Microcystic Lymphatic Malformations Research Articles

Retrospective analysis of classification and treatment of microcystic lymphatic malformations of tongue

Objective: To explore the clinical classification of microcystic lymphatic malformations of tongue and observe the treatment of microcystic lymphatic malformations of tongue by retrospective analysis, in order to provide reference for clinical practice. Methods: From October 2005 to October 2015, the complete data of 220 cases of microcystic lymphatic malformations of tongue (115 males and 105 females) received and treated in Provincial Special Department of Vascular Anomalies, Linyi Tumor Hospital was analyzed retrospectively. The age ranged from 8 months to 52 years old, with a median age of 16 years old. All patients were followed up for 3 years, and according to their clinical manifestations, they were divided into three types: localized type of 23 cases, diffuse type of 161 cases, and megaloglossia type of 36 cases. Injection with pingyangmycin merely was performed on 58 cases, whereas merely surgery on 20 cases, injection with pingyangmycin combined with high frequency electrocoagulation on 55 cases, and surgery combined with injection with pingyangmycin on 87 cases. The therapeutic effect was evaluated according to the grade 4 standard. The χ(2) test was used for statistical analysis of count data. Rank sum test was used for statistical analysis of ranked data. Results: The percentage of surgery merely of localized type was 87.0% (20/23), significantly higher than that of other types of lesions [0% (0/197)] (χ(2)=178.060, P<0.001). The percentage of injection with pingyangmycin of diffuse type was 100% (161/161), significantly higher than that of other types of lesions [66.1% (39/59)] (χ(2)=60.034, P<0.001). The percentage of surgery combined with injection with pingyangmycin of megaloglossia type was 100% (36/36), significantly higher than that of other types of lesions [27.7% (51/184)] (χ(2)=65.800, P<0.001). After follow-ups for 3 to13 years, there were 0 cases of gradeⅠ, 11 cases of grade Ⅱ, 50 cases of grade Ⅲ, and 159 cases of grade Ⅳ. There were statistically significant differences in clinical efficacy among different clinical types (H=158.668, P<0.001). The percentage of level Ⅳ efficacy of localized type, diffuse type and megaloglossia type were 100% (23/23), 82.6% (133/161) and 8.3% (3/36) respectively. Local mucosa ulcer appeared in 45 cases and was cured through oral care and expectant treatment. Fever occurred in 28 cases and returned to normal within 24 h after expectant treatment. The lingual frenum was shortened in 16 cases. There were 12 cases with mild tongue swelling, 6 cases with influence on eating but without influence on breathing, and recovered spontaneously one week later. Conclusions: The choice of different treatment methods of microcystic lymphatic malformations of tongue should be made according their clinical classification. The only surgical resection is recommended for localized protrude lesions. Injection with pingyangmycin in high tension combined with surgical resection or high frequency electrocoagulation is effective for diffuse lesions. Surgical resection combined with injection with pingyangmycin is suitable for the patients with megaloglossia type.

Vascular malformations of the orbit (lymphatic, venous, arteriovenous): Diagnosis, management and results

Vascular malformations are often found inside the orbit. Isolated venous malformations (frequently misnamed as cavernous hemangiomas) are the most frequent among these. However, also lymphatic and arteriovenous malformations can affect the orbit. The complex anatomy of the orbit and the fact that its content easily suffers from compartmental syndrome explain why treating orbital vascular malformations can be challenging and technically demanding.In this study, two institutions have retrospectively collected their cases, consisting in a total of 69 vascular malformations of the orbit. Each type of malformation has been evaluated separately in terms of diagnosis, indications for treatment, techniques and outcomes. Moreover, the authors have analyzed in detail venous malformations, identifying three different types, named orbital venous malformation (OVM) 1, 2 and 3. These behave differently from each other, and a prompt differential diagnosis is mandatory to pose correct indications, minimize risks and improve results.Overall, surgery was the technique of choice for OVM1, microcystic lymphatic malformations (LM) and arteriovenous malformations (AVM). A pure transnasal approach with mass removal and reconstruction of the medial wall with polyethylene sheets was chosen for OVM1 (intra- or extraconal) located in the medial or superomedial compartment.Sclerotherapy had a role in treating macrocystic LM and OVM3.

