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Objective: To investigate the characteristics, diagnosis and therapeutic effect of acquired lymphangiectasia of the vulva (ALV). Methods: A retrospective analysis of clinicopathological and follow-up data was conducted on the patients treated in Capital Medical University Affiliated Beijing Shijitan Hospital due to female ALV from July 2009 to July 2023. The patients who completed the staged operations [partial labiectomy and reconstruction + thoracic ductplasty and (or) perineal lymphovenous anastomosis] were included in the study and followed up. The improvement of perineal swelling, blister range, fluid leakage volume and frequency were evaluated through outpatient visits by the symptom rating scale of ALV (hereinafter referred to as the symptom rating scale) before and after surgery. Results: A total of 48 patients were treated due to ALV from July 2009 to July 2023, of which 98% (47/48) were postoperative pelvic malignant tumors and 94% (45/48) had a history of radiotherapy. A total of 10 patients with ALV who completed the staged operations were included in this study. (1) Clinical characteristics and diagnosis: 10 patients had a median age of 60 years old (50, 63 years old ). The median duration from cervical cancer surgery and radiation therapy to vulvar swelling was 1.5 years (0.0, 2.0 years), and the median duration from vulvar swelling to blister formation and leakage was 0.0 years (0.0, 4.8 years). Seven patients (7/10) had a history of recurrent erysipelas; 7 patients (7/10) had the most severe symptom (widespread blisters, persistent fluid leakage, and large amount of fluid leakage); noncontrast magnetic resonance lymphography (NCMRL) showed edema signals in the perineal region of all the patients, and increase of agent in the perineal region was observed in lymphoscintigram (LS). (2) Surgical treatment and postoperative pathological examination: of the 10 ALV patients who completed staged surgical treatment, 6 cases (6/10) were diagnosed with thoracic duct outlet obstruction and underwent thoracic ductplasty and partial labiectomy and reconstruction. Perineal lymphovenous anastomosis and partial labiectomy and reconstruction were performed in 4 cases (4/10) without thoracic duct outlet obstruction. Postoperative routine pathological examination of 10 patients (10/10) showed dermal papilla lymphangiectasia. Immunohistochemical tests were performed on 5 patients, all of which were positive for D2-40 and negative for CD 34 . (3) Efficacy: 8 patients completed the postoperative follow-up, and the median follow-up time was 31.0 months (17.5, 78.3 months). The perineal swelling and the blister fluid leakage were all significantly improved after the staged operations. All indexes of the symptom rating scale, including the degree of perineal swelling, blister range, fluid leakage volume and frequency, were significantly improved in 8 follow-up patients, and 3 (3/8) of them were cured; the median symptom score decreased significantly from 11.0 before surgery to 3.0 after surgery ( P <0.001). The incidence of erysipelas was significantly reduced from 7/10 before surgery to 2/8 after surgery ( P =0.035). Conclusions: The main causes of female ALV are pelvic tumor surgery and radiotherapy. The clinical diagnosis is made from relevant medical history, clinical manifestations, LS and magnetic resonance imaging. The diagnosis is confirmed by histopathological findings. Pathological results show lymphangiectasia in the dermal papilla, and immunohistochemical staining show positive for D2-40 and negative for CD 34 . The effect of staged surgery on ALV is remarkable and even cured, and could effectively reduce the incidence of erysipelas.

Competing Interests: Competing interests: None declared.

