Chinese Medical Journal 2012;125(13):2386-2389
Sclerosing angiomatoid nodular transformation of the spleen: report of five cases and review of literature

WANG Hao-lu,  LI Ke-wei,  WANG Jian

WANG Hao-lu (Department of General Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China)

LI Ke-wei (Department of General Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China)

WANG Jian (Department of General Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China)

Correspondence to:WANG Jian,Department of General Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China (Tel: 86-21-50903241. Fax:86-21-58393018. E-mail:dr_wangjian@yahoo.com.cn)
Keywords
sclerosing angiomatoid nodular transformation; spleen
Abstract
Sclerosing angiomatoid nodular transformation (SANT) of the spleen, a newly defined primary lesion of the spleen, is very rare. Immunohistochemistry is the only way to confirm the diagnosis of SANT. We present the clinical characteristics and postoperative outcomes of five SANT cases that underwent splenectomy from January 2007 to October 2010. Although SANT had specific imaging findings, differential diagnosis from other splenic tuomrs or malignant lesions preoperatively was difficult. The hand-assisted laparoscopic splenectomy was a useful and effective technique for the management and postoperative diagnosis of SANT. All SANT patients had good prognosis without recurrence after splenectomy.
The majority of spleen’s primary lesions are sarcomas and lymphomas. Primary splenic tumors of a vascular nature are uncommon. Two major types of vascular tumors of the spleen are littoral cell angioma and hemangioma. Another type of the primary splenic vascular lesions, sclerosing angiomatoid nodular transformation (SANT) of the spleen was newly defined by Martel et al1 in 2004. Since the original description in 2004, several subsequent case reports have been described.2,3 However, most of the articles focused on the pathological aspects and the image diagnosis of SANT.
 
SANT is a kind of benign lesion for which the curative treatment is splenectomy.4 Herein, we present the clinical characteristic and surgical treatment of one case that underwent laparoscopic splenectomy and four cases that underwent open surgery from January 2007 to October 2010. This is the second largest reported series since 2004. A further comprehensive discussion of related literature on diagnosis and treatment of SANT is included.
 
CASE REPORT
 
Five patients underwent regular clinical examinations including abdominal ultrasonography (US), CT and/or MRI. An additional SPECT/CT scan was performed in one case. Four patients underwent open splenectomy, and a hand-assisted laparoscopic splenectomy as described by Feldman5 was performed in one case because the splenic mass was limited in size and had not invaded the adjacent organs.
 
After splenectomy, the tumors were evaluated by immunohistochemistrical examination following standard protocols. The primary antibodies included CD34 (Dako, Denmark), CD8 (Dako), CD31 (Dako), F8 (1:25, Dako), CD68 (Dako), Vimentin (1:100, Dako), smooth muscle antibodies (SMA) (1:100, Dako), Actin (1:50, Dako), Collagen IV (1:25, Dako) , CD21 (1:15, NeoMarkers, USA), Desmin (1:50, NeoMarkers), Neuron Specific Enolase (NSE) (Dako).
 
Clinical features
The clinical features are summarized in Table 1. The male to female ratio was 3 to 2. The patients ranged from 28 to 52 years (median, 44 years). Two patients were incidentally found to have an asymptomatic splenic mass during physical check-up on ultrasound (USA). Three patients presented with abdominal pain or epigastric discomfort and were found to have a splenic mass on US initially. US was performed in all five patients and it revealed hypoechoic masses in four cases and isoechoic mass in one case. CT scan was performed in three patients, and revealed heterogeneous, low-attenuation splenic lesions of unenhanced images in three cases. In two cases visible septa within the mass were identified. The splenic mass had peripheral and septal enhancement on arterial and portal venous phase images and still enhanced on delayed imaging (Figure 1A). MRI was performed in two cases, which showed several areas of different signal in the mass on T1- and T2-weighted images (Figure 1B). A SPECT/CT scan in case 5 showed no evidence of increased uptake of the mass inside the spleen.
 

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Table 1. Clinical features of SANT
 
The total operation time of laparoscopic splenectomy and the estimated intraoperative blood loss were 195 minutes and 270 ml, respectively, in case 1. The patient had an uneventful hospital course and discharged on the eighth postoperative day. The operation time was 95 to 140 minutes (median, 115 minutes) in four cases that underwent open splenectomy. The estimated blood loss was 350 to 900 ml (median, 680 ml) and the length of stay in hospital was 11 to 15 days (median, 13 days). None of the five patients had evidence of recurrent disease during follow-up for 2–31 months (median, 28 months).
 
