Diagnostic interobserver variability in Crohn's disease- and ulcerative colitis-associated dysplasia: a multicenter digital survey from the IG-IBD Pathologists Group.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis, two forms of inflammatory bowel disease (IBD), are chronic and relapsing conditions of the gastrointestinal tract both characterized by long lasting chronic inflammation and increased risk of dysplasia and colorectal cancer (CRC). The aim of our study was to evaluate the interobserver agreement about IBD-associated dysplasia among pathologists belonging to the Italian Group for Inflammatory Bowel Diseases (IG-IBD P). METHODS: The present multicenter survey was performed using telepathology, supported by an open source E-learning platform. Biopsy specimens from 30 colonoscopies and from 20 patients were included. The glass slides of any case, including clinical and endoscopic data, were digitalized and uploaded on the E-learning platform. All the digital slides were grouped in 54 diagnostic "blocks". Blinded histopathological evaluation on all the digital slides was performed by 20 gastrointestinal pathologists. Closed-ended questions about (1) the occurrence of IBD; (2) the classification of IBD (as UC or CD); (3) the presence of active versus quiescent disease; (4) the presence of dysplasia; (5) the possible association of dysplasia with the sites of disease (dysplasia-associated lesion or mass-DALM vs adenoma-like mass-ALM); (6) the grading of dysplasia according to the ECCO guidelines (negative, indefinite, low grade, high grade categories) and (7) the presence of associated serrated features, were proposed in each case. Inter-observer agreement was evaluated by mean agreement percentage and kappa statistic, when suitable. RESULTS: The diagnosis of IBD was confirmed in 19 of 20 patients, 17 of 19 being classified as UC, 2 as CD. The mean interobserver agreement percentages about (1) the evidence of IBD, (2) the presence of either UC or CD and (3) the activity grading resulted to be 80%, 69% and 86%, respectively. Dysplasia was detected in 8/20 patients, with moderate agreement between pathologists (mean 72%, k 0.48). Particularly, low grade dysplasia was found in 13 biopsies (combined k 0.38), whereas high grade dysplasia in 8 (combined k 0.47). When the endoscopic and histopathological data were combined, features consistent with DALM were found in 6 of 20 patients with low grade dysplasia and those consistent with ALM in 2 patients with low grade dysplasia in a single biopsy (mean agreement: 86%). An associated serrated pattern was discovered in 4 patients (7 biopsies). CONCLUSIONS: Our study showed moderate interobserver agreement about the histopathological detection and classification of IBD-associated dysplasia. Further efforts should be undertaken to integrate the histopathological data with both the ancillary tests and molecular investigations.

Histopathology of Celiac Disease. Position Statements of the Italian Group of Gastrointestinal Pathologists (GIPAD-SIAPEC).

Celiac Disease (CeD) is an immune-mediated inflammatory disorder of the small intestine, affecting genetically susceptible individuals when exposed to gluten. Small intestinal biopsy interpretation has been the "gold standard" for celiac disease (CeD) for over 50 years. Despite today's availability of sensitive and specific serological tests, the histopathological features from mucosal biopsy play a key role in diagnosing when CeD is suspected. Such a diagnostic approach requires a multidisciplinary team to optimize both tissue sampling and interpretation via the interaction between the pathologist and the gastroenterologist. Pathologists of the Italian Group of Gastrointestinal Pathology (GIPAD-SIAPEC), together with a member (TR) of the Italian Society of Technicians (AITIC) and an expert gastroenterologist (CC), provide position statements as a practical tool for reading and interpreting the report. Moreover, a position statement was formulated about the recently described condition known as Non-Celiac Gluten Sensitivity (NCGS). Within such a diagnostic setting, both the architectural abnormalities of the duodenal mucosa, namely glandular hyperplasia, and villous atrophy and the number of intraepithelial T-lymphocytes should be well highlighted. Ancillary tests such as anti-CD3 stain are useful for an accurate count of the intraepithelial T lymphocytes when CeD or NCGS is suspected. Moreover, anti-CD3 and anti-CD8 stains are recommended in patients not responding to the gluten-free diet (GFD) to confirm a diagnosis of Refractory Celiac Disease (RCeD). Diagnostic clues about the differential diagnosis of both CeD and RCeD have also been rendered.

Aggressive fibromatosis of the larynx: report of a new case in an adult patient and review of the literature.

We describe a case of aggressive fibromatosis of the larynx occurring in a 75-year-old man. The lesion manifested with voice hoarseness and swallowing difficulty. A computerized tomographic scan of the neck revealed distortion of the glottic profile. A malignant tumor was suspected. Although a laryngoscopy-driven biopsy was non-diagnostic, total laryngectomy was done, since the lesion was not deemed amenable to conservative therapy. Grossly, the glottic rim was infiltrated by a hard, grey-white tissue showing a tentacular outline. Tissue sections featured a moderately cellular lesion composed of spindle cells with bland, tapered nuclei, enmeshed in a variably collagenized ground substance. Delicate spindle cell fascicles surrounded the native submucosal seromucous glands and had invaded the thyroid cartilage and the thyroid gland as well. The spindle cells were immunopositive for actins and vimentin, and negative for keratins, epithelial membrane antigen, desmin, and S-100 protein. No further therapy was administered. Periodic follow-up visits were negative. The patient died 5 years after surgery of myocardial infarction with no clinical evidence of lesion recurrence. Based on the available literature, our data confirm that laryngeal fibromatosis in adult patients is a locally infiltrating and progressive disease. Total laryngectomy with clear margins is needed as to avoid the high risk of local recurrence.

Ki-67 expression in vulvar carcinoma. Preliminary results.

A proliferating cell nuclear antigen (Ki-67) expression was investigated in 73 cases of invasive vulvar cancer, to detect new diagnostic and prognostic factors. We individualized, like Hendriks (1994), two general patterns of reactivity: 1) diffused positivity in all tumoral tissue with a bad prognosis; 2) focal positivity, localized at the edge of tumoral aggregates. Moreover, within focal patterns, one group with positivity to MIB-l of 0.2-6% and another group of 7-9% with different prognoses (better in the first group). Histotype, lymph-nodal status, FIGO stage are strictly correlated with distribution of Ki-67; on the contrary, no correlation was found with grading and number of mitoses.