Residency Program - Case of the Month

Answer:

Littoral Cell Angioma of the spleen

Tumor description

Macroscopically, littoral cell angiomas (LCA) usually form multiple nodules of varying sizes throughout the spleen but they can also rarely present as solitary lesions.^1,2 LCAs are dark, spongy with hemorrhagic spaces and are grossly distinct from normal splenic parenchyma. Microscopically, the vascular spaces are lined by plump to tall cells with enlarged nuclei and small nucleoli. Nuclear pleomorphism and mitotic figures are not present (Figure 2). These lining cells also form tufts or micropapillary structures with histiocytes or lining cells present in the lumina.³

Immunohistochemistry

The lining cells of the LCA have a unique immunophenotype that helps to differentiate it from other types of splenic tumors. Normal sinus lining cells stain positive for CD-8 whereas the lining cells of LCA do not express CD-8 (Figure 3). CD-31, a vascular-associated antigen (Figure 7), von Willebrand factor (vWF), and Ulex europaeus are expressed on the lining cells of LCA. CD-34 is not expressed (Figure 8). An important distinguishing immunophenotype of LCA is the expression of the histiocyte-associated antigen CD-68 (Figure 5) and the complement receptor, CD-21 (Figure 4).³

Differential diagnosis

The primary tumors in the differential diagnosis of LCA are hemangioma and angiosarcoma.³ Hemangiomas are CD-34 positive, CD-21 negative, and do not have enlarged nuclei and papillary features. Angiosarcomas are also CD-21 negative and have true nuclear pleomorphism, mitotic figures and necrosis. These features are absent in LCA. The main differentiating feature of LCA is the positive expression of CD-21 (Table 1). Although hemangiomas and angiosarcomas usually do not express CD-68, some subgroups are known to be positive for CD-68.

Table 1. Immunophenotype of the Lining Cells of Splenic Vascular Tumors3

Abbrevations: LCA, littoral cell angioma; vWF, von willebrand factor; Ulex, Ulex europaeu.

Discussion:

Introduction. LCA of the spleen is a rare vascular tumor that was first described by Falk S et al. in 1991.⁴ These benign tumors are unique to the spleen because they are presumably derived from the normal splenic littoral cells found in the splenic red pulp sinuses. The tumor cells are characterized by the expression of both histiocytic (CD-68) and vascular endothelial markers (CD-31). Therefore, they are different from hemangiomas and hamartomas of the spleen. LCA has no predilection for any particular age-group or sex and cases have been reported in the age range of 1-77 years old with the median age of 50.^5,6

Clinical symptoms. Patients with LCA may present with an abdominal mass from splenomegaly, or with thrombocytopenia and/or anemia⁷ secondary to the splenomegaly. Some patients may not present with any symptoms at all and the tumor in these cases are identified incidentally. LCA can also occur in accessory spleens of the pancreas⁸. In addition, case reports have presented associated symptoms such as portal hypertension and pyrexia of unknown origin with LCA².

Diagnosis. Radiographic findings on CT imaging appear as hypoattenuating nodules ranging in size that demonstrate contrast enhancement on the portal venous phase. However, imaging can rarely lead to a definitive diagnosis because many other splenic neoplasms, such as hemangiomatosis, lymphangiomatosis, harmatomas, metastasis, lymphoma and Kaposi sarcoma, have similar appearances.⁹ Percutaneous fine needle aspiration has been used successfully in some cases. Nagarajan and authors suggest that endoscopic ultrasound guided fine needle aspiration biopsy is a safe and reliable method in diagnosing vascular lesions in the spleen.¹⁰ Treatment involves splenectomy and immediate resection is not indicated unless the lesion is symptomatic. However, the benign form needs to be differentiated from the malignant variant, the littoral cell angiosarcoma. Therefore, splenectomy is curative and can provide the final diagnosis¹¹. Partial splenectomy has also been performed for a solitary LCA in an 18 year-old girl in order to preserve splenic function.¹

Conclusion. To date the etiology of the LCA has not been identified and as most of the cases are reported to be benign, the malignant variant known as littoral cell angiosarcoma has been reported to metastasize.^4,12 Tan and authors postulate that there is a relationship between LCA and an altered immune host response as well as an association with malignancy. Out of the 36 published cases of LCA, a third was associated with visceral malignancies and two with lymphomas. The most common malignancy in these cases was colorectal adenocarcinoma.²  Therefore, close follow up of these patients for malignancy is recommended. In addition, some authors suggest that the chronic systemic inflammatory state in Gaucher's disease could also contribute to the pathogenesis of LCA.^13,14

References:

1. Mac New HG, Fowler CL. Partial splenectomy for littoral cell angioma. J Pediatr Surg. 2008; 43: 2288-2290.
2. Tan YM, Chuah KL, Wong WK. Littoral Cell Angioma of the Spleen. Ann Acad Med Singapore. 2004;33:524-6.
3. Arber DA, Stricker JG, Chen YY, Weiss LM. Splenic vascular tumors: a histologic, immunophenotypic and virologic study. Am J Surg Pathol. 1997;21:827-35.
4. Falk S, Stutte HJ, Frizzera G. Littoral cell angioma. A novel splenic vascular lesion demonstrating histiocytic differentiation. Am J Surg Pathol. 1991;15:1023-33.
5. Levy AD, Abbott RM, Abbondanze SL. Littoral cell angioma of the spleen: CT features with clinicopathologic correlation. Radiology. 2004;230:485-90.
6. Anton-Pacheco J, Ayuso RM, Cano I, et al. Splenic littoral cell angioma in an infant. J Pediatr Surg. 35:508-509.
7. Chourmouzi D, Psoma E, Drevelegas, A. Littoral cell angioma, a rare cause of long standing anemia: a case report. Cases Journal. 2009;2:9115.
8. Pilz JB, Sperschneider, T, Lutz, T, et al. Littoral cell angioma in main and accessory intrapancreatic spleen presenting as splenic rupture. Am J Surg. 2011 Feb;201(2):e15-7.
9. Bhatt, S, Huang J, Dogra V. Littoral Cell Angioma of the Spleen. AJR. May 2007;188:1365-1366.
10. Nagarajan P, Cai G, Padda M, et al. Littoral cell angioma of the spleen diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy. Diagnostic Cytopathology, 2010 May.
11. Akyildiz H, Akcan A, Soyuer I, et al. Littoral cell angioma mimicking pancreatic tumor. Surgery. 2007;141:690-1.
12. Rosso R, Paulli M, Gianelli U, et al. Littoral cell angiosarcoma of the spleen. Case report with immunohistochemical and ultrastructural analysis. Am J Surg Path. 1995;19:1203-8.
13. Gupta MK, Levin M, Aguilera NS, et al. Littoral cell angioma of the spleen in a patient with Gaucher's disease. Am J Hematol. 68:61-62.
14. Forest F, Duband S, Clemenson A, et al. Traumatic subcapsular splenic hematoma revealing littoral cell angioma and Gaucher's disease. Ann Hematol.2010;89:1061-1062.