Multimodality Imaging of Abdominopelvic Tumors with Venous Invasion
Jordan D. LeGout, MD Ryan E. Bailey, MD Candice W. Bolan, MD Andrew W. Bowman, MD, PhD Frank Chen, MD Joseph G. Cernigliaro, MD Lauren F. Alexander, MD
Abbreviations: DWI = diffusion-weighted im- aging, EMVI = extramural vascular invasion, HCC = hepatocellular carcinoma, ICC = in- trahepatic cholangiocarcinoma, IVC = inferior vena cava, PNET = pancreatic neuroendocrine tumor, RCC = renal cell carcinoma
RadioGraphics 2020; 40:2098-2116 https://doi.org/10.1148/rg.2020200047
Content Codes: GI GU OI VA
From the Department of Radiology, Mayo Clinic Florida, 4500 San Pablo Rd, Jacksonville, FL 32224. Presented as an education exhibit at the 2019 RSNA Annual Meeting. Received March 23, 2020; revision requested May 22 and received June 16; accepted June 26. For this journal-based SA-CME activity, the authors, ed- itor, and reviewers have disclosed no relevant re- lationships. Address correspondence to J.D.L. (e-mail: LeGout. Jordan@mayo.edu).
ORSNA, 2020
SA-CME LEARNING OBJECTIVES
After completing this journal-based SA-CME activity, participants will be able to:
Differentiate tumor from bland throm- bus at multimodality assessment and avoid common pitfalls and mimics.
·Formulate a differential diagnosis based on the site of venous invasion and the organ of origin.
Recognize the imaging features of the most common tumors that invade the veins of the abdomen and pelvis.
See rsna.org/learning-center-rg.
A broad range of abdominal and pelvic tumors can manifest with or develop intraluminal venous invasion. Imaging features at cross- sectional modalities and contrast-enhanced US that allow differ- entiation of tumor extension within veins from bland thrombus include the expansile nature of tumor thrombus and attenuation and enhancement similar to those of the primary tumor. Venous in- vasion is a distinctive feature of hepatocellular carcinoma and renal cell carcinoma with known prognostic and treatment implications; however, this finding remains an underrecognized characteristic of multiple other malignancies-including cholangiocarcinoma, adrenocortical carcinoma, pancreatic neuroendocrine tumor, and primary venous leiomyosarcoma-and can be a feature of benign tumors such as renal angiomyolipoma and uterine leiomyomatosis. Recognition of tumor venous invasion at imaging has clinical signif- icance and management implications for a range of abdominal and pelvic tumors. For example, portal vein invasion is a strong negative prognostic indicator in patients with hepatocellular carcinoma. In patients with rectal cancer, diagnosis of extramural venous invasion helps predict local and distant recurrence and is associated with worse survival. The authors present venous invasion by vascular dis- tribution and organ of primary tumor origin with review of typical imaging features. Common pitfalls and mimics of neoplastic throm- bus, including artifacts and anatomic variants, are described to help differentiate these findings from tumor in vein. By accurately diag- nosing tumor venous invasion, especially in tumors where its pres- ence may not be a typical feature, radiologists can help referring clinicians develop the best treatment strategies for their patients.
ºRSNA, 2020 · radiographics.rsna.org
Introduction
Neoplastic intraluminal venous invasion, or tumor thrombus forma- tion, is most commonly associated with malignancies and is rarely seen as an aggressive feature of benign tumors. In the adult abdomen and pelvis, hepatocellular carcinoma (HCC) and renal cell carci- noma (RCC) have a well-known propensity for this growth pattern, and accurate description of the extent of venous invasion is part of tumor staging and treatment planning for these malignancies (1,2). Venous invasion may be an overlooked feature of a variety of other abdominopelvic tumors with myriad implications for prognosis and treatment, requiring accurate identification and full description at radiologic assessment.
This article reviews imaging diagnosis of tumor thrombus with US, CT, and MRI. Tumor thrombus involvement of the inferior vena cava (IVC), portal veins, splanchnic veins, and pelvic veins is discussed, with differential diagnosis according to organ and imaging features. Tumors with a propensity for venous invasion are contrasted to those for which it would be an atypical feature. Common mimics and areas
TEACHING POINTS
At imaging, tumor thrombus is more expansive than bland thrombus, demonstrates enhancement, and may have im- aging features similar to those of the primary malignancy. Another helpful indicator of tumor thrombus is contiguity with the primary mass.
Tumor types most commonly associated with invasion of the IVC are RCC, HCC, adrenocortical carcinoma, and primary leiomyosarcoma of the IVC.
