Abstract
Background
Sclerosing angiomatoid nodular transformation (SANT) is a rare benign primary vascular lesion of the spleen. Although there have been many reports about the pathology of SANTs of the spleen, there have been no comprehensive descriptions of the imaging findings of SANTs of the spleen.
Purpose
To determine the clinical characteristics and imaging findings of SANTs of the spleen.
Material and Methods
We retrospectively evaluated seven patients with pathologically confirmed SANT, who underwent CT (n = 7), MRI (n = 4), ultrasonography (n = 4), and PET/CT (n = 3). Follow-up CT examinations were obtained in five patients. Clinical characteristics such as symptoms and concurrent disease were assessed. CT and MRI findings were evaluated by two radiologists, including the number, border, signal intensity, enhancement pattern, hemorrhage, and cystic change or necrosis. The longest diameter of each tumor was measured on CT. Echogenicity on ultrasonography and standardized uptake value on PET/CT were also evaluated.
Results
No specific symptom was associated with SANT. Two patients had a history of malignancy, one with cervical cancer and the other with early gastric cancer. Tumor growth was observed in four of five patients. On CT, all seven SANTs appeared as single, well-demarcated masses. CT showed a heterogeneous enhancement in seven patients. MRI showed centripetal progressive enhancement and absence of cystic change or necrosis in four patients, with three of these patients showing evidence of old hemorrhage. Ultrasonography showed heterogeneous hypoechoic mass in four patients. PET/CT showed increased standardized uptake value, ranging from 2.0 to 2.8, in three patients.
Conclusion
SANT of the spleen is a single, well-demarcated solid mass without cystic change or necrosis. Increased FDG activity and tumor growth on follow-up imaging are common.
Sclerosing angiomatoid nodular transformation (SANT) is a rare benign primary vascular lesion of the spleen, first described in 2004 (1). Although there have been many reports about the pathology of SANT of the spleen (1–3), descriptions of imaging characteristics have been limited to case reports (4–10). To our knowledge, there have been no comprehensive descriptions of the CT, MRI, ultrasonography, and PET/CT features of SANT of the spleen. Moreover, clinical characteristics such as follow-up results using cross-sectional imaging have not yet been studied. We have encountered several patients with SANT of the spleen in recent years. We describe here their clinical characteristics and imaging features.
Material and Methods
Patients
This study was approved by our institutional review board (2011-0813), which waived the requirement for informed consent. Between January 2000 and April 2011, there were seven patients with pathologically confirmed SANT of the spleen. The pathologic diagnosis of SANT was made according to the morphologic features and microscopic findings, described by Martel et al. (1). Six patients underwent splenectomy, and one underwent a splenic biopsy.
Clinical data
All clinical data were reviewed by a radiologist who did not take part in the imaging analysis. Symptoms at presentation, concurrent disease, and CT follow-up period were recorded.
Imaging techniques
Seven patients underwent contrast-enhanced CT during portal venous phase. Three of seven patients underwent two CT examinations and two of seven patients underwent three CT examinations. The remaining two patients underwent one CT examination, which was immediately followed by splenectomy. CT examinations were performed using Somatom Sensation 16 (Siemens Medical Systems, Erlangen, Germany) and LightSpeed 16 or LightSpeed QX/I (GE Healthcare, Milwaukee, WI, USA) multidetector scanners. Non-enhanced CT was obtained in three patients. Four patients underwent MRI, using 1.5 T scanners (Magnetom Vision or Magnetom Avanto; Siemens, Erlangen, Germany). Axial dual-echo T1-weighted image (T1WI), T2-weighted image (T2WI), and contrast-enhanced fat-saturated axial dynamic T1WI were obtained. Hepatobiliary phase images were obtained in two patients. Diffusion-weighted image (DWI) and apparent diffusion coefficient (ADC) map were obtained in three patients. Ultrasonography was performed in four patients, using various units equipped with curved array probes. PET/CT was performed in three patients, using an integrated PET/CT system (Biograph Sensation 16; Siemens Medical Solutions, Knoxville, TN, USA).