Despite being rarely discussed, perinephric lymphatics are involved in many pathological and benign processes. The lymphatic system in the kidneys has a harmonious dynamic with ureteral and venous outflow, which can result in pathology when this dynamic is disturbed. Although limited by the small size of lymphatics, multiple established and emerging imaging techniques are available to visualize perinephric lymphatics. Manifestations of perirenal pathology may be in the form of dilation of perirenal lymphatics, as with peripelvic cysts and lymphangiectasia. Lymphatic collections may also occur, either congenital or as a sequela of renal surgery or transplantation. The perirenal lymphatics are also intimately involved in lymphoproliferative disorders, such as lymphoma as well as the malignant spread of disease. Although these pathologic entities often have overlapping imaging features, some have distinguishing characteristics that can suggest the diagnosis when paired with the clinical history., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The hamartomatous polyp is a rare benign hamartoma of the palatine tonsil, usually encountered during the second decade of life. It may be reported under various terms in the literature, like lymphangioma of the tonsil, angiofibrolipoma, lymphangiomatous tonsillar polyp and lymphangiectatic fibrous polyp. Macroscopically, it appears as a large, pale, pedunculated mass. Typically, a hamartomatous polyp is asymptomatic or manifests mild symptoms, like foreign body sensation. It is not related to a generalised lymphatic malformation process. Despite its typical appearance, an excisional biopsy is necessary to rule out a malignancy. Histological findings are consistent with a squamous epithelial covering, a core of loose fibrous and adipose tissue with sparse lymphoid aggregations and dilated lymphatic channels filled with lymph and lymphocytes. Several embryologically based theories suggested its pathogenesis; however, recurrent tonsillitis does not play an established role. A typical tonsillectomy is suggested as a sufficient therapeutical approach with no tendency for recurrence., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Diffuse pulmonary lymphangiomatosis (DPL) is rare in adults. It is characterized by abnormal proliferation, dilatation, and thickening of the lymphatic channels in the lungs, pleura, and mediastinal soft tissue. Here, we report a case of DPL in a young adult man with recurrent productive cough. Chest computed tomography (CT) showed bilateral interlobular septal and peribronchovascular thickening and mediastinal soft tissue infiltration. Lung biopsy through video-assisted thoracic surgery demonstrated proliferation and dilatation of irregular lymphatic spaces, lined by flattened endothelial cells that were positive for CD31, D2-40, and factor VIII-related antigen on immunohistochemical staining. After treatment with propranolol for six months, the chest CT showed improved interlobular septal and peribronchovascular thickening and a unilateral pleural effusion, which turned bloody. Radiologic features can suggest the diagnosis of DPL. Surgical biopsy with adequate section size is critical in the diagnosis. Propranolol might be an effective and safe therapeutic option for patients with DPL., Competing Interests: Declaration of Competing Interest The author has no financial or other conflicts of interest to disclose., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Renal lymphangiectasia is a rare disorder where perirenal, parapelvic, and/or intra-renal lymphatics are dilated. The clinical presentation of renal lymphangiectasia can range from asymptomatic to renal failure. Ultrasound, computed tomography and magnetic resonance imaging have been used for the diagnosis. Management of such cases varies from conservative to nephrectomy. We report three cases of pediatric renal lymphangiectasia that were managed by recurrent sclerothera-pies and medical supportive treatment at our institution. A literature review is also presented. To the best of our knowledge, there are 83 reported cases in the literature, 60 adults and 23 pediatrics.

Visceral vascular anomalies are common in patients with vascular malformations in other parts of the body and can include lymphatic, venous, and arteriovenous malformations. Depending on the organ or organs involved they may present differently and pose different treatment challenges. Defining the malformation and understanding its extent is paramount in devising management regimens. Medical, interventional, and surgical therapies are often required in combination to treat these complex lesions. There are new and promising advances in the development of therapeutic agents targeting the PI3K/AKT/mTOR pathway. Due to the complex nature of these lesions a coordinated, multi-disciplinary approach is necessary to manage and mitigate symptoms and complications of this diverse group of vascular malformations., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: Diffuse pulmonary lymphangiomatosis (DPL) is a rare condition. Most patients with DPL present dyspnea, cough, expectoration, and hemoptysis. There are few reports of DPL accompanied by thrombocytopenia, whose cause remains unknown., Patient Concerns: An 18-year-old male patient presented with recurrent cough, expectoration, and dyspnea for 5 years, and thrombocytopenia was observed during a 2-month follow-up., Diagnosis: Chest computed tomography showed diffuse patchy shadows in both lungs, and pleural and pericardial effusions. Immunohistochemical lung tissue staining showed lymphatic and vascular endothelial cells positive for D2-40, CD31 and CD34. Routine blood test revealed platelets at 62 × 10 cells/L during follow-up. Bone marrow biopsy was normal. Ultrasound revealed no hepatosplenomegaly. Finally, the patient was diagnosed with DPL accompanied by thrombocytopenia., Interventions: He was treated by subtotal pericardial resection, thoracocentesis, and anti-infective therapy. Oral prednisone was administered for 2 months., Outcomes: The symptoms of cough and shortness of breath were improved, but thrombocytopenia persisted. We investigated the cause of thrombocytopenia. Whole-exome sequencing identified a mutation in exon 3 of the TNFRSF13B gene in this patient., Conclusion: DPL may present with thrombocytopenia and DIC. Patients with thrombocytopenia but not DIC and splenomegaly should be screened for gene mutations.

We report a rare presentation of vulvar lymphangiectasia that developed secondary to gastrointestinal tuberculosis in a teenager, and its spontaneous resolution after anti-tuberculous treatment was completed., (© 2019 Wiley Periodicals, Inc.)

Background: Renal lymphangiectasia is a rare and poorly understood lymphatic disease associated with lymphatic dilation and leakage. To our knowledge, no cases have been described in the context of a transplanted kidney., Methods: We describe 2 cases of renal lymphangiectasia in transplanted kidneys, both from pediatric donors., Results: The cases of allograft lymphangiectasia are characterized by severe, symptomatic ascites refractory to attempts at medical and surgical management, and ultimately requiring allograft nephrectomy., Conclusions: While lymphatic complications, particularly lymphoceles, are not uncommon in renal transplantation, lymphangiectasia is a distinct condition which should be considered in renal transplant patients with ascites, after all other sources have been ruled out.