The growth pattern of ICC with respect to the veins is typically more encasement with narrowing or occlusion rather than ve- nous invasion with tumor thrombus. Some studies have re- ported the presence of macrovascular portal tumor thrombus in up to 15%-20% of cases of ICC, suggesting that tumor in vein may be an overlooked feature.
PNETs most commonly invade the splenic vein but can also extend into or separately involve the superior mesenteric or main portal vein or uncommonly smaller branch veins, de- pending on the location of the primary tumor. Tumor throm- bus can be extensive, resulting in significant venous hyperten- sion and venous collateral formation, including formation of gastric varices.
At US of the iliac or femoral veins, an overly expansive throm- bus or a thrombus that deforms or extends beyond the vessel wall should raise suspicion for venous leiomyosarcoma and prompt careful Doppler interrogation for internal flow or fur- ther characterization with multiphase CT or MRI.
of diagnostic challenge are reviewed to help dif- ferentiation from tumor in vein. Recognition and thorough description of tumor venous invasion are critical for diagnosis and treatment planning.
Diagnosis of Tumor in Vein
Confident diagnosis of venous thrombosis and differentiation of bland versus malignant throm- bus play a significant role in tumor staging, management, and treatment. At imaging, tumor thrombus is more expansive than bland throm- bus, demonstrates enhancement, and may have imaging features similar to those of the primary malignancy (3,4). Another helpful indicator of tumor thrombus is contiguity with the primary mass (4-6) (Table 1). In addition, both tumor and bland thrombus may coexist, so careful evaluation of the entire thrombus burden is war- ranted (7,8).
US is a sensitive technique for detecting ve- nous thrombosis, but it can be challenging to dis- tinguish between neoplastic and bland thrombus (6,8). At gray-scale US, malignant thrombus can have similar echogenicity to that of the primary tumor and is more likely to expand the vessel. Color and spectral Doppler US may demonstrate low-resistance arterialized flow in the thrombus (9) (Fig 1). Contrast-enhanced US is an effective technique for evaluating for thrombus enhance- ment in patients with HCC, with sensitivity and specificity as high as 100% and 83%-92%, re-
spectively, for discriminating between benign and malignant thrombus (6) (Fig 2).
With CT, the shared imaging features of tu- mor thrombus-including direct extension from the primary tumor into a vein, overly expansive thrombus, and thrombus enhancement-can be accurately assessed. Detection of neovascular- ity in a portal vein thrombus at CT has been reported to be 100% specific for malignancy (10) (Fig 3). The enhancement pattern of the tumor thrombus may match that of the primary malignancy, such as arterial hyperenhancement and later-phase washout in cases of HCC (7).
Thin-section CT acquisition allows high- quality multiplanar reconstruction to optimally display the thrombus and evaluate the relation- ship between the tumor and surrounding ves- sels, increasing reader confidence. Reconstruc- tions provide a road map for surgical planning when necessary. Dual-energy CT can be used to confirm enhancement characteristics and has been shown to have sensitivity and specificity of more than 90% for thrombus differentiation, with malignant thrombus demonstrating higher iodine indexes than bland thrombus (10).
Fluorodeoxyglucose (FDG) PET with CT has also been reported as valuable in diagnosis of tu- mor thrombus. Malignant thrombi have a higher maximum standardized uptake value (SUV) than benign thrombi, with reported sensitivity, specificity, and accuracy of 94%, 80%, and 89%, respectively, when an SUV cutoff of 3.35 is used for diagnosis of portal tumor thrombus across a variety of tumor types (11) (Fig 4). However, PET/CT may be of limited utility in tumor types that are not typically FDG avid, such as HCC. While PET/CT is helpful for identifying distant metastases in HCC, it has limited utility for tu- mor detection and local staging, as less than 40% of HCCs demonstrate FDG uptake (12).
MRI offers superior soft-tissue contrast resolu- tion in comparison with US and CT while also providing multiple opportunities for evaluating the venous system, with assessment of different signal intensity characteristics and visualization in multiple planes (4). T2-weighted and diffusion- weighted imaging (DWI) sequences are helpful for assessment of tumor thrombus in addition to the shared imaging features discussed earlier. On T2-weighted images, loss of flow void in a vessel can be caused by either bland or tumor thrombus. However, bland thrombus more often demonstrates low T2 signal intensity, while tumor thrombus is more often of intermediate T2 signal intensity (4,7) (Fig 5a, 5c).
