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Other non-neoplastic disease

Pulmonary hypertension

Reviewers: Elliot Weisenberg, M.D. (see Reviewers page)
Revised: 18 August 2013, last major update December 2011
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Clinical features

● Defined clinically as mean resting pulmonary artery pressure > 25 mm Hg or systolic > 30 mm Hg, usually not symptomatic until 60 mm Hg
● Also defined as 25% or more of systemic pressure (normal is 10%)
● Classified based on consensus conference (J Am Coll Cardiol 2009;54:43)

Pulmonary arterial hypertension (PAH):
● Idiopathic
● Familial
● Associated with: collagen vascular disease, congenital systemic to pulmonary shunts, portal hypertension, HIV infection, drugs and toxins (historically diet drug fenfluramine and phentermine fen-phen), other
● Associated with significant venous or capillary involvement: a) Pulmonary venous occlusive disease, b) Pulmonary capillary hemangiomatosis

Pulmonary venous hypertension:
● Left sided atrial or ventricular heart disease
● Left sided valvular heart disease

Pulmonary hypertension associated with hypoxemia:
● Interstitial lung disease
● Sleep-disordered breathing
● Alveolar-hypoventilation disorders
● Chronic exposure to high altitudes

Pulmonary hypertension due to chronic thrombotic or embolic disease:
● Thromboembolic obstruction of proximal pulmonary arteries
● Thromboembolic obstruction of distal pulmonary arteries
● Nonthrombotic pulmonary embolism (tumor, parasites and foreign material)
● Miscellaneous (sarcoidosis, Langerhan cell histiocytosis and compression of pulmonary vessels)

● In secondary forms, endothelial cell dysfunction initiates the disorder; causes decreased production of nitric oxide and prostacyclin and increased levels of endothelin, leading to endothelial cell activation, constriction and thrombogenesis; usually women ages 20-40 years; some patients have vasospastic element

● Sporadic, requires exclusion of other known causes
● Usually women 20-40 years old
● Sometimes children are initially asymptomatic, then shortness of breath, fatigue, angina, progressing to right ventricular hypertrophy, cor pulmonale, pulmonary emboli or pneumonia

● Rare, autosomal dominant with incomplete penetrance
● Mutations in bone morphogenic protein receptor 2 signalling pathway (BMPR2)


● Vasodilators, calcium channel blockers, nitric oxide, antithrombotic medications, prostacyclin analogues, endothelial cell receptor antgonists, phosphodiesterase-5 inhibitors and lung transplant in selective patients
● Disease reversible if arterial lesions restricted to medial hypertrophy, intimal thickening of longitudinal smooth muscle or cellular intimal proliferation

Gross images


Micro description

● Organizing thrombi (suggests recurrent pulmonary emboli)
● Interstitial fibrosis if hypoxia
● Changes in major vessels / branches are similar to systemic atherosclerosis
● Small vessels have medial hypertrophy and intimal fibrosis, which may narrow lumina to pinpoint
Plexogenic arteriopathy: tuft of capillaries spanning lumina of arteries, changes can be quantified using Reid index

Plexiform arteriopathy


● Historical term based on lesions induced by congenital heart disease
● Heath and Edwards Classification from 1958 (modified below) still in widespread use
● Open lung biopsy in patients with congenital heart disease may be performed to determine if corrective vascular surgery will be beneficial

Micro description

Grade I (early):
● Muscularization and media hypertrophy (> 7% of lumen) of pulmonary arteries

Grade II:
● Intimal hyperplasia causing attenuation of vascular lumen

Grade III:
● Subintimal fibrosis with onion-ring appearance
● Marked reduplication of internal elastic membrane
● Arteries and arterioles resemble pipes

Grade IV to V:
● Dilation and plexiform lesions, aneurysmal dilation of small pulmonary arteries, plexiform and glomeruloid nodules
● Fibrin thrombi within plexiform lesion, old / new hemorrhage present

Grade VI:
● Uncommon, acute necrotizing arteritis with fibrinoid necrosis and acute inflammation of vessel wall, similar to polyarteritis nodosa
● Associated with extreme pulmonary hypertension

Micro images

Plexiform lesion: note: lesions #2-#4 are actually from secondary hypertension

Differential diagnosis

Secondary pulmonary hypertension: similar histology, different history

Thrombotic pulmonary hypertension


● Often young women with collagen vascular disease

Micro description

● Recent and organized intravascular thrombi
● Eccentric intimal fibrous plaques, bands and septa
● Recanalization may resemble a plexiform lesion
● No marked intimal fibroplasia, no plexiform lesions and no arteritis

Differential diagnosis

● Plexogenic hypertension: may also have thromboemboli

Multiple pulmonary emboli


● Older men and women, emboli cause pulmonary hypertension

End of Lung-nontumor > Other non-neoplastic disease > Pulmonary hypertension

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