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Incidental littoral cell angioma of the spleen Tee, May; Vos, Patrick; Zetler, Peter; Wiseman, Sam M Aug 19, 2008

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ralWorld Journal of Surgical OncologyssBioMed CentOpen AcceCase reportIncidental littoral cell angioma of the spleenMay Tee1, Patrick Vos2, Peter Zetler3 and Sam M Wiseman*4Address: 1Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada, 2Department of Radiology, St. Paul's Hospital & University of British Columbia, Vancouver, British Columbia, Canada, 3Department of Pathology & Laboratory Medicine, St. Paul's Hospital & University of British Columbia, Vancouver, British Columbia, Canada and 4Department of Surgery, St. Paul's Hospital & University of British Columbia, Vancouver, British Columbia, CanadaEmail: May Tee - mctee@interchange.ubc.ca; Patrick Vos - pvos@providencehealth.bc.ca; Peter Zetler - PZetler@providencehealth.bc.ca; Sam M Wiseman* - smwiseman@providencehealth.bc.ca* Corresponding author    AbstractBackground: Littoral cell angioma (LCA) is a recently described primary vascular neoplasm of thespleen that may be associated with other malignancies and may itself also have malignant potential.Case presentation: We present a case of LCA that was discovered incidentally in a 52-year-oldwoman who presented with biliary colic at the time of consultation for cholecystectomy. Thisvascular neoplasm was evaluated by ultrasound, CT, MRI, Tc-99m labelled red blood cellscintigraphy, and core biopsy. A splenectomy revealed LCA by pathological evaluation. Post-operative outcome was favourable with no evidence of complication or recurrent disease.Following this case presentation, clinical, radiographic, and pathological features of LCA will bereviewed as well as recent advances in our understanding of this uncommon splenic lesion.Conclusion: LCA is a rare, generally benign, primary vascular tumour of the spleen that typicallyis discovered incidentally. Individuals diagnosed with this tumour must be carefully evaluated toexclude primary, secondary, and synchronous malignancies.BackgroundLittoral Cell Angioma (LCA) of the spleen was recentlydescribed by Falk et al. in 1991 [1]. This group reviewed200 surgical specimens of benign vascular splenictumours and found 17 similar tumours that appearedrelated to the cells lining the red pulp splenic sinuses [1].These tumours were unique in that they displayed bothepithelial and histiocytic properties based on their cell oforigin, the splenic littoral cells [1]. From these observa-tions, this group designated this new vascular tumour ofthe spleen LCA [1].presentation of LCA ranges from being completely asymp-tomatic and discovered incidentally, to presenting with aconstellation of signs and symptoms such as abdominalpain, vague constitutional symptoms, splenomegaly, andhypersplenism [2-6]. Although first described as benign,LCA has recently been shown to exhibit malignant poten-tial [11,12] and may also be associated with other visceralmalignancies [13]. In this report, we present a case of LCAincluding its diagnostic work-up, surgical treatment, path-ological evaluation, and post-operative outcome. A dis-cussion regarding the clinical, radiological, andpathological features of LCA, as well recent advances inPublished: 19 August 2008World Journal of Surgical Oncology 2008, 6:87 doi:10.1186/1477-7819-6-87Received: 14 January 2008Accepted: 19 August 2008This article is available from: http://www.wjso.com/content/6/1/87© 2008 Tee et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 5(page number not for citation purposes)Since this initial description, there have been scatteredcase reports and few case series of LCA [2-10]. The clinicalour understanding of this uncommon splenic tumour arealso presented.World Journal of Surgical Oncology 2008, 6:87 http://www.wjso.com/content/6/1/87Case presentationA 52-year-old woman was evaluated for symptoms of bil-iary colic for possible cholecystectomy. She describedintermittent episodes of right upper quadrant pain withno history of jaundice, nausea, vomiting, or changes inbowel habits. Laboratory tests revealed elevated liverenzymes of a cholestatic nature but total bilirubin withinnormal limits (ALP = 