Background: Cutaneous microcystic lymphatic malformations (CMLMs) are rare conditions in children and adults. They present as clusters of vesicles full of lymph and blood to various extents, inducing maceration, esthetic impairment, pain, and impaired quality of life. The treatment is challenging. Sirolimus is an inhibitor of mammalian target of rapamycin (mTOR) involved in angio-lymphangiogenesis. Topical sirolimus has recently been reported as effective in a few reports of patients with CMLMs. The objective is to compare the efficacy and safety of a 12-week application of 0.1% topical sirolimus versus topical vehicle in CMLMs in children and adults., Methods: This French blinded multicenter within-person randomized controlled phase 2 trial aims to include 55 patients aged ≥ 6 years who have a primary CMLM. The CMLM will be divided into two equal areas that will be randomly allocated to 0.1% topical sirolimus or topical vehicle applied for 12 weeks. At the end of the 12-week period, the patient/parent will treat the whole area of CMLM with 0.1% topical sirolimus on remaining lesions, for eight more weeks. Patients will be seen at week 20 (treatment will be stopped) and at month 12 to evaluate long-term efficacy. The primary outcome will be improvement of the CMLM in the area treated with topical sirolimus compared to the area treated with topical vehicle by the investigator physician (blinded to the treatment) with the Physician Global Assessment score at week 12. Secondary outcomes will include: assessment of efficacy by independent experts on the basis of standardized photographs; impact on quality of life; efficacy for oozing, bleeding, erythema, and thickness evaluated by the investigators; and global efficacy as well as efficacy for functional and aesthetic impairment evaluated by the patient. Systemic passage of sirolimus will be measured at weeks 6, 12, and 20, and at week 16 for CMLMs ≥ 900 cm 2 ., Discussion: For patients with CMLMs, topical sirolimus could be a non-invasive and well-tolerated therapeutic option. If the trial demonstrates efficacy and safety of this treatment, this result will lead to a real change in the management of this condition, and 0.1% sirolimus cream would become the first-line treatment., Trial Registration: ClinicalTrials.gov, NCT03972592. Registered on 3 June 2019. EU Clinical Trials Register EudraCT, 2018-001359-11.

Rationale: Diffuse pulmonary lymphangiomatos (DPL) is a rare aggressive lymphatic disorder characterized by proliferation of anastomozing lymphatic vessels and extremely rare in adult patients., Patient Concerns: We report a case of diffuse pulmonary lymphangiomatosis in 59-year-old man presented with cough and sputum for 2 months., Diagnoses: Combining clinical manifestations with results of radiological, bronchoscopy, and surgical lung biopsy, it was consistent with the diagnosis of DPL., Interventions: After bronchoalveolar lavage and biopsy, symptom of cough got worse suddenly accompanied by excessive chyloptysis. The patient received an emergency surgical intervention and low fat medium chain fat treatment., Outcomes: The patient was discharged with a much better health condition., Lessons: This case report is the oldest patient reported in the English literature, to the best of our knowledge. Serious complications of bronchoscopy should be considered, especially in DPL patients with severely enlarged mediastinum or with thin-walled translucent vesicles under endoscopy.

General lymphatic anomaly (GLA) is a very rare disorder, characterised by multifocal lymphatic malformations into various tissues that is due to congenital abnormalities of lymphatic development. No treatment has ever proved its efficiency.We report a 22-year-old man with recurrent bronchial casts due to thoracic involvement of GLA. After a 6-month treatment with sildenafil (20 mg three times a day), a phosphodiesterase 5 inhibitor, chest CT scan showed a complete regression of ground-glass opacities and lung function test results improved substantially and remained stable for 1 year. The treatment was well tolerated.This observation suggests that sildenafil may be a therapeutic approach to be tested in thoracic involvement of GLA., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Kaposiform lymphangiomatosis (KLA) is a vascular anomaly featuring lymphatic expansion. It has no known cause, no effective treatment, and is associated with high morbidity. Proliferative cells from 3 KLA patient lesions were characterized relative to adiopose-derived mesenchyme stem cells (ADSCs) and cells derived from a patient with the related disease kaposiform hemangioendothelioma (KHE). KLA cells variably expressed markers of mesenchyme stem cells (CD73, CD90, CD105, CD146) and lacked endothelial cell markers (CD31, CD34) as determined by flow cytometry. They expressed markers of vascular pericytes (neural/glial antigen 2, alpha-smooth muscle actin, platelet-derived growth factor-beta receptor, and CXCL12) as determined by quantitative reverse transcription polymerase chain reaction. Lesion cells transcribed vascular markers VEGFC and VEGFD, as well as VCAM-1, the latter of which was confirmed by flow cytometry, consistent with angiogenic MSC-like pericytes. Furthermore, conditioned medium from each was shown to promote the proliferation of growth factor-starved lymphatic endothelial cells. Unlike kaposiform hemangioendothelioma-derived MSC-like pericytes and ADSCs, KLA isolates were defective in support of vascular network formation in co-cultures with either vascular or lymphatic endothelial cells. Genetic analysis by whole exome sequencing revealed novel variant alleles in 2 populations of KLA cells (BAD, TSC1) that may bear on aberrant pericyte growth and function.

