Dense Inflammatory Infiltrate Research Articles

Characterization of Oral Squamous Cell Carcinoma Associated Inflammation: A Pilot Study.

Background: Oral squamous cell carcinoma (OSCC) is a devastating disease that is usually associated with a dense associated inflammatory infiltrate. Characterizing tumor-associated inflammation is critical to understand the pathogenies of tumor development and progression.Methods: We have tested a protocol to analyze tissue and salivary immune cells and mediators of 37 patients with OSCC at different stages and compared to eight chronic periodontitis patients and 24 healthy controls. Tissue analysis was based on fluorescent immunohistochemistry (FIHC) and inflammatory mediators were analyzed using a Luminex-based 30-Plex panel. Immune cells were analyzed using multichannel flow cytometry including CD45, CD66b, CD3, CD4, CD8, CD25, CD56, CD68, CD138, PD-1, and PD-L1.Results: We show an increase in OSCC-associated inflammation characterized by increased pro-inflammatory cytokines including IL-6, IL-8, TNFα, and GMCSF and increased salivary immune cells.Conclusion: We described a new method to analyze salivary inflammatory markers that can be used in future studies to monitor disease progression and prognosis.

Hemodynamics and remodeling of the portal confluence in patients with malignancies of the pancreatic head: a pilot study towards planned and circumferential vein resections.

We designed a retrospective computational study to evaluate the effects of hemodynamics on portal confluence remodeling in real models of patients with malignancies of the pancreatic head. Patient-specific models were created according to computed tomography data. Fluid dynamics was simulated by using finite-element methods. Computational results were compared to morphological findings. Five patients underwent total pancreatectomy, one had duodenopancreatectomy. Vein resection was performed en-bloc with the specimen. Histopathological findings showed that in patients without a vein stenosis and a normal hemodynamics, the three-layered wall of the vein was preserved. In patients with a stenosis > 70% of vein diameter and modified hemodynamics, the three-layered structure of the resected vein was replaced by a dense inflammatory infiltrate in absence of tumor infiltration. The portal confluence involved by malignancies of the pancreatic head undergoes a remodeling that is not mainly due to a wall infiltration by the tumor but instead to a persistent pathological hemodynamics that disrupts the balance between eutrophic remodeling and degradative process of the vein wall that can lead to the complete upheaval of the three-layered vein wall. This finding can have useful surgical application in planning resection of the vein involved by tumor growth.

HPV-negative Squamous Cell Carcinomas of the Cervix With Special Focus on Intraepithelial Precursor Lesions.

Recently, the World Health Organization (WHO) recognized human papilloma virus (HPV)-independent invasive cervical squamous cell carcinoma (SCC) without recognizing the existence of precursor lesions. This is a detailed characterization of 3 preinvasive lesions and 6 invasive SCC negative for HPV-DNA (32 genotypes), HPV-mRNA (14 genotypes) and genomic HPV sequencing. We evaluated histologic features, expression of p16ink4a, p53, CK7, and CK17, aberrations in 50 cancer genes and chromosomal copy number variations. HPV-negative preinvasive lesions were extensive basaloid or highly differentiated keratinizing intraepithelial proliferations of 3 to 20 cell layers thickness, partly with prominent cervical gland involvement. Overall, 2/3 intraepithelial lesions and the in situ component of 1/6 SCC showed p16ink4a block staining, while 1/6 in situ component revealed heterogenous p16ink4a staining. All invasive components of keratinizing SCC were p16ink4a-negative. Preinvasive and invasive SCC showed inconsistent CK7 and CK17 staining. Nuclear p53 overexpression was restricted to the TP53 gene mutated SCC. The highly vascularized peritumoral stroma showed a dense inflammatory infiltrate including plasma cells and intratumoral and peritumoral eosinophilic granulocytes. Inconsistent somatic gene mutations (PIK3CA, STK11, TP53, SMARC2B, and GNAS) occurred predominantly in nonhotspot locations at low mutational frequency in 3/6 SCC. Consistent aberrations included the pathogenic (angiogenic) germline polymorphism Q472H in the KDR gene (7/9 patients), and chromosome 3q gains (4/9 patients). In conclusion, HPV-negative intraepithelial cervical precancerous lesions exist, either as highly differentiated keratinized intraepithelial proliferations reminiscent of differentiated vulvar intraepithelial neoplasia, or undifferentiated basaloid intraepithelial lesions with occasional p16ink4a block staining resembling high-grade squamous intraepithelial lesion. Gains of chromosome 3q, angiogenic germline variants the inflammatory infiltrate may contribute to progression of HPV-negative cervical carcinogenesis.

