Chronic Inflammatory Infiltrate Research Articles

ORAL MANIFESTATION OF CROHN DISEASE - A CASE REPORT

A 29-year-old male patient was referred to a specialized service with gingival lesions that lasted 10 years. The medical history showed untreated Crohn disease. Intraoral examination detected firm nodules at the vestibular retromolar region of the right and left mandibular molar, red in color, recovered by ulcerated mucosa, and both measuring 2 cm. The buccal mucosa revealed a swollen, cobllestone appearance and showed deep linear ulcerations. Incisional biopsy was performed, and histopathologic analysis showed a connective tissue with intense chronic inflammatory infiltrate and neutrophils, blood vessel neoformation, and epithelioid cells. We recommended the use of 0.12% topical chlorhexidine. Because of persistent oral lesions, the patient was redirected to a gastroenterologist for further investigations and systemic treatment. Clinical control remains for 2 months. Approximately one-third of Crohn disease patients develop extraintestinal manifestations. Treatment of oral lesions included treatment of the intestinal disease and cooperation between gastroenterologists and specialists in oral medicine.

PLASMA CELL GINGIVITIS MIMICKING GINGIVAL HYPERPLASIA: CASE REPORT

Plasma cell gingivitis features a distinctive and rare pattern of gingival inflammation characterized by infiltration of plasma cells in the oral tissues with unknown reason or generally related to an allergen. A 20-year-old female patient attended a surgery service, showing a generalized and painless enlargement of gingiva, with a discrete erythema. She did not have any systemic disease and was not on medication. There was a previous excisional biopsy with an inconclusive diagnosis. The lesion resurged in 3 months, and a new biopsy in the posterior gingiva was then performed with a hypothesis of gingival hyperplasia. Histopathology revealed fibrous connective tissue characterized by deposition of collagenous fibers and intense chronic inflammatory infiltrate predominantly composed of plasma cells but also lymphocytes and eosinophils. The diagnosis of plasma cell gingivitis was then established. Several recommendations were given to the patient in relation to her eating habits and allergen possibilities.

NASOPALATINE DUCT CYST: A CASE REPORT

Nasopalatine duct cyst is the most common nonodontogenic cyst of the jaws. The cyst is believed to arise from rests of the nasopalatine duct epithelium. A 59-year-old white female patient was attended by the oral pathology service to evaluate painful swelling in the anterior palate. Intraoral examination showed an erythematous 1.5 × 1.5 cm nodule in the anterior edentulous palate. Occlusal and periapical radiographs showed a well-defined, unilocular, radiolucent image with a size of 1.5 × 1.5 cm, near to the midline of the anterior palate. Surgical excision was performed and the specimen revealed a fragment of cystic capsule lined with stratified squamous epithelium with areas of cuboid simple epithelium. The cystic capsule was composed by dense fibrous connective tissue, showing a chronic inflammatory infiltrate and large blood vessels. The diagnosis was nasopalatine duct cyst. The postoperative course was uneventful, and no signs of recurrence have been noted 7 months later. Support: FAPEMIG.

Feline Lymphoplasmacytic Gingivostomatitis: Clinical and Anatomopathological Aspects