Gene Expression Differences in Pediatric Lymphatic Malformations: Size Really Matters.

Lymphatic malformations (LMs) are congenital vascular anomalies characterized by dilated and cystic lymphatic channels. They are subdivided into macrocystic and microcystic lesions based upon the predominant size of the cysts involved. However, significant differences in clinical characteristics, treatment outcomes, and prognosis between macrocytic and microcytic disease suggest variation in underlying biologic and genetic influences. Indirect differential expression analysis revealed that 426 genes are significantly different (p < 0.01) in a small sample of LM subtypes. Functional analyses on the differentially expressed gene sets showed that microcystic LM gene expression favors a prooncogenic profile with upregulation of MYC target genes and cell cycle proteins, whereas macrocystic expression demonstrates hypoxic events that lead to angiogenesis and cell proliferation. Therefore, microcystic and macrocystic LMs, although histologically and physiologically similar, may occur under the influence of vastly different biological pathways and mechanisms of action.

CHOICE OF TREATMENT OPTIONS FOR CYSTIC LYMPHSTIC MALFORMATIONS IN THE HEAD AND NECK REGION: TREATMENT EXPERIENCE OF 81 CHILDREN

Background. Surgery has previously been the only treatment for lymphatic malformations (LMs), but in the head and neck region is challenging due to the risk of scarring, nerve damage, recurrence. Sclerotherapy may be a perfect alternative.Objective. The aim of the study is to determine the efficacy and safety of the OK-432 sclerotherapy in the children with craniofacial LMs.Methods. 81 children with head and neck LM between December 2010 and March 2017were involved into the study. The follow-up period was from 6 to 79 months. According to the size of cysts, LMs were classified into macrocystic, microcystic, and mixed. The result of the treatment of LMs was determined by the percentage of reduction in size as excellent (decrease by more than 90%), good (by 50%-89%), satisfactory (by 20%-49%) and none (by less than 20%).Results. The macrocystic LMs diagnosed in 41.97% of patients, microcystic - in 12.35%, and mixed – in 45.68% of children. OK-432 sclerotherapy only was performed for 83.9% of patients and in 12.3% in combination with surgery. The range of sclerotherapy sessions was from 1 to 11. An excellent result in 96.97% of cases was evidenced in the patients with macrocystic LM. Poor result was proved in the patients with microcystic LMs; the most of them (55.56%) had satisfactory result. In the patients with mixed LM, an excellent and good result was evidenced in 83.33%. After 198 sessions of OK-432 sclerotherapy, complications associated with the treatment occurred in 5 (2.52%) cases.Conclusions. OK-432 sclerotherapy is a safe and effective treatment of head and neck LMs in children. Macrocystic LMs proved the best response to OK-432 treatment.

Lymphographic-Like Technique for the Treatment of Microcystic Lymphatic Malformation Components of

The treatment of microcystic lymphatic malformations remains challenging. Our aim was to describe the lymphographic-like technique, a new technique of slow bleomycin infusion for the treatment of microcyst components of <3 mm, performed at our institution. A retrospective analysis of a prospectively collected lymphatic malformation data base was performed. Patients with at least 1 microcystic lymphatic malformation component demonstrated on MR imaging treated by lymphographic-like technique bleomycin infusion were included in the study. Patient interviews and MR imaging were performed to assess subjective and objective (microcystic lymphatic malformation size decrease of >30%) clinical improvement, respectively. Patients were reviewed 3 months after each sclerotherapy session. Lymphographic-like technique safety and efficacy were assessed. Between January 2012 and July 2016, sixteen patients (5 males, 11 females; mean age, 15 years; range, 1-47 years) underwent the bleomycin lymphographic-like technique for microcystic lymphatic malformations. Sixty sclerotherapy sessions were performed, with a mean of 4 sessions per patient (range, 1-8 sessions) and a mean follow-up of 26 months (range, 5-58 months). We observed no major and 3 minor complications: 1 eyelid infection, 1 case of severe postprocedural nausea and vomiting, and 1 case of skin discoloration. One patient was lost to follow-up. Overall MR imaging objective improvement was observed in 5/16 (31%) patients; overall improvement of clinical symptoms was obtained in 93% of treated patients. The bleomycin lymphographic-like technique for microcystic lymphatic malformations is safe and feasible with objective improvement in about one-third of patients. MR signal intensity changes after the lymphographic-like technique are associated with subjective improvement of the patient's symptoms.