26537 Immunohistochemical pitfalls in poorly differentiated spindle-cell neoplasms

An 86-year-old male presented with a rapidly enlarging tumor on his face for 4 months. Physical examination revealed a 5.5 × 4.0 cm erythematous exophytic tumor on his left cheek. Incisional biopsy demonstrated an atypical, poorly differentiated spindle-cell proliferation with a dense inflammatory infiltrate. Immunohistochemistry (IHC) analysis was negative for endothelial (CD31, CD34, D2-40), melanocytic (HMB-45, Melan-A, SOX-10, S100), viral (HHV-8), and epithelial markers (CKAE1/AE3, EMA, CK7, CK20). The inflammatory infiltrate was positive for CD3, CD4, CD7, CD8, and CD68. The specimen was sent for consultation where additional IHC studies revealed the neoplastic cells were strongly positive for erythroblast transformation specific–related gene (ERG), consistent with the diagnosis of poorly differentiated angiosarcoma. The differential diagnosis of atypical spindle cell cutaneous neoplasms includes spindle cell squamous cell carcinoma, melanoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, Kaposi sarcoma, leiomyosarcoma, and angiosarcoma. The diagnosis of angiosarcoma is usually straightforward provided the tumor shows vasoformative elements and stains positively to commonly employed endothelial markers such as CD31 and CD34. However, a small subset of poorly differentiated angiosarcomas, including those with spindled morphology, present a diagnostic challenge as they may lose immunoreactivity to CD31 and CD34. ERG is a proto-oncogene of the ETS transcription family that has shown promising results as a highly sensitive and specific diagnostic marker in poorly differentiated angiosarcomas. This case highlights the importance of including ERG testing in the IHC evaluation of atypical spindle cell neoplasms. Awareness of this potential immunohistochemical pitfall is essential for timely diagnosis and treatment of this highly aggressive malignancy.

27437 Disseminated Candida tropicalis in an immunocompromised pediatric patient

We report a case of a 12-year-old female with newly diagnosed B-cell acute lymphoblastic leukemia status post induction chemotherapy with hospital course complicated by Candida tropicalis fungemia requiring fluconazole. Two weeks after treatment initiation, she presented with a new onset fever and discrete erythematous papules, some with pseudovesicular appearance, along with erythematous macules and thin plaques localized to the upper extremities. At presentation, labs demonstrated pancytopenia, elevated beta-D-glucan assay (>500), and Candida tropicalis growth on both wound and tissue culture. Blood cultures were negative. Computed tomography with contrast demonstrated hypodense areas involving the liver, spleen, and pectoralis major muscle concerning for fungemic microabscesses. A right arm punch biopsy revealed a dense dermal inflammatory infiltrate consisting of numerous neutrophils, histiocytes, lymphocytes and eosinophils. Periodic acid Schiff diastase and Gomori methenamine silver stains highlighted many associated fungal organisms. A diagnosis of disseminated candida tropicalis was rendered. Treatment was changed from oral fluconazole to intravenous micafungin. Although her cutaneous involvement improved, she remained febrile. She was switched to amphotericin B and prednisone with marked improvement. This case highlights the difficulty in management of disseminated Candida tropicalis in immunosuppressed pediatric patients. The observed disseminated disease may be explained by emerging resistance of Candida tropicalis to fluconazole. Improvement of fever with prednisone supports the hypothesis that disseminated candidiasis causes an inflammatory response and emphasizes the importance of adjuvant corticosteroid therapy. Cutaneous involvement may indicate underlying disseminated disease, and dermatologists are crucial in the diagnosis and treatment of this opportunistic, often fatal disease.

