Lymphoplasmacytic Infiltration Research Articles

Corneal Melting in Undiagnosed Goujerot Sjogren’s Syndrome: A Case Report

Keratolysis or corneal melting is a very rare situation that might occur in different inflammatory systemic diseases such as Sjogren syndrome. In the case of sterile corneal ulcers, characterized by the absence of ocular inflammation, the optimal treatment has not yet been established. We report the case of a unilateral aseptic keratolysis revealing primitive Sjogren guzzler syndrome and having responded well to the treatment. Clinical case: a 56-year-old woman who presented with a notion of inflammatory polyarthralgia for 4 years with self-medication by oral non-steroidal anti-inflammatory drugs NSAID presented a month before her first examination, a reduced visual acuity with foreign body sensation in both eyes. After a month of ophthalmic examination for a corneal ulcer, the visual acuity dropped to HM, and the examination found a corneal perforation measuring less than 1 mm with a positive spontaneous seidel and an athalamia. A treatment with cyanoacrylate glue was performed along with medical treatment. A labial biopsy performed found a lymphoplasmacytic infiltration of the exocrine gland in favor of a primitive Gougerot Sjogren syndrome. Gougerot-Sjögren syndrome is a systemic autoimmune disease characterized by damage to the exocrine glands, in particular the lacrimal and salivary glands. The treatment of corneal perforations is based on different choices such as cyanoacrylate glue, amniotic graft, conjunctival recovery, and keratoplasty.

Recurrence of autoimmune liver diseases after liver transplantation: Review and expert opinion statement.

Autoimmune liver diseases (AILDs) constitute the fourth most common indication for liver transplantation (LT) across the world. In general, the outcomes after LT are acceptable; however, disease recurrence after LT is common for all AILD, which can negatively affect graft and overall survival. Several questions persist, including the risk factors associated with recurrent disease, optimal antirejection medications, strategies to reduce the risk of recurrence, and how to best incorporate these strategies into clinical practice. For that reason, we assembled an international group of experts to review evidence to address these outstanding questions regarding LT for AILD. Survival rates after LT are ~90% and 70% at 1 and 5 years, and recurrent disease occurs in 10%-50% of patients with AILD. In patients with disease recurrence, graft survival decreased by 18% and 28% and overall survival by 8% and 12% at 5 and 10 years after LT, respectively. Recurrent autoimmune hepatitis is associated with high aminotransferases and immunoglobulin G (IgG) before LT, lymphoplasmacytic infiltrates in the explants, and may be associated with the absence of steroids after LT. However, the efficiency and safety of triple immunosuppressive maintenance therapy is still debatable. Younger age at diagnosis with primary biliary cholangitis or LT is associated with primary biliary cholangitis recurrence. Preventive use of ursodeoxycholic acid reduces the risk of recurrence and has a benefit in graft and patient survival. Episodes of systemic inflammation, including T-cell-mediated rejection, active ulcerative colitis, and episodes of cholangitis, are associated with recurrent PSC. Recurrent disease for AILD is associated with worse graft and patient survival. Patients with autoimmune hepatitis could be considered for long-term low-dose predniso(lo)ne, whereas patients with primary biliary cholangitis should be placed on preventive ursodeoxycholic acid after LT. There are no specific treatments for PSC recurrence; however, adequate control of inflammatory bowel disease and optimal immunosuppression to avoid T-cell-mediated rejection should be encouraged.

Pneumocystis murina lesions in lungs of experimentally infected Cd40l-/- mice.

