Chronic Inflammatory Cell Infiltration Research Articles

GRK2 Mediated Abnormal Transduction of PGE2-EP4-cAMP-CREB Signaling Induces the Imbalance of Macrophages Polarization in Collagen-Induced Arthritis Mice.

Rheumatoid arthritis (RA) is characterized by the massive infiltration of various chronic inflammatory cells in synovia. In synovial fluid of patients with RA, M1 macrophages are dominant among all subtypes of macrophages, the mechanisms of macrophages polarization imbalance in RA has not been fully illuminated. The prostaglandin E2 (PGE2) augments M2 polarization in part via the cyclic adenosine monophosphate (cAMP)-cyclic AMP responsive element binding (CREB) signaling. However, previous study found constant stimulus of PGE2 on fibroblast-like synovial cells of adjuvant arthritis rats induced the decrease of cAMP, which is primarily caused by G protein-coupled receptor kinase 2 (GRK2)-induced EP4 over- desensitization. Whether GRK2 mediated-EP4 over-desensitization reduces the level of cAMP and inhibits M2 polarization in RA is unclear. Here we observed M1 macrophages were dominant in peritoneal macrophages (PMs), bone-marrow-derived macrophages (BMMs) and synovial macrophages of collagen-induced arthritis (CIA) mice. PGE2 stimulated M2 polarization via the EP4-cAMP-CREB in normal mice, while failed to promote M2 polarization in the PMs of CIA mice. Further, we found the EP4 over-desensitization stimulated by PGE2 induced abnormal PGE2-cAMP-CREB signaling as well as the imbalance of macrophage polarization. Targeted disruption of GRK2 in Raw264.7 (RAW) through GRK2 siRNA or CRISPR/Cas9 downregulated the M1 macrophage markers, upregulated the M2 macrophage markers and the EP4 membrane localization. The reduced M1/M2 ratio and increased p-CREB expression were observed in BMMs and PMs of GRK2+/− mice. This study highlighted a novel role of GRK2 in regulating macrophages function in RA and provided new idea for precision treatment of RA.

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).

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.

Inflammasome activity in leucocytes decreases with abdominal aortic aneurysm progression.

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. The present extended immunohistochemistry study aimed to characterize inflammation in AAA and aortic control samples. In specific, the composition of the infiltrating immune cells and the expression of five inflammasome components in these immune cells were evaluated, in order to characterize their role in AAA development. A total of 104 biopsies from 48 AAA patients and 40 healthy specimens from organ donors were evaluated for their grade of inflammation. Infiltrating leukocytes were characterized by specific markers (CD3, CD20 and CD68), intramural localization and inflammasome protein expression [NLR family pyrin domain containing 3 (NLRP3), absent in melanoma 2 (AIM2), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), Caspase-1 and Caspase-5]. Macrophages, B and T lymphocytes were detected to a similar extent in grade 1, 2 and 3 AAA specimens, whereas in control samples, B and T lymphocytes were rarely observed in grade 1 lesions. Expression frequencies of NLRP3, AIM2 and Caspase-5 were significantly higher in grade 1 lesions of AAA samples compared with grade 1 lesions in control samples. Finally, AIM2, ASC, and Caspase-5 displayed significantly lower expression frequencies in grade 3 compared with grade 2 AAA specimens, and all inflammasome components were less frequently detected in grade 3 than in grade 1 lesions of AAA. This indicates that inflammasome activities decrease with AAA progression in infiltrating leukocytes. No statistically significant association was found for grade 2 and grade 3 lesions and total leukocyte count, C-reactive protein levels, maximal aortic diameter, plasma cholesterol level or biomechanical parameters (derived from finite element analysis) of the respective patients. Overall, the aortic wall of AAA contained lymphocytes and macrophages with different states of activity. The present data suggested that therapeutic inhibition of specific inflammasome components might counteract AAA development and progression.