Congenital pulmonary lymphangiectasia (CPL) is a rare but fatal disease, usually having an onset from the first few hours to days after birth. Inconsistent nomenclatures were used for CPL in the past decades. Patients often present with intractable respiratory failure, hydrops fetalis and even sudden death. The etiologies of CPL remain unclear. Previous hypotheses suggested that CPL might be caused by conditions preventing normal regression of the lymphatics after the 18th-20th week of gestation. Up-to-date biological studies on lymphatic development, lymphatic valve formation and occurrence of hydrops fetalis revealed possible causative relations with mutations of genes of the vascular endothelial growth factor receptor (VEGFR), RAS/MAPK, PI3K/AKT and NF-κB signaling pathways. Lung biopsy with subsequent histological and immunohistochemical studies is a gold standard of CPL diagnosis. Apart from symptomatic and supportive treatments, novel regimens including sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, one of the inhibitors of the pertinent signaling pathways and ethiodized oil lymphatic embolization under ultrasound-guided intranodal lymphangiography have shown encouraging short-term therapeutic effects for lymphatic anomalies. Surgical operations (lobectomy or pneumonectomy) can be the treatment of choice for patients with CPL confined to one lobe or one lung. Patients with CPL usually have a poor prognosis and often die during the neonatal period. Their prognoses are expected to improve with the development of modern therapeutic agents.

Background: Diffuse pulmonary lymphangiomatosis (DPL) mainly affects the lung and pleura. There are very few pathological reports of lung damage accompanied by diffuse involvement of the extrapulmonary lymph nodes and surrounding soft tissue. The clinicopathological significance of coexistence of pulmonary and extrapulmonary lesions is unknown., Methods: Here, we report a 16-year-old male patient. The pathological specimens of the supraclavicular lymph node and soft tissue together with the lung biopsy were analyzed by pathological observation and immunohistochemical staining. Literatures were reviewed and clinical and imaging findings were discussed., Results: The patient presented with coughing and expectoration for 1 year and intermittent hemoptysis for 4 months. Ultrasound revealed swollen lymph nodes in bilateral neck, left armpit, and pubic symphysis. Chest CT scan showed diffuse grid and linear shadows, bilateral pleural thickening, and nodule formation. Multiple enlarged lymph nodes were mainly investigated in bilateral hilar, mediastinal, para-aortic, lesser curvature, and retroperitoneal. Supraclavicular lymph node biopsy confirmed the lymphatic hyperplasia and expansion in the capsule and surrounding soft tissue. The thoracoscopic examination found bloody chylothorax on the left chest. And lung biopsy showed the lymphatic vessel hyperplasia and expansion on the pleura and adjacent lung tissue. Immunohistochemical stains showed that the lymphatic endothelial cells were positive for D2-40 and CD31. Lymphangiomatosis involving the pulmonary and extrapulmonary lymph nodes and surrounding soft tissue was diagnosed based on the aforementioned histological findings., Conclusion: Lymphangiomatosis of superficial lymph node mainly involves the capsule of lymph nodes and its surrounding soft tissue. The information obtained from the lymph node biopsy can prompt and assist the diagnosis of DPL.

Objectives: Pulmonary lymphangiectasia associated with hypoplastic left heart syndrome with an intact or restrictive atrial septum may result from increased left atrial pressure, and is associated with worse outcomes following staged reconstruction due to lung dysfunction and significant hypoxaemia. Our objective was to characterise the incidence of pulmonary lymphangiectasia in cases of early mortality following stage 1 reconstructions., Methods: An institutional cardiac surgical database was retrospectively searched for patients who died within 30 days following a stage 1 reconstruction between 1 January, 1984 and 31 December, 2013. During that period, 1669 stage 1 procedures were performed. Autopsy lung specimens were reviewed by a paediatric pathologist. Patients who died of suspected technical issues were excluded., Results: A total of 54 patients were included, and of these seven cases (8.5%) of pulmonary lymphangiectasia were identified. The mean estimated gestational age was 38.2±2.4 weeks, and the mean birth weight was 3.0±0.6 kg. The median interval between surgery and death was 1 day (with a range from 0 to 18 days). The atrial septum was intact in one patient (14.3%), restrictive in three patients (42.9%), and unrestrictive in three patients (42.9%)., Conclusions: Pulmonary lymphangiectasia may develop in hypoplastic left heart syndrome with or without a restrictive atrial septum. As standard prenatal diagnostic evaluations and treatment methods for pulmonary lymphangiectasia are limited, this may be an important contributor to early and late mortality following stage 1 reconstruction for hypoplastic left heart syndrome.

