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Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread. [ABSTRACT FROM AUTHOR]

A structural weakness of the mucus barrier (MB) is thought to be a cause of ulcerative colitis (UC). This study aims to investigate the mucin (MUC) composition of MB in normal mucosa and UC. Ileocolonic biopsies were taken at disease onset and after treatment in 40 patients, including 20 with relapsing and 20 with remitting UC. Ileocolonic biopsies from 10 non-IBD patients were included as controls. Gut-specific MUC1, MUC2, MUC4, MUC5B, MUC12, MUC13, MUC15, and MUC17 were evaluated immunohistochemically. The promoters of mucin genes were also examined. Normal mucosa showed MUC2, MUC5B, and MUC13 in terminal ileum and colon, MUC17 in ileum, and MUC1, MUC4, MUC12, and MUC15 in colon. Membranous, cytoplasmic and vacuolar expressions were highlighted. Overall, the mucin expression was abnormal in UC. Derangements in MUC1, MUC4, and MUC5B were detected both at onset and after treatment. MUC2 and MUC13 were unaffected. Sequence analysis revealed glucocorticoid-responsive elements in the MUC1 promoter, retinoic-acid-responsive elements in the MUC4 promoter, and butyrate-responsive elements in the MUC5B promoter. In conclusion, MUCs exhibited distinct expression patterns in the gut. Their expression was disrupted in UC, regardless of the treatment protocols. Abnormal MUC1, MUC4, and MUC5B expression marked the barrier dysfunction in UC. [ABSTRACT FROM AUTHOR]

Mucosal healing (MH) is the main treatment target in ulcerative colitis (UC) and Crohn's disease, and it is defined by the combination of complete endoscopic and histologic remission. The complete resolution of mucosal inflammation should be confirmed by histology but its assessment is not always univocal. Neutrophil infiltration represents the unique histological marker in discriminating the active vs. quiescent phases of the disease, together with crypt injuries (cryptitis and crypt abscesses), erosions, and ulcerations. On the contrary, basal plasmacytosis is not indicative of activity or the remission of inflammatory bowel diseases (IBDs) but instead represents a diagnostic clue, mostly at the onset. Several histological scoring systems have been developed to assess grade severity, particularly for UC. However, most are complex and/or subjective. The aim of this review was to summarize available scores, their characteristics and limitations, and to present the advantages of a simplified mucosa healing scheme (SHMHS) based on neutrophils and their distribution in the gut mucosa. Finally, we overview future developments including artificial intelligence models for standardization of disease assessments and novel molecular markers of inflammation with potential application in diagnostic practice. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) and Crohn's Disease (CD) are chronic relapsing inflammatory diseases that are caused by genetic, environmental, and immune factors. Treatment strategies are currently based on symptomatic control by immunosuppression. The glucocorticoid-induced leucine zipper (GILZ), a mediator of several effects of glucocorticoids, was recently found to be secreted by goblet cells and play a role in inflammatory bowel disease (IBD). This study investigates which genes GILZ is associated with in its role in intestinal barrier functions. We examined datasets from the Gene Expression Omnibus (GEO) and ArrayExpress profiles of the gut of healthy subjects (HSs), as well as UC and CD patients. The human colonic epithelial HT29 cell line was used for in vitro validation experiments. GILZ was significantly correlated with MUC2, TLR2, and TLR4. In particular, an inverse correlation was found between the GILZ and MUC2 in HS and patients with IBD, mostly in those with an active disease. Further, direct pairwise correlations for GILZ/TLR2 and GILZ/TLR4 were found in HSs and UC patients, but not in CD patients. Overall, our results reveal the crosstalk at the transcription level between the GILZ, MUC2, and TLRs in the mucosal barrier through common pathways, and they open up new perspectives in terms of mucosal healing in IBD patients. [ABSTRACT FROM AUTHOR]

Lichen planus (LP) is an immune-mediated chronic inflammatory disease affecting the skin and mucosal membranes, either alone or in combination. LP rarely occurs in the larynx, where it presents as leukoplakia. Additionally, due to its responsiveness to corticosteroid drugs, differential diagnosis from other causes of laryngeal leukoplakia is needed (e.g., dysplasia and squamous cell carcinoma [SCC]). A 71 years old male smoker presented with progressive hoarseness and cough without fever. Vocal folds' motility was preserved. At fiberoptic laryngoscopy, he presented with bilateral cordal erythema and leukoplakia of the right true vocal fold. A sub-epithelial CO2 laser cordectomy was performed. Histological findings were consistent with mucosal LP. After surgical excision, the patient experienced symptomatic relief without medical treatment. A relapsing lesion became clinically evident six months later. A pinch biopsy was performed, and the histological examination confirmed the presence of laryngeal-LP. Hence, the patient underwent a 10-week corticosteroid-based treatment. After that, and during the subsequent 12 months of follow-up, the patient showed no signs of recurrence. LP is an exceedingly rare cause of leukoplakia in the larynx. Histological evaluation plays a key role in the diagnosis, in order to establish a proper therapeutic approach. Since LP is responsive to corticosteroid drugs and untreated disease tends to relapse, the medical treatment is advisable in such instances. [ABSTRACT FROM AUTHOR]

