This case report describes a novel presentation of littoral cell angioma (LCA) and lymphatic malformations involving the omentum and mesentery. To our knowledge, these 2 entities have not been reported in the same patient. A 1-month term infant male presented with chylous ascites. During his workup, imaging detected splenic nodules. Biopsies revealed that the nodules were LCA and the chylous ascites was secondary to microscopic mesenteric and omental lymphatic malformations. Evaluation for a secondary malignancy, an underlying immunologic defect, and genetic causes were unrevealing. The presence of LCA and lymphatic malformations in the same patient suggests a genetic link between these 2 rare vascular disorders and may help elucidate the etiopathogenesis of these 2 poorly understood anomalies.
- CT —
- computed tomography
- LCA —
- littoral cell angioma
- TPN —
- total parenteral nutrition
A 26-day term male with uncomplicated birth history presented to the emergency department with progressive abdominal distension since birth. Before admission, he had increasing nonbloody, nonbilious emesis with the distension but was otherwise asymptomatic. Family history was significant for his mother, because she had 3 previous miscarriages. Examination was remarkable for a soft, distended abdomen with a fluid wave. Initial workup included an abdominal ultrasound (Fig 1) that found significant ascites and a normal-sized spleen with multiple nodular masses; the liver and kidneys were normal in size and appearance. Fluid from diagnostic paracentesis revealed chylous ascites (peritoneal fluid triglyceride 701 mg/dL, serum triglyceride 192 mg/dL). Laboratory analysis was significant for thrombocytopenia, nadir of 49 K/μL that resolved the next day without intervention, and normal urine homovanillic acid and vanillylmandelic acid levels. To better characterize the splenic nodules, chest, abdomen, and pelvis computed tomography (CT) scans (Fig 2) and an abdominopelvic MRI scan (Fig 3) were obtained. These showed multiple 1 to 3.5 cm splenic nodules that were hypoechoic on CT and had decreased T1 and increased T2 signal intensities on MRI. The patient was started on Enfaport with minimal ascites re-accumulation. Given clinical improvement, he was discharged from the hospital with the plan to complete workup as an outpatient. However, he presented 3 days later with increasing abdominal distension and cool lower extremities. Complete blood count on readmission was normal. A therapeutic paracentesis was performed that, again, revealed chylous ascites.
Further workup of this patient included plasma and urine amino acids, lactate dehydrogenase, ammonia, lysosomal storage disease panel, and collagen and calcium binding EGF domains 1 gene testing (evaluating for Hennekam lymphangiectasia-lymphedema syndrome), which were all normal. A nonfasting lipid profile and comprehensive metabolic panel were obtained, notable for mildly elevated serum triglyceride (162 mg/dL) and low total protein but normal albumin. Four paracenteses were performed because of progressive distension, persistent emesis, and patient discomfort. He developed leukopenia with hypogammaglobulinemia and lymphopenia after paracenteses. Bone marrow, splenic wedge, liver, omental, and mesenteric biopsies were also obtained. The bone marrow biopsy was unremarkable. Splenic biopsy was consistent with littoral cell angioma (LCA)1,2 with normal splenic tissue compressed by the angioma.
Histologically, the LCA lesion showed anastomosing vascular channels lined by tall-to-flat endothelial cells with vesicular nuclei (Fig 4). Immunohistochemical staining of lesional cells revealed strong positivity for ERG (a marker for vascular endothelial tumors) scattered positivity for CD68 and CD21, and no reactivity for CD8, CD34, and WT1 (Fig 5). Omental and mesenteric biopsies were consistent with lymphatic malformations, because they both showed a proliferation of thin walled vascular spaces with variable amounts of smooth muscle that were associated with scattered lymphoid aggregates (Fig 6). The ectatic lymphatic channels showed strong to faint immunoreactivity with D2-40 (Fig 7).3
For the patient’s treatment, his diet was changed to Enfaport and fat-free breast milk to prevent ascites re-accumulation. However, the ascites re-accumulated despite 4 days of daily paracenteses. He was then made to have nothing per mouth and started on total parenteral nutrition (TPN) with improvement in his distension. He was discharged on TPN and sips of Pedialyte with close follow-up in gastroenterology clinic. After 6 1/2 weeks, he was titrated up on fat-free then full-fat breast milk diet while weaning off TPN. At 8 weeks, he was taking full-fat breast milk without ascites re-accumulation and adequate weight gain.
Given normal splenic tissue and no evidence of aggressive malignancy, it was decided to closely monitor his LCA. He has been asymptomatic for 7 months with no recurrence of thrombocytopenia or ascites and no change to size of splenic or splenic nodules on repeat ultrasound.
To our knowledge, this is the first report of LCA in a neonate and the first case of concomitant lymphatic malformations and LCA. The presence of 2 rare vascular disorders in the same patient suggests the presence of an underlying genetic link and may shed new light on the pathogenesis of these 2 diseases.