Congenital pulmonary lymphangiectasia (CPL) is a rare developmental disorder of the lung, characterized by dilation of pulmonary subpleural, interlobar, perivascular and peribronchial lymphatics. The incidence of CPL among stillborn and neonates was estimated to be <1%. The etiology of CPL is unknown. However, it has been suspected to be of a genetic background. Recent basic studies revealed that it might be caused by the FOXC2, Vegfr-3 and integrin α9β1gene mutations. A clinical diagnosis of CPL can be made much easier in full-term neonates who present with respiratory distress, pleural (especially chylous) effusions with or without generalized edema. In infancy, the diagnosis seems to be more difficult due to the nonspecific respiratory symptoms like persistent tachypnea, cough and wheeze. Lung biopsy with subsequent histological and immunohistochemical studies is the golden diagnostic method of CPL. Immunohistochemical staining for endothelial cell markers CD31, CD34 and D2-40 confirms lymphatic origin. Therapeutic strategies include supportive, nutritional, investigational, aggressively interventional and surgical regimens, most of which have shown promising outcomes. Although CPL was once regarded as a disorder of very poor prognosis in neonatal onset cases, teenager and adult patients have shown good outcomes upon long-term follow-up.Die angeborene pulmonale Lymphangiektasie (CPL) ist eine seltene Entwicklungsstörung der Lunge, die durch eine Dilatation der pulmonalen subpleuralen, interlobären, perivaskulären und peribronchialen Lymphgefäße charakterisiert ist. Die Inzidenz der CPL bei Totgeburten und Neugeborenen wird <1% geschätzt. Die Ätiologie der CPL ist unbekannt. Allerdings wird ein genetischer Hintergrund vermutet. Neuere Grundlagenstudien zeigten, dass die CPL durch FOXC2, Vegfr-3 und Integrin α9β1-Genmutationen verursacht sein könnte. Die klinische Diagnose der CPL ist sehr viel einfacher in Reifgeborenen zu stellen, die Atemnot, Pleuraergüsse (vor allem chylöse) mit und ohne generalisiertem Ödem aufweisen. In der frühen Kindheit ist die Diagnose aufgrund der unspezifischen respiratorischen Symptomatik wie persistierende Tachypnoen, Husten oder Röcheln schwerer zu stellen. Die Lungenbiopsie mit anschließenden histologischen und immunhistochemischen Untersuchungen ist der Goldstandard für die Diagnose der CPL. Die immunhistochemische Färbung der Endothelzellmarker CD31, CD34 und D2-40 bestätigt den lymphatischen Ursprung. Die Behandlungsstrategien umfassen unterstützende, alimentäre, in Erprobung befindliche, aggressiv-interventionelle und chirurgische Behandlungspläne, von denen die meisten ermutigende Ergebnisse zeigten. Obwohl die CPL einst bei Fällen mit Ausbruch im Neugeborenenalter als Erkrankung mit sehr schlechter Prognose galt, zeigen Teenager und erwachsene Patienten in der Langzeit-Nachbeobachtung gute Verläufe., Competing Interests: Conflict of interest: The authors have no conflict of interest to disclose., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Acquired lymphangiectasia of the vulva (ALV) is a rare condition thought to be secondary to pelvic lymphatic obstruction. Although benign, this entity often occurs after previous malignancy and can be confused with conditions such as genital warts. We sought to clarify the clinicopathologic features of ALV by studying affected patients from our institution and from the existing literature., Methods: We reviewed retrospectively the clinical and histopathologic characteristics of patients with ALV from our institution and performed an extensive literature search to identify all published cases of ALV., Results: Eleven patients with ALV were identified from our institution. Three patients had Crohn disease, three had malignancies involving the pelvic region (rectal adenocarcinoma, cervical carcinoma, endometrial carcinoma), and three (two with pelvic malignancy) had previous radiation therapy. One patient had Proteus syndrome. Of 67 distinct cases of ALV identified in the literature, 41 (61%) had a history of malignancy., Conclusions: In any acquired or clinically unusual lymphatic process in the skin and soft tissues, a lesion or obstructive process of the draining lymphatics should be investigated., (© 2016 The International Society of Dermatology.)

