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Annals of Clinical & Laboratory Science, vol. 42, no. 4, 2012

Littoral Cell Angioma: Diagnosis by Image-Guided Biopsy

Vincent A. Leung1, Shangguo Tang2, Etienne Mahe2, and Michael N. Patlas1

1Departments of Radiology and 2Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

Abstract. We report a case of littoral cell angioma (LCA) diagnosed by percutaneous core needle biopsy during the workup of a patient with multiple splenic lesions. Splenectomy was not performed. The patient has remained asymptomatic during 4 years of follow-up. Our findings raise interesting questions about the feasibility of core needle biopsy for the diagnosis of LCA. Clinicians should be aware of LCA as an unusual benign entity in the differential diagnosis of multiple splenic lesions.

Key words: littoral cell angioma, core biopsy, spleen

Address correspondence to Michael N. Patlas, MD, FRCPC, Department of Radiology, Hamilton General Hospital, 237 Barton Str. East, Hamilton, ON, Canada, L8L 2X2; phone: 905 529 3732; fax: 905 527 5761; e mail: patlas69@yahoo.com

0091-7370/12/0400-417. © 2012 by the Association of Clinical Scientists, Inc.

Introduction

Littoral cell angioma (LCA) is a rare primary be-nign vascular neoplasm of the spleen that was first described by Falk et al in 1991 [1]. LCAs arise from littoral cells which line the sinuses of the red pulp. LCAs are often detected during the workup of ane-mia and/or thrombocytopenia, in patients with non-specific symptoms such as abdominal pain, weakness, and fatigue, or as an incidental finding [2]. The majority of reported LCAs have been diag-nosed by splenectomy, while only a few cases have been identified by percutaneous biopsy. We de-scribe a case of LCA detected incidentally during workup for acute abdominal pain, which was diag-nosed by core biopsy.

Case Report

A 58 year old man presented to the emergency de-partment with sudden onset of retrosternal and epigastric pain. A complete blood count was nor-mal with a leukocyte count of 7.6 x 109/L, hemo-globin of 168 g/L, and platelet count of 196 x 109/L. The gamma-glutamyltransferase (GGT)

was elevated (231 U/L), but transaminases, alka-line phosphatase and bilirubin, were normal.The patient was referred to ultrasound, which dem-onstrated an impacted stone in the gallbladder neck with associated gallbladder wall thickening and a trace of pericholecystic fluid in keeping with a diagnosis of cholecystitis. Incidentally, it was not-ed that the spleen was enlarged, measuring 15.6 cm, and contained multiple hyperechoic lesions of varying sizes (Figure 1). The finding raised suspi-cion for malignancy.

The patient was further evaluated with both non-enhanced and contrast enhanced computed to-mography (CT) of the abdomen and pelvis. CT confirmed splenomegaly and demonstrated multi-ple rounded non-enhancing hypoattenuating le-sions ranging from 3 mm to 2.5 cm (Figure 2). Several borderline enlarged lymph nodes were not-ed in the peripancreatic region, favored to be reac-tive secondary to the cholecystitis. Core biopsy of the spleen was performed to rule out malignancies such as lymphoma and metastatic disease. Under ultrasound guidance, multiple 20 gauge core nee-dle biopsies were obtained. The patient did not have any complications from the procedure.

Histologic sections from the splenic core biopsies revealed an admixture of normal-appearing splenic

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red-pulp (highlighted by the arrowhead in Figure 3 outset) and tumoral tissue composed of thick-walled vascular channels lined internally with abnormal cells. These abnormal cells, unlike normal endothelial cells, appeared larger, with slightly vacuolated cytoplasm and lumen-polarized nuclei (Figure 3 inset). The ex-treme nuclear pleomorphism, hyperchromasia, and numerous mitotic figures and apoptotic bodies char-acteristic of malignant vascular lesions were not appar-ent. Evaluation of the hematolymphoid components

in the biopsy also failed to demonstrate any features supportive of a hematolymphoid ma-lignancy. In particular, there were no evident aggregates of atypical hematolymphoid cells, nor were there any cytologically aberrant he-matolymphoid cells.

Confirmatory immunohistochemical studies were undertaken (Figure 4). The abnormal vascular cells noted previously stained strongly and diffusely positive for Factor VIII, support-ive of a vascular origin. Likewise, these cells were positive for CD31. They were, however, negative for CD34, unlike typical endothelial cells. Furthermore, unlike normal endothelial cells, the abnormal cells in question were posi-tive for CD68 (a marker normally positive in cells of the monocyte/macrophage lineage). This staining pattern was in keeping with that of a littoral cell angioma.

The patient was initially managed conserva-tively with antibiotics and underwent laparo-scopic cholecystectomy 6 weeks thereafter. Splenectomy was not performed. The patient has been subsequently observed and has re-mained asymptomatic for 4 years.

DiscussionFirst described by Falk et al in 1991 [1], LCAs arise from littoral cells, which line the sinuses of the red pulp. The littoral cell is a cell which possesses, in addition to other endothelial cell properties, positive staining for histiocytic markers [3]. As such, the littoral cell may play a phagocytic role and therefore contribute to the filtration role of the spleen. Among the limited case reports of LCAs, there is a slight male predominance with a male: female ratio of 1.05: 1. LCAs are most frequently detected in adulthood (median age of 58 years), but have also been seen in pediatric populations [4].

