History: A 58-year-old African-American man with chronic thrombocytopenia for five years was found by abdominal imaging to have a 12.8 x 9.1 x 9.6 cm solid splenic mass encompassing the vast majority of the spleen. A 603 gram diffusely dark red spleen was removed which showed at least six well demarcated nodules. They compressed surrounding tissues. The capsule was intact.
Microscopically, a vaguely nodular to diffuse intra-sinusoidal proliferation of plump, bland-appearing histiocytoid cells with vesicular nuclear chromatin and clear cytoplasm was noted (Fig. 1, 2, 3). Pseudopapillary vascular architecture was present in some areas (Fig. 4). Also present were scattered hemosiderin-laden macrophages, occasional residual lymphocytes and extravasated red blood cells. Immunohistochemical stains (Fig. 5) showed that the intra-sinusoidal histiocytoid cells expressed CD68, CD31, and CD4, but were negative for CD8, CD34, and CD79a. Flow cytometry showed no evidence of a lymphoid neoplasm. Normalization of platelet count was achieved after splenectomy.
Diagnosis: “Littoral Cell Angioma of the Spleenâ€
Marnelli A. Bautista-Quach MD, Michael Kyle MD, Jeffrey D. Cao MD,
and Donald R. Chase MD
Department of Pathology and Human Anatomy, Loma Linda University and Medical Center
California Tumor Tissue Registry, Loma Linda, CA 92354
Discussion: Splenic masses are commonly due to hematolymphoid neoplasms or metastatic malignancies. However, it is important to recognize the infrequent primary vascular lesions which comprise the majority of non-hematolymphoid splenic neoplasms. Littoral cell angioma (LCA) is a rare splenic vascular tumor with less than 70 reported cases. It was first described by Falk and colleagues in 1991. Computed tomography (CT) with or without contrast generally demonstrates enlarged a spleen with multiple hypoattenuating lesions. However, homogeneous enhancement and thus, isoattenuation is observed when using delayed contrast-enhanced imaging. LCA appears to arise from the sinusoidal lining cells of the red pulp.
Grossly, the spleen consists of multiple focal, relatively uniform, well delineated non-encapsulated dark red to dark brown nodules. Most show distinct margins but cases with poorly defined borders have also been observed. Our case showed a focally nodular spleen with diffusely dark red parenchyma and sinusoidal compression. No distinct demarcation between the uninvolved spleen and mass was identified suggesting almost complete effacement by the tumor.
Histologically, LCA is characterized by a proliferation of anastomosing vascular conduits lined by tall or histiocytoid, bland-appearing cells having either central or eccentrically located nuclei and distinctly clear cytoplasm. Mitotic figures are usually rarely encountered. Pseudopapillary configurations and/or cavernous dilatation of the vessels may also be present. The neoplastic Littoral cells typically co-express CD68 and CD31 indicating both macrophage and endothelial cell features but are negative for CD8 and CD34, whereas the normal endothelial cells lining the splenic venous sinuses are CD34 and CD8 positive. In summary, immunophenotypically, LCA frequently exhibits positivity for CD68, CD31, CD21, CD163, factor VIII, and negativity for CD8 and CD34. Only one reported case failed to expression CD21.
LCA usually has an indolent course; nonetheless, an aggressive type (Littoral cell angiosarcoma) has been encountered, described as having atypical cells, increased mitotic figures and metastatic foci. As such, LCA has been classified as having variable or uncertain biologic behavior. Furthermore, presence of concomitant visceral malignancies, most commonly colorectal adenocarcinoma, or other hematolymphoid neoplasms (33%) occur. An association with congenital and/or immunological disorders is documented in about 17% of the cases.
Splenectomy remains the gold standard in treatment although other modalities, such as partial splenectomy, glucocorticoid therapy, and angioembolization have been described.
Differential Diagnoses:
• Benign
o Hamartoma is mainly a propagation of red pulp with prominent fibrous cords and disordered, endothelium-lined vascular channels. Organized lymphoid follicles are not seen.
o Hemangioma or lymphangioma reflect proliferation of vascular or lymphatic channels lined by a flat, single layer of endothelial cells. Hemangiomas contain blood, while lymphangiomas are filled with proteinaceous substance.
