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BACKGROUND AIMS Current therapeutic goals in ulcerative colitis (UC) include clinical and endoscopic remission, named mucosal healing (MH). Despite MH, a proportion of patients suffer a clinical relapse, which has been related to histological inflammation. We aimed to identify which histopathological features or histopathological index cut-off was associated with endoscopic relapse (ER) in UC patients with MH. METHODS Retrospective analysis of UC patients who underwent surveillance colonoscopy showing complete MH (endoscopic Mayo subscore=0) with random biopsies, and at least one more endoscopy along the follow-up. After a consensus meeting, expert pathologist performed histological assessment according to Simplified Geboes Score (SGS), Nancy Index (NI) and Robarts Histopathological Index (RHI). Other histopathological features were also evaluated. Patients were followed until ER or last endoscopy performed showing persistence of MH. RESULTS A total of 95 patients (150 colonoscopies) were included. After mean follow-up of 31.2 months (SD 21.7), 33 patients (34.7%) suffered ER. Neutrophils in lamina propria (OR 2.6; P = 0.037), within the epithelium (OR 2.6; P = 0.03), SGS ≥3.1 (OR 2.6; P = 0.037), NI ≥2 (OR 2.6; P = 0.03) and RHI ≥5 (OR 2.6; P = 0.037) were associated with ER in univariate analysis. In multivariate analysis, eosinophils in the lamina propria (HR 2.5; P = 0.01) and clinical remission

Supplemental Digital Content is available in the text, Objective: Proton pump inhibitors (PPIs) are an effective treatment for eosinophilic esophagitis (EoE); however, only 30% to 60% of patients respond. Common genetic variants in CYP2C19 and STAT6 associate with PPI plasma concentration and magnitude of inflammatory response, respectively. Our objective was to determine if genetic variation in the genes for CYP2C19 and STAT6 influence differentiation between PPI responsive esophageal eosinophilia versus PPI nonresponsive EoE (PPI-REE, PPI-nonresponsive EoE). Methods: Genomic DNA was isolated from 92 esophageal tissue biopsies collected from participants of a prospective clinical trial of high-dose PPI therapy for esophageal eosinophilia in children. Results: Of the 92 patients examined, 57 (62%) were PPI-REE and 35 (38%) were PPI-nonresponsive EoE. Forty-six of the 92 patients were further characterized by pH probe monitoring; there was no association between reflux index and carriage of CYP2C19∗17 (P = 0.35). In children who received a PPI dose between ≥1.54 and ≤2.05 mg/kg/day, binary logistic regression modeling showed that carriage of CYP2C19∗17 associated with PPI-nonresponsive EoE (odds ratio (OR) [95% confidence interval (CI)] = 7.71 [1.21, 49.11], P = 0.031). Carriage of STAT6 allelic variant rs1059513 predicts PPI-REE (OR [95% CI] = 6.16 [1.44, 26.4], P = 0.028), whereas carriage of STAT6 rs324011 synergizes with CYP2C19∗17 to predict PPI-nonresponsive EoE (rs324011 OR [95% CI] = 5.56 [1.33, 20.72], P = 0.022; CYP2C19∗17 OR [95% CI] = 8.19[1.42, 50.57], P = 0.023). Conclusions: Common variants in CYP2C19 and STAT6 associate with a PPI-nonresponsive EoE outcome of PPI therapy for esophageal eosinophilia suggesting that response rates may be improved by adopting a genotype-guided approach to PPI dosing.