Isocitrate dehydrogenase (IDH)1/2 mutations are the most frequent druggable alterations in intrahepatic cholangiocarcinoma (iCCA), reported in ~20% of cases. Preclinical evidence indicates that these mutations are associated with homologous recombination deficiency (HRD), which could be exploited as a target for platinum chemotherapy (ChT) and PARP inhibitors. However, the role of IDH1/2 mutations as surrogate biomarkers for platinum efficacy is unknown. We conducted a multicenter, propensity score‐matched analysis to investigate the impact of IDH1/2 mutations on progression‐free survival (PFS), overall response rate (ORR) and disease control rate (DCR) in patients with iCCA treated with platinum‐based ChT. An exploratory comparison of complex HRD estimates between IDH1/2 mutated and wild‐type tumors from TCGA was also performed. A total of 120 cases were matched in a 1:1 ratio (60 IDH1/2 mutant and 60 wild‐type). No differences were observed for platinum‐based PFS (7.7 vs 7.3 months, P =.970), DCR (66.1% vs 74.1%, P =.361) and ORR (27.8% vs 25.0%, P =.741). IDH1/2 mutations showed mutual exclusivity with genomic alterations in ATM, BRCA2, MST1R, NF1, FGFR2 and CDKN2A/B losses, respectively, with no clear survival and response differences. Among TCGA tumors, IDH1/2 mutated CCA did not show higher HRD compared to wild‐type cases. IDH1/2 mutations are not associated with increased sensitivity to platinum‐based ChT in iCCA patients. Deeper genomic sequencing is needed to elucidate the HRD phenotype in IDH1/2 mutant iCCA and exploit its therapeutic vulnerabilities. [ABSTRACT FROM AUTHOR]

Glucocorticoid-induced leucin zipper (GILZ) mediates the effects of glucocorticoids in immune cells, but little is known about its role in both the gastro-intestinal (GI) mucosa and inflammatory bowel diseases (IBD) in humans. To investigate the GILZ protein expression profile in the GI tract, mucosal biopsies from 80 patients were retrospectively enrolled in this study and subdivided into three groups: 1) patients without clinical-endoscopic and histological evidence of IBD; 2) IBD patients; 3) patients with chronic atrophic gastritis (CAG) and Barrett esophagus (BE), both characterized by intestinal metaplasia (IM). GILZ expression was assessed by immunohistochemical and immunofluorescence methods. Our results showed that GILZ protein was strongly expressed in the secretory cells in healthy mucosa. GILZ expression was reduced in goblet cells in active disease, whereas it was restored in quiescent diseases. Conversely, entero-endocrine cells were not involved in such inflammation-driven dynamics, as GILZ expression remained detectable in active disease. Moreover, GILZ was expressed in IM, but was limited to CAG, and was not detected in BE. In summary, GILZ acts as a secretory protein in the GI mucosa in healthy, hyperplastic and metaplastic conditions. Its secretion by goblet cells is mostly affected by neutrophils mucosal infiltration and seems to be directly related to active mucosal inflammation in IBD. Overall, our findings suggest that GILZ is a suitable molecule to be considered as a histological marker of mucosal healing. [Display omitted] • GILZ was recognized to play a secretory role in the gut mucosa. • Secretory cells, both goblet and entero-endocrine cells, are involved in the GILZ secretory dynamics. • The inflammatory state of the gut mucosa heavily affects GILZ protein expression. • Such assumptions make GILZ suitable to be considered a candidate marker of mucosal healing in IBD. [ABSTRACT FROM AUTHOR]

