Dense Inflammatory Infiltrate Research Articles

S3588 Eosinophilic Gastroenteritis and Colitis After Intragastric Balloon Placement

Introduction: Eosinophilic gastrointestinal diseases (EGIDs) are a group of rare disorders characterized by infiltration of eosinophils in the gastrointestinal tract. Hypersensitivity to food or environmental allergens is believed to play a pivotal role in the pathogenesis. Intragastric balloon (IGB) has been demonstrated as an effective and safe therapy for weight loss. Interestingly, a previous report described development of eosinophilic esophagitis (EoE) following IGB placement, suggesting a possible association between IGB and EGIDs. Case Description/Methods: A 61-year-old male underwent endoscopic placement of an Orbera® intragastric balloon for weight reduction. Forty days later, he presented with a 3-day history of watery and non-bloody diarrhea, abdominal pain, and nausea. Labs were notable for severe peripheral eosinophilia over 15,000/mL. Extensive infectious workup were unremarkable. His IGB was removed as he had reached his goal weight. Then, he underwent esophagogastroduodenoscopy and flexible sigmoidoscopy with biopsy. Endoscopic exam was notable for diffuse erythema in the stomach and duodenum, and congestion in the colon. Histologically, dense inflammatory infiltration of eosinophils and plasma cells in the lamina propria was found in the stomach, duodenum, and colon. After removal of the IGB, his symptoms and peripheral eosinophilia improved rapidly, and were resolved completely within 1 month without need for immunomodulatory therapies or diet modifications. Discussion: We describe a case of eosinophilic gastroenteritis and colitis with severe peripheral eosinophilia following IGB placement, in whom rapid resolution occurred after IGB removal without additional therapies. To our knowledge, this is the first case report that suggests a possible association between IGB and non-EoE EGIDs, which warrants clinicians' awareness and further studies.

English

Historically Artemisia herba alba (AHA) is widely used in traditional Moroccan medicine. Few studies have been carried out to confirm its traditional use, in particularly immunological studies and to the authors’ knowledge; no study has treated the in vivo immunomodulatory effect of AHA aqueous extracts. This work was established to assess the immunological effects of AHA, including the humoral and cellular immunity effects in vivo. The immunomodulatory effect was assessed by measuring the titer of specific antibodies by the agglutination technique after immunization of Wistar rats with sheep red blood cells, while the pro-inflammatory effect was performed using a carrageenan-induced rat paw edema model. Administered AHA’s aqueous extract (AE) appears to have significantly (p < 0.01) stimulated the production of anti-SRBC antibodies with a dose-dependent effect compared to the control. These results were confirmed by a significant increase in the levels of white blood cells in particular neutrophils, lymphocytes, monocytes and eosinophils (p<0.05) for the doses 0.5 and 1 g/ml/bw. For the same doses of the extract, a proinflammatory effect was observed by the size of edema and the presence of very dense inflammatory infiltrate made up of lymphocytes, plasma cells and polymorphonuclear neutrophils. The AHA’s AE have shown an important immunomodulatory and pro-inflammatory activities in vivo by enhancing the production of antibodies and the inflammatory reaction. Key words: Artemisia herba alba, Immunomodulatory effect, In vivo, pro-inflammatory effect, antibodies production, aqueous extract.

Post-Covid-19 Immunological Disorder: A Possible Pathological Entity in a 43 Year Old Man