Deep Herpes.

Herpes viruses are known for infecting epithelial cells and manifesting as vesicles. However, herpes viruses can also infect stromal cells. While established in the ocular setting, cutaneous stromal herpes (deep herpes) is previously unreported and may evade clinical and microscopic detection. We searched for skin biopsies with herpes stromal disease. Clinical information was retrieved via electronic medical records and pathology records system. Hematoxylin and eosin slides, immunohistochemical staining, and polymerase chain reaction detection of viral DNA was performed. We identified 12 specimens from 10 patients with cutaneous stromal herpes simplex virus 1/2 (n=7) or varicella-zoster virus infection (n=5). The most common site involved was the buttocks/perianal region (n=6). Ulceration was a frequent dermatologic finding (n=8). Pyoderma gangrenosum was clinically suspected in 6 specimens (50%). Eight patients (80%) were immunosuppressed. Biopsies frequently demonstrated a dense dermal mixed inflammatory infiltrate with subcutaneous extension and enlarged cells with viral cytopathic changes confirmed by herpes simplex virus 1/2 or varicella-zoster virus immunohistochemistry (n=10) or polymerase chain reaction (n=2). Most specimens (67%) lacked evidence of characteristic epidermal keratinocyte infection. This study presents the first known report of the ability of herpes virus to infect deep stromal cells of the dermis. We raise awareness of cutaneous stromal herpes in patients presenting with atypical clinical lesions, particularly while immunocompromised. Establishing the correct diagnosis is critical for initiating therapy.

AN UNUSUAL CASE OF ORAL TRAUMATIC ULCERATIVE GRANULOMA

<h3>Background</h3> Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is an uncommon condition considered to be a benign, reactive lesion that usually affects the tongue. The exact pathogenesis is not clear. However, trauma has been found to be a contributing factor in a majority of cases. Here, we present an unusual case of TUGSE in an adult patient. <h3>Case Report</h3> A 26-year-old male patient was referred to the Kuwait University Dental Center with a painful lesion on the dorsal surface of the tongue that had been present for 7 months. On examination, a diffuse ulcerative proliferative lesion with erythematous borders was seen on the dorsal surface of the tongue. On palpation, the lesion was very tender and deep clefts were observed. After a week of prednisolone mouthwash, the patient felt that his pain had reduced and he was able to eat. Incisional biopsies showed partially ulcerated stratified squamous epithelium covered by fibrin. The underlying stroma was edematous and highly vascular with dense inflammatory infiltrate, the majority of which were eosinophils, histiocytes, and plasma cells. The inflammatory infiltrate extended into the underlying skeletal muscle. These features were suggestive of TUGSE. Immunohistochemical analysis showed positivity to T-cell markers CD-3 and CD-30; B-cell marker CD-20; and histiocyte marker CD-68, implying a mixed inflammatory infiltrate. On follow-up, the patient reported improvement but was concerned that the lesion has not healed completely. <h3>Conclusions</h3> Recognition of the lesion is important because it often mimics malignancy. However, traumatic granuloma is a self-limiting lesion that usually heals within 2 to 3 weeks.

