A Rare Case of Massive Gastrointestinal Bleeding as a Cause of Death in a Young Adult with Catastrophic Granulomatosis Polyangiitis

AUTOPSY FINDINGS (DR UMA NAHAR SAIKIA)

Good morning, everyone. Indeed, the patient had GPA; however, it was refractory to treatment and catastrophic in spite of adequate treatment leading to complications and the demise of the patient.

A complete autopsy was performed on this patient. Prosectors at the time of the autopsy noticed 1 L of straw-colored fluid in the peritoneal cavity. The pleural and pericardial cavities did not reveal any excess fluid.

Lungs: Both lungs weighed 1600 gm, heavy double the normal weight and diffusely firm to feel. The pleura of both lungs were thickened with the presence of pleural tags (Fig. 1A). On the cut section, the upper lobes of both lungs were consolidated, whereas the lower lungs showed diffuse hemorrhagic areas (Fig. 1B). The upper lobes showed numerous small cavitary nodular lesions coalescing to form large lesions with central areas of necrosis adjacent to the segmental bronchi causing bronchial destruction and centered around pulmonary vessels (Fig. 1B). The periphery of these lesions appeared brownish, with adjacent lung parenchyma showing consolidation.

Microscopic examination showed thickened pleura due to deposition of fibrin admixed with mixed inflammatory cells and fibrosis with vascular proliferation resulting in fibrinous pleuritis. The underlying lung parenchyma showed multiple nodular necrotising lesions of variable size, which were vasculocentric and bronchocentric with central areas of necrosis bordered by dense inflammatory infiltrate with predominant population of neutrophils and nuclear debris admixed with fibrin (Fig. 1C). The inflammation at the periphery of these lesions comprised of lymphocytes, plasma cells with very few multinucleated giant cells destroying the muscular and cartilage layers of bronchial wall with ulceration of bronchial epithelium. Occasional blood vessels near the nodular lesions showed fibrinoid necrosis of the wall with transmural extensive neutrophilic debris and luminal occlusion. The adjacent alveoli show features of capillaritis with neutrophilic infiltration and red blood cell extravasation along with intra-alveolar fibrin deposition (Fig. 1D). Focally, the large arteries and venules showed features of necrotizing vasculitis with endothelial lifting, fibrin deposition, and deposition of myxoid material beneath the internal elastic lamina (Fig.1E). However, no well-formed granulomas were seen in any of the microscopic sections though occasional multinucleated giant cells were seen in the wall of larger veins (Fig.1G). In addition, chronic lesions were also noted in the vessels in the form of fibrosis, hyalinization, subendothelial edema, and narrowing of the lumen. Recanalized thrombi accompanied by reduplication and disruption of the internal elastic lamina was highlighted by elastic Van Gieson stain around cavitary lesions suggesting vascular involvement (Fig.1F). Furthermore, hemosiderin-laden macrophages were seen in sections from the brownish discolored area around these lesions. The immunofluorescence performed for IgG, IgA, and complement component (C3) were negative in the lung tissue.

The microscopy of hemorrhagic consolidated areas in both lungs showed confluent bronchopneumonia having mixed inflammatory infiltrates rich in neutrophils with focal organization, causing obliteration of the bronchial lumen. The adjacent lung revealed alveolar hemorrhage. The Gram Twort highlighted gram-negative cocci within these areas. Focally alveoli showed exuberant type 2 pneumocyte hyperplasia with diffuse alveolar damage by the presence of eosinophilic material deposition lang alveolar wall highlighted on Periodic acid-Schiff’s (PAS) stain (Fig. 1H).