• Uncertain biologic behavior
o Adult Hemangioendothelioma (HAE) is an angiocentric vascular tumor consisting of strands or nests of rounded to slightly spindle-shaped endothelial cells. However, large vascular channels are rarely encountered. Small intracellular lumens mimicking vacuoles or mucin are typically formed in the tumor cells. These cytoplasmic lumens frequently contain red blood cells. Most cases show bland neoplastic cells. Yet, approximately 25% of the cases demonstrate atypia, increased mitotic activity, and focal necrosis. When present, these features are associated with a more aggressive behavior.
o Hemangiopericytoma (HPC)/Solitary fibrous tumor (SFT) is a Proliferation of round, fusiform to spindle-shaped cells (pericytes) supported by and compressing distinct branching, dilated, “staghorn†or “antler-like†sinusoidal vessels which are lined by endothelial cells. A thick layer of collagen usually surrounds the larger vessels. The neoplastic cells, which are located external to the vascular channel basement membrane, are highlighted by a reticulum stain.
• Malignant
o Angiosarcoma of the spleen is a rare entity; however, it is the most frequent malignant non-hematolymphoid neoplasm encountered in the spleen. Increased numbers of large atypical cells with irregular nuclear contour and hyperchromatic nuclei line the disorganized vascular channels. Increased mitotic figures and apoptotic bodies are also present.
• Other considerations:
o Inflammatory Pseudotumor (IPT) or Inflammatory Myofibroblastic Tumor (IMT) was initially described in 1954 from several sites such as the respiratory tract, gastrointestinal tract and liver and recently has been described in virtually all possible sites. However, splenic IPT/IMT is extremely rare. Reportedly, it is well-circumscribed with focal areas of necrosis. The lesion consists of polymorphous lymphocytes, plasma cells and histiocytes and occasionally neutrophils and eosinophils, with propagation of fairly uniform spindle cells that demonstrate anti-smooth muscle actin (SMA) positivity, implying myofibroblastic origin. Some areas of fibroblastic proliferation may show a storiform appearance. Vascular proliferation is also seen.
o Sclerosing Angiomatoid Nodular Transformation of the Spleen (SANT) is a rare, benign entity was first described by Martel and colleagues in 2004. Nodular proliferation of intertwining slit-like vessels lined by bland, plump and occasionally spindled endothelial cells is seen. The vascular nodules are surrounded by prominent collagen bands with interspersed lymphocytes and plasma cells. The absence of the latter features distinguishes this entity from LCA.
o Myoid Angioendothelioma (MAE) was originally described in 1999 by Kraus and Dehner as a benign tumor consisting of small tubular vessels arranged in a sieve-like pattern. The vessels are lined by endothelial cells with small nuclei and scant cytoplasm which express CD34 but are negative for CD8. Bland, intervascular, medium-sized, polygonal to spindle-shaped stromal cells with fibrillary eosinophilic cytoplasm and condensed chromatin are present, in contrast to the histiocytoid cells seen in LCA. Moreover, the stromal cells in MAE characteristically show reactivity with SMA and actin suggesting myoid or myofibroblastic differentiation.
Suggested Reading:
• Abbott RM, Levy AD, Aguilera NS, Thompson WM. From the archives of the AFIP: Primary vascular neoplasms of the spleen: radiologic-pathologic correlation. Radiographics 2004; 24(4):1137-63.
• Arber DA, Stricker JG, Chen YY, Weiss LM. Splenic vascular tumours: a histologic, immunophenotypic and virological study. Am J Surg Pathol 1997; 21:827-35.
• Chourmouzi D, Psoma E, Drevelegas A. Littoral cell angioma, a rare cause of long standing anemia: a case report. Cases J 2009; 4 pages, doi: 10.1186/1757-1626-2-9115.
• Colović R, Suvajdzić N, Grubor N, Colović N, Terzić T. Atypical immunophenotype in a littoral cell angioma. Vojnosanit Pregl 2009; 66(1):63-5.
• Falk S, Stutte HJ, Frizerra G Littoral cell angioma. A novel splenic vascular lesion demonstrating histiocytic differentiation. Am J Surg Pathol 1991; 15:1023-33.
• Hsu CW, Lin CH, Yang TL, Chang HT. Splenic inflammatory pseudotumor mimicking angiosarcoma. World J Gastroenterol 2008; 14(41): 6421-24.
• Karim RZ, Ma-Wyatt J, Cox M, Scolyer RA. Myoid angioendothelioma of the spleen. Int J Surg Pathol 2004; 12(1):51-56.
• Kraus MD, Dehner LP. Benign vascular neoplasms of the spleen with myoid and angiendotheliomatous features. Histopathology 1999; 35:328-36.
