Background COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital. Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.Methods We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020. The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h. Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.Findings All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases). The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases). Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.Interpretation The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent. Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.

SARS2‐CoV‐2 breakout in Italy caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection, very few information are available about liver involvement, possibly evocating a systemic disease. Post‐mortem wedge liver biopsies from 48 patients died from severe pulmonary COVID‐19 disease with respiratory failure were collected from two main hospitals in northern Italy. No patient had clinical symptoms of liver disease or signs of liver failure before and during hospitalization; for each of them liver function tests were available. All liver samples showed minimal inflammation features. Histological pictures compatible with vascular alterations were observed, characterized by increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic. SARS‐CoV‐2 was found in 15 of 22 samples tested by in situ hybridization method. Our preliminary results confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage. Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels. It still remains unclear if the mentioned changes are directly related to virus infection or if SARS‐CoV‐2 triggers a series of reactions leading to striking vascular alterations.

Asian series have shown 5 year survival of ∼70% after resection of hepatocellular cancer (HCC) <2cm. Western outcomes with resection have not been as good. In addition ablation of HCC ≤ 2cm has been shown to achieve competitive results leaving the role of resection unclear in these patients. Records of patients undergoing resection at two Western centers between 1/1990 and 12/2009 were reviewed. Patients with a single HCC ≤ 2cm on pathology were included. Thirty clinical variables including demographics, liver function, tumor characteristics, nature of the surgery, and the surrounding liver were examined. An exploratory statistical analysis was conducted to determine variables associated with recurrence and survival. The study included 132 patients with a median follow-up of 37.5 months. There was 1 (<1%) 90-day mortality. There were 32 deaths with a median survival of 74.5 months and 5-year survival of 70% (63% in cirrhotics). Median time-to-recurrence was 31.6 months and 5-year recurrence rate was 68%. Presence of satellites (HR=2.46, p=0.031) and platelet count <150,000/μl (HR=2.37, p=0.026) were independently associated with survival. Presence of satellites (HR=2.79, p=0.003), cirrhosis (HR=2.3, p=0.010), and non-anatomic resection (HR=1.79, p=0.031) were independently associated with recurrence. Patients with a single HCC ≤ 2cm and platelet count ≥150,000/μl achieved median and 5-year survivals of 138 months and 81%, respectively. Conclusion Resection of HCC ≤ 2cm is safe and achieves excellent results in Western centers. Recurrence continues to be a significant problem. Presence of satellites, platelet count, anatomic resection and cirrhosis are associated with outcomes after resection even among such early tumors. Resection should continue to be considered a primary treatment modality in patients with small HCC and well preserved liver function.

Importance. The analysis of lung tissues of patients with COVID-19 may help understand pathogenesis and clinical outcomes in this life-threatening respiratory illness. Objective.To determine the histological patterns in lung tissue of patients with severe COVID-19.Design and participants. Lungs tissues of 38 cases who died for COVID-19 in two hospital of Northern Italy were systematically analysed. Hematoxylin-eosin staining, immunohistochemistry for the inflammatory infiltrate and cellular components, electron microscopy were performed.Results. The features of the exudative and proliferative phases of Diffuse Alveolar Disease (DAD) were found: capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia, platelet-fibrin thrombi. The inflammatory infiltrate was composed by macrophages in alveolar lumens and lymphocytes mainly in the interstice. Electron microscopy revealed viral particles in the cytoplasm of pneumocytes.Conclusions and relevance. The predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERS-CoV. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy.

A personalized approach aimed to treat recurrent hepatocarcinoma is possible through analysis of tumoral molecular pathways. Partial success of the selected combination of sorafenib and everolimus supports the pivotal role of mTOR signalling and highlights the importance of reliable biomarkers to route the best molecular-based therapeutic options in HCC.