Allergic fungal rhinosinusitis caused by <i>Aspergillus flavus</i>

Allergic fungal rhinosinusitis is a chronic inflammatory disorder of the sinonasal mucosa, with or without nasal polyps, which is frequently associated with microbial colonization including fungi. A case of fungal rhinosinusitis in Aseer area, Saudi Arabia, is described. The patient was admitted with common symptoms including nasal obstruction accompanied by itching, sneezing, rhinorrhea, epistaxis and recurrent headache. The patient was examined clinically and by CT scan. Nasal sinus swabs and a biopsy specimen were submitted for microbiological analysis. Polyps were surgically removed during functional endoscopic sinus surgery. Histopathology showed the presence of acute and chronic inflammatory cell infiltrates (rich in eosinophils) in the covering epithelium layers. Aspergillus flavus was isolated and identified from the lesions. The patient was discharged after showing good recovery, and home follow-up revealed no recurrences.Keywords: Paranasal sinuses, Polypoidal disease, Rhinorrhea, Fungi, Endoscopic sinus surgery

Possible Cytotoxic Effects of Silver Nanoparticles on the Parotid Glands of Albino Rats

Background: Silver has found to have many uses in the medical field due to its unique properties on the nanoscale, therefor the toxicity of nanosilver has become a hot topic and interesting area of research. Aim of the study: The study aimed to explore whether the silver nanoparticles (AgNPS) have a cytotoxic effect on the parotid gland of male albino rats. Materials and methods: The sample of study consisted of 30 adult male albino rats whose average body weight ranged from 250 to 300 grams and they were divided into two groups: Group 1 was consisted of 10 rats and served as controls, they received 0.5 ml deionized water per os using curved metallic oro-pharyngeal tube for 21 days. Group 2 was consisted of 20 rats, they received 10mg/kg b.w/day AgNP solution (in deionized water) with particle sizes ranging from 3 to 20 nm per os using curved metallic oro-pharyngeal tube (the recommended dose of each rat is 1.5-1.8 mg dissolved in 0.5 ml deionized water) for 21 days. The animals were observed for any body weight changes. The 30 rats were sacrificed after ending the experiment and dissection and separation were applied to their parotid salivary glands which were then fixed in 10% neutral buffered formalin. Afterwards, they were processed, fixed in paraffin, separated and stained with: 1-Hematoxylin and Eosin for histological evaluation of the parenchymal and stromal elements of the glands to detect any histological changes. 2-Streptavidin-biotin immunohistochemical method for localization of Ki67 for detection of the proliferation of cells. Results: The study found that the serous acini swelled with abnormal architecture and ill-defined outline. In addition, the study could not distinguish the lining cells of the serous acini. The serous acinar cells showed deeply stained, large hyperchromatic nuclei and mitotic cell division of the acinar cells. Focal oncocytic changes of acinar cells were observed. There was a dilation of the excretory ducts with wide lumen and they were vacuolated degenerated thick epithelial lining. As a result of the effect of the AgNPs, the connective tissue septa of the parotid glands widened and resulted in an in increase in the fibrosis with chronic inflammatory cells infiltration. Blood vessels showed dilatation and engorged with RBCs. In the lobes of parotid gland, the focal areas revealed that their secretory elements have been completely degraded, resulting in a large empty vacuole which was surrounded by deep infiltration of chronic inflammatory cells. Immunohistochemical examination revealed intense nuclear and cytoplasmic Ki67 immunoreactivity of acinar cells, ductal cells and endothelial cells lining blood vessels. Conclusion: Silver nanoparticles causing dramatic changes in the parotid gland. Even though, AgNPs have several therapeutic uses, their toxicity and therapeutic benefits should be weighed before a clinical decision to use them is reached.

Hepatitis B virus-related liver cirrhosis complicated with dermatomyositis: A case report.