Background: Feline lymphoplasmacytic gingivostomatitis (FLPG) is an idiopathic, multifactorial and highly challenging condition, since the results of the available treatments are partial and transitory. A set of lesions triggered by inflammatory reaction is observed, sometimes with ulcerations in the oral mucosa, leading to algia and discomfort. Histopathological examination figures as the definitive diagnostic tool, presenting distinct cellular elements. The present study aims to report three cases of FLPG, firstly addressing the anatomopathological findings, as well as the therapeutic approach used and the results obtained in each case.Cases: Case 1- Occurred in a feline Siamese male 15-year-old, weighing 3.8 kg, which was admitted at a local clinic, under the complaint of prostration, dysphagia, and weight loss, signs that were noticed approximately 5 days before. Clinical evaluation revealed multiple proliferative and ulcerative lesions, extending until the isthmus of the fauces, erythematous areas around the teeth and multifocal gingival reabsorption. Once the clinical signs and lesions were observed, samples were collected for histopathological examination and sent to the Laboratory of Animal Pathology (LAP) of Faculty of Agronomy and Veterinary Medicine of the University of Passo Fundo (FAVM-UPF). Histologically, both fragments presented lymphoplasmacytic infiltration, with large and intensely eosinophilic cytoplasm, often with granular aspect, central to lateralized hyperchromatic nuclei, located predominantly in lamina propria and mucosa, as well as a discrete Mott cell infiltrate. It was also observed the presence of diffuse suppurative chronic inflammatory infiltrate, predominantly in lamina propria and mucosa, as well as foci of edema and hemorrhage, in addition to loss of tissue architecture establishing the definitive diagnosis of FLPG. The tutor went to another veterinarian for a second opinion, but the patient died within four months. Case 2- Occurred in a no defined-breed male feline 7-year-old, weighing 3.9 kg, on complaint of hyporexia, inappetence, progressive thinning and greasy-looking fur. The tutor reported that the patient showed an increasing disinterest for offered feed, for approximately three weeks, but in recent days, consumption had declined dramatically. Clinical evaluation showed the same pattern of lesions in case 1, but with higher intensity, especially in the fauces area, as well as multifocal periodontal lesion and gingival retraction areas in several teeth. After the clinical signs and lesions were observed, samples were collected for histopathological examination and sent to the LAP of the FAVM-UPF, having the same diagnosis of case 1. The patient was submitted to a complete teeth extraction and, up to date, is asymptomatic, with a positive evolution. Case 3- Occurred in a no defined-breed female feline 6-year-old, weighing 4.1 kg, showing bleeding gums, reluctance to eat and mild halitosis, signs noticed around two weeks before. The patient was submitted to clinical evaluation, with lesions that consisted of erythematous areas, more evident in molar teeth, as well as ulcerated foci of the oral mucosa. Samples were collected for histopathological examination and sent to the LAP of the FAVM-UPF, with the same diagnosis as previous cases. The therapeutic approach used consisted of immunodulation and immunosuppression, using cyclosporin and prednisolone, respectively. Up to present, the patient shows control on severity of lesions, maintaining a good life quality. Discussion: The present study observed that clinical and anatomopathological findings corroborate with those cited in the literature, with special emphasis on the presence of Mott cells as well as the marked lymphoplasmacytic infiltrate, common in all three cases. The results of chosen treatments showed variation in results, even with the individualization of the therapeutic approach in the three cases.

Effect of Sofosbuvir Administration and Its Withdrawal on the Submandibular Salivary Gland of Adult Male Albino Rats: A Histological and Ultra-Structural Study.

BACKGROUND:Sofosbuvir (SOF) was approved in 2013 as a part of first-line treatment for hepatitis C virus (HCV); it has activity against all genotypes with extrahepatic adverse effects have recently arisen.AIM:Investigating sofosbuvir-induced alterations in the rat submandibular salivary gland (SMSG).METHODS:A group of 80 adult albino rats weighing about ± 150 gm were used in the experiment. The rats were divided into 3 groups: Group I (control group) received distilled water, Group II (experimental group) divided into 2 subgroups and received SOF 40 mg/kg/day dissolved in distilled water for 1 and 3 months and Group III (recovery group) allowed for 1 month of recovery after SOF withdrawal. All animals were sacrificed; the SMSG was dissected, and specimens were examined histologically and ultra-structurally.RESULTS:Compared to Group I, Group II subgroup (1) showed acinar and ductal vacuolisation, discontinuity of the epithelial lining associated with retained secretion and congested blood vessels. These changes were found to be exaggerated in the subgroup (2) accompanied by acinar and ductal shrinkage, interstitial oedema, haemorrhage, chronic inflammatory cells infiltration and loss of gland compactness. Amelioration of the histological changes was detected in Group III after SOF withdrawal. The ultrastructural examination confirmed these histological results.CONCLUSION:SOF had induced apparent alterations in the structure and ultrastructure of SMSG. The SOF-induced alterations were time-dependent, attributed mainly to mitochondrial toxicity and partially ameliorated by its withdrawal.

Criterios histopatológicos para el diagnóstico de fibrosis pulmonar idiopática

In the latest update of the ATS/ERS/JRS/ALAT Clinical Practice Guidelines for idiopathic pulmonary fibrosis (IPF), a new way of classifying histopathological patterns in 4 types is proposed: definitive usual interstitial pneumonia (UIP), probable UIP, indeterminate and alternative to UIP. A heterogeneous fibrotic remodeling of the normal architecture of the pulmonary parenchyma, with destructive scarring in the form of “honeycomb”, presence of fibroblastic foci and predominantly subpleural and paraseptal distribution, with scarce chronic interstitial inflammatory infiltrate, associated with the absence of elements suggestive of secondary causes such as bronchiolocentric distribution, predominanceof inflammatory interstitial infiltrates or poorly formed granulomas, allows an accurate diagnosis of IPF in an appropriate clinical-radiological scenario.

