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Original article

Diagnosis of intravenous leiomyomatosis extending to heart with emphasis on magnetic resonance imaging

KANG, Li-qing; ZHANG, Bin; LIU, Bao-gang; LIU, Feng-hai

Section Editor(s): WANG, De

Author Information
doi: 10.3760/cma.j.issn.0366-6999.2012.01.007

Abstract

Intravenous leiomyomatosis (IVL) is a rare neoplasm characterized by nodular masses of histologically benign smooth muscle growing within veins.1 Because of its rarity, it is often overlooked, and probably missed even at the time of operation.2 In rare cases the lesion can extend to the inferior vena cava, to the right cardiac chambers or even to the pulmonary artery, causing severe clinical symptoms and even be life-threatening.3-5 When the right atrium was involved, the patients were often misdiagnosed with primary atrium tumors. To our knowledge, fewer than 300 cases of IVL are described in the literature, and the majority of cases were diagnosed by echocardiography. However, there seems to be an increased number of IVL cases reported over the last few years, and cardiac involvement is seen in 10%-40% of cases.6,7 In this article, we will describe the imaging features of IVL with cardiac extension, and will discuss the differential diagnosis of the disease.

METHODS

Between July 2005 and May 2010, seven cases of tumors that extended from the inferior vena cava into the right atrium were resected at the Cangzhou Central Hospital. Four of the tumors were histopathologically diagnosed as IVL, two as atrial myxoma, and one as intravenous angioleiomyolipoma. Meanwhile, 22 other tumors involving the inferior vena cava and right atrium that were histopathologically proven through percutaneous puncture biopsy were also included into this study for discussion of differential diagnosis. Of the 22 tumors, eight cases were renal cell carcinomas, two were Wilms' tumors, and 12 were hepatocellular carcinomas. All four of the IVL patients were females, from 34 to 56 years old (averaged 46 years). Three cases had echocardiography performed, two had post contrast scans of CT performed, and two had MRI performed. Of the 25 other tumors involving the inferior vena cava and right atrium, 16 patients were males and nine were females, ages ranging from 38 to 76 years (averaged 53 years). Eighteen cases had echocardiography performed, 21 had post contrast scans of CT performed, and 15 had MRI performed. All the MRI examinations were performed on a GE Signa infinity 1.5T Twinspeed MR Scanner (GE Medical System, Milwaukee, USA). The following sequences were performed: SE T1WI axial sequence (TR 600 ms, TE 10 ms, with respiratory trigger), FSE T2WI axial, sagittal, and coronal sequences (TR 6000 ms, TE 90 ms, with or without fat saturation), and 2D FIESTA coronal sequence (TR 3-5 ms, TE minimum). In patients with irregular respiration, an SSFSE sequence was used to replace FSE T2WI sequences. All the CT examinations were performed on a GE LightSpeed VCT scanner (GE Medical System). Three phase spiral scans of CT were acquired after injection of 50 ml iopromide (Ultravist, 370 mgI/ml, Schering Company, Berlin, Germany) at a speed of 2.5-4 ml/s through the cubitus vein using a power injector. Scan delay time was 20-25 seconds for the arterial phase, 60-70 seconds for the venous phase, and 2-3 minutes for the delayed phase. Multiplanar reformation (MPR) images were acquired for all CT examinations. All the echocardiography examinations were performed on a Siemens Sequia 512 Color Doppler Ultrasonography (Acuson, Siemens Medical Systems, Mountain View, CA, USA). United trans-thoracic and trans-abdominal scanning was performed using a 4VIC-S heart probe and 4CI-S abdominal probe. The clinical symptoms and imaging appearances were analyzed for all cases, and pathological findings of the resected tumors were also discussed.

RESULTS

Clinical symptoms

Clinical symptoms of IVLs

Three of the four cases had a uterus myoma diagnosed and treated earlier (one had a myomectomy four years previously, and a hysterectomy two years previously because of recurrence of the tumor, and the other two had had a hysterectomy), and the fourth patient had the uterus myoma diagnosed during the MRI examination of the tumor in right atrium and inferior vena cava and was untreated. Edema of bilateral eyelids and lower extremities appeared in two cases, and irregular vaginal bleeding appeared in the patient who had a uterus myoma untreated. Abdominal distension was found in two cases. Dyspnea and palpitation occurred in two cases, and one of them was accompanied by sweating, nausea, vomiting, and cyanotic lips. All the above symptoms were seen intermittently and were aggravated after movement, and the fourth patient was accompanied by syncope.