139 U/L, GGT = 67 U/L, totalbilirubin = 6 μmol/L). Haemoglobin, white blood cells,and platelet counts were within normal limits. Ultra-sound (US) revealed cholelithiasis, a normal appearingbiliary tree, and fatty infiltration of the liver. Notably, USalso identified a hyperechoic, well-circumscribed, 3 cmlesion located at the inferior aspect of the spleen (figure1). No significant vascularity was noted on the color Dop-pler images.The splenic lesion was further evaluated with CT, MRI. Ahypodense well defined lesion with some internalenhancement in the arterial and venous phases was dem-onstrated on the contrast enhanced CT scan (Fig. 2A, 2B).The lesion was isodense compared to the surroundingsplenic parenchyma on the 5 minutes delayed images(Fig. 2C). On MR, the lesion was hypointense on the T1,and hyperintense on the T2-weighted sequences (Fig. 3A).After the administration of IV gadolinium the lesion dem-onstrated some internal linear enhancement in the portalvenous phase on the T1-weighted fat suppressed sequence(Fig. 3B) and became isointense on the delayed images. ATc-99m labelled red blood cell scan showed the spleniclesion to be 'cold'. A percutaneous ultrasound guided corebiopsy of the lesion was subsequently carried out but wasnondiagnostic as histological evaluation showed skeletalmuscle. Overall, it was felt that the splenic lesion had abenign appearance and would be followed up with imag-ing.A laparoscopic cholecystectomy was performed. Nosplenic lesion was grossly evident at the time of laparos-copy. The postoperative course was uneventful and epi-sodes of abdominal pain resolved post-operatively. Acolonoscopy was also performed, which was normal. Arepeat CT scan 6 months postoperatively showed intervalenlargement of the splenic lesion as well as the develop-ment of an adjacent satellite lesion with a similar radio-logical appearance. As a result of the enlargement of thelesion, and development of a new lesion, a decision wasmade to carry out a splenectomy.At the time of open splenectomy, the spleen was unre-markable in terms of size and appearance, and wasremoved in its entirety for pathological evaluation. Thispatient had an uneventful post-operative recovery and hasremained well at fifteen months of post-operative follow-up. Pathologic evaluation identified a non-encapsulatedbut well-circumscribed reddish nodule that was 4 × 3 × 3cm in size and located at the anterior-inferior pole of thespleen. Histologically, this lesion was described as a vas-cular neoplasm forming anastomosing vascular channelslined by histiocytes with occasional papillary structure,consistent with Littoral Cell Angioma (Fig. 4).DiscussionPrimary vascular tumours of the spleen are uncommonbut represent the majority of non-hematolymphoidsplenic tumours [14]. The differential diagnosis of splenicvascular tumours is broad and may represent benign (hae-mangioma, haemartoma, lymphangioma), indeterminate(littoral cell angioma, haemangioendothelioma, haeman-giopericytoma), or malignant neoplasms (angiosarcoma)[14]. LCA is a recently described vascular tumour of thespleen that is now classified as having uncertain biologicalbehaviour, given several case reports which have identi-fied malignant potential [14].The exact incidence of LCA is unknown although the inci-dence of splenic haemangioma varies from 0.03% to ashigh as 14% in one reported autopsy series [15]. LCA doesnot have any particular gender or age predilectionalthough the median age in Falk et al.,'s original study ofLCA was 49 years [1,14]. As was the case for our patient,LCA may be completely asymptomatic and represent anincidental finding by imaging [13,16]. LCA may alsopresent with a myriad of possible signs and symptoms,such as: splenomegaly with or without abdominal pain,Ultrasound of the spleen demonstrates a well-defined hyper-echoic lesionFigure 1Ultrasound of the spleen demonstrates a well-defined hyper-Page 2 of 5(page number not for citation purposes)hypersplenism with ensuing anaemia and/or thrombocy-topenia, and constitutional symptoms such as intermit-echoic lesion.World Journal of Surgical Oncology 2008, 6:87 http://www.wjso.com/content/6/1/87tent fevers. More dramatically, LCA has been reported topresent as splenic rupture and haemoperitoneum [13-15].LCAs are believed to originate from the littoral cells, thecells that line red pulp sinuses of the spleen [1,17]. Fromstudies performed as far back as the 1930s, endothelialcells lining the vascular sinuses of the spleen were consid-ered unique in that they exhibited both phagocytic andhematopoietic properties [10]. Neoplasia of these cellsresults in the formation of LCA, which exhibit histologicand molecular features consistent with both these epithe-lial and histiocytic cell types [17,18].The pathogenesis of LCA remains unclear, but given itsassociation with autoimmune disorders such as Crohn'sdisease and inborn metabolic diseases such as Gaucher'sdisease, immune system dysfunction has been postulatedas a possible important pathogenic mechanism [10,19].Supporting this hypothesis, other reports have suggestedthat chronic infection and systemic immunosuppressionmay contribute to LCA development [13,18].Indeed, immune system dysregulation may explain theassociation of LCA with other cancer types. The other can-cer types associated with LCA include: thyroid, colorectal,renal, pancreatic, hematologic (lymphoma), ovarian, andtesticular cancer [10,13,18,20,21]. These observationsCT scan after oral and iv-contrast in the arterial phase A and portal venous phase B demonstrates a hypodense well defined round lesion in the posteri r por ion of the spleen with some line r internal enhancementFigure 2CT scan after oral and iv-contrast in the arterial phase A and portal venous phase B demonstrates a hypodense well defined round lesion in the posterior portion of the spleen with some linear internal enhancement. C. The lesion is isodense compared to the normal spleen on the 5 minutes delayed image.A. The lesion is hyperintense on the T2 weighted fast recovery fast spin echo (FRFSE) imageFigur  3A. The lesion is hyperintense on the T2 weighted fast recovery fast spin echo (FRFSE) image. B. Internal linear enhancement is Page 3 of 5(page number not for citation purposes)noted on the T1 weighted fat saturated image after iv-gadolinium in the portal venous phase.World Journal of Surgical Oncology 2008, 6:87 http://www.wjso.com/content/6/1/87have prompted recommendations to closely evaluate andprovide surveillance to patients with LCA for the develop-ment of other malignancies [20]. Conversely, the associa-tion of LCA with other cancer types may also be a result ofmaking an incidental diagnosis of LCA during extensiveradiological imaging for other diseases, given the largelyasymptomatic presentation of these tumours [22].However, close follow-up of LCA may be warranted due tothe potential for their malignant transformation. The twosubtypes of LCA with malignant potential have beendescribed as "littoral cell angiosarcoma" [18,23,24] and"littoral cell haemangioendothelioma" [11,12,18]. TheseLCA variants may present with distant metastasis severalmonths after splenectomy; histologic evaluation revealsfeatures consistent with LCA histopathology as well asabnormal architecture, nuclear atypia, and necrosis[11,12,23,24].Radiologically, LCA may be evaluated by several imagingmodalities such as US, CT, MRI, or nuclear medicine stud-ies (Tc-99m labelled RBC scintigraphy). US may reveallobular splenomegaly with heterogeneous nodules (eitherhypo- or hyper-echoic) that may be solitary or multiple(Figure 1) [25]. On non-contrast CT, LCA appear as hypo-attenuating masses; given the vascular nature of these neo-plasms, they tend to enhance homogeneously. On MRI, aminority of cases may be hypointense on both T1-weighted and T2-weighted scans because of hemosiderincontent of the tumour [14]. However, as significantsiderosis is seen in less than 50% of LCA cases [1], lesionsstudies with Tc-99m labelled RBC scintigraphy can be use-ful to differentiate splenic lesions from splenic haemangi-omas [27,28]. However, the radiologic features of LCA arerarely diagnostic since many other splenic neoplasmssuch as haemartomas, haemangiomas, lymphomas, met-astatic disease and infectious processes exhibit similarimaging characteristics [29].Gross pathology of LCA is characterized by single, or morecommonly, multiple pigmented focal nodules well-delin-eated from normal spleen parenchyma [28,30]. The col-our of these nodules may be dark red, brown, or