Current status, pitfalls and future directions in the diagnosis and therapy of lymphatic malformation.

Lymphatic malformations are complex congenital vascular lesions composed of dilated, abnormal lymphatic channels of varying size that can result in significant esthetic and physical impairment due to relentless growth. Lymphatic malformations comprised of micro-lymphatic channels (microcystic) integrate and infiltrate normal soft tissue, leading to a locally invasive mass. Ultrasonography and magnetic resonance imaging assist in the diagnosis but are unable to detect microvasculature present in microcystic lymphatic malformations. In this review, we examine existing tools and elaborate on alternative diagnostic methods in assessing lymphatic malformations. In particular, photoacoustics, low-toxicity nanoparticles and optical clearing can overcome existing challenges in the examination of lymphatic channels in vivo. In combination with photothermal scanning and flow cytometry, Photoacoustic techniques may provide a versatile tool for lymphatic-related clinical applications, potentially leading to a single diagnostic and therapeutic platform to overcome limitations in current imaging techniques and permit targeted theranostics of microcystic lymphatic malformations.

Lymphatic Malformation Architecture: Implications for Treatment With OK-432.

Herein, the authors aim to describe their findings of novel architectural types of lymphatic malformations (LM) and explain the relationship between these architectures and OK-432 treatment outcomes. A retrospective review was conducted of all patients diagnosed with a LM treated with OK-432 at the Vascular Anomalies Clinic at BC Children's Hospital from December 2002 to January 2012. Twenty-seven patients were included in the study. Sixty percent of lesions were present by 2 years of age with the majority located in the head and neck (59%). The average number of sclerotherapy procedures was 1.4 per patient. Treatment under fluoroscopic guidance revealed 3 new LM architectures: open-cell microcystic, closed-cell microcystic, and lymphatic channel. Response to treatment was complete or good for 14/19 macrocystic and for 1/2 mixed lesions. Open-cell microcystic LMs gave a complete or good response for 3/3, which was attributed to OK-432 freely communicating between cysts. Closed-cell microcystic LM had localized cysts that did not allow OK-432 to freely communicate and were associated with partial responses, 2/2. The lymphatic channel had a partial response. There were 2 minor complications and 1 instance of recurrence. The identification of 3 new LM architectures expands the current accepted classification to include: open-cell microcystic, closed-cell microcystic, and lymphatic channels. The majority of complete responses to OK-432 were found with macrocystic lesions. Open-cell microcystic lesions respond better to OK-432 than closed-cell microcystic lesions, and lymphatic channels may respond to OK-432. These key architecture-response relationships have direct clinical implications for treatment with OK-432 sclerotherapy.