Clinical symptoms of other kinds of tumors

The 25 cases of other tumors in right atrium and inferior vena cava were associated with right-sided congestive symptoms such as abdominal distension, anorexia, and peripheral edema. The patients with renal carcinoma had also suffered from painless hematuria, and the patients with hepatocellular carcinoma had also suffered from nausea, hematemesis, jaundice, and severe pain in the right hypochondrium.

Imaging appearance

Imaging appearance of IVLs

Echocardiography was performed in three cases, and all showed a hyperechoic elongated mobile mass extending from the inferior vena cava or even from the ipsilateral internal iliac vein to the right atrium, and in one case the mass protruded into the right ventricle and moved to and fro in accord with the systolic movement and the left atrium enlarged (Figure 1). In another case, the lump seemed attached to the free wall of the right atrium, and was misdiagnosed as myxoma.

Figure 1.
Figure 1.:
Echocardiography of an IVL shows a hyperechoic mass in the right atrium and inferior vena cava (arrows).

Two cases had post-contrast CT scans, showing a heterogeneously enhanced filling defect in the distended right atrium and inferior vena cava. The patient who had the untreated uterus myoma had a filling defect that involved the right internal iliac and ovarian veins, and soft-tissue masses could be found in the uterus. In one case, the mass in the right atrium looked like a luffa vegetable sponge on the post-contrast CT scans (Figure 2A).

Figure 2.
Figure 2.:
CT and MRI demonstrations of the same patient as Figure 1. 2A: Post-contrast scans of CT shows a mass in the right atrium looks like a luffa vegetable sponge (arrow), part of the tumor protrudes into the right ventricle. 2B: Fiesta sequence coronal image shows an irregular mass in the right corner of the uterus with a cystic change (arrowhead). The mass extends into the right internal iliac vein and inferior vena cava looks like a luffa vegetable sponge (arrows), a cyst was found in the left ovary. 2C: T2WI axial image shows the mass in the inferior vena cava looks like a sieve pore (arrow).

MRI was also performed in two cases, and both showed an irregular mass in the inferior vena cava with extension to the right atrium, and in one case the mass protruded into the right ventricle through the tricuspid valve. The mass showed mixed hyper intensity on both T1-weighted images and T2-weighted images compared with muscles, and looked like a luffa vegetable sponge on FIESTA coronal images and a sieve pore on T2-weighted axial images (Figure 2B and 2C).

Imaging appearance of other kinds of tumors

The two atrial myxomas were lobular in shape, with a pedicle attached to the wall of the atrium seen on echocardiography. All the tumor emboli of the malignant tumors from kidney and liver had the same imaging features as the primary tumors and were often directly connected with them. The inferior vena cava was often distended by a large tumor embolus (Figures 3 and 4). The one case of intravenous angioleiomyolipoma extended from the left renal parenchyma and the renal sinus had a typical fat component within the tumor and tumor embolus that could easily be found by MRI (Figure 5A and 5B).

Figure 3.
Figure 3.:
Post contrast scan of CT in a hepatocellular carcinoma with the inferior vena cava tumor embolus shows the inferior vena cava is distended, and the tumor embolus has the same enhancement features as the connected primary tumor (arrows).
Figure 4.
Figure 4.:
MRI of a Wilms' tumor in the left kidney with left renal vein and inferior vena cava extension shows the left renal vein and the inferior vena cava is distended, and the tumor embolus (arrows) has the same signal intensity with the connected renal tumor.
Figure 5.
Figure 5.:
MRI of an intravenous angioleiomyolipoma extended from the left renal parenchyma and the renal sinus shows a typical fat component within the tumor embolus, which has hyper signal intensity (5A), that has low signal intensity on a fat-suppressed image (5B).

