Gastrointestinal Imaging
Original Research
Sclerosing Angiomatoid Nodular Transformation of the Spleen: CT and MRI Features With Pathologic Correlation
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OBJECTIVE. The objective of this study was to describe the CT and MRI features of sclerosing angiomatoid nodular transformation of the spleen with pathologic correlation.
MATERIALS AND METHODS. Nine patients with surgically resected and pathologically confirmed sclerosing angiomatoid nodular transformation were included in the study. Clinical history was reviewed to determine patient demographics and symptoms at presentation. Gross pathologic, histologic, and immunohistochemical findings were recorded. CT (n = 9) and MRI (n = 4) examinations were evaluated for lesion shape and margins, intrinsic characteristics, and enhancement pattern.
RESULTS. Patients included were six women and three men, with a mean age of 41.2 years. Pathologic features of sclerosing angiomatoid nodular transformation included multiple angiomatous nodules in a radiating pattern with a central stellate fibrous scar and evidence of hemosiderin deposition. On imaging, the lesions were solitary and round, 78% having a lobulated margin. They were heterogeneously hypoenhancing during the arterial and portal venous phases of contrast-enhanced CT or MRI, with peripheral enhancing radiating lines in 88% of lesions. They showed progressive enhancement and were isoenhancing or hyperenhancing in the delayed phase. A hypoenhancing central scar was shown on imaging in 22% of lesions. All lesions were hypointense on T2-weighted images.
CONCLUSION. Sclerosing angiomatoid nodular transformation shows characteristic CT and MRI findings reflecting the underlying pathology. Typical features are a solitary, round, lobulated mass with early peripheral enhancing radiating lines and progressive enhancement of the angiomatous nodules; delayed enhancement of the fibrous tissue; and hypo-intense T2 signal intensity from hemosiderin deposition.
Keywords: CT, MRI, pathologic findings, sclerosing angiomatoid nodular transformation, splenic mass
Initially described in 2004 by Martel et al. [1], sclerosing angiomatoid nodular transformation (SANT) is a benign vascular splenic lesion consisting of multiple angiomatoid nodules surrounded by dense fibrous tissue that often coalesces centrally to form a scar. It has previously been referred to by numerous pathologic terms, including cord capillary hemangioma and multinodular hemangioma, and prior cases have also been classified as hamartomas, hemangioendotheliomas, sclerosed hemangiomas, and inflammatory pseudotumors [1, 2].
The angiomatoid nodules are composed of several types of blood vessels normally found in splenic red pulp, which can be distinguished on the basis of their immunohistochemical profiles. These include capillaries (CD31+CD34+CD8−), small veins (CD31+CD34−CD8−), and sinusoids (CD31+CD34−CD8+) [1]. However, the pathogenesis of SANT is unclear. It may represent a de novo lesion, a hamartomatous response of the splenic red pulp to a vascular insult or stromal proliferation, a spectrum of IgG4-sclerosing disease, or a final stage of inflammatory pseudotumor, hamartoma, or organized hematoma [1, 3–5].
SANT lesions are most often discovered as incidental findings, although 20% of affected patients are reported to have synchronous or metachronous malignancies [1]. SANT can rarely cause abdominal pain, splenomegaly, or anemia. SANT appears to have a benign clinical course, with splenectomy being curative in all patients.
To the best of our knowledge, there have been only six radiology reports to date on the imaging features of SANT, consisting of case reports [6–10] in addition to a single small case series of three patients focused on sonographic findings [11]. The purpose of our study was to define the CT and MRI features of SANT with pathologic correlation in a series of nine patients.
| Materials and Methods |   |
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This retrospective study was approved by our institutional review board. Informed consent was not required. A review of the radiologic pathology archives of the Armed Forces Institute of Pathology over a 25-year period (1985–2010) identified six patients with a diagnosis of SANT. Because of the pathologic similarities to sclerosed hemangiomas, all cases of sclerosed hemangiomas from the same time period were also retrieved (five patients), three of which met pathologic criteria for SANT. Therefore, our final study group consisted of nine patients: six women and three men, with an average age of 41.2 years (range, 27–68 years). SANT was an incidental finding in six patients (67%). Presenting symptoms included left upper quadrant pain (n = 1) and anemia (n = 1). The remaining patient had cervical lymphadenopathy, fever, and night sweats, and biopsy of a cervical lymph node revealed reactive changes. All patients underwent splenectomy. The clinical, pathologic, and imaging findings are summarized in Table 1. Because this lesion is a newly recognized entity with interesting pathologic and imaging features, two of the cases (patients 7 and 8) were included in previous case reports [8, 10].