Abstract: Venous Anastomosis to Control Lymph Flow for Lymphatic Malformations

INTRODUCTION: There are several lymphatic diseases that could be treated surgically. Lymphatic venous anastomosis (LVA) was developed to improve lymphedema. On the other hand, in children settings, the majority of lymph diseases are not lymphedema, but lymphangioma or also called lymphatic malformations (LM). This LM especially micro-cystic type LM (mLM) had been challenging to treat because the conventional therapy had been limited efficacy and highly cause complications. To change the strategy, focusing on the lymph flow was the key for this disease. Thus we modified and analysed LVA to improve mLM of children. METHODS: We indicated 14 sequential cases of mLM patients who appeared to our clinic from July 2015 to June 2016, 10 males and 4 females, between 0 to 12 (mean 4) year-old. All cases underwent indocyanine green (ICG) lymphangiography and modified LVA under general anesthesia. Single surgeon (presenting author) performed all surgeries. Depend on the ICG findings of flow pattern we classified anastomosis manners into 2 groups; 1, LVA to decrease the in-flow and 2, increase the out-flow directly from the cysts. RESULTS: In all cases successful assessment with ICG were possible. 11 out of 14 (79%) cases were improved their situations such as size decrease, vesicle disappearance, or prevent following functional loss. Only one case increased vesicles on the surgical site. No complications such as allergy reactions, lymphorrhea, functional loss, surgical site infections or post-operative bleeding were observed. CONCLUSION: We applied ICG and modified LVA for mLM patients and found they are effective. This flow oriented surgical strategy with ICG and LVA for LM was very unique. To our best knowledge, this is the first report that shows the effectiveness of ICG and of LVA on LM. mLM were considered that related to the obstruction of lymph flow proximally. Conventional surgeries were limited, so this surgical strategy could be a break-through for this challenging disease. And also ICG and LVA could spread their indications to a new field. The limitation of this study was the short time follow-up period after the surgery, so more cases should be indicated.

Magnetic resonance imaging of head and neck vascular anomalies

Purpose: The aim of this study was to describe typical MRI features of the head and neck vascular anomalies and the possible diagnostic pitfalls. Patients and methods: Patients with extracranial vascular anomalies of the head and neck, who underwent MRI examinations between January 2013 and January 2016, were included in the study. Precontrast and postcontrast T1-WI,T2-WI, with and without fat saturation were acquired. When indicated, a noncontrast MR angiography was performed. Dynamic postcontrast MRI techniques were available in six children. Results: The study included 33 patients (age ranged from 10 to 20 years, mean: 49 months). MRI confirmed the clinical diagnosis in equivocal cases, and provided proper determination of lesion extension and/or associated intracranial anomalies. The study included 10 cases of vascular tumors (hemangioma), whereas the remaining 23 cases had the diagnosis of vascular malformations (one patient with arteriovenous malformation, one with capillary malformation, seven with venous, nine with macrocystic lymphatic, and five with microcystic lymphatic malformations). Conclusion: Vascular anomalies in the head and neck are mostly diagnosed on clinical basis; however, when the history is uncertain or the diagnosis is equivocal, a well-tailored MR examination can be a single valuable diagnostic tool providing structural and functional information. Keywords: children, head and neck, hemangioma, lymphatic malformation, magnetic resonance angiography, venous malformation

Percutaneous ultrasound-guided sclerotherapy with polidocanol microfoam for lymphatic malformations.

Lymphatic malformations (LMs) are low-flow congenital lesions that consist of cysts of varying size. Sclerotherapy with intralesional bleomycin and OK-432 has been reported to yield dramatically beneficial results for this disorder. However, inflammation-related symptoms are often seen after treatment with these sclerosing agents. On the other hand, polidocanol (POL) is reportedly associated with fewer allergic and inflammatory reactions. Up to now, however, very few reports have documented the use of POL microfoam for treatment of LMs. This study was performed to assess the efficacy and safety of POL microfoam sclerotherapy for LMs. Between 2003 and 2016, cases were identified from a prospectively compiled database on low-flow congenital vascular malformations before undertaking a retrospective electronic chart review. Patients were included if they had LMs that had been treated by POL microfoam sclerotherapy. The location, size, and type of LMs were assessed using ultrasound and magnetic resonance imaging. Twenty-gauge venous catheters were inserted into the lymphatic space under ultrasound visualization. The LMs were then fully aspirated if they were macrocystic in form. Microfoam composed of 3% POL was then injected under ultrasound guidance. Microcystic LMs were treated by direct injection with POL microfoam under ultrasound guidance. The outcome was assessed by clinical examination combined with findings of postsclerotherapy imaging using ultrasound and magnetic resonance imaging. During a 13-year period, 32 patients met the inclusion criteria. These were 11 (34%) male patients and 21 (66%) female patients with a mean age of 18years. The LMs were localized to the head and neck (47%), the trunk (38%), and the extremities (15%). The lesions were subdivided into macrocystic (56%), mixed macrocystic and microcystic (31%), and microcystic (13%) LMs. The average lesion size was 6.6× 4.6× 3.0cm. The mean number of treatment sessions was 2.8 (range, 1-15), with a mean foam volume of 4.6 (range, 1-10) mL. Excellent (47%) and moderate (41%) responses were seen in 88% of the patients. Notably, half of the patients achieved excellent or moderate resolution with a single treatment session. Intralesional hemorrhage occurred in four patients (13%) but resolved spontaneously. Only one patient with mixed macrocystic and microcystic LMs developed post-therapy infection. However, the other patients did not develop any post-therapy inflammation-related symptoms, including fever, pain, and marked swelling. Percutaneous sclerotherapy using POL microfoam appears to be safe and effective for treatment of LMs. Ultrasound-guided POL microfoam sclerotherapy should be considered for such lesions, particularly those that are exclusively macrocystic.