The Cd40l-/- mouse is a well-established model of X-linked hyper-immunoglobulin M (IgM) syndrome, an immunodeficiency disorder of human beings characterized by the lack of expression of the CD40 ligand (CD40L) on activated T-cells, predisposing to infections with opportunistic pathogens like Pneumocystis jirovecii. The aim of our study was to describe the pulmonary lesions in Cd40l-/- mice experimentally infected with Pneumocystis murina, in comparison with naturally infected severe combined immunodeficient (SCID) mice. Formalin-fixed paraffin-embedded lungs from 26 Cd40l-/-, 11 SCID, and 5 uninfected Cd40l-/- mice were examined by histology and immunohistochemistry for the presence of the pathogen and for leukocyte populations (CD3, CD4, CD45R/B220, CD8a, Iba-1, Ly-6G, CD206, MHC II, and NKp46/NCR1). Infection was confirmed by immunohistochemistry in 18/26 (69%) Cd40l-/- mice and in 11/11 (100%) SCID mice. Fourteen out of 26 (54%) Cd40l-/- mice had interstitial pneumonia. Twenty-three out of 26 (88%) Cd40l-/- mice had peribronchiolar/perivascular lymphoplasmacytic infiltrates, rich in B-cells and Mott cells. Acidophilic macrophage pneumonia was additionally found in 20/26 (77%) Cd40l-/- mice. Only 4/11 (36%) SCID mice had interstitial pneumonia, but no peribronchiolar/perivascular infiltrates or acidophilic macrophage pneumonia were observed in this strain. This study represents the first description of pulmonary histopathological lesions in Cd40l-/- mice infected with P. murina. We speculate that the singular characteristics of the inflammatory infiltrates observed in Cd40l-/- mice could be explained by the specific immune phenotype of the model.

The etiology and differential diagnosis of "autoimmune hepatitis-like liver disease" in children: a single-center retrospective study.

Children with autoimmune hepatitis (AIH) often present with symptoms similar to those of other liver diseases. This study consists of a comparison between the clinical and histological characteristics of AIH and those of other four AIH-like liver diseases [i.e., drug-induced liver injury (DILI), gene deficiency, infectious liver disease and other etiology of liver disease], as well as an evaluation of the AIH scoring system's diagnostic performance. All children with AIH-like liver disease at our center from January 2013 to December 2022 were included. The clinical and histological characteristics of the AIH group were retrospectively analyzed and compared with those of the other four groups. A total of 208 children were included and divided into AIH group (18 patients), DILI group (38 patients), gene deficiency group (44 patients), infectious liver disease group (74 patients), and other etiology group (34 patients). The antinuclear antibodies (ANA) ≥ 1:320 rate was significantly higher in the AIH compared to the other four groups after multiple testing correction (p < 0.0125), while patients with positive antibodies to liver-kidney microsomal-1 (anti-LKM1, n = 3) and smooth muscle antibodies (SMA, n = 2) were only observed in the AIH group. The positive rates of antibodies to liver cytosol type1 (anti-LC1) and Ro52 were higher than those in the other four groups. The serum immunoglobulin G (IgG) and globulin levels, as well as the proportions of portal lymphoplasmacytic infiltration, lobular hepatitis with more than moderate interface hepatitis, and lobular hepatitis with lymphoplasmacytic infiltration, were significantly higher in the AIH group than in the other four groups after multiple testing correction (p < 0.0125). The cirrhosis rate in the AIH group was higher than that in the DILI and infectious liver disease groups (p < 0.0125). Both the simplified (AUC > 0.73) and the revised systems (AUC > 0.93) for AIH have good diagnostic performance, with the latter being superior (p < 0.05). Positive autoantibodies (ANA ≥ 1:320 or anti-LKM1 positive, or accompanied by SMA, anti-LC1 or Ro-52 positive) and elevated serum IgG or globulin levels contribute to early recognition of AIH. The presence of lobular hepatitis with more than moderate interface hepatitis and lymphoplasmacytic infiltration contribute to the diagnosis of AIH.

Waldenstrom Macroglobulinemia Recurrence with Bing–Neel Syndrome Presentation

Bing–Neel syndrome (BNS) is a rare condition that may occur in patients with Waldenstrom macroglobulinemia (WM) and is caused by lymphoplasmacytic infiltration into the central nervous system. BNS is an extramedullary manifestation of WM which may present with various neurological signs and symptoms that make the diagnosis difficult to achieve. We present a case of BNS in a 60-year-old patient diagnosed 6 years after recovering from Waldenstrom’s macroglobulinemia. We observed the patient for a secondary generalized focal motor seizure. Unenhanced brain CT revealed slight hyperdensity of left parietal subarachnoid spaces. The MRI of the brain and spinal cord showed leptomeningeal enhancement in both parietal lobes. The presence of monoclonal bands (light chain k and IgM) was found in cerebrospinal fluid, leading to the diagnosis of BNS. The patient started treatment with ibrutinib and remains clinically stable during a 1-year follow-up. However, the MRI showed the appearance of a new subcortical left parietal lesion. BNS is an extremely rare presentation of WM that should be recognized and considered early in the presence of unexplained neurological symptoms in patients with a history of WM, even if the patient appears to have recovered.