Pathology and surgical records were reviewed for the number and sizes of the tumors. Histopathology reports and slides were available for all patients. Two pathologists with 35 and 19 years of experience in hematopathology reviewed the H and E–stained slides in every case to confirm or establish the diagnosis of SANT on the basis of criteria originated by Martel et al. [1] The presence of a capsule and hemosiderin deposition were documented. Immunohistochemistry reports were available for five patients. These were assessed for immunoreactivity to the vascular markers CD8, CD31, and CD34. For eight patients, photographs were available of the cut resected gross specimen, and the remaining patient had a description of the gross specimen in the pathology report. These were evaluated for the presence of a central scar and the presence and distribution of red-brown nodules.
Imaging was performed at multiple institutions using a variety of equipment and protocols regarding slice thickness, IV contrast injection, and MRI sequence parameters. All patients underwent abdominal CT. Eight patients had contrast-enhanced CT scans. Six of these patients had imaging during a single phase of enhancement: two during the arterial phase, three during the portal venous phase, and one during the delayed phase. Two patients had dynamic imaging, one with arterial and portal venous phase images and one with unenhanced, arterial phase, portal venous phase, and delayed phase images. One patient had an un-enhanced CT scan only. MRI was performed for four patients. All MRI examinations included un-enhanced T1- and T2-weighted sequences and dynamic fat-saturated gadolinium-enhanced T1-weighted sequences. One MRI examination included in-phase and out-of-phase sequences.
Two abdominal radiologists with 5 and 4 years of experience reviewed all images retrospectively during one session. Final interpretation was reached by consensus. The radiologists knew of the diagnosis of SANT but were unaware of the specific pathologic findings. CT and MR images were evaluated for the presence and number of masses within the spleen. The shape and margins of each mass were documented. The attenuation or signal intensity of the lesion was compared with the normal spleen on unenhanced CT and MR images in addition to lesion homogeneity or heterogeneity. Each splenic mass was also evaluated for the presence of a central scar and calcification.
The enhancement of the majority of a lesion, with the exception of the central scar, was compared with the spleen in each phase in addition to assessing whether enhancement was homogeneous or heterogeneous. The following patterns of enhancement were also documented: rim enhancement, enhancement of peripheral radiating lines, and the presence and enhancement of a central scar. In cases with dynamic imaging, the enhancement of each phase was compared visually to the previous phase for progressive enhancement, no change, or washout. One investigator reviewed the gross and histologic pathology findings and correlated them with the imaging features.
| Results | |
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On histologic examination, all tumors consisted of multiple angiomatous nodules in a fibrous stroma (Fig. 1A). The nodules contained multiple slitlike, round, or irregular vascular spaces lined by plump endothelial cells (Fig. 1B). The surrounding stroma varied from myxoid to dense fibrous tissue and contained myofibroblasts, plasma cells, lymphocytes, and hemosiderin-laden macrophages (Fig. 1C). Hemosiderin deposition was found in all cases. The tumors were not encapsulated. All five lesions with immunohistochemistry reports were positive for CD31, CD34, and CD8.
 View larger version (218K) | Fig. 1A —Histopathologic features of sclerosing angiomatoid nodular transformation in 67-year-old man. A, Photomicrograph (original magnification, ×1.25; H and E stain) shows multinodular mass with variably sized nodules and intervening fibrous tissue. |
 View larger version (211K) | Fig. 1B —Histopathologic features of sclerosing angiomatoid nodular transformation in 67-year-old man. B, Photomicrograph (original magnification, ×40; H and E stain) of angiomatous nodule shows plump endothelial cells lining numerous vascular spaces filled with erythrocytes. |
 View larger version (217K) | Fig. 1C —Histopathologic features of sclerosing angiomatoid nodular transformation in 67-year-old man. C, Photomicrograph (original magnification, ×4; H and E stain) of dense fibrous stroma between angiomatous nodules. Scattered brown granules (arrows) are hemosiderin pigment. |
All patients underwent splenectomy. A solitary splenic mass was found in all patients, with an average size of 5.8 cm (range, 3.5–10.2 cm). A central tan-white stellate fibrous scar was present in eight cases (89%). The remaining case had scattered white fibrous areas without a coalescent scar. The lesions were otherwise composed of multiple red-brown nodules. In the cases with central scars, the nodules were located mainly around the periphery and in a radiating pattern toward the center of the lesion between the stellate projections of the fibrous scar (Fig. 2B). In the lesion without a coalescent scar, the nodules were diffusely distributed.
