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Sclerosing angiomatoid nodular transformation (SANT) of the spleen was first described by Martel et al.1 in 2004, and this rare benign vascular lesion is composed of angiomatoid nodules, a sclerotic internodular stroma, and a lymphoplasma cell infil-tration.2 Macroscopically, the tumor presents as a multinodular, uncapsulated, well-circumscribed mass in the fibrosclerotic background. Angiomatoid nodules which is the most charac-teristic microscopic feature of SANT are composed of three types of endothelial cells; the cord capillary-type, the sinusoid-type, and the small vein-type, resembling the normal vascular structure of splenic red pulp. Martel et al.1 suggested that angi-omatoid nodules may represent an unusual transformation of the red pulp of the spleen in response to the vascular blockage.

The clinical process of SANT is benign without recurrence after splenectomy. We report herein on the first Korean case of SANT in the spleen with its pathologic features, and we review the related literature.

CASE REPORT

A 50-year-old woman presented with mild left upper quad-rant discomfort and tenderness. She had a history of iodine-ab-lation therapy due to hyperthyroidism 8 years ago and she was then medicated for hypothyroidism. The computed tomogra-phy image showed a lobulated and heterogeneously enhanced,

Sclerosing Angiomatoid Nodular Transformation (SANT) in Spleen - A Case Report -

Hyun-Jung Lee1 ∙ Song-Yi Choi1 Song Mei Huang1 ∙ Ji-Young Sul2

Jin-Man Kim1,3

Departments of 1Pathology and 2Surgery; 3Cancer Research Institute, Daejeon Regional Cancer Center, and Infection Signaling Network Research Center, Chungnam National University College of Medicine, Daejeon, Korea

Sclerosing angiomatoid nodular transformation (SANT) of spleen is a rare inflammatory tumor-like vascular lesion composed of angiomatoid nodules in a fibrosclerotic background. We report here-in on a case of SANT in the spleen with its pathologic features, and review the related literature. A 50-year-old woman presented with mild left upper quadrant discomfort and tenderness and she showed a 6 cm-sized solitary splenic mass on computed tomography. She underwent laparo-scopic splenectomy. Grossly, the spleen showed a well circumscribed round-shaped solid mass with multinodular hemorrhagic surfaces. Microscopically, the mass consisted of multiple angio-matoid nodules surrounded by collagen bundles with fibroblasts and a lymphoplasma cell infiltra-tion. Immunohistochemically, the cells of the angiomatoid nodules were positive for CD31, CD30, CD34, alpha-smooth muscle actin, and VWF-VIII, but they were negative for CD8, anaplastic lym-phoma kinase protein, and D2-40. The patient has been under close follow-up without recur-rence.

Key Words: Spleen; Hamartoma; Antigens, CD31

Received: June 2, 2009Accepted: November 24, 2009

Corresponding AuthorJin-Man Kim, M.D.Department of Pathology, Cancer Research Institute, Daejeon Regional Cancer Center, and Infection Signaling Network Research Center, Chungnam National University College of Medicine, 6 Munhwa 1-dong, Jung-gu, Daejeon 301-131, KoreaTel: +82-42-580-8237Fax: +82-42-581-5233E-mail: jinmank@cnu.ac.kr

*This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2010-0001284 : 2010-0001287) and by a grant from the National R&D Program for Cancer Control Ministry of Health & Welfare, Republic of Korea (No: 0720560).

The Korean Journal of Pathology 2011; 45: 111-114DOI: 10.4132/KoreanJPathol.2011.45.1.111

� Hyun-Jung�Lee·Song-Yi�Choi·Song�Mei�Huang,�et�al.112

6 cm-sized solitary mass in the spleen (Fig. 1A). The spleen was resected by laparoscopy under the clinical diagnosis of tumor of the spleen. Grossly, the resected spleen weighed 102 g. There was a relatively well-circumscribed, round-shaped, and solid mass that measured 6.5×6.0×3.5 cm in size. The external sur-face of the mass was multinodular and red-brown in color. On sectioning, the tumor was composed of multiple small hemor-rhagic nodules separated by fibrous bands (Fig. 1B). Microscop-ically, multiple nodular vascular lesions presented in a fibrocol-lagenous connective tissue background (Fig. 2A). Each nodule was composed of irregular-shaped vessels lined by prominent endothelial cells (Fig. 2B). The endothelial cells were bland-looking and intermingled with perinodular fibroblasts. Cellular atypia and mitotic activity were rarely identified (Fig. 2C). With Masson-trichrome staining, the interangionodular spaces consisted of dense fibrous and collagenous tissue (Fig. 2D). The nodules contained spindle cells without atypia and inflammato-ry cells, and especially lymphocytes and plasma cells. Dispersed red blood cells and hemosiderin-laden macrophages were iden-tified in both the nodular and interangionodular spaces. No ne-crosis was presented in the mass.