Microcystic Lymphatic Malformation Successfully Treated With Topical Rapamycin.

Microcystic lymphatic malformations (MLM) are low-flow vascular malformations composed of multiple small cysts. MLM usually affect deep-lying structures, which makes their treatment even more difficult and complex. A novel and interesting treatment is rapamycin, a mammalian target of rapamycin inhibitor that when orally administrated has offered favorable results. However, until recently, topical rapamycin had not been used in the treatment of MLM. Case 1 is a girl aged 13 years with extensive MLM affecting the muscles in the right buttock. The patient had received frequent cycles of cryotherapy, but they had failed to control the associated symptoms. In the previous 12 months, the patient had reported greater discomfort, swelling, exudate, and superinfection of the affected region. Because no specific treatment has yet been approved for MLM, and as a step before the use of aggressive systemic or intralesional treatments, it was decided to initiate treatment with 1% rapamycin ointment. After 4 months of treatment, the patient presented a marked improvement, with a significant reduction of associated complications and no major side effects. Case 2 is a boy aged 5 years who underwent surgery for an intergluteal lipoblastoma at 3 weeks of life and developed a MLM on the scar 6 months afterward. The lesion showed slow growth and continuous exudation with frequent episodes of superinfection. Treatments with laser multiplex and intralesional bleomycin were performed unsuccessfully. In the previous 4 months, the patient had been treated with 1% rapamycin ointment with significant improvement and no side effects.

Multistage Sclerotherapy for Extensive Lymphatic Malformations With Airway Involvement in Infant: A Protocol to Prevent Tracheotomy

The management of extensive head and neck lymphatic malformations (LMs) in infants is challenging because of life-threatening upper airway compression. The aim of this study was to present a management protocol and evaluate the clinical outcomes for preventing tracheotomy in these patients. Fifteen infants with extensive head and neck LMs and airway involvement were enrolled from August 2010 through September 2015 at the Qilu Hospital of Shandong University (Jinan, China). According to various key factors associated with airway compression of patients in the perioperative period, different anesthesia types, treatment times, sclerosant concentrations, and sclerotherapy protocols were used. Multistage sclerotherapy was performed with bleomycin A5. All patients were followed at 1, 3, 6, and 12months. More extended follow-up was offered if patients had a residual lesion requiring supplementary sclerotherapy. Reviews on the site and size of the lesion, timesand durations of treatments, therapeutic response, airway complications, and conduction of tracheotomy were performed. LM lesions in the head and neck were located in the floor of the mouth, tongue, and neck. An overall average of 5 treatments was required; a lesion volume decrease of more than 50% was achieved in all patients. For efficacy, morphologic resolution was achieved in 3 of 15 cases (20%), and there was a substantial response in 12 of 15 cases (80%). Eight of 15 patients (53.3%) with microcystic LMs exhibited immediate swelling and had more serious upper airway symptoms than preoperatively, and 2 of 15 patients (13.3%) had feeding difficulty. No upper airway obstruction occurred and no tracheotomy was performed in the patients in this study. Multistage sclerotherapy with bleomycin A5 is a safe and effective treatment for extensive head and neck LMs in infants with airway involvement. A routine perioperative protocol is essential for decreasing airway complications.

