Case 311: Generalized Lymphatic Anomaly.

HISTORY: A 14-year-old boy presented with asthenia, low back pain, and abdominal distention. The onset of symptoms was slow and progressive over a few months. The patient had no contributing past medical history. At physical examination, all vital signs were normal. Only pallor and positive fluid wave test results were noted; there was no lower limb edema, mucocutaneous lesions, or palpable lymph node enlargement. Laboratory work-up revealed a decreased hemoglobin concentration of 9.3 g/dL (normal range, 12-16 g/dL) and a decreased hematocrit level of 29.8% (normal range, 37%-45%), but all other laboratory values were normal. Contrast-enhanced CT of the chest, abdomen, and pelvis was performed.

Breast-implant Related Silicone Lymphadenopathy: Asteroid Bodies do not Always Equal Sarcoidosis!

Silicone breast implants are frequently used for breast augmentation for cosmetic purposes, as well as for breast reconstruction after prophylactic or therapeutic mastectomy. Silicone lymphadenopathy is a well-known complication of silicone breast implants. Silicone droplets are present in the breast tissue through 'silicone bleeding' of the implant or because of implant rupture. These silicone particles can migrate from the breast to the regional lymph nodes. Silicone lymphadenopathy is caused by a substantial foreign body reaction against these silicone particles, and is frequently associated with asteroid body-containing multinucleated giant cells. Similar multinucleated giant cells are often observed in the capsule surrounding the silicone breast implant, and the number of associated asteroid bodies is highly variable. Here, we discuss a series of twelve women with breast implant-related asteroid bodies in their lymph nodes and/or breast tissue. This pictorial essay illustrates that the presence of asteroid bodies in a lymph node does not necessarily suggests a diagnosis of sarcoidosis. Clinical information about the patient having (or having had) silicone breast implants is often lacking. The encounter of asteroid body-containing giant cells in lymph node cytology, biopsies or resections should therefore lead to reflex clinical-pathological correlation, before establishing a final diagnosis.

Lymphatic Disorders and Management in Patients With Congenital Heart Disease.

Congenital heart disease can lead to notable lymphatic complications such as chylothorax, plastic bronchitis, protein-losing enteropathy, and ascites. Recent improvements in lymphatic imaging and the development of new lymphatic procedures can help alleviate symptoms and improve outcomes.

Children with cervical lymphadenopathy: reactive or not?

BACKGROUND: This study aims to evaluate the etiology of cervical lymphadenopathies in children and to define the significance of demographic, clinical, and laboratory features in the prediction of malignancy. METHODS: Medical records of 527 patients were reviewed retrospectively between 2015 and 2019. The patients were examined in terms of demographics, clinical, radiologic, and serologic findings. A lymph node biopsy was performed in selected patients. The risk factors for malignancy were evaluated. RESULTS: Out of 527 children, 26 had neck masses mimicking lymphadenopathy; 501 had lymphadenopathy. The most common location was the anterior cervical region and the median age was 5.7 years. Thirty-nine patients had malignancy (lymphoma in 34, nasopharyngeal carcinoma in 3, leukemia in 1 and neuroblastoma in 1). The risk of malignancy was associated with older age, duration of > 4 weeks, lymph node size > 3 cm, supraclavicular location, presence of systemic symptoms, and hepatosplenomegaly (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001). On laboratory evaluation, anemia, leukocytosis, and increased erythrocyte sedimentation rate were found to be associated with malignancy (p < 0.001, p=0.003, p < 0.001). CONCLUSIONS: Cervical lymphadenopathies in children are generally benign but patients with persisting cervical lymphadenopathy, adolescent age, accompanying systemic symptoms and abnormal laboratory findings should be considered for an early biopsy.

Refractory Hepatic Lymphorrhea: Percutaneous Transhepatic Lymphangiography and Embolization with n-Butyl-2-Cyanoacrylate Glue.