The influence of Zingiber officinale Roscoe on the histological changes of soft palatal mucosa in streptozotocin-induced type 3 diabetes rat model

Background: Zingiber officinale Roscoe presents valuable outcomes in some neurodegenerative diseases.Objective: This study aimed to evaluate Zingiber oil extract efficacy in the regression of Type3 diabetes mellitus (T3DM) induced in rat model.Methodology: 28 adult male albino rats were divided into four equal groups: Control-ve group received no injections; Control+ve group received a single bilateral intra-cerebroventricular (ICV) injection of sterile 0.9% saline, T3DM group received a single bilateral ICV injection of streptozotocin (3 mg/kg) dissolved in sterile 0.9% saline; Zingiber treated group five weeks after ICV- STZ, received orally 100 mg/kg/day Zingiber oil extract for two months. Soft palate oral mucosal sections were processed for H&E, fluorescence staining (using thioflavin-T dye) and immunohistochemical (using anti-caspase-3 and anti-VEGF antibodies) examination.Results: Both control groups were almost identical. Some T3DM sections histopathologically displayed inflammatory signs represented by cloudy swelling of keratinocytes, nuclear degenerative signs, apparently increased apoptotic keratinocytes, subepithelial degeneration, chronic inflammatory infiltrates, congested dilated blood vessels, hyperplasia and dilatation of palatal glandular acini and excretory duct. Irregular and decreased palatal fungiform papillae with few vacuolated taste cells were illustrated. Comparing to control groups, significant strong diffuse thioflavin-T fluorescence in oral epithelium, palatal acini, endothelium of blood vessels along with subepithelial amyloid deposits in some T3DM specimens were detected. Likewise, caspase-3 immunoreactivity in oral epithelial and connective tissue cells significantly increased in T3DM group. Similarly, significant positivity to VEGF in oral epithelium and in the significantly increased blood vessels in wall thickness and distribution were exhibited in T3DM sections. All T3DM results were significantly restored in Zingiber group except for the low significant decrease of caspase-3 reactivity in this group.Conclusions: It was concluded that Zingiber oil extract was an appropriate selected approach to ameliorate the possible T3DM associated peripheral tissue insults but most probably in a higher dose or prolonged supplementation.

Complete histologic normalisation is associated with reduced risk of relapse among patients with ulcerative colitis in complete endoscopic remission.

Clinical and endoscopic remission are treatment targets in ulcerative colitis (UC). The value of histologic healing in altering clinical outcomes among patients with complete endoscopic healing is not well established. To quantify the association between histologic activity and clinical relapse among patients with UC who were in complete endoscopic remission. This study included patients with UC from a prospective registry who were in complete endoscopic remission. Histologic activity was quantified by a senior gastrointestinal pathologist. Histologic activity was defined as lack of normalisation (Geboes score>0) as well as histologically active disease (Geboes score ≥2.1 and ≥3.1). The primary outcome was clinical relapse within 2years. Multivariable regression adjusting for potential confounders examined the independent predictive value of histologic changes. The study included 83 patients (51% women) (median age 44years; median disease duration 11years). Forty-one (49%) had complete histologic normalisation. Within two years, 26 (31%) experienced clinical relapse. Patients with complete histologic normalisation were less likely to experience relapse (5/41, 12%) compared to those without normalisation (21/42, 50%, P<0.001) (multivariable OR 7.22, 95% confidence interval (CI) 2.48-24.70) by the Geboes score. The individual components of the Geboes score predictive of relapse were architectural changes (P=0.03) and increased chronic inflammatory infiltrate (P<0.001). Complete histologic healing using the Geboes score was associated with reduced rates of clinical relapse among patients with UC in endoscopic remission.

Inflammatory Myofibroblastic Tumor of the Liver in Children

Abstract Inflammatory Myofibroblastic Tumor (IMT) was originally described in the lungs but it has been reported to occur at extrapulmonary sites. These are benign tumors which have a tendency either to be aggressive or regress spontaneously as reported by other authors. Histologically it is characterized by prominent spindle cell proliferation with a chronic inflammatory infiltrate thus IMT's have been given synonyms including plasma cell granuloma, inflammatory pseudotumor and inflammatory fibrosarcoma. It is a rare tumor that occurs in various parts of the body including the abdomen, soft tissue and liver. We report a case of a 4 year old female child with a liver IMT and present a review of various features of liver IMT in children. This child underwent resection of the liver IMT with an unremarkable post-operative course and upon histological examination confirmed features of IMT.