Abstract: Glandular hamartoma is an extremely rare congenital malformation of the larynx. Presenting symptoms result from airways obstruction and may include slowly rising respiratory distress, stridor, changes in voice, eating and activity levels. Management consists in local mass excision with a good functional result and prognosis. Recurrences are usually associated with incomplete removal. We present a 3-month-old infant with a history of stridor and respiratory distress caused by a firm 0.4cm wide and 1.4cm long mass arising in the supraglottic region and detected with endoscopic approach. The lesion was excised endoscopically with an uneventful postoperative course and an excellent long-term prognosis. Histopathologically the lesion consisted of mature tissues with abnormal growth and disorganized architecture, chiefly composed of mature glandular structures, smooth muscular fibers, mature fat, surrounded by fibrous stroma and covered by typical squamous epithelium. The aim of our report is to underline how this condition must be considered by physicians, paediatricians and anaesthetists as an important cause of airway obstruction. [Copyright &y& Elsevier]

• Digital pathology facilitates sharing of cases between colleagues working in different places. • Digital pathology allows the creation of a network with a lot of relevant practical usefulness. • Digital pathology shows agreement with traditional means, being thus a promising tool. • Digital pathology could be helpful in particular circumstances requiring remote working. The aim of the study is to report the experience of the pathologists of the Italian Group for the Study of Inflammatory Bowel Disease (IBD) (group formed by pathologists with various experience) on the morphological assessment of digital slides pertaining to IBD and Non-IBD colitis underlining the necessity to implement this tool in daily routine and its utility to share opinions on difficult cases. Forty-eight histological slides stained with haematoxylin and eosin obtained from ileo-colorectal endoscopic biopsies were digitized using Menarini D-Sight 2.0 system, uploaded onto a website platform and shared among 40 pathologists participating in the study. Information regarding the site of biopsy was disclosed; clinical data were blinded. Each participant was committed to write a comment on microscopic features purposing diagnostic opinion. One month after the last uploaded case, a form was sent to each participant to evaluate the personal experience on digital slide sharing. Sixteen pathologists out of 40 (40%) had consistently accessed to the site,9/40 (22%) commented on all slides, a diagnostic opinion was rendered in 8 slides. Most common critical issues were: A) poor internet connection resulting in ineffective evaluation of the digital slides, B) time-consuming cases raising difficult diagnostic interpretation, C) lack of clinical history. Overall, 24 participants (60%) found the forum valuable for practical training and educational purposes. Sharing scanned slides circulating within a dedicated forum is an effective educational tool in both IBDs and Non-IBDs colitis. Although our results demonstrated a substantial compliance of the participants, their limited participation was an objective shortcoming. Hence, further efforts are needed to encourage this potentially rewarding practice among the pathologist community. [ABSTRACT FROM AUTHOR]

Non-IBD colitides (NIBDC) are intestinal diseases clinically and endoscopically overlapping with Inflammatory Bowel Diseases (IBD), sometimes with a similar histological picture. NIBDC include entities such as infectious colitis, ischemic colitis, pseudomembranous colitis, eosinophilic colitis, autoimmune enterocolitis, segmental colitis associated with diverticulosis, drug-induced colitis, radiation-induced colitis, diversion colitis, and microscopic colitis, this last including two entities: collagenous and lymphocytic colitis. The knowledge of the most useful histological features and the main clinical data for each entity is mandatory in daily clinical practice, for correct pathological diagnosis and clinical management., (Copyright © 2021 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Inflammatory bowel diseases (IBDs) are lifelong disorders in which an interaction between genetic and environmental factors is involved. IBDs include two entities: Crohn's disease (CD) and ulcerative colitis (UC); these can be adequately diagnosed and distinguished with a correct methodological approach based on communicating exhaustive clinical, endoscopic and laboratory information to the pathologist and performing adequate bioptic sampling and precise morphological signs including crypt architecture, distribution of inflammation and granulomas, when present. IBD needs to be distinguished from non-IBD colitis, mostly at its onset. Moreover, IBDs are associated with an increased risk of developing colorectal adenocarcinoma. In daily pathological practice, correct diagnosis of IBD and its subclassification as well as a correct detection of dysplasia is imperative to establish the best therapeutic approach., (Copyright © 2021 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Celiac disease is a multi-factorial chronic inflammatory intestinal disease, characterized by malabsorption resulting from mucosal injury after ingestion of wheat gluten or related rye and barley proteins. Inappropriate T-cell-mediated immune response against ingested gluten in genetically predisposed people, leads to characteristic histological lesions, as villous atrophy and intraepithelial lymphocytosis. Nevertheless, celiac disease is a comprehensive diagnosis with clinical, serological and genetic characteristics integrated with histological features. Biopsy of duodenal mucosa remains the gold standard in the diagnosis of celiac disease with the recognition of the spectrum of histological changes and classification of mucosa damage based on updated Corazza-Villanacci system. Appropriate differential diagnosis evaluation and clinical context also for the diagnosis of complications is, moreover, needed for correct histological features interpretation and clinical management., (Copyright © 2020 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)