At DWI, restricted diffusion in malignant thrombus has been shown to be an effective tool for differentiating malignant from benign
| Table 1: Imaging Features of Bland and Malignant Thrombi | ||
|---|---|---|
| Imaging Feature | Bland Thrombus | Malignant Thrombus |
| General features | ||
| Expansive | No or yes | Yes |
| Enhancing | No | Yes |
| Similar imaging features to primary tumor | No | Yes |
| Contiguous to primary mass | No | Yes |
| US feature | ||
| Arterial flow in thrombus | No | Yes |
| CT feature | ||
| Neovascularity in thrombus | No | Yes |
| PET feature | ||
| FDG avidity | Lower | Higher |
| MRI features | ||
| Signal intensity on T2-weighted images | Low | Intermediate |
| Diffusion restriction at DWI | No | Yes |
Note .- DWI = diffusion-weighed imaging, FDG = fluorodeoxyglucose.
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thrombus. Malignant thrombus is hyperintense on high-b-value diffusion-weighted images with corresponding low signal intensity on apparent diffusion coefficient (ADC) maps, while bland thrombus is typically hyperintense on ADC maps (3) (Fig 5b, 5d). In addition to these sequences, subtraction imaging with contrast-enhanced MRI also allows confident confirmation of thrombus enhancement (13) (Fig 6).
Tumor in IVC
Tumor types most commonly associated with invasion of the IVC are RCC, HCC, adrenocorti- cal carcinoma, and primary leiomyosarcoma of the IVC (Table 2). This differential diagnosis can be narrowed on the basis of the clinical history,
risk factors, and appearance at imaging, par- ticularly if the organ of origin can be confidently determined. For large masses involving the IVC and of uncertain origin, this differential diagnosis can serve as a helpful starting point for directing imaging assessment.
Renal Cell Carcinoma
If the tumor can be clearly seen to arise from the kidney, then the most likely diagnosis is RCC, which represents more than 90% of all renal malignancies and has a well-known propensity for tumor thrombus formation (14). Venous invasion occurs in up to 10% of RCCs, more frequently in larger more advanced tumors (15). Tumor thrombus is most commonly associated with the
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clear cell subtype of RCC but can be seen with other less common subtypes as well (16).
Identification of tumor thrombus is a criti- cal part of radiologic evaluation of patients with RCC for staging, prognosis, and surgical plan- ning. The presence of tumor thrombus is part of American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging of RCC, with tumor thrombus corresponding to T3a dis- ease when confined to the renal vein, T3b disease when within the infradiaphragmatic IVC, and T3c disease when there is supradiaphragmatic extension or tumor invades the wall of the IVC (2). In general, tumor thrombus in RCC is a poor prognostic feature, with 5-year cancer-free survival after successful surgery of approximately 50% (17).
In addition to describing the full extent of tumor thrombus, it is important to assess for presence or absence of invasion of the IVC wall, as IVC wall invasion complicates surgery and could require IVC resection and reconstruction in place of tumor thrombectomy for successful treatment. The MRI features helpful for diag- nosing IVC wall invasion preoperatively include breach of the vessel wall and complete IVC oc- clusion, with high sensitivity (92%) and specific- ity (86%) (18) (Fig 7).
Other Renal Neoplasms
Renal vein and IVC tumor thrombus arising from other renal tumors is rare. Urothelial carcinoma of the renal pelvis is much less common than RCC, accounting for less than 10% of renal ma- lignancies (14). Urothelial carcinoma-associated tumor thrombus is an atypical feature and rarely reported, with the largest case series consisting of just five patients (19).
Differentiation between centrally located RCC and renal pelvis urothelial carcinoma with CT has been shown to have high accuracy but can be challenging and may not be possible in all cases, especially in the rare cases of urothe- lial carcinoma with vein invasion (Fig 8). CT features shown to be predictive of renal urothe- lial carcinoma rather than RCC include tumor centered in the collecting system, collecting system extension to the ureteropelvic junction or into the ureter, homogeneous moderate tumor enhancement, lack of cystic or necrotic change, and preservation of the renal contour (20). If the diagnosis is in question, then biopsy should be performed owing to the differences in treatment of these tumor types.
Angiomyolipoma is the most common benign solid renal tumor and one of the rare benign neoplasms that can exhibit venous invasion. This tumor is more common in women and has syn- dromic associations with tuberous sclerosis and lymphangioleiomyomatosis. Angiomyolipoma is typically diagnosed at imaging by the presence of macroscopic fat, which can be readily identified
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as areas of fat attenuation at CT or chemical shift and frequency-selective fat-suppression signal in- tensity at MRI. Approximately 5% of angiomyo- lipomas are fat poor or fat invisible and therefore are more difficult to differentiate from RCC with imaging, sometimes necessitating biopsy for con- fident diagnosis (21).
