Figures
- Fig. 1—
Intimal fibrosis of alveolar interstitial vessels. No distinction could be made between arteriole and venule on the basis of anatomic localisation (elastica von Gieson stain). a) Concentric intimal fibrosis (case 2, table 3⇑) and b, c) complete obliteration (case 6, table 3⇑). Original magnification: a and b) ×200, c)×100.
- Fig. 2—
a) Pulmonary veno-occlusive disease (PVOD) pattern with patchy capillary congestion (arrows; case 4, table 3⇑). b) PVOD pattern with patchy capillary congestion (arrow), deposition of iron salts on elastine fibres (black arrowhead) and giant cells (white arrowhead; case 2, table 3⇑). c) PVOD pattern with patchy capillary congestion (arrows), iron deposition on elastine fibres and vasculitis with transmural infiltration of lymphocytes (dashed arrow; case 2, table 3⇑). Haematoxylin and eosin stain. Original magnification: ×100.
- Fig. 3—
a) Single lesion in the systemic sclerosis-associated pulmonary arterial hypertension (PAH) group mostly resembling a plexiform lesion (case 3, table 3⇑): localisation adjacent to a bronchiolus (arrow); intimal fibrosis with recanalisation (black arrowheads); and dilated vessel segments (white arrowhead). b) Plexiform lesion in a patient with idiopathic PAH adjacent to a feeding artery, with intimal fibrosis and slit-like channels lined by cuboidal endothelial cells (arrowhead) and dilated vessel segments (arrow; case 19, table 3⇑). a) elastica von Gieson stain, b) haematoxylin and eosin stain. Original magnification: ×100.
- Fig. 4—
a, b) Pulmonary artery with concentric laminar intimal fibrosis and some perivascular mononuclear cell infiltration (case 6, table 3⇑). a) Haematoxylin and eosin stain, b) elastica von Gieson stain. Original magnification: ×200.
Tables
- Table 1—
Characteristics of systemic sclerosis patients
Subjects 8 LcSSc 8 (100) Disease duration# yr 10±4 Antibody profile Anti-nuclear antibody 8 (100) Anti-centromere 6 (75) Anti-ribonucleoprotein 1 (12.5) Anti-phospholipid auto-antibodies 0 Pericardial effusion 3 CT abnormalities associated with PVOD 7 Lymphadenopathy 3 Septal lines 3 Ground glass 6 Data are presented as n, n (%) or mean±se. LcSSc: limited cutaneous systemic sclerosis; CT: computed tomography; PVOD: pulmonary veno-occlusive disease. #: since first non-Raynaud symptom, at time of diagnosis of pulmonary arterial hypertension.
- Table 2—
Haemodynamic, lung function and exercise data at pulmonary arterial hypertension(PAH) diagnosis
SScPAH IPAH p-value Subjects n 8 11 P̄ra mmHg 8 (3–15)/6 10 (4–19)/9 0.30 Ppa,sys mmHg 73 (35–101)/8 100 (62–128)/11 0.15 P̄pa mmHg 45 (25–71)/8 60 (43–76)/9 0.08 PCWP mmHg 7 (4–12)/8 7 (5–12)/9 0.57 PVR dyn·s·cm−5 654 (227–3278)/6 920 (346–1587)/9 0.41 CI L·min·m2 2.4 (1.1–3.6)/6 2.5 (1.3–3.2)/9 0.69 FEV1 % pred 88 (77–97) 80 (66–86) 0.15 TLC % pred 88 (81–115)/6 93 (78–115)/9 0.78 VC % pred 97 (84–115)/7 89 (58–110)/8 0.34 TL,CO % pred 40 (26–58)/7 68 (39–89)/10 0.01 TL,CO/VA % 39 (26–69)/7 58.5 (52–87)/10 0.01 Pa,O2mmHg 73 (58–88) 65.5 (52–80) 0.46 6MWD m 278 (0–382) 400 (100–570) 0.15 Smoking history (never/current/former) n 0/0/3 0/0/3 Therapy at time of death Prostacycline n 7 10 ERA n 1 1 PDE-5 inhibitor n 1 ABS n 2 Data are presented as median (range)/n or median (range), unless otherwise stated. SScPAH: systemic sclerosis-associated PAH; IPAH: idiopathic PAH; P̄ra: mean right atrial pressure; Ppa,sys: systolic pulmonary artery pressure; P̄pa: mean pulmonary artery pressure; PCWP: pulmonary capillary wedge pressure; PVR: pulmonary vascular resistance; CI: cardiac index; FEV1; forced expiratory volume in 1 s; % pred: % predicted; TLC: total long capacity; VC: vital capacity; TL,CO: transfer factor of the lung for carbon monoxide; VA: alveolar volume; Pa,O2: arterial oxygen tension; 6MWD: 6-min walk distance; ERA: endothelin receptor antagonist; PDE-5: phosphodiesterase 5; ABS: atrial balloon septostomy.
- Table 3—
Parameters of pulmonary vascular morphology: systemic-sclerosis associated pulmonary arterial hypertension (PAH)
Case no.# Lung sample Plexiform lesions PTEIF Concentric laminar intimal fibrosis SVIF PVOD/CH HV Congestion¶ IFV/interlobular veins PVI/vasculitis+ Pneumonitis§ Fibrosisƒ 1 LTX N Y Y## Y N N 1 N 2 3 1 2 A N Y N Y Y## N 1 Y 1 1 N 3 A N N N Y## N N N Y 1+3 2 N 4 A N Y N Y Y## N 1 Y N 1 N 5 B N Y Y Y N N N Y N 2 N 6 A N Y Y Y Y## N 2 Y 1 2 N 7 LTX N Y N Y## N N N Y N 4 2+3 8 A N Y N Y## Y## N 1 Y 1 N N 9 A N Y N Y## N N N N 2 1 N 10 A Y## Y N N N N 3 N 2 1 N 11 LTX Y## Y N N N N N N 2 1 N 12 A Y## Y N N N N 1+3 Y 2 N N 13 A Y## Y N N N N 1+3 N N 1 N 14 A Y## Y N Y N N 1+3 Y 1 N N 15 A Y## Y## N N N N N N N 1 N 16 A Y## Y N N N N 1+3 N N N N 17 A Y## Y N N N N N Y 1 N N 18 A Y## Y N Y N N N N N 1 N 19 A Y## Y N N N N N N N N N PTEIF: post-thrombotic eccentric intimal fibrosis; SVIF: small vessel intimal fibrosis; PVOD: pulmonary veno-occlusive disease; CH: capillary haemangiomatosis; HV: hypoxic vasculopathy; IFV: intimal fibrosis venules; PVI: pulmonary vascular inflammation. N: no; Y: yes; A: autopsy; B: biopsy. #: cases 1 to 8 : systemic sclerosis-associated PAH; cases 9 to 19: idiopathic PAH; ¶: 1 = diffuse; 2 = patchy; 3 = vasodilation related; LTX: lung explantation; +: 1 = lymphocytic; 2 = perivascular infiltrate, insufficient for vasculitis; 3 = granulocytic; §: 1 = sparse interstitial aggregates; 2 = diffuse interstitial infiltrate, mild, no fibrosis; 3 = diffuse interstitial infiltrate, moderate, no fibrosis; 4 = diffuse interstitial infiltrate and fibrosis; 5 = infiltrate confined to fibrotic areas; ƒ: 1 = mild, some interstitial fibrosis; 2 = moderate, architectural changes; 3 = severe, honeycombing; ##: predominant pattern.