PD-L1 EXPRESSION IN ORAL DYSPLASIA: A PILOT STUDY

<h3>Background</h3> Immune checkpoint inhibitor therapy has a recognized role in oral squamous cell carcinoma (OSCC). Assessment of programmed death-ligand 1 (PD-L1) expression by immunohistochemistry by a trained histopathologist is the current standard method of stratifying patients for immunotherapy. However, to date, limited work has been undertaken on PD-L1 expression in oral dysplastic lesions (ODLs). <h3>Methods and Objective</h3> The principal aims of this study were to assess the expression of PD-L1 in ODL and OSCC using a clinically validated, companion diagnostic antibody (Dako 22C3 PharmDx) and to construct a comprehensive clinicopathologic database of OSCC and ODL. PD-L1 immunohistochemistry was assessed using the combined positive score (CPS) method by a trained histopathologist. In select cases, CD3 and CD8 expression were also assessed in lymphocytes. Statistical analysis was performed using Fisher exact and Pearson chi-square tests. <h3>Results</h3> The majority of OSCC cases tested were positive for PD-L1 using the CPS method (63%; 19/30). PD-L1 expression had a positive association with lymph node metastasis but this was not statistically significant (<i>P</i> > .05). In contrast, a smaller proportion of ODLs were positive for PD-L1 (20%; 4/20), all of which were severely dysplastic. Interestingly, PD-L1 in ODL expression was associated with the presence of a dense chronic inflammatory cell infiltrate. <h3>Conclusions</h3> Evaluating PD-L1 expression using CPS could identify patients with OSCC who may respond to immune checkpoint inhibitors. We have observed PD-L1 expression in a small number of severe ODLs, the significance of which is uncertain at present. Replication in larger patient cohorts is recommended for validation.

AN UNEXPECTED CAUSE OF ULCERATION IN THE ORAL CAVITY

<h3>Clinical Presentation</h3> A 38-year-old male patient presented to the local oral and maxillofacial surgery department with a 3-month history of a persistent ulcer on the left lateral border of the tongue. The ulcer had raised edges but was not painful to palpation. The patient was fit and well and a nonsmoker. Clinical photographs and an incisional biopsy were used to investigate the cause. <h3>Histology</h3> Histologic examination showed oral mucosa comprising parakeratinized, stratified squamous epithelium that centrally was ulcerated. A dense chronic inflammatory infiltrate dominated by plasma cells was identified within connective tissue extending into muscle. Numerous neutrophils were noted in the surface layers of the epithelium. The findings of special stains for fungal hyphae were negative; however, the finding of immunohistochemistry for <i>Treponema pallidum</i> was positive, highlighting the spirochete organisms. The lesion was diagnosed as a syphilitic ulcer. <h3>Further Investigations</h3> Following the histologic diagnosis, the patient was referred to the genitourinary medicine department for further investigations, including blood serology and definitive treatment. <h3>Discussion</h3> There has been a recent increase in the number of reported cases of syphilis. Primary presentation of the sexually transmitted disease is in the form a chancre, a solitary ulcer, at the site of infection. Although chancres typically present within the genital region, oral presentation is also possible and is perhaps overlooked as a differential diagnosis of ulceration within the oral cavity. We will discuss the case in detail, focusing on the clinical presentation, differential diagnoses, and treatment rationale.

PLASMA CELL CHEILITIS TREATED WITH TOPICAL CORTICOSTEROID AND PHOTODYNAMIC THERAPY—CASE REPORT

<h3>Background</h3> Plasma cell cheilitis (PCC) is a rare, idiopathic, and benign inflammatory mucosal condition of unknown etiology, characterized by a dense plasma cell infiltrate within mucosa, principally affecting the lip. Treatment includes topical, intralesional, or systemic steroids; oral griseofulvin; liquid nitrogen; radiotherapy; and surgical excision. In most cases, PCC is resistant to topical treatment. <h3>Objective</h3> To report the treatment of PCC associated with topical corticosteroid with photodynamic therapy (PDT). <h3>Methods</h3> A 68-year-old woman was referred to the oral medicine ambulatory of the Clinical Hospital of São Paulo State University, Medical School, Botucatu, Brazil, for the appearance of sore wound with crust on the lower lip with progressive worsening without comorbidities, present for 5 months. Clinical examinations showed an ulcerated area with crust all over the lower lip. Diagnostic hypotheses were exfoliative cheilitis, cheilitis granulomatosa, and squamous cell carcinoma. Incisional biopsy revealed dense inflammatory infiltrate within the superficial corium, which consisted of sheets of plasma cells with occasional active blast cells. The treatment was topical 0.05% clobetasol gel twice a day with PDT twice/week (0.01% methylene blue topical for 3 minutes; irradiation was punctual by contact, energy 9 J, 660 nm, 100 mW, per point in 2 points until complete healing). <h3>Results</h3> The lesions were regressing with decreased pain. Total healing occurred in 3 months. <h3>Conclusions</h3> The association of topical corticosteroid with PDT is an alternative for the treatment of PCC.