Renal vein and IVC invasion by angiomyo- lipoma rarely occur, with less than 100 cases reported in the literature (22) (Fig 9). Large size and central location are thought to be predispos- ing factors. While the presence of venous invasion by angiomyolipoma may necessitate treatment owing to tumor thrombus size or location, it does
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| Table 2: Common Neoplasms with Venous Invasion by Location | |
|---|---|
| Veins | Common Invasive Neoplasms |
| Inferior vena cava (IVC) | Renal cell carcinoma (RCC) |
| Hepatocellular carcinoma (HCC) | |
| Adrenocortical carcinoma | |
| Primary venous leiomyosarcoma | |
| Portal veins | Hepatocellular carcinoma |
| Intrahepatic cholangiocarcinoma | |
| Splanchnic veins | Pancreatic neuroendocrine tu- mors (PNETs) |
| Pelvic veins | Rectal carcinoma |
| Osteosarcoma | |
| Benign uterine leiomyomatosis | |
| Uterine leiomyosarcoma | |
| Primary venous leiomyosarcoma | |
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not connote malignant transformation or risk for metastatic disease (23).
Adrenal Malignancies
If the organ of tumor origin can be established as the adrenal gland, then the most likely diagnosis is adrenocortical carcinoma. Adreno- cortical carcinoma is a rare malignancy, with a reported annual incidence of one case per 1 million in the United States, and is more com- mon in whites than in nonwhites (6.3:1) and in females than in males (1.34:1). Although it can occur at any age, adrenocortical carcinoma has a mean age at diagnosis of around 55 years (24).
Adrenocortical carcinoma is most often spo- radic but has known associations with multiple hereditary syndromes, including Beckwith-Wie- demann syndrome, Li-Fraumeni syndrome, and multiple endocrine neoplasia type 1 (25). This tumor can be discovered incidentally or manifest symptomatically with pain or with symptoms related to mass effect or hormonal hypersecretion, including Cushing syndrome, hyperaldosteronism, or virilization or feminization. While surgical resec- tion can be curative, adrenocortical carcinoma is an aggressive malignancy that often manifests at an advanced stage, with poor prognosis and reported median survival of 17 months (24).
Adrenocortical carcinoma most often mani- fests as a large suprarenal mass measuring 12 cm on average, with fewer than 5% measuring 6 cm or less at presentation. Masses are typically uni- lateral and have a slight left-sided predominance (26). These tumors often have irregular margins and when large are characteristically heteroge- neous, with areas of necrosis and hemorrhage. Calcification is present in around 30% of masses.
Areas of macroscopic fat at CT or MRI or microscopic fat at chemical shift MRI can be present in some lesions. However, the areas of fat deposition are usually small and nonuniform. The uniform microscopic fat deposition characteristic
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of lipid-rich adrenal adenomas does not occur. Metastases are common at presentation and are most frequently to the lymph nodes, lung, liver, and bone (27).
The propensity of adrenocortical carcinoma to invade the renal veins and IVC via the adre- nal veins ranges from 9% to 19% of tumors (28) (Fig 10). Limited treatment and prognostic data are available for these patients, but the over- all prognosis is poor, with no 5-year survivors in one cohort of 28 surgically treated patients with IVC tumor thrombus (29). Invasion of these veins by other tumors of adrenal origin is exceedingly rare but has been reported with malignant pheochromocytoma (30).
Primary Venous Leiomyosarcoma
If a mass is isolated to the IVC or is a large tumor involving the IVC and multiple organs of possible origin, then primary leiomyosarcoma of the IVC can be included in the differential diagnosis. Primary venous leiomyosarcoma is
rare, making up 5% of all leiomyosarcomas, but involves the IVC in the majority of cases. Venous leiomyosarcoma is an aggressive group of tumors with high rates of recurrence and frequent metastases, most commonly to the lung and liver. Surgical resection is the mainstay of treatment, with 5-year survival rates as high as 65% after complete resection.
Primary leiomyosarcoma of the IVC is found in women in more than three-fourths of cases and occurs at a mean age of 54 years (31). Primary leiomyosarcoma originating from the renal vein is extremely rare, occurring much less frequently than leiomyosarcoma of the IVC. When reported, primary leiomyosarcoma of the renal vein is more commonly found on the left, likely owing to the longer length of the left renal vein (32) (Fig 11).
Three main growth patterns for primary leiomyosarcoma of the IVC have been described in relation to the IVC lumen, with extraluminal growth most common in 62% of cases, combined
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extraluminal and intraluminal growth in 33%, and entirely intraluminal growth in 6% (33). Other authors have described the growth pattern as predominantly extraluminal (76%) or predom- inantly intraluminal (20%) (31) (Fig 12). The site of origin from the IVC is most commonly the middle segment (from the renal veins to the hepatic veins) in 43% of cases, the lower (infra- renal) segment in 37%, and the upper segment (above the hepatic veins) in 19% (31).
