Pulmonary Vascular Lesions in Chronic Thromboembolic Pulmonary Hypertension

Abstract

To the Editor:We thank Dr. Kay for expressing his views. However, we respectfully disagree with his conclusions, for the reasons enumerated below.In our article, we grouped together under the term “plexogenic,” lesions which others have subgrouped into “plexiform” or “angiomatoid” lesions. We, and other experienced pathologists who reviewed these lesions, think they are clearly plexiform lesions, not recanalized thrombotic lesions. Further, these lesions are consistent with the definition of such lesions used in two other, related studies by Lloyd et al1Yaginuma G Mohri H Takahashi T Distribution of arterial lesions and collateral pathways in the pulmonary hypertension of congenital heart disease: a computer-aided reconstruction study.Thorax. 1990; 45: 586-590Crossref PubMed Scopus (49) Google Scholar and Pietra et al.2Lloyd JE Atkinson JB Pietra CC Virmani RN Newman JH Heterogeneity of pathology lesions in familial primary pulmonary hypertension.Am Rev Respir Dis. 1988; 138: 952-957Crossref Scopus (82) Google Scholar We curiously find Dr. Kay's assertion that, based on Yaginuma's paper,3Pietra CC Edwards WD Kay JM Histopathology of primary pulmonary hypertension.Circulation. 1989; 89: 1198-1206Crossref Scopus (398) Google Scholar plexiform lesions occur only in vessels 100- to 150-μm diameter when Pietra's report, of which Dr. Kay was a co-author, indicates that such lesions were present in vessels 100- to 300-μm diameter.Substantial literature exists indicating that plexiform lesions are not specific to primary pulmonary hypertension. In addition to the several references in our paper documenting this, we note that early experimental studies by Liebow and his colleagues4Downing SE Vidone RA Brandt HM The pathogenesis of vascular lesions in experimental hyperkinetic pulmonary hypertension.Am J Pathol. 1963; 43: 739-765PubMed Google Scholar, 5Saldana ME Harley RA Liebow AA Experimental extreme pulmonary hypertension and vascular disease in relation to polycythemia.Am J Pathol. 1968; 52: 935-981PubMed Google Scholar, 6Friedman PJ Direct magnification angiography and correlative pathophysiology in experimental pulmonary hypertension.Invest Radiol. 1972; 7: 474-495Crossref PubMed Scopus (6) Google Scholar indicating that the plexiform lesions arise from phenomena related to increased pressure and flow, phenomena which occur in multiple clinical contexts.We certainly cannot accept the statement that such lesions have never been found in patients with chronic thromboembolic pulmonary hypertension. As we pointed out in our paper, the references cited by Dr. Kay (Presti B, et al, Hum Pathol 1990; 21:601-06; Wagenvoort CA, Mooi WJ, Biopsy pathology of the pulmonary vasculature, 1989; and Harris P, Heath D, Human pulmonary circulation, 1986), which we carefully reviewed, do not contain adequate hemodynamic or microscopic information to allow one to reach such a conclusion. Importantly, which patients had chronic, major vessel thromboembolic pulmonary hypertension is not clear. Indeed, as we indicated, the only paper which included clearly defined patients with CT-E PH did indicate that “dilatation lesions” were common.7Anderson EG Simon G Reid L Primary and thromboembolic pulmonary hypertension.J Pathol. 1972; 110: 273-293Crossref Scopus (52) Google ScholarTherefore, we stand strongly behind our concluding statement which is, to reiterate it, that the diagnosis of potentially surgically remediable chronic, major vessel thromboembolic pulmonary hypertension should not be deterred by the finding of small vessel “pulmonary hypertensive” lesions on lung biopsy, including plexogenic lesions. Certainly, all would agree that the most frequent lesions in the small arteries of pulmonary hypertensive patients are muscular hypertrophy, intimal proliferation, and thrombosis—and such lesions lack differential diagnostic value.The “bottom line,” as our large experience documents, is that lung biopsy findings cannot and should not be relied on to distinguish among the various pulmonary hypertensive disorders. Such reliance can be particularly harmful to patients with chronic major vessel thromboembolic pulmonary hypertension if it dissuades physicians from pursuing diagnostic studies that could lead to a correct diagnosis and a potential surgical cure by pulmonary thromboendarterectomy. We expect that ongoing research will, ultimately, define those mediators which induce medial hypertrophy, intimal proliferation, thrombotic lesions, and the vessel injury which plexogenic lesions represent. As these insights are gained, physicians must diligently pursue the differential diagnosis of pulmonary hypertensive states because the therapy of the various forms deviates so widely. In this differential diagnostic pursuit, in our view, the small vessel arterial changes available from lung biopsy are of limited—if any value and, if wrongly interpreted, they can deflect physicians from the correct diagnosis. To the Editor: We thank Dr. Kay for expressing his views. However, we respectfully disagree with his conclusions, for the reasons enumerated below. In our article, we grouped together under the term “plexogenic,” lesions which others have subgrouped into “plexiform” or “angiomatoid” lesions. We, and other experienced pathologists who reviewed these lesions, think they are clearly plexiform lesions, not recanalized thrombotic lesions. Further, these lesions are consistent with the definition of such lesions used in two other, related studies by Lloyd et al1Yaginuma G Mohri H Takahashi T Distribution of arterial lesions and collateral pathways in the pulmonary hypertension of congenital heart disease: a computer-aided reconstruction study.Thorax. 