Background: Sometimes acquired lymphangiectasia (lymphangioma circumscriptum), the pathological mechanism of which is unknown, accompanies lymphedema. The purpose of this study was to better understand the pathological changes present in acquired lymphangiectasia., Methods and Results: We examined the pathological characteristics of acquired lymphangiectasia with lymphedema among patients treated at the University of Tokyo Hospital from March 2008 to December 2015. In total, 16 biopsies from 10 patients were investigated. The average age of the patients was 57.2 years (range 43-69), and all were female with secondary lymphedema. Surgical specimens were fixed in formalin, and tissue sections were stained with hematoxylin-eosin. Additional immunostaining (podoplanin, lymphatic vessel endothelial hyaluronan receptor [LYVE] -1, CD4, CD8, CD20, and CD31) was performed in cases 1-3 and 8-10. Dilation of lymphatic vessels in the papillary dermis was present in all 10 cases. Infiltration of inflammatory cells, most of which were lymphocytes, was also observed in the dermis and the epidermis in all cases, even though there were no clinical signs of inflammation. The infiltrating lymphocytes were mainly CD4+ T cells, and less commonly, CD8+ T cells and CD20+ B cells. The number of three types of lymphocytes was significantly larger in the superficial layer of the dermis than in the deep layer, which may indicate that they oozed out from the dilated lymphatic vessels located in the superficial dermis. CD8+ T cells infiltrated the epidermis in seven of eight specimens. In case 4, coagulated lymphatic fluid inside the lymphatic vessel was observed. Proliferation of collagenous fiber in the dermis and acanthosis were observed., Conclusions: Lymphatic dilation and proliferation of collagenous fiber in the dermis were seen in cases of acquired lymphangiectasia (lymphangioma circumscriptum). Constant infiltration of lymphocytes in the dermis and the epidermis may have a relation to frequent cellulitis, which is often seen in lymphedema patients.

Purpose: Acne agminata has only been rarely reported in the ocular adnexa. This study was undertaken to identify histopathological, clinical, and management features of this disorder., Methods: A computerized database was utilized to identify cases of ocular adnexal acne agminata. Via chart review and light microscopy, clinical and histopathologic aspects of this dermatosis were collected, and statistical analyses were performed., Results: Twelve cases (5 males, 7 females, mean age = 50.5 years) of clinically and histopathologically confirmed ocular adnexal acne agminata were identified. The main variant of granuloma was sarcoidal in 6 cases (50%) and tuberculoid in 5 cases (41.7%), although 9 specimens (75%) displayed greater than 1 variant of granuloma. In addition, specimens demonstrated varying degrees of fibrosis (8 cases, 66.7%), necrosis (6 cases, 50%), spongiosis (5 cases, 41.7%), and perifollicular inflammation (6 cases, 50%). All specimens showed signs of lymphstasis-lymphangiectasis. At a minimum of 6-month postprocedure interval, all patients experienced complete relief of their symptoms and did not experience recurrence., Conclusions: This study represents the largest cohort of ocular adnexal acne agminata, and revealed a spectrum of granulomatous subtypes, including coexistence of different granuloma subtypes within the same specimen. Lymphangiectases is a hallmark of this disorder, and varying features of tissue reaction are typical features of acne agminata. All of these cases were successfully cured by surgical resection of lesions without recurrence at last follow-up, and this modality should be considered the standard of care in the management of this problem.

Congenital pulmonary lymphangiectasia (CPL) is a rare congenital disorder that typically presents with intractable respiratory failure in the first few days of life. There is an association non-immun hydrops and CPL. In this study we reviewed four CPL cases between January 2006 and January 2014 among 684 fetal-pediatric autopsies. All cases were in the second trimester. In light microscopy there were marked dilatated channels in the subpleural -peribronchial-subseptal region of the lungs. The channels were lined with flattened cells which were expressing CD 31 and D2-40, negative for CD34. Although pulmonary interstitial emphysema (PIE) was considered an important differential diagnosis, a giant cell reaction surrounding the interstitial cystic lesions, a histological hallmark of PIE. CPL is characterized by dilatation of the pulmonary lymphatic vessels and occurs as a congenital anomaly. Noonan classified it into three groups. Primary developmental defect of pulmonary lymphatics is group 3. Group 3 is called also as CPL; normal regression of the connective tissue elements fails to occur after the 16th week of fetal life, associated with an aggressive clinical course, poor prognosis. In fetal autopsy examination CPL should be recognized if there is a fetus with pleural effusion, non-immune hydrops. There is no clinical evidence for CPL.

