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Background and Aims: In recent years an increasing number of studies on Non-Celiac Gluten/Wheat Sensitivity (NCG/WS) have been published but no markers of this condition have as yet been found. Although the NCG/WS clinical presentation often overlaps with IBS, no previous study evacuate colon or rectal histology in NCG/WS patients. Patients and Methods: We performed a prospective study on 78 patients (66 females, 12 males, mean age 36. 4 years) diagnosed with NCG/WS by double-blind wheat challenge, presenting at two tertiary care centers in Italy from January 2015 through September 2016. Data were also collected from 55 control patients either with celiac disease (CD) or with self-reported NCG/WS who tested negative at the wheat challenge. Duodenal immunohistochemistry studies were performed to evaluate the number of intra-epithelial CD3+ lymphocytes (IEL), lamina propria CD45+ immunocytes, CD3+, CD4+ and CD8+ lymphocytes, mast cells, eosinophils, and presence and size of lymphoid nodules. Identical studies were performed on the rectal mucosa of NCWS patients and of self-reported NCG/WS with a negative wheat challenge. Results: In the duodenum, NCG/WS patients showed a significantly higher number of CD3+ IEL, lamina propria (LP) CD4S+ immunocytes and eosinophils than self-reported NCG/WS with a negative wheat challenge. NCG/WS patients with dyspepsia had a higher number of LP eosinophils than those not reporting upper digestive tract symptoms. In the rectal mucosa, NCG/WS patients showed enlarged lymphoid follicles more frequently than self-reported NCG/WS subjects with a negative wheat challenge, and a higher number of CD3+ intra-epithelial lymphocytes and LP CD45+ and eosinophils than control patients. The CD controls had the highest number of immunocytes (CD3+, CD45-P, eosinophils) of the 3 groups studied, both in the duodenum and in the rectum. Conclusions: Both the duodenal and rectal mucosa are inflammed in NCG/WS patients and eosinophils are increased in these districts. NCG/WS could be considered an inflammatory condition of the entire intestinal tract, mainly involving the rectum, and eosinophil infiltration a key candidate player in the pathogenesis of NCG/WS. The study was supported by the Italian Foundation for Celiac Disease (FC) Grant for Project 013/2014.

Non-familial small bowel carcinomas are relatively rare and have a poor prognosis. Two small bowel carcinoma subsets may arise in distinct immune-inflammatory diseases (celiac disease and Crohn's disease) and have been recently suggested to differ in prognosis, celiac disease-associated carcinoma cases showing a better outcome, possibly due to their higher DNA microsatellite instability and tumor-infiltrating T lymphocytes. In this study, we investigated the histological structure (glandular vs diffuse/poorly cohesive, mixed or solid), cell phenotype (intestinal vs gastric/pancreatobiliary duct type) and Wnt signaling activation (beta-catenin and/or SOX-9 nuclear expression) in a series of 26 celiac disease-associated small bowel carcinoma, 25 Crohn's disease-associated small bowel carcinoma and 25 sporadic small bowel carcinoma cases, searching for new prognostic parameters. In addition, non-tumor mucosa of celiac and Crohn's disease patients was investigated for epithelial precursor changes (hyperplastic, metaplastic or dysplastic) to help clarify carcinoma histogenesis. When compared with non-glandular structure and non-intestinal phenotype, both glandular structure and intestinal phenotype were associated with a more favorable outcome at univariable or stage-and microsatellite instability/tumor-infiltrating lymphocyte-inclusive multivariable analysis. The prognostic power of histological structure was independent of the clinical groups while the non-intestinal phenotype, associated with poor outcome, was dominant among Crohn's disease-associated carcinoma. Both nuclear beta-catenin and SOX-9 were preferably expressed among celiac disease-associated carcinomas; however, they were devoid, per se, of prognostic value. We obtained findings supporting an origin of celiac disease-associated carcinoma in SOX-9-positive immature hyperplastic crypts, partly through flat beta-catenin-positive dysplasia, and of Crohn's disease-associated carcinoma in a metaplastic (gastric and/or pancreatobiliary-type) mucosa, often through dysplastic polypoid growths of metaplastic phenotype. In conclusion, despite their common origin in a chronically inflamed mucosa, celiac disease-associated and Crohn's disease-associated small bowel carcinomas differ substantially in histological structure, phenotype, microsatellite instability/tumor-infiltrating lymphocyte status, Wnt pathway activation, mucosal precursor lesions and prognosis.

