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Littoral cell angioma of the spleen revealed by a Kasabach-Merritt syndrome in a 22-month-old child.


Kasabach-Merritt syndrome (KMS) is characterized by the association of a vascular tumor, a major thrombocytopenia and a potentially life-threatening coagulopathy. It develops in infancy and is associated with a high morbidity and mortality rate [1], as a result of severe bleeding, sepsis or invasion in vital organs [2].

Interaction between platelets and endothelial cells, and the resulting proangiogenic phenotype, has been recognized to underlie the pathogenesis of this disorder [3].

KMS is not associated with infantile hemangiomas (which are common benign vascular lesions) but occurs almost exclusively as a complication of other rare entities such as kaposiform hemangioendotheliomas (KHE) and tufted angiomas (TA). Many arise from the soft tissue of the extremities and slightly more than 10% of all cases lack cutaneous manifestations [4]. Littoral cell angioma (LCA) is another rare and benign vascular lesion, first described in 1991 by Falk et al [5], which may be complicated by life-threatening KMS.

We report here on a patient with a littoral cell angioma of the spleen who displayed a severe KMS with complex diagnosis. The occurrence of this uncommon internal tumor is very rare and may be considered as an unusual presentation.

Case Report

A 22-month-old child was referred to our hospital for incidental discovery of thrombocytopenia in a context of asthenia. He was the second child of Caucasian parents and had no medical history except for recurrent ear, nose and throat (ENT) infections.

Clinical examination showed ecchymotic purpura of the lower limbs and petechial purpura of the upper limbs. He was also found with mild conjunctival icterus, no tumoral syndrome, no hepato-splenomegaly and good general condition.

His laboratory parameters showed regenerative hemolytic anemia (hemoglobin: 10.2 g/dL, reticulocytosis: 180 G/L, haptoglobin < 0.08 g/dL) and thrombocytopenia (platelets: 32 G/L with normal mean platelet volume). The rest of his laboratory evaluation revealed elevated white blood cells count (15.3 G/L), normal liver and pancreatic function tests, decreased prothrombin ratio (59%), low fibrinogen level (1.4 g/L), presence of fibrin degradation products, positive D-dimer test and low factor V level. Abdominal ultrasound showed an enlarged homogeneous spleen (131 mm) with no other abnormalities observed. Bone marrow aspiration and biopsy were performed and showed a high megakaryocyte count with no neoplastic infiltration. Complementary investigations ruled out Wilson's disease, viral infections, thrombotic thrombocytopenic purpura and constitutional red blood cell disorders. Our main hypothesis remained a thrombotic microangiopathy (TMA) despite the absence of schistocytes on repeated blood tests.

Given the absence of diagnosis and complication, no treatment was undertaken. The child was regularly followed-up in consultation for two months, during which time his platelet count ranged between 25 and 45 G/L. He was then re-examined in consultation for acute clinical and biological worsening. Physical examination revealed persistent purpura and conjunctival icterus, associated with appearance of palpable splenomegaly (measuring 158 mm on ultrasound control with a heterogeneous pattern). He presented hematomas after venipunctures and active bleeding after a second bone marrow aspiration was performed (yielding the same results as in the first analysis). At admission to hospital, his hematological parameters revealed thrombocytopenia (27 G/L), anemia (Hb: 9.7 g/dL), high reticulocytosis (368 G/L), persistent stigmata of hemolysis, decreased prothrombin ratio (48%), low fibrinogen (0.8 g/L) and low factor V level (45%). The following days, we noted a rapid deterioration of his biological parameters with daily transfusion requirements. The patient presented prolonged prothrombin time and unmeasurable fibrinogen levels. Partial and transitory improvement was observed after fibrinogen supplementation followed by secondary deterioration.