Multi-organ IgG4-related sialadenitis diagnosed via core needle biopsy: A case report

Diagnosing Immunoglobulin G4-related sialadenitis (IgG4-RS) remains challenging due to its rarity and similarity to other forms of sclerosing sialadenitis. Controversies persist regarding biopsy approaches. We presented a case with sclerosing sialadenitis in the major salivary glands, pancreatitis, elevated serum IgG4 levels, and core needle biopsy (CNB) revealed lymphoplasmacytic infiltration. This case report aims to raise awareness of the potential use of CNB in suspected IgG4-RS cases, minimizing associated risks compared to open biopsy.

Clinicopathological and molecular genetic features of Crohn's disease

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

Histological changes of the esophageal mucosa in patients with achalasia

Background. Morphological changes in the esophageal mucosa (EM) depend on the type of esophageal achalasia (ЕA). In types I and II of ЕA, morphological changes are subtle, but in types III and IV, dystrophic changes are clearly visible. ЕA can transform from one type to another. This mainly concerns the pathological transition from inflammation to fibrosis. The purpose is to investigate the histological and morphometric differences of the EM depending on the type of ЕA. Materials and methods. We studied 51 biopsy specimens of the EM in patients with ЕA. The distribution of biopsies for histo-morphometric characterisation of changes in the EM in ЕA was used according to the radiological classification of the Japanese Society of the Esophagus (2017). To study the general histological structure of the EM, biopsy sections of 5–7 μm thickness were cut using a rotary microtome RM60-ECA, stained with hematoxylin-­eosin according to the standard method, and staining for fibrosis was performed according to the Mallory-Slinchenko method. For morphometric study, the sections were photographed using a light microscope XSZ-21 (Ukraine) and measured with the Image J.45S software (USA). Results. In histological examination, the development of structural changes in the EM on the background of ЕA in 24.1 % of cases of type III was accompanied by migration of eosinophils into the lamina propria, and in 100 % — by epithelial atrophy. Dense lymphoplasmacytic infiltration was noted in all patients with types III and IV of ЕA, as well as in 93.3 % of patients with type II, whereas in type I of ЕA, this sign was diagnosed in 20 % of cases (p = 0.005 and p = 0.0001 compared with types II and III of ЕA). Ballooning degeneration was detected in 20 % of patients with EA type II, in 57.1 % with type III and in 100 % of patients with type IV. Fibrosis in the EM was observed only in ЕA type IV. Thickening of the basal layer of the squamous epithelium of the EM was noted in all patients with type IV ЕA and 86.2 % with type III ЕA, while in types I and II, it was observed in only 20 and 13.3 % of cases, respectively (p = 0.007 and p &lt; 0.001 compared with type III ЕA). Expansion of the intercellular space was detected in 100 % of patients with types II, III and IV, and in only 40 % with type I (p = 0.009 and p = 0.0017 compared with types II and III ЕA). According to the morphometric study, the squamous epithelial height was largest in type IV ЕA — 343.40 μm versus 325.45 μm in type I ЕA (p = 0.028). The height of the basal layer was the lo­west in type II ЕA (about 40 µm) and the largest in type IV ЕA (about 50 µm) (p = 0.074). An increase in the intercellular space by 41.6 % was noted with the progression of ЕA (p = 0.001). The height of the papillae is the lowest in type II ЕA — 125.05 μm and the largest in type IV ЕA — 134.70 μm (p = 0.006). Conclusions. All types of AE are accompanied by esophagitis, histological examination of which revealed an increase in the height of the basal layer, papillae height, expansion of the intercellular space, balloon degeneration, fibrous changes in the lamina propria, lymphoplasmacytic and eosinophilic infiltration of the EM that progress depending on the type of ЕA. Morphometric studies of the EM in terms of increasing the height of the epithelium (p = 0.028), the height of the papillae (p = 0.006), the height of the basal layer (p = 0.074), and the expansion of the intercellular space (p = 0.001) allow to detect the type of ЕA.

Sino-Orbital IgG4 Related Disease- An Uncommon Entity.