Pathological findings of the resected tumors

All four IVLs were operated on under complex general intravenous and inhalation anesthesia, low temperature, and cardiopulmonary bypass through a median incision, and longitudinal sternotomy. Tumors in the right atrium were resected and the cord like extension of the tumor into the inferior vena cava and iliac veins were gently pulled out. The patient with an untreated uterus myoma underwent a second operation two months after the first operation, with hysterectomy and resection of the residual tumor mass in the right internal iliac vein. The gross specimen of the IVL looked pale to pink and the part from the right atrium looked like an ophicephalous and the part in the inferior vena cava looked like a cord. The surface of the specimen was smooth but irregular, with some fissures parallel to the long axis of the cordlike tumor (Figure 6). There were many small vessels on the axial sections of the specimen. Histopathology showed that the tumors consisted of proliferating smooth muscle fibers consistent with IVL (Figure 7). Postoperative recovery was good for all patients, and follow-up of one year to four years revealed no recurrence.

Figure 6.
Figure 6.:
Gross specimen of an IVL shows a pink snake-like mass, and there are some fissures (arrow) on the surface of the specimen.
Figure 7.
Figure 7.:
Histological image of an IVL shows benign smooth-muscle proliferation (H&E staining, original magnifcation×200).

The specimen of the two atrial myxomas were ovoid shaped smooth soft masses, and histopathological examination revealed a tumor showing myxoid areas with thin walled vascular channels as seen in classical atrial myxomas. The one case of intravenous angioleiomyolipoma was an extension of a renal angioleiomyolipoma. The surface of the specimen was smooth, and was snake shaped. On histopathological examination, it was composed of smooth muscle cells, fat, and proliferating blood vessels.

DISCUSSION

IVL is defined by the proliferation of benign smooth muscle within veins outside the confines of a uterine leiomyoma or even when no leiomyoma is present.8 It was first described by Birch-Hirschfield in 1896 and further elaborated by Norris and Parmley in 1975.9 The IVL extension to the heart was first reported by Dürkin in 1907, and open heart surgery was first reported by Mandelbaum et al in 1974.9 It is also described as a smooth-muscle tumor with unusual growth pattern.10 The lesion can grow and extend directly to pelvic organs, or embolize to the pelvic veins, to the inferior vena cava, to the right cardiac chambers or even to the pulmonary artery.3 Moreover, lung metastasis has been reported.10

IVL is a rare condition that usually affects premenopausal women, but there seems to be an increasing number of IVL cases reported over the last few years. The majority (90%) of women are parous. The tumor is often unrecognized prior to surgery1 and the diagnosis of IVL must be considered when facing a middle aged woman with a right heart tumor, especially in cases of patients with a previous hysterectomy.11 While pathogenesis of the tumor remains controversial, there are two main theories regarding its origin: intravenous extension of the uterine leiomyoma, or direct tumorigenesis from the wall of the venous system. Histologically it is a benign smooth muscle tumor, arising from either a uterine myoma or the walls of a uterine vessel, with extension into veins.12

Patients often have a history of uterus myoma, myomectomy or hysterectomy.13 Cardiac involvement typically presents with right-sided congestive symptoms, such as in our cases, including abdominal pain or distension, nausea, vomiting, anorexia, jaundice, and peripheral edema. When the tricuspid valve is intermittently obstructed by the mass in the right atrium, patients may suffer from dyspnea, chest tightness, palpitations, and even clinical manifestations of syncope.9

Echocardiographic features of IVL with cardiac extension include a hyperechoic elongated mobile mass extending from the inferior vena cava and an irregular mass in the right atrium and sometimes with the mass protruding into the right ventricle.12 The mass will often have multiple attachments to the veins. Echocardiographic examination often misdiagnoses the tumor in the right atrium as myxoma, as happened in one of our cases. Atrial myxoma is the commonest primary tumor of the heart and the second most common cause of a right heart mass after metastasis.14 The majority of atrial myxomas are found in the left atrium, and the right antrium is a less common site.14,15 Myxoma is often lobulated in shape, with a pedicle attached to the wall of the atrium in the area of the oval fossa, and the tumor is often pushed to the atrium-ventricle valve by the blood flow.16 Extension to the inferior vena cava does not often happen in myxoma, but when this happens the extension is less obvious than that seen in IVL. On the other hand, IVL nearly always has a large component in IVC and with varying parts of the tumor extending to the right atrium and no pedicle found attached to the atrium wall.17

Contrast-enhanced CT often reveals that the distal inferior vena cava and right atrium are distended and filled with enhancing mass. The common iliac vein, the ipsilateral internal iliac and ovarian veins are often involved. The inferior vena cava proximal to the enhancing mass can be distended with non-enhancing thrombus. In addition, the uterus myoma demonstrates enlargement with heterogeneous contrast enhancement.

