Sclerosing angiomatoid nodular transformation of the spleen masquerading as a sarcoma metastasis

Introduction

Sclerosing angiomatoid nodular transformation (SANT) is a relatively new diagnosis that describes a benign change in the spleen. This is a rare condition, with only 82 cases reported since it was first described by Martel et al. in 2004, ¹ but recently more case reports are being published. Specifically, SANT is a vascular lesion of the red pulp of the spleen. We describe a case of SANT in a patient with a prior history of intermediate-grade spindle cell sarcoma of the retroperitoneum.

Case Report

A 65-year-old Ukrainian male with a history of type II diabetes, hypertension, and symptomatic cholelithiasis presented with a retroperitoneal spindle cell sarcoma. He underwent a margin-negative resection of a retroperitoneal spindle cell sarcoma with en bloc hemicolectomy and right nephrectomy. No adjuvant therapy was given. He was followed-up thereafter with chest imaging and magnetic resonance imaging (MRI) of the abdomen and pelvis every 3 to 4 months. At a two-year follow-up, a surveillance MRI demonstrated a new enhancing mass in the gastric cardia and a hypoenhancing mass in the spleen (Figure 1). Endoscopic ultrasound-guided fine needle aspiration (FNA) of the gastric lesion revealed spindle cells suspicious for either gastrointestinal stromal tumor or recurrent sarcoma. However, FNA of the spleen was non-diagnostic. With no evidence of metastatic disease, the patient underwent an operative exploration, with partial gastrectomy and splenectomy. Owing to his symptomatic biliary disease, a cholecystectomy was also performed.

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The partial gastric resection revealed a leiomyoma. The gallbladder showed chronic cholecystitis with cholelithiasis. The spleen was congested and enlarged, weighing 750 g and measuring 15×12×6 cm, with a very dark red but unremarkable parenchyma. Focally, a 2-cm well-circumscribed nodule with an area of central fibrosis was identified on further sectioning (Figure 2). Histological examination of a hematoxylin-and-eosin (H&E) stained section revealed a micronodular proliferation of vascular spaces lined by plump endothelial cells in a dense, collagenous stroma (Figure 3). Immunohistochemical stains performed on this lesion revealed a proliferation of cells that were positive for CD68 and smooth muscle actin (SMA), but negative for CD34 and CD8. The same cells also stained with periodic acid-Schiff (PAS). The histomorphology and staining profile taken together support the diagnosis of sclerosing angiomatoid nodular trans formation. The patient was discharged on postoperative day 5, after an uncomplicated hospital course.

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Discussion

SANT is a recently described benign splenic condition with a variable clinical presentation. Martel et al. reported that most patients with SANT were asymptomatic at presentation, although some had non-specific abdominal pain and discomfort or splenomegaly. ¹ Similarly, in a second series published by Diebold et al., the majority of patients were also asymptomatic, but had splenomegaly or abdominal pain. ² As in the present case, these splenic lesions are often incidental findings on imaging studies performed for other reasons. On computer tomography scans (CT) and MRI, SANT is a hypodense mass.^3–5 Because the differential diagnosis for a hypodense mass in the spleen includes lymphoma, metastasis, and benign lesions such as hamartoma,^6,7 diagnostic studies are essential in the management. FNA and core biopsy carry risks of bleeding and needle tract seeding. Therefore, splenectomy may be the preferred modality to rule out malignancy or other pathological processes.

Vascular lesions in the spleen include hemangioma, littoral cell angioma, lymphangioma, hemangioendothelioma, and splenic hamartoma. SANT is best differentiated from these tumors by immunohistochemical staining, but it also has a different histological appearance. SANT has vascular nodules of an angiomatoid appearance in a fibrous stroma.^1,8The nodules are angiomatoid because of their thin, round, or irregularly-shaped vessels lined by thick endothelial cells with spindly or ovoid cells. ¹ Three distinct types of vessels appear in angiomatoid nodules of SANT: CD34⁺/CD8⁻/ CD31⁺ capillaries, CD34⁻/CD8⁺/CD31⁺ sinusoids, and CD34⁻/CD8⁻/CD31⁺ small veins. ¹ In addition, cells in SANT stain for SMA and CD68.^2,4,9,10 Other splenic vascular lesions do not meet these criteria. Hamartomas have normal elements of red pulp, but have abnormal quantitative ratios of these constituents and abnormal distribution. They are round, sharply delineated, solitary tumors. ⁸ Their sinusoids express CD8 and CD31 but are negative for CD34 on immunohistochemical staining. SANT is different because of the combination of sinusoids, capillaries, and small veins. ⁹ Grossly, hemangiomas have a red, honeycomb appearance. Microscopically, they have distended blood vessels lined with a single layer of endothelium. ⁸ Lymphangiomas have subcapsular and peritrabecular cystic or solid lesions grossly, and cystic spaces lined with flattened endothelial cells histologically. ⁸ Hemangio-endotheliomas have ill-defined vascular spaces, minimal cellular atypia, and epithelioid or spindle cell morphology, but they have a range of appearances. ⁹ Littoral cell angiomas are spongiform, cystic nodules grossly, ⁸ and histologically are seen to be composed of vasculature lined by sinusoid lining cells (littoral cells). These cells are positive for CD31 and negative for both CD34 and CD8, unlike the sinusoids of SANT, which are positive for CD8. ¹

The pathogenesis of SANT is unknown. Diebold et al. postulate that passive congestion of the red pulp may cause metabolic changes in those areas, damaging the sinus endothelial cells. This may cause fibrin deposition and inflammation, as seen in granulation tissue. ² Martel et al. hypothesized that SANT was a response to stromal proliferation and that the internodular zones were very similar to inflammatory pseudotumor. ¹ Given the similar immunohistochemical staining to that of splenic hamartoma, SANT may be on the spectrum of hamartomas because of the red pulp tissue composition, as theorized by Awamleh and Perez-Ordonez. ⁹ Kuo et al. have connected the plasma cells and stromal sclerosis present in SANT to IgG4-related sclerosing disease. ¹¹ This idea is supported further by a recent report of three cases by Koreishi et al., in which all three cases had positive IgG4 plasma cells. ¹² A link with Epstein-Barr virus has also been postulated by Weinreb et al.; however, in their set of six cases only one was positive for the virus. ¹³ Koreishi et al. also tested for the Epstein-Barr virus, and in their three cases, all were negative. ¹² SANT is a benign lesion, and splenectomy is curative. Martel et al. surmised that the relatively high rate (20%) of coexisting current or history of malignancy and SANT is because of imaging done for the malignancy; comprehensive imaging finds these asymptomatic lesions. ¹ In the cases reported to date, recurrence of SANT does not occur. ¹ More research about SANT is necessary, but as more cases are described, an etiology will likely be discovered.