Microcystic Lymphatic Malformation Research Articles

Parotid Gland Microcystic Lymphatic Malformation Producing Obstructive Symptoms

Background: Salivary gland obstruction can present as unilateral, episodic facial swelling. Vascular malformations as a cause of parotid duct obstruction with associated unilateral cheek swelling and pain are rare. Case description: We describe the case of a 16-year-old female with a protracted 2-year history of unilateral facial swelling and pain that was misdiagnosed as recurrent parotitis on computed tomography and sialoendoscopy. Eventually, the 16-year-old female was diagnosed by magnetic resonance imaging to have a microcystic lymphatic malformation of the parotid duct as the cause of her cheek swelling and pain. Afterwards, the patient was referred to undergo interstitial bleomycin sclerotherapy. Conclusions: This case demonstrates a unique microcystic lymphatic malformation producing obstructive symptoms as well as the utility of magnetic resonance imaging for the diagnosis of a patient presenting with recurrent unilateral facial pain and swelling.

Treatment of Microcystic Lymphatic Malformation with Oral Sildenafil Suspension in Paediatric Age Group

Treatment of Microcystic Lymphatic Malformation with Oral Sildenafil Suspension in Paediatric Age Group

Pelvic Microcystic Lymphatic Malformation.

Pelvic Microcystic Lymphatic Malformation.

Lymphatic disorders caused by mosaic, activating KRAS variants respond to MEK inhibition.

Central conducting lymphatic anomaly (CCLA) due to congenital maldevelopment of the lymphatics can result in debilitating and life-threatening disease with limited treatment options. We identified 4 individuals with CCLA, lymphedema, and microcystic lymphatic malformation due to pathogenic, mosaic variants in KRAS. To determine the functional impact of these variants and identify a targeted therapy for these individuals, we used primary human dermal lymphatic endothelial cells (HDLECs) and zebrafish larvae to model the lymphatic dysplasia. Expression of the p.Gly12Asp and p.Gly13Asp variants in HDLECs in a 2‑dimensional (2D) model and 3D organoid model led to increased ERK phosphorylation, demonstrating these variants activate the RAS/MAPK pathway. Expression of activating KRAS variants in the venous and lymphatic endothelium in zebrafish resulted in lymphatic dysplasia and edema similar to the individuals in the study. Treatment with MEK inhibition significantly reduced the phenotypes in both the organoid and the zebrafish model systems. In conclusion, we present the molecular characterization of the observed lymphatic anomalies due to pathogenic, somatic, activating KRAS variants in humans. Our preclinical studies suggest that MEK inhibition should be studied in future clinical trials for CCLA due to activating KRAS pathogenic variants.

Endoscopic Resection for Vascular Anomalies in Children: A New Standard.

To report an innovative endoscopic surgery for subcutaneous vascular malformations and intramuscular fibro-adipose vascular anomaly (FAVA) at our center. Historically, open surgical resection has been the treatment of choice. Recent advances in minimally invasive surgery have led to the successful application of endoscopic resection techniques for the surgical management of diseases of soft tissue. Patients who underwent endoscopic resection of vascular anomalies were included in this retrospective review. Data were extracted from our Vascular Anomalies Center database between September 2019 and October 2022, including sex, age, symptoms, diagnosis, sites of surgery, previous treatment, surgery, and follow-up. There were 13 females and 15 males in the current study, with ages ranging from 1 to 17 years. The diagnoses included microcystic lymphatic malformation (LM) (n = 8), Klippel-Trénaunay syndrome (n = 7), venous malformation (n = 6), FAVA (n = 6), and mixed cystic LM (n = 1). Surgical sites included the lower extremity (n = 24), abdominal wall (n = 2), upper extremity (n = 1), and thoracic wall (n = 1). Five patients had an intramuscular lesion (FAVA). The endoscopic technique used 2 or 3 small ports in a gas inflation manner. Surgery included thrombectomy, radical resection, and debulking of vascular anomalies. Postoperative sclerotherapy with bleomycin was performed through a drainage tube in 6 patients with microcystic LM. Technical success was obtained in 27 patients. The conversion to open surgery was performed in one patient owing to the deep location of the lesion. No wound-related complication was observed. Endoscopic surgery is a minimally invasive, effective, and safe treatment for subcutaneous vascular malformations and intramuscular FAVA. This approach can set a new standard that minimizes wound complications and reduces recovery time in patients undergoing resection for benign soft-tissue lesions.

