4. Discussion
Lymphatic malformations are a rare but costly disorder with a recent
trend towards higher inpatient costs and resource
utilization.5 A recent study examining characteristics
of inpatients with LM showed more admissions in urban centers and in
children under age 3.11 Our series of patients with
ILM demonstrated a bimodal distribution. 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.1,12 With recent MRI advances, fetal
diagnosis is possible.13 Ultrasound provides
convenient growth monitoring though MRI evaluates the anatomic extent
and involvement of the LM respective to other
structures.14 There are three subtypes of lymphatic
malformations: macrocystic, microcystic, and mixed macro-microcystic.
Macrocystic LM’s have cysts >2 cm. Microcystic malformation
often appear as a “cluster of grapes” on MRI (Fig.
2).1,12
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.15Sclerotherapy 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 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.16 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.7–10 This therapeutic benefit is
believed to be related to sirolimus’ ability to inhibit lymphatic vessel
invasion and regeneration through the mTor
pathway.17,18 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 symptoms. New medications that also target the
mTOR/PIK3CA pathway are on the horizon. BYL719 has shown to have promise
in both safety and efficacy and shown relatively dramatic improvement in
the size of malformations.19 It is still in clinical
trials and will hopefully be approved for use in the coming years.
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.20
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. There is also a limitation of
identifying patients with intraabdominal malformations in a
retrospective manner. The ICD-10 codes for vascular malformations are
ambiguous and therefore limited the ability to capture all patients that
may have met inclusion criteria.
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.21 Many
of our patients had other associated vascular anomalies. Patients with
PIK3-CA Related Overgrowth Syndromes, Generalized Lymphatic Anomaly
syndrome, and those who have other vascular malformations are at risk
for 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.1,12 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 procedure. Surgical resection is often required when the
diagnosis is in question or when more conservative therapies are no
longer efficacious.
Conflict of interest:
The authors have no conflicts of interest.
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Legends/Figures
Figure 1. Bimodal distribution of age at diagnosis of intra-abdominal
lymphatic malformations.