Imaging Features of Sclerosed Hemangioma

Sclerosed Hemangioma Abdominal Imaging Clinical Observations Deirdre J. Doyle 1 Korosh Khalili 1 Maha Guindi 2 Mostafa Atri 3 Doyle DJ, Khalili K, Guindi M, Atri M Keywords: abdominal imaging, CT, liver, MRI, radiologic pathologic correlation DOI:10.2214/AJR.06.1076 Received August 13, 2006; accepted after revision October 31, 2006. 1 Department of Medical Imaging, University Health Network and Mount Sinai Hospital, 610 University Ave., Toronto, Ontario, M5G 2M9, Canada. Address correspondence to D. J. Doyle (Deirdre.Doyle@uhn.on.ca). 2 Department of Pathology, University Health Network and Mount Sinai Hospital, Toronto, Ontario, Canada. 3 Department of Medical Imaging, Sunnybrook and Women s Hospital, Toronto, Ontario, Canada. AJR 2007; 189:67 72 0361 803X/07/1891 67 American Roentgen Ray Society Imaging Features of Sclerosed Hemangioma OBJECTIVE. The purpose of this study was to review the imaging features of sclerosed hemangioma. CONCLUSION. In our series, suggestive features of sclerosed hemangiomas include geographic outline, capsular retraction, decrease in size over time, and loss of previously seen regions of enhancement. Additional features include presence of transient hepatic attenuation difference (THAD), rim enhancement, and nodular regions of intense enhancement as seen in typical hemangiomas. Although not pathognomonic, some features of sclerosed hemangioma can suggest it as a diagnostic possibility and lead to biopsy rather than more extensive intervention. avernous hemangioma is the most C common noncystic hepatic lesion, the reported incidence being as high as 20% [1]. Most hemangiomas remain stable on follow-up imaging [2]; growth and spontaneous regression are reported to be very rare [3]. Hemangiomas that undergo degeneration and fibrous replacement are called sclerosed, thrombosed, or hyalinized hemangiomas [4]. Although there have been isolated case reports of sclerosed hemangioma [4 7], no case series have been reported, to our knowledge. It has been suggested that prospective diagnosis of sclerosed hemangioma is impossible [5]. Our aim was to review the imaging features of a series of proven sclerosed hemangiomas to determine whether there are features that would allow prospective diagnosis. Materials and Methods This retrospective study was approved by our institutional research ethics board, and informed consent was waived. A retrospective search through pathology reports from August 2001 to January 2005 for the diagnosis of sclerosed hemangioma in hepatectomy or liver biopsy specimens yielded seven hemangiomas in five patients who underwent imaging before intervention. Percutaneous biopsy was performed in four lesions, intraoperative biopsy was performed in one lesion, and a right hepatectomy yielded two sclerosed hemangiomas. Four of five patients had known primary malignant tumors (two of the colon, one of the rectum, and one gastrointestinal stromal tumor). One patient had a history of hepatitis B and C, but the liver did not appear cirrhotic. Twenty-five additional patients were found through retrospective review of the radiology information system from December 2000 through December 2004 with the search terms sclerosed/sclerosing, thrombosed/thrombosing, hyalinized/hyalinizing, and hemangioma. Inclusion criteria used for the imaging diagnosis of sclerosed hemangioma were available previous triphasic CT scans showing peripheral nodular enhancement with further filling of the lesion on delayed images (Fig. 1A) and follow-up CT scans showing change in morphologic characteristics over time (Fig. 1B). Only three of these 25 patients were eligible for inclusion because they had undergone previous CT that showed typical hemangioma with subsequent change in imaging characteristics over 9 20 months. In total, 10 sclerosed hemangiomas were identified in eight patients (four men, four women) with an age range of 46 77 years (mean, 58 years). Imaging findings on CT (10 lesions), MRI (six lesions), and sonography (five lesions) were analyzed. Lesion size, number, morphologic features, calcification, relative attenuation, T1- and T2-weighted signal intensity, and enhancement characteristics were analyzed. Follow-up images of six lesions were available after the initial appearance of sclerosis, and these images were assessed for changes in lesion size and enhancement pattern. CT was performed with a 4-MDCT (n =4), 8-MDCT (n =3), 16-MDCT (n =1), or 64-MDCT (n = 2) scanner (LightSpeed QX/I or Ultra, GE Healthcare; Sensation 16, Siemens AJR:189, July 2007 67

