Littoral cell angioma (LCA) is a rare primary splenic hemangioma, which can appear in the red sinus shore cells of the reticuloendothelial system (RES) in the spleen. Falk et al. were the first to describe and name LCA in 1991. Most of the reported cases are that of a benign tumor and can present as a single lesion as well as multiple recurrent lesions. The cells express both endothelial as well as histiocytic antigens, a characteristic feature of double differentiation of littoral cells, in contrast to the splenic red pulp cells that only express endothelial markers. The diagnosis of LCA relies on morphology and immunohistochemical studies. Fine needle aspiration cytology can aid in some cases in narrowing the differential before the operative excision of the tumor.
The etiology of littoral cell angioma remains mostly unknown. However, there seems to be a role of immune dysregulation, as evident from the concomitant presence of other tumors and inflammation in the reported cases. It is a primary vascular tumor arising from the cells lining the splenic red pulp venous sinuses, hence the name littoral cells. This lesion is a distinct entity from other splenic vascular lesions, e.g., angiosarcoma, as suggested by the dual (endothelial and histiocytic) differentiation pattern of the LCA. The immunohistochemical feature of the LCA cells is typical for co-expression of CD 68 and lysozyme (macrophage markers), and factor VIII and CD 31 (endothelial markers). The expression of the CD 68 marker is suggestive of the fact that the tumor is likely originating from the cells lining the splenic sinuses.
LCA is a rare splenic vascular tumor discovered either as an incidental finding or patients may present with abdominal pain. It appears to affect individuals of age group. However, most of the reported cases are in the middle-aged adult population and very few in the children. There is no gender predilection, and the incidence appears to be equal in both males and females.
The exact pathogenesis mechanism leading to the development of LCA is not known. However, the association of the LCA with congenital and immunological disorders does point towards the possible role immune dysregulation plays in the pathogenesis of these tumors. There have been case reports describing the association of cancers of lung, colon, pancreas, kidney, and ovary with LCA. Also rarely reported are leiomyosarcoma, lymphoma, and melanoma. Therefore, one should always be mindful of the possibility of and rule out other neoplasms in all patients diagnosed with LCA. In a retrospective case study conducted in 17 cases of LCA by Bi et al., 17% of the cases were found to correlate with congenital and immunological disorders like ankylosing spondylitis, aplastic anemia, myelodysplastic syndrome, chronic glomerulonephritis, Gaucher disease, Crohn disease, Wiskott-Aldrich syndrome, lymphocytic colitis, and Epstein syndrome. The case study also proposed that the hyperplasia and anastomosis changes in the littoral cells could be secondary to hemodynamic disturbances in the spleen. These disturbances lead to hemangioma like growth in the littoral cells along with histiocytic reaction.
The majority of the LCAs are known to be benign, though there have been reported cases of two subtypes of malignant LCA, known as littoral cell angiosarcoma and littoral cell hemangioendothelioma.
The gross appearance of the spleen can be slight to moderately enlarged size and weight, with a cross-section showing widened splenic trabeculae and more commonly multifocal than a solitary nodule. The histological examination shows sinus like anastomosing channels with an irregular lumen that resemble splenic sinusoidal architecture. These channels can have a papillary pattern as well as cyst-like space that is lined by tall, plump endothelial cells. These endothelial cells can have hemophagocytosis and lack features of nuclear atypia or mitotic activity.
The immunohistochemical staining for littoral cells usually reveals a dual differentiation pattern. The cells stain positive for both endothelial markers, e.g., factor VIII (FVIII), CD31, von Willebrand factor (vWF), CD34, as well as histiocytic markers, e.g., CD 68.
A case report of 3 cases by Jun et al. studies the electron microscopic finding of LCA. It shows polygonal tumor cells surrounded by blood vessels. Of note, the vessels were lacking smooth muscles as were found to have a lining of medium electron density homogenous basilar membrane only. The researchers noted that the tumor cells had an abundant cytoplasm that was rich in mitochondria, rough endoplasmic reticulum, and lysosome. Some cells showed bundles of intermediate filaments and lipofuscin bodies.