Reduced expression of programmed cell death 1 and programmed cell death ligand 1 in infiltrating inflammatory cells of lichen planus without administration of immune checkpoint inhibitors.

Keratinocytes are the main targets of infiltrating T cells in the pathogenesis of lichen planus. However, the mechanisms of dense inflammatory infiltrates beneath the epidermis remain unknown. The aim of the present study was to clarify the roles of programmed cell death 1 (PD-1) and its ligand (PD-L1) in the pathogenesis of lichen planus. Immunohistochemistry of PD-1 and PD-L1 in 12 cases each of lichen planus and dermal-type erythema multiforme was performed. The expression of PD-1 and PD-L1 on infiltrating inflammatory cells, predominantly lymphocytes in lichen planus, was significantly less compared to that in dermal-type erythema multiforme. By dual immunofluorescence, the overlap between PD-1 and leukocyte common antigen, CD4, CD8, CD68, and factor XIIIa was limited and found in only a very small portion of lichen planus cells. Our data suggest that decreased expression of PD-1 and PD-L1 could play a role in accelerating inflammatory cell infiltration targeting the epidermis in the pathogenesis of lichen planus.

P507 Vulvar Crohn’s disease: A challenging diagnosis

Abstract Background Crohn’s disease is an inflammatory bowel disorder with several well-known extraintestinal manifestations, such as erythema nodosum, uveitis, and arthritis. Less commonly observed are cutaneous, so-called metastatic lesions of the vulva, which represent a diagnostic and therapeutic dilemma and require a multidisciplinary approach. The objective of this study was to report a case series of patients with vulvar Crohn’s disease (VCD), describe its clinical features, histopathologic characteristics and therapeutic management. Methods In this retrospective study, we reviewed all cases of VCD seen in our department between 2008 and 2016. Data concerning age at diagnosis of VCD, vulval symptoms at presentation, histologic findings, and different treatment modalities were recorded. Only patients with both clinical features of VCD [knife-cut fissures, edema, ulceration] and histologic confirmation were included. A total of 3 cases were identified among 106 female patients with CD. Results Case 1: A 58-year-old patient, presented with a 4-year history of vulvar pain and itching. She had no bowel complaints. Clinical examination revealed hypertrophic exophytic lesions associated with linear ulcearations involving the vulva. A biopsy from the lesional skin showed non caseating gigantocellular granuloma. In view of the clinical and histopathological features, a diagnosis of Crohn’s disease of the vulva was made. Anti TNF treatment with adalimumab was started, resulting in a significant regression of the lesions. Case 2: A 47-year-old patient presented to our department with complaints of painful, persisting vulvar ulcers, and resulting dysperunia for 2 years. On clinical examination she had unilateral vulvar oedema with multiple “knife-cut” linear ulcers. A skin biopsy was done which revealed dense inflammatory lymphocytic infiltrate with non caseating granulomas. Treatment with adalimumab was initiated. An improvement of symptoms was noted. Case 3: A 16-year-old patient with no remarkable medical history, presented with a 2-year- history of persistent cheilitis and vulvar pain. Clinical examination of the external genitalia revealed ‘knife-cut’ vulvar fissures with important bilateral labial swelling and multiple papules on the surrounding skin. Histological analysis showed chronic inflammatory infiltrate with noncaseating tuberculoid granulomas. Anti-TNF treatment with infliximab was started with partial regression of lesions. Conclusion Our findings highlight the importance of keeping VCD on the differential diagnosis when faced with a range of vulvar symptoms. Anti-TNF agents seem to be an efficient treatment strategy for this particular localization.

