedure would comprise initial resection of the intracardiac tumor and of the IVL in the superior segment of the IVC, followed by IVL resection in the inferior segment of the IVC and radical hysterectomy during a second surgical procedure. Bilateral salpingo-oophorectomy must be performed due to the tumor’s sensitivity to estrogen. The choice of surgical strategy depends on the patient’s condition and clinical stability, the center’s experience, and the degree of IVL extension. Following surgery, aromatase inhibitors or gonadotropin-releasing hormone agonists should be started to inhibit estrogen-mediated growth, but their effect on the decrease in recurrence is controversial; patients with IVL and cardiac extension on antiestrogen therapy have reported recurrence rates between 20% and 50%. Mortality is < 1% if surgical intervention is elective and timely, and the patient is clinically stable.
Clinical Course Twelve hours following admission, the patient became hypotensive with signs of poor tissue perfusion. She required endotracheal intubation, IV resuscitation with crystalloids, and the infusion of norepinephrine (0.6 mg/ kg per minute). The patient underwent surgery with an initial en bloc resection of the abdominal tumor followed by cavoatrial tumor removal. Following removal of the extracorporeal circulation pump, she remained hemodynamically unstable and in heart failure despite the use of inotropic drugs and progressed to refractory cardiac arrest. The diagnosis of intravascular leiomyomatosis was confirmed by histopathologic examination (Fig 3).
Clinical Pearls 1. IVL extending to the IVC or into the heart is an extremely rare entity (200 reported cases), characterized by anomalous intravascular proliferation of
e71
Figure 3 – A, Transverse cut of the uterine tumor. B, Subserosal uterine vessels (black arrows) seen as tortuous and dilated, and with tumoral intravascular involvement (black asterisk). C, The neoplasia is observed according to microscopy (right side of image) with a positive immunohistochemical reaction to smooth muscle actin and an integral vascular wall (blue asterisk). D, Intracardiac tumor (68 35 mm) of solid consistency and smooth edges. E, Hematoxylin and eosin microscopy revealed fusiform cell fascicles without atypia. F, The immunohistochemistry for smooth muscle actin was positive.
smooth muscle cells with benign histologic characteristics but with potentially deadly clinical behavior. 2. IVL should be suspected in any woman with a history of uterine leiomyomatosis and symptoms of right-sided heart failure without an obvious initial diagnosis, associated with the extension of a tumor into the IVC and right heart cavities. 3. The definitive treatment of IVL is the radical resection of the tumor and adjuvant antiestrogen therapy with aromatase inhibitors or gonadotropin-releasing hormone agonists due to the tumor’s sensitivity to estrogen. 4. Tumor recurrence despite use antiestrogen therapy is high, with recurrence rates between 20% and 50%.
Acknowledgments Financial/nonfinancial disclosures: None declared.
e72 Pulmonary, Critical Care, and Sleep Pearls
Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.
Suggested Readings Roques F, Sanchez B, Bucher B, Larivière J. Role of pre-operative assessment in the surgical management of leiomyoma extended to the right heart chambers: a compendium of information from isolated reports. Eur J Cardiothorac Surg. 2001;19(4):522-524. Kocica MJ, Vranes MR, Kostic D, et al. Intravenous leiomyomatosis with extension to the heart: rare or underestimated. J Thorac Cardiovasc Surg. 2005;130(6):1724-1726. Du J, Zhao X, Guo D, Li H, Sun B. Intravenous leiomyomatosis of the uterus: a clinicopathologic study of 18 cases, with emphasis on early diagnosis and appropriate treatment strategies. Hum Pathol. 2011;42(9):1240-1246. Zhang G, Yu X, Shi H, Fan Q, Lang J, Liu B. Clinical characteristics and prognostic features of intravenous leiomyomatosis with inferior vena cava or intracardiac extension. J Vasc Surg Venous Lymphat Disord. 2017;5(4):485-492. Chiang CS, Chen PL, Kuo TT, Chen IM, Wu NY, Chang HH. One-stage surgery for removal of intravascular leiomyomatosis extending to right ventricle. Medicine (Baltimore). 2018;97(11):e0051.
[
156#3 CHEST SEPTEMBER 2019
]