Imaging analysis
Two radiologists blinded to the diagnosis of SANT evaluated all images in consensus. The number and border (well or poorly demarcated) of focal splenic lesions in each patient on CT were recorded. The density of each focal splenic lesion was recorded as hypo-, iso-, or hyperdense compared with the surrounding normal splenic parenchyma, and the homogeneity of each lesion was recorded as homogeneous or heterogeneous. The longest diameter of each tumor on contrast-enhanced axial CT images was measured using electronic calipers. The presence of calcification (high density, similar to that of cortical bone) was also recorded. On MRI, the signal intensity of each lesion on dual-echo T1WI was recorded as signal decrease in out-of-phase, signal decrease in in-phase, or iso-signal intensity in both phases. Signal intensities on T2WI, non-enhanced T1WI, and contrast-enhanced arterial, portal venous, delayed, and hepatobiliary phase images were recorded. The signal intensity of each focal splenic lesion was recorded as hypo-, iso-, or hyperintense compared with the surrounding normal splenic parenchyma, and the homogeneity of each lesion was recorded as homogeneous or heterogeneous. Signal intensities on DWI and ADC map were recorded as hypo-, iso-, or hyperintense compared with the surrounding normal splenic parenchyma. The enhancement pattern of each lesion on contrast-enhanced dynamic T1WI was recorded as centripetal or centrifugal and progressive or wash-out. Progressive enhancement was defined as more enhancement of the lesion on delayed phase than enhancement on arterial or portal venous phase image. Wash-out was defined as prominent enhancement of the lesion on arterial phase and decrease in enhancement on portal or delayed phase image. The border of each lesion on contrast-enhanced dynamic T1WI was recorded as well or poorly demarcated. Finally, the presence of hemorrhage (high signal intensity foci on non-contrast fat-saturated T1WI) and cystic change or necrosis (high signal intensity area similar to that of water on T2WI, not showing enhancement on dynamic study) were determined. On ultrasonography, the echogenicity (hypo-, iso-, or hyperechoic) and homogeneity (homogeneous or heterogeneous) of each focal splenic lesion were recorded. For PET/CT, hypermetabolic lesion in the spleens was checked. When such a lesion was present, its pattern (homogeneous or heterogeneous) was recorded, and the maximum standardized uptake value (SUV), normalized to the lean body mass of the lesion, was measured.
Pathologic analysis
The seven SANTs were reviewed by a pathologist. The histologic presence of inflammatory cells, hemorrhage, and sclerosis were determined.
Results
Clinical findings
The clinical data of the seven patients are summarized in Table 1. There were four men and three women, ranging in age from 39–50 years (median age, 42 years). One patient complained of flank pain due to acute pyelonephritis, but none had any symptoms specifically associated with SANT. SANTs were discovered during evaluation or follow-up of other disease in three patients (patients 1, 6, and 7) and incidentally during health check program in four patients (patients 2–5).
Clinical data of patients with SANT of the spleen
*Follow-up period was defined as the time from first CT examination to last CT examination before surgery in four patients or as the time from first CT examination to last CT examination in one patient who underwent splenic biopsy
†Treated 28 months previously for squamous cell carcinoma in situ of the uterine cervix
‡A splenic biopsy was taken from this patient
§Splenectomy was performed without follow-up CT
**This patient underwent splenectomy, subtotal gastrectomy, and small bowel resection at the same time
APN, acute pyelonephritis; DM, diabetes mellitus; EGC, early gastric cancer; FU, follow-up; GIST, gastrointestinal stromal tumor
Imaging findings
The imaging findings of the seven patients are summarized in Table 2. Each patient had one focal splenic lesion. Five patients underwent follow-up CT, with these images showing no specific difference from the initial CT except that four showed an increase in the longest diameter of the tumor (Fig. 1). The growth rates of these SANTs varied, with one (patient 6) showing a 23% increase in the longest diameter over 6 months, and one (patient 3) showing no change over 13 months (Table 1). On CT, all SANTs appeared as a hypodense mass with heterogeneous enhancement and well-demarcated border. There was no evidence of calcification on CT. MRI was performed in four patients. On dual echo axial T1WI, three SANTs showed a signal decrease in in-phase images (Fig. 2). On contrast-enhanced dynamic T1WI, the SANTs in four patients showed centripetal and progressive enhancement (Fig. 1). Small high signal intensity foci on T1WI suggesting hemorrhage was present in one patient (patient 3). Cystic change or necrosis was absent in all four patients. On ultrasonography, all four SANTs appeared as heterogeneously hypoechoic masses (Fig. 2). On PET/CT, three patients showed heterogeneous increased activity. Their maximum SUV, normalized to the lean body mass ranged from 2.0 to 2.8 (Fig. 2).