Pathological findings
At gross inspection in the five cases, the splenic tumor nodules had a well-circumscribed but nonencapsulated border. A white central fibrosclerotic scar was visible, with yellow or white, spoke-shaped fibrous strands. The remainder of the spleen was unremarkable (Figure 2A).
 
Histological examination revealed the formation of nodules of varying size separated by sclerotic fibrotic stroma in a background of splenic red pulp. In one typical nodule, the central portion was composed of irregular vascular spaces lined by plump endothelial cells that contained numerous erythrocytes compatible with angiomatoid nodule (Figure 2B). The vascular spaces were surrounded by concentric fibrosis with different amounts of hemosiderin granules. No malignancy was found.
 

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Figure 1. Unenhanced CT image in case 5: hypodense splenic lesion with faintly visible septa from the periphery (1A). T2-weighted MR image of spoke-wheel pattern in case 4: hyperintense septa penetrating the hypointense center of the lesion from the periphery (1B).
Figure 2. Gross appearance of the tumor in case 1: a yellow central fibrosclerotic scar was visible, with white, spoke-shaped fibrous strands and a well-circumscribed but nonencapsulated border (2A). Histopathological findings of the central portion of the nodule in case 1: small vessels with fibrosclerotic stroma (2B) (HE staining, original magnification ´400).
 
Immunohistochemical stains revealed an admixture of blood vessels within the angiomatoid nodular. Capillary-like structures (CD34+/CD8–/CD31+) were the predominant vessel type in the angiomatoid nodular of all the five cases. Small vein-like structures (CD34−/CD8−/ CD31+) and sinusoid-like structures (CD34−/CD8+/ CD31+) were also present. Some cells in the angiomatoid nodular were F8+. Some cells around the angiomatoid nodular were CD68+ and some were smooth muscle and collagen fiber (vimentin+/SMA+/actin+/collagen IV+). All cells were CD21−/Desmin−/NSE+. The histomorphology and staining profile taken together finally confirmed the diagnosis of five cases as SANT.
 
DISCUSSION
 
In isolated reports before 2004, SANT was described as multinodular hemangiomas, splenic hamartomas, splenic hemangioendotheliomas, or cord-capillary hemangioma.6 These various pathological terms reflect different perspectives of this disease adopted by different authors in interpreting its histogenesis and histological features. According to its characteristic morphological appearance, immunophenotype, and benign clinical course, Martel et al1 designated this kind of distinctive nonneoplastic vascular lesion of the spleen as SANT. It is a rare, benign disorder of uncertain etiology and with no tendency of recurrence or malignant transformation.3
 
Histologically, SANT usually appears as non-encapsulated but circumscribed from the normal spleen tissue. A typical angiomatoid nodular of SANT is composed of differently shaped vessels lined by endothelial cells separated by sclerotic fibrotic stroma. Post-operative immunohistochemistry is the only way to confirm the diagnosis of SANT.7 Vessels in the angiomatoid nodular are the combination of three different types: capillaries (CD34+/CD8−/CD31+), small veins (CD34−/CD8−/CD31+) and sinusoids (CD34−/ CD8+/CD31+). Some cells in SANT are CD68+ and SMA+. There are no such histological and immunohistochemical appearances in other splenic vascular lesions such as hemangiomas, littoral cell angioma or hamartomas.1
 
The mean age of presentation was in the fifth decade, although a wide age range of 22–74 years has been reported.6,8 In the present report, the five patients did not reveal sex predominance but a female-to-male ratio of 2:1 is shown in other sources.6,8 Many patients, including two of our current cases (Table 1), were asymptomatic and detected incidentally. However, there were reports which revealed that about half of the patients with SANT had epigastric or abdominal discomfort. The widespread use of imaging during physical check-up and the increasing acquaintance to this disease will probably increase the number of the diagnosed SANT.
 