Renal injury following long-term exposure to carbon disulfide: analysis of a case series

BackgroundTo investigate the clinicopathological characteristics of renal damage caused by long-term exposure to carbon disulfide (CS2) in nine patients.MethodsAll the patients underwent ultrasound-guided renal biopsy. All specimens were examined by light microscopy and immunohistochemistry (IHC). Samples form one patient were further analyzed using transmission electron microscopy.ResultsSimilar pathological changes were observed in all patients, but the degrees of lesions were different. All cases had moderate to severe nodular mesangial hyperplasia; among these, type “Kimme1stie1-Wi1son” (K-W nodule for short) was observed in four cases, type “K - W nodule” refer to nodular hyperplasia of mesangial membrane like letter K or W. four cases had proliferative extracapillary glomerulonephritis (GN), while there were no concomitant changes in one patient. Besides, six cases had diffuse basement membrane thickening, focal segmental sclerosis or bulbar sclerosis; two cases had diffuse glomerular sclerosis, and one case had focal segmental capillary hyperplasia. Moreover, all patients had renal tubular atrophy/interstitial fibrosis with less to moderate chronic inflammatory cell infiltration, as well as renal arteriosclerosis. IHC showed that the depositions of IgA, IgM, C3d, C4d, C1q and Fib were not specific; while IgG, type III collagen, Fibronectin, Amyloid A, Igκ, Igλ, HBsAg and HBcAg were all negative.ConclusionDiffuse nodular mesangial hyperplasia/sclerosing glomerular nephropathy is characterized by nodular mesangial hyperplasia with type “K-W nodules” formation, which we speculate is a special pathological manifestation of renal damage caused by carbon disulfide (CS2).

Lung Biopsy Findings in Severe Pulmonary Illness Associated With E-Cigarette Use (Vaping).

The aim of this report is to describe the lung biopsy findings in vaping-associated pulmonary illness. Lung biopsies from eight patients with vaping-associated pulmonary illness were reviewed. The biopsies were from eight men (aged 19-61 years) with respiratory symptoms following e-cigarette use (vaping). Workup for infection was negative in all cases, and there was no evidence for other etiologies. Imaging showed diffuse bilateral ground-glass opacities in all patients. Most recovered with corticosteroid therapy, while one died. Lung biopsies (seven transbronchial, one surgical) showed acute lung injury, including organizing pneumonia and/or diffuse alveolar damage. Common features were fibroblast plugs, hyaline membranes, fibrinous exudates, type 2 pneumocyte hyperplasia, and interstitial organization. Some cases featured a sparse interstitial chronic inflammatory infiltrate. Although macrophages were present within the airspaces in all cases, this feature was not prominent, and findings typical of exogenous lipoid pneumonia were absent. The histopathology of acute pulmonary illness related to e-cigarette use (vaping) is characterized by acute lung injury patterns, supporting the contention that vaping can cause severe lung damage.

In vivo tissue reaction within the outflow conduit in patients supported by HeartWare HVAD

The frequency, extent, and nature of tissue ingrowth within the continuous-flow left ventricular assist device (cf-LVAD) outflow conduit has not been systematically assessed. We sought to characterize conduit histopathology at explantation in a cohort of patients with HeartWare ventricular assist device (HVAD) and assess the effect on pump performance. Patients undergoing routine histopathological assessment of a HeartWare HVAD removed at transplantation or autopsy were assessed. Outflow conduits were examined macroscopically, and visible tissue was sectioned for microscopic evaluation. In patients who had undergone prior contrast-enhanced computerized tomography (CT) with HVAD in situ, the outflow conduit was measured at the aortic anastomosis and 5cm proximal to the anastomosis, in the axial and sagittal planes. All patients had their pump flow, flow pulsatility, current, and speed determined from log files examined at 1, 3, 6, 9, and 12 months after LVAD implantation. Twenty-five consecutive patients were assessed (24 LVAD, 1 biventricular assist device (BiVAD)). Of the 26 outflow grafts assessed, there was evidence of tissue ingrowth reaction in 24 (92%) grafts. The most common site was the distal anastomosis (18/24, 75%), with the graft body involved in 14 of 24 (58%) grafts. Microscopic evaluation revealed acute inflammatory infiltrate in 4 of 24 grafts (17%), chronic inflammatory infiltrate in 14 of 24 (58%), neointima formation in 18 of 24 (75%) and fibrosis in 18 of 24 (75%) grafts. The median depth of tissue was 1mm (range, 0-2mm). The mean conduit diameter was 9.5±0.6mmat the aortic anastomosis compared with 11.1±0.5mm 5cm proximal to the anastomosis (p<0.0001). In patients with unchanged pump speed one month after implantation, analysis of log files revealed a significant (5.8±8.6%) decrease in pump flow (4.65±0.86 vs 4.38±0.92L/min, p=0.01) and flow pulsatility (5.00±1.10 vs 4.16±1.05L/min, p=0.006). There is evidence of tissue formation within the HVAD outflow conduit in the vast majority of patients, most commonly located at the aortic anastomosis. This is associated with significantly decreased pump flow over time.