Hepatic lymphorrhea is a leakage from the liver's lymphatic ducts into the abdominal cavity and an extremely rare complication associated with injury of the hepatoduodenal ligament, which can lead to refractory ascites. Hepatic lymphorrhea is constituted by non-chylous ascites and can be visualized by transhepatic lymphangiography instead of pedal or intranodal lymphangiography. To date, only a few successfully treated cases using interventional procedures have been reported. Although n-butyl-2-cyanoacrylate (NBCA) glue is widely used in various cases of vascular embolization and other lymphatic leak treatments, there have been no reports of its use for post-surgical hepatic lymphorrhea. The NBCA glue embolization described in this case report may be one of the treatment options to control the refractory ascites derived from hepatic lymphorrhea.

Comorbidity and Lymphatic Disease: The Lymphatic Continuum Re-Examined.

It has now been ∼20 years since the original Lymphatic Continuum conference was convened, and this continuum has transitioned from a compelling concept to a reality. The explosive growth in our comprehension of lymphatic genetics, development, and function has expanded and modified our traditional views regarding what is, and is not, lymphatic disease. Groundbreaking investigations over the past decade have now defined a large and growing list of pathological conditions in which morphological or function lymphatic alterations can be identified. This list includes atherosclerosis and dyslipidemia, hypertension and other cardiovascular diseases, inflammation and inflammatory bowel disease, obesity, narrow angle glaucoma, and, most recently and compellingly, neurodegenerative disease. The sometimes overlapping but largely disparate nature of these various aforementioned disease categories suggests that the presence, or absence, of structural or functional lymphatic derangements may represent a previously unrecognized unifying influence in the maintenance of health and the promotion of disease. Future investigation of lymphatic mechanisms in disease will likely continue to elucidate the influences of lymphatic dysfunction, perhaps subtle, that can invest other, seemingly unrelated, diseases. In future, such discoveries will provide mechanistic insights and may potentiate the development of a new lymphatic-based approach to human disease diagnosis and therapeutics.

Lymphatic Vasculature: An Emerging Therapeutic Target and Drug Delivery Route.

The lymphatic system has received increasing scientific and clinical attention because a wide variety of diseases are linked to lymphatic pathologies and because the lymphatic system serves as an ideal conduit for drug delivery. Lymphatic vessels exert heterogeneous roles in different organs and vascular beds, and consequently, their dysfunction leads to distinct organ-specific outcomes. Although studies in animal model systems have led to the identification of crucial lymphatic genes with potential therapeutic benefit, effective lymphatic-targeted therapeutics are currently lacking for human lymphatic pathological conditions. Here, we focus on the therapeutic roles of lymphatic vessels in diseases and summarize the promising therapeutic targets for modulating lymphangiogenesis or lymphatic function in preclinical or clinical settings. We also discuss considerations for drug delivery or targeting of lymphatic vessels for treatment of lymphatic-related diseases. The lymphatic vasculature is rapidly emerging as a critical system for targeted modulation of its function and as a vehicle for innovative drug delivery.

Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas.

RATIONALE: Despite the availability of multi-"omics" strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures. OBJECTIVE: To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). METHODS: Transcriptomic profiles of immune-related gene from micro-dissected sarcoidosis granulomas within lung and mediastinal lymph node tissues and compared to infectious granulomas from paraffin-embedded blocks. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. RESULTS: Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers (STAB1, HBEGF, and NOTCH4), excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, NPR1 and CXCL2. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level. CONCLUSION: These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.

Abnormal pulmonary lymphatic flow in patients with paediatric pulmonary lymphatic disorders: Diagnosis and treatment.

Pulmonary lymphatic disorders are characterized by the presence of the abnormal lymphatic tissues in the thoracic cavity, presenting clinically as chylothorax, chylopericardium, chyloptysis, interstitial lung disease and plastic bronchitis. These conditions include: neonatal chylothorax, cardiac and non-cardiac plastic bronchitis, non-traumatic chylothorax, post congenital cardiac surgery chylothorax and complex lymphatic malformations. Recently developed lymphatic imaging techniques, such as intranodal lymphangiography and dynamic contrast enhanced magnetic resonance lymphangiography demonstrated abnormal pulmonary lymphatic flow from thoracic duct into pulmonary parenchyma as a pathophysiological mechanism of these diseases. Novel minimally invasive lymphatic interventions, such as thoracic duct embolization, interstitial lymphatic embolization and surgical lympho-venous anastomosis, provide an effective treatment of these conditions.