 View larger version (196K) | Fig. 2A —67-year-old man with sclerosing angiomatoid nodular transformation (same patient as in Fig. 1). A, Arterial phase contrast-enhanced axial CT image shows smooth, round mass with rim enhancement. |
 View larger version (125K) | Fig. 2B —67-year-old man with sclerosing angiomatoid nodular transformation (same patient as in Fig. 1). B, Cut surface of resected specimen shows numerous dark red nodules around periphery of lesion and in radiating pattern between stellate yellow fibrous scar. |
On CT, all lesions were solitary and round, with a lobulated (n = 7) or smooth (n = 2) margin. Both lesions with unenhanced CT images were homogeneous and slightly hypoattenuating. In the seven cases with arterial or portal venous phase contrast-enhanced CT images, all lesions were heterogeneous and hypoenhancing. Six of these showed peripheral enhancing radiating lines, and two cases had rim enhancement (Figs. 2 and 3). Two lesions with imaging during the delayed phase showed homogeneous enhancement, either isoenhancing (n = 1) or hyperenhancing (n = 1) relative to the spleen. The two cases with dynamic imaging showed progressive enhancement. Central scars were present in two lesions (22%), which were hypoenhancing in all phases. One lesion contained multiple scattered punctate calcifications.
 View larger version (177K) | Fig. 3A —37-year-old man with sclerosing angiomatoid nodular transformation. A, Arterial phase contrast-enhanced axial CT image shows hypoattenuating mass with peripheral enhancing radiating lines (arrows). |
 View larger version (180K) | Fig. 3B —37-year-old man with sclerosing angiomatoid nodular transformation. B, Portal venous phase contrast-enhanced axial CT image shows progressive, heterogeneous enhancement. |
In the four patients who underwent MRI, the lesions were isointense on T1-weighted images, with two being homogeneous and the other two heterogeneous. All lesions were heterogeneous and predominantly hypointense on T2-weighted images. One case with chemical-shift imaging showed multiple low-signal-intensity foci with increased prominence on the in-phase as compared with the outof-phase images (Fig. 4). A central scar was present in one case, which had high signal intensity on T2-weighted images but was not revealed on T1-weighted images.
 View larger version (156K) | Fig. 4A —44-year-old man with sclerosing angiomatoid nodular transformation. A, In-phase (A) and out-of-phase (B) axial MR images. Increased prominence of low-signal-intensity foci on in-phase image is compatible with presence of hemosiderin. |
 View larger version (188K) | Fig. 4B —44-year-old man with sclerosing angiomatoid nodular transformation. B, In-phase (A) and out-of-phase (B) axial MR images. Increased prominence of low-signal-intensity foci on in-phase image is compatible with presence of hemosiderin. |
 View larger version (131K) | Fig. 4C —44-year-old man with sclerosing angiomatoid nodular transformation. C, T2-weighted fat-saturated axial image shows numerous low-signal-intensity foci throughout lesion. |
 View larger version (150K) | Fig. 4D —44-year-old man with sclerosing angiomatoid nodular transformation. D, Cut surface of gross specimen shows prominent tan-colored central scar with surrounding numerous coalescent red-brown nodules. |
On gadolinium-enhanced images, all lesions were heterogeneously hypoenhancing during the arterial phase. In the portal venous phase, the lesions were heterogeneous and predominantly hypointense (n = 2) or isoin-tense (n = 2). During the arterial and portal venous phases, all lesions had peripheral enhancing radiating lines (Fig. 5), and one case showed rim enhancement. On delayed phase images, the lesion was isointense (n = 2) or hyperintense (n = 2) relative to the spleen; three cases were heterogeneous, with the remaining case showing homogeneous delayed enhancement. The lesions all progressively enhanced. A central scar was identified in one case (25%), which was hypoenhancing on all contrast-enhanced phases (Fig. 5).