At imaging, primary leiomyosarcoma of the IVC is typically a large heterogeneous mass that frequently contains areas of necrosis. In con- trast to adrenocortical carcinoma, calcification is uncommon (33). In cases of a predominantly extraluminal growth pattern, differentiation from other retroperitoneal sarcomas or the other tumors described earlier may be difficult. Limited data are available for imaging differen- tiation of leiomyosarcoma of the IVC from other tumors. One small CT series suggested that an imperceptible IVC at the point of maximal contact with the tumor was specific for primary leiomyosarcoma of the IVC versus tumors of primary retroperitoneal origin (34).
Hepatic Malignancies
Invasion of the IVC by hepatic tumor is most commonly attributed to HCC via invasion of the hepatic veins (Fig 13). HCC has a well-known tendency for venous invasion, most commonly involving the portal veins. Hepatic vein invasion with extension into the IVC occurs in less than 5% of cases (35,36). Invasion of these veins is traditionally considered advanced-stage disease, with treatment options limited to chemotherapy and survival times of less than 1 year. However, improved outcomes have been shown with surgi- cal resection for patients with isolated hepatic vein tumor thrombus (36).
HCC is discussed in additional detail in the portal vein section. Invasion of the IVC by other tumors of the liver is rare but has been reported with intrahepatic cholangiocarcinoma (ICC) and metastatic disease (37,38).
Tumor in Portal Veins
Portal vein tumor thrombus is most commonly seen with HCC, occasionally with ICC, and rarely with some metastases or other uncommon hepatic tumors.
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Hepatocellular Carcinoma
HCC most commonly occurs in the setting of cirrhosis or in at-risk populations, including those with chronic infection with hepatitis B or C, alcoholic liver disease, or nonalcoholic fatty liver disease (39). Tumor in vein is a common feature of the natural course of HCC, with a frequency of 44%-62% at the time of death in autopsy studies (40,41). Portal vein invasion is a strong negative prognostic indicator, with a short me- dian survival time of 2-4 months without ther- apy. Treatment of these patients is traditionally limited to chemotherapy with the tyrosine kinase inhibitor sorafenib. However, in select patients, surgical resection or local-regional therapies, such as transarterial radioembolization, may result in improved outcomes (42).
Histopathologic confirmation of HCC tumor thrombus is typically not required, as a confident diagnosis can usually be established with imaging. HCC has three growth patterns, described as nodular, massive, and infiltrative. Tumor thrombus associated with the nodular and massive forms of HCC can most often be readily identified at imaging by contiguity with the primary tumor and an enhancement pattern typical of HCC, with arterial hyperenhancement and portal venous or delayed phase washout.
HCC with an infiltrative growth pattern, which is associated with venous invasion in 68%-100% of cases, can be more difficult to diagnose at imaging, as it can be radiologically occult at US and single-phase CT and relatively inconspicuous compared with the nodular form of HCC even at multiphase contrast-enhanced imaging. MRI can be helpful for diagnosis, as infiltrative HCC can be more conspicuous on nonenhanced images as areas of hyperintensity on T2-weighted and diffusion-weighted images and hypointensity on T1-weighted images compared with background liver. Identification of the associated tumor throm- bus may be the key to imaging diagnosis in these
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cases, and the additional parameters of MRI can be helpful for identifying the full extent of infiltra- tive tumor (43,44) (Fig 14).
Several classification systems for portal tumor thrombus have been described; however, none have gained widespread clinical use (45-47). Whether or not a classification system is used, it is critical to describe the full extent of tumor thrombus, differentiating between thrombus limited to intrahepatic portal branches, throm- bus extending into the right or left portal vein or both, and thrombus extending into the main portal vein, as the extent of thrombus is impor- tant for surgical and local-regional treatment decision making.
Intrahepatic Cholangiocarcinoma
ICC is the second most common liver cancer, representing around 10%-15% of malignancies, although its incidence continues to rise (48,49). The growth pattern of ICC with respect to the
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veins is typically more encasement with narrow- ing or occlusion rather than venous invasion with tumor thrombus (Fig 15). Some studies have reported the presence of macrovascular portal tumor thrombus in up to 15%-20% of cases of ICC, suggesting that tumor in vein may be an overlooked feature (50-52).
Portal vein tumor thrombus is more com- monly associated with central ICC toward the liver hilum than those at the liver periphery (53). All ICCs, and especially those occurring cen- trally, should be closely scrutinized for evidence of portal invasion. ICC is an aggressive malig- nancy with overall outcomes poorer than those of HCC. Portal vein invasion is an independent negative prognostic factor for ICC, with reported 5-year survival after surgical resection of 0% for patients with portal vein invasion compared to 23% for patients without (51).