A 5 YEAR-OLD BOY WITH ATYPICAL UPPER LIP SWELLING

<h3>Introduction</h3> Lip swelling is a common chief complaint in the allergy clinic, but not all swelling is angioedema. Clinicians should keep their differential diagnoses broad when evaluating these patients. This is a case of lymphatic malformation (LM) in a boy with atypical upper lip swelling. <h3>Case Description</h3> A 5-year-old boy with a past medical history of asthma, tree nut allergy, allergic rhinitis, and atopic dermatitis presented for evaluation of persistent upper lip and maxillary gingival swelling. His lip swelling started suddenly and persisted for two years. The family reported intermittent "white fluid" drainage from the affected gingiva. Physical examination showed diffuse upper lip swelling and maxillary gingival swelling. Given his clinical history, his family and pediatrician attributed this swelling to an allergic reaction. He reported no improvement with daily antihistamines, but he did experience transient improvement with oral steroids. Contrast enhanced facial MRI was nonspecific, demonstrating a poorly defined area of mucosal thickening involving the upper lip and anterior maxillary alveolar ridge. He was evaluated by pediatric ENT who referred him to pediatric neurointerventional radiology for suspicion of LM. An ultrasound demonstrated a microcystic LM, notable for tiny anechoic areas without internal flow in the superior lip. The parents are considering definitive diagnosis with a biopsy and treatment options such as sclerotherapy. <h3>Conclusion</h3> LMs can be misdiagnosed as angioedema and should be considered in the differential diagnoses in patients with atypical lip swelling. Contrast enhanced MRI and ultrasound with color Doppler imaging are the recommended imaging modalities for evaluation.

Effect of Injection Bleomycin on Lymphangioma Circumscriptum with Keloid Formation and Secondary Infection

Lymphangioma circumscriptum is a microcystic lymphatic malformation localized to an area of the skin, subcutaneous tissue, and muscle which presents with vesiculo-papules or warty lesions, resembling a “frog spawn.” Keloids develop due to the proliferation of dermal tissue following skin injury. We present a case of lymphangioma circumscriptum with secondary infection and keloid formation treated with intralesional bleomycin.

SUCCESSFUL NON-OPERATIVE TREATMENT IN MICROCYSTIC LYMPHATIC MALFORMATION OF THE TONGUE: A CASE REPORT

Background: Microcystic lymphatic malformation (MLM) is an abnormal congenital growth of lymphatic vessels. It may occur in any part of the human body, with 75 % cases found in the head and neck, including in oral cavity. This case report aimed to describe a case of MLM in a child who was successfully treated non-operatively with antibiotics and corticosteroid. Case Report: A 4-year-old child came to Oral Medicine Clinic of Dr. Hasan Sadikin General Hospital, Bandung, with a chief complaint lesions of the tongue since a year ago, accompanied by bleeding in the affected areas but not pain. Patient gave history of recurrent episodes of the symptoms since 7 months old. Result : Ultrasonography was performed and diagnosis of microcystic lymphatic malformation was established. Systemic oral corticosteroid, antibiotics, and multivitamins were given and the lesions showed significant improvement after 2-weeks treatment. Conclusion: Therapy of MLM with antibiotics and systemic oral corticosteroid significantly improved patient’s condition, and ultrasonography may be used as a diagnostic modality in MLM diagnosis.

Liposuction-Like Sclerotherapy Technique for Microcystic Lymphatic Malformation

BackgroundThe treatment for microcystic lymphatic malformation (LM) remains challenging. We describe the liposuction-like sclerotherapy technique, a new treatment for extensive microcystic LM.MethodsLM data was retrospectively reviewed. This study included patients with a microcystic LM component treated by liposuction-like technique with bleomycin sclerotherapy.ResultsBetween June 2016 and October 2019, 39 consecutive patients (male/female ratio: 21:18; mean age, 33.6 months; range: 5 months to 15 years) with microcystic LM were treated by liposuction-like sclerotherapy (LS-LS) technique. Fifty-six sessions of LS-LS were performed (mean of 1.44 sessions per patient; range: one to four sessions). Follow-up ranged 6-30 months (mean of 21 months). We observed no major complications. Transient minor complications included: postoperative noninfectious fever, vomiting, temporary skin edema, pigmentation, mild local depressions, and/or irregularities, and a small hyperpigmented scar at the incision. No postoperative infection, skin ulcer, or necrosis occurred. The patients’ symptoms were successfully resolved or stable. A sub-complete response and partial response were observed for 26 (76%) and 13 patients (33%), respectively.ConclusionThe LS-LS technique for microcystic LMs is safe, feasible, and effective. This technique is an effective intervention with which it is possible to manage and potentially cure microcystic LM clinically.