Titanium particles: An emerging risk factor for peri-implant bone loss

ObjectiveTo investigate the presence of titanium particles in peri-implant tissues in cases diagnosed with peri-implantitis, and to identify immunological reactions that these particles may elicit. MethodsTen peri-implant tissue biopsies of patients diagnosed clinically and radiographically with peri-implantitis were obtained from the archives of Oral Pathology Centre, University of Otago. The inclusion criteria involves: bleeding on probing, ≥6 mm probing depth and ≥3 mm radiographic bone loss around the dental implant. Peri-implant tissue samples were evaluated using scanning electron microscopy-energy dispersive x-ray spectroscopy (SEM-EDS) to identify of sites with/without titanium particles. Antibodies against human transforming growth factor beta 1 (TGF-β1), receptor activator of nuclear factor kappa-B ligand (RANKL), interleukin 33 (IL-33) and cluster of differentiation 68 (CD68) were used to stain the specimens. ImageJ software was used to standardise the sampling area, compare and characterise the inflammatory infiltrate in tissues with/without titanium particles. Inflammatory cytokines positivity was assessed using the immunoreactive scores (IRSs). ResultsLight microscopy and SEM-EDS analysis identified titanium wear particles in 90% of the tissue samples, associated with a mixed chronic inflammatory infiltrate. Quantification analysis of RANKL revealed significantly higher IRS and intensity scores (p < 0.05) in areas containing titanium. High intensity, proportion and IRSs of TGF-β1 and IL-33 were observed in areas with titanium. CD68 had higher IRSs in the absence of titanium particles. ConclusionsSignificant overexpression of the cytokine RANKL was observed, with a trend for over-expression of IL-33 and TGF-B1 in areas with titanium. Further studies with large sample size and appropriate control group for quantification analysis is needed to confirm the role of titanium particles in initiating bone loss.

1351P - Clinicopathologic characteristics of immune colitis in melanoma patients treated with combination ipilimumab and anti-PD1 (IPI+PD1) and PD1 monotherapy

BackgroundColitis is one of the major immune-related adverse events (irAEs) to immunotherapy that leads to significant morbidity and discontinuation of treatment. Despite being a frequent irAE, clinical presentation, endoscopic and pathological features, and management of colitis in patients (pts) treated with combination IPI+PD1 and PD1 monotherapy are not well- defined. MethodsPts with locally advanced or metastatic melanoma who received combination IPI+PD1 or PD1 monotherapy and developed clinically significant colitis (requiring systemic corticosteroids) were identified retrospectively from 2 academic centers. Clinical data were collected on all pts; endoscopic and histopathologic data were examined on a subset. Results112 patients were identified who developed significant colitis between May 2013 and October 2018; 73 treated with IPI+PD1 and 33 treated with PD1 monotherapy. Six pts were excluded from the analysis that received ipilimumab alone (3 pts) or received treatment (3 pts) on clinical trials (blinded). Endoscopic and histopathologic data were available on 63 pts. Combination therapy induced colitis was earlier onset (8.8 weeks vs 44.6 weeks, p<0.0001) and more severe (Grade 3/4; 66% vs 31%, p=0.0014) than with monotherapy. Infliximab and immunosuppressive agents beyond corticosteroids were required in most pts with combination therapy (54% vs 30% with monotherapy, p=0.02). Five pts (3 combination, 2 monotherapy) underwent colectomy due to complicated steroid refractory disease (3/5 were infliximab refractory). There were no colitis related deaths. The presence of moderate to severe, diffuse inflammation was more common on combination therapy than monotherapy (51% vs 33%, p=0.36). A chronic inflammatory infiltrate was more common on histopathology with combination colitis compared to monotherapy (46% vs 20%, p=0.12). ConclusionsClinically significant colitis due to immunotherapy varies in presentation, response to immunosuppression and endoscopic/histologic features. IPI+PD1 colitis has an earlier onset, is more severe yet resistant to corticosteroids than PD1 induced colitis. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureM.S. Carlino: Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. R.A. Scolyer: Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Novartis; Advisory / Consultancy: Myriad; Advisory / Consultancy: NeraCare. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: BMS; Advisory / Consultancy: MERCK MSD; Advisory / Consultancy: Mass-Array; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche. A.M. Menzies: Advisory / Consultancy: BMS; Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy: Roche; Advisory / Consultancy: Pierre Fabre. All other authors have declared no conflicts of interest.

