A Frequent Diagnostic Pitfall: Dermatological Clinical Features and Pathological Results in Diagnosing Pagetoid Squamous Cell Carcinoma in situ (Case Series).

Squamous cell carcinoma (SCC) in situ can occur on any skin or mucus surface and is more commonly found in elderly patients on areas of skin that have been sunburnt. Most previous case reports are from dermatologists, with few published reports from pathologists. In this study, three patients underwent pathological routine and auxiliary immunohistochemical (IHC) examination and were ultimately diagnosed with pagetoid SCC in situ - a different diagnosis from the initial clinical assessment. All three patients received a complete resection of the skin mass. After follow-up, as of June 2023, the patients had no tumour recurrence or metastasis. Pagetoid SCC in situ is a particular type of SCC in situ that has no specific features in clinical manifestations, gross diagnosis or histopathological sections. The final diagnosis depends on IHC staining. Pagetoid SCC in situ expresses EMA, CK5/6 and p63 but not CEA, CK8 or S-100, which are expressed in extramammary Paget's disease. Pagetoid SCC in situ is usually only locally invasive, and the main treatment is complete surgical resection. The prognosis is related to human papillomavirus infection, surgical margin closure, disease location, tumour thickness and other factors.

Clinicopathological Analysis of Epstein-Barr Virus-Positive Inflammatory Follicular Dendritic Cell Sarcoma of the Spleen: A Case Report.

OBJECTIVE: The present study aims to explore the clinicopathological characteristics of Epstein-Barr virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (IFDCS; EBV+ IFDCS). CASE REPORT: The case involved a 32-year-old woman who underwent surgical resection of a splenic nodule. Histological examination and immunohistochemistry were performed using cluster of differentiation (CD) markers, and in-situ hybridization was conducted to detect EBV-encoded RNA (EBER). RESULTS: A microscopic analysis revealed neoplastic cells with various morphologies, including round, ovoid, or spindled shapes, dispersed within a prominent lymphoplasmacytic infiltrate. The tumor cells exhibited nuclear atypia, with some resembling Reed-Sternberg cells. The immunohistochemistry demonstrated focal positivity for follicular dendritic cell markers, such as CD21, CD23 and CD35, and focal negativity for other markers, including CD3, CD34, CD20, CD79a, myeloperoxidase and HMB45. Additionally, the EBER staining showed strongly positive results. The patient showed no local recurrence or metastasis during the 13-month follow-up. CONCLUSION: A comprehensive understanding of EBV+IFDCS, including its clinicopathological features and immunohistochemical characteristics, is crucial for accurate diagnosis and differential diagnosis of this rare tumor.

IGSF6 is a novel biomarker to evaluate immune infiltration in mismatch repair-proficient colorectal cancer.

Immunotherapy has dramatically changed the landscape of treatment for colorectal cancer (CRC), but currently lack of effective predictive biomarker, especially for tumors with mismatch repair (MMR) proficiency. The response of immunotherapy is associated with the cell-cell interactions in tumor microenvironment, encompassing processes such as cell-cell recognition, binding, and adhesion. However, the function of immunoglobulin superfamily (IGSF) genes in tumor immune microenvironment remains uncharacterized. This study quantified the immune landscape by leveraging a gene expression matrix from publicly accessible databases. The associations between IGSF6 gene expression and immune cell infiltration were assessed. The expression levels of IGSF6, CD8+ T cells, CD4+ T cells and CD68+ macrophage cells in cancer tissues from CRC patients and CRC cell lines were evaluated. IGSF6 was more highly expressed in CRC tumor tissues than adjacent normal tissues. And IGSF6 was significantly correlated with immune cell infiltration in MMR-proficient patients. Remarkably, MMR-proficient patients with high IGSF6 expression showed more sensitive to immunotherapy and chemotherapy than those with low IGSF6 expression. In summary, IGSF6 could be a novel biomarker to evaluate immune infiltration and predict therapeutic effect for MMR-proficient CRC.