Bronchiolitis obliterans (BO) is the most common expression of chronic allograft dysfunction in lung transplantation. Moreover, BO represents the major cause of death in the long-term after this procedure. On the other hand, mesenchymal stem cells have been tested in animal models of BO aiming to interfere in its development. The aim of this experimental study is to explore the role of bone-marrow derived stem cells (BMSCs) as a preventive intervention of BO occurrence.This an experimental randomized study. A bronchiolitis obliterans animal model in rats was reproduced: heterotopical tracheal transplant model in lung parenchyma. Five of these animals were used as control group. After setting up the model, individuals were divided in 3 groups of treatment (n=15), in which BMSCs were administered in 3 different time points after the tracheal transplant (tracheal transplantation and BMSCs administration occurred the same day, group G0; after 7 days, group G7; after 14 days, group G14. In addition, within each group, BMSCs were administered through 3 different routes: endotracheally, endovascular and topically in the lung parenchyma). Animals were sacrificed at 21 days. Histology, fluorescence in situ hybridization and immunohistochemistry techniques were performed for identifying stem cells.Compared to control group, animals receiving BMSCs showed large neovessels in a loose fibrous matrix. Group G7 showed less fibrosis (p0.033) and edema (p0.028). Moreover, G7 animals receiving stem cells endotracheally showed no fibrosis (p0.008). Alveolar-like patches of tissue were observed among all groups (53.4%, 46.7% and 40% in G0, G7 and G14 respectively), consisting of cells expressing both stem and alveolar cells biomarkers.BMSCs modify the course of bronchiolitis obliterans and differentiate into alveolar cells. Endotracheal administration of BMSCs 7 days after the heterotopical tracheal transplant might be considered an effective way to prevent BO in this animal model.

T1 colorectal polyps with at least 1 risk factor for metastasis to lymph node should be treated surgically and are considered endoscopically unresectable. Optical analysis, based on the Narrow-Band Imaging International Colorectal Endoscopic (NICE) classification system, is used to identify neoplasias with invasion of the submucosa that require endoscopic treatment. We assessed the accuracy of the NICE classification, along with other morphologic characteristics, in identifying invasive polyps that are endoscopically unresectable (have at least 1 risk factor for metastasis to lymph node).We performed a multicenter, prospective study of data collected by 58 endoscopists, from 1634 consecutive patients (examining 2123 lesions) at 17 university and community hospitals in Spain from July 2014 through June 2016. All consecutive lesions10 mm assessed with narrow-band imaging were included. The primary end point was the accuracy of the NICE classification for identifying lesions with deep invasion, using findings from histology analysis as the reference standard. Conditional inference trees were fitted for the analysis of diagnostic accuracy.Of the 2123 lesions analyzed, 89 (4.2%) had features of deep invasion and 91 (4.3%) were endoscopically unresectable. The NICE classification system identified lesions with deep invasion with 58.4% sensitivity (95% CI, 47.5-68.8), 96.4% specificity (95% CI, 95.5-97.2), a positive-predictive value of 41.6% (95% CI, 32.9-50.8), and a negative-predictive value of 98.1% (95% CI, 97.5-98.7). A conditional inference tree that included all variables found the NICE classification to most accurately identify lesions with deep invasion (P.001). However, pedunculated morphology (P.007), ulceration (P = .026), depressed areas (P.001), or nodular mixed type (P.001) affected accuracy of identification. Results were comparable for identifying lesions that were endoscopically unresectable.In an analysis of 2123 colon lesions10 mm, we found the NICE classification and morphologic features identify those with deep lesions with96% specificity-even in non-expert hands and without magnification. ClinicalTrials.gov number NCT02328066.

Tumors of the chorda tympani are extremely rare. To date only 15 cases have been reported in the literature. Slow growing rate and nonspecific clinical features allow these lesions to reach a large size and resemble more common otological entities such as cholesteatoma. Diagnosis is usually established after surgical resection. However, lack of specifity of conventional pathological studies emphasizes the importance of immunohistochemical studies for final diagnosis. It is advisable to use the correct terms when reporting the histology of chorda tympani tumors in literature.