black,consistent with blood or blood products of varying chro-nicity [28]. Rarely, LCA appears white on gross pathology[1,30]. The size of these lesions varies and may range from0.1 cm to 11 cm in diameter [1,30,31]. The spleen itselfmay appear grossly enlarged or, as was true for our case,look otherwise unremarkable [31,32].Microscopically, there are several distinguishing histolog-ical and molecular features of LCA. Histologically, LCAhas specific features that differentiate it from other pri-mary vascular tumours, including angiosarcoma [1]. LCAare composed of anastomosing vascular channels resem-bling splenic sinusoids and have irregular lumina featur-ing papillary projections and cyst-like spaces (Figure 4)[1]. Tall endothelial cells with histiocytic properties thatslough off into the vascular lumen are common, as is theabsence of atypical cells and presence of low mitotic activ-ity [1]. By immunohistochemical staining, these tumourcells will express endothelial and histiocyte antigens, areflection of the distinct dual differentiation potential ofLCA [1]. Such expression includes endothelial markers(factor VIII Ag and CD 31/BMA 120) as well as histiocyticmarkers (CD 68/KP 1 and lysozyme) [1,4,30,31,33]. Theexpression of these molecular markers has also been dem-onstrated in fine-needle aspiration biopsies of LCA [33].Symptomatic LCA are often relieved by splenectomy, andgiven the association of LCA with other malignancies andreported cases of metastasizing LCA, splenectomy is bothdiagnostic and therapeutic. While there have been reportsof medical therapy with glucocorticoids and angioembol-ization of splenic haemangiomas [34], splenectomy is stillconsidered the gold standard for treatment of vascularsplenic tumours [15].ConclusionLCA is a recently described primary vascular neoplasm ofthe spleen that may be associated with other malignanciesand may itself also have malignant potential. Several radi-ological studies may suggest LCA, although a pathologicaldiagnosis, either by core biopsy or diagnostic splenectomyAnastamosing vascular channels lined by plump cells with the appearance of sinus lining (arrow: 'littoral' cells) (H&E 100×)Figure 4Anastamosing vascular channels lined by plump cells with the appearance of sinus lining (arrow: 'littoral' cells) (H&E 100×).Page 4 of 5(page number not for citation purposes)tend to be hyperintense on the T2 weighted images, as wasthe case in our patient (Figure 3) [26]. Nuclear medicineis imperative. This rare case illustrates the importance ofthoroughly evaluating incidental vascular splenicPublish with BioMed Central   and  every scientist can read your work free of charge"BioMed Central will be the most significant development for disseminating the results of biomedical research in our lifetime."Sir Paul Nurse, Cancer Research UKYour research papers will be:available free of charge to the entire biomedical communitypeer reviewed and published immediately upon acceptancecited in PubMed and archived on PubMed Central World Journal of Surgical Oncology 2008, 6:87 http://www.wjso.com/content/6/1/87tumours. Although the vast majority of LCAs are benign,their differential diagnosis must include both primary andsecondary malignancy, given LCA's association with othercancer types as well as their uncertain malignant poten-tial. With this in mind, gold standard managementremains splenectomy and long-term follow-up for thedevelopment of synchronous tumours or metastaticlesions is advised.Competing interestsThe authors declare that they have no competing interests.Authors' contributionsMT performed the literature review and drafted the man-uscript. PV reviewed and revised the manuscript and pro-vided radiographic images. PZ reviewed and revised themanuscript and provided pathologic images. SW origi-nated the idea and assisted with drafting and revising themanuscript. All authors read and approved the final man-uscript.AcknowledgementsWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written con-sent is available for review by the Editor-in-Chief of this journal.References1. Falk S, Stutte HJ, Frizzera G: Littoral cell angioma – a novelsplenic vascular lesion demonstrating histiocytic differentia-tion.  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