Expression of Angiotensin II Receptor 2 in Microcystic Lymphatic Malformation

Objectives: To investigate the presence of components of the renin-angiotensin system (RAS) on the embryonic stem cell (ESC)–like population in microcystic lymphatic malformation (mLM). Methods: mLM tissue samples from 18 patients underwent immunohistochemical staining for RAS components including angiotensinogen, renin, prorenin receptor (PRR), angiotensin-converting enzyme (ACE), ACE2, and angiotensin II receptor 2 (AT2R). Snap-frozen mLM tissues from 6 of the patients were used to confirm protein expression by western blotting for angiotensinogen, PRR, ACE, ACE2, and AT2R. Reverse transcription quantitative polymerase chain reaction was used to detect transcript expression of angiotensinogen, renin, PRR, ACE, ACE2, AT1R, and AT2R in 5 of the mLM tissue samples. Results: Immunohistochemical staining demonstrated expression of AT2R in all, and PRR in 1, while angiotensinogen, renin, ACE, and ACE2 were not observed in any of the 18 mLM samples. Western blotting showed expression of angiotensinogen, PRR, and ACE, but not ACE2 or AT2R in all 6 mLM tissue samples. Reverse transcription quantitative polymerase chain reaction demonstrated transcript expression of angiotensinogen, PRR, ACE, and ACE2 in all, AT1R in 4, AT2R in 2, and renin in 1 of the 5 mLM tissue samples. Immunofluorescence dual-staining in 2 mLM tissue samples demonstrated expression of AT2R on the OCT4+ cells. Conclusion: This study shows expression of angiotensinogen, PRR, ACE. ACE2, AT1R, and AT2R transcripts and AT2R protein, in mLM tissue samples, with AT2R localizing to the OCT4+ ESC-like population. This suggests the ESC-like population may be a novel therapeutic target by modulation of the RAS.

Vulval Mixed Macrocystic and Microcystic Lymphatic Malformation in an Adolescent Girl Showing Cyclical Changes with Menstrual Cycles.

Vulval Mixed Macrocystic and Microcystic Lymphatic Malformation in an Adolescent Girl Showing Cyclical Changes with Menstrual Cycles.

Expression of Cathepsins B, D, and G in Microcystic Lymphatic Malformation.

Background: This study investigated the expression and localization of cathepsins B, D, and G in relationship to the embryonic stem cell (ESC)-like population we have previously identified in microcystic lymphatic malformation (mLM). Methods and Results: Immunohistochemical staining demonstrated expression of cathepsins B, D, and G in cervicofacial mLM tissue samples from 11 patients. Immunofluorescence staining of two representative mLM samples showed localization of cathepsins B and D to the OCT4+ and the c-MYC+ cells on the endothelium of lesional vessels and the stroma, while cathepsin G was localized to the OCT4+/tryptase+ cells within the stroma. Transcript expression of cathepsins B, D, and G was confirmed using reverse transcription quantitative polymerase chain reaction (RT-qPCR; n = 5). Western blotting (n = 3) performed on the mLM tissue samples revealed protein expression of cathepsins B and D, which were demonstrated to be enzymatically active using enzymatic activity assays. Conclusion: This study demonstrated expression of cathepsins B and D by the ESC-like cells on the endothelium of lesional vessels and the stroma, while cathepsin G was localized to the OCT4+ phenotypic mast cells within the stroma of mLM.

Diffuse mesenteric microcystic lymphatic malformation in a 12-year-old girl

Abstract Mesenteric lymphatic malformation (MLM) is a rare disease. Most cases of symptomatic MLMs present with abdominal pain and distension and may have localized abdominal masses. The standard treatment is complete resection. However, in diffuse-type MLMs, complete resection has a high risk of complications, such as short bowel syndrome. Alternative treatment options for macrocystic MLM include sclerotherapy and fenestration. Conventionally, localized macrocystic MLMs are easily resectable or only require alternative treatments. Herein, we report a rare case of diffuse microcystic MLM with volvulus, which had a high risk of developing complications following complete resection. Conservative management or alternative treatment options are recommended for such high-risk cases.

