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Dirty necrosis (DN) is a form of tumor necrosis (TN) with prominent neutrophil infiltration and cell detritus in the necrotic foci. This study aimed to characterize the clinicopathological features of DN in metastatic lung cancers of the colon and rectum (MLCRs). A total of 227 patients who underwent pulmonary metastasectomy and complete resection for MLCR were included in this study. TN was evaluated using digitally scanned resection specimens. These slides were immunostained for biomarkers of NETosis (citrullinated histone H3 [citH3] and myeloperoxidase [MPO]), and the area positive for citH3 and MPO was further quantified. TN was observed in 216 cases (95.2%), and 54 (25.0%) of these cases had DN. The presence of TN was not associated with a worse prognosis; however, patients with DN had a significantly shorter overall survival than those without DN (p 0.01). Furthermore, the presence of DN was a poor prognostic factor in both the univariate and multivariate analyses. Immunohistochemical analysis revealed that the percentage of citH3-positive and MPO-positive areas in the DN-positive cases was significantly higher than that in the DN-negative cases (p 0.01 and p 0.01, respectively). In surgically resected MLCR, DN is the characteristic TN subtype associated with poor prognosis and neutrophil extracellular traps (NETs).

The purpose of this study was to investigate the clinicopathological, gene expression and genetic features of stage I lung adenocarcinoma with necrosis.We retrospectively reviewed 521 cases with pathologic stage I lung adenocarcinoma resected by lobectomy and lymph node dissection. We calculated the ratio of tumor necrotic area by digital image analysis and investigated the relationship between tumor necrosis and prognosis. Furthermore, we analyzed the differentially expressed genes between cases with and without necrosis using The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) dataset. Using whole exon sequencing data (n = 97), we examined whether tumor necrosis correlates with single nucleotide variants (SNVs) and driver mutations.Eighty four (16%) cases of the study cohort had tumor necrosis. The presence of necrosis significantly correlated with poorer prognosis (5-year overall survival: 91.9% vs. 75.4%, p 0.001; 5-year recurrence-free survival: 86.0% vs. 59.0%, p 0.001); however, the ratio of necrotic area did not correlate with prognosis. In multivariable analysis, invasive component size, vascular invasion, and tumor necrosis were independently associated with a higher risk of recurrence (hazard ratio, 1.652; 95% confidence interval, 1.033-2.641; p = 0.036). Gene expression analysis of TCGA stage I lung adenocarcinoma revealed enrichment of biological processes, such as cell cycle and response to hypoxia, in cases with necrosis. The cases with tumor necrosis had more SNVs than those without tumor necrosis (p = 0.027), especially in smokers.Stage I lung adenocarcinoma with tumor necrosis has worse prognosis than that without, and has distinctclinicopathological features in terms of gene expression and genetic features.

Dirty necrosis (DN) in renal cell carcinoma (RCC) is morphologically characterized by abundant neutrophil infiltration and has significant potential as an unfavorable prognostic indicator. This study aimed to analyze the pathological and biological features of DN.A total of 81 RCC tumors, including 33 cases of DN and 48 cases of tumor necrosis without DN features (ghost necrosis [GN]), were enrolled in this study. We compared the number of neutrophils; the activation of cell death pathways, including ferroptosis, NETosis, and apoptosis; the rate of epithelial-mesenchymal transition (EMT); and proliferation status using immunohistochemistry. We further assessed the effect of the necrosis type on systemic inflammation.DN tumors had a significantly higher number of neutrophils in both areas around the necrotic foci and far from the necrotic foci. Ferroptosis status did not differ between DN and GN; however, DN tumors had significantly larger areas exhibiting cell detritus with neutrophil extracellular traps (NETs) detected by citrullinated histone H3 (citH3) than GN tumors. DN tumors also had more apoptotic cells within areas around the necrotic foci. There was no significant difference between the EMT and proliferation status between DN and GN groups. Systemic inflammation markers including C-reactive protein (CRP), CRP-to-albumin ratio (CRP/Alb), platelet-to-lymphocyte ratio (PLR), and hemoglobin were significantly higher in patients with DN. In addition, some of these inflammation markers (CRP/Alb and PLR) significantly decreased after surgery.DN in RCC is characterized by NETs production and systemic inflammation.

Tumor necrosis is a negative prognostic factor in various cancers. High-grade neuroendocrine carcinomas (HGNEC) of the lung, such as small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC), commonly have histopathological features of tumor necrosis. However, the prognostic value of tumor necrosis remains unknown.A total of 81 patients with HGNEC (SCLC, n = 42; LCNEC, n = 39) who underwent complete resection were enrolled. The proportion of necrosis in the tumor tissues was quantified using digital image analysis. We analyzed the relationship between the proportion of necrosis, clinicopathological factors, and prognosis. Moreover, we examined the correlation between genomic alterations and proportion of necrosis.The median proportion of necrosis was 10.6 % (range, 0-62.8 %). The proportion of necrosis was not significantly different between SCLC (median, 5.1 %; range, 0-62.8 %) and LCNEC (median: 14.2 %; range, 0-59.3 %) (p = 0.14). The cumulative incidence of recurrence (CIR) and lung cancer-specific cumulative incidence of death (LC-CID) were significantly higher in patients with 10 % or higher necrosis (necrosis ≥ 10 %) than in those with less than 10 % (necrosis10 %) (hazard ratio [HR], 2.94; 95 % confidence interval [CI], 1.30-6.64, and HR, 2.87; 95 % CI, 1.13-7.29, respectively). In the bivariate analysis, necrosis ≥ 10 % was independently associated with higher CIR and tended to be associated with higher LC-CID. The frequency of genomic alterations in the PI3K/AKT/mTOR pathway, MYC family, MAPK/ERK pathway, and major RTK signaling pathways were not different between the necrosis ≥ 10 % and necrosis10 % groups for both SCLC and LCNEC.High proportion of tumor necrosis (≥ 10 %) had a negative prognostic value in surgically resected HGNEC.

Tumor necrosis (TN) is one of the unfavorable prognostic factors in renal cell carcinoma (RCC). We identified two patterns of TN according to their morphology: dirty necrosis and ghost necrosis. We aimed to elucidate the morphological features and unfavorable prognostic impact of dirty necrosis in RCC. A total of 261 tumors collected after nephrectomy, which were pathologically identified as RCC, were analyzed in this study. We classified TN as dirty necrosis or ghost necrosis and compared their clinicopathological features. We also assessed their morphological features using digitally analyzed slides. The correlation between tumor size and necrosis area or the number of necrotic foci was calculated. There were 77 tumors (30%) with TN, and the presence of TN was significantly associated with unfavorable clinicopathological factors. Thirty tumors (39%) had dirty necrosis, and 47 tumors (61%) had ghost necrosis. There were significantly higher numbers of unfavorable factors associated with dirty necrosis than with ghost necrosis. In dirty necrosis, both the TN area and the number of necrotic foci were correlated with tumor size (p