Diffuse Lymphoplasmacytic Infiltration Research Articles

Pseudotumor inflamatorio ocular asociado a IgG4. Reporte de un caso

IgG4-associated ocular inflammatory pseudotumor is a rare, non-neoplastic inflammatory process with an incidence of 0.28-1.08 per 100,000 people. The diagnosis of this pathology is one of exclusion, having to meet histopathological criteria, enlargement of a specific organ, and serious concentrations of IgG4. Treatment aims to avoid secondary complications. Clinical case: A 54-year-old woman with no previous re-ported pathologies, reports that for the past 6 months she has itching at the level of the eyeball and the left eyelid, suddenly and without apparent cause, in addition to decreased visual acuity and retro-ocular pain; this is why she asked for the evaluation. The physical examination revealed normal eye movements, left proptosis, pain on palpation, subconjunctival hyperemia, corneal opacity, absence of red reflex, and the left eye being more resistant to pressure in relation to the contralateral eye. The cranio-thoraco-abdominal tomography reported images at the left ocular level that were suggestive of choroidal melanoma without findings of metastatic activity. Enucleation of the left eye was performed. The specimen was sent to pathology which reported diffuse lymphoplasmacytic infiltrate positive for IgG4. Conclusion: Ocular IgG4 disease is a very rare pathology with non-specific symptoms and complex diagnosis. However, a quick and correct approach is essential to avoid complications.

DISRUPTION OF THE UROTHELIAL BARRIER UNDER BENIGN PROSTATIC HYPERPLASIA AS A COMPONENT OF BLADDER DECOMPENSATION

Introduction. The urothelial barrier resists the aggressive effect of urine on the bladder tissues. Chronic retention of urine causes the development of an infectious and non-infectious inflammatory process with metaplasia and desquamation of the urothelial layer of the bladder. With long-term infravesical obstruction, the contact density between urothelial cells is disturbed, which leads to the loss of the barrier function of the mucous membrane of the urinary bladder.
 The purpose of the study is to investigate the role of urothelial barrier disruption in the development of urinary bladder decompensation in patients with BPH.
 Materials and methods. 70 patients with BPH were selected, their average age was 67.94±7.42 years. They underwent a bladder biopsy during the operation, followed by a pathomorphological examination.
 According to clinical manifestations, patients were divided into three groups: group I included 20 patients with bladder compensation (I-PSS – 16±4.5, Qmax – 15.8±2.4 ml/s, Qave – 12.8±2.8 ml/s, without post void residual); group II involved 20 patients with bladder subcompensation (I-PSS – 26±3.9, Qmax – 10.8±2.5 ml/s, Qave – 4.4±1.4 ml/s, post void residual – 150.1 ±80.8 ml.); and III group included 30 patients with bladder decompensation (before the cystostomy I-PSS – 33.1±1.88, post void residual – 1093.3±458.8 ml).
 Results. In the compensation stage of the bladder there is found multilayer transitional cell urothelium that often forms folds, causing pseudoepithelial outgrowths. The detrusor is represented by hypertrophied smooth muscle cells, with the phenomena of moderate hydropic dystrophy in individual myocytes, with isolated small foci of sclerosis. In the stage of bladder subcompensation we observe foci of desquamation of the surface layers of the urothelium and dystrophic changes in epitheliocytes. Areas of atrophy are combined with foci of hyperplasia of epitheliocytes with stratification of the epithelium (up to 14 - 18 layers or more). The lamina propria of the mucous membrane is swollen in most cases, the formation of lacuniform slits is seen. There are often foci of lymphoplasmacytic infiltration. The detrusor is mostly represented by hypertrophied smooth muscle cells, a significant number of which have signs of hydropic dystrophy.
 In the stage of bladder decompensation the foci of total desquamation of all layers of the urothelium can be observed; pronounced dystrophic changes of epitheliocytes also take place. The own plate of the mucous membrane is sharply thickened: due to the formation of numerous lacuniform slits it has a porous appearance. Erosive changes in the mucous membrane of the urinary bladder are accompanied by pronounced sclerosis of the stroma. In places of desquamation of the urothelium, submucosal foci of sclerosis are observed, which penetrate into the detrusor. The latter is represented by hypotrophied smooth muscle cells with signs of hydropic dystrophy. Due to the massive proliferation of connective tissue, muscle fibres are divided into separate bundles. Diffuse lymphoplasmacytic infiltration is observed in all layers of the bladder.
 Conclusion: The results of pathomorphological studies in the context of clinical and functional characteristics enables to distinguish three stages of SM remodelling in BPH: compensation, subcompensation and decompensation. Long-term chronic retention of urine causes a violation of the urothelial barrier, urine impregnation of all layers of the CM with the development of aseptic inflammation. A progressive increase in the specific weight of connective tissue, dystrophic changes in myocytes and nerve fibres become the cause of decompensation of the CM with a violation of the contractile ability of the detrusor.