Crohn's disease patients with L4-esophagogastroduodenal phenotype is associated with a better prognosis: A retrospective cohort study.

Background: In the Montreal classification, L4 Crohn's disease (CD) is defined as an ileal disease, including L4-esophagogastric duodenum (EGD), L4-jejunum, and L4-proximal ileal involvement. According to the previous studies, the prognosis of L4 disease was worse than that of non-L4 disease. Among L4 diseases, the phenotypes of L4-jejunum and L4-proximal ileum indicated that the risk of abdominal surgery was higher. However, the prognosis of L4-esophagogastroduodenal remains largely elusive. Therefore, we aim to investigate whether the prognosis differs between CD patients with and without esophagogastroduodenal involvement. Methods: In this study, patients with L4-EGD phenotype (n = 74) who underwent gastroscopy, ileocolonoscopy, biopsies, and CTE from 2018 to 2020 were compared with L4 non-EGD controls (n = 148) who were randomly selected at a ratio of 1:2 in the same period. Demographic information inclusive of disease conduct and location, important points of the surgery, and hospitalization have been collected. The distinction between L4-EGD patients and non-L4-EGD patients was identified by way of multivariable logistic regression analysis. The Kaplan-Meier technique was used to consider the possibility of abdominal surgical operation and complications, observed by means of Cox percentage hazard fashions to decide if L4 EGD independently estimated the endpoints inclusive of the abdominal surgery and the occurrences of complications. Results: L4-EGD group (n = 74) had a lower proportion of intestinal fistula than the control group (n = 148) (17.6% versus 34.5%; p = 0.009), and the probabilities of requiring abdominal surgery and multiple abdominal surgeries were also lower (21.6% versus 36.5%; p = 0.025), (6.8% versus 18.9%; p = 0.016), respectively. The frequency of hospitalization was lower in the L4-EGD group than in the control group (3-7 versus 4-9; p = 0.013). L4-EGD phenotype was found to be an independent protective factor for abdominal surgery and intestinal fistula in the Cox regression model, with HRs of 0.536 (95%CI: 0.305-0.940; p = 0.030) and 0.478 (95%CI: 0.259-0.881; p = 0.018), respectively. Conclusion: Our data suggest that the L4-EGD phenotype may have a better prognosis compared to the Non-L4-EGD phenotype. Our data may advocate a revision of the Montreal classification including separate designations for L4-EGD disease.

Identification of an Autophagy-Related Gene Signature for the Prediction of Prognosis in Early-Stage Colorectal Cancer.

Purpose: A certain number of early-stage colorectal cancer (CRC) patients suffer tumor recurrence after initial curative resection. In this context, an effective prognostic biomarker model is constantly in need. Autophagy exhibits a dual role in tumorigenesis. Our study aims to develop an autophagy-related gene (ATG) signature-based on high-throughput data analysis for disease-free survival (DFS) prognosis of patients with stage I/II CRC. Methods: Gene expression profiles and clinical information of CRC patients extracted from four public datasets were distributed to discovery and training cohort (GSE39582), validation cohort (TCGA CRC, n = 624), and meta-validation cohort (GSE37892 and GSE14333, n = 420). Autophagy genes significantly associated with prognosis were identified. Results: Among 655 autophagy-related genes, a 10-gene ATG signature, which was significantly associated with DFS in the training cohort (HR, 2.76[1.56-4.82]; p = 2.06 × 10-4), was constructed. The ATG signature, stratifying patients into high and low autophagy risk groups, was validated in the validation (HR, 2.29[1.15-4.55]; p = 1.5 × 10-2) and meta-validation cohorts (HR, 2.5[1.03-6.06]; p = 3.63 × 10-2) and proved to be prognostic in a multivariate analysis. Functional analysis revealed enrichment of several immune/inflammatory pathways in the high autophagy risk group, where increased infiltration of T regulatory cells (Tregs) and decreased infiltration of M1 macrophages were observed. Conclusion: Our study established a prognostic ATG signature that effectively predicted DFS for early-stage CRC patients. Meanwhile, the study also revealed the possible relationship among autophagy process, immune/inflammatory response, and tumorigenesis.