Fig. 1 72-year-old woman with sclerosed hemangioma. A, Axial contrast-enhanced CT scan shows large hypoattenuating classic hemangioma of segment II of liver with peripheral nodular enhancement. B, Follow-up arterial phase CT scan 21 months after A shows decrease in hemangioma size with rim enhancement in keeping with sclerosis. Medical Solutions; Aquilion 64, Toshiba). Protocols included portal venous phase only (70 seconds, 5-mm slice thickness, 2.5-mm reconstruction interval) for three lesions and a triphasic liver protocol for seven lesions (unenhanced, 25 and 65 seconds, 5-mm slice thickness, 2.5-mm reconstruction interval). All patients were given IV contrast material: iodixanol (Visipaque 270, GE Healthcare) in six cases and iohexol (Omnipaque, GE Healthcare) in two cases. The dosage was a volume of 100 160 ml at a rate of 5 ml/s with exposure factors of 120 kv and 140 415 ma. The following MR images were acquired with a 1.5-T system (Genesis Sigma and Sigma Excite, GE Healthcare): axial spoiled gradient-recalled in- and out-of-phase T1-weighted images (TE, 4.2 and 2.1), coronal single-shot fast spin-echo T2- weighted, axial T2-weighted breath-hold fast-recovery fast spin-echo (TE, 90), and axial singleshot fast spin-echo T2-weighted images (TE, 180). Dynamic contrast-enhanced, fat-saturated, fast spoiled gradient-recalled (minimum TE) images were obtained after administration of gadodiamide (Omniscan, GE Healthcare) (four lesions) and gadobenate dimeglumine (MultiHance, Bracco Diagnostics) (two lesions). Gadobenate dimeglumine was used for improved detection of liver lesions in the delayed parenchymal phase in the one patient with known metastatic disease. At present, however, this agent is not routinely used at our institution for detection of metastatic disease. Delayed contrast-enhanced spoiled gradientrecalled T1-weighted images with fat saturation were also obtained 5 minutes after gadodiamide injection and 5 minutes and 3 hours after gadobenate dimeglumine injection. A Results Morphologic Appearance Lesion size ranged from 1.4 to 7.7 cm (mean, 3.7 cm). All 10 lesions had a geographic pattern (Fig. 2A). Seven of 10 lesions exhibited volume loss, which manifested as capsular retraction or concavity over the lesion. This finding appeared on follow-up images of an additional lesion (Table 1). Calcification was found in only one lesion. In five patients, additional hemangiomas found in the liver had a typical enhancement pattern (Fig. 2A). Enhancement Characteristics Dynamic enhancement characteristics were present in eight of 10 sclerosed hemangiomas, three with CT, one with MRI, and four with both techniques. Dynamic studies of the other two lesions showed no visual evidence of internal enhancement (Figs. 2A and 2C). In one patient, enhancement was found only in the venous phase of CT. Unenhanced CT images of six lesions showed hypoattenuation compared with adjacent liver tissue. Arterial phase Nodular foci of enhancement, not necessarily in the periphery of the lesions, were found in the arterial phase of CT of six of eight lesions. In addition, wedgeshaped regions of transient hepatic attenuation difference around the lesion were found in five of eight lesions (Figs. 3 and 4A). Transient rim enhancement was found in two of eight lesions (Figs. 1B, 3, and 4C). Portal venous phase In five of six lesions, the nodular foci of enhancement were the same size in the venous phase but had grown in one of six lesions (Figs. 3 and 4A). In one patient, slight peripheral nodular enhancement was found in the venous phase only. In another patient, rim enhancement also was found in the venous phase. Delayed phase Delayed-phase images were available for six of the 10 lesions. Three of these lesions were visualized on CT, two on MRI, and one on both CT and MRI. Images of five of the six lesions showed new, irregular regions of delayed enhancement within the lesions that manifested as areas of mild hyperattenuation or hyperintensity compared with adjacent liver (Fig. 4D). In one patient who received gadobenate dimeglumine, typical hemangiomas were homogeneously hypointense with the liver on the delayed images. The two sclerosed hemangiomas were homogeneously isointense or nearly isointense with the liver and therefore were almost imperceptible (Fig. 2D). This patient also had a hepatic metastatic lesion from a colorectal primary lesion that exhibited heterogeneous uptake of the contrast agent in the delayed phase (Fig. 2D). MRI Signal Intensity Six lesions in four patients were evaluated with MRI. All lesions appeared hypointense on T1-weighted images. High signal intensity such as that of typical hemangioma on T2- weighted images with intermediate and long echo times was present to variable degree in all lesions (Fig. 4B). In two sclerosed hemangiomas in the same patient, the entire lesion was of homogeneous high signal intensity (greater than that of spleen but darker than that of CSF) B 68 AJR:189, July 2007

