Goodpasture syndrome is an autoimmune disease characterized by the simultaneous development of proliferative glomerulonephritis (typically crescentic) and necrotizing, hemorrhagic interstitial pneumonitis. Epidemiologically, it is associated with certain HLA subtypes and shows a male predominance; presentation is typically in the teens or twenties. Pathogenetically, IgG autoantibodies are directed against an epitope on the α3 chain of collagen IV. Collagen IV is non-fibrillar and is a key component of basement membranes. The autoantibody-induced basement membrane damage results in clinically significant glomerular and pulmonary injury. With respect to gross pulmonary disease, lungs are heavy, consolidated, and discolored red-brown. Microscopically, the Goodpasture syndrome lung shows focal alveolar wall necrosis with intra-alveolar acute hemorrhage and alveolar septal fibrotic thickening (Fig. 26.6).
In this example of Goodpasture syndrome, the lung shows extensive acute hemorrhage with focal interstitial thickening. From Travis et al. Atlas of Nontumor Pathology: Volume 2: Non-Neoplastic Disorders of the Lower Respiratory Tract, American Registry of Pathology; 2002.
CLINICAL CORRELATION 26.2
In the setting of suspected Goodpasture syndrome, immunofluorescence analysis of lung and/or kidney can be informative. In this disease, immunofluorescent labeling with IgG will show a linear basement membrane label of alveoli (Fig. 26.7) and glomeruli, rather than a granular basement membrane label typical of immune complex deposition. Immunofluorescence analysis requires frozen, nonfixed tissue. Consequently, in any situation in which immunofluorescence analysis would be helpful, it is important to promptly deliver fresh tissue to the pathologist to be frozen and sectioned for immunofluorescence labeling rather than placing the tissue in a fixative (eg, 10% formalin), as is typically done with biopsy specimens.
Immunofluorescent labeling of alveolar parenchyma with IgG. See Clinical Correlation 26.2 for more details. From Travis et al. Atlas of Nontumor Pathology: Volume 2: Non-Neoplastic Disorders of the Lower Respiratory Tract, American Registry of Pathology; 2002.
Clinically, the presentation of Goodpasture syndrome typically involves hemoptysis with the subsequent development of rapidly progressive renal insufficiency. Therapy involves removal of the pathologic autoantibodies by plasmapheresis and reduction of autoantibody production through immunosuppression.
Wegener's granulomatosis is a systemic vasculitis with a peak incidence in the fifth decade. Pathogenetically, it is likely a form of hypersensitivity, and patients typically have anti-neutrophil cytoplasmic antibodies with cytoplasmic localization (c-ANCA). Simplistically, the antibodies activate neutrophils, which then attack vascular luminal surfaces, resulting in vasculitis of small and medium-sized vessels. Like Goodpasture syndrome, the clinical scenario in Wegener's granulomatosis is dominated by simultaneous pulmonary and renal disease. Morphologically, respiratory tract involvement in Wegener's granulomatosis includes upper tract vasculitis, mucosal granulomata, and ulcers rimmed by granulomatous inflammation as well as lower tract necrotizing granulomatous inflammation (often with cavitation) and necrotizing or granulomatous vasculitis (Fig. 26.8). Renal involvement is typified by necrotizing glomerulonephritis, typically with crescent formation (extracapillary proliferation).
Wegener's granulomatosis. Granulomatous inflammation with a multinucleated giant cell (arrow) is in the center of the image. To the left is a mononuclear inflammatory infiltrate; to the right is necrosis infiltrated by neutrophils.
Idiopathic pulmonary hemosiderosis is a disease of children and young adults characterized by the insidious development of hemoptysis, anemia, and weight loss. Morphologically, lungs are heavy, consolidated, and discolored red to red-brown. Microscopically, lungs show alveolar epithelial degeneration, shedding, and hyperplasia; intra-alveolar siderophages; marked congestion of alveolar septal capillaries; and varying degrees of fibrosis.
CLINICAL CORRELATION 26.3
Figure 26.9 shows Prussian blue staining (Pearl reaction, iron stain) of the cytospin preparation from bronchoalveolar lavage fluid in the setting of idiopathic pulmonary hemosiderosis. Numerous hemosiderin-laden macrophages are seen, from which the disease takes its name. With this stain, hemosiderin is blue.
Prussian blue staining of the cytospin of cells recovered by bronchoalveolar lavage. See Clinical Correlation 26.3 for details.