Inherited, complete deficiency of human HOIL-1, a component of the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylopectinosis. We report the clinical description and molecular analysis of a novel inherited disorder of the human LUBAC complex. A patient with multiorgan autoinflammation, combined immunodeficiency, subclinical amylopectinosis, and systemic lymphangiectasia, is homozygous for a mutation in HOIP, the gene encoding the catalytic component of LUBAC. The missense allele (L72P, in the PUB domain) is at least severely hypomorphic, as it impairs HOIP expression and destabilizes the whole LUBAC complex. Linear ubiquitination and NF-κB activation are impaired in the patient's fibroblasts stimulated by IL-1β or TNF. In contrast, the patient's monocytes respond to IL-1β more vigorously than control monocytes. However, the activation and differentiation of the patient's B cells are impaired in response to CD40 engagement. These cellular and clinical phenotypes largely overlap those of HOIL-1-deficient patients. Clinical differences between HOIL-1- and HOIP-mutated patients may result from differences between the mutations, the loci, or other factors. Our findings show that human HOIP is essential for the assembly and function of LUBAC and for various processes governing inflammation and immunity in both hematopoietic and nonhematopoietic cells., (© 2015 Boisson et al.)

Lymphangiomatosis is an uncommon proliferative disorder of the lymphatic vasculature whose etiology remains poorly understood. The lymphangiomatosis spectrum encompasses a remarkable heterogeneity in its potential presentation, including micro- and macrocystic isolated lymphatic malformations, thoracic and intraabdominal diffuse lymphangiomatosis, and osseous and soft-tissue presentations known as Gorham-Stout disease. Recent therapeutic advances are empirical in nature or, at best, inferential, reflecting the scanty availability of laboratory-based model systems for the mechanistic study of this disease. Several promising model systems are reviewed here. The laboratory investigation of lymphangiomatosis will likely continue to benefit from the remarkable growth of insights into the mechanisms of lymphangiogenesis and vascular development., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: A pattern of abnormal signal at fetal MRI may be seen in the setting of primary or secondary congenital lymphangiectasia, manifested as a heterogeneous appearance of the lung parenchyma and the presence of subtle T2-hyperintense branching tubular structures that emanate from the hila. We have named this pattern the nutmeg lung., Objective: We describe the nutmeg lung appearance seen in fetal MRI scans, with discussion of possible etiologies and outcomes in a series of eight fetuses., Materials and Methods: We retrospectively reviewed imaging from a database of patients demonstrating features of nutmeg lung on fetal MRI. Medical records were used to determine the postnatal diagnosis, clinical course and outcome., Results: Among the eight fetal cases of nutmeg lung, two had postnatal confirmation of primary lymphangiectasia and the remaining six had secondary lymphangiectasia, presumably secondary to congenital cardiac anomalies. There were various-size pleural effusions in all cases. Only one of the cases demonstrated hydrops fetalis., Conclusion: We present the description of the nutmeg lung sign on fetal MRI as T2-hyperintense heterogeneous lungs with fluid-filled, serpiginous branching structures that extend from the pulmonary hila to the periphery of the lung, often accompanied by pleural effusions. The sign denotes findings of primary or secondary lymphangiectasia. Findings of secondary lymphangiectasia in our series were a result of cardiac insufficiency. Recognizing this sign might be helpful in the diagnostic algorithm of the fetus with abnormal lung parenchyma.

Noonan Syndrome is an autosomal dominant disorder characterized by short stature, congenital heart defects, developmental delay, dysmorphic facial features and occasional lymphatic dysplasias. The features of Noonan Syndrome change with age and have variable expression. The diagnosis has historically been based on clinical grounds. We describe a child that was born with congenital refractory chylothorax and subcutaneous edema suspected to be secondary to pulmonary lymphangiectasis. The infant died of respiratory failure and anasarca at 80 days. The autopsy confirmed lymphatic dysplasia in lungs and mesentery. The baby had no dysmorphic facial features and was diagnosed postmortem with Noonan syndrome by genomic DNA sequence analysis as he had a heterozygous mutation for G503R in the PTPN11 gene.

Congenital pulmonary lymphangiectasia (CPL) is a rare lymphatic pulmonary abnormality. CPL with respiratory distress has a poor prognosis, and is frequently fatal in neonates. We report a case of pneumonectomy for CPL in a newborn. An infant girl, born at 39 weeks' after an uncomplicated pregnancy, exhibited respiratory distress 1 hr after birth, which necessitated intubation and aggressive ventilator care. Right pneumonectomy was performed after her symptoms worsened. Histologic examination indicated CPL. She is currently 12 months old and developing normally. Pneumonectomy can be considered for treating respiratory symptoms for improving chances of survival in cases with unilateral CPL.