IgG4 related disease (IgG4-RD) is an auto immune fibro-inflammatory condition, characterised by presence of IgG4 positive lymphoplasmacytic infiltrates and extensive fibrosis of the involved organ. It commonly affects pancreas, biliary tract and salivary glands. Sino-orbital involvement is a relatively rare presentation. There is extensive fibrosis of the involved organ. Biopsy is often diagnostic and it shows extensive necrosis and lymphoplasmocytic infiltrates. They show dramatic response to steroid therapy. Here we present three cases of IgG4-RD disease involving orbit and para nasal sinuses who were evaluated and treated in a tertiary care teaching hospital over a period of 2 years.

Persistent Lumbar Pain and Fever: Osteomyelitis as Diagnosis Challenge

Objective: This study aimed to evaluate the clinical characteristics and diagnostic challenges associated with osteomyelitis in patients presenting with persistent lumbar pain and fever. Methods: We conducted a descriptive observational study, reviewing four cases of osteomyelitis diagnosed at our hospital’s Emergency Department in 2022. Data on patient demographics, medical history, clinical presentation, diagnostic methods, and treatment outcomes were analyzed. Findings: The cases included middle-aged to elderly men, with predisposing factors such as urological interventions and immunodeficiency. Imaging studies, particularly CT-scan and MRI, were instrumental in diagnosing lumbar spondylodiscitis. Biopsies revealed lymphoplasmacytic infiltrates and treatment responses were positive in all cases after eight months of follow-up. The study highlights the importance of considering osteomyelitis in the differential diagnosis of lumbar pain and fever, necessitating multidisciplinary collaboration for timely management.

Abstract 6166: A whole-organ ex vivo optical imaging technique for non-destructive, more precise identification of serous tubal intraepithelial carcinoma (STIC) in fallopian tubes

Abstract Objective With the recent discovery of the fallopian tube (FT) origin of the most common and lethal type of ovarian cancer, high grade serous cancer (HGSC), engineering solutions to overcome the limitations of standard histopathology to more reliably identify incipient HGSCs and their serous tubal intraepithelial carcinoma (STIC) precursors are much needed. This investigation tests the potential of whole-organ ex vivo optical imaging of freshly excised FTs to label and sample abnormal tubal epithelium prior to formalin fixation and paraffin embedding for standard histopathology. Methods This investigation prototyped “OVASEEK”, a whole-organ, near-infrared optical imaging platform for identification of STICs. This prospective biospecimen protocol with annotated clinical data was approved by the IRB. Following salpingectomy at the time of hysterectomy for benign indications, FTs from study participants are longitudinally bivalved. Half of the FT is retained for routine evaluation using the Sectioning and Extensively Examining the Fimbriated end (SEE-FIM) protocol by Johns Hopkins gynecologic pathologists (Gyn Path), while the other half is sent overnight in organ transplant media to MIT for imaging on OVASEEK. Hyperspectral “label free” first pass imaging is performed using a series of band-pass filters. Second pass fluorescence imaging is then performed using nanoparticles tagged with anti-LAMC1 antibodies targeting laminin γ1, a known STIC surface marker. Abnormal signal(s) on OVASEEK imaging of the FT epithelium are tattooed with black ink, the tissue is formalin fixed and returned to Gyn Path for serial sectioning. Research findings are reported in an addendum to the formal pathology report in the electronic medical record and discussed with the patient by the gynecologic oncologist co-investigator. Results OVASEEK enabled non-destructive imaging over a wide field-of-view ~ 12×12 cm, with features of interest in the 1,050-1,550 nm range. In this pilot study, OVASEEK identified histopathologic abnormalities missed by standard SEE-FIM in 20% of FTs (n=2 out of 10). In each case, OVASEEK found microscopic (~200 µm) foci of salpingitis, a lymphoplasmacytic infiltrate consistent with inflammation. Performance of serial sectioning and histopathologic examination of the tattooed epithelium yielded this diagnosis. Conclusion Work is ongoing to improve the resolution, speed and sensitivity of OVASEEK for STIC detection. Identification of µm-sized foci of inflammation using OVASEEK is proof-of-principle that whole-organ ex vivo imaging of freshly excised FTs may be an innovation that improves the diagnostic performance of routine histopathology. Accurate and reproducible diagnosis of STIC and concurrent microscopic HGSC is imperative to the understanding of the early pathogenesis of HGSC in clinically actionable ways. Citation Format: Neelkanth M. Bardhan, Vivek Rastogi, Rebecca L. Stone, Angela M. Belcher. A whole-organ ex vivo optical imaging technique for non-destructive, more precise identification of serous tubal intraepithelial carcinoma (STIC) in fallopian tubes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6166.