Even if no schistocytes were found on repeated peripheral blood smears, TMA remained our main hypothesis with suspicion of an unusual spleen-localized presentation. However, successive blood cell counts showed fluctuating leukocytosis with monocytosis at the upper limit of normal, stressing out the need to rule out a hemopathy like juvenile myelomonocytic leukemia, finally refuted.

At day 6 of hospitalization, a bluish subcutaneous nodular skin lesion appeared on the anterior face of the tibia. A biopsy was performed in search for leukemia cutis but no neoplastic infiltration was found and histopathology yielded non-contributory results.

Due to worsening hemorrhagic symptoms and persistent daily transfusion requirements, steroids therapy was started at a dose of 2 mg/kg/day, with no improvement in the following 48 hours. Indeed, the patient continued to display severe disseminated intravascular coagulation associated with a rapid enlargement of the spleen after each transfusion.

At day 7, a CT scan was performed and found a voluminous spleen with a persistent heterogeneous pattern, measuring 185 mm, extending to the pelvis, along with increased pancreas and posterior mediastinal masses which were interpreted at this time as lymphadenopathies (Figure 1).

Despite supportive care, the patient's general condition gradually worsened. In fear of a life-threatening spleen rupture, splenectomy was performed at day 8 under cover of platelet and fresh frozen plasma transfusions. No peroperative bleeding complication occurred. The surgeon macroscopically described diffuse angiomatosis and splenic lymphangiectasia. Anatomo-immunohistochemical analysis revealed a vascular lesion infiltrating the whole spleen, compatible with a littoral cell angioma.

Within 48 hours after splenectomy, the patient showed rapid clinical improvement and complete hematological normalization (except for post-splenectomy thrombocytosis at 738 G/L). One month later, a CT scan control showed normal pancreas and disappearance of the posterior mediastinal masses (which were then interpreted as lymphangiomas in the light of the previous diagnosis of littoral cell angioma of the spleen). No major complication occurred during follow-up.


In 1940, Kasabach and Merritt reported the case of an infant with a capillary hemangioma associated with extensive purpura responsible for thrombocytopenia, thrombotic microangiopathy and consumption coagulopathy [6]. This condition, although benign, can be life-threatening due to hemorrhagic complications with a mortality rate ranging from 30 to 40 % [7].

KMS pathophysiology is presumed to be related to platelet trapping, activation and consumption within the abnormal vascular structure [3] leading to activation of the coagulation cascade. Intra-lesional bleeding may occur as well as distant bleeding and purpura due to systemic coagulation abnormalities.

KMS is mostly described in cutaneous hemangiomas. Rare cases of splenic hemangiomatosis associated with KMS have been reported in literature. The spleen is a highly vascular organ and is susceptible to a wide range of complications, including vascular and hematological disorders. Splenic hemangiomas are usually asymptomatic and incidentally discovered [8] but patients may also present with abdominal pain, large splenomegaly or KMS at diagnosis.

When associated with external vascular tumors, the diagnosis of KMS is more easily performed. It gets harder when hemangiomas develop in organs such as liver and spleen. Biopsy is rarely performed because of the high risk of hemorrhage and even more so when KMS is associated. Moreover, imaging characteristics of splenic hemangiomas vary depending of their size and composition and are usually nonspecific [8]. In our patient, the heterogeneous pattern of the spleen on sonography and CT scan oriented towards a malignant process. The posterior mediastinal masses on CT scan were interpreted at first as lymphadenopathies, thus supporting diagnosis of hematological malignancy. However, both bone marrow aspiration and biopsy refuted this diagnosis.

Given the poor specificity of imaging and the hemorrhagic risks associated with percutaneous biopsy, splenectomy was performed for both diagnostic and therapeutic purposes.

The diagnosis of littoral cell angioma (LCA) was finally made, which is a different vascular tumor with a resemblance pathologically to either tufted angioma (TA) or kaposiform hemangioendothelioma (KHE) in association with lymphatic-like vessels [9]. It is important to point out that most reported cases of KMS were associated with KHE and TA, rarely with LCA [10].