ACUTE PULMONARY GRAFT VS HOST DISEASE RESPONDING TO IBRUTINIB THERAPY

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) usually involves the liver, skin and gut and lung involvement is rare. We report a case of acute GVHD with respiratory failure developing 18 months post allogeneic HSCT that was successfully treated with Ibrutinib. CASE PRESENTATION: A 58-year old male with relapsed small lymphocytic lymphoma (SLL) following matched, sibling-donor allogeneic HSCT complicated by chronic GVHD presented with acute onset shortness of breath following completion of slow corticosteroid taper. He presented 18 months post-transplant with a one-week history of progressive dyspnea, anorexia, weight loss, diarrhea, lower extremity edema, dizziness and lethargy. Dyspnea rapidly progressed to acute hypoxemic respiratory failure requiring high-flow oxygen therapy (HFOT). CT chest progressed from right middle and lower lobe ground glass opacities on admission to bilateral multi-lobar parenchymal opacities (Figure 1). Oxygen requirements progressed in spite of broad-spectrum antibacterial and antifungal therapy; he underwent bronchoscopy with transbronchial biopsy that showed chronic interstitial inflammatory infiltrate with scattered T cells, with no evidence of SLL/CLL (Figure 2). Microbiological testing, including bronchoalveolar lavage fluid cultures, was negative. The diagnosis of acute GVHD was made and the patient was started on high-dose IV methylprednisolone on hospital day (HD) 9. After 5 days, he remained on HFOT; he received tocilizumab and was started on ibrutinib on HD 14. By HD 18, his pulmonary status had significantly improved. By HD 22, he was off supplemental oxygen, and by HD 23, his chest CT demonstrated resolution of lung opacities. DISCUSSION: Non- infectious lung complications (NILC) is a nonspecific term that includes pulmonary edema, diffuse alveolar haemorrhage, idiopathic pneumonia syndrome, post-transplant lymphoproliferative disorder and many other pulmonary complications that can occur in patients post HSCT (1). Acute GVHD is one of the complications responsible for severe morbidity and often, mortality. As per the 2014 NIH consensus criteria, diagnosis of acute GVHD depends on clinical manifestations, not to the temporal relationship with transplantation (2). The clinical course of acute GVHD typically mimics steroid-responsive cryptogenic organizing pneumonia; however in certain cases, it may be refractory to even high doses of steroids. Our patient’s clinical improvement following initiation of immunomodulatory therapies including tocilizumab and ibrutinib, provides support for using these novel agents. CONCLUSIONS: Ibrutinib is a tyrosine kinase inhibitor that has been shown to benefit patients with chronic GVHD (3). Our case highlights its use with a positive outcome in acute GVHD refractory to steroids. Reference #1: Pena E, Souza CA, Escuissato DL, Gomes MM, Allan D, Tay J, et al. Noninfectious pulmonary complications after hematopoietic stem cell transplantation: practical approach to imaging diagnosis. Radiographics. 2014;34(3):663-83. Reference #2: Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389-401.e1. Reference #3: Miklos D, Cutler CS, Arora M, Waller EK, Jagasia M, Pusic I, et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017;130(21):2243-50. DISCLOSURES: No relevant relationships by Divyansh Bajaj, source=Web Response No relevant relationships by Nancy Hardy, source=Web Response No relevant relationships by Van Holden, source=Web Response No relevant relationships by Shreya Kanth, source=Web Response No relevant relationships by Akshay Kohli, source=Web Response No relevant relationships by Laura Malone, source=Web Response Consultant relationship with Medtronic Please note: $1001 - $5000 Added 03/17/2019 by Edward Pickering, source=Web Response, value=Consulting fee Consultant relationship with Medtronic Please note: $1001 - $5000 Added 03/13/2019 by Ashutosh Sachdeva, source=Web Response, value=Consulting fee Unrestricted education grant relationship with Olympus Please note: $1001 - $5000 Added 03/13/2019 by Ashutosh Sachdeva, source=Web Response, value=Grant/Research Support

1397 Intrahepatic Bile Duct Adenoma: A Diagnostic Dilemma

INTRODUCTION: Intrahepatic bile duct adenoma (BDA) is a rare tumor arising from the epithelial cells of the bile ducts. BDA has been usually found incidentally by intra-abdominal surgery and autopsy. BDA is clinically significant because of its benign prognosis but also its difficulty differentiating from malignant neoplasms of the liver by imaging studies. CASE DESCRIPTION/METHODS: A 52-year-old male presented with hematuria. A CT abdomen and pelvis showed an incidental, 1.5 cm lesion in the right hepatic lobe. Following fine needle aspiration biopsy of the lesion, the tissue demonstrated a slightly irregular hepatic duct proliferation, for which a differential diagnosis of bile duct adenoma and well-differentiated cholangiocarcinoma was considered. Alpha-fetoprotein, carbohydrate antigen 19-9, and carcinoembryonic antigen were normal. An MRI was obtained to better ascertain the lesion, which demonstrated a 1.1 × 1.1 cm lesion within the right hepatic lobe, segment 6. The decision was made to pursue a hepatic resection. On gross examination, the specimen revealed an ovoid, well-circumscribed, white-tan, firm lesion measuring 1.4 cm in greatest dimension, and located 0.5 cm from the hepatic capsule. Microscopically, there was a well-circumscribed lesion composed of small biliary-type glands in tubular and branching trabecular patterns with a mild nuclear enlargement and inconspicuous mitotic activity. The lesion was well-delineated and the interphase with hepatocytes was regular without infiltrative growth (Figure 2). Immunohistochemically, CD56 stain was focally positive in the tumor. DISCUSSION: The main characteristics of BDA are as follows: the lesion is small-sized, with a diameter ranges between 1 to 20 mm; the lesion is always detected under the hepatic capsule, with clear borders but without capsule; the majority of the proliferated bile ducts are observed in the lesion, accompanied by plenty of chronic inflammatory cell infiltration; immunohistochemical stain for CK7, CK19, and CD56 are positive, whereas Ki67 and p53 are negative. Gütgemann et al. suggested that CD56 expression can aid the differential diagnosis of cholangiocarcinoma and a benign lesion such as BDA. Since our case showed positive CD56 stain along with other aforementioned features, the appropriate diagnosis was BDA. Since there are no definite imaging characteristics or tumor markers that allow a preoperative diagnosis, surgical resection followed by microscopic and immunohistochemical findings is crucial for the diagnosis of BDA.