Staged surgical management of an extensive penoscrotal and perineal microcystic lymphatic malformation in an adolescent male

Abstract This case reports details a successful approach to the surgical management of an extensive penoscrotal microcystic lymphatic malformation in an adolescent male. The patient had staged total excision of skin and subcutaneous tissue and reconstruction was achieved with a combination of thick and thin split thickness grafts.

Microcystic lymphatic malformation localized within the diaphragm

Abstract Localization of a microcystic lymphatic malformation within the diaphragm is an extremely rare vascular anomaly of the lymphatic system. We report the case of a 3-year-old boy who had a localized intrathoracic mass that was detected after birth. As the feeding artery to the mass was detected on computed tomographic images before surgery, we suspected the mass to be an extralobar pulmonary sequestration. Thoracoscopic findings indicated that the mass was localized within the left diaphragm and had an indiscrete margin with the diaphragm. An excisional biopsy was performed to avoid resection of the diaphragm itself. The mass was diagnosed as a microcystic lymphatic malformation based on pathological findings. When an accurate diagnosis of the mass within the diaphragm cannot be made preoperatively, a biopsy under thoracoscopic surgery may be an effective method to diagnose microcystic lymphatic malformations.

Expression of Embryonic Stem Cell Markers in Microcystic Lymphatic Malformation.

Aim: To investigate the expression of embryonic stem cell (ESC) markers in microcystic lymphatic malformation (mLM). Methods and Results: Cervicofacial mLM tissue samples from nine patients underwent 3,3'-diaminobenzidine (DAB) immunohistochemical (IHC) staining for ESC markers octamer-binding protein 4 (OCT4), homeobox protein NANOG, sex determining region Y-box 2 (SOX2), Krupple-like factor (KLF4), and proto-oncogene c-MYC. Transcriptional activation of these ESC markers was investigated using real-time polymerase chain reaction (RT-qPCR) and colorimetric in situ hybridization (CISH) on four and five of these mLM tissue samples, respectively. Immunofluorescence (IF) IHC staining was performed on three of these mLM tissue samples to investigate localization of these ESC markers. DAB and IF IHC staining demonstrated the expression of OCT4, SOX2, NANOG, KLF4, and c-MYC on the endothelium of lesional vessels with abundant expression of c-MYC and SOX2, which was also present on the cells within the stroma, in all nine mLM tissue samples. RT-qPCR and CISH confirmed transcriptional activation of all these ESC markers investigated. Conclusions: These findings suggest the presence of a primitive population on the endothelium of lesional vessels and the surrounding stroma in mLM. The abundant expression of the progenitor-associated markers SOX2 and c-MYC suggests that the majority are of progenitor phenotype with a small number of ESC-like cells.

Late-onset microcystic lymphatic malformation: a case report

Late-onset microcystic lymphatic malformation: a case report

An unusual case of microcystic lymphatic malformation discovered after wisdom teeth extraction

Lymphangioma is a benign vascular malformation of the lymphatic vessels. In 90% of cases it is diagnosed during the first 2 years of life. As seen in 75% of cases, the head and neck region are the preferred location. This report represents an original case of lymphatic malformation (LM) in a 15-year-old patient discovered during an unscheduled postoperative symptomatology of third molar germectomies. Two biopsies, one non-contributory, were required to make the diagnosis. Lymphangiomas are classified as LM. They are usually non-regressive. Their etiology remains controversial.

A case of microcystic lymphatic malformation successfully treated with topical sirolimus

Microcystic lymphatic malformation (MLM), also known as "lymphangioma circumscriptum," is a lymphatic malformation which may involve the skin and subcutaneous tissues. Progressive growth of lesions may cause pressure to the surrounding organs. Lesions frequently reoccur after treatment with surgery, sclerotherapy, radiotherapy, and laser therapy. In the last decades, oral sirolimus has been successfully used in lymphatic malformations. Since systemic treatment with sirolimus is associated with various side effects, topical form of the drug has been used with satisfying results, especially for the angiofibromas. Promisingly, few case studies indicate topical sirolimus as a potential treatment for the lymphatic malformations. Here, we report an 8-year-old girl with MLM on left trunk whose lesions recurred after the surgery that has been performed at 1 year of age. We administered twice daily topical sirolimus at 0.75 mg/ml concentration. After 2 weeks, a local irritation occurred and the dose was decreased to once daily. The treatment was stopped at the end of 3 months as the lesions were almost cleared and the patient did not want to continue to therapy. There were no new lesions after 8 months of follow up.

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.