Background: Post-COVID-19 systemic inflammatory syndrome is considered to be an aquired immunological disorder, which may develop in some individuals after the remission of infection with SARS-CoV-2 and defined by inflammatory clinical manifestations (fever, arthralgias, cutaneous and mucosal pallor, physical weakness) and modified biological parametres (normochromic normocytic anaemia, increased serum levels of C reactive protein and rheumatoid factor), with no proof of an infectious process, to which corticotherapy may be a suitable therapeutic strategy. Case Report: A 43 year old male was admited in the Department of Internal Medicine for high fever (39,4°C), moderate polyarthralgias and physical weakness, with a negative test result of SARS-CoV-2 RT-PCR. The patient had been previously diagnosed with a moderate-to-severe form of COVID-19, a month prior to the current admission. The patient also experienced transitory dry cough for a month, with no other relevant clinical abnormalities. Upon physical examination, cutaneous and scleral pallor was observed and lung auscultation revealed hardened vesicular murmur bilaterally. Blood analysis revealed normochromic normocytic anaemia and increased serum levels of rheumatoid factor and of C reactive protein, which suggested a nonspecific inflammatory syndrome. Although blood cultures and other microbiological tests were negative for an infectious process, a chest X-ray was performed, which detected the presence of a nodular formation in the superior left lung lobe. Several differential diagnoses were taken into consideration, including pulmonary sarcoidosis and granulomatosis with polyangiitis, both of which were excluded, clinically and biologically. A thoracic computed tomography (CT) was later performed, which revealed the presence of a tumoral nodule in the left lung, associated with multiple mediastinal and supraclavicular lymphadenopathies, indicative of lung cancer. However, lung cancer was also excluded upon the histopathological examination of paratracheal lymphnodes, which detected multiple areas of parenchymal necrosis surrounded by dense inflammatory infiltrates, formed predominantly by histiocytes. All of these findings resulted in the diagnosis of a post-COVID-19 rheumatoid syndrome, the only therapeutic strategy being the administration of high doses of intravenous and oral methylprednisolone, which improved the patient’s health. Conclusion: Post-COVID-19 immunological disturbances should be taken into consideration in patients who experience repetitive clinical and biological inflammatory manifestations after the remission of the infection with SARS-CoV-2, which may be improved through high dose corticosteroid therapy

DENTIGEROUS CYST IN AN EDENTULOUS ELDERLY PATIENT WITH TOOTH DILACERATION

An 87-year-old female patient complained of a severe pain and swelling in the anterior maxilla with a 1-month history. There were no changes in the extraoral clinical examination on the day of the appointment. The patient was edentulous for several years. The intraoral examination revealed swelling of firm consistency covered by an intact mucosa in the left anterior maxilla, extending to the hard palate and buccal vestibule. Radiographic examination showed a tooth with severe dilaceration within a well-defined unilocular radiolucency measuring 2 × 2.5 cm. The differential diagnosis included benign odontogenic cyst or tumor. Aspiration puncture revealed a yellowish, opaque liquid. Excisional biopsy and extraction of impacted tooth was carried out. Microscopic examination showed a cystic cavity limited by two-layered cubic epithelium and areas of hyperplasia. The cystic capsule exhibited dense mononuclear inflammatory infiltrate. The diagnosis of dentigerous cyst was established. After 6 months of follow-up, no recurrences were detected. An 87-year-old female patient complained of a severe pain and swelling in the anterior maxilla with a 1-month history. There were no changes in the extraoral clinical examination on the day of the appointment. The patient was edentulous for several years. The intraoral examination revealed swelling of firm consistency covered by an intact mucosa in the left anterior maxilla, extending to the hard palate and buccal vestibule. Radiographic examination showed a tooth with severe dilaceration within a well-defined unilocular radiolucency measuring 2 × 2.5 cm. The differential diagnosis included benign odontogenic cyst or tumor. Aspiration puncture revealed a yellowish, opaque liquid. Excisional biopsy and extraction of impacted tooth was carried out. Microscopic examination showed a cystic cavity limited by two-layered cubic epithelium and areas of hyperplasia. The cystic capsule exhibited dense mononuclear inflammatory infiltrate. The diagnosis of dentigerous cyst was established. After 6 months of follow-up, no recurrences were detected.

Equine cutaneous habronematidosis

Clinical history: A 4-year-old Quarter Horse stallion was unsuccessfully treated for a circumscribed and ulcerated lesion of unknown duration located lateral to the prepuce. Microscopic description: The superficial and deep preputial dermis contains multifocal to coalescing, well-demarcated eosinophilic granulomas characterized by a central area of abundant eosinophilic necrotic debris mixed with degenerate eosinophils surrounded by numerous epithelioid macrophages and occasional multinucleated giant cells (foreign-body type), rimmed by ill-defined layers of fibrous connective tissue. In the center of the granulomas, there are cross-sections of degenerate nematode larvae. The adjacent dermal collagen is expanded by dense inflammatory infiltrate composed mainly of eosinophils and a few lymphocytes and plasma cells. The dermal microvasculature is prominent, with hypertrophic reactive endothelial lining. There is also vascular proliferation amidst perpendicularly oriented plump fibroblasts embedded in collagen (granulation tissue). In addition, there are numerous shrunken, hypereosinophilic, fragmented or hyalinized collagen bundles, occasionally surrounded by degranulated eosinophils.