BACKGROUNDTwenty percent of patients infected with hepatitis B virus (HBV) develop extrahepatic manifestations with HBV detected in the lymph nodes, spleen, bone marrow, kidneys, and skin. HBV infection has been associated with some autoimmune disorders. Dermatomyositis (DM) is an idiopathic inflammatory myopathy, which involves a viral infection, and DM has been identified in patients infected with HBV, but there is no direct histological evidence for an association between HBV and DM.CASE SUMMARYWe describe a familial HBV-infected patient admitted with liver function abnormality, rashes, a movement disorder, and an elevated level of creatine kinase (CK). A computed tomography scan of the lung showed pulmonary fibrosis, and a liver biopsy identified nodular cirrhosis. An electromyogram revealed myogenic damage, and a muscle biopsy showed nuclear migration in local sarcolemma and infiltration of chronic inflammatory cells. Immunohistochemical staining showed negative results for HBsAg and HBcAg. Fluorescence in situ hybridization showed a negative result for HBV DNA. The patient was diagnosed with HBV-related liver cirrhosis complicated with DM and was treated with methylprednisolone, mycophenolate mofetil, and lamivudine. Eight months later, the patient was readmitted for anorexia and fatigue. The blood examination showed elevated levels of aminotransferases and HBV DNA, however, the CK level was within the normal range. The patient developed a virological breakthrough and lamivudine was replaced with tenofovir.CONCLUSIONDM in chronic HBV-infected patients does not always associate with HBV. Antiviral and immunosuppressive drugs should be taken into consideration.

Biocompatibility and osteogenic potential of the new bioceramic endodontic material “EndoSeal MTA”

Aim: This study was conducted to analyze the biocompatibility of EndoSeal MTA® in rat subcutaneous tissue and to detect the osteogenic effect of this material. Methods: The biocompatibility was assessed using the subcutaneous implantation technique. Thirty male albino rats were the subjects used during current research. Animal subjects were anaesthetized, shaved in two areas of the dorsal surface of both of the lower limbs and subcutaneous pockets were made to accommodate the material, which was placed in a polyethylene tubes. Empty polyethylene tubes were used as control. Fifteen animals were sacrificed at each observation period (1 month and 3 months implantation). A wide excision of the tissues surrounding the implant was taken, managed and histo-stained with Haematoxylin and Eosin stain for histopathological evaluation of the inflammatory and vascular responses. The Von Kossa histochemical stain was used for demonstration of the mineralized structures. The stained sections were examined using light microscopy. Quantitative analysis of the inflammatory cells was performed using an image analyzer computer system. Results: After one month of tube implantation, mild chronic inflammatory cell infiltration, loosely organized collagen fibers and few slightly dilated blood vessels were observed in the control group. In the experimental group, the inflammatory reaction ranged from mild to moderate. The inflammatory reaction significantly subsided with time in both groups. The difference between the control and experimental group regarding the total number of inflammatory cells was not statistically significant in the both observation periods. No evidence of tissue necrosis was found in the control or experimental groups throughout the experiment. Conclusions: It could be concluded that EndoSeal MTA® is well tolerated by the subcutaneous connective tissues of rat. The study showed osteogenic potential of EndoSeal MTA®.

Xanthogranulomatous Oophritis masquerading as ovarian neoplasm: a case report

Xanthogranulomatous inflammation is a special form of chronic inflammation that is destroying normal tissue of affected organs which are replaced by chronic inflammatory cell infiltrate admixed with foci or sheets of foam cells, fibroplasia, chronic inflammatory cell infiltrate and vascular proliferation. Only a few cases of xanthogranulomatous oophoritis have been reported.We report a case of 35 year old female who presented with lower abdominal pain and polymennorhea.A total hysterectomy with bilateral salpingoopherectomy was performed on the suspicion of an ovarian neoplasm.

Tumefactive Multiple Sclerosis Clinically Mimicking Acute Stroke and Lesional Migration Along the Biopsy Tract: A Case Report

