Table 1.
Patients’ characteristics at first diagnosis
| Case | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | Patient 10 | Patient 11 | Patient 12 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age at diagnosis | 42 | 13 | 37 | 29 | 27 | 63 | 44 | 55 | 53 | 59 | 27 | 52 |
| Sex | Female | Female | Female | Male | Female | Female | Female | Male | Female | Male | Male | Male |
| Symptoms | Chyloptysis, haemoptysis | Dyspnoea, cough, haemoptysis | Dyspnea, fatigue | Chyloptysish, haemoptysis, night sweating, loss of weight, pericarditis | Dyspnea, chyloptysis, fatigue, night sweating | Dyspnea, chyloptysis, pneumothorax | Dyspnea, haemoptysis, cough | Dyspnea | Dyspnea, cough, white sputum, join pain | Dyspnea, cough | Hemoptysis, dyspnea, night sweats, chylous fluid obtained during thoracenteses | Dyspnea, thoracic pain while breathing |
| Smoking Status | Non-smoker | Non-smoker | 6 py (ex-smoker) | 16 py (ex-smoker) | Non-smoker | Non-smoker | Non-smoker | Non-smoker | Non-smoker | Non-smoker | 4 pack-years (ex-smoker) | Non-Smoker |
| Comorbidities | Autoimmun-Thyreoiditis | None | Melanoma, arterial hypertension, hyperlipidemia | Right heart insufficiency, liver cysts, nephrolithiasis, cholecystolithiasis | None | Pulmonary embolism, arterial hypertension, chronic kidney failure, thyroid hypofunction, chronic pain syndrome | None | Coronary calcifications, cholecystolithiasis, arterial hypertension | Asthma, diabetes mellitus 2, thyroid hypofunction, arterial hypertension, hepatic steatosis | Arterial hypertension, depression, factor V Leiden mutation, spinal stenosis, spondylarthrosis, degenerative scoliosis, sulcus ulnaris syndrome, coxarthrosis, gonarthrosis | Pulmonary embolism, sinus tachycardia, autoimmune thyroiditis | Littoral cell angioma, thyroid hypofunction, arterial hypertension |
| Medication at diagnosis | Thyroxine, citaloprame, oral contraceptive | None | None | Digoxine,torasemide, metoprolol, pantoprazol, oxycodone, morphin | Inhalative beclometasone/formoterole, pantoprazole, thyroxine | Furosemide, spironolacton, pantoprazole, tilidin | Pantoprazole, hydrochlorothiazide, potassium | Bisoprolol, torasemide, vitamin B complex | inhaled corticosteroid/long-acting beta-agonist, long-acting anticholinergics, salbutamol, thyroxine, dapagliflozin, sartan, hydrochlorothiazide, ibuprofen, magnesium | None | Rivaroxaban, methylprednisolone, metoprolol | Thyroxine, sartan |
| FVC (l/%) at baseline | 3.46/99 | 0.89/24 | 3.62/102 | 1.34/26 | 3.62/93 | – | 1.30/36 | -/60 | 2.62/83 | 1.94/36 | 2.87/43 | 2.35/46 |
| FEV1 (l/%) at baseline | 2.29/76 | 0.814/26 | 3.01/99 | 1.23/30 | 2.74/81 | – | 1.26/43 | 2.41/62 | 2.30/91 | 1.63/40 | 2.40/44 | 1.56/39 |
| FEV1%FVC (%) at baseline | 63 | 92 | 84 | 92 | 76 | – | 96 | 82 | 88 | 81 | 84 | 65 |
| DLCO SB (mmol/min/kPa/%) at baseline | 6.54/72.7 | n.a. | n.a. | n.a. | 9.76/64 | – | 8.40/35 | -/83 | 6.55/86 | 5.35/49 | – | 6.48/62 |
| 6MWD (m) | 535 | n.a | 500 | – | – | 252 | 285 | – | – | 485 | 358 | – |
| Histology | Bronchial vascular and subpleural ectatisis lymphatics intra-alveolar hemorrhages. Lymphatic vessels D2-40 -positive | Lymphangiomas with lymphoid endothelial cells. Lymphatic vessels D2-40 -positive | Fibromuscular soft tissue with endothelial lined cavities; CD34 and D2-40 positive | Benign lymphohematoid lesion mediastinal lymphangioma | Soft tissue with lymphangioma | Soft tissue with lymphangioma | Dilated lymphatic vessels (D2-40, CD31, CD34 positive) besides lymphoidcellaggregation | No evidence for lymphangiectasia or lymphangiomatosis | No evidence for lymphangiectasia or lymphangiomatosis | Conspicuous vessel architecture (CD31 and D2-40 positive) | H&E-stained and D2-40 immunohistochemistry of lung tissue showing dilated lymphatic vessels, secondary changes, including thickened pleura, bullous alveoli and organizing pneumonia | Dilated lymphatic vessels (D2-40 positive) |
| Diagnostic procedure | Surgical lung biopsy (SLB): 1 sample (wedge biopsy), from diseased, sample size 6 × 3x2cm |
SLB: 2 wedge biopsies, from diseased, sample size 12.5 × 9.3x6.5 cm and 13.8 × 4.2x4.1 cm |
SLB: 1 sample from mediastinal tumor + pericard + thymus, from diseased, max. sample size 4 × 3x1cm | SLB: samples from pleura, from diseased, max. sample size 17 × 112x4cm | SLB: 1 wedge biopsy and samples from mediastinum + pericard, from diseased, sample size max. 4.3 × 1.3x1.3 cm | SLB: 1 from mediastinal tumor, from diseased, sample size 7.5 × 3.7x1cm | Transbronchial cryo-biopsy (TBCB): 4 samples, from diseased, sample size max. 0.6 cm | SLB: 1 sample from pleura, random location, sample size 2.5 × 1.8x0.8 cm | Endo bronchial biopsy (EBB): 2 samples, from diseased, sample size max. 0.3 cm | EBB: 5 samples from 2 different locations, from diseased, sample size max. 1,2 cm | SLB: 1 atypical resection, from diseased, sample size 9 × 2.8x2.4 cm | EBB: 1 sample, from diseased, sample size max. 1.3 cm |
| VEGF-D (ng/ml) | – | – | – | – | 0.390 | – | – | 0.407 | – | 0.248 | – | 0.019 |