Pituitary Abscess as Manifestation of IgG4-Related Hypophysitis: A Case Report

IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition with heterogeneous organ-specific manifestations. IgG4-related hypophysitis results from pituitary involvement and represents a rare neuro-ophthalmic complication of IgG4-RD, but the presentation as pituitary abscess is exceptional. We report the case of a 38-year-old otherwise healthy woman with a 3-year history of relapsing pituitary sterile abscess repeatedly treated with neurosurgery and antimicrobials. Histological re-examination of pituitary biopsy specimens revealed a dense inflammatory infiltrate rich in IgG4-positive plasma cells. Serum IgG4 levels were normal and circulating plasmablasts were increased. A diagnosis of IgG4-related hypophysitis was made and the patient treated with high-dose steroid pulse therapy with subsequent reduction of the pituitary lesion and resolution of symptoms. This case highlights how the diagnostic intuition on the basis of histopathology has changed management with prompt dramatic response to steroid therapy.

A patient with fever and umbilicated papules

A patient with fever and umbilicated papules

Calcipotriol: A novel tool in treatment of acne vulgaris.

Retinoids and active vitamin D3 analogues regulate the proliferation and differentiation of keratinocytes. Retinoids are the main stay in the treatment of acne vulgaris through their comedolytic and anti-inflammatory effects. However, the effect of calcipotriol on the different forms of acne lesions has not been reported. This split face prospective study aimed to detect the efficacy of topical calcipotriol in the treatment of acne lesions in comparison with that of adapalene. Forty patients with acne vulgaris were treated with topical calcipotriol (0.005%) cream and 0.1% adapalene gel on the right and left sides of the face respectively. Clinical and histological assessment of the used treatments was done 2months after the start of treatment. Two months after treatment, there was significant reduction of all acne lesions with significant decrease of physician global assessment and patient global assessment scores (p=0.0001) on both sides of the face with no significant difference between both sides. Histologically, there was significant decrease in the density of inflammatory infiltrate, which was more significant on the right side (p < 0.0001). Topical calcipotriol can serve a significant role in the treatment of acne vulgaris, through its anti-inflammatory effect which was comparable to that of adapalene.

Clinical and pathologic characteristics of gastric adenocarcinoma associated with Epstein-Barr virus in a region with a high incidence of gastric cancer in Colombia

Introduction and aimsEpstein-Barr virus (EBV) infection is an etiologic factor in EBV-associated gastric carcinoma (EBVaGC). The aim of our study was to describe the clinical and histopathologic characteristics of EBV infection in intestinal-type gastric adenocarcinoma samples. Material and methodsOf 180 paraffin-embedded gastrectomy samples, 28 were studied. Chromogenic in situ hybridization was performed to detect EBV. Sociodemographic and histopathologic data were obtained from the patients’ clinical histories. ResultsA total of 21.4% of the samples were positive for EBV. The predominant morphologic characteristic was the lace pattern, with dense inflammatory infiltration. Fifty percent of the EBVaGC+ patients were men, and the median age of the positive patients was 59 years (range: 50–75); 77.2% of the EBVaGC− patients were men, and the median age of the negative patients was 66 years (range: 34–89). Helicobacter pylori infection was associated with 10.7% of the EBVaGC+ patients and 53.6% of the EBVaGC− patients. In the EBVaGC+ patients, the cardia was the most frequent tumor location (17.9%), 7.1% had histologic grades 2 and 3, and 17.9% presented with Borrmann classification type III. In the EBVaGC− patients, the cardia and fundus were the most frequent tumor locations (71.4%), 35.7% had histologic grade 2, and 39.3% and 21.4% presented with Borrmann classification type III and IV, respectively. ConclusionsThe present study describes the clinical and histopathologic characteristics associated with EBVaGC positivity. Those data may aid in the selection of cases that are candidates for analysis through molecular methods aimed at identifying EBV infection in intestinal-type gastric adenocarcinoma.