1990; 45: 586-590Crossref PubMed Scopus (49) Google Scholar and Pietra et al.2Lloyd JE Atkinson JB Pietra CC Virmani RN Newman JH Heterogeneity of pathology lesions in familial primary pulmonary hypertension.Am Rev Respir Dis. 1988; 138: 952-957Crossref Scopus (82) Google Scholar We curiously find Dr. Kay's assertion that, based on Yaginuma's paper,3Pietra CC Edwards WD Kay JM Histopathology of primary pulmonary hypertension.Circulation. 1989; 89: 1198-1206Crossref Scopus (398) Google Scholar plexiform lesions occur only in vessels 100- to 150-μm diameter when Pietra's report, of which Dr. Kay was a co-author, indicates that such lesions were present in vessels 100- to 300-μm diameter. Substantial literature exists indicating that plexiform lesions are not specific to primary pulmonary hypertension. In addition to the several references in our paper documenting this, we note that early experimental studies by Liebow and his colleagues4Downing SE Vidone RA Brandt HM The pathogenesis of vascular lesions in experimental hyperkinetic pulmonary hypertension.Am J Pathol. 1963; 43: 739-765PubMed Google Scholar, 5Saldana ME Harley RA Liebow AA Experimental extreme pulmonary hypertension and vascular disease in relation to polycythemia.Am J Pathol. 1968; 52: 935-981PubMed Google Scholar, 6Friedman PJ Direct magnification angiography and correlative pathophysiology in experimental pulmonary hypertension.Invest Radiol. 1972; 7: 474-495Crossref PubMed Scopus (6) Google Scholar indicating that the plexiform lesions arise from phenomena related to increased pressure and flow, phenomena which occur in multiple clinical contexts. We certainly cannot accept the statement that such lesions have never been found in patients with chronic thromboembolic pulmonary hypertension. As we pointed out in our paper, the references cited by Dr. Kay (Presti B, et al, Hum Pathol 1990; 21:601-06; Wagenvoort CA, Mooi WJ, Biopsy pathology of the pulmonary vasculature, 1989; and Harris P, Heath D, Human pulmonary circulation, 1986), which we carefully reviewed, do not contain adequate hemodynamic or microscopic information to allow one to reach such a conclusion. Importantly, which patients had chronic, major vessel thromboembolic pulmonary hypertension is not clear. Indeed, as we indicated, the only paper which included clearly defined patients with CT-E PH did indicate that “dilatation lesions” were common.7Anderson EG Simon G Reid L Primary and thromboembolic pulmonary hypertension.J Pathol. 1972; 110: 273-293Crossref Scopus (52) Google Scholar Therefore, we stand strongly behind our concluding statement which is, to reiterate it, that the diagnosis of potentially surgically remediable chronic, major vessel thromboembolic pulmonary hypertension should not be deterred by the finding of small vessel “pulmonary hypertensive” lesions on lung biopsy, including plexogenic lesions. Certainly, all would agree that the most frequent lesions in the small arteries of pulmonary hypertensive patients are muscular hypertrophy, intimal proliferation, and thrombosis—and such lesions lack differential diagnostic value. The “bottom line,” as our large experience documents, is that lung biopsy findings cannot and should not be relied on to distinguish among the various pulmonary hypertensive disorders. Such reliance can be particularly harmful to patients with chronic major vessel thromboembolic pulmonary hypertension if it dissuades physicians from pursuing diagnostic studies that could lead to a correct diagnosis and a potential surgical cure by pulmonary thromboendarterectomy. We expect that ongoing research will, ultimately, define those mediators which induce medial hypertrophy, intimal proliferation, thrombotic lesions, and the vessel injury which plexogenic lesions represent. As these insights are gained, physicians must diligently pursue the differential diagnosis of pulmonary hypertensive states because the therapy of the various forms deviates so widely. In this differential diagnostic pursuit, in our view, the small vessel arterial changes available from lung biopsy are of limited—if any value and, if wrongly interpreted, they can deflect physicians from the correct diagnosis. Pulmonary Vascular Lesions in Chronic Thromboembolic Pulmonary HypertensionCHESTVol. 105Issue 5PreviewTo the Editor: Full-Text PDF