Tumefactive multiple sclerosis is a form of demyelinating disease which patient can present with acute stroke. We reported a case of a 49-year-old woman with well controlled hypertension, who presented with right hemiplegia 15 hours prior to admission. The initial diagnosis of acute stroke was made. Emergency computed tomography showed hypodense lesion at the left lentiform nucleus and posterior limb of the left internal capsule. The magnetic resonance imaging (MRI) study showed hyperintense FLAIR lesion in the left lentiform nucleus, left internal capsule, left thalamus, and periventricular area of the left frontoparietal region, some areas of restricted diffusion and inhomogeneous enhancement. The MR spectroscopy (MRS) of the lesion showed increased choline peak, decreased creatine and NAA peaks, and maximal choline to creatine ratio 2.25. Her symptoms deteriorated with progressive headache and motor aphasia. The follow up MRI showed extension of the inhomogeneous enhancing lesion along the biopsy tract at the left frontal lobe with the enhancing and MR spectra pattern similar to the lesion. The craniotomy with left frontal lesion excision included the mass and the biopsy tract was done. The lesion showed acute and chronic inflammatory cell infiltration with macrophages, necrotic tissue and reactive gliosis. The further pathological worked up demonstrated foci of demyelination with relative axonal preservation, numerous CD68+ macrophages with intracyto-plasmic Luxol fast blue(+) myelin debris. Perivascular and parenchymal CD3+ T-cells were identified, especially in demyelinating foci. These findings supported the diagnosis of tumefactive multiple sclerosis. Her conditions were improved after treating with pulse methylprednisolone and intravenous immunoglobulin (IVIG). Follow up MRI study 4 months after treatment revealed almost resolution of the preexisting inhomogeneous enhancing lesion.

Inflammatory myofibroblastic tumour; a case report with a unique ROS1 fusion variant

Inflammatory myofibroblastic tumours (IMTs) are a distinctive spindle cell lesion with a prominent infiltrate of chronic inflammatory cells including lymphocytes and plasma cells. It is often seen in children and young adults, although it can affect any age. Common sites of involvement include the lung, abdominal cavity and retroperitoneum. Around 50% of IMTs harbour rearrangements of the ALK (anaplastic lymphoma kinase) gene, enabling treatment with tyrosine kinase inhibitors such as crizotinib. Recently, a few other genomic alterations, including ROS1 gene mutations have been identified in a population of ALK negative IMTs. The current reported fusions include YWHAE-ROS1 and TFG-ROS1.

Inflammatory and fibrosis infiltration in synovium associated with the progression in developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder characterized by progressive joint soreness and limited mobility. The aim of the present study was to investigate the pathological changes and inflammatory infiltration in the hypertrophic synovium of the hip joint associated with the progression of DDH. Synovial biopsies in the hip joint are obtained from patients with moderate DDH and severe DDH during surgery. These biopsies are processed for histological and immunohistochemical (IHC) analysis and investigation of the pathological processes in a synovium, including types of inflammatory cell infiltration, synovial angiogenesis and fibrosis, neuron endings and neuropeptide invasion. Correlation analysis was performed between the mean optical density (MOD) of each antibody, and Harris hip score (HHS) and visual analogue score (VAS) using the Spearman correlation test. Chronic inflammation in the synovium was observed via the positive IHC staining of inflammatory cells, such as T cells, B cells, macrophages and leukocytes. Excessive staining of vimentin and α smooth muscle actin in the synovium of severe DDH represented significant fibrosis and angiogenesis. These targets were also significantly correlated with HHS in severe DDH. The MOD levels of CD68 (indicators of macrophage) indicated apparent correlations with HHS and VAS in patients with severe DDH. The labels of nerve fibers and pain transmission indicators were as follows: Neurofilament‑200 and substance P. Calcitonin gene‑related peptide was upregulated in the synovium of severe DDH in contrast to that in the synovium of moderate DDH. The MOD levels of NF‑200, SP and CGRP were correlated with VAS in severe DDH. The pathology of DDH includes chronic inflammatory cell infiltration corresponding with nerve fibers and fibroblastic proliferation, which might contribute to arthritis progression and joint soreness in DDH.

Inflammatory Pseudotumor of the Liver

Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion, characterized by chronic infiltration of inflammatory cells and areas of necrosis mimicking a malignant tumor. Few cases have been reported, and the precise etiology is still unknown. Patients usually present with abdominal pain, fever, and jaundice. Herein, we report the case of a 78-year-old male with a history of diabetes mellitus who had abdominal fullness and body weight loss for 4 months. A computed tomography scan showed a 15-cm liver tumor in segment 2 and 3 and suspected hepatocellular carcinoma. Left hepatectomy was performed, and the pathology showed IPT. After surgery, the symptom of abdominal fullness subsided.