A 48-year-old woman (patient 6) with sclerosing angiomatoid nodular transformation of the spleen. (a, b) Axial contrast-enhanced CT image shows the splenic mass (a, arrow) with heterogeneous enhancement and well-demarcated borders. Six months later, there is an increase in the longest diameter of the splenic mass (b, arrow) from 30 mm to 37 mm. (c, d) DWI (c) (b-factor 900 s/mm2) and ADC map (d) show no evidence of restricted diffusion in the splenic mass (arrow). (e, f) Gadoxetic acid-enhanced axial dynamic T1-weighted images show heterogeneous hypointense signal intensity of the mass (e, arrow) in the portal venous phase and heterogeneous hyperintensity of the mass (f, arrow) in the delayed phase. Contrast-enhanced dynamic MR shows centripetal progressive enhancement of the mass (e, f, arrow). (g) Gadoxetic acid-enhanced axial hepatobiliary phase image shows the mass (arrow) with homogeneous hyperintensity
A 39-year-old man (patient 5) with sclerosing angiomatoid nodular transformation of the spleen. (a) Gray-scale ultrasonography shows a heterogeneously hypoechoic mass (arrow). (b, c) There is a signal decrease of the mass (arrow) on the in-phase image (TR, 164 ms; TE, 4.6 ms) (b) relative to the out-of-phase (TR, 164 ms, TE, 2.3 ms) (c) image. (d) Axial T2-weighted image shows a heterogeneous, hypointense mass (arrow) in the spleen. (e, f) DWI (e) (b-factor 900 s/mm2) and ADC map (f) show low signal intensity of the mass (arrow). (g) PET/CT shows the heterogeneous increase in FDG-activity, with a maximum SUV of 2.8 in the mass (arrow). (h) Photograph of the gross pathologic specimen shows a solitary, well-demarcated mass with yellow-white bands of sclerosis entrapping red-brown nodules
CT, MRI, ultrasonography, and PET/CT findings of patients with SANT of the spleen
ADC, apparent diffusion coefficient; AP, arterial phase; DP, delayed phase; DWI, diffusion-weighted image; HB, hepatobiliary; Hetero, heterogeneous; Homo, homogeneous; Hyper, hyperdense, hyperintense, hyperechoic relative to normal spleen on CT, MRI, and ultrasonography, respectively; Hypo, hypodense, hypointense, hypoechoic intense relative to normal spleen on CT, MRI, and ultrasonography, respectively; IP, in-phase; Iso, iso-dense, iso-intense, iso-echoic intense relative to normal spleen on CT, MRI, and ultrasonography, respectively; Max SUV, maximum standardized uptake value; NA, not available; Non, non-enhanced CT or T1-weighted image; PVP, portal venous phase CT; Well, well-demarcated
Pathologic findings
Fragmented and extravasated red blood cells were identified in all patients. Three patients (patient 2, 4, 5) showed evidence of hemosiderin deposition due to old hemorrhages. Variable amounts of scattered inflammatory cells, mainly lymphocytes and plasma cells, were present in all patients.
Discussion
SANT is a non-committal descriptive designation owing to its uncertain etiology and pathogenesis (1). It represents the gross morphology of the cut surface of the tumor, which consists of dense fibrosis and angiomatoid nodules. Most patients with SANT of the spleen have solitary splenic lesions (1) and all of our patients had solitary lesions. To our knowledge, there have been no reports on imaging follow-up of patients with SANT of the spleen. In our study, five patients underwent follow-up CT, with four showing an increase in the longest diameter of the tumor and one showing no change. This change was quite variable, ranging from 0% over 13 months to about 23% over 6 months.
Most published reports of SANT have focused on its pathological aspects, with descriptions of imaging features limited to case reports (4–10). We found that the CT features of SANT of the spleen were relatively uniform in our patients. They included a solitary, well-demarcated splenic mass with heterogeneous enhancement on portal venous phase images. They showed hypodensity relative to normal splenic tissue on portal venous phase image. According to the previous reports, SNATs showed near iso-density relative to normal splenic tissue on delayed phase images on CT (5–7).