The presentation of LCAs is variable. A num-ber of asymptomatic cases have been discov-ered during the workup of anemia and/or thrombocytopenia, as well as during follow-up of malignancy [2, 5]. Cases have been

Figure 1. Ultrasound demonstrates multiple hyperechoic splenic lesions.

Figure 2. IV contrast enhanced CT in portal venous phase demonstrates rounded hypoattenuating lesions of varying sizes in an enlarged spleen.

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diagnosed in patients with non-specific symptoms such as abdominal pain, weak-ness, and fatigue [6]. In addition, LCAs have been detected during the workup of abdominal emergencies, including traumat-ic splenic rupture [7].

On ultrasound, LCAs typically present as solitary or multiple hyperechoic lesions in an often enlarged spleen, although cases of hypoechoic LCAs have been reported [4]. On CT, LCAs are isoattenuating relative to the splenic parenchyma on non-enhanced images, homogenously hypoattenuating on early portal venous phase, and fill to be-come less hypoattenuating or even isoat-tenuating by late portal venous phase [8]. On MRI, some case reports have described T1 hypointensity and T2 hyperintensity, with contrast enhancement similar to that seen on CT studies [9]. However, LCA has also presented as hypointense on both T1 and T2 weighted sequences, which could be related to hemosiderin deposition causing magnetic susceptibility artifact [10].

Commonly, the imaging appearances are non-specific. The differential diagnosis in-cludes metastases, lymphoma, and primary splenic neoplasms [11, 12]. In clinical prac-tice, multiple splenic nodules are most often related to metastases or lymphoma [10]. Disseminated fungal disease, septic emboli, and granulomatous diseases such as sarcoid-osis and tuberculosis are also considered in the differential [8].

Histopathologically, LCAs are character-ized by a proliferation of anastomosing vas-cular spaces lined by plump, often vacuolat-ed, cells [3]. These cells are distinguished from normal endothelial cells not only by their relative size and distinct cytoplasm, but also by the frequent lumen-polarized nuclei. Tumor cells have also been observed to project into the vascular lumina in papil-lary formations; they may detach into these lumina and may also demonstrate hemo-phagocytosis [3].

Most reported cases of LCA were diagnosed by splenec-tomy. The use of fine needle aspiration biopsy (FNAB) and core biopsy has been limited, likely due to concern for hemorrhage [13]. More recently, studies have support-ed the safety and efficacy of percutaneous biopsy of the spleen, with a diagnostic yield of core needle biopsy of over 88% in adults and 83% in children [14]. The sensi-tivity of FNAB may be slightly lower, with diagnostic yields ranging from 63% to 89% [15]. Our case was con-fidently diagnosed on percutaneous core biopsy, thereby avoiding the potential morbidity and mortality related to splenectomy.

A possible association of LCAs with malignancies and immunodysregulation has been reported. However, given the lack of prospective studies, it is difficult to determine whether there is a true association, or whether LCAs are simply detected more frequently in populations that re-quire increased imaging. Regardless, some authors sug-gest screening for malignancies when an LCA is detected [6].

While most LCAs are benign, there have been several re-ports of LCA demonstrating potentially malignant be-havior. One of the patients in the original case series was noted in follow-up to have vascular lesions in the liver and retroperitoneal lymph nodes with histopathologic characteristics similar to the patient’s splenic LCA [1, 16]. Even at this patient’s original presentation, atypical

Figure 3. Outset: Intermediate power H&E (50x) photomicro-graph demonstrating a core of tumor (left) and a fragment of nor-mal splenic red pulp (arrowhead). Inset: high power H&E (400x) photomicrograph of tumour highlighting the relatively thicker-walled vascular structure containing large vacuolated cells with lumen-polarized nuclei.

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histopathological features were noted in the splenic lesion, including solid intraluminal proliferation of neoplastic cells. Several cases of littoral cell heman-gioendothelioma, with features similar to LCA but with atypical histological changes, have been re-ported; some of these cases have also demonstrated spread to the liver and retroperitoneum [17]. In ad-dition, Rosso et al reported a case of littoral cell angiosarcoma, which shared the dual histiocytic and endothelial differentiation of LCA, but had malignant nuclear features and solid nests of cells with mitotic figures [18].

There are no clear guidelines for the treatment of LCA diagnosed preoperatively. Given the indeter-minate biologic behavior, elective splenectomy has been reported in several studies [19, 20]. However, in an asymptomatic patient, close follow-up may also be an appropriate approach [21].

In summary, we describe a case of LCA, inciden-tally detected in a patient presenting with cholecys-titis. The imaging characteristics were nonspecific and given the presence of multiple splenic lesions, metastases and lymphoma could not be excluded. Diagnostic core biopsy was performed without

complication. The patient was managed non-oper-atively and has remained asymptomatic for 4 years. This case report demonstrates that LCA should be considered in the differential diagnosis for multiple focal splenic lesions.

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Figure 4 - Avidin-Biotin immunohistochemical stains (100x) demonstrating tumour cell positivity for Factor VIII, CD 31 and CD 68 and negative staining with CD 34 (the peripheral stromal cells are staining positive).

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