Immunohistochemically, CD31, CD30, CD34, and VWF-VIII were detected in the plump endothelial cells of the angio-matoid nodule, but CD8 was not detected (Fig. 3A). Alpha-smooth muscle actin antigen was positive in the vascular net-work and the spindle cells of the interangionodular spaces (Fig. 3B). Reactivity for anaplastic lymphoma kinase protein, and D2-40 was not identified. The Ki-67 proliferation index was approximately 10%. The lesion was negative for Epstein-Barr

virus in situ hybridization.

DISCUSSION

SANT was recently described by Martel et al.1 in 2004 as a vascular lesion in the splenic red pulp. SANT presents as a well-circumscribed, but unencapsulated, solid single mass with a round to bosselated contour. The mass shows numerous variable sized red brown nodules separated by whitish fibrous tissue. The most distinctive microscopic finding in SANT is multiple angiomatoid nodules separated by collagenous bundles.3 The angiomatoid nodules are composed of variable shaped vessels that are lined by prominent, bland-looking endothelial cells. Cellular atypia and mitotic activities are extremely rare. The angiomatoid nodules are composed of three types of blood ves-sels; the cord capillary-type that are, CD31+/CD34+/CD8-, the sinusoid-type that are, CD31+/CD34-/CD8+, and small vein-type that are, CD31+/CD34-/CD8-, and these blood vessels re-semble the normal vascular structure of splenic red pulp.1 The endothelial cells that composed the angiomatoid nodules also express CD30, which is an activation marker of endothelial cells.2 In our case, the angiomatoid nodules showed prominent proliferation of the cord capillary type (CD31+/CD34+/CD8-) and small vein type (CD31+/CD34-/CD8-) blood vessels. More-over, the immunohistochemical staining for CD30 in this case showed positive reactivity. An inflammatory cell infiltration was present and this was, mostly cytotoxic T lymphocytes and polytypic plasma cells in an interangionodular, collagenous

A B

Fig. 1. (A) Post-contrast abdominal computed tomography shows a lobulated and heterogeneously enhanced, 6 cm-sized solitary mass in the spleen. (B) The solitary, well-circumscribed round tumor, measuring 6.5 cm in diameter. The cut surface shows multiple hemorrhagic nodules separated by fibrocollagenous stroma.

113Sclerosing�Angiomatoid�Nodular�Transformation�(SANT)

stroma, but the inflammatory cell infiltration was not promi-nent like that in inflammatory pseudotumor. The differential diagnosis for SANT includes other splenic vascular tumors such

as hamartoma, hemangioma, littoral-cell angioma, hemangio-endothelioma, and nodular transformation of the red pulp in association with metastatic carcinoma.

A B

C D

Fig. 2. (A) The angiomatoid nodules are surrounded by a dense fibrocollagenous stroma. (B) The angiomatoid nodule shows complex vas-cular networks with extravasted red blood cells. (C) The endothelial cells are plump and bland-looking without cellular atypia. (D) Masson-tri-chrome staining shows extensive collagen deposition in the interangionodular spaces (Masson-trichrome).

A B

Fig. 3. (A) Immunohistochemical staining for CD31 shows nodular positive staining. (B) The vascular network and the spindle cells of the in-terangionodular spaces are reactive for alpha-smooth muscle actin antigen.

� Hyun-Jung�Lee·Song-Yi�Choi·Song�Mei�Huang,�et�al.114

The cases of SANT reported by Martel et al.1 had been de-scribed as splenic hamartoma4 or hemangiendothelioma.5 Some authors have designated SANT with using different terms.

After using the designation of SANT, a total of sixty two cas-es have been reported in the English medical literature.1-3,6-10

In the literature, SANT was more frequent in females with a fe-male to male ratio of 1.4 : 1 and it showed broad age range from 22 years old to 82 years old. Most patients were asymptomatic and SANT was founded incidentally in the stage of evaluating for malignancy. Only 11 patients presented mild abdominal or back pain. Fever, an elevated erythrocyte sedimentation rate, and splenomegaly were observed in a minority of cases.1,3 Fifty five patients underwent splenectomy and thirty six patients were followed up without recurrence.

The pathogenesis of angiomatoid nodules is still unknown. Martel et al.1 proposed that angionodular transformation of the red pulp was the result of vascular obstruction. Diebold et al.3

who reported on 16 cases, suggested that disturbance of the in-trasplenic blood circulation in the red pulp as a possible mecha-nism of angiomatoid nodules. They also pointed that all their cases showed inflammatory pseudotumor (IPT)-like lesion in the interangionodular spaces and so this may imply an associa-tion between SANT and IPT. Although Martel et al.1 proposed that many lesions arose from IPT, Diebold et al.3 considered SANT and IPT to be related to one disease and they recom-mended careful examination for the presence of angiomatoid nodules. One case of SANT reported by Lee et al.7 presented with the coexistence of two rare lesions of SANT and calcifying fibrous pseudotumor. They supposed that these two lesions may have a common mechanism. Weinreb et al.2 reported on six cas-es of SANT and they described the the expression of CD30 in the endothelial cells of the angiomatoid nodules.

SANT is a distinctive benign splenic lesion. Our new case is in accordance with the pathologic findings of Martel et al.1 that SANT may represent a peculiar transformation of the red pulp in response to an exaggerated stromal proliferation.

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