Thrombotic sinusoiditis and local diffuse intrasinusoidal coagulation in the liver of subjects affected by COVID-19: the evidence from histology and scanning electron microscopy.

OBJECTIVE: Liver injury has been reported in patients with COVID-19. This condition is characterized by severe outcome and could be related with the ability of SARS-CoV-2 to activate cytotoxic T cells. The purpose of this study is to show the histological and scanning electron microscopy features of liver involvement in COVID-19 to characterize the liver changes caused by the activation of multiple molecular pathways following this infection. PATIENTS AND METHODS: Liver biopsies from 4 patients (3 post-mortems and 1 in vivo) with COVID-19 were analyzed with histology and by scanning electron microscopy. RESULTS: The liver changes showed significant heterogeneity. The first case showed ground glass hepatocytes and scattered fibrin aggregates in the sinusoidal lumen. The second evidenced intra-sinusoidal thrombi. The third was characterized by sinusoidal dilatation, atrophy of hepatocytes, Disse's spaces dilatation and intra-sinusoidal aggregates of fibrin and red blood cells. The fourth case exhibited diffuse fibrin aggregates in the dilated Disse spaces and microthrombi in the sinusoidal lumen. CONCLUSIONS: In COVID-19-related liver injury, a large spectrum of pathological changes was observed. The most peculiar features were very mild inflammation, intra-sinusoidal changes, including sinusoidal dilatation, thrombotic sinusoiditis and diffuse intra-sinusoidal fibrin deposition. These findings suggested that a thrombotic sinusoiditis followed by a local diffuse intra-vascular (intra-sinusoidal) coagulation could be the typical features of the SARS-CoV-2-related liver injury.

Thalidomide-induced granuloma annulare.

Granuloma annulare (GA) is an acquired, usually self-limiting, asymptomatic granulomatous skin disease with well recognized clinical and histological features that occurs in children and adults generally before the age of 30. Five clinical types are described including the localized, generalized, subcutaneous, perforating, and patch forms. The possible role of immune dysregulation has been pointed out in the pathogenesis of GA, as it has been reported in association with several diseases and conditions like diabetes, thyroid diseases, malignancies, tuberculosis, human immunodeficiency, Epstein Barr and hepatitis C virus infection. Drug-induced GA is a rare presentation, that can appear similar or identical to idiopathic GA. We present a 75-year-old Caucasian man with a violaceous ring-like firm, papular eruption, localized on the dorsal aspect of both hands, with histological features of GA, which subsequently resolved with the discontinuation of thalidomide he had started 1 month earlier for the treatment of a multiple myeloma. The lesions appeared with renewed intensity after resuming a therapy cycle. Jones's algorithm for the diagnosis of adverse drug reactions (ADR) showed a certain association, thus the final diagnosis of thalidomide-induced GA was made.