Abstract 888: Uncovering clinically relevant omics signatures from pan-cancer imaging and multi-omics data integration

Abstract Despite advancements in deep learning for histopathology, integrating these insights with multi-omics data to uncover clinically relevant omics pathway-level signatures remains a challenge. Our study addresses this gap by applying unsupervised learning techniques on pan-cancer multi-omics data, leveraging 3,080 Hematoxylin and Eosin (H&amp;E) images from 1,010 patients in Clinical Proteomic Tumor Analysis Consortium (CPTAC) to uncover omics pathway-level signatures that drive discernable morphology phenotypes at the tissue level. First, imaging models were trained to predict clinical and mutation outcomes, and thereafter, integrated with transcriptomic and proteomic expression data using sparse canonical correlation analysis. Our findings reveal that images of TP53 mutated samples exhibited increased nuclear size and dense lymphoplasmacytic infiltration. These morphological changes correlated with neutrophil and macrophage signaling at the proteomic level, and IL-1 mediated signaling at the transcriptomic level, highlighting the complementary perspectives different omics can provide. To further elucidate immune interactions, we applied multi-omics deconvolution to identify 7 immune subtypes, characterizing each with gene set enrichment, germline DNA variations, and kinase activations. We show that imaging models trained to predict these subtypes differentiate tissue morphologies corresponding to immune enrichment (AUROC: 0.84). To further confirm the robustness of our approach, we trained models to predict co-regulated proteomic modules clustered by independent component analysis. We demonstrate a signature in pan-squamous tumors, consisting of T cell markers and interferon-gamma response proteins like CD4, CD48, and GBP5, which imaging models can successfully predict from histopathology. Manual review from pathologists confirmed lymphocytic T-cell density as a differentiator in samples with the highest and lowest T-cell signaling. Together, these approaches demonstrate that genomic characteristics discovered via unbiased mining of pan-cancer multi-omics data manifest as quantitative imaging phenotypes. These results underscore the potential of multi-omics and digital pathology to integratively uncover and confirm new cancer biology. Our ongoing work will explore predicting drug response and survival from morphology patterns related to multi-omics signatures. Citation Format: Joshua Wang, Runyu Hong, Jimin Tan, Wenke Liu, David Fenyȯ. Uncovering clinically relevant omics signatures from pan-cancer imaging and multi-omics data integration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 888.

Concomitant Tuberculous and Lepromatous Lymphadenitis: Clues and Pitfalls of Leprosy Concealed by Tuberculosis in Lymph Nodes.

Comorbidities between tuberculosis and leprosy are expected in endemic regions. Pulmonary tuberculosis and cutaneous leprosy are the most prevalent coinfections. One of the common manifestations of tuberculosis is generalized lymphadenopathy. In contrast, leprosy is clinically less suspected to manifest as a generalized lymphadenopathy, and it is pathologically unusual to diagnose leprosy primarily in lymph nodes. Concomitant tuberculous and lepromatous lymphadenitis are unprecedented and clinically unexpected, particularly in nonendemic countries. This imposes diagnostic challenges. We report concurrent tuberculosis and leprosy that were diagnosed in a lymph node in 45-year-old man with generalized lymphadenopathy. The effaced lymph node was predominantly replaced by caseating epithelioid granulomas alternating with foamy histiocytes. Ziehl-Neelsen stain showed positive acid-fast bacilli in the necrotizing granulomas only. The initial differential diagnosis of the nodal foamy macrophages included fungal infections, leishmaniasis, and Whipple disease, for which the special stains were negative. The vacuolated macrophages were disregarded as nonspecific lipogranuloma. A modified acid-fast stain was not considered. The histopathologic clues to nodal lepromatous leprosy included the presence of intracytoplasmic globi, intermixed microabscesses, and lymphoplasmacytic infiltrate and involved pericapsular nerves. Wade-Fite stain was subsequently performed. It revealed numerous lepra bacilli within the foamy histiocytes. The final diagnosis was concurrent disseminated tuberculosis and leprosy. Nodal lepromatous leprosy could be missed when compounded by concurrent nodal tuberculosis, particularly in developed countries. The clinicians and pathologists should have a high index of suspicion, particularly in patients from or with history of travel from endemic regions. Certain histopathologic features are helpful clues to avoid pitfalls.