MRI can provide important information that is unavailable with other imaging technics because of its superb soft tissue contrast resolution, direct multi-planar imaging capability and unique ability to assess blood flow without contrast injection.2,18,19 It is also a safer examination, as the gadolinium chelate is a much safer contrast agent compared with the water-soluble contrast agent used in CT scanning, and there is no irradiation to the patients. The appearance of IVL on MRI depends on the amounts of smooth muscle and fibrous tissue that each lesion contains. The typical appearance is low to intermediate signal intensity on T1-weighted images and low signal intensity on T2-weighted images.20 However, these signal intensity features are not specific for leiomyomas, and some IVL may appear as high signal intensity on both T1-weighted and T2-weighted images. Because of the benign nature of the tumor, it often grows slowly, and with the turbulent flow in the inferior vena cava, the surface of the tumor is often irregular with some fissures parallel to the long axis of the cordlike tumor, and blood may flow through these fissures. This growth mode together with the small vessels within the tumor and tortuous course of the tumor in the inferior vena cava often make it looks like a luffa vegetable sponge on ‘white blood’ coronal images and a sieve pore on T2-weighted axial images, as were seen in our cases and illustrated in the literature.4,7 The so called ‘white blood’ sequence is a kind of steady state free precession technique (SSFP) such as the FIESTA sequence used in GE MR scanners, in which the blood looks bright. On T2-weighted axial images the flowing blood looks dark because of flow void effect. Both sequences can make an excellent contrast between lesions in vessels and the flowing blood without administration of contrast medium. Lai et al2 believe that, while TOF techniques provide a good evaluation of intraluminal lesions in the venous system, contrast injection is required to make the important differentiation of tumors from thrombus. However, with the features mentioned above, we believe that the diagnosis can often be made without administration of contrast medium.

An important condition in the differential diagnosis of IVL with cardiac extension is right-sided heart thrombus-in-transit, which typically occurs in the setting of a postoperative state, indwelling central lines, or chronic debility, and appears as elongated mobile masses of venous casts giving a “popcorn” appearance within the cardiac chambers.21 Other tumors, such as carcinomas, originating from the kidney, liver, or adrenal gland may extend into the right-side cardiac chambers via the inferior vena cava. Tumor embolus of the above mentioned malignant tumors are a much more common cause of inferior vena cava masses. However, these tumors rarely have multiple endocardial attachments and a mass-like appearance rather than that of a venous cast of long, thin, mobile structures.21 Besides, the tumor emboli of theses malignant tumors often have the same imaging features as the primary tumors and are often directly connected with them; such as in our cases. Although some tumor emboli of hypervascular carcinoma may have heterogeneous enhancement on the arterial phase of post contrast scans with CT or MRI, which may have a ‘luffa vegetable sponge’ appearance, the enhanced parts are often irregular and no ‘sieve pore’ like appearance can be found on T2-weighted axial images. The difference is due to the capillary vessels of the tumor emboli not being large enough to cause the flow void signal. In addition, the primary tumor is often large enough to influence the diagnosis. The one case of intravenous angioleiomyolipoma in our group, which may be a rare subtype of IVL,22 has a typical fat component within the primary tumor and the tumor embolus that can easily be found by MRI.

In short, the imaging appearance of IVL has some features, like luffa vegetable sponge and sieve pore like appearance demonstrated on MRI, which may be helpful for differential diagnosis. MRI may be more useful than CT and echocardiography in defining the extent of the lesion, which is critical to surgical planning.2 An early diagnosis relies on a high index of suspicion.

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Keywords:

leiomyomatosis; vena cava, inferior; heart; echocardiography; tomography, X-ray computed; magnetic resonance imaging

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