Our main hypothesis had remained a thrombotic microangiopathy despite the absence of peripheral schistocytosis and intrasplenic TMA was finally confirmed by these vascular lesions.

Management of KMS is still controversial as the choice of treatment is usually empirical and response to treatment, unpredictable. Non-surgical treatment of KMS classically includes steroids therapy, interferon alpha2, vincristine, ticlopidine/aspirin association, radiation and embolization [3, 7, 10, 11]. Combined use of steroids and propranolol can be considered under careful monitoring of the side-effects with the aim of improving coagulopathy and thrombocytopenia as well as reducing tumor size [12] with a variable response [13]. Sirolimus (also known as rapamycin) is an inhibitor of the mammalian target of rapamycin (mTOR) and has been shown to be a safe and effective treatment option in some children [14, 15] and may be used as a first-line therapy [16]. Antiangiogenic treatment (such as anti-VEGFR drugs) could play a role in these new treatment regimens but more trials are needed before it can be recommended [17]. When possible, tumor resection provides complete cure. Platelet transfusions should be avoided, except in life-threatening situations. Indeed, exacerbations of bleeding and swelling of the tumors have been reported presumably due to intra-tumoral trapping and activation of platelets [18] (as seen in our patient with rapid deterioration after daily transfusions). Although first described as benign, LCA may have malignant potential and has been shown to be rarely associated with visceral malignancies [19, 20], thus requiring long-term follow-up.

In our patient, the diagnosis of littoral cell angioma of the spleen associated with intrasplenic KMS was established following splenectomy and histopathological analysis. KMS should be suspected in patients presenting with splenomegaly and features of thrombotic microangiopathy. This rare case illustrates the diagnostic difficulties met in dealing with such internal tumors, with possible atypical biological parameters and nonspecific imaging characteristics at presentation.


Littoral cell angioma is a rare and benign vascular tumor which can be discovered incidentally or in a context of various signs and symptoms such as abdominal pain, splenomegaly and hypersplenism. This condition may be complicated by a life-threatening Kasabach-Merritt syndrome due to high risk of hemorrhage. Vascular lesions of the spleen (such as LCA, KHE and TA) should be suspected in patients presenting with splenomegaly and features of thrombotic microangiopathy. Long-term follow-up is necessary in patients diagnosed with LCA due to increased risk of developing malignant diseases.

DOI: 10.22551/2017.17.0404.10112

Conflict of interest

The authors have no conflict of interest to declare.

Patient consent

Written informed consent was obtained from the patient's legal guardians for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


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Marie-Amelyne Le Rouzic (1), Julie Valduga (1), Aurelie Phulpin-Weibel (1), Ludovic Mansuy (1), Audrey Contet (1), Fanny Fouyssac (1), Imane Athmani (1), Marie-Agnes Galloy (2), Michel Wassef (3), Pascal Chastagner *, (1)

(1) Department of Pediatric Hematology and Oncology, Children's University Hospital, Nancy, France, (2) Department of Pediatric Radiology, Children's University Hospital, Nancy, France, (3) Department of Pathological Anatomy, Lariboisiere Hospital, Paris

Received: October 2017; Accepted after review: December 2017; Published: December 2017.

* Corresponding author: Prof. Pascal Chastagner, Department of Pediatric Hematology and Oncology, Children's University Hospital, 11 Allee du Morvan, 54511 Vandoeuvre, France.


Caption: Fig. 1. Coronal and sagittal thoraco-abdominal CT scan showing huge heterogeneous spleen extending to the pelvis, along with increased pancreas and posterior mediastinal masses
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Author:Le Rouzic, Marie-Amelyne; Valduga, Julie; Phulpin-Weibel, Aurelie; Mansuy, Ludovic; Contet, Audrey;
Publication:Archive of Clinical Cases
Date:Dec 1, 2017
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