Clinical Characteristics and Treatment Outcome of Waldenstrom Macroglobulinemia: Experience from a Tertiary Cancer Centre

Background: Waldenstroms macroglobulinemia (WM) or Lymphoplasmacytic lymphoma is a rare B cell lymphoproliferative malignancy characterized by serum monoclonal immunoglobulin M (IgM) protein and lymphoplasmacytic infiltration in the bone marrow. Patients usually present in their seventh decade with symptoms related to the infiltration of the marrow or the effects of monoclonal IgM in the blood. Objective: Was to study the clinical characteristics and treatment outcome of patients diagnosed with WM. Materials and Methods: This is a retrospective analysis of 26 cases of WM treated at a tertiary cancer centre. Results: WM constituted 0.68% of our nonHodgkin’s lymphoma. The median age at presentation was 67 years with a male to female ratio of 2:1. Four patients had lymphadenopathy, six had splenomegaly and four patients had evidence of hyper viscosity. All patients had IgM paraproteinemia, the M band was IgM-kappa in 19 patients and IgM-lambda in seven patients. All patients had a histopathological confirmation. According to IPSS-WM, 12 patients each were in the intermediate and high risk group and 2 in the low risk group. Among the 26 patients, 20 patients received upfront treatment and four patients were kept under observation. The indications for treatment were cytopenia in ten patients, constitutional symptoms in five, hyper viscosity in four and symptomatic lymphadenopathy in one patient. Sixteen patients received rituximab-based chemotherapy. Four patients with features with hyper viscosity underwent plasmapheresis. The three year progression free survival and overall survival were 69.4% and 78 % respectivel. Conclusions: WM is a low grade B cell lymphoproliferative disorder having an indolent course and do not require treatment for prolonged period. Diagnosis is challenging due to lack of distinct diagnostic features. Rituximab containing regimens are the standard of care. Newer targeted treatment options may improve the outcome of this incurable disease.

A comparative study of uncomplicated acute non-A-E hepatitis with acute viral hepatitis and acute onset autoimmune hepatitis.

Non-A-E hepatitis (NAEH) not leading to acute liver failure (ALF) is poorly documented. The objective was to compare clinical and laboratory features of uncomplicated acute NAEH with acute viral (AVH) and autoimmune hepatitis (AIH) and histopathology in NAEH and AIH. Cases of hepatocellular jaundice were included. These were grouped into AVH, AIH and NAEH based on clinical, laboratory and, when indicated, liver biopsy findings. NAEH and AIH were followed up at three months. Of 336 patients with hepatocellular jaundice, 15 (5%) were NAEH, 25 (7%) acute AIH and 45(14%) AVH. Among NAEH patients, seven (46.7%) were males with a mean age of presentation 39 years. Jaundice (100%) was the most common presentation of NAEH. Peak bilirubin was 10.7 mg/dL. Peak aspartate and alanine aminotransferase (AST, ALT) were 512 and 670 U/L. Five (33.3%) patients had positive anti-nuclear antibody and one had anti-smooth muscle antibody. Mean immunoglobulin G (IgG) levels were 1829. On liver biopsy, all had ballooning degeneration, four (26.7%) had mild and three (20%) moderate interface hepatitis, four (26.7%) mild lymphoplasmacytic infiltrate, one (6.7%) rosette formation, bridging necrosis in none and stage 1 fibrosis in one. Comparing NAEH with AIH, AIH showed significantly older age at presentation, female predisposition, past history of jaundice, lower ALT, more autoantibodies, higher IgG, higher grade interface hepatitis, lymphoplasmacytic infiltrate, rosette formation and higher bilirubin, AST at three months. NAEH and viral hepatitis had similar features. Etiology of NAEH is unlikely to be autoimmune and is probably viral, unidentified as yet. Uncomplicated NAEH likely has self-limiting course even without specific treatment.