Diagnosis of invasive Mucormycosis on Histopathological examination at a tertiary referral hospital

This study is conducted with an aim to Diagnosis of invasive Mucormycosis on Histopathological examination at a tertiary referral hospital. Rhino cerebral Mucormycosis is the current life-threatening infection commonly affecting immunocompromised patients especially post COVID-19 within 6 weeks having poor glycemic control, Intravenous drug users, ICU patients, post chemotherapy, iron overload, persistent neutropenia and follow-up cases of hematological malignancies. It affects the nasal and paranasal sinuses by air-borne spores producing the infection. A prospective case series conducted at the department of pathology, KAMSRC ‘between’ May 1to September 30th 2021 with a study population of 27 cases. Variables included age, gender, and history of covid, duration and development of symptoms, Clinical presentation, clinical diagnosis, co-morbidities, histopathological examination and microbiological correlation. The most prevalent isolated agent is Mucor (48.1%) followed by Rhizopus (18.5%), Aspergillus (11.1%) and mixed mucor with aspergillus (11.1%).A prospective case series conducted at the department of pathology, KAMSRC, reported 27 cases of post covid-19 Mucormycosis aged 30-68 years. Clinical features at presentation included unilateral facial pain with proptosis (80%), loss of vision, headache, nasal crusting, Cough with dyspnea and mild fever. All cases were admitted in ICU with severity in symptoms with 7 deaths recorded during treatment (25.9%). Immunofluorescence with Robin blue/Calcofluor white stainfor fungal elements was also combined to highlight Mucor species.Fungal cultures were diagnostic for fungal elements obtained after 48hrs on Sabouraud’s/Potato dextrose agar(SDA/PDA). Three cases were negative for fungal elements withonly dense mixed inflammatory infiltrate admixed necrosis. Correlation with KOH mount &amp; fungal culture on SDA/PDA showed 13 cases of mucor, 5 cases of rhizopus, 3 cases of aspergillus &amp; 2 cases of mucor with aspergillus growth, 3 cases were negative with no fungal growth. Also correlated with the microbiology department where nasal crusting and nasal tissue was obtained for fungal elements for KOH wet mount and fungal culture. KOH wet mount microscopy revealed Broad aseptate hyphae with wide angle branching suggestive of Mucormycosis. Simultaneous analytical study of CBP showed raised total WBC counts in 4 individuals (19,620-24,670 cumm) with others having normal CBC.CRP was in the range of 32-68mg/dl with ESR 35-98 mm/hr. : Understanding the mechanism of host innate immunity and specific preventive strategies are important for favorable prognosis. Histopathological examination aids in early diagnosis of Mucormycosis.

Características clínico-patológicas del adenocarcinoma gástrico asociado al virus de Epstein-Barr en una región de alta incidencia de cáncer gástrico en Colombia

Introduction and aimsEpstein-Barr virus (EBV) infection is an etiologic factor in EBV-associated gastric carcinoma (EBVaGC). The aim of our study was to describe the clinical and histopathologic characteristics of EBV infection in intestinal-type gastric adenocarcinoma samples. Material and methodsOf 180 paraffin-embedded gastrectomy samples, 28 were studied. Chromogenic in situ hybridization was performed to detect EBV. Sociodemographic and histopathologic data were obtained from the patients’ clinical histories. ResultsA total of 21.4% of the samples were positive for EBV. The predominant morphologic characteristic was the lace pattern, with dense inflammatory infiltration. Fifty percent of the EBVaGC + patients were men, and the median age of the positive patients was 59 years (range: 50-75); 77.2% of the EBVaGC– patients were men, and the median age of the negative patients was 66 years (range: 34-89). Helicobacter pylori infection was associated with 10.7% of the EBVaGC + patients and 53.6% of the EBVaGC– patients. In the EBVaGC + patients, the cardia was the most frequent tumor location (17.9%), 7.1% had histologic grades 2 and 3, and 17.9% presented with Borrmann classification type III. In the EBVaGC– patients, the cardia and fundus were the most frequent tumor locations (71.4%), 35.7% had histologic grade 2, and 39.3% and 21.4% presented with Borrmann classification type III and IV, respectively. ConclusionsThe present study describes the clinical and histopathologic characteristics associated with EBVaGC positivity. Those data may aid in the selection of cases that are candidates for analysis through molecular methods aimed at identifying EBV infection in intestinal-type gastric adenocarcinoma.