Application of flow cytometry in the analysis of lymphoid disease in the lung and pleural space.

Various types of lymphoid neoplasms can occur in the lung. Lung parenchyma, the pleura or the pleural cavity can be the primary site of a lymphoid neoplasm or can be involved secondarily as a result of systemic dissemination from a separate primary site. Recognition of pulmonary lymphoid neoplasms (PLN) has increased secondary to technological advances in the medical field. Multiparameter flow cytometry (FC) is a one of the diagnostic tools that serves an essential role in the detecting and categorizing PLNs. FC allows for rapid identification and immunophenotypic characterization of PLN. In this article, we discuss the role of FC in the diagnosis of the most commonly encountered PLNs as well as their basic clinicopathologic features. We briefly discuss the role of FC in identifying non-hematolymphoid neoplasms in lung specimens as well.

Giant cervicomediastinal thymic cyst in an elderly: diagnosis by multimodality imaging and fine-needle aspiration cytology with immunocytochemistry.

A 65-year-old woman, a non-smoker, presented to the pulmonary medicine outpatient department with chest pain, mild dyspnoea, right side neck swelling and mild facial puffiness. The cervical swelling was soft, non-tender and fluctuant on palpation. Multimodality imaging revealed a large, thin-walled cervicomediastinal cystic lesion with septations, haemorrhage, septal calcification and without any solid component. Image-guided fine-needle aspiration cytology from the septa with immunocytochemistry helped to establish the thymic origin and benign nature of the cyst preoperatively and differentiate it from cystic thymoma, lymphangioma, thymic carcinoma or lymphoma with confidence. As the haemorrhage resolved, the size of the swelling was significantly reduced, and the patient became asymptomatic due to which she deferred surgery but remained on close follow-up and was doing well. Thymic cysts can occur in a cervicomediastinal location, rare in elderly age, usually asymptomatic and clinically apparent when intracystic haemorrhage leads to an increase in size and chest pain.

Triage of patients with venous and lymphatic diseases during the COVID-19 pandemic - The Venous and Lymphatic Triage and Acuity Scale (VELTAS) : A consensus document of the International Union of Phlebology (UIP), Australasian College of Phlebology (ACP), American Vein and Lymphatic Society (AVLS), American Venous Forum (AVF), European College of Phlebology (ECoP), European Venous Forum (EVF), Interventional Radiology Society of Australasia (IRSA), Latin American Venous Forum, Pan-American Society of Phlebology and Lymphology and the Venous Association of India (VAI) This consensus document has been co-published in Phlebology [DOI: 10.1177/0268355520930884] and Journal of Vascular Surgery: Venous and Lymphatic Disorders [DOI: 10.1016/j.jvsv.2020.05.002]. The publications are identical except for minor stylistic and spelling differences in keeping with each journal's style. The contribution has been published under a Attribution-Non Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0), (https://creativecommons.org/licenses/by-nc-nd/4.0/).

The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semi-urgent (to be attended to within 30-90 days), example highly symptomatic chronic venous disease, and (4) discretionary/non-urgent- (to be seen within 6-12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.

Triage of patients with venous and lymphatic diseases during the COVID-19 pandemic - The Venous and Lymphatic Triage and Acuity Scale (VELTAS):: A consensus document of the International Union of Phlebology (UIP), Australasian College of Phlebology (ACP), American Vein and Lymphatic Society (AVLS), American Venous Forum (AVF), European College of Phlebology (ECoP), European Venous Forum (EVF), Interventional Radiology Society of Australasia (IRSA), Latin American Venous Forum, Pan-American Society of Phlebology and Lymphology and the Venous Association of India (VAI).

The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semiurgent (to be attended to within 30-90 days), example highly symptomatic chronic venous disease, and (4) discretionary/nonurgent- (to be seen within 6-12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.