Classic Hodgkin Lymphoma - Old Disease, New Directions: An Update on Pathology, Molecular Features and Biological Prognostic Markers.

The aim of this paper is to review morphologic, immunophenotypic, and molecular features of classic Hodgkin lymphoma, as well as different prognostic markers in this neoplasm. Classic Hodgkin lymphoma (CHL) accounts for 15-25% of all lymphomas in the Western world. The hallmark of this disease is the neoplastic Hodgkin/Reed-Sternberg (HRS) cell, which is favored to be derived from germinal center B-cells but has lost many of the B-cell markers. HRS cells are scattered within a dense inflammatory infiltrate, and through a network of cytokines and chemokines they shape their microenvironment, evade immune response, survive, and grow. In the last two decades multiple prognostic markers related to HRS cells, the microenvironment or both, have been evaluated in patients with CHL. They include clinical, immunohistochemical, cytogenetic, and molecular markers that can predict survival and identify high-risk patients who will likely relapse after therapy. More recently, circulating tumor DNA analysis by next-generation sequencing has opened new avenues for diagnosis and disease monitoring after therapy. The increased understanding of molecular mechanisms underlying CHL pathogenesis has led to successful implementation of novel therapies, such as anti-PD-1 antibodies, which are becoming a mainstay of treatment in relapsed/refractory patients. CONCLUSION: Currently, pathologic prognostic markers are not routinely assessed at initial diagnosis of CHL. However, as more therapies become available, it will be important to identify patients with high-risk disease who may benefit from more intense or targeted therapy upfront.

Unusual manifestation of gastric mucormycosis in a patient with rheumathoid arthritis

Introduction. Mucormycosis is a life-threatening opportunistic infection whose incidence has significantly risen during the last two decades. The gastrointestinal form is very rare, with the stomach as the most common site of infection, followed by the colon and ileum. Risk factors include uncontrolled diabetes mellitus, corticosteroid use, and organ transplantation. We report a patient with a history of rheumatoid arthritis who has developed gastrointestinal mucormycosis. To the best of our knowledge, this is the first such case reported in the literature. Case report. A 53-year-old female patient with a prior medical history of rheumatoid arthritis was admitted to the hospital due to persisting diarrhea. Physical examination revealed diffuse abdominal tenderness to palpation without meteorism and peritoneal signs. Laboratory results demonstrated systemic inflammation, so antibiotic therapy was administered. Abdominal computed tomography findings revealed inflammation of the rectum and the left colon. Colonoscopy findings were indicative of Crohn?s disease. Additionally, the patient had developed profuse rectal bleeding and consequently underwent emergency surgery. Subtotal colectomy with ileostomy and partial gastrectomy was performed. The patient?s condition rapidly worsened after the operation, and she died due to multi-organ failure. Histologic findings of resection specimens discovered chronic active colitis and extensive gastric necrosis associated with dense mixed inflammatory infiltration and numerous non-septate and 90-degree branching hyphae. Diagnosis of invasive gastric mucormycosis was obtained, but unfortunately, several days after the patient?s death. Conclusion. It is very important to obtain high awareness among clinicians of this deadly infection to achieve a prompt diagnosis and effective therapy.