Inflammatory pseudotumour of the spleen

Inflammatory pseudotumour (IPT) of the spleen is a very rare benign entity that can clinically and radiologically be misconstrued as malignant. We describe a case in a 62-year-old woman who was incidentally found to have a 5.3 cm mass on abdominal ultrasound. On MRI, the mass had irregular margins and internal necrosis, raising suspicion for a malignancy. The woman then underwent a splenectomy. Histology showed a well circumscribed lesion characterised by a proliferation of bland uniform spindle cells in a background dense mixed inflammatory infiltrate consisting of lymphocytes, plasma cells and eosinophils.

Post-Covid-19 Immunological Disorder: A Possible Pathological Entity in a 43 Year Old Man

Abstract Background. Post-COVID-19 systemic inflammatory syndrome is considered to be an aquired immunological disorder, which may develop in some individuals after the remission of infection with SARS-CoV-2 and defined by inflammatory clinical manifestations (fever, arthralgias, cutaneous and mucosal pallor, physical weakness) and modified biological parametres (normochromic normocytic anaemia, increased serum levels of C reactive protein and rheumatoid factor), with no proof of an infectious process, to which corticotherapy may be a suitable therapeutic strategy. Case report. A 43 year old male was admited in the Department of Internal Medicine for high fever (39,4°C), moderate polyarthralgias and physical weakness, with a negative test result of SARS-CoV-2 RT-PCR. The patient had been previously diagnosed with a moderate-to-severe form of COVID-19, a month prior to the current admission. The patient also experienced transitory dry cough for a month, with no other relevant clinical abnormalities. Upon physical examination, cutaneous and scleral pallor was observed and lung auscultation revealed hardened vesicular murmur bilaterally. Blood analysis revealed normochromic normocytic anaemia and increased serum levels of rheumatoid factor and of C reactive protein, which suggested a nonspecific inflammatory syndrome. Although blood cultures and other microbiological tests were negative for an infectious process, a chest X-ray was performed, which detected the presence of a nodular formation in the superior left lung lobe. Several differential diagnoses were taken into consideration, including pulmonary sarcoidosis and granulomatosis with polyangiitis, both of which were excluded, clinically and biologically. A thoracic computed tomography (CT) was later performed, which revealed the presence of a tumoral nodule in the left lung, associated with multiple mediastinal and supraclavicular lymphadenopathies, indicative of lung cancer. However, lung cancer was also excluded upon the histopathological examination of paratracheal lymphnodes, which detected multiple areas of parenchymal necrosis surrounded by dense inflammatory infiltrates, formed predominantly by histiocytes. All of these findings resulted in the diagnosis of a post-COVID-19 rheumatoid syndrome, the only therapeutic strategy being the administration of high doses of intravenous and oral methylprednisolone, which improved the patient’s health. Conclusion. Post-COVID-19 immunological disturbances should be taken into consideration in patients who experience repetitive clinical and biological inflammatory manifestations after the remission of the infection with SARS-CoV-2, which may be improved through high dose corticosteroid therapy.

Morphology of cells undergoing epithelial mesenchymal transition in microinvasive and early invasive oral squamous cell carcinom a – a light microscopic study

The present study focuses on identification of cancer attributes of epithelial mesenchymal transition (EMT) at the earliest possible stage (microinvasion) under alight microscope by using hematoxylin and eosin stains, making it feasible for researchers to investigate such cases with ease without the use of extensive setups. The present study is the first in the English literature to define EMT features in micro-invasive and early invasive oral squamous cell carcinoma (OSCC) under alight microscope. This is aretrospective study of histological sections of 43 cases of OSCC from the Department of Oral Pathology and Microbiology. The data collected were later statistically analyzed. Atotal of 11 micro-invasive and 32 early invasive OSCC cases were assessed for core features of EMT. The predominant feature defining EMT found was dense inflammatory infiltrate in both microinvasive (91%) and early invasive OSCC (88%) followed by cell individualization in 82% of microinvasive and 75% of early invasive OSCC, which was then followed by other features. Reporting EMT in histopathological reports on adaily basis can aid in early diagnosis of OSCC as well as understanding carcinogenesis in early stages. Thereby, inclusion of EMT targeting therapeutics in early stages of OSCC can significantly alter the prognosis of cancer.

