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Background: Cancer-associated venous thromboembolism (VTE) is a critical complication in patients with cancer. However, the pathological findings of VTE are limited. Here, we investigated the histopathological features of cancer-associated VTE in human autopsy cases. Methods: We clinically examined the autopsy cases of VTE with (n=114) and without cancer (n=66) and immunohistochemically analyzed the expression of prothrombotic factors in intrathrombus cancer cells, the thrombus contents of erythrocytes, fibrin, platelets, citrullinated histone H3, and degree of organization. Results: Vascular wall invasion or small cell clusters of cancer cells was observed in thrombi in 27.5% of deep vein thrombosis and 25.9% of pulmonary embolism cases. The majority of the cancer cells in deep vein thrombi appeared to be invading the vessel wall, whereas the majority of pulmonary thrombi had cancer cell clusters, consistent with embolization via blood flow. These cancer cells were immunohistochemically positive for TF (tissue factors) or podoplanin in up to 88% of VTE cases. The frequency of TF-positive monocyte/macrophages in thrombi was higher in cancer-associated VTE than that in VTE without cancer. Citrullinated histone H3 was predominantly observed in the early stages of organizing thrombi. There was no significant difference in thrombus components between VTE with cancer and without cancer groups. Conclusions: Vascular wall invasion or cancer cell clusters in thrombi might influence thrombogenesis of cancer-associated VTE. TF and podoplanin in cancer cells and in monocyte/macrophages may induce coagulation reactions and platelet aggregation. Neutrophil extracellular traps may play a role in the early stages of VTE, regardless of cancer status.

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Placental inflammatory lesions are important findings that lead fetal and neonatal morbidity and mortality, and can be divided into two broad subcategories, acute inflammation caused by microorganisms and chronic inflammation caused by host immune responses. Recently, a diagnostic framework for these lesions has been established, and uniform diagnostic criteria have been recommended by the Amsterdam International Consensus Group. Chorioamnionitis is representative of the acute inflammatory lesion, and is the most frequent pathological diagnosis in placental pathology. The hallmark of chorioamnionitis is neutrophil infiltration in the membrane/chorioamnionic plate and fetal vessels. The inflammatory response can be both maternal (inflammation in the membrane or chorioamnionic plate) and fetal (inflammation in the fetal vessels-umbilical vessels or chorionic vessel). Recent studies have shown that the fetal inflammatory response is associated with neonatal mortality and morbidity. Furthermore, chronic inflammatory lesions, such as villitis of unknown etiology and chronic histiocytic intervillositis, are also important. Although their etiology remains unknown, the maternal immune response against paternal antigens has been considered a possible factor. These inflammatory lesions are associated with fetal demise and fetal growth restriction. Inflammatory lesions in the placenta are useful for understanding intrauterine conditions, guiding treatment, and predicting complications.

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The effects of interferon-gamma and interleukin-2 on liver regeneration after 70% hepatectomy in rats was studied immunohistologically, with special attention paid to major histocompatibility complex class II antigen expression. Liver regeneration 2 days after partial hepatectomy as assessed on the basis of bromodeoxyuridine labeling index revealed that regeneration was inhibited significantly in rats given a single dose of interleukin-2 or interferon-gamma compared with rats that underwent only partial hepatectomy. Simultaneous administration of interleukin-2 and interferon-gamma inhibited liver regeneration more markedly than administration of either drug. In rats subjected to partial hepatectomy, Kupffer cells around the portal vein expressed slightly more major histocompatibility complex class II antigen than did sham-operated controls. In the group given interferon-gamma, major histocompatibility complex class II antigen expression was markedly increased. Major histocompatibility complex class II antigen expression was greatest in most Kupffer cells of rats given both interleukin-2 and interferon-gamma. These results suggest that interferon-gamma activates (proliferating) Kupffer cells, in turn leading to suppression of liver regeneration. These major histocompatibility complex class II antigen-positive Kupffer cells act as antigen-presenting cells and present hepatocyte as antigen, the so-called abnormal self, to helper and cytotoxic T cells. Both types of T cells, in turn, may suppress hepatocyte proliferation. The various cytokines induced by the activated Kupffer cells and helper T cells seem to form a network with interferon-gamma to regulate liver regeneration.

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Aim To evaluate whether there is a stepwise increase in the prevalence of maternal clinical signs according to the severity of histological inflammation in the chorioamniotic membranes, placenta, and umbilical cord in preterm deliveries. Methods This retrospective study, conducted between January 2007 and May 2017, included patients with preterm delivery between 22 and 33 weeks. The histological findings of maternal/fetal inflammatory responses were staged and graded according to the Amsterdam Placental Workshop Group consensus statement. Correlations between the histological severity of maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and clinical signs were evaluated using the Cochran–Armitage trend test. Results A total of 138 patients were included. The stage and grade of the maternal inflammatory response were correlated with earlier gestational weeks at delivery and lighter birth weight. The prevalence of clinical chorioamnionitis was significantly correlated with a higher stage and grade of the maternal inflammatory response (Gibbs/Lencki criteria: 15.8%/15.8% in Stage 3, 16.3%/14% in Grade 2). No significant correlations were observed between gestational weeks at delivery and birth weight and stage/grade of fetal inflammatory response. The prevalence of clinical chorioamnionitis was significantly correlated with higher stage and grade of fetal inflammatory response (Gibbs/Lencki criteria: 25%/25% in Stage 3 and 29.4%/29.4% in Grade 2). Conclusion Correlations exist between the severity of histological maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and positive maternal clinical signs in preterm deliveries. However, the prevalence of clinical chorioamnionitis was 20%–30% even in the most severe fetal inflammatory responses.