Treatment of autoimmune hepatitis-First-line, second-line and third-line treatment

Autoimmune hepatitis (AIH) is a rare autoimmune inflammation of the liver mostly with a chronic course, which can also be acutely manifested up to acute liver failure. It affects women 3-4 times more frequently than men and can be diagnosed in all age groups. In one third of the patients a liver cirrhosis is present at the time of diagnosis. It is characterized by a hepatic inflammation pattern, a polyclonal hypergammaglobulinemia of immunoglobulin G and the detection of autoantibodies. A liver biopsy is necessary to make the diagnosis. The AIH is histologically characterized in particular by a lymphoplasmacytic infiltrate in the portal fields. In cases with a relevant disease activity, AIH is typically treated by immunosuppression. The immunosuppressive treatment is associated with a prevention of disease progression to liver cirrhosis and a better survival. The success of treatment is measured by achieving biochemical remission, i.e., normalization of the transaminase and immunoglobulin G levels as a good noninvasive predictor of a histological remission. Another treatment target is an improvement of the symptoms of the patient. The first-line treatment consists of a glucocorticoid, mostly prednisolone or in cases without advanced fibrosis budesonide, and azothioprine. For reduction of steroid-specific treatment side effects the maintenance treatment should be carried out steroid-free whenever possible. In cases of insufficient response to azothioprine or side effects a treatment attempt using antimetabolites, such as 6‑mercaptopurine or mycophenolate mofetil is primarily carried out as second-line treatment. For patients who do not achieve biochemical remission through first-line or second-line treatment, a variety of medications are available for third-line treatment, e.g., rituximab, calcineurin inhibitors or antitumor necrosis factor (anti-TNF) antibodies. Third-line treatment should be carried out in expert centers and registered in the European Reference Network for Rare Liver Diseases in order to improve the currently sparse database for these forms of treatment in the future.

Diagnostic informativeness of biopsy for chronic kidney disease in cats

The biopsy is a diagnostic method that allows in vivo sampling of kidney tissue material for histopathological examination to identify structural changes in the organ. The study aims to study the informativeness of intravital diagnosis of stage II chronic kidney disease (according to IRIS) in cats based on the results of histological and histochemical studies of biopsies. A kidney biopsy was performed on two cats aged 6 and 8 years. Research methods: histological (hematoxylin and eosin, Heidenhain test) and histochemical (PAS reaction, Gomori (PAMS)). The diagnosis of chronic kidney disease was made based on history, clinical symptoms, and blood and urine test results. Based on the biopsy, acute extracapillary serous-desquamative glomerulonephritis was established in cats with II-stage chronic kidney disease, which was characterized by vacuolar dystrophy of renal tubule epitheliocytes, desquamation of glomerular capsule epithelium. In addition, lymphoplasmacytic infiltration of the renal stroma, thickening of the Shumlyansky-Bowman capsule with significant deposition of PAS-positive substances, the collapse of the glomerular loops, and focal atrophy of the proximal tubules of the kidney pronounced extra capillary desquamation of the glomerular epithelium, segmentation of the vascular glomerulus, and dystrophy of single tubules were noted. The detected changes in kidney biopsies of cats in the II stage of chronic kidney disease are characteristic of this pathology, which makes it possible to develop and carry out effective treatment of animals promptly and improve their quality of life.

Gene-expression profiling of endomyocardial biopsies from dogs with dilated cardiomyopathy phenotype

IntroductionThe employment of advanced molecular biology technologies has expanded the diagnostic investigation of cardiomyopathies in dogs; these technologies have predominantly been performed on postmortem samples, although the recent use of endomyocardial biopsy in living dogs has enabled a better premortem diagnostic approach to study the myocardial injury. Animals, materials, and methodsEndomyocardial biopsies were collected in nine dogs with a dilated cardiomyopathy phenotype (DCM-p) and congestive heart failure and submitted to histologic examination, next-generation sequencing (NGS), and polymerase chain reaction analysis. Data from three healthy dogs (Fastq files) were retrieved from a previously approved study and used as a control group for ribonucleic acid sequencing. ResultsHistologic examination revealed endocardial fibrosis in 6 of 9 dogs, whereas lymphocytic interstitial infiltrates were detected in two of nine dogs, and lymphoplasmacytic and macrophage infiltrates were detected in one of nine dogs. On polymerase chain reaction analysis, two dogs tested positive for canine parvovirus two and one dog for canine distemper virus. Gene-expression pathways involved in cellular energy metabolism (especially carbohydrates-insulin) and cardiac structural proteins were different in all DCM-p dogs compared to those in the control group. When dogs with lymphocytic interstitial infiltrates were compared to those in the control group, NGS analysis revealed the predominant role of genes related to inflammation and pathogen infection. ConclusionsNext-generation sequencing technology performed on in vivo endomyocardial biopsies has identified different molecular and genetic factors that could play a role in the development and/or progression of DCM-p in dogs.