At MRI, a target appearance at DWI with peripheral hyperintensity and a central area of
hypointensity favors the diagnosis of ICC, al- though it is not present in all lesions (55). Tumor thrombus from ICC may show similar enhance- ment and heterogeneity. If the diagnosis of HCC versus ICC is in question at imaging, then biopsy of the mass should be pursued.
Other Hepatic Neoplasms
Invasion of the portal veins by other liver neoplasms is exceedingly rare. Fibrolamellar HCC accounts for less than 1% of HCCs, and less than 10% of those patients are reported to have venous invasion. This tumor can be considered in younger (<40 years) patients without underlying liver disease (56). Portal vein invasion by metastatic disease is most commonly reported with colorectal cancer but remains rare (likely present in <1% of cases) (57).
Venous invasion can also occur with primary hepatic sarcomas, which represent 0.1% of all liver cancers. Hepatic sarcomas include a range of histopathologic behavior, from the relatively
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indolent hemangioendothelioma to the highly aggressive angiosarcoma. Primary leiomyosar- comas of the hepatic or portal venous system make up just a small subset of hepatic sarcomas (58,59) (Fig 16).
Tumor in Nonportal Splanchnic Veins
Invasion of the portal vein by a tumor not arising from the liver or invasion of the splenic, superior mesenteric, or other mesenteric veins is uncom- mon. Tumor thrombus in these veins is most often associated with pancreatic neuroendocrine tumors (PNETs).
Pancreatic Neuroendocrine Tumors
PNETs account for less than 2% of pancreatic tumors, although the prevalence may be increas- ing (60,61). Venous invasion is typically associ- ated with nonfunctioning nonsyndromic tumors, which make up the vast majority of PNETs. Owing to their clinical silence, these tumors often manifest at a later stage than their functional or syndromic counterparts.
Unfortunately, venous invasion by PNETs is underreported at imaging, being inaccurately
described in up to 60% of patients at retrospec- tive imaging review in one study (62). The exact prevalence of venous tumor invasion by PNETs is not known but may be as high as 20%-33% of cases (62,63). Presence or absence of venous involvement should be part of the search pattern and reporting for all PNETs, as this information is invaluable for surgical planning and may have prognostic significance, including association with reduced survival (62,63).
PNETs most commonly invade the splenic vein but can also extend into or separately involve the superior mesenteric or main portal vein or uncom- monly smaller branch veins, depending on the location of the primary tumor (62,63) (Fig 17). Tumor thrombus can be extensive, resulting in sig- nificant venous hypertension and venous collateral formation, including formation of gastric varices (Fig 17b). Upper gastrointestinal bleeding has rarely been reported as a presenting manifestation of PNET (64). PNETs are typically hypervascular at imaging, with most demonstrating hyperen- hancement in the arterial or portal venous phase (65). Similarly, tumor thrombus from PNET can also be hypervascular (Fig 18).
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Other Pancreatic Neoplasms
The tendency for PNETs to invade the splanch- nic veins is in stark contrast to the most common pancreatic tumor, pancreatic ductal adenocarci- noma (PDAC), which has a well-known pro- pensity to infiltrate along, encase, and narrow or occlude the peripancreatic vasculature. Intra- luminal tumor growth by PDAC is extremely rare and isolated to a few case reports (66) (Fig 19). This feature is so uncommon with PDAC that its presence at imaging should prompt consideration of PNET or other uncommon pancreatic tumors in the differential diagnosis.
Other pancreatic tumors are rare, and venous invasion associated with these tumors is even rarer. Case reports have described the phenom- enon in association with solid pseudopapillary tumor (67), anaplastic carcinoma (68), acinar cell carcinoma (69), tubular adenocarcinoma (70), or metastatic disease (71). Invasion of the portal veins or nonportal splanchnic veins by tumors with origins other than the liver or pancreas is also uncommon. Invasion of these veins has
been reported as a rare atypical manifestation of lymphoma (72) (Fig 20), gastric adenocarcinoma (73), or colon adenocarcinoma (74), as well as rarely reported primary venous leiomyosarcoma of these vessels (75,76).
Tumor in Pelvic Veins
While uncommon, invasion of the large pelvic veins is usually attributed to pelvic sarcomas. Invasion of the large pelvic veins by other ma- lignancies is possible but would be considered a rare atypical manifestation rather than a typical feature. For example, while testicular cancer is associated with vascular invasion pathologically, it is rarely evident at imaging and seen in only 1% of cases at CT (77). Invasion of small pelvic branch veins is not easily assessed at routine pelvic imaging. However, small-vessel venous in- vasion has an important role in imaging of rectal cancer.