Introduction Bronchiolitis obliterans (BO) is the major cause of death in lung transplantation after 1 year. On the other hand, mesenchymal stem cells (MSC) have shown to participate in reparative processes. Objectives To reproduce a BO animal model and assess the effect of MSC for preventing the histologic lesion. Methods We developed an heterotopic tracheal transplantation rat model of BO. BO lesion was successfully reproduced at day 21 (control group). Then, we transplanted in 45 rats bone marrow-derived MSC through 3 routes (topical, endotracheal, endovascular) and at 3 time points (same day of tracheal grafting, at day 7 and 14) [5 individuals each group]. Variables: grade of tracheal lumen obliteration, fibrosis, neovascularization, histologic pattern. Flourescence In Situ Hibridation (FISH) and Inmunohistochemistry (IHQ) were used to detect MSC. Results All MSC groups had significant differences in histologic pattern with regard to control group (p 0.006), showing more neovessels and less fibrosis. The group who received MSC at day 7 presented less fibrosis (p 0.033), and the subgroup who received MSC at day 7 by endotracheal route showed less fibrosis and grade of lumen obliteration (p 0.048). FISH-IHQ showed MSC expressing type II neumocite markers and were localized into a neoformed alveolar-like tissue. Conclusions Reproducibility of a BO animal model is feasible. MSC transplanted in that model are able to modify the typical BO lesion, so a reparative effect might be attributed to MSC. Expression of a neumocite marker by MSC localized in neo alveolar-like tissue shows a certain degree of regenerative effect. Endotracheal route appears to be the best one to MSC transplantation.

Aims and background Primary pulmonary lymphoma is an uncommon disease with a poorly defined management. We reviewed and followed the cases of primary pulmonary lymphoma in our institution to gather an estimation of this entity in our population. Design and methods We reviewed the records of all patients with biopsy-proven lymphoma of the lung. The main diagnostic criterion for primary pulmonary lymphoma was the absence of extrapulmonary involvement. Results We identified 6 cases of primary pulmonary lymphoma among 33 patients with biopsy-proven lymphoma of the lung evaluated in our center in a 12-year period. A radiological abnormality in an asymptomatic patient was the most common clinical presentation. Four cases were low-grade and two cases high-grade non-Hodgkin PPL. Histopathologic analyses of lung specimens obtained by transbronchial biopsy were sufficient for a diagnosis in 5 of the 6 cases and avoided invasive surgical maneuvers. Most patients followed an indolent course, but with a tendency to relapse. Conclusions Although clinical management of this entity is undefined, we feel bronchoscopic study, which is less aggressive than surgery, may be an adequate procedure for a diagnosis. Mono-chemotherapy using alkylating agents and careful clinical observation may be the best therapeutic approach for these patients, since most of them have favorable outcomes, whatever the treatment modalities.

We describe a patient with an intracranial extra skeletal myxoid chondrosarcoma (EMC), an unusual neoplasm of the deep soft tissues of the extremities. Very rarely are they localised as an intracranial lesion, and we believe it is very important to accurately distinguish EMC from other intracranial tumours such as classical or “skeletal” chondrosarcomas, mesenchymal chondrosarcoma, enchondroma, and myxoid tumours (chordoma, and chondromyxoid fibroma) in order to determine their prognostic implications. Furthermore, this case presents with the second local recurrence, higher-grade cellular areas, such an event has never been reported in intracranial cases. A 17 year-old female presented with tonic and clonic seizures, episodic left hemiplegia and intense right-sided headaches. Computed tomography and magnetic resonance of the skull showed a right fronto-parietal cortical lesion. Complete surgical excision of the lesion through a right parieto-temporal craniotomy was performed. The tumoral lesion recurred locally twice (16 and 19 months after the initial surgery respectively). First and second surgical specimens where diagnosed as extra skeletal myxoid chondrosarcoma. Microscopically, the third specimen (second local recurrence) showed abrupt transition from areas of conventional myxoid chondrosarcoma to high-grade cellular areas with fusiform features. Extra skeletal myxoid chondrosarcoma is very rarely described as an intracranial lesion. Reference on this topic is very confusing as there is no clear-cut distinction between skeletal chondrosarcomas with prominent myxoid matrix and extra skeletal myxoid chondrosarcoma which is a definite entity first defined by Enzinger and Shiraki in 1972 in deep soft tissues of the extremities. We review the cases reported in the literature with the diagnosis of myxoid chondrosarcoma either of extra skeletal origin or with skeletal attachment, and analyse their clinic and pathological features.