An enigmatic case of pure neuritic leprosy with trophic ulcers

Leprosy is one of the most common diseases of peripheral nerves. In pure neuritic leprosy, skin along the distribution of the affected nerve is usually hypo-anesthetic or anesthetic, and as a rule, no classical leprosy skin lesions/patches should be present. However, depending on the severity of sensory and autonomic dysfunction, there could be a variable degree of hypo/anhidrosis, xerosis, fissuring, and ulcers along its distribution. Diagnosis of leprosy in the absence of typical dermatological features is difficult and requires histopathological confirmation using nerve biopsy. We report a case of leprosy with peripheral neuropathy without skin lesions. Nerve biopsy showed chronic inflammatory cell infiltration, epithelioid-cell granulomas, and the presence of Mycobacterium leprae on Modified Ziehl-Neelson stain. Hence, in leprosy prevalent countries like India, this form of leprosy should be thoroughly investigated, especially in patient without skin changes and presenting with trophic ulcers. It was a diagnostic challenge requiring high degree of clinical suspicion and thorough investigations.

Synovial Lipomatosis with Chondroblastoma in an 8-year-old Female: A Previously Unreported Entity.

Introduction:Synovial lipomatosis is a rare disease entity and a very small number of cases have been reported so far. It is characterized by villous proliferation of the synovium with expansion by mature adipose tissue. The etiology is unclear, thought cases can be seen secondary to injury, inflammation, chronic degenerative changes and neoplasms. Etiopathogenesis is still unclear, however is seen secondary to injury, inflammation, chronic degenerative conditions and neoplasms.Case Report:An 8-year-old female child presented with pain and swelling in the left knee. Radiological examination suggested of a lytic lesion in upper tibia along with reactive synovial thickening. The lytic lesion was excised and an incisional biopsy was taken from the hyperplastic synovium. Histopathological examination of the synovial tissue showed villi-like structures with mature adipose tissue expanding the synovial lining along with the presence of mild chronic inflammatory cell infiltrate. The lytic lesion showed a cartilaginous tumor comprising mineralized chicken wire matrix surrounding the chondroblasts. A final diagnosis of synovial lipomatosis with chondroblastoma was made on histopathological examination.Conclusion:This may be the first case report in medical literature of synovial lipomatosis coexisting with chondroblastoma in an adolescent girl. It also highlights the need for its increased awareness among young radiologists and pathologists so that an early diagnosis directs correct management and prevents further joint morbidity.

THE EFFECT OF PRETREATMENT WITH TOLL-LIKE RECEPTOR 4 ANTAGONIST RESATORVID ON METHOTREXATE-INDUCED LIVER INJURY IN RATS: HISTOPATHOLOGICAL STUDY

Objective: This research aims to evaluate the histopathological changes after pretreatment with resatorvid against methotrexate induced-liver injury.Methods: 28 male albino-wistar rats divided into random 4 groups (7 rats in each). Control group: Rats left untreated. Vehicle pre-treated group: Rats were administered dimethyl sulfoxide (DMSO) followed by methotrexate (MTX). Methotrexate treated group: Rats left untreated then administered MTX. Resatorvid pre-treated group: Rats were administered resatorvid followed by MTX. 24 h after the end of treatment, the animals were sacrificed. Liver tissue samples dissected out immediately and fixed in 10% formalin. The traditional procedures (paraffin-embedded method) was used to prepare liver tissue for microscopic evaluation by none alcoholic fatty liver disease (NAFLD) Activity Score Components.Results: Liver tissue sections of MTX-treated group show moderate-to-severe steatosis of hepatic cells and micro- and macro- hepatocellular fatty degeneration and giant fatty cysts with chronic inflammatory cells infiltration. While liver tissue sections of the resatorvid pre-treated group show moderate hepatic cellular fatty degeneration, with a decreased number of fatty cysts chains and the inflammation disappeared.Conclusion: Resatorvid hepatoprotective effect against MTX-induced injury was promising throughout resolving the accompanying inflammation and partial restoring histopathological fatty alterations.