An Overview of Immunoglobulin G4-related Ophthalmic Diseases Accompanied by a Case Report

Immunoglobulin G4-related diseases (IgG4-RDs) are immune-mediated, fibroinflammatory conditions that are characterised by affected organ enlargement, lymphocyte, plasma cell infiltration (determined with IgG4-positive plasma cells) and serum IgG4 level elevation. When the disease affects ocular adnexal tissues (such as the lacrimal gland, extraocular muscles, trigeminal nerve branches and orbital fat), it is called IgG4-related ophthalmic disease (IgG4-ROD). The diagnosis of IgG4-ROD is made by physical examination, biochemical findings and histopathological evaluation. It is characterized by elevated serum IgG4 levels and distinctive histopathological features, including IgG4+ plasma cell infiltration, the presence of fibrosis in the storiform pattern and the presence of a dense lymphoplasmacytic inflammatory infiltrate, including eosinophils. It is rare in the ocular region and cause diagnostic confusion. There is a high probability of misdiagnosis when the disease is not recognized. Here, a rare case of eye involvement is presented and IgG4-RDs are discussed with the literature.

Value of the toluidine blue test as an aid to determine the biopsy site in actinic prurigo cheilitis

ABSTRACTActinic prurigo (AP) is a type of photodermatosis that primarily affects the Latin American mestizo population. Histologically, AP cheilitis exhibits acanthosis with spongiosis and vacuolation of the basal cell layer overlying a dense lymphocytic inflammatory infiltrate that forms well-defined lymphoid follicles. Toluidine blue is a thiazide, acidophilic, and metachromatic dye used in vivo to selectively stain the acidic components of tissues such as sulfates, carboxylates, and phosphate radicals that are incorporated into DNA and RNA. It is necessary to develop a method that allows detecting, on clinical grounds the area of the lesion in which it is more feasible to find such structures. Thus to increase the sensitivity of the biopsy, in AP cheilitis to accurately identify where the lymphoid follicles reside, based on the higher concentration of DNA in such structures and thus confirm the diagnosis. In this study, staining was positive in 85% of patients with AP cheilitis, in 14 of whom 82% lymphoid follicles were observed by histopathology. One of the pathologist’s problems in establishing the diagnosis of AP is that the main histopathological characteristics are not always identified in the submitted samples because it is not easy to clinically identify the most representative site of the lesion selected for performing a biopsy. Based on our results, we propose using toluidine blue as an auxiliary method to choose a tissue sample to facilitate the diagnosis and allow clinicians to make clinical correlations between the histopathological and therapeutic findings.

Disseminated acanthamoebiasis in a horse

Amoebic infections have been described in humans and animals, causing lesions in specific organs or as systemic infections. In both animals and humans, immunocompromised patients are predisposed to the infection. The present report described the macroscopic and histologic findings in a Quarter horse filly who presented with a systemic infection caused by Acanthamoeba spp. that was characterized by multinodular lesions in lung, kidney, heart, submandibular lymph node, and lip. Histopathology revealed dense inflammatory infiltrates composed of neutrophils, histiocytes, occasional multinucleated giant cells, and numerous intralesional trophozoites. Immunohistochemistry was positive for Acanthamoeba spp trophozoites in lungs, kidneys, heart, submandibular lymph node, and lip. No predisposing conditions were identified.

Liver biopsy can be a tool for unravelling a rare diagnosis

A 5-year-old male child presented with fever, cough, wheeze, lung infiltrates, mild hepatomegaly and eosinophilia that was refractory to antibiotics and antihelminthics. He had no history of asthma, atopy, repeated...

Inflammatory milieu of muscle biopsies in juvenile dermatomyositis.