The LCA can present as an incidental finding in an asymptomatic patient or as abdominal pain. The physical exam can reveal the presence of splenomegaly in some cases. Other less common clinical features include the presence of anemia, thrombocytopenia, hepatitis, cirrhosis, and portal hypertension. There also have been reported cases describing the association of LCA with extramedullary hematopoiesis.
The diagnosis of LCA is only possible by histopathological examination. Fine needle aspiration cytology (FNAC) is an option for splenic masses; however, it is not very specific and is not recommended given the risk of bleeding and tumor cell dissemination if the tumor is malignant.
The radiological imaging studies like magnetic resonance imaging (MRI) and computed tomography scan (CT scan) have not proven to be adequate in diagnosing littoral cell angioma, given that it is difficult to differentiate from other splenic neoplasms like angiosarcomas, lymphomas, metastatic tumors on imaging. Owing to the hemosiderin deposits in the tumor cells, hypodense lesions are visible on T1 and T2 weighted MRI images. Sonography evaluation is not helpful because of the variable findings of heterogeneous echotexture and no definite lesions.
Currently, splenectomy followed by long term follow up is the recommended treatment for LCA given its malignant potential. Since LCA can be associated with splenomegaly, performing a laparoscopic splenectomy (LS) can be a challenging task. It should only be performed by an experienced surgeon with particular attention to prevent splenic capsule rupture and, consequently, any tumor cell dissemination. A study done by Cai et al. demonstrated that it is feasible and safe to do LS for patients with LCA. Conversion to hand-assisted laparoscopic splenectomy (HALS) or even open surgery, may be necessary when dealing with cases having extensive adhesions or massive splenomegaly, especially in patients with malignant tumors.
The differential diagnosis includes other vascular neoplasms of the spleen, including splenic hemangioma, lymphangioma, hamartoma, angiosarcoma. The LCA can be differentiated from these lesions based on the histopathological and immunophenotyping findings, as detailed above. Imaging studies (MRI, CT scan, ultrasound) have not demonstrated usefulness in differentiating between these.
The LCA is typically benign with an excellent prognosis post-splenectomy. However, there have been reported cases of malignant LCA. A literature review by Sarandria et al. of 180 LCA cases revealed that massive splenomegaly (splenic weight greater than or equal to 1500 gm and/or length greater than 20 cm preoperatively) is associated with malignant transformation (p-value < 0.05). Patients with massive splenomegaly and undergoing splenectomy need to have close follow up to monitor for recurrences and tumor dissemination.
The complications of littoral cell angioma could be secondary to hypersplenism leading to anemia, thrombocytopenia, abdominal pain, and weight loss. Additionally, the patient can develop early postoperative complications of splenectomy performed for treatment of LCA like bleeding, incision site infection, hernia, atelectasis, pulmonary and abdominal sepsis, pancreatitis, pulmonary embolism. Asplenic patients are at an increased lifelong risk of developing post-splenectomy septic syndrome and infections with encapsulated organisms. The administration of appropriate immunizations does not eliminate the risk (for example, pneumococcal vaccination).
LCA diagnosis is mostly an incidental finding in asymptomatic patients. However, patients should maintain a consistent follow up for evaluation of a suspected splenic lesion. Also, post-splenectomy recommendations on immunizations need followup to prevent serious, life-threatening infections from the encapsulated organisms for which these patients are at risk.
Following the identification of a suspicious splenic lesion, it is imperative to follow an integrated approach with the interprofessional team of internal medicine physicians, hematologist-oncologist, pathologist, radiologist, and general surgeons. A management plan that is best suited for the patient based on the patient and tumor characteristics, ensuring prudent long term follow up is necessary for best clinical outcomes.
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