Sclerosed Hemangioma (Fig. 2B). In the other lesions, variable degrees of peripherally based areas of high T2- weighted signal intensity were mixed with areas of isointensity to hypointensity compared with the liver. The areas of high signal intensity corresponded to regions of early and nodular enhancement, whereas the isointense to hypointense areas exhibited enhancement only on 5-minute delayed images (Figs. 4B and 4D). Sonographic Features Four lesions were heterogeneously hyperechoic. A 5.3-cm lesion in one patient was not prospectively detected on sonography. A C Fig. 2 56-year-old woman with colon cancer. A, Axial contrast-enhanced CT scan at presentation shows two classic hemangiomas in left lobe (arrows). Pathologically proven sclerosed hemangioma (arrowheads) in segments VI and VII has geographic pattern, exhibits hypoattenuation with capsular retraction, and exhibits no enhancement. B, Follow-up T2-weighted axial MR image 64 months after presentation shows interval development of metastatic lesion of colon carcinoma in liver segments V and VI. Two classic hemangiomas of high signal intensity persist. Previously seen sclerosing hemangioma (arrowhead) in segments VI and VII has higher signal intensity than spleen. C, Axial MR image obtained after administration of gadobenate dimeglumine shows rim enhancement of metastatic lesion and absence of enhancement of sclerosing hemangioma (arrowhead). D, Delayed MR image after administration of gadobenate dimeglumine shows heterogenous signal intensity of metastatic lesions, hypointense classic hemangioma, and isointense sclerosing hemangioma (arrowhead). Follow-Up Imaging Follow-up imaging of six lesions over 7 64 months (average, 32 months) showed that the size of four of the lesions decreased. In four lesions, internal enhancement had been found in the venous phase of the original scan. The follow-up images showed that in three of the four lesions, the regions of enhancement decreased in size and number or entirely disappeared. Discussion Many incidental benign liver lesions are found during routine examinations and during staging of known malignant disease. In addition, the high incidence of hemangioma increases the probability of encountering atypical manifestations, including sclerosis. It has been suggested [5] that prospective differentiation of a sclerosed hemangioma from a malignant tumor is not possible. In our series of 10 lesions, we found features suggestive of sclerosed hemangioma. All 10 lesions had a geographic pattern, and volume loss manifested by capsular retraction eventually was seen in eight lesions. The presence of transient hepatic attenuation difference in the arterial phase (five of eight lesions), nodular regions of enhancement (six of eight lesions), and addi- B D AJR:189, July 2007 69

TABLE 1: Imaging Findings in 10 Cases of Sclerosed Hemangioma Patient Imaging Volume Rim Age (y) Sex Technique Loss Arterial Phase Enhancement THAD Portal Venous Phase Delayed Phase Follow-Up Finding 72 F CT Yes No Yes No No internal nodules NA Decreased size 62 M CT Yes No No No No internal nodules NA NA 46 F Sonography, CT Yes Internal nodules No Yes Static internal nodules No change Decreased size and number of nodules 61 F CT, MRI Yes Internal nodules Yes Yes Static internal nodules Delayed enhancement Decreased size 77 M a Sonography, CT, MRI Yes Internal nodules No No Internal nodules Delayed enhancement NA 77 M a Sonography, CT, MRI Yes Internal nodules No Yes Growing internal Delayed enhancement NA nodules 53 M CT, MRI No Internal nodules No Yes Static internal nodules Delayed enhancement Decreased size and number of nodules 56 F b Sonography, CT, MRI No No No Yes No internal nodules NA Decreased size 56 F b Sonography, CT, MRI Yes Internal nodules No No Static internal nodules Delayed enhancement Decreased size and number of nodules 40 M CT Yes NA No No Static internal nodules NA NA Note THAD = transient hepatic attenuation difference, NA = not available. a Same patient. b Same patient. Fig. 3 61-year-old woman with gastrointestinal stromal tumor and biopsy-proven sclerosed hemangioma. Axial arterial phase CT scan shows geographic lesion in left lobe of liver with rim and nodular enhancement and peripheral transient hepatic attenuation difference (arrowhead). tional typical hemangiomas (five of eight patients) further increase suspicion. Rim enhancement, seen in three of 10 lesions, has been described in case reports [5 7]. Although it is not unique, this sign can be helpful when present. The heterogeneity of signal intensity of sclerosed hemangiomas on T2-weighted images in our series detract from the normally high specificity of high T2 signal in the recognition of hemangiomas. However, areas of typical high T2-weighted signal intensity on the long TE (180 milliseconds) sequences, which correspond to areas of enhancement, may be of minor help. Areas of unusually low T2-weighted signal intensity, which may represent regions of sclerosis (fibrosis) may also provide assistance. Ultimately, apart from previous documentation of typical hemangioma, we have not found features definitive for the diagnosis of sclerosis. However, the combination of findings may be enough to suggest biopsy for diagnosis instead of