Morphologic features of extrahepatic manifestations of hepatitis C virus infection

Huaibin M Ko, Juan C Hernandez-Prera, Hongfa Zhu, Steven H Dikman, Harleen K Sidhu, Stephen C Ward, Swan N Thung, Huaibin M Ko, Juan C Hernandez-Prera, Hongfa Zhu, Steven H Dikman, Harleen K Sidhu, Stephen C Ward, Swan N Thung

Abstract

Cirrhosis and hepatocellular carcinoma are the prototypic complications of chronic hepatitis C virus infection in the liver. However, hepatitis C virus also affects a variety of other organs that may lead to significant morbidity and mortality. Extrahepatic manifestations of hepatitis C infection include a multitude of disease processes affecting the small vessels, skin, kidneys, salivary gland, eyes, thyroid, and immunologic system. The majority of these conditions are thought to be immune mediated. The most documented of these entities is mixed cryoglobulinemia. Morphologically, immune complex depositions can be identified in small vessels and glomerular capillary walls, leading to leukoclastic vasculitis in the skin and membranoproliferative glomerulonephritis in the kidney. Other HCV-associated entities include porphyria cutanea tarda, lichen planus, necrolytic acral erythema, membranous glomerulonephritis, diabetic nephropathy, B-cell non-Hodgkin lymphomas, insulin resistance, sialadenitis, sicca syndrome, and autoimmune thyroiditis. This paper highlights the histomorphologic features of these processes, which are typically characterized by chronic inflammation, immune complex deposition, and immunoproliferative disease in the affected organ.

Figures

Figure 1
Figure 1
Leukocytoclastic vasculitis: predominantly lymphocytic mixed inflammatory infiltrate involving small vessels in the dermis (hematoxylin-eosin, original magnification ×200).
Figure 2
Figure 2
Leukocytoclastic vasculitis: fibrinoid necrosis of dermal vessels (hematoxylin-eosin, original magnification ×100) (photo courtesy of Dr. Rajendra Singh).
Figure 3
Figure 3
Membranoproliferative glomerulonephritis: PAS-positive “hyaline thrombi” seen within the capillary lumina (PAS, original magnification ×400).
Figure 4
Figure 4
Membranoproliferative glomerulonephritis: endocapillary proliferation with extensive subendothelial deposits along the glomerular capillary walls. Mesangial deposits are present as well (electron microscopy).
Figure 5
Figure 5
Membranoproliferative glomerulonephritis: subendothelial electron dense deposits in a patient with mixed essential cryoglobulinemia showing microtubular architecture. Microtubules measure approximately 30 nm in diameter (electron microscopy).
Figure 6
Figure 6
Porphyria cutanea tarda: subepidermal bulla and festooning of the dermal papilla are prominent. There is no significant inflammatory infiltrate (hematoxylin-eosin, original magnification ×100).
Figure 7
Figure 7
Lichen planus: there is a band-like infiltrate of lymphocytes at the epidermal-dermal junction with damage to the basal cell layer and pigment incontinence. The epidermis has a saw-toothed appearance (hematoxylin-eosin, original magnification ×200).
Figure 8
Figure 8
Necrolytic acral erythema: epidermal pallor in the stratum corneum, hyperkeratosis, dyskeratotic keratinocytes, spongiosis, and a superficial perivascular mixed inflammatory infiltrate in the dermis are seen (hematoxylin-eosin, original magnification ×200) (photo courtesy of Dr. Rajendra Singh).
Figure 9
Figure 9
Diabetic Nephropathy: extensive mesangial expansion is seen, with rounded acellular mesangial nodules (Kimmelstiel-Wilson nodules) (hematoxylin-eosin and PAS, original magnification ×400).
Figure 10
Figure 10
Marginal zone lymphoma of the spleen: (A) there is effacement of splenic architecture by sheets of monotonous small-to-medium size lymphocytes (hematoxylin-eosin, original magnification ×200). Immunohistochemical stains show that the lymphocytes are positive for BCL2 (B) and CD20 (C), and negative for CD10 (D) (immunoperoxidase, original magnifications ×200 ((A) through (D))).
Figure 11
Figure 11
Sialadenitis: there is extensive lymphoid infiltrate with interstitial fibrosis and acinar atrophy (hematoxylin-eosin, original magnification ×100).
Figure 12
Figure 12
Hashimoto thyroiditis: there is extensive lymphocytic infiltrate with germinal center formation. Follicular cells are slightly enlarged with partial nuclear clearing (hematoxylin-eosin, original magnification ×100).
Figure 13
Figure 13
Graves disease: there is follicular hyperplasia with intracellular colloid droplets, cell scalloping, a reduction in follicular colloid, and a multifocal lymphocytic infiltrate (hematoxylin-eosin, original magnification ×200).

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