A Rare Case of Purely Cutaneous Rosai–Dorfman’s Disease

Rosai–Dorfman’s disease (RDD) is sinus histiocytosis with massive lymphadenopathy. Cutaneous RDD is a rare entity that presents with isolated skin involvement without any systemic involvement. We report a 35-year-old man with an asymptomatic large nodule on the preauricular region of the face with an irregular surface and multiple yellow studded nodules. On detailed physical and systemic examination, there was no lymph node or systemic involvement. Skin biopsy on histopathology showed dense dermal inflammatory infiltrate and foamy histiocytes with emperipolesis. Immunohistochemical markers were positive for S100 protein and CD68 protein but negative for CD1a. Thus, a diagnosis of cutaneous RDD was made.

Eosinophilic ulcer of the oral mucosa: An update on clinicopathologic features, pathogenesis, and management.

Eosinophilic ulcer of the oral mucosa is a benign, reactive, self-limited lesion. Its pathogenesis is unclear, and it clinically manifests as a punched-out ulcer with surrounding indurated border, raising suspicion for a possible malignancy. On histology, an acute and chronic dense inflammatory infiltrate can be appreciated, which can extend to the deep underlying tissue (including skeletal muscle). Eosinophils are especially conspicuous on hematoxylin and eosin staining and might play an important role in the development of the ulcer. Removal of possible triggers followed by monitoring and possible biopsy are among the initial recommendations. Most lesions heal spontaneously without the need for intervention. This review aims at assisting dermatologists to easily recognize this entity, avoiding unnecessary interventions and apprehension.

Gastric marginal zone lymphoma of mucosa-associated tissue and Epstein-Barr Virus associated lymphoepithelioma gastric carcinoma: Two primaries with an unusual metachronous presentation

Abstract Introduction/Objective Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and Epstein-Barr virus (EBV) lymphoepithelioma gastric carcinoma, are two distinct gastric malignancies, with well-known clinicopathological characteristics. Synchronous or metachronous presentation of both entities in the same patient is extremely rare. Methods/Case Report We report a case of a 78-year-old woman, who presented with a 3 cm gastric body mass. Histologically, the biopsy showed H. pylori gastritis, with diffuse monotonous atypical lymphocytic cells and prominent lymphoepithelial lesions. CD20 immunostain was diffusely positive in these cells, supporting the diagnosis of MALT lymphoma. The patient was treated for H. pylorieradication, followed by Rituxan for resistant MALT lymphoma found in a surveillance biopsy. After being free of disease for one year, the patient developed a 2.0 cm, ulcerated lesion adjacent to the previous site. Biopsy of this lesion showed gastric mucosa with diffuse lymphoepithelial lesions, and atypical epithelial cells highlighted by pan-cytokeratin. The associated dense inflammatory infiltrate was comprised predominantly of CD3 T-lymphocytes. EBV was detected by in-situ hybridization (ISH) for EBV encoded RNA, and was positive in the epithelial cells, but negative in lymphocytes. These findings are consistent with EBV associated lymphoepithelioma carcinoma. Results (if a Case Study enter NA) NA Conclusion This case is presented due to its rarity, with only two cases reported previously, which invokes further research into the interaction between both infectious agents. Secondly, lymphoepithelial lesions are a common finding in both diseases, and in small biopsies, these entities can mask or mimic each other. EBV ISH and background B and T lymphocytes may be a clue and help in the diagnosis.

O29 Keeping a watchful eye: IgG4-positive lymphoma masquerading as IgG4-related ocular disease