An 11-gene signature for the prediction of systemic recurrences in colon adenocarcinoma.

BACKGROUND: Prognosis varies among patients within the same colon adenocarcinoma (COAD) stage, indicating the need for reliable molecular markers to enable individualized treatment. This study aimed to investigate gene signatures that can be used for better prognostic prediction of COAD. METHODS: Gene-expression profiles of COAD patients were obtained from the Gene Expression Omnibus database (n = 332) and The Cancer Genome Atlas database (n = 431). The relationship between gene signature and relapse-free survival was analysed in the training set (n = 93) and validated in the internal validation set (n = 94) and external validation sets (n = 145 and 431). RESULTS: Overall, 11 genes (N-myc downstream regulated gene 1 [NDRG1], fms-like tyrosine kinase 1 [FLT1], lipopolysaccharide binding protein [LBP], fatty acid binding protein 4 [FABP4], adiponectin gene [ADIPOQ], angiotensinogen gene [AGT], activin A receptor, type II-like kinase 1 [ACVRL1], CC chemokine ligand 11 [CCL11], cell division cycle 42 [CDC42], T-cell receptor alpha variable 9_2 [TRAV9_2], and proopiomelanocortin [POMC]) were identified by univariable and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Based on the risk-score model, the patients were grouped into the high-risk or low-risk groups using the median risk score as the cut-off. The area under the curve (AUC) values for 1-, 3-, and 5-year recurrence were 0.970, 0.849, and 0.859, respectively. Patients in the high-risk group had significantly poorer relapse-free survival than did those in the low-risk group. The predictive accuracy of the 11-gene signature was proven in the validation sets. Our gene signature showed better predictive performance for 1-, 3-, and 5-year recurrence than did the other four models. CONCLUSIONS: The 11-gene signature showed good performance in predicting recurrence in COAD. The accuracy of the signature for prognostic classification requires further confirmation.

Glioblastoma in a female neurofibromatosis 1 patient without IDH1, BRAF V600E, and TERT promoter mutations: A case report.

RATIONALE: Glioblastoma is the most lethal and common malignant brain tumor but rare in patients with neurofibromatosis type 1. The clinical findings and pathological findings with gene signatures in female patients have not been well clarified. PATIENT CONCERNS: A 51-year-old female patient complained of headache and left limb weakness lasting for 20 days. The patient underwent a cesarean section 20 years ago and hysterectomy 1 year ago because of uterine leiomyomas. Multiple café-au-lait spots and neurofibromas were found over patient's chest, neck, back, and arms. The myodynamia of left distant and proximate epipodite were grade 0 and grade 1 respectively. The myodynamia of lower left limb was grade 3. DIAGNOSES: Magnetic resonance imaging revealed a malignant lesion which was most likely a glioblastoma in the right temporo-parietal lobe, approximately 5.6 × 5.9 × 6.9 cm in size with a rounded boundary. INTERVENTIONS: A right temporo-parietal craniotomy was performed to resect the space-occupying lesion for gross total removal. Then, the patient received concurrent chemoradiotherapy. Histological examination confirmed a glioblastoma without v-RAF murine sarcoma viral oncogene homolog B1 gene, isocitrate dehydrogenase 1 gene, and telomerase reverse transcriptase gene promoter mutations. OUTCOMES: After surgery, the headache was relieved and the muscular strength of left limbs did improve. After receiving the standard treatment regimen, the patient was alive at 13 months follow-up. LESSONS: This is the first reported glioblastoma in female neurofibromatosis type 1 patient without v-RAF murine sarcoma viral oncogene homolog B1 gene, isocitrate dehydrogenase 1 gene, and telomerase reverse transcriptase gene promoter mutations. Tumors in adult patients with these signatures were less aggressive with well-circumscribed border and had long-term survivals which strengthened the evidence that these patients may comprise a unique subset in glioblastoma.