Pelvic Sarcoma
Pelvic sarcomas are rare and represent a wide range of histopathologic types, but in general comprise a subset of relatively aggressive malig- nancies that have variable propensity for venous invasion. For example, up to 45% of primary
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pelvic osteosarcomas are associated with venous invasion (78) (Fig 4), while venous invasion is seen in 10%-20% of uterine leiomyosarcomas (79) (Fig 21). The most common pelvic sarcoma is liposarcoma, which can typically be diagnosed at imaging by the presence of fatty elements at CT or MRI. Liposarcomas are most commonly well differentiated, tend to displace rather than invade adjacent structures, and are not associated with venous invasion (80). However, the dediffer- entiated form of liposarcoma demonstrates more aggressive features, including metastases and in- vasion of adjacent structures, and has rarely been reported to invade veins (81,82).
Primary Venous Leiomyosarcoma
As discussed earlier, primary venous leiomyosar- coma is rare and most commonly involves the IVC, but has been reported in veins of the pelvis, including the iliac and femoral veins. While it is
uncommon, it is important for radiologists to be aware of the possibility of these tumors. Our experience and those reported in the literature suggest that pelvic venous leiomyosarcoma can be misdiagnosed as deep-vein thrombosis (DVT) and treated with anticoagulation, being correctly diagnosed only when symptoms persist or worsen despite therapy (83-86). DVT is common and pelvic venous leiomyosarcoma is rare, so this mis- diagnosis is an understandable pitfall. At US of the iliac or femoral veins, an overly expansive throm- bus or a thrombus that deforms or extends beyond the vessel wall should raise suspicion for venous leiomyosarcoma and prompt careful Doppler interrogation for internal flow or further character- ization with multiphase CT or MRI (Fig 22).
Uterine Leiomyomatosis
A benign cause of venous invasion has been described in the pelvis in the form of intravenous
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leiomyomatosis, a rare atypical form of uterine leiomyomatosis with growth of tumor within the intrauterine veins and spread to the extrauterine pelvic veins and beyond. While clinically aggres- sive, this variant remains histologically benign (87). Growth within the uterine and pelvic veins is common in this condition, but extensive ve- nous involvement is possible, with venous exten- sion into the right heart reported in 10%-40% of cases (88,89). Like all uterine leiomyomas, leio- myomatosis with intravascular extension occurs most commonly in premenopausal women.
Imaging features of intravenous leiomyomato- sis are similar to those of leiomyomas seen in the uterus. US may show vascular masses within the vessels of the pelvis, while CT shows relatively homogeneous soft-tissue masses in the uterus with extension into the surrounding veins (Fig 23). MRI classically shows low to intermediate T1 signal intensity and characteristic low T2 signal intensity, usually with homogeneous en- hancement. The intravascular masses have been described as having a characteristic sausage-like appearance (87,90). The main differential diag- nostic consideration is primary leiomyosarcoma, and histologic confirmation is usually required to confirm the diagnosis.
The prognosis for patients with intravenous leiomyomatosis depends on the vascular tumor burden and whether complete surgical resection is possible. These tumors are frequently responsive to antiestrogenic hormonal therapy, which can be used in combination with surgical resection or de- bulking. Tumor recurrence is not uncommon and is thought to be secondary to incomplete resec- tion. These tumors can grow slowly, and long- term imaging surveillance is recommended after presumed successful treatment (91-93).
Rectal Adenocarcinoma
Rectal cancer is a common disease with over 43 000 new cases diagnosed annually in the United States, mostly in the form of rectal adenocarcinoma (14). Preoperative staging with imaging allows accurate determination of patients who may benefit from neoadjuvant chemoradia- tion therapy versus those who can be treated with primary resection. MRI has proved to be an ef- fective tool for assessment of the surgical circum- ferential resection margin and depth of tumor extension beyond the muscularis propria (94). In addition, MRI has been shown to be useful for identifying the presence or absence of extramural vascular invasion (EMVI).
EMVI is defined as presence of tumor cells in the blood vessels outside the muscularis propria. Classically, EMVI is present in 17%-52% of rectal tumors at pathologic assessment. Although not a component of rectal cancer staging, EMVI does carry significant prognostic information. This feature is associated with more advanced tumors and is an independent predictor of both local and distant recurrence (95-99). Most sig- nificantly, the presence of EMVI portends poorer survival (100,101).