Kidneys: Both weighed 370 gm. The renal arteries were patent without narrowing of the lumen and thrombosis macroscopically. Grossly, both kidneys were swollen with mottling on the external surface, and no petechial lesions were seen (Figs 2A and B). The cut surface shows distinct corticomedullary differentiation; no focal lesions were seen. On microscopy, glomeruli were crowded due to tubular loss and interstitial fibrosis secondary to ischemia caused by the vasculitic process (Fig. 2C). Almost all the glomeruli showed varying ages of crescents (Fig. 2C), including cellular to fibrocellular and fibrous crescents, with underlying tufts demonstrating basement membrane thickening and wrinkling with a break in the Bowman’s capsule highlighted on PAS stain (Fig. 2D). There were no necrotizing lesions, no fibrin thrombi noted within the glomeruli and no granulomas or giant cells were seen. The interlobular small vessels show recanalization thrombi with endothelial swelling accompanied by edema (Figs 2E and F). The tubules show hyaline casts and focal calcification. The arcuate vessels and branches of the main renal artery did not show any active vasculitis or thrombosis. Immunofluorescence on renal tissue was negative for IgG, IgA, and IgM. However, focal 2+ granular deposits of C3 were seen along the capillaries.

The adrenals show features of shock information of lipid depletion and no vasculitis.

Liver: The liver weighed 1600 gm, mildly enlarged with smooth outer and cut surface showed exaggerated mottling (Fig. 2G). There were no nodules and thrombosis of the portal veins. The microscopic examination of the liver shows preserved lobular architecture; there is no evidence of active or healed vasculitis. There was mild sinusoidal congestion in the centrizonal areas (Fig. 2H). The pancreas was grossly unremarkable. The pancreatic and peri-pancreatic blood vessels also do not show active or healed vasculitis.

Spleen: The spleen was shrunken and weighed 80 gm. The cut surface reveals multiple infarcts with scarring leading to prominent crenulations of its borders (Fig. 3A). The microscopy of the spleen reveals thickened capsule with a peripheral old infarct bordered by hyalinization and hemosiderin-laden macrophages (Fig.3B). The hilar and parenchymal blood vessels showed recanalized thrombus with luminal narrowing (Fig.3C). There were no features of active vasculitis in these blood vessels.

Grossly, the small intestine, ileocecal valve, and ascending colon show multiple hemorrhagic lesions surrounded by a blood clot, which were more prominent in the ascending colon (Fig. 3D). These lesions were very firm with ulcerated overlying mucosa (Fig. 3E). The microscopy of these lesions shows linear ulceration of the mucosa covered with fibrin-rich exudates, bacterial colonies, and pauci-cellular inflammatory infiltrate (Figs 3F and G). The underlying capillaries show fresh fibrin thrombi. The adjacent nonulcerated mucosa shows extensive mucosal and submucosal hemorrhage with fibrin thrombi in the capillaries (Fig. 3H). The submucosal vessels showed luminal occlusion due to fibro intimal hyperplasia. The esophagus and stomach also show similar morphological findings (Fig. 3H). The mesenteric and celiac blood vessels do not show features of active or healed vasculitis.

The microscopy from both testes showed features of healed vasculitis in testicular blood vessels along with thickening of the basement membrane of seminiferous tubules due to ischemia (Fig. 4).

Heart: The heart weighed 310 gm. The right inflow and outflow tracts were normal, except for right ventricular thickening, which measured 6 mL. The left inflow and outflow tract show subendocardial hemorrhages (Fig. 4A). Grossly, coronaries do not display any luminal narrowing or thrombosis. Microscopy of the left marginal artery shows intimal proliferation and subendothelial edema with perivascular inflammation extending into the vessel wall (Fig. 4B). The adjacent myocardium shows interstitial edema and no myocardial injury. Similar morphological findings were also observed in the pericardial blood vessels (Fig. 4C). However, sections from the left ventricle, coronary and mural blood vessels do not show any features of vasculitis (Figs 4G and E).

The brain was grossly normal and weighed 1100 gm; microscopic sections revealed capillary hemorrhages with fibrin thrombi in the white matter and the cerebellum (Figs 4F and G).

Lymph nodes and bone marrow show features of hemophagocytosis.