LCA is a benign vascular splenic neoplasm that arises from littoral cells (normal splenic cells that line venous sinusoids). LCA is rarely diagnosed in children (9 of ∼224 cases reported to date).1,4–8 Before this report, the youngest reported patient diagnosed with LCA was 1 year of age.4 Approximately 30% of cases are diagnosed incidentally. The remaining patients present with nonspecific signs or symptoms such as fever, abdominal pain, splenomegaly, or thrombocytopenia.9 Although LCA is considered a benign lesion, there are other littoral cell tumors named littoral cell hemangioendothelioma (also known as low-grade littoral cell angiosarcoma)10 and littoral cell angiosarcoma that are malignant, more aggressive, and have been shown to metastasize. These are differentiated from LCA based on more malignant characteristics on histopathology, namely poorly circumscribed areas with solid tumor nests instead of cystic spaces on macroscopic appearance, and, microscopically, showing nuclear atypia, numerous mitoses, spindle cells, and necrotic areas. It is yet unknown if littoral cell hemangioendothelioma and littoral cell angiosarcoma are progressions from LCA or separate entities. Although the presence of massive splenomegaly or suspicious liver nodules have been associated with a malignant littoral cell tumor, the only definitive method of differentiating LCA from its malignant counterparts is with histopathology. Thus, tissue diagnosis is imperative in any suspected LCA case to exclude a more aggressive malignancy.9
Most LCA cases are treated with splenectomy. However, there are 3 reported cases of solitary splenic nodules of LCA that were treated with tumor resection alone.7,11,12 Unfortunately, long-term follow-up of these patients is unknown, considering 1 patient was managed for an indefinite time period, 1 was managed for only 3 months (both were without evidence of disease recurrence on imaging),7,11 and the third report did not discuss follow-up.12 In our case, isolated tumor resection was impossible because of the extent of disease. Thus, the patient’s parents and clinical team elected to monitor his tumor with close surveillance. At 7 months, there is no sign of tumor progression.
LCA portends a good prognosis. Two percent of patients had unfavorable courses after partial or complete splenectomy. These included persistent anemia and thrombocytopenia, death attributable to sepsis 3 months postsplenectomy, and 1 death secondary to non-LCA brain and liver metastases. However, long-term surveillance of all patients with LCA is recommended. This is to monitor for malignant transformation, which is speculated to occur, and development of a new malignancy because there is a high correlation between LCA and secondary malignancies.9
Approximately 27% of patients who are diagnosed with LCA have a coexistent visceral malignancy, and 17% have immune dysregulation in the form of chronic immunosuppression or an autoimmune condition (such as Crohn disease, Epstein syndrome, Castleman Disease, Evans Syndrome, Gaucher Disease, and Wiskott-Aldrich Syndrome).6,9,13,14 Thus, there is speculation that an underlying immune dysregulation contributes to the development of LCA. However, the rarity of LCA has limited research to test this hypothesis.9 Fortunately for our patient, a thorough workup for another malignancy was unrevealing. In addition, it is unlikely a primary immune deficiency contributed to his LCA. His leukopenia and hypogammaglobulinemia occurred after LCA was identified and was attributed to removal of lymph fluid by serial paracenteses. This hypothesis is supported by primary immunodeficiency panels showing normal lymphocyte percentages and a low absolute lymphocyte count that improved after resolution of his chylous ascites. He also had a serum lymphocyte antigen and mitogen proliferation panel that were unremarkable. The presence of multiple splenic lesions identified in infancy in our patient suggests that some forms of LCA are a congenital, not acquired, anomaly. This hypothesis is supported by a report of siblings diagnosed with LCA.15
Lymphatic malformations, benign anomalies of lymph vascular channels, are uncommon in the abdomen. They represent only 5% to 10% of all lymphatic malformations and are usually identified in adults.16,17 In children, lymphatic malformations are usually in the head and neck, although there is 1 report of abdominal cystic lymphangioma in a neonate.16 The malformations are theorized to result from abnormal development or sequestration of lymphatic channels. Some single gene disorders (eg, Hennekam lymphangiectasia-lymphedema syndrome) and chromosomal anomalies (eg, Turner syndrome) reveal lymphatic malformations as a prominent feature. The authors of 1 report link diffuse lymphangiomatosis in a newborn to a mosaic deletion on chromosome 15,18 suggesting that a chromosomal abnormality with a contiguous gene effect should be considered to explain the concurrent diagnoses in our patient.
The presence of 2 rare vascular entities, LCA and lymphatic malformations, in our patient suggests they are related. The lymphatic malformations are unlikely a direct result of LCA because the splenic and mesenteric lymphatics are not in direct communication; they both independently drain into celiac lymph nodes.19 Because the ascites fluid had elevated triglyceride levels, its source was the mesenteric lymphatics, not the splenic lymphatic system.
Because lymphatic proliferations and LCA are vascular malformations, it is possible our patient has a genetic mutation that led to abnormal proliferation of the splenic littoral cells and mesenteric lymphatic vessels. He did not have characteristic physical examination findings to suggest the presence of a known genetic syndrome. Although there are some researchers who are evaluating the etiopathogenesis of lymphatic malformations,16–19 little is known about the pathophysiology of LCA.9 This hinders our ability to further speculate on the relation between our patient’s 2 anomalies.
This case study is the first known report of concomitant LCA and lymphatic malformations and the first known case of LCA in a neonate. Although a link between our patient’s diagnoses has not been identified, the presence of 2 rare vascular anomalies occurring in an infant is suspicious for an underlying congenital disorder. We hope this novel report will lead to an improved understanding of the pathogenesis of LCA and lymphatic malformations, guiding future research of these poorly understood diseases.
We thank Dr Angelica Putnam for her significant contributions to this patient’s care and this manuscript and Dr John Rampton for his assistance in obtaining and interpreting the radiographic images.
- Accepted October 19, 2017.
- Address correspondence to Lindsey Gakenheimer-Smith, MD, Department of Pediatrics, University of Utah, 81 N Mario Capecchi Dr, Salt Lake City, UT 84113. E-mail:
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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