Contrast-enhanced dynamic T1WI in four of our patients showed progressive and centripetal enhancement. On delayed phase images, each tumor was hyper- or iso-intense relative to the normal spleen. T2WI showed heterogeneous hypointensity of each mass. The enhancement pattern and signal intensity on T2WI of SANT may be due to the gross feature of the cut surface of the tumor, which contain dense fibrosis and angiomatoid nodules. Dual echo T1WI showed signal decrease on in-phase in three patients. Since iron deposition causes signal loss on longer TE images, the lesion losing signal on the longer TE images may be the manifestation of the iron deposition. In our cases, hemosiderin deposition due to old hemorrhage may cause signal decrease on in-phase. Previous reports have shown hyperintensity on T1WI, suggesting hemorrhage (5, 9), however, this hyperintensity was very subtle in one study (5). Our pathologic review showed hemorrhage in all SANTs of the spleen. However, high signal intensity on T1WI suggesting hemorrhage was present in only one patient. There is a possibility that the amount of hemorrhage is not enough for definite high signal intensity on T1WI in our study. There was only one report on DWI of SANT, which showed low signal intensity on DWI and high signal intensity on ADC map (8), similar to our patients. However, one of our patients showed hypointensity in both DWI and the ADC map. This tumor showed a prominent signal decrease on in-phase image, suggesting that a susceptibility artifact caused by iron deposition may have resulted in hypointensity of the SANT on both DWI and ADC map in this patient.
Two previous reports have described the ultrasonographic features of SANTs (4, 10). Ultrasonography showed heterogeneously hypoechoic masses (4, 10), similar to our findings. Two previous reports on the PET/CT findings of SANTs found maximum SUVs of 2.2 and 4.5 (5, 8). In three of our patients, the maximum SUVs were 2.0, 2.7, and 2.8, respectively. A suggested SUV threshold for discriminating benign from malignant solid splenic masses is 2.3 (11). Our pathologic analyses showed inflammatory cell infiltrations within SANT, suggesting that variations in the degree of inflammation may affect the SUV of the SANTs.
The radiologic differential diagnosis of SANT includes angiosarcoma, lymphoma, littoral cell angioma, hamartoma, hemangioma, and metastasis. It is important to differentiate among these neoplasms because their prognoses differ markedly. Angiosarcoma, although rare, is the most common non-hematopoietic malignant tumor of the spleen, usually containing areas of hemorrhage and necrosis (12). Hemorrhage may present, however necrosis is usually absent in SANT of the spleen. Lymphoma is the most common malignancy that involves the spleen, with splenic involvement usually being part of generalized systemic involvement. Splenomegaly and abdominal lymphadenopathy may be helpful in the diagnosis of lymphoma (9). Littoral cell angioma may mimic SANT, but most of these angiomas have been found to be multiple nodules of varying sizes in the spleen (13). Multiplicity is usually rare in SANT of the spleen. The imaging features of splenic hamartoma may be similar to those of SANT, although identification of old hemorrhages on dual-echo T1WI and dense fibrosis on T2WI and contrast-enhanced dynamic T1WI may be helpful in distinguishing SANT from hamartoma. Finally, hemangioma may resemble SANT of the spleen. Hemangiomas may show various imaging features because larger cavernous hemangiomas may have areas of thrombosis, infarction, fibrosis, and cystic degeneration (12). Hyperintensity on T2WI and multiplicity of hemangioma of the spleen may be helpful in the differential diagnosis. Splenic metastases usually are seen in patients with widespread disseminated malignancies (14). Types of splenic involvement can be solitary nodule, multiple nodules, or diffuse infiltration. Solitary splenic metastasis in the absence of other metastases is rare. Splenic metastases are usually hyperintense on T2WI (14). Metastases in other organs, multiplicity, and hyperintensity on T2WI may be helpful in the diagnosis of splenic metastasis.
This study had several limitations. First, it included a small number of patients owing to the rarity of this tumor. Second, our patients were not assessed by dynamic CT or contrast-enhanced ultrasonography, which may reveal other features that can be used to diagnose SANT of the spleen.
In conclusion, SANT of the spleen usually presents as a solitary, well-demarcated mass with centripetal progressive enhancement on MRI. Absence of necrosis or cystic changes and the presence of old hemorrhages on MRI may be important features. Although SANT of the spleen is a totally benign disease, it can show various growth rates on follow-up CT, as well as various ranges of maximum SUV on PET/CT. Contrast-enhanced portal venous phase CT can reveal non-specific heterogeneous enhancement, whereas MRI may show important features, such as old hemorrhage, centripetal progressive enhancement, and absence of necrosis or cystic change.