While involvement of very small perirectal veins cannot be diagnosed with imaging, di- agnosis of EMVI involving the midrectal and superior rectal veins is achievable with current high-resolution rectal cancer MRI protocols. The primary sequence for such examinations remains small field-of-view T2-weighted imaging. EMVI is diagnosed when the normal hypointense vessel lumen is replaced by the intermediate T2 signal intensity of adjacent tumor, or more convincingly, when this feature is combined with irregularity of the lumen border and expanded appearance of
the vessel (Fig 24). The venous tumor in EMVI also follows the signal intensity characteristics of the adjacent primary tumor with other MRI sequences, including hyperintensity at DWI and enhancement at postcontrast imaging. Given its importance in prognosis, the presence or absence of EMVI should be described in all rectal cancer staging examinations and is part of rectal cancer staging reporting templates, typically listed as present, absent, or equivocal (102).
Pitfalls and Mimics of Tumor in Vein
Because accurate diagnosis of venous tumor inva- sion affects prognosis and therapeutic planning for a wide variety of tumors, awareness of com- mon mimics and diagnostic challenges is impor- tant for image interpretation. Pitfalls and mim- ics of tumor in vein include flow artifact, bland thrombus, cavernous transformation of the portal vein, and pseudolipoma of the IVC.
Flow Artifact
The most common mimic of venous thrombus at contrast-enhanced imaging is flow artifact, result- ing from mixing of enhanced and nonenhanced blood in the vessels. When this occurs in proxim- ity to an abdominopelvic tumor, the appearance can be confused with that of tumor thrombus.
Flow artifact typically occurs central to the confluence of draining veins from different terri- tories that have different degrees of enhancement. At CT or MRI, a linear appearance of different intraluminal attenuation or signal intensity can often be followed to the opacified or nonopacified veins. With CT, additional delayed imaging of the area of concern can be performed if it is observed at the time of scanning. MRI has the benefit of multiple nonenhanced parameters and mul- tiple phases of enhancement, which allow easier confirmation of flow artifact, with fill-in at later phases of enhancement and lack of filling defects at nonenhanced flow-sensitive imaging (103) (Fig 25). Multiplanar MRI is important to distinguish slow flow from true thrombus at nonenhanced imaging, as thrombus will have similar signal in- tensity in multiple planes, but slow-flowing blood will change signal intensity relative to the imaging plane (104).
Bland Thrombus and Cavernous Transformation
Bland venous thrombus can be found in patients with malignancy, hypercoagulable state due to various causes, venous stasis due to immobil- ity or extrinsic venous compression, current or previous venous catheterization, or idiopathic causes (103). A retrospective study of nearly 11 000 patients with primary or metastatic ab-
*
dominal malignancy found that 0.5% of patients had bland thrombus at MRI, most commonly in the IVC with retroperitoneal malignancies and in the portal vein with hepatic malignancies (4).
As discussed earlier, bland thrombus is best differentiated from tumor thrombus by lack of enhancement in the clot at CT and MRI and lack of Doppler flow in the clot at US. However, as the thrombus ages, it may recanalize with peripheral nonenhancing or calcified thrombus. This recana- lized central flow can be confused with tumoral enhancement at Doppler US (105). CT, and particularly MRI with subtraction imaging, allows easier differentiation of the chronic eccentric com- ponents of thrombus from recanalized central flow.
Chronic thrombosis of the extrahepatic portal vein can result in cavernous transformation, or development of numerous small and tortuous collateral veins at the liver hilum, arising from biliary, gastric, pancreaticoduodenal, splenic, and mesenteric venous tributaries in varying degrees (106). These small slow-flow collaterals can have intermediate signal intensity on T2-weighted images and a tangled confluent appearance on contrast-enhanced images, which could be con- fused with tumor infiltration and enhancement. Identification of the absent portal vein and other venous collaterals can help establish the correct diagnosis (107).
Pseudolipoma of IVC
A normal variant of fat deposition adjacent to the IVC at the level of the diaphragmatic vena caval foramen has rarely been mistaken for bland or tumor thrombus within the IVC (108,109). This
*
*
a.
b.
so-called pseudolipoma is an uncommon ana- tomic variant seen in 0.5% of patients at CT. It is usually a round or oval collection of fat located medial or anterior to the IVC at a level at or above the hepatic venous confluence (110) (Fig 26). Awareness of this normal finding can prevent misdiagnosis and avoid undue patient anxiety and unnecessary workup.
Conclusion
Differentiation of bland versus tumor thrombus is of critical clinical importance and can be accu- rately diagnosed with multiple imaging modalities, including advanced techniques. Identification and accurate description of tumor thrombus at imag- ing can inform prognosis and guide appropriate clinical management and treatment planning. A
variety of abdominopelvic tumors can manifest with venous invasion, including tumors of the liver, kidneys, adrenal glands, and uterus and of the veins themselves. The thrombus location, organ of tumor origin, frequency of tumor type for venous invasion, and imaging characteristics can guide the radiologist to the correct diagnosis or an appropriately narrow differential diagnosis.
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