Rationale: Lymphatic vessels in the respiratory tract normally mature into a functional network during the neonatal period, but under some pathological conditions they can grow as enlarged, dilated sacs that result in the potentially lethal condition of pulmonary lymphangiectasia., Objective: We sought to determine whether overexpression of the lymphangiogenic growth factor (vascular endothelial growth factor-C [VEGF-C]) can promote lymphatic growth and maturation in the respiratory tract. Unexpectedly, perinatal overexpression of VEGF-C in the respiratory epithelium led to a condition resembling human pulmonary lymphangiectasia, a life-threatening disorder of the newborn characterized by respiratory distress and the presence of widely dilated lymphatics., Methods and Results: Administration of doxycycline to Clara cell secretory protein-reverse tetracycline-controlled transactivator/tetracycline operator-VEGF-C double-transgenic mice during a critical period from embryonic day 15.5 to postnatal day 14 was accompanied by respiratory distress, chylothorax, pulmonary lymphangiectasia, and high mortality. Enlarged sac-like lymphatics were abundant near major airways, pulmonary vessels, and visceral pleura. Side-by-side comparison revealed morphological features similar to pulmonary lymphangiectasia in humans. The condition was milder in mice given doxycycline after age postnatal day 14 and did not develop after postnatal day 35. Mechanistic studies revealed that VEGF recptor (VEGFR)-3 alone drove lymphatic growth in adult mice, but both VEGFR-2 and VEGFR-3 were required for the development of lymphangiectasia in neonates. VEGFR-2/VEGFR-3 heterodimers were more abundant in the dilated lymphatics, consistent with the involvement of both receptors. Despite the dependence of lymphangiectasia on VEGFR-2 and VEGFR-3, the condition was not reversed by blocking both receptors together or by withdrawing VEGF-C., Conclusions: The findings indicate that VEGF-C overexpression can induce pulmonary lymphangiectasia during a critical period in perinatal development.

Disorders of the pulmonary lymphatic system include macro- and microcystic lymphatic malformations, primary or secondary lymphangiectasias, generalized lymphatic anomalies, diffuse pulmonary lymphangiomatosis, and combinations of lymphatic and other tissue anomalies, including lymphangioleiomyomatosis (LAM). We report a case of a patient with a newly defined entity classified as kaposiform lymphangiomatosis (KLA). This 50-year-old nonsmoking Hispanic woman presented with a 20-year history of cough, hemoptysis, chyloptysis, and pleuritic chest pain. Laboratory evaluation demonstrated a low normal platelet count, elevated d-Dimer, low normal fibrinogen, and elevated fibrin split products. Chest computerized tomography imaging showed enlarged hypodense lymph nodes in the mediastinum and hila, and peribronchovascular thickening, without evidence of cystic parenchymal lesions. Magnetic resonance imaging of the chest showed cystic mediastinal lymph nodes with heterogeneously increased T2 and decreased T1 signal intensity. Fiberoptic bronchoscopy revealed hyperemic mucosa with granular appearance suggestive of a submucosal infiltrative process. Pathological specimens revealed dilated, malformed lymphatic channels within the pleura, pulmonary septa, and bronchovascular bundles, and foci of perilymphatic and intralymphatic spindle cells which reacted with the Prospero homeobox protein 1 (PROX-1) immunostain. The morphology and immunohistochemistry results were consistent with a diagnosis of KLA. This newly recognized clinical-pathological entity among intrathoracic lymphatic anomalies is distinguished from generalized lymphatic anomaly and diffuse pulmonary lymphangiomatosis in part by characteristic hematological abnormalities and hemorrhagic complications, including hemoptysis, as experienced by our patient.

Objective: To investigate the relationship between the occurrence and development of conjunctivochalasis and bulbar conjunctival lymphangiectasia., Methods: Case control study. One hundred cases with conjunctivochalasis treated from January to March 2012 were selected to study, and 100 cases with no conjunctivochalasis as the control group at the same time. To observe bulbar conjunctiva lymphatic duct dilatation using slit lamp microscope, analysis bulbar conjunctiva and fascia images by OCT scanning, and ablate lymphatic of conjunctival tissue for pathologic examine., Results: Twenty-nine eyes of the bulbar conjunctiva lymphangiectasia associated with 100 cases (183 eyes) conjunctivochalasis patients, accounting for 15.84%; 8 eyes of the ball conjunctival lymphatic dilation in control group of 100 cases ( 200 eyes), accounting for 4.00%. The difference between the two groups was statistically significant (χ(2) = 15.36, P < 0.001). OCT scanning showed that lymphangiectasia of the conjunctiva is at the subcutaneous mainly, some in the conjunctival lamina propria. They are border-clear, full-filled fluid, single-lumen or multi lumens, not involving the fascia. The histopathological examination showed that the lamina propria of the bulbar conjunctiva mildly chronic inflammatory changes accompanied by a large number of lymphangiectasia., Conclusion: Bulbar conjunctival lymphangiectasia may be one of the reasons for the conjunctivochalasis.