Prognostic significance of tumour budding, tumour–stroma ratio and desmoplastic stromal reaction in gall bladder carcinoma

Aims and methodsThe prognostic role of tumour budding (TBd) and its interaction with the stromal microenvironment has gained a lot of attention recently, but remains unexplored in gall bladder cancer (GBC). We aimed to study the interrelationship of TBd by International Tumour Budding Consensus Conference scoring system, tumour–stroma ratio (TSR) and desmoplastic stromal reaction (DSR) with the conventional clinicopathological prognostic factors, mortality and overall survival (OS) in 96 patients of operated GBC.ResultsHigher age, high TNM stage, lymphovascular and perineural invasion, positive resection margins, higher TBd score, low TSR and immature DSR were significantly associated with worse OS. However, on multivariate analysis, only metastases, positive resection margins and TSR <50% proved to be independent prognostic factors. The TBd score of stroma-rich tumour group (6.40±4.69) was significantly higher than that of stroma-poor group (2.77±3.79, p≤0.001). The TBd score of immature and intermediate DSR groups was significantly higher than that of mature group (p≤0.001 and p=0.002, respectively). There was a strong interobserver agreement for TBd score, TSR and type of DSR (Cohen’s Kappa=0.726 to 0.864, p≤0.001). Stroma-rich tumours were significantly associated with immature DSR and fibrotic DSR with high TSR (p≤0.001).ConclusionA high TBd, low TSR and immature DSR were significantly associated with several high-risk clinicopathological parameters and poor OS in GBC. These novel, simple, reproducible and cost-effective parameters may be included in the routine reporting checklist for GBC as additional prognostic parameters that can substratify the high-risk patients.

High-risk morphological features are less prevalent among small (<5mm) papillary thyroid microcarcinomas compared to larger (≥5mm) tumors: a study of 206 cases

Introduction: Papillary thyroid microcarcinoma (PTMC) is defined as a PTC measuring 1 cm or less, incidentally discovered. The aim of this study was to determine whether small (<5mm) tumors by contrast with large (≥5mm) ones are less frequently associated with high-risk morphological features, predictive of tumor aggressiveness. Materials and methods: All consecutive PTMC cases registered at the Department of Pathology, Târgu-Mureş Emergency County Hospital between 2003-2014 were reviewed. The following have been assessed: tumor size, subcapsular versus nonsubcapsular location, extrathyroidal extension/invasion into the perithyroidal adipose tissue, multifocality, resection margins, lymph node involvement, histological variant, tumor border, stromal reaction (fibrosis/desmoplasia/sclerosis), presence of plump pink cells, nuclear features of the tumor cells, intratumoral lymphocytic infiltrate, multinucleated giant cells, psammoma bodies and stromal calcification. The cases were split in two categories: small (< 5mm) and large (≥ 5mm) PTMCs and the pathological features were evaluated in comparison. Results: Our study included 206 cases, 91 large and 115 small PTMCs, respectively. Large PTMCs were significantly associated with the presence of plump pink cells (p=0.002), well developed PTC nuclear features (p=0.003), stromal reaction (fibrosis/desmoplasia/sclerosis) (p<0.001), infiltrative tumor border (p=0.011), subcapsular location (p<0.001), positive resection margins (p=0.022), stromal calcifications (p<0.001) and intratumoral multinucleated giant cells (p<0.001). Small PTMCs were generally well circumscribed and nonsubcapsular. Conclusions: Our results have shown that small (<5mm) PTMCs are less frequently associated with high-risk morphological features, predictive of tumor aggressiveness compared with large (≥5mm) tumors and could thus be considered as low-risk cancers.

Dynamic correlation between corneal sensitivity and subjective symptoms in patients with Chronic corneal ulcers

Purpose: This study assessed the correlation between corneal sensitivity and subjective symptoms in patients with chronic corneal ulcers before and after treatment. Methods: Corneal sensitivity was measured with Cochet-Bonnet aesthesiometry in twenty patients with mean age of53 years SD±20.65. Impression cytology was used to assess conjunctivalization, inflammation and keratinization. The epithelial integrity and stromal reaction were determined by anterior segment OCT. Treatment included either conservative measures or surgical ocular surface reconstruction. A questionnaire on subjective symptoms was implemented in order to obtain comparable data about their severity and effect on everyday life. Results: Mean corneal aesthesiometry was 143.03±81.68 mm/grms before treatment and 72.48±72.80 mm/grms on follow-up (p=0.001). An inverse correlation between age and corneal sensitivity was observed before treatment (p=0.002), but not after (p=0.102). Anterior segment OCT on follow-up demonstrated epithelialized corneal surface, reduced stromal reaction and scar tissue preventing further melting. All tested subjective symptoms demonstrated significant change after treatment except driving. Spearman’s analysis demonstrated a correlation between corneal sensitivity and pain (p=0.033), hyperemia (p=0.009) and driving (p=0.043). The change in corneal sensitivity correlated with tearing reduction (p=0.046) and prolonged tolerance to phone use (p=0.044). Conclusions: Cochet-Bonnet aesthesiometry is a useful diagnostic tool for evaluating corneal nerve function and monitoring the effect of treatment.

Expression of Extracellular Matrix-Related Genes and Their Regulatory microRNAs in Problematic Colorectal Polyps

Colorectal carcinoma usually evolves gradually, forming a spectrum of lesions, due to accumulation of genetic mutations and epigenetic alterations. Many early lesions are detected since the introduction of screening programs. The greatest challenge is to distinguish between adenomas with epithelial misplacement (AEM) and adenomas with early carcinoma (AEC), considering the diagnosis affects prognosis and treatment. We analyzed the expression of selected extracellular matrix (ECM)-related genes and proteins, and their regulatory microRNAs using RT-qPCR and immunohistochemistry in biopsies from 44 patients. Differences were observed in AEM in comparison to AEC for DCN, EPHA4, FN1, SPON2, and SPP1, reflecting inflammatory stromal reaction to traumatisation and misplacement of dysplastic glands in the submucosa in the former, and desmoplastic stromal reaction to true invasion of dysplastic glands in the submucosa in the latter. Expression of regulatory microRNAs hsa-miR-200c and hsa-miR-146a significantly negatively correlated with the expression of their regulated genes, while significant difference between AEM and AEC was observed only for hsa-miR-29c. The described expression patterns are too complex to be used in diagnostic work, but might contribute to better understanding ECM changes in colorectal carcinoma development, helping to find new markers in the future.

Histologic Findings of Uterine Niches

Objectives The disruption or defect of the myometrium in the uterine scar of a cesarean section (CS) has been known by various names, such as uterine niche, isthmocele, deficient uterine scar, scar pouch, or diverticulum. Symptomatology, risk factors for niche development, and available treatment modalities have been recently studied. However, the histologic features of this disease remain unknown. Methods The histologic features of eight uterine niches are thoroughly described and a summary of the most important aspects of the uterine niche literature is provided. Five cases of CS scars without niche formation are comparatively examined. Results Most uterine niches harbor endocervical mucosa, often cystically dilated and/or an atrophic or disorganized endometrial mucosa of lower uterine segment origin. Regenerative epithelial atypia and fibroblastic stromal reaction are frequent features. No granulomatous reaction, important inflammation, or hemorrhage is seen. CS scars without niche formation do not harbor endocervical mucosa or inclusion cysts, fibroblastic stroma, or regenerative atypia. Conclusions As more prospective studies of uterine niche development and treatment will be conducted, a detailed pathologic report with the criteria proposed herein can be designed.