An Unusual Occurrence of Immunoproliferative Small Intestinal Disease in Elderly Patient Presenting with Chronic Diarrhea - A Rare Case Report

Immunoproliferative small intestinal disease (IPSID) is a rare type of indolent B-cell lymphoma. It is a variant of extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue. It is commonly seen in older children and young adults in the age group of 10-35 years. It is more common in males with Male: Female ratio of 2.4:1. Duodenum and jejunum are the commonly involved areas in small intestine. Colicky abdominal pain and intermittent diarrhoea are the common symptoms. Here by, we report a rare case in a 74-year-old male patient presented with chief complaints of abdominal pain, diarrhea and weight loss for 3 months. CT scan findings revealed thickening of small intestinal wall and mesenteric lymphadenopathy. Upper gastrointestinal endoscopy findings revealed nodular and ulcerative mucosa in the duodenum. Histopathological examination revealed flattening of mucosa with villous atrophy, destruction of crypts and intraepithelial lymphocytic infiltrate is noted. Interstitium shows dense and diffuse collection of lymphoplasmacytic infiltrate. Immunohistochemistry was done and it showed CD20 positive lymphoid cells. Based on the above findings the case was reported as Immunoproliferative small intestinal disease. Clinicians should suspect IPSID in cases presenting with chronic diarrhea and abdominal pain refractory to treatment. Immunoproliferative small intestinal disease has indolent clinical course and it can be cured with antibiotics in early stages. Late stages have high mortality rate and has poor prognosis. Keywords: IPSID, Alphachain disease, B cell lymphoma, duodenum, villous atrophy, lymphoplasmacytic infiltrate

A178 GASTROINTESTINAL STRICTURES IN A PEDIATRIC PATIENT WITH SATOYOSHI SYNDROME

Abstract Background Satoyoshi syndrome (SS) is a rare, progressive, multisystem disease including muscle spasms, alopecia, skeletal deformities, and diarrhea, with suspected autoimmune etiology. Treatment includes corticosteroids, immunoglobulin therapy, or immunosuppression. Reported endoscopic findings include loss of intestinal folds and nodularity in the stomach and the intestine, with histology showing gastritis cystica polyposa and lymphoplasmacytic infiltrate, as well as fibrosis noted on autopsy reports. To date, no cases of intestinal stricture have been described in SS. Aims To describe an original case of intestinal strictures in SS. Methods Case report and literature review. Results We present a case of a 10-year-old girl with chronic diarrhea and intermittent hematochezia, postprandial abdominal pain, intermittent non-bilious emesis, stunted growth, and weight loss, with acquired alopecia and severe muscle cramps. Examination showed a non-dysmorphic, small child with alopecia totalis and a distended, tender abdomen. Investigations demonstrated an unremarkable endocrine work-up, mild hypoalbuminemia, microcytic anemia, and anti-transglutaminase serology at 3-4x ULN with no improvement on the gluten-free diet. Endoscopy identified a duodenal stricture with a very distended stomach and duodenal bulb, mucosal nodularity and bridging creating a web-like appearance, and edema and friability of the left-sided colon. MR enterography confirmed an isolated duodenal stricture. Pathology displayed patchy fibrosis with crypt/glandular dilatation in the antrum, duodenum, and rectum. Skeletal imaging detected physeal widening and sclerosis with mild slipping of the epiphyses. Auto-immune markers included positive ENA profile for anti-Sm, anti-Sm/RNP, and anti-RNP-A. The patient was treated with corticosteroids in addition to a series of endoscopic dilatations for duodenal stricture with symptomatic benefit, with addition of upadacitinib for alopecia management. Follow-up revealed intermittent worsening of symptoms with steroid taper, necessitating further duodenal dilatations, and evidence of a new anal stricture. The patient remains on corticosteroid therapy with ongoing surveillance. Conclusions This case identifies the first report of intestinal strictures in SS, which may suggest that in addition to suspected autoimmune pathogenesis, disorders of fibrogenesis may need to be considered. Funding Agencies None