US is capable of detecting vascular masses in the spleen but the US findings of SANT were inconclusive. The published reports have referred to the typical cross-sectional imaging appearance of SANT as vascular with a hypoechoic halo on conventional US images and a spoke-wheel pattern on contrast-enhanced untrasonography (CEUS).9 CEUS can provide more direct visualization of vessel structure and morphologic characteristics than conventional US. CT or MRI examination of SANT would reveal a hypovascular center with an enhancing rim and radiating vascularized or fibrotic tissue penetrating from the periphery to the center.3 In multiphasic imaging, the splenic mass showed peripheral enhancement on the early arterial phase, then the center of the mass was progressively enhancing in a radiating pattern with delayed imaging, or remained hypodense and hypointense. The diagnosis of SANT may be offered when CT or MRI reveals a typical spoke-wheel pattern of the splenic lesion. However, in our cases, only two in five cases (cases 4 and 5) were similar to the typical spoke-wheel pattern. The SPECT/CT imaging findings of SANT is scarcely published. Only one prior published case revealed that SANT showed a lack of radiopharmaceutial uptake and the etiology for the splenic lesion remained indeterminate on SPECT/CT scan.3 In our case 2, similarly, SPECT/CT scan could not exclude neoplasm in diagnosing SANT.
 
Splenic lesions include both benign and malignant disease. It is difficult to rule out other benign pathological conditions of the spleen such as inflammatory pseudotumor or hamartoma using imaging modalities. Usually the hyperechoic lesions in the spleen are considered as the benign ones such as SANT, while malignant lesions are mostly hypoechoic and occur most frequently in lymphomas.10 Unlike lymphoma, a prevalent primary tumor of the spleen, SANT is a solitary tumor, without intra-abdominal lympadenopathy. The general well-being of the patient and the absence of symptoms regarding lymphoma may also be useful hints for diagnosing SANT. Angiosarcoma is a primary malignant tumor of the spleen with a highly aggressive biological nature. Distant metastasis is not unusual. Littoral cell angioma could be differentiated by its typical multiple hypodense nodules in CT or MRI.11 Although there are some specific imaging features of SANT, it is also difficult to distinguish SANT from malignant lesions of the spleen such as carcinomatosis. Similar to some malignant tumor in imaging findings, SANT mass may still have multiple nodules12 and two prior published reports of FDG-PET behavior of SANT showed hypermetabolic activity, simulating neoplasm.3 In our series, only two of the present cases had the typical imaging features and case 3 was misdiagnosed as lymphoma before intra-operative frozen section biopsy. Due to the difficulties of preoperative diagnosis, percutaneous biopsy of the spleen was suggested by Gutzeit et al.13 Nevertheless, high frequency of complications such as bleeding or splenic rupture was noted after percutaneous biopsy of vascular splenic lesions.
 
Asympotomatic patients of benign vascular splenic lesions can adopt conservative management. Because of no reports of malignant transformation, asympotomatic patients of SANT may be observed with close untrasound follow-up to exclude splenic rupture or significant expansion. However, due to the difficulties in pre-operative diagnosis to exclude malignancy and the only way to confirm SANT being immunohistochemistry, splenectomy is indicated when a vascular splenic lesion in imaging findings suggests the diagnosis of SANT. Surgical resection has proven to be both diagnostic and therapeutic in our series and also in all prior reported cases of SANT.7 Although operative time is longer for laparoscopic splenectomy than for open surgery, laparoscopy has the advantage of lower complication rates and shorter hospital stays.5 Nowadays laparoscopic splenectomy has become the choice for not only the surgical management of idiopathic thrombocytopenic purpura but also for some splenic tumors.14 Laparoscopic splenectomy is preferable to the open approach for most indications except uncorrected coagulopathy, severe portal hypertension and massive splenomegaly. Although two previous reports of laparoscopic splenectomy for SANT have been published,4,15 to the best of our knowledge, our present case is the first one reported in detail in English. In our case, the laparoscopic procedure was longer than open splenectomy (195 vs. 115 minutes). Our data showed an improvement in the length of stay in hospital (8 vs. 13 days) and a decrease in estimated blood loss (270 vs. 680 ml) in the laparoscopic splenectomy for SANT compared with the open surgery group. The hand-assisted approach is a useful adjunct in laparoscopic splenectomy and is recommended in difficult cases such as significant splenomegaly, hilar lymph nodes or perisplenic inflammation detected preoperatively.5 The hand port site is particularly useful in removing an intact specimen for pathological analysis without the requirement for an additional incision, while in a completely laparoscopic splenectomy the spleen has to be morcellated in the bag to allow for removal. No post-operative complications and evidence of recurrence were observed in our five cases during the follow-up (Table 1).
 