BACKGROUND: The incidence of central nervous system involvement has increased in the setting of acquired immune deficiency syndrome (AIDS). Although rarely reported, spinal cord compression, in the setting of AIDS, has been associated with primary lymphoma or opportunistic infections. CASE REPORT: The authors describe the case of a young man who was admitted to our institution with rapid and progressive paraplegia. Imaging studies revealed an extramedullary lesion compressing the spinal cord spanning 3 thoracic levels. Surgical treatment was performed, and the compressing process completely excised. Histologic examination of the lesion showed a chronic inflammatory tissue with many necrotic areas without signs of infection or lymphoma. The patient progressively regained normal strength in his legs and was discharged home. CONCLUSIONS: In patients with HIV, chronic inflammation can lead to a lesion that compresses the spinal cord and should be considered in the differential diagnosis. Knowledge of this entity gains importance with the increasing incidence of HIV because timely excision can restore neurologic deficits. This condition may be considered a new clinical entity, the true incidence of which will be established using the diagnostic protocols provided and further case reports

Primary malignant fibrous histiocytoma (MFH) is a rare and biologically aggressive tumor. Differential diagnosis must include cystic neoplasms of the pancreas (mucinous and serous cystoadenoma or cystocarcinoma), cystic lymphangioma or mesothelioma and retroperitoneal haematoma. Making the right diagnosis preoperatively may be often difficult, but MFH may be suspected when a huge retroperitoneal mass is found at imaging in elderly patients. We report a case of a primary abdominal MFH originating from the mesocolon transversum.

Background and Objectives. Essential thrombocythemia (ET) is a Philadelphia chromosome-negative chronic myeloproliferative disorder (CMPD) whose diagnosis, according to the Polycythemia Vera Study Group (PVSG) criteria, does not include histopathological data. The new WHO classification of CMPD has supplied new diagnostic guidelines which highlight the value of histopathology and facilitate a more precise differentiation of ET from reactive conditions and other CMPD. Design and Methods. Bone marrow biopsies from 142 adult patients diagnosed with ET according to PVSG criteria were evaluated using the new WHO classification. Megakaryocyte morphology and arrangement, amount of fibrosis and a clustering index were studied along with determination of microvessel density (MVD), amount of CD34(+) cells and percentage of MIB-1(+) cells and megakaryocytes. The last value, indicated as megakaryocyte proliferation index (MPI), was determined and expressed as a percentage of the counted cells. Results. According to WHO criteria the 142 biopsies were classified as follows: ET (21%); idiopathic myelofibrosis (IMF) grade 0 (30%), IMF-1 (34%), IMF-2 (10%) and ET/IMF-0 (5%). A significant difference (p

Background and aims An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC]. Methods A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations. Results CD-SBC showed a significantly better sex-, age-, and stage-adjusted overall and cancer-specific survival than CrD-SBC, whereas no significant difference was found between spo-SBC and either CD-SBC or CrD-SBC. CD-SBC exhibited a significantly higher rate of MSI and median tumour-infiltrating lymphocytes [TIL] than CrD-SBC and spo-SBC. Among the whole SBC series, both MSI─which was the result of MLH1 promoter methylation in all but one cases─and high TIL density were associated with improved survival at univariable and stage-inclusive multivariable analysis. However, only TILs retained prognostic power when clinical subgroups were added to the multivariable model. KRAS mutation and HER2 amplification were detected in 30% and 7% of cases, respectively, without prognostic implications. Conclusions In comparison with CrD-SBC, CD-SBC patients harbour MSI and high TILs more frequently and show better outcome. This seems mainly due to their higher TIL density, which at multivariable analysis showed an independent prognostic value. MSI/TIL status, KRAS mutations and HER2 amplification might help in stratifying patients for targeted anti-cancer therapy.

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn’s disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1+ immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1+ cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1+ microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.

The personalized medicine is in a rapidly evolving scenario. The identification of actionable mutations is revolutionizing the therapeutic landscape of tumors. The morphological and histological tumor features are enriched by the extensive genomic profiling, and the first tumor-agnostic drugs have been approved regardless of tumor histology, guided by predictive and druggable genetic alterations. This new paradigm of "mutational oncology", presents a great potential to change the oncologic therapeutic scenario, but also some critical aspects need to be underlined. A process governance is mandatory to ensure the genomic testing accuracy and homogeneity, the economic sustainability, and the regulatory issues, ultimately granting the possibility of translating this model in the "real world". In this position paper, based on experts' opinion, the AIOM-SIAPEC-IAP-SIBIOC-SIF Italian Scientific Societies revised the new agnostic biomarkers, the diagnostic technologies available, the current availability of agnostic drugs and their present indication.