definitive therapy for some lesions. The findings on 3-hour delayed gadobenate dimeglumine images of a patient with rectal carcinoma and hepatic metastasis adjacent to the larger hemangioma, which led to resection, were intriguing. The sclerosed hemangiomas were long-standing and on delayed imaging became isointense to the adjacent liver. The contrast agent was taken up by the hepatocytes in the adjacent liver tissue and was retained in the lesions, presumably because of their highly fibrous nature. The other typical hemangiomas appeared well defined and hypointense, but the metastatic lesions had a highly heterogeneous appearance. The finding of homogeneous delayed retention of contrast agent raises the possibility of differentiating long-standing sclerosed hemangiomas with this technique. This possibility warrants further study. Haratake et al. [5] and Takayasu et al. [6] described histologically proven sclerosed hemangiomas that exhibited persistent irregular ring and slight peripheral enhancement on CT. Yamashita et al. [7] described a lesion with marginal pooling of contrast material on CT and MRI. Those authors suggested that sclerosing hemangioma be included in the differential diagnosis of colorectal metastasis. Aibe et al. [8] proposed that sclerosing hemangioma be included in the differential diagnosis of hepatic lesions with delayed enhancement. Another report [9] describes nonenhancing, well-demarcated nodular areas proven at pathologic examination to be sclerotic nodules responsible for the atypical CT findings. Cheng et al. [4] described hyalinized hemangiomas showing lower signal intensity than CSF on T2-weighted images, lack of early enhancement, and slight peripheral enhancement in the late phase. Ros et al. [10] found that nodular areas of reduced signal intensity on T2-weighted images corresponded to the histologic finding of fibrosis. Fibrosis when present occurs within the body of a hemangioma, beginning in the center and extending more peripherally to a variable degree [11]. Sometimes a sclerotic nodule can grow large enough to replace the entire hemangioma, mimicking other solid tumors [5]. Col- 70 AJR:189, July 2007

Sclerosed Hemangioma A C Fig. 4 53-year-old man with hepatitis B and C and biopsy-proven sclerosed hemangioma. A, Axial contrast-enhanced CT scan shows large hypoattenuating lesion of liver segments VII and VIII with central and peripheral nodular areas of enhancement and large peripheral transient hepatic attenuation difference (arrowheads). B, Axial T2-weighted MR image shows central and peripheral regions of increased signal intensity corresponding to foci of enhancement in A and larger regions appearing isointense or hypointense. C, Gadolinium-enhanced MR image shows peripheral rim enhancement. D, Delayed-phase gadolinium-enhanced MR image shows regions of delayed contrast enhancement. lagen-rich and relatively acellular mature fibrous tissue is generally of lower signal intensity than muscle on T2-weighted images because of decreased free-water content and low mobile proton density [6]. Tung et al. [12] proposed that the appearance of hemangiomas on T2-weighted images should reflect the opposing influences on T2-weighted relaxation of slowly flowing blood in vascular spaces and connective tissue. A complicating factor is the contribution to signal heterogeneity of hemorrhage, thrombosis, hyalinization, calcification, and cystic cavities [6, 10]. The process of sclerosis generally begins in the center of a hepatic hemangioma and can extend to involve the entire lesion. The term sclerosed is reserved for hemangiomas that are predominantly fibrosed with near complete obliteration of the vascular spaces [13]. The term sclerosing is used to describe partially affected lesions. The histologic appearance of sclerosed hemangiomas is different from the areas of thrombosis seen in giant hemangioma. The extent to which sclerosing and sclerosed hemangiomas are related is unresolved. Results of one study [13] suggest that sclerosed hemangiomas develop from capillary hemangiomas but that sclerosing hemangiomas arise from cavernous hemangiomas. In our series, all of the lesions diagnosed on the basis of pathologic findings fit the definition of sclerosed hemangioma, not hemangioma with an area of sclerosis. Moreover, all of the lesions had imaging appearances that did not fit the imaging criteria for hemangioma, with or without scarring. In our series, features suggestive of sclerosed hemangiomas included geographic pattern, capsular retraction, decrease in size over time, and loss of previously seen regions of enhancement. Additional features included the presence of transient hepatic attenuation difference, rim enhancement, and nodular regions of intense enhancement as seen in typical hemangioma. A combination of these findings should raise the possibility of the B D AJR:189, July 2007 71

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