2686 Collagenous Gastritis: A Rare Entity

INTRODUCTION: Collagenous gastritis is a rare entity characterized by subepithelial deposition of collagen bands thicker than 10 μm and the infiltration of inflammatory mononuclear cells in the lamnia propia. While collagenous colitis has become more common in clinical practice, collagenous gastritis is rare. These two entities generally present differently. Collagenous colitis presents more commonly with diarrhea, while collagenous gastritis presents more commonly with abdominal pain. Since the disease was reported in 1989, only 60 cases have been documented in English literature. We present a case of collagenous gastritis in a pediatric patient. CASE DESCRIPTION/METHODS: A 17-year-old male patient presents to our office with a three month history of epigastric pain with no changes in bowel habits. He denies any previous past medical or surgical history. He immigrated to the United States from China. Physical examination was unremarkable aside from mild epigastric tenderness. A CMP, CBC and celiac serologies were unremarkable. Upper endoscopy was performed which revealed moderate erythematous mucosa in the gastric antrum (Figures 1 and 2). Biopsies of the antrum yielded mild chronic gastritis with sub-epithelial collagenous gastritis in the antrum (Figure 3). Helicobacter Pylori was negative. Patient symptoms gradually responded to a proton pump inhibitor. DISCUSSION: Collagenous gastritis is a rare condition with limited data in the literature. Most patients are young, abdominal pain and anemia occur secondary to stomach-specific infiltration. The etiology is mostly unknown and hypothesized. The endoscopic findings that are commonly reported include nodular changes in the mucosa, due to chronic inflammatory infiltration, mucosal atrophy and deposition of bands of collagen. Compared with the diffuse and continuous deposition seen in collagenous colitis, the changes in collagenous gastritis are heterogenous. Collagenous gastritis as a rare entity should be in the differential in younger patients who present with epigastric pain.

2258 Cascara Sagrada: A Dangerous Herbal Stool Softener: A Case Report and Literature Review

INTRODUCTION: The percentage of drug-induced liver injury due to the use of herbal supplements has exponentially increased over the last decade from 7% to about 20%. Liver injury attributed to supplement use is associated with more deaths than cases attributed to anabolic steroid use or even allopathic medications. CASE DESCRIPTION/METHODS: 53-year-old female presented with jaundice, pruritus, fatigue, clay-colored stools and dark-colored urine for 4 days. She reported taking an herbal supplement called cascara sagrada for constipation over an 8-week period. On physical examination she appeared jaundiced, abdomen was non-tender, non-distended, and there was no hepatomegaly. Laboratory tests were significant for total bilirubin 8.2 mg/dL, direct bilirubin 5.5 mg/dL, ALP 459 U/L, GGT 733 U/L, AST 1274 U/L, ALT 1711 U/L, INR 0.97, ferritin 1409 ng/ml, transferrin saturation 59%, viral hepatitis antigens and antibodies were negative and an autoimmune panel was unremarkable. Liver ultrasound revealed coarse echotexture with no hepatomegaly and no biliary dilatation. Patient was discharged with close follow up. Five days after discharge, total bilirubin was 19 mg/dL with worsening symptoms necessitating re-admission. Further workup with liver biopsy showed marked portal and lobular chronic inflammatory infiltrate and focal bile duct injury and cholestasis; iron stain showed minimal Kupffer cell iron deposition but no hepatocellular deposition. Patient improved clinically and biochemically after discontinuation of cascara sagrada, with normalization of liver function tests after 3 months of the initial presentation. DISCUSSION: Cascara Sagrada is a herbal medication used for short term treatment of constipation, generally well tolerated but is known to cause liver injury when used in higher doses than recommended. Anthraquinone derivatives are the active laxative components; promoting peristalsis and inhibiting reabsorption of water and electrolytes. Cascara is slightly absorbed, and typical recommended courses are for less than 7 days. The mechanism of liver injury is not well understood but it has been hypothesized that it is mediated by the direct toxicity of anthraquinone derivatives. Liver injury can present with a pattern of serum enzyme elevation that can be either hepatocellular or cholestatic and ranges in severity from mild transaminase elevation to severe hepatitis with associated portal hypertension and ascites. Nevertheless, injury is usually self-limited and typically reversible upon discontinuation.

