Lymphangiopathy in neurofibromatosis 1 manifesting with chylothorax, pericardial effusion, and leg edema

Josef Finsterer,1 Claudia Stollberger,2 Elisabeth Stubenberger,3 Sasan Tschakoschian4 1Krankenanstalt Rudolfstiftung, Vienna, Austria; 2Medical Department, Krankenanstalt Rudolfstiftung, Vienna, Austria; 3Thoracic Surgery Department, Vienna, Austria; 4Interne Lungenabt, Vienna, Austria Background: This case report documents the affliction of the lymph vessels as a phenotypic feature of neurofibromatosis-1 (NF-1). Methodology: Routine transthoracic echocardiography, computed tomography scan of the thorax, magnetic resonance angiography of the renal arteries, and conventional digital subtraction angiography were applied. Comprehensive NF-1 mutation analysis was carried out by fluorescence in situ hybridization analysis, long-range reverse transcriptase polymerase chain reaction, and multiple-ligation probe assay. All other investigations were performed using routine, well-established techniques. Results: The subject is a 34-year-old, half-Chinese male; NF-1 was suspected at age 15 years for the first time. His medical history included preterm birth, mild facial dysmorphism, "café au lait" spots, subcutaneous and paravertebral fibromas, multifocal tachycardia, atrial fibrillation, and heart failure in early infancy. Noncalcified bone fibromas in the femur and tibia were detected at age 8 years. Surgical right leg lengthening was carried out at age 11 years. Bilateral renal artery stenosis, stenosis and aneurysm of the superior mesenteric artery, and an infrarenal aortic stenosis were detected at age 15 years. Leg edema and ectasia of the basilar artery were diagnosed at age 18 years. After an episode with an erysipela at age 34 years, he developed pericardial and pleural effusion during a 4-month period. Stenosis of the left subclavian vein at the level of thoracic duct insertion was detected. After repeated pleural punctures, pleural effusion was interpreted as chylothorax. Reduction of lymph fluid production by diet and injection of talcum into the pleural cavity had a long-term beneficial effect on the chylothorax. Leg edema and chylothorax were attributed to affliction of the lymph vessels by the NF-1. Discussion: Lymphangiopathy resulting in impaired lymph fluid flow and sequestration of lymph fluid into the pleural sinus and the legs may be a rare phenotypic feature of NF-1. Keywords: angiodysplasia, lymph edema, lymph fluid, Recklinghausen's disease, genetics, mutatio

Biomarkers for Malignant Pleural Mesothelioma—A Novel View on Inflammation

Malignant pleural mesothelioma (MPM) is an aggressive disease with limited treatment response and devastating prognosis. Exposure to asbestos and chronic inflammation are acknowledged as main risk factors. Since immune therapy evolved as a promising novel treatment modality, we want to reevaluate and summarize the role of the inflammatory system in MPM. This review focuses on local tumor associated inflammation on the one hand and systemic inflammatory markers, and their impact on MPM outcome, on the other hand. Identification of new biomarkers helps to select optimal patient tailored therapy, avoid ineffective treatment with its related side effects and consequently improves patient’s outcome in this rare disease. Additionally, a better understanding of the tumor promoting and tumor suppressing inflammatory processes, influencing MPM pathogenesis and progression, might also reveal possible new targets for MPM treatment. After reviewing the currently available literature and according to our own research, it is concluded that the suppression of the specific immune system and the activation of its innate counterpart are crucial drivers of MPM aggressiveness translating to poor patient outcome

Biomarkers for Malignant Pleural Mesothelioma—A Novel View on Inflammation

Malignant pleural mesothelioma (MPM) is an aggressive disease with limited treatment response and devastating prognosis. Exposure to asbestos and chronic inflammation are acknowledged as main risk factors. Since immune therapy evolved as a promising novel treatment modality, we want to reevaluate and summarize the role of the inflammatory system in MPM. This review focuses on local tumor associated inflammation on the one hand and systemic inflammatory markers, and their impact on MPM outcome, on the other hand. Identification of new biomarkers helps to select optimal patient tailored therapy, avoid ineffective treatment with its related side effects and consequently improves patient’s outcome in this rare disease. Additionally, a better understanding of the tumor promoting and tumor suppressing inflammatory processes, influencing MPM pathogenesis and progression, might also reveal possible new targets for MPM treatment. After reviewing the currently available literature and according to our own research, it is concluded that the suppression of the specific immune system and the activation of its innate counterpart are crucial drivers of MPM aggressiveness translating to poor patient outcome