In conclusion, SANT of the spleen is a rare disease. Although SANT has specific imaging findings, preoperative differential diagnosis from other splenic tumors or malignant lesions is difficult. Immunohistochemistry is the only way to confirm the diagnosis of SANT. The hand-assisted laparoscopic splenectomy is a useful and effective technique for the management and postoperative diagnosis of SANT. All SANT patients have good prognosis with no recurrence after splenectomy.
 
REFERENCES
 
1.  Martel M, Cheuk W, Lombardi L, Lifschitz-Mercer B, Chan JK, Rosai J. Sclerosing angiomatoid nodular transformation (SANT): report of 25 cases of a distinctive benign splenic lesion. Am J Surg Pathol 2004; 28: 1268-1279.
2.  Koreishi AF, Saenz AJ, Fleming SE, Teruya-Feldstein J. Sclerosing angiomatoid nodular transformation (SANT) of the spleen: a report of 3 cases. Int J Surg Pathol 2009; 17: 384-389.
3.  Thacker C, Korn R, Millstine J, Harvin H, Van Lier Ribbink JA, Gotway MB. Sclerosing angiomatoid nodular transformation of the spleen: CT, MR, PET, and 99(m)Tc-sulfur colloid SPECT CT findings with gross and histopathological correlation. Abdom Imaging 2010; 35: 683-689.
4.  Mohr Z, Klippel S, Spiethoff A, Trick D, Willis S. Laparoscopic splenectomy for sclerosing angiomatoid nodular transformation. Chirurg 2011; 82: 714-718.
5.  Feldman LS. Laparoscopic splenectomy: standardized approach. World J Surg 2011; 35: 1487-1495.
6.  Awamleh AA, Perez-Ordonez B. Sclerosing angiomatoid nodular transformation of the spleen. Arch Pathol Lab Med 2007; 131: 974-978.
7.  Sitaraman LM, Linn JG, Matkowskyj KA, Wayne JD. Sclerosing angiomatoid nodular transformation of the spleen masquerading as a sarcoma metastasis. Rare Tumors 2010; 2: e45.
8.  Zeeb LM, Johnson JM, Madsen MS, Keating DP. Sclerosing angiomatoid nodular transformation. Am J Roentgenol 2009; 192: W236-W238.
9.  Cao JY, Zhang H, Wang WP. Ultrasonography of sclerosing angiomatoid nodular transformation in the spleen. World J Gastroenterol 2010; 16: 3727-3730.
10.  Woszczyk D, Kolodziej-Jaskula A, Mykala-Ciesla J, Bal A, Labuzek K, Gasinska T. Focal lesions in the ultrasonographic examination of the spleen as a symptom of various disease statuses: literature survey and case descriptions. Med Sci Monit 2006; 12: CS67-CS73.
11.  Karaosmanoglu DA, Karcaaltincaba M, Akata D. CT and MRI findings of sclerosing angiomatoid nodular transformation of the spleen: spoke wheel pattern. Korean J Radiol 2008; 9: S52-S55.
12.  Kuo TT, Chen TC, Lee LY. Sclerosing angiomatoid nodular transformation of the spleen (SANT): clinicopathological study of 10 cases with or without abdominal disseminated calcifying fibrous tumors, and the presence of a significant number of IgG4+ plasma cells. Pathol Int 2009; 59: 844-850.
13.  Gutzeit A, Stuckmann G, Dommann-Scherrer C. Sclerosing angiomatoid nodular transformation (SANT) of the spleen: sonographic finding. J Clin Ultrasound 2009; 37: 308-311.
14.  Zheng CX, Zheng D, Chen LH, Yu JF, Wu ZM. Laparoscopic splenectomy for immune thrombocytopenic purpura at a teaching institution. Chin Med J 2011; 124: 1175-1180.
15.  Bamboat ZM, Masiakos PT. Sclerosing angiomatoid nodular transformation of the spleen in an adolescent with chronic abdominal pain. J Pediatr Surg 2010; 45: E13-E16.