 View larger version (176K) | Fig. 5A —27-year-old woman with sclerosing angiomatoid nodular transformation. A, Contrast-enhanced axial MR images in arterial phase (A) and portal venous phase (B) show lobulated, heterogeneous, hypointense mass. Note multiple peripheral enhancing radiating lines (arrows), central hypoenhancing scar (arrowheads), and progressive enhancement. |
 View larger version (172K) | Fig. 5B —27-year-old woman with sclerosing angiomatoid nodular transformation. B, Contrast-enhanced axial MR images in arterial phase (A) and portal venous phase (B) show lobulated, heterogeneous, hypointense mass. Note multiple peripheral enhancing radiating lines (arrows), central hypoenhancing scar (arrowheads), and progressive enhancement. |
 View larger version (163K) | Fig. 5C —27-year-old woman with sclerosing angiomatoid nodular transformation. C, Delayed phase contrast-enhanced axial MR image shows continued progressive enhancement, with mass now isointense except for central scar (arrowheads). |
 View larger version (170K) | Fig. 5D —27-year-old woman with sclerosing angiomatoid nodular transformation. D, T2-weighted fat-saturated axial image shows heterogeneous hypointense mass with hyperintense central scar (arrowheads). |
| Discussion | |
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SANT is a recently described lesion within the spleen consisting of vascular nodules in a fibrous stroma. It is most commonly an incidentally discovered, asymptomatic lesion. Although sometimes found in the setting of malignancy, SANT is thought to be coincidentally discovered during routine imaging evaluation or follow-up of the patient's primary tumor [1]. SANT itself appears to be a benign lesion with no recurrence or malignant behavior reported to date [12].
The study group's demographic and clinical characteristics were similar to those in prior reports. The patients in our study had a mean age of 41.2 years and a 2:1 female-to-male ratio, and most were asymptomatic. The approximately 100 patients with SANT reported in the English-language literature have a mean age of 47.4 years and a slight female preponderance (1.3:1 female-to-male ratio), and SANT was an incidental finding in the majority (63%) of patients reported [1–27].
The pathologic features of SANT were originally described in a series of 25 patients [1] and in multiple subsequent case series [2, 4, 5, 16, 22, 25]. SANT is a vascular lesion, composed of numerous angiomatous nodules that are surrounded by bands of collagen fibers that often form a central stellate scar. The nodules contain multiple types of blood vessels normally found in splenic red pulp; cord capillaries, splenic sinusoids, and small veins are present and can be identified by their various staining patterns. Other splenic vascular lesions—including hemangioma, hamartoma, and littoral cell angioma—lack the nodular pattern of SANT, and each stains only for a single type of vascular channel [1, 28].
The imaging findings characteristic of SANT have been reported in the radiology literature in a small number of case reports [6–10], and a single case series of three patients focused on the sonographic findings [11]. Limited imaging features have also been reported in single-case descriptions in the pathology [3, 12, 19–21, 25, 26, 28] and surgery [13–15] literature, as well as in a pathology case series of three patients [5].
Our series of patients with SANT shows several characteristic imaging features with pathologic correlation. Peripheral enhancing radiating lines were present in seven (88%) and rim enhancement in two (25%) of the lesions evaluated with contrast-enhanced CT or MRI during the arterial or portal venous phases. This pattern of enhancement corresponded on histopathology to the concentration of angiomatous nodules around the periphery of the lesion, as well as in a radiating pattern between the branches of the fibrous scar; Karaosmanoglu et al. [7] and Gutzeit et al. [6] referred to this pattern of enhancement as a “spoke wheel” appearance on contrast-enhanced ultrasound, CT, and MRI.
Our study supports previous findings of progressive or persistent enhancement of SANT [3, 6–11, 15, 21]. Progressive enhancement was seen in our series in all six cases with dynamic contrast-enhanced CT or MRI studies. A heterogeneous appearance during the arterial and portal venous phases most likely reflects the enhancement of the angiomatous nodules. Progressive enhancement in the delayed phase, with half of the cases homogeneously enhancing in this phase, probably reflects delayed enhancement of the fibrous tissue in addition to the continued enhancement of the angiomatous tissue.