РОЛЬ СКЛЕРОЗУВАЛЬНОЇ ТЕРАПІЇ У ЛІКУВАНН І СУДИННИХ МАЛЬФОРМАЦІЙ У ДІТЕЙ

&lt;p&gt;РЕЗЮМЕ. Сучасні підходи до лікування судинних мальформацій (СМ) – це використання хірургічних, консервативних та ендоваскулярних способів, де склерозувальна терапія відіграє важливу роль. Мета дослідження – визначення ефективності і безпечності різних способів склеротерапії периферійних СМ у дітей. У дослідження включено 96 пацієнтів віком від 1 до 17 років з СМ за період січень 2011 р. – березень 2016 р. Період спостереження складав від 3 до 63 місяців. Склерозування венозних мальформацій (ВМ) виконано у 10 дітей за показаннями: больовий синдром (n=7), повторні кровотечі (n=2), психологічний дискомфорт (n=1). Склерозування проводили полідоканолом та тетрадецилсульфатом натрію у вигляді «піни» в концентрації 0,5–1 %. «Пінне» склерозування артеріовенозних мальформацій (АВМ) виконано у 2 дітей після попередньої емболізації. Склерозування кістозних лімфатичних мальформацій (ЛМ) з використанням ОК-432 проведено у 84 пацієнтів, серед яких макрокістозні діагностовано у 34 (40,5 %) дітей, мікрокістозні – у 9 (10,7 %) та змішані ЛМ у 41 (48,8 %). Результатом склерозувальної терапії ВМ було припинення кровотеч (n=2), покращення естетичного вигляду (n=2), зменшення больового синдрому (n=7). Після емболізації та склерозування АВМ кровотеч не було. Результатом склерозування ВМ та АВМ є досягнення косметичного результату та зменшення симптомів, проте не одужання. У 84 пацієнтів з кістозними ЛМ виконано 194 сесії склеротерапії ОК-432. Результат лікування ЛМ оцінювали у відсотках зменшення об’єму ЛМ. Результат лікування макрокістозних ЛМ: відмінний – у 94,1 % пацієнтів, добрий – у 5,8 %; мікрокістозних – відмінний – 0, добрий – у 55,6 %, задовільний – у 33,3 %, відсутній – в 11,1 %; результат склеротерапії змішаних ЛМ: відмінний – у 19,5 %, добрий – у 61,0 %, задовільний – у 17,1 %, відсутній – у 2,4 %. Ускладнення – шкірна алергічна реакція – виникло в 1 пацієнта (1,1 %). Склерозувальна терапія є безпечним і ефективним способом лікування СМ у дітей. Для лікування ВМ і АВМ використовували детергенти у вигляді «піни», для лікування кістозних ЛМ використовували ОК-432. Відмінний і добрий результат склеротерапії кістозних ЛМ отримано у 85,7 % пацієнтів, у 2,4 % результат лікування був незадовільний. Використання склеротерапії у дітей з ВМ і АВМ приводить до досягнення контролю за симптомами, тоді як ЛМ з переважанням макрокістозного компонента можуть бути успішно вилікувані.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;

Treatment of deep-seated facial microcystic lymphatic malformations with intralesional injection of pingyangmycin.

