Ulcerative colitis (UC) is defined as an idiopathic inflammatory disorder primarily involving the mucosa and submucosa of the colon. UC-associated colon cancers (also known as colitic cancers) develop through the inflammation–dysplasia sequence, which is a major problem affecting the prognosis of patients with UC. It is therefore very important to detect malignancy from UC at an early stage. As precancerous lesions arising in UC, there are pathological adenomatous changes, basal cell changes, in situ anaplasia, clear cell changes, and pan-cellular change. It is considered that the mutation of the p53 gene plays a crucial role, and the protein expression of p53 in dysplastic crypts may serve as a good biomarker in the early stages of UC-associated colon carcinogenesis. Immunohistochemistry for p53 is a very valuable diagnostic tool in UC-associated colon cancers. However, protein expression of p53 is not always universal, and additional methods may be required to assess p53 status in UC-associated colon cancers.

Chromophobe renal cell carcinoma (chRCC) is a renal tumor subtype with a good prognosis, characterized by multiple chromosomal copy number variations (CNV). The World Health Organization (WHO) chRCC classification guidelines define a classic and an eosinophilic variant. Large cells with reticular cytoplasm and prominent cell membranes (pale cells) are characteristic for classic chRCC. Classic and eosinophilic variants were defined in 42 Swiss chRCCs, 119 Japanese chRCCs and in whole-slide digital images of 66 chRCCs from the Cancer Genome Atlas (TCGA) kidney chromophobe (KICH) dataset. 32 of 42 (76.2%) Swiss chRCCs, 90 of 119 (75.6%) Japanese chRCCs and 53 of 66 (80.3%) TCGA-KICH were classic chRCCs. There was no survival difference between eosinophilic and classic chRCC in all three cohorts. To identify a genotype/phenotype correlation, we performed a genome-wide CNV analysis using Affymetrix OncoScan^® CNV Assay (Affymetrix/Thermo Fisher Scientific, Waltham, MA, USA) in 33 Swiss chRCCs. TCGA-KICH subtypes were compared with TCGA CNV data. In the combined Swiss and TCGA-KICH cohorts, losses of chromosome 1, 2, 6, 10, 13, and 17 were significantly more frequent in classic chRCC (p < 0.05, each), suggesting that classic chRCC are characterized by higher chromosomal instability. This molecular difference justifies the definition of two chRCC variants. Absence of pale cells could be used as main histological criterion to define the eosinophilic variant of chRCC.

Purpose: Upregulation of type I interferon (IFN) signaling has been increasingly detected in inflammatory diseases. Recently, upregulation of the IFN signature has been suggested as a potential biomarker of IFN-driven inflammatory diseases. Yet, it remains unclear to what extent type I IFN is involved in the pathogenesis of undifferentiated inflammatory diseases. This study aimed to quantify the type I IFN signature in clinically undiagnosed patients and assess clinical characteristics in those with a high IFN signature.Methods: The type I IFN signature was measured in patients’ whole blood cells. Clinical and biological data were collected retrospectively, and an intensive genetic analysis was performed in undiagnosed patients with a high IFN signature.Results: A total of 117 samples from 94 patients with inflammatory diseases, including 37 undiagnosed cases, were analyzed. Increased IFN signaling was observed in 19 undiagnosed patients, with 10 exhibiting clinical features commonly found in type I interferonopathies. Skin manifestations, observed in eight patients, were macroscopically and histologically similar to those found in proteasome-associated autoinflammatory syndrome. Genetic analysis identified novel mutations in the PSMB8 gene of one patient, and rare variants of unknown significance in genes linked to type I IFN signaling in four patients. A JAK inhibitor effectively treated the patient with the PSMB8 mutations. Patients with clinically quiescent idiopathic pulmonary hemosiderosis and A20 haploinsufficiency showed enhanced IFN signaling.Conclusions: Half of the patients examined in this study, with undifferentiated inflammatory diseases, clinically quiescent A20 haploinsufficiency, or idiopathic pulmonary hemosiderosis, had an elevated type I IFN signature.

Kawaguchi M, et al. Korean J Radiol. 2020 Jan;21:e8. https://doi.org/10.3348/kjr.2019.0508

Background: The recent improvement of peroral cholangioscopy (POCS) maneuverability has enabled the precise, targeted biopsy of bile duct lesions under direct cholangioscopic vision. However, as only small-cup biopsy forceps can pass through the scope channel, the resulting small sample size may limit the pathological diagnosis of biopsy specimens. This study compared the diagnostic abilities of POCS-guided biopsy and conventional fluoroscopy-guided biopsy for bile duct cancer. Method: This multicenter, retrospective cohort study included patients exhibiting bile duct stricture with suspected cholangiocarcinoma in whom POCS-guided and fluoroscopy-guided biopsies were performed in the same session. The primary endpoint was the diagnostic sensitivity for malignancy. The size and quality of the biopsy specimens were also compared. Result: A total of 59 patients were enrolled. The sensitivity of POCS-guided biopsy was similar to that of fluoroscopy-guided biopsy (54.0% and 64.0%, respectively). However, when the modalities were combined, the sensitivity increased to 80.0%. The mean specimen size from POCS-guided biopsy was significantly smaller than that from fluoroscopy-guided biopsy. The specimen quality using fluoroscopy-guided biopsy was also better than that using POCS-guided biopsy. Conclusions: The diagnostic sensitivity of POCS-guided biopsy is still insufficient, mainly because of the limited specimen quantity and quality. Therefore, conventional fluoroscopy-guided biopsy would be helpful to improve diagnostic sensitivity.

Proto-oncogene survivin is a member of the inhibitor of apoptosis (IAP) family of proteins. The presence of serous antibodies against survivin in patients with systemic sclerosis has been previously reported; however, there are few reports regarding the pathophysiological relationship between survivin and systemic sclerosis. We herein investigated the expression and function of survivin in SSc patients. We performed immunohistochemistry analyses to determine the expression of XIAP, cIAP and survivin in skin lesions from patients with SSc and non-SSc. The expression levels of survivin in peripheral blood mononuclear cells (PBMCs) obtained from SSc patients and healthy controls were evaluated using RT-PCR and flow cytometry. Additionally, the function of survivin was verified with overexpression experiments using monocyte-derived dendritic cells (Mo-DCs). The expression patterns of both XIAP and cIAP were similar, while only the survivin expression differed between the SSc and non-SSc skin lesions. Survivin-overexpressing cells were detected in the SSc dermis frequently. The positive rate of survivin in SSc dermis (64.3 %, 9/14) was higher than that in non-SSc dermis (11.2 %, 1/9). Furthermore, survivin+ cells expressed CD1a, one of the DC markers. Real-time PCR and FACS analyses revealed that the survivin-WT (wild type) expression levels in PBMCs, in particular CD14+ monocytes, from SSc patients were higher than that from healthy controls. Additionally, the overexpression experiments showed that survivin-WT-overexpressing CD1a+ Mo-DCs have the characteristics of promoting cell cycle progression and decreasing apoptotic cells. These findings suggest that dermal survivin+ CD1a+ cell infiltration may be a potential biomarker of SSc skin lesions. PBMCs and monocytes from SSc patients also overexpressed survivin; therefore, dermal survivin+ DC may be derived from peripheral blood monocytes. Additionally, survivin may be involved in dermal CD1a+ DC proliferation through cell cycle activation and resistance to apoptosis. Survivin may be an important molecule for the pathogenesis of SSc.