A Rare Case of Desmoplastic Mesothelioma With Good Survival Despite Lymph Node Metastasis

Abstract Introduction Desmoplastic mesothelioma (DMM), a rare histological subtype of malignant pleural mesothelioma (MPM), is lethal and has very poor prognosis. Metastasis is commonly reported in DMM compared to other histological subtypes. Here we report a case of DMM with good survival (&gt;1 year) despite lymph node metastasis. Case Report A 62-year-old female with a history of smoking and possible asbestos exposure presented with cough and wheeze in 2012. Computed tomography (CT) revealed left-sided pleural plaques and multiple ground-glass pulmonary nodules. In 2017, repeat CT showed increased diffuse left nodular pleural thickening. Positron emission tomography revealed hypermetabolic, nodular pleural thickening in the hemithorax, compatible with neoplasia. Needle biopsy in January 2018 showed pleural tissue with haphazard, nodular growth of spindled mesothelial cells, suspicious for desmoplastic mesothelioma. Definitive diagnosis was not possible due to lack of fat invasion and absence of supportive evidence by immunohistochemical stains. The patient underwent pleurectomy in February 2018. On histopathology, the majority of the tumor showed a desmoplastic pattern, composed of malignant spindled cells arranged haphazardly in a dense hyalinized stroma with chronic inflammatory infiltrate. AE1/AE3, calretinin, and D2-40 immunohistochemical stains highlighted the infiltrating neoplastic cells, which were negative for WT-1. BAP-1 was retained. The pattern of immunoreactivity supported the diagnosis of DMM. The tumor also involved visceral pleura, pulmonary parenchyma, and pericardium. It invaded into fat and displayed lymphovascular invasion. A metastatic focus of DMM was present in a lymph node. The tumor was staged as pT3N1. On recent examination, the patient only had complaints of mild breathlessness and stable hydro-pneumothorax, without any other comorbidities. Conclusion Our finding is unusual, since among the mesothelioma subtypes, DMM has the shortest survival, usually not more than 6 months. We report an extremely rare case of DMM with survival of &gt;1 year despite invasion of lung parenchyma and lymph node metastasis.

The Many Faces of Cardiac Sarcoidosis

Abstract Introduction Cardiac involvement by sarcoidosis, a disease characterized by nonnecrotizing granulomas of unknown etiology, is rare and affects up to 7% of sarcoidosis patients clinically, but with an autopsy prevalence of 15% to 90%. The clinical presentation, as well as macroscopic and microscopic findings in cardiac sarcoidosis patients, varies. Methods Retrospective clinical chart review and gross and microscopic examination of surgical specimen from two adult cardiac sarcoidosis patients with literature review were performed. Results Case 1: A 23-year-old woman with no past medical history presented with 2 months of heart failure symptoms following a viral gastrointestinal infection. Endomyocardial biopsy showed a dense chronic inflammatory infiltrate, without giant cells. Anterior mediastinal lymph node biopsy and left apical core showed effacement by nonnecrotizing granulomas with giant cells and multifocal calcification, supporting cardiac sarcoidosis. Twelve months later, she underwent cardiac transplantation. The explanted heart showed concentric ventricular scarring, which microscopically corresponded to myocardial fibrosis with scattered lymphocytic inflammation with no residual granulomas. Case 2: A 52-year-old man with a medical history significant for ischemic cardiomyopathy and cutaneous sarcoidosis with lung involvement presented with congestive heart failure. Endomyocardial biopsy and left apical core showed myocyte hypertrophy and scattered interstitial inflammation. Mediastinal lymph node showed nonnecrotizing granulomas, consistent with sarcoidosis. Eighteen months later, he underwent cardiac transplantation. The explanted heart showed biventricular dilatation with interstitial fibrosis. There was also mild diffuse inflammation and occasional granulomas with rare focal necrosis. Conclusion Though the gold standard for diagnosing cardiac sarcoidosis is demonstration of myocardial nonnecrotizing granulomas, the sensitivity of endomyocardial biopsy is low. This is due to sampling error and stage of disease. Chronic end-stage disease can lead to fibrous encasement of granulomas and end-stage heart failure, necessitating cardiac transplantation. Current guidelines employ a combination of clinical, radiologic, and histologic criteria for diagnosing cardiac sarcoidosis.