Treatment of microcystic lymphatic malformations (LMs) is still a great challenge to physicians in the field of managing vascular anomalies. Several kinds of treatment have been proposed for microcystic LMs, but the responses to these treatment modalities vary considerably among individuals. The aim of the study was to investigate the safety and efficacy of intralesional injection of pingyangmycin for microcystic LMs located in the deep facial region.Twenty-one consecutive patients with deep-seated facial microcystic LMs were treated with intralesional injection of pingyangmycin between March 2010 and April 2015. The patients received 2 to 8 injections, and the average session was 3.7. The therapeutic efficacy was accessed on the basis of the imaging findings and clinical measurements.Among the 21 patients, the clinical responses were excellent in 7 patients (33.33%), good in 9 patients (42.86%), fair in 3 patients (14.29%), and poor in 2 patients (9.52%). No severe side effects were encountered. Furthermore, therapeutic outcomes were significantly associated with lesion location (P = 0.006) and number of injections (P = 0.003).Our study supports that sclerotherapy with pingyangmycin is safe and effective for the treatment of deep-seated facial microcystic LMs.

Lymphatic malformations in the head and neck area

Lymphatic malformations are congenital malformations of the lymphatic system. They are mainly located in the head and neck area, and grow proportional to the patients' body growth. Depending on the morphology, it can be distinguished between macrocystic, microcystic and mixed lymphatic malformations. Due to their infiltrative growth, microcystic lymphatic malformations are particularly difficult to treat. Therapeutic approaches include conventional surgical resection, laser therapy, sclerotherapy and systemic drug therapies.

Guidelines and parameters: percutaneous sclerotherapy for the treatment of head and neck venous and lymphatic malformations

Vascular anomalies are classified broadly into vascular tumors and vascular malformations.1 Vascular malformations are further subdivided based on the histology of the lesion and whether the lesion is ‘high flow’...

Fractional carbon dioxide laser ablation for the treatment of microcystic lymphatic malformations (lymphangioma circumscriptum) in an adult patient with Klippel-Trenaunay syndrome.

Lymphangioma circumscriptum (LC) is a rare, benign, vascular malformation of dilated superficial lymphatic channels. Treatment is typically undertaken for cosmetic reasons or complications such as fluid drainage, pain, and infection risk that can negatively impact quality of life. Management of LC remains challenging because of high recurrence rates, regardless of the treatment modality chosen. Treatment of LC with the fully-ablative carbon dioxide (CO2 ) laser has been reported widely, however, treatment with the fractionated CO2 laser has been limited to one case in the pediatric population. Our objective was to test the usefulness of the fractionated 10,600-nm CO2 laser in the management of symptomatic LC in an adult. We report a case of a 27-year-old female with Klippel-Trenaunay Syndrome (KTS) who presented with a 5-year history of well-circumscribed lesions on the right lateral and anterior thigh that drained clear lymphatic and serosanguineous fluid, respectively. These lesions caused her significant emotional distress because of extensive drainage. After only one treatment utilizing the fractionated 10,600-nm CO2 laser, the patient had improvement with cessation of fluid drainage, and the lesions are still asymptomatic 6 months since initial treatment. The favorable results observed in our patient suggest that fractionated CO2 laser may be an additional well-tolerated, low downtime option for palliation of symptoms in patients with LC. We recognize that short-term follow-up cannot conclusively demonstrate effectiveness and durability of this treatment and that, given the high risk of recurrence, a longer-term observation is needed before making definite conclusions. Lasers Surg. Med. 47:539-541, 2015. © 2015 Wiley Periodicals, Inc.

Sildenafil for microcystic lymphatic malformations of the head and neck: A prospective study

BackgroundMicrocystic lymphatic malformations (LM) are congenital birth defects that can cause severe functional or esthetic deformity. At this time, several treatment interventions are possible, but there is no ideal therapy. A recently published article noted a coincidental improvement in microcystic LMs with the use of sildenafil for pulmonary hypertension, but conclusive and reproducible data is lacking regarding its efficacy. Methods and resultsA prospective study was conducted to examine the subjective and objective results associated with sildenafil use in the treatment of microcystic LMs. Patients under the age of 18 were enrolled, and after evaluation with pre-intervention magnetic resonance imaging (MRI) studies, each was given a 6-week course of sildenafil. Subjective outcomes were obtained, and postoperative MRIs were used to objectively quantify changes.Five patients between the ages of 4 and 11 were enrolled in the study. All patients had microcystic LMs of the head and neck. All patients had undergone previous treatment interventions utilizing various modalities, and each was now seeking treatment for functional and cosmetic purposes. All patients had minimal to no response from a subjective standpoint. Comparison of pre- and post-treatment MRIs also demonstrated minimal to no response. ConclusionsThe use of sildenafil for the treatment of microcystic lymphatic malformations did not have any appreciable effect on our selected population of pediatric patients who had been resistant to previous therapies. Further studies would be necessary to determine if other cohorts may benefit.