Low signal intensity on T2-weighted images was present in all four lesions evaluated with MRI. T2 hypointensity compared with the spleen was also seen in all 10 cases with MRI in the literature [5, 7–9, 11, 13, 14, 20, 25]. This is most likely from hemosiderin deposition, found in all our cases on histopathology. This is supported by the decrease in signal intensity on in-phase compared with out-of-phase images in the one case with chemical-shift imaging. A similar pattern was also seen by Thacker et al. [9] in the only previous description of chemical-shift imaging in SANT of which we are aware.
A coalescent central or eccentric scar, though commonly seen on the cut gross specimens, was present on imaging in only 22% of cases in our series. This may be partly explained by the scars in some cases consisting of thin radiating septa that may be difficult to distinguish on imaging. Additionally, we hypothesize that the persistent enhancement of the angiomatous nodules and concurrent delayed enhancement of the fibrous tissue makes it difficult to distinguish a central scar on imaging. Foci of calcification are sometimes identified histologically within large areas of hyalinization [1]; however, they are rarely seen radiologically. Punctate foci of calcification were present in just one (11%) of our cases and have been described previously in only one case that we are aware of in the literature [21].
The differential diagnosis of a splenic mass is broad and includes many benign and malignant entities. The most common splenic masses are cysts, including congenital true cysts, posttraumatic pseudocysts, and echinococcal disease. These can easily be distinguished from SANT, in which cystic changes have not been reported.
Solid splenic masses pose more of a diagnostic dilemma. In particular, hemangiomas are the most common benign primary neoplasm of the spleen and can show progressive enhancement, sometimes with a central fibrous scar [29]; they may be distinguished from SANT by their high T2 signal intensity. Hamartomas likewise are hyperintense compared with the spleen on T2-weighted images. Angiosarcoma also can be distinguished by its high T2 signal intensity, and it often has cystic areas from hemorrhage or necrosis [29, 30]. Lymphoma is the most common malignant tumor of the spleen and can present as a solitary mass or multiple nodules; it has been described as isointense or hypointense relative to the spleen on T2-weighted images but typically shows little enhancement rather than a progressively enhancing pattern [30, 31].
Littoral cell angioma is a rare vascular neoplasm of the spleen, and, like SANT, it may show progressive enhancement and low T2 signal intensity owing to hemosiderin deposition [29]. However, innumerable lesions throughout the spleen are typical of littoral cell angioma, in contrast to SANT, which is solitary in 95% of reported cases. Other splenic lesions can also be distinguished by their propensity for multiplicity, including fungal infection and metastatic disease. The clinical history is often helpful in these cases. Patients with disseminated fungal abscesses are generally immunocompromised, particularly neutropenic patients with leukemia. The spleen is an uncommon site for metastatic disease, usually discovered late in the course in patients with a known primary malignancy and widespread disease [30].
We recognize several limitations of our study. This is a retrospective review of only nine patients with SANT, and only four of these patients underwent MRI. Dynamic contrast-enhanced imaging was performed in only six patients. We did not use independent blind review of images by multiple radiologists because of the small cohort. Additionally, because the cases were submitted from multiple institutions, there was a lack of standardization of CT and MRI techniques. To our knowledge, however, this is the largest group of patients with SANT evaluated radiologically, and we believe our findings are useful for diagnosis of this lesion.
In summary, SANT often displays characteristic CT and MRI findings, including arterial or portal venous phase peripheral enhancing radiating lines, progressive enhancement, and hypointense T2 signal intensity. Peripheral enhancing lines and, in some cases, rim enhancement correspond histologically to multiple angiomatous nodules concentrated around the periphery and in a radiating, spoke wheel pattern. Delayed enhancement of the fibrous tissue contributes to the progressive enhancement pattern. Low T2 signal intensity and decrease in signal intensity on in-phase as compared with out-of-phase imaging relate to hemosiderin deposition. We believe these imaging features suggest the diagnosis of SANT and may help distinguish SANT from other solid splenic masses.
The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Army, Air Force, Department of Defense, nor the U.S. Government.
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