Urocystitis, pyelonephritis, renal papillary necrosis and chronic tubulointerstitial disease causing chronic renal insufficiency in a Siberian tiger (Panthera tigris altaica): a case report

The present case report describes a case of chronic renal failure characterised by renal medullary fibrosis and renal papillary necrosis in a male Siberian tiger (Panthera tigris altaica). A 12-year-old male Siberian tiger presented with depression, anorexia and weight loss. Blood urea nitrogen (> 50.4 mmol/l) and ammonia (71.7 µmol/l) were increased, suggesting chronic renal failure and uraemia. The tiger died secondary to gastric haemorrhage. At necropsy, the kidneys had yellow lesions in the medulla and renal papillae and petechiae in the cortex. The stomach had multiple mucosal ulcers and haemorrhage. Microscopically, marked renal medullary fibrosis and renal papillary necrosis were observed with tubular atrophy, degeneration, coagulative necrosis, calcification and chronic inflammatory cell infiltration. The renal cortex showed moderate interstitial inflammation. The urinary bladder exhibited epithelial desquamation and submucosal fibrosis. The tiger was diagnosed with chronic renal failure secondary to renal papillary necrosis and medullary fibrosis.

Incidental Finding of a Colonic Gastrointestinal Stromal Tumor (GIST) in Screening Colonoscopy: A Case Report and Review of Literature

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gut. GISTs arise due to mutation in the c-kit tyrosine kinase of the interstitial cells of cajal (ICCs) that leads to continuously activated state of tyrosine kinase and thus results in formation of GISTs. GISTs are most common in stomach (75%) and small intestine (25%). Less than 5 % of GISTs occur in colon and rectum. We present a 50 year old male who underwent a routine screening colonoscopy and was otherwise asymptomatic. Physical examination was unremarkable. Past medical history was significant for developmental delay and chronic constipation. Colonoscopy revealed a submucosal appearing lesion with an overlying ulcer at the hepatic flexure. Histopathology revealed spindle cells are arranged in a storiform-type pattern with chronic inflammatory cell infiltrate including several eosinophils, reactive epithelial cell changes and focal ulceration without any adenomatous change is observed. Immunohistochemical stains were positive for DOG -1 and CD117. CT scan of the abdomen with contrast did not reveal any evidence of metastatic lesions. GISTs account for less than 1% of gastrointestinal (GI) malignancies and only make up to 0.1% of colorectal tumors. A few other cases of colonic GIST have been reported in literature, however, they are still rare and account for less than 2% of all GISTs. Median age of presentation is 60 years with a slight male predominance. The most common clinical presentation is abdominal pain followed by gastrointestinal bleeding, obstruction and perforation. CD117 is the most important diagnostic marker and is positive in more than 95% of cases and CD34 is positive in 70% of cases. The most common cellular morphology noted in histopathology is spindle cell type followed by epithelioid and mixed cellular types. Approximately 30% of GISTs have malignant potential. Prognosis depends on the size of the tumor, histology, mitotic potential and local invasion. CT scan with contrast is the preferred imaging modality of choice for initial staging. Treatment is surgical resection and adjuvant therapy with Imatinib (tyrosine kinase inhibitor). Close surveillance is recommended in the first 3 to 5 years after treatment due to maximum risk of recurrence within that time frame. A screening colonoscopy prevented adverse outcomes in this patient who could not report symptoms due to intellectual disability.1533_A Figure 1. GIST CD117 Positive1533_B Figure 2. GIST - Spindle cell histopathology1533_C Figure 3. Hepatic flexure lesion with a central ulceration

Clinicopathologic features and immunophenotype of pseudosarcomatous myofibroblastic proliferation of urinary bladder

