Histopathological changes of lymphatic malformation after bleomycin injection / Alterações histopatológicas da malformação linfática após injeção de bleomicina

ABSTRACT Lymphatic malformation is a rare orbital tumor that used to be treated surgically, with high complication rates, or recently with intralesional bleomycin injection. We report for the first time the histopathological changes of eyelid lymphatic malformation after water-soluble intralesional bleomycin injection in a 20-year-old woman who had unsuccessful orbital surgical debulking during childhood. The changes confirmed the assumption of fibrosis induced by intralesional bleomycin injection. The minimal bleeding during surgical intervention made it much easier than the usual lymphatic malformation bloody procedure, without postoperative recurrences and with favorable aesthetic outcomes.

RESUMO A malformação linfática é um tumor orbital raro que costumava ser tratado cirurgicamente, com alta taxa de complicações. Mais recentemente, passou a ser tratado com uma injeção intralesional de bleomicina. Este é o primeiro relato sobre as alterações histopatológucas da malformação linfática palpebral após uma injeção intralesional de bleomicina hidrossolúvel em uma mulher de 20 anos de idade que sofreu uma cirurgia malsucedida de debulking orbital durante a infância, confirmando a suposição de fibrose induzida por injeções intralesionais de bleomicina. O sangramento mínimo durante a intervenção cirúrgica tornou esta muito mais fácil que o procedimento sangrento habitual, sem recidivas pós-operatórias e com desfechos estéticos favoráveis.

Systematic lymphatic abnormality-related osseous lesions: a study based on CT lymphangiography.

Background: Few studies have focused on the morphology of systematic lymphatic abnormality-related osseous lesions. In this study, we classified systematic lymphatic abnormality-related osseous lesions into four types based on their morphology and density. We also discussed the imaging features of computed tomography lymphangiography (CTL) in this disease. Methods: In this retrospective cohort study, the clinical and imaging data of 39 patients with systematic lymphatic abnormality-related osseous lesions were collected. All patients underwent computed tomography (CT) scans of the chest and abdomen after direct lymphangiography, and two experienced radiologists evaluated the CTL features of intraosseous and extraosseous lymphatic vessel abnormalities. Results: Intraosseous osteolytic changes were observed in all 39 patients. According to the morphological density of the lesions, systematic lymphatic abnormality-related osseous lesions were classified into four types: cyst-like (76.9%), canal-like or honeycomb-like (87.2%), osteoporosis-like (41.0%), and osteosclerosis-like (20.5%), with abnormal deposits of lipiodol seen in the first two types. Enhanced CT of the thorax and abdomen was performed in 11 cases, and enhancement was not seen in any intraosseous lesions. Conclusions: The CTL features of systematic lymphatic abnormality-related osseous lesions have specific characteristics and are often accompanied by extraosseous abnormalities, which can provide a vital imaging basis for the diagnosis and differentiation of this disease.

Kaposiform lymphangiomatosis effectively treated with MEK inhibition.

Kaposiform lymphangiomatosis (KLA) is a rare lymphatic anomaly primarily affecting the mediastinum with high mortality rate. We present a patient with KLA and significant disease burden harboring a somatic point mutation in the Casitas B lineage lymphoma (CBL) gene. She was treated with MEK inhibition with complete resolution of symptoms, near-complete resolution of lymphatic fluid burden, and remodeling of her lymphatic system. While patients with KLA have been reported to harbor mutations in NRAS, here we report for the first time a causative mutation in the CBL gene in a patient with KLA, successfully treated with Ras pathway inhibition.

Late diagnosis of generalized lymphangiomatosis in a woman presenting with respiratory distress.

Generalized lymphangiomatosis (GLA) is a rare lymphatic abnormality, mostly affects children and young individuals and can be a diagnostic challenge because of wide spectrum of clinical manifestations. A 26-year-old woman presented to the emergency department of our institution with respiratory distress and hypoxia. The patient reported similar episodes for the past 10 years without a definite diagnosis. The imaging study demonstrated findings suggestive of GLA with pulmonary, retroperitoneal and osseous involvements which was confirmed on pathological studies from a lung biopsy. A concise review of the clinical, imaging and pathological findings of GLA is provided in this study. A comprehensive history and physical examination, laboratory and pathological work up and imaging is required to make the diagnosis of GLA. The characteristic imaging findings play an essential role to rule out other possible diagnoses and raise the possibility of GLA.

Genetic dissection of tie pathway in mouse lymphatic maturation and valve development.

OBJECTIVE: The genetic program underlying lymphatic development is still incompletely understood. This study aims to dissect the role of receptor tyrosine kinase with immunoglobulin-like and EGF (epidermal growth factor)-like domains 1 (Tie1) and Tie2 in lymphatic formation using genetically modified mouse models. APPROACH AND RESULTS: We generated conditional knockout mouse models targeting Tie1, Tie2, and angiopoietin-2 in this study. Tie1(ΔICD/ΔICD) mice, with its intracellular domain targeted, appeared normal at E10.5 but displayed subcutaneous edema by E13.5. Lymph sac formation occurred in Tie1(ΔICD/ΔICD) mice, but they had defects with the remodeling of primary lymphatic network to form collecting vessels and valvulogenesis. Consistently, induced deletion of Tie1-ICD postnatally using a ubiquitous Cre deleter led to abnormal lymphangiogenesis and valve formation in Tie1-ICD(iUCKO/-) mice. In comparison with the lymphatic phenotype of Tie1 mutants, we found that the diameter of lymphatic capillaries was significantly less in mice deficient of angiopoietin-2, besides the disruption of collecting lymphatic vessel formation as previously reported. There was also no lymphedema observed in Ang2(-/-) mice during embryonic development, which differs from that of Tie1(ΔICD/ΔICD) mice. We further investigated whether Tie1 exerted its function via Tie2 during lymphatic development. To our surprise, genetic deletion of Tie2 (Tie2(iUCKO/-)) in neonate mice did not affect lymphatic vessel growth and maturation. CONCLUSIONS: In contrast to the important role of Tie2 in the regulation of blood vascular development, Tie1 is crucial in the process of lymphatic remodeling and maturation, which is independent of Tie2.