Lymphatic malformations are a rare but costly disorder with a recent trend towards higher inpatient costs and resource utilization [6]. A recent study examining characteristics of inpatients with LM showed more admission in children under age 3 [12]. Our series of patients with ILM demonstrated a peak incidence curve as seen in Figure 1. This is consistent with hormonal sensitivity of these lesions as patients demonstrate hormonally driven growth in the first two years of life as well as hormone surges around the onset of puberty.

MRI was the most commonly used form of imaging for the diagnosis of ILM and has been shown to be sensitive and specific for the diagnosis of low-flow ILM [1,13]. With recent MRI advances, fetal diagnosis is possible [14]. Ultrasound provides an ideal modality for interval surveillance though MRI evaluates the anatomic extent and involvement of the LM respective to other structures (15). Specifically, MRI helps evaluate subtypes of lymphatic malformations, including macrocystic, microcystic, and mixed macro-microcystic (Figure 2).

This differentiation is necessary to direct approach to sclerotherapy. Macrocystic lesions may be approached directly, with a pigtail drain placed within the cavity for sclerosant access, while microcystic lesions are typically approached individually with small angiocatheters. Figure 3 describes a proposed pathway for management of abdominal lymphatic malformations.

Two of our patients had melena as a symptom on presentation. Venous enlargement adjacent to lymphatic malformations are frequent, though venous malformations associated with lymphatic malformations is rare. Thus, the bleeding may be from an associated engorged vein and not necessarily the malformation itself. Surgical resection may allow for decompression of the venous collaterals.

Most patients presented with mild to moderate symptoms, generally pain, mass, or distension [2]. 95.8% of our patients needed either sclerotherapy or surgery, with interventional treatment rates ranging from 60-100% similar to other reports [16]. Sclerotherapy was highly effective with only 4 of 16 sclerotherapy patients needing subsequent treatment with laparoscopic or open surgery. Sclerotherapy at our institution is typically image guided by ultrasound and fluoroscopy, the lesion aspirated, fluid collections drained, and doxycycline instilled as the sclerosing agent. Sclerotherapy for intraabdominal vascular malformations has been shown to be safe and effective in previous studies with demonstrated success rates of 96.7% and a low rate of complications [2]. Our follow up for most patients ranged from one to 5 years. Success with sclerotherapy on these lesions is characterized by both symptomatic relief and volumetric reduction in size of these lesions and not based on complete radiographic resolution as this is rarely achieved and should not be the goal of therapy [2]. Sclerotherapy is traditionally known to be more helpful in patients with macrocystic lesions, however, Chaudry, et al. demonstrates the utility of bleomycin as a sclerosing agent for the treatment of microcystic or mixed lesions [17]. One patient who developed a recurrent ILM years after treatment with sclerotherapy underscores the importance for long term management in a multi-disciplinary clinic and a high index of suspicion if recurrent symptoms develop.

Sirolimus has demonstrated both safety and efficacy in multiple studies on the use in patients with PROS and other lymphatic malformations [8–11]. This therapeutic benefit is believed to be related to sirolimus’ ability to inhibit lymphatic vessel invasion and regeneration through the mTor pathway [18,19]. Twenty-five percent of patients in our study were treated with sirolimus, which plays an important role in the multi-modal treatment of patients with PROS. It was difficult in this study to delineate with certainty if the patients treated with sirolimus required less interventions, however their treatment was aimed toward improvement in overall symptoms. Length of sirolimus prescription was not recorded. medications that also target the mTOR/PIK3CA pathway are on the horizon. BYL719 (alpelisib) has shown to have promise in both safety and efficacy and shown relatively dramatic improvement in the size of malformations, with recent approval [20].

Childbearing females may also note exacerbations or enlargement of their vascular malformations during pregnancy. One patient successfully brought two pregnancies to term and developed increase pain in her head and neck lymphatic malformation but did not report any significant increase in symptoms relating to her intraabdominal malformation. Female patients should be counseled to avoid taking exogenous estrogen containing medications as these can worsen symptoms from vascular malformations. Counseling becomes especially important as the patients near puberty and late adolescence, as many are lost to follow up.

One patient in our study was presumed to have mixed macro-microcystic ILM on preoperative MRI, however the surgical pathology returned Ewing’s Sarcoma. This underscores the importance of following the patient and considering surgical resection or at least biopsy should the course of the lesion not follow typical patterns. Rapid growth and changing symptoms should raise suspicion for malignancy [21].

Limitations of this study are its retrospective nature as well as the challenge of gathering data from a complex chart review process. Many of our patients are referred from outside facilities including across the country as well as from international centers which may affect our rates of procedures or interventions.

Intra-abdominal vascular malformations have a bimodal distribution pattern of presentation, shortly after birth and at puberty. Half of our patients presented with abdominal signs and symptoms such as abdominal pain, distension, constipation, and nausea which was consistent with presentations reported in existing literature [22]. Many of our patients had other associated vascular anomalies. Patients with PROS, GLA, and those who have other vascular malformations are at risk for the presence of intra-abdominal vascular malformations. There is a population of patients who have isolated intra-abdominal vascular malformations, therefore clinical suspicion and abdominal signs and symptoms should guide the diagnostic work up to rule out ILM. MRI appears to be the most accurate modality for treatment/intervention planning [1,13]. Interventional procedures such as sclerotherapy and medical therapy with sirolimus can be used with excellent efficacy and should be considered first line therapies. Surgery should not be considered as primary therapy unless the patient develops peritonitis or bowel obstruction. Despite the use of sirolimus, most patients will need an intervention at some point during childhood or adolescence for symptoms related to their ILM. Only one patient in our series was treated with sirolimus alone, the rest requiring some form of intervention. Surgical resection is often required when the diagnosis is in question or when more conservative therapies are no longerefficacious and in our experience in a last-line therapy.

Conflict of interest: The authors have no conflicts of interest. No funding received.