Management of periorbital microcystic lymphatic malformation with blepharoptosis: Surgical treatment combined with intralesional bleomycin injection

ObjectivesPeriorbital microcystic lymphatic malformations (LM) can cause severe symptoms, such as blepharoptosis, amblyopia, chemosis, strabismus, diminished vision, and blindness. The purpose of this study was to evaluate the clinical outcome in periorbital microcystic LM patients with blepharoptosis who underwent surgical treatment combined with intralesional bleomycin injection. Patients and methodsA retrospective study including nine patients diagnosed as periorbital microcystic LM with blepharoptosis was conducted. All of the patients underwent surgical treatment and bleomycin injection from January 2010 to January 2014. The lesion was resected through the lower eyebrow and/or a coronal incision at the first stage, and levator resection was performed at the second stage. Any persistent lesion or its recurrence was managed by intralesional bleomycin injection. ResultsBlepharoptosis and visual obstruction were corrected in all patients. Mean follow-up was 24.6months. Six patients had recurrence during the follow-up, and two patients who had partial eyelid closure after the second stage surgery recovered in three months. Amblyopia, astigmatism, and strabismus were not improved after treatment. All of the patients had excellent aesthetic improvement and corrected blepharoptosis. ConclusionsResection through a lower eyebrow and coronal incision and levator resection performed in two stages can quickly correct the visual impairment caused by periorbital microcystic lymphatic malformation with blepharoptosis. Intralesional bleomycin injection is a promising adjunctive therapy for residual or recurrent lesions after surgery.

AKT hyper-phosphorylation associated with PI3K mutations in lymphatic endothelial cells from a patient with lymphatic malformation.

Lymphatic malformations (LM) are characterized by abnormal formation of lymphatic vessels and tissue overgrowth. The lymphatic vessels present in LM lesions may become blocked and enlarged as lymphatic fluid collects, forming a mass or cyst. Lesions are typically diagnosed during childhood and are often disfiguring and life threatening. Available treatments consist of sclerotherapy, surgical removal and therapies to diminish complications. We isolated lymphatic endothelial cells (LM-LEC) from a surgically removed microcystic LM lesion. LM-LEC and normal human dermal-LEC (HD-LEC) expressed endothelial (CD31, VE-Cadherin) as well as lymphatic endothelial (Podoplanin, PROX1, LYVE1)-specific markers. Targeted gene sequencing analysis in patient-derived LM-LEC revealed the presence of two mutations in class I phosphoinositide 3-kinases (PI3K) genes. One is an inherited, premature stop codon in the PI3K regulatory subunit PIK3R3. The second is a somatic missense mutation in the PI3K catalytic subunit PIK3CA; this mutation has been found in association with overgrowth syndromes and cancer growth. LM-LEC exhibited angiogenic properties: both cellular proliferation and sprouting in collagen were significantly increased compared with HD-LEC. AKT-Thr308 was constitutively hyper-phosphorylated in LM-LEC. Treatment of LM-LEC with PI3-Kinase inhibitors Wortmannin and LY294 decreased cellular proliferation and prevented the phosphorylation of AKT-Thr308 in both HD-LEC and LM-LEC. Treatment with the mTOR inhibitor rapamycin also diminished cellular proliferation, sprouting and AKT phosphorylation, but only in LM-LEC. Our results implicate disrupted PI3K-AKT signaling in LEC isolated from a human lymphatic malformation lesion.