December 2013

A 65-year-old female with abdominal pain

Maggie Yell, M.D., Jeffrey Vos, M.D., Olukemi Esan, M.D.

Overview

A 65-year-old female presented with intermittent inexplicable abdominal pain as well as intermittent fatigue.  A computed tomography (CT) scan revealed a 2.2 cm hypodensity in the spleen.  An open splenectomy was performed.

Gross Description

A 270g, 13.3 x 8.1 x 7.2 cm spleen was received. The capsular surface was grey and smooth with no obvious defects.  Sectioning revealed a 2.0 x 2.0 x 2.0cm soft, ill-defined, hemorrhagic area, which was 0.2 cm subjacent to the capsule.  The remainder of the splenic parenchyma was dark red and unremarkable. Microscopic examination showed the following:

fig-1-he.jpg
Figure 1: 20X magnification. The lesion (arrows) is well demarcated from an edge of normal spleen. Cavernous spaces and connecting vascular channels can be appreciated at this power.
fig-2-he.jpg
Figure 2: 400X magnification. The lesion contains larger lining cells that protrude into the cyst-like spaces. Some of these cells have sloughed off into the lumen.
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Figure 3: 400X magnification. CD31 stains the flat endothelial lining cells of the lesion.
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Figure 4: 400X magnification. A dilated cyst-like space (arrowheads) is lined by larger lining cells (arrows), which are highlighted by an S100 immunohistochemical stain. The majority of these cells have sloughed off into the lumen.
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Figure 5: 100X magnification. CD8 stains the lining cells of the normal sinuses (arrows), but neither the tall cells nor the flat endothelial cells, which line the cyst-like spaces of the lesion. Scattered CD8+ T cells are seen in the both the lesion and unaffected splenic parenchyma.
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Figure 6: 400X magnification. A lysozyme immunohistochemical stain highlights the large lining cells. CD68 showed a similar staining pattern.

Diagnosis

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Answer

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Discussion

Littoral cell angioma is a vascular lesion of the spleen that was initially described by Falk et al. in 1991 [1].  This is a rare splenic vascular tumor that is located in the splenic red pulp as single or multiple lesions and is likely derived from the so-called littoral cells of the splenic red pulp [2].  Historically, this is regarded as a benign lesion; however, due to the extremely rare possibility of transformation to an angiosarcoma, it is now regarded as having uncertain biologic behavior [3]. 

Grossly, littoral cell angioma usually presents as multiple spongy, red-brown hemorrhagic nodules, which are within the red pulp, are typically well circumscribed, and may compress the adjacent splenic tissue [1,4].  The size of the lesion can range from tiny foci to large areas that can replace most of the splenic parenchyma.  The microscopic architecture consists of anastomosing vascular channels that appear similar to normal splenic sinuses but are less well organized, show areas of dilation and often have papillary fronds.  The vascular channels may become cystic and are lined by two cell types.  One cell type resembles the flat endothelial cells that line normal splenic sinuses [1].  The other lining cells, typically seen interspersed among the flat cells, are larger by comparison. These larger lining cells protrude and often slough off into the cyst-like spaces and are characterized by large nuclei with vesicular chromatin, small nucleoli and a moderate amount of eosinophilic cytoplasm [1,4].  These tall, plump lining cells show no cytologic atypia and have few mitotic figures [4].

Immunohistochemically, the tall lining cells express endothelial markers (factor VIIIAg, CD31) and histiocytic markers (CD68, lysozyme, CD21) [1,4,5].  This staining pattern highlights the dual histocytic and endothelial nature of the littoral cell angioma.   The reticuloendothelial cells that normally line the splenic sinuses have a dual differentiation potential that is unique to the spleen and thus, provides the most likely explanation for the histogenesis of this tumor.  In addition to histiocytic and endothelial markers, these cells will occasionally express S-100 protein [1].  They stain negatively for CD34 and CD8 which, in contrast, will highlight normal splenic sinus lining cells [3,4].

Before being recognized as a distinct entity by Falk et al. in 1991, cases of littoral cell angioma were most likely originally diagnosed as hemangiomas, angiosarcomas, or vascular hamartomas [1].  Though the clinical and macroscopic presentation is similar to other vascular tumors of the spleen, littoral cell angioma has a distinct morphologic features and immunophenotypic staining pattern that differentiates it from these other tumors.  Splenic hemangioma is composed of cavernous vascular spaces that are lined by flat endothelium with inconspicuous nuclei.  This entity lacks the papillary fronds and tall lining cells that are typical of littoral cell angioma. Splenic hemangiomas do not express CD68 or S-100 protein. Angiosarcoma is composed of haphazardly anastomosing vascular channels with papillary, pseudosinusoidal, or solid components.  Spindle cells, along with nuclear atypia, mitotic activity, and necrosis can be seen. In comparison, littoral cell angioma is arranged in an organized fashion [1].  Splenic hematoma, sometimes referred to as “splenoma”, is an anomalous growth composed of disorganized red pulp tissue without malpighian corpuscles. The lining cells of the sinuses are positive for CD8, CD31 and factor VIII while variable for CD34, essentially mimicking the phenotype of normal sinus lining cells of the spleen [6].

Littoral cell angioma mostly occurs in the age range of 35-60 years and is equally represented in men and women [5].  Clinically, it is associated with the typical signs and symptoms of most splenic tumors [1].  These include splenomegaly, left upper quadrant abdominal pain or left flank pain, weakness, fatigue, weight loss, and anorexia.  Patients presenting solely with fever or elevated ESR have been reported in some cases [1]. The most efficient way to diagnose littoral cell angioma is by splenic biopsy [4] or resection.  Close follow-up of the suspected lesion with imaging studies or treatment with splenectomy is recommended due to the very rare, but possible malignant transformation to littoral cell angiosarcoma [3]. Case studies have shown possible associations with various types of malignancies at other sites including lymphomas, carcinomas, melanoma and, leukemias [4]. There is also a possible association with immunologic disorders including Crohn disease, aplastic anemia, ankylosing spondylitis, and chronic glomerulonephritis [4]. 
Post-operatively, the patient became asymptomatic and was followed up with routine screenings including a mammogram and colonoscopy, both of which were negative for malignancy. 

References

  1. Falk S, Stutte HJ, Frizzera G. Littoral Cell Angioma: A Novel Splenic Vascular Lesion Demonstrating Histiocytic Differentiation. The American Journal of Surgical Pathology. 1991; 15 (11): 1023-1033.
  2. Emir S, Sozen S, Yazar MF, Altinsoy HB, Solmaz OA, Ozkan Z. Littoral-cell angioma of the spleen. Archives of Iranian Medicine. 2013; 16 (3): 189-191. 
  3. Kranzfelder M, Bauer M, Richter T, Rudelius M, Huth M, Wagner P, Friess H, Stadler J. Littoral Cell Angioma and Angiosarcoma of the Spleen: Report of Two Cases in Siblings and Review of the Literature. Journal of Gastrointestinal Surgery. 2012; 16 (4): 863-867. 
  4. Craig J, Goyal M, Kim B, Wasdahl D, Nazinitsky K. Littoral Cell Angioma. Clinical Imaging. 2007; 31 (1): 27-31.
  5. Lin XY, Li JM, Wang QX, Feng JZ, Zhao MQ, Zhong WX, Li JF. Littoral Cell Angioma of the Spleen: Report of three cases and a review of the literature. Chinese Medical Journal. 2011; 124 (20): 3423-3426.
  6. Lee H, Maeda K. Hamartoma of the Spleen. Archives of Pathology & Laboratory Medicine. 2009; 133:147-151.