Case report - IntroductionIgG4-related disease (IgG4-RD) is increasingly recognised in rheumatology practice. We describe a case of orbital swelling initially diagnosed as IgG4-RD. It was exquisitely steroid responsive and she was treated with 6 years of immunosuppression but her symptoms later deteriorated. She developed worsening left eye swelling that required debulking surgery; histopathology demonstrated IgG4-positive lymphoma. She had an excellent response to localised radiotherapy and remains in remission. Although her initial presentation was typical of IgG4-RD, her subsequent lack of response to steroids prompted reconsideration of the initial diagnosis and re-examination of her previous biopsy specimen, confirming IgG4-positive Iymphoma at both timepoints.Case report - Case descriptionA 25-year-old lady presented in 2008 with a swollen left eye. She had a history of childhood eczema, asthma and sinusitis. Diagnostic excision was undertaken; histology was considered to show chronic inflammation, scattered eosinophils, dense fibrosis and no granulomas. She was diagnosed with a ‘granulomatosis with polyangiitis-like’ orbital pseudotumour. It was exquisitely steroid responsive; mycophenolate mofetil was added from an early stage of treatment.The patient was referred to rheumatology 3 years after diagnosis as she was unable to reduce her prednisolone below 5mg daily. Her immunology screen was negative. Although her plasma IgG4 levels were normal at 0.14g/L, the original histology was reviewed and immunostained for IgG4. This demonstrated more than 80% of plasma cells to be IgG4 positive, with the previously noted dense fibrosis and chronic inflammatory infiltrate. Her diagnosis was revised to orbital IgG4-RD. She commenced azathioprine as she was planning a pregnancy.Following an uncomplicated pregnancy in 2014, her symptoms significantly deteriorated, with worsening pain, discharge and swelling in her left eye. A repeat MRI scan showed a new cuff of abnormal tissue within the lateral aspect of the left orbit. She was referred to ophthalmology and underwent left anterior orbitotomy with debulking. Histopathology at this time was consistent with extranodal marginal zone lymphoma (EMZL) of MALT (mucosa-associated lymphoid tissue) type, IgG4 positive. An extraordinary feature was an abundance of crystal-storing histiocytes, presumed to contain ingested IgG4.To investigate whether she had an IgG4-secreting lymphoma from the beginning or whether there had been malignant transformation of her orbital IgG4-RD, the histology from 2009 was reviewed. This was considered to indicate a MALT-type EMZL.The patient was referred to haematology and she was treated with localised radiotherapy with an excellent response. She remains in remission following this and she has subsequently been discharged from haematology follow-up.Case report - DiscussionIgG4-RD is a condition involving fibroinflammatory lesions that can affect any organ in the body. As a newly recognised condition, the role of IgG4 in IgG4-RD is still not fully understood. Questions that remain unanswered include whether or not IgG4 is directly pathogenic and whether there is an increased risk of malignancy in patients with IgG4-RD.Our patient’s case demonstrates how IgG4-positive lymphoma can mimic IgG4-RD. It is important to keep a broad differential diagnosis in complex cases, and to support the eventual diagnosis with blood results, imaging studies and histology. It is essential to involve colleagues in radiology and histopathology so that a multidisciplinary decision can be made with regards to management. IgG4-RD is a steroid-responsive condition. When there is poor response to conventional treatment, this should raise doubts regarding the diagnosis, and it would be prudent to consider a repeat biopsy as well as obtaining previous pathology specimens so that they can be re-reviewed.Ocular adnexal lymphomas form 1—2% of non-Hodgkin lymphomas and 8% of extranodal lymphomas. Over recent decades the incidence has increased, partly reflecting better diagnostic techniques. The most common subtype of ocular adnexal lymphomas are EMZL of MALT type, as in our patient.There are several case reports of lymphoma arising in patients with established IgG4-RD, raising the question of potential lymphomagenesis in IgG4-RD. The earliest reports come from Asia and most have been reported in patients with ocular IgG4-RD. However, the link between malignancy and IgG4-RD is still being investigated. It is important to consider a potential malignancy when managing patients with IgG4-RD, especially if there is a lack of response to steroids.Case report - Key learning pointsThere is no single diagnostic test for IgG4-RD. Diagnosis should be based on the overall clinical picture, supported by blood results, imaging and histopathology.IgG4-RD is a steroid-responsive disease. If there is a poor response to treatment, the diagnosis should be re-considered.Re-examination of previous biopsy specimens can be invaluable, especially in patients refractory to standard treatment.The link between IgG4-RD and malignancy has not been established and it is important to remain vigilant. As ocular adnexal lymphomas are not uncommon, it is important to keep this differential diagnosis in mind when reviewing patients with eye swelling thought to be secondary to IgG4-related ocular disease.

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.