Intraoperative sentinel lymph node biopsy is widely used in patients with early-stage breast cancer for staging the axilla. The conventional analysis of the SLN has classically been performed by frozen section or touch imprint with a rapid H&E (hematoxylin and eosin) staining. Because of the risk of false-negative results, it has been replaced by the one-step acid amplification (OSNA) assay, a molecular diagnostic assay for the detection of cytokeratin 19 mRNA expression. Due to the controversial for the use of OSNA to evaluate the SLN because of its cost-effective and the lack of consensus to perform or avoid a lymphadenectomy when there is micrometastasis, we analyze 410 patients subjected to SLN biopsy in Hospital Puerta de Hierro, Madrid (Spain). Of the total of nodes, 223 (54.4 %) were processed throughout frozen-section examination and imprint cytology and 187 (45.6 %) throughout OSNA. The specificity of the frozen-section histological examination was of 100 %, with a sensitivity of 83.33 % (95 % CI 73.07–93.60). Of the 40 patients with definitive micrometastasis in the SLN, axillary dissection was performed in 90 % of the patients, with subsequent positive affectation in four of them (11.11 %). Based on our result and taking into account that 10 % of the lymphadenectomy performed after micrometastasis are positive, we do not believe that lymphadenectomy should be avoided after N(mi+) is detected in a SLN.

Para-articular chondroma is a rare tumor that has been reported in only 30 cases adjacent to large joints in the Anglo-Saxon literature. We report three new cases of this entity, describe its clinical, radiological and pathological features, and review the previous literature. Para-articular chondromas have an insidious clinical presentation and on radiographs show a large soft tissue mass with variable ossification. They appear as a lobulated mass of hyaline cartilage with variable endochondral ossification in the central area. These rare benign tumors arise from the capsule or the para-articular connective tissue of a large joint (mainly the knee), which suffers cartilaginous metaplasia and subsequent ossification. Cases 1 and 2 of this presentation fit all the features described previously. Case 3 has identical clinical features but differs from the former two cases in its microscopic appearance, being composed almost entirely of fibrocartilage and myxoid areas within the fibroadipose tissue of the joint instead of mature trabecular bone surrounded by hyaline cartilage. To the best of our knowledge this is the first description of this histological variant of para-articular chondroma.

Primary cutaneous signet-ring cell carcinoma (CSRCC) is a very unusual but distinctive clinicopathologic entity. It is defined as a diffuse malignant epithelial neoplasia localized in dermis and subcutis without epidermal involvement, showing variable amounts of signet ring cells, without evidence of a visceral adenocarcinoma. We report a case of CSRCC in a 70-year-old man along with its histologic and ultrastructural characteristics, and review of previous cases. We describe their main diagnostic features and discuss its wide differential diagnosis.

Small cell carcinoma is a malignant tumor composed of small cells with a diffuse growth pattern. It has immunohistochemical and ultrastructural features of both neuroendocrine and epithelial neoplasms. These tumors constitute 10% to 20% of malignant tumors in the lung, which is their most frequent site. They have been described in other extrapulmonary sites, where they are defined using the same criteria as used in the lung. These tumors are rarely found in the genitourinary tract. Fewer than 30 cases have been reported in the kidney. The differential diagnosis mainly includes other small round cell tumors and metastatic small cell lung carcinoma. We present and discuss a primary small cell carcinoma of the kidney (to our knowledge the 9th to be reported in the literature), which we studied with light microscopy, immunohistochemistry, electron microscopy, and, for the first time, flow cytometry.

Laryngeal and hypopharyngeal liposarcomas are extraordinarily infrequent tumors. To the best of our knowledge there are fewer than 40 well-documented cases re ported to date. Almost all of them are well-differentiated liposarcomas, with only 2 laryngeal-hypopharyngeal dedifferentiated liposarcomas. Dedifferentiated liposar coma is defined as a well-differentiated liposarcoma with areas of high-grade spindle cell nonlipogenic sarcoma. The well-differentiated areas may be of a lipoma like, sclerosing, or mixed type, and the dedifferentiated areas most frequently are of malignant fibrous hystiocytoma-like type. Despite its commonly pleomorphic his tology, dedifferentiated liposarcoma does not behave as aggressively as most pleo morphic sarcomas of adulthood; however, it has the capacity to metastasize, in contrast to its well-differentiated counterpart. We present a case of dedifferentiated liposarcoma arising in the pyriform sinus, an event only twice reported previously in the literature. Int J Surg Pathol 10(1):75-79, 2002