Juvenile dermatomyositis (JDM) is an inflammatory myopathy which causes severe morbidity and high mortality if untreated. In this study, we aimed to define the T-helper cell profile in the muscle biopsies of JDM patients. Muscle biopsies of twenty-six patients (50% female) were included in the study. Immunohistochemical expression of CD3, CD20, CD138, CD68, IL-17, Foxp3, IFN-ɣ, IFN-alpha and IL-4 was studied and muscle biopsies were scored using the JDM muscle biopsy scoring tool. Inflammatory cells were in small clusters in perimysium and perivascular area or scattered throughout the endomysium in most biopsies; however in 2 biopsies, lymphoid follicle-like big clusters were observed, and in one, there was a very dense and diffuse inflammatory infiltration nearly destroying all the muscle architecture. Seventy-three per cent of the biopsies had T cells, 88% had B cells, 57% had plasma cells, and all had macrophages. As for T-helper cell subtypes, 80% of the biopsies were Th1 positive, 92% Th17 positive and 30% Treg positive. No IL-4 positive inflammatory cell was detected, and only 2 biopsies showed IFN-alpha positivity. The mean JDM biopsy score was 17.6, meaning moderate to severe muscular involvement. Visual analogue score of the pathologist was strongly correlated with histopathological features. B cells, macrophages, plasma cells and T cells constitute the inflammatory milieu of the JDM muscle biopsies. As for T cells, JDM is a disease mainly related with Th1 and Th17 T-helper cell subtypes and to some extend Treg. Th2 cells are not involved in the pathogenesis.

S2672 Influenza a Virus as a Trigger for Autoimmune Hepatitis

INTRODUCTION: Autoimmune hepatitis (AIH) is a chronic liver disease caused by an immune-mediated destruction of the hepatocytes. Studies have shed the light on the important role of infections in triggering AIH as many viral infections and vaccines have been associated with it. We present an atypical case of AIH possibly triggered by Influenza A virus. To our knowledge, this is the first case report showing autoimmune hepatitis induced by influenza A virus. CASE DESCRIPTION/METHODS: A 52-year-old previously healthy female presented with new-onset jaundice after Influenza A viral infection. Initial laboratory investigations revealed an aspartate aminotransferase level of 1211 U/liter, an alanine aminotransferase level of 1506 U/liter, an alkaline phosphatase level of 305 U/liter, a total bilirubin level of 5.1, a direct bilirubin level of 3.4 and an international normalized ratio of 1. Serologic testing for hepatitis A, B, and C, HSV, CMV, and EBV were negative. Influenza A PCR was detected on nasopharyngeal sampling. Covid-19 test was negative. ASMA was positive with a titer of 1:80. ANA was positive with a titer of 1:80. Anti-mitochondrial antibody was negative. IgG, Alpha 1 antitrypsin, ceruloplasmin levels were within normal limits. No acetaminophen was detected in the blood. A CT abdomen showed normal biliary tree with no biliary strictures and no cirrhotic changes of the liver. Her liver biopsy showed acute hepatitis with moderate acute hepatocellular injury and hepatocellular necrosis with mixed portal infiltrates which include both plasma cells and eosinophils. Based on the revised International Autoimmune Hepatitis Group Scoring System for the Diagnosis of Autoimmune Hepatitis, her pretreatment score was 13 points. She was started on prednisone and had significant biochemical improvement. Her steroids were tapered and steroid sparing therapy with azathioprine was initiated. DISCUSSION: Influenza virus and vaccine have been proposed to cause autoimmune disease in the literature such as type 1 diabetes, narcolepsy, recurrent ITP, and multiple sclerosis. There has been an association as well between influenza vaccine and AIH. In a study published by Saski et al, they describe two cases of middle-aged women who developed autoimmune hepatitis after receiving influenza vaccine. We suggest that in our patient, the influenza A virus infection triggered autoimmune hepatitis. Autoimmune hepatitis should be considered in patients with persistently elevated liver enzymes following infections such as influenza.Figure 1.: Liver biopsy cores show findings suggestive of acute hepatitis. Dense portal inflammatory infiltrates are present, comprised of macrophages, lymphocytes, neutrophils, eosinophils and plasma cells. Piecemeal acute hepatocellular necrosis is also noted at the limiting plate (H&E, original magnification 10x).Figure 2.: Prominent bile stasis with sinusoidal Kupffer cell hyperplasia (H&E, original magnification 10x).