Objective: To investigate the clinicopathologic features, immunohistochemical phenotypes and biological behavior of pseudosarcomatous myofibroblastic proliferation (PMP) of the urinary bladder which may be misdiagnosed as a malignant neoplasm and undergo extensive treatment. Methods: Six cases of PMP of the urinary bladder were collected from 2001 to 2016 at Beijing Tiantan Hospital, Capital Medical University. The clinicopathologic features and immunophenotypic profile were studied by histopathological and immunohistochemical investigations with clinical follow-up. At the same time, the translocation of ALK gene was detected by fluorescence in situ hybridization (FISH). Immunohistochemistry was carried out using EnVision method for the expression of AE1/AE3, vimentin, EMA, SMA, Caldesmon, Calponin, desmin, ALK, Ki-67, MyoD1, myoglobin, CD34, S-100, CD117, CK7, CK20, GATA3, p63 and CK5/6. The related literature was reviewed. Results: There were two male and four female patients, significantly more common in women. The age of the patients was 27 to 53 years, and the median age was 35 years. The main clinical symptom was painless gross hematuria, one case with dysuria, and one case showed recurrent cystitis. There was no history of surgery and trauma. Follow-up ranged from 4 months to 13 years and showed five cases without recurrence and one case with recurrence. Microscopy showed submucosal lesion with inflammatory exudate and bleeding on the surface, in some cases extending to the superficial muscles of the bladder wall. The lesion was characterized by the proliferation of plump spindle cells, which were loose or dense in arrangement. There were varying degrees of acute and chronic inflammatory cells infiltration in the myxoid matrix. Spindle cells arranged in disorder, or a dense stranding, especially abundant in the cell region. The median mitotic rate was <2/10 HPF cells, but there were no pathological mitotic figures and without nuclear atypia in most spindle cells. Spindle cells with eosinophilic cytoplasm showed long tapering cytoplasmic projections. Oval or short spindle nuclei had vacuolization with prominent nucleoli, looking like ganglionic cells. There were scarce collagen fibers, and a few spindle cells degenerated with chromatin blurred. Some areas showed a granuloma-like pattern and neutrophils within vascular cavity. Immunohistochemically, the spindle cells were diffusely positive for vimentin, SMA and caldesmon. CKpan was strongly and diffusely positive. Desmin and calponin expression was varying. Ki-67 positive cells were about 35% to 55%, but the spindle cells were negative for myoglobin, S-100, CD117, CD34, p63 and CK5/6. FISH test showed that there was no ALK isolated signal in 6 cases of PMP, and so no positive cases were found. Conclusions: PMP of the urinary bladder is a benign non-neoplastic myofibroblastic proliferative lesion. Morphology is extremely easy to be misdiagnosed as malignant tumors, and therefore more attention should be paid to avoid this misdiagnosis.

3. An enigmatic case of undiagnosed severe diarrhoea post living donor liver transplant

Background and Aims: Graft versus Host Disease (GVHD) after orthotopic liver transplant (OLT), although rare, carries >80% mortality. Early diagnosis, prompt treatment, and aggressive supportive care are imperative to potentially reverse this otherwise fatal ailment. We describe a case of recurrent severe diarrhoea post living donor OLT who was diagnosed with acute GVHD. Case Summary: A 56 year old lady underwent an uneventful (swap) living donor OLT for Hepatitis C related chronic liver disease with multifocal hepatocellular carcinoma. Initial immunosuppression consisted of tacrolimus, mycophenolate mofetil and prednisolone. At ten weeks post- transplantation, sirolimus was introduced and Tacrolimus tapered gradually. At 78 and 84 weeks post-transplantation she had two episodes of acute cellular rejection treated with pulse methylprednisolone therapy. She developed profuse watery painless diarrhoea with significant nocturnal symptoms at 90 weeks post-transplantation, for which she was admitted on several occasions. Multiple stool examinations were bland (no pus cells, red blood cells, mucus, ova and cysts), negative for cryptosporidium and clostridium difficile (antigen + toxin) and there was no Cytomegalovirus viremia. Laboratory parameters revealed mild anemia, thrombocytopenia, hypoalbuminemia and transaminitis. Celiac serology was negative. Every time her symptoms settled with intravenous fluids and antibiotics, only to recur within few days. An upper gastrointestinal endoscopy and duodenal biopsy was normal. Random normal appearing terminal ileum and colonic mucosal biopsies revealed mild active GVHD. Lamina propria showed mild chronic inflammatory cell infiltrate along with lymphoid aggregates. Few crypts demonstrated apoptosis (Fig. 1). There were no crypt dropouts, cryptitis or crypt abscesses (GVHD grade I). She was started on oral budesonide therapy. Her symptoms responded briskly and diarrhoea subsided. At six months follow-up, she was completely asymptomatic. Conclusions: This is the first case of GVHD with isolated gastrointestinal manifestations post OLT to be reported from India and treated successfully with oral budesonide. The authors have none to declare.