S3677 Tissue Is the Issue: A Rare Case of Collagenous Gastritis

Introduction: Collagenous gastritis (CG), collagenous sprue, and collagenous colitis are rare forms of collagenous gastroenteritides marked by subepithelial collagen deposition of more than 10 mm and inflammatory infiltrate in the lamina propria. CG was first identified in 1989. It's a rare disease, with just 100 cases reported so far. Here, we present a distinct case of collagenous gastritis. Case Description/Methods: 52-year-old female with no chronic medical conditions presented with symptoms of mild reflux, epigastric pain, and intermittent diarrhea up to 5 times per day. She had sporadic Ibuprofen use for headaches. Her mother was diagnosed with lupus and a half-sister with a history of mixed connective tissue disorder. Initial upper endoscopy revealed grade B esophagitis and gastritis, biopsies showed CG. Colonoscopy with random biopsies showed no evidence of collagenous colitis. She was treated with high dose proton pump inhibitor (PPI) and repeat endoscopy in 4 weeks with biopsies via Sydney protocol was performed. Additional blood work was normal including normal thyroid panel, celiac screen (anti-transglutaminase IgA: < 1.0 U/ml, IgA: 2.34 g/L) and IgG4 titer (0.27 g/L.) Repeat EGD with biopsies per Sydney protocol confirmed CG in all gastric quadrants, except fundus. After stopping NSAIDs and continuing on PPI, her symptoms resolved with a plan for surveillance endoscopy in 6 months (Figure 1). Discussion: In our patient, the diagnosis of CG led to further investigations to rule out possible associated autoimmune diseases. The occasional ibuprofen may have been contributory, but the repeat biopsies on the second endoscopy confirmed the presence of CG despite cessation. The only contributing factor in her case is positive family history. There are very few cases reported in the literature with the possible association of lupus with CG. This distinctive case of CG is an important contribution to the limited pool of existing cases as the patient herself did not have any preexisting allergic or autoimmune conditions and it appears that this process occurred idiopathically. Given the rarity of the condition and limited literature available, we emphasize the importance of delineated medical guidelines for appropriate screening and surveillance.Figure 1.: Endoscopic appearance of collagenous gastritis. A, B. body, C. Antrum D. fundus ; E, F: Histology of collagenous gastritis characterized by thickening of sub epithelial basement membrane accompanied by diffuse superficial lymphoplasmacytic infiltrates and surface epithelial degeneration. Table 1. - Summary of Collagenous gastritis (CG) COLLAGENOUS GASTRITIS (CG) - Characterized by marked sub epithelial collagen deposition with associated inflammatory infiltrate. EPIDEMIOLOGY - Female Preponderance - All age groups but primarily affects adults. ETIOLOGY - The etiology is unknown - Stancu et al. outlined three pathogenic mechanisms that may lead to collagen deposition in cases of CG: (1) Chronic inflammation (2) Fibroblast sheath abnormality (3) Leakage of plasma proteins and fibrinogen ASSOCIATIONS - Intestinal and autoimmune disorders, including celiac disease. collagenous enteritis, collagenous colitis, sjogren syndrome, SLE, juvenile arthritis, RA, Hashimoto's thyroiditis, Grave's disease, Diabetes mellitus type 1, and CVID. - Medications such as Olmesartan, Venlafaxine SYMPTOMS AND SIGNS - Epigastric and or abdominal pain, anemia , gastrointestinal bleeding, diarrhea, nausea and vomiting, perforated ulcer, weight loss, abdominal distension, fatigue, dyspepsia, retrosternal pain, constipation and dysphagia. DIAGNOSIS - EGD with biopsy TREATMENT - Anti-secretory agents including PPIs, and H2 receptor antagonists, steroids, iron supplementation and hypoallergenic diets have been tried with limited success. - Other treatment modalities , such as sucralfate, mesalazine, bismuth subsalicylate, furazolidone, sulfasalazine, azathioprine, and parenteral nutrition have also been tested.

Odontogenic Keratocyst: The Dos and Don’ts in a Clinical Case Scenario

Patient: Male, 19-year-old Final Diagnosis: Odontogenic keratocyst Symptoms: Swelling Medication:— Clinical Procedure: Enucleation Specialty: Otolaryngology Objective: Challenging differential diagnosis Background:Odontogenic keratocysts are odontogenic cysts that increase in dimension based on growth factors and have a high recurrence rate. The radiological features of odontogenic keratocysts can be confusing owing to their similarity with other intraosseous cysts. The aim of treatment is to minimize patient morbidity and to reduce the risk of recurrence, along with complete surgical excision.Case Report:We report a case of a young man who presented to our hospital for a cystic lesion located in the posterior left mandible with clinical and radiological features of a dentigerous cyst. The lesion was treated accordingly for this diagnosis by enucleation. During surgery, a thick and firm cystic membrane was identified. Histopathological examination of the specimen established the final diagnosis of odontogenic keratocyst by identifying squamous epithelium with focal parakeratosis and ulceration and a diffuse inflammatory lymphoplasmacytic infiltrate. The patient’s evolution was favorable, with no sign of recurrence on cone beam computed tomography examination at the 6-month follow-up and with healing of the surgical defect.Conclusions:The diagnosis of odontogenic keratocyst is challenging, requiring preoperative 3-dimensional imaging and biopsy for extensive lesions. Adjuvant biochemical and immunological examination of cystic aspirate could sometimes be helpful for making a correct diagnosis. The treatment needs to be individualized according to the patient’s age and the tumor’s histopathological type and features. If the histopathological examination of surgical specimen indicates a more aggressive lesion than expected, a careful and individualized follow-up is imperative. No reintervention is needed if the patient does not present evidence of recurrence.

Specimen Adequacy and Clinicopathological Evaluation of Inflammatory Bowel Disease Colorectal Biopsies in Cipto Mangunkusumo Hospital Jakarta

Background: Colorectal mucosal biopsies account for majority of daily practice specimens in the field of gastrointestinal pathology. Most of them were sent for inflammatory bowel disease (IBD) evaluation. Due to broad spectrum of histologic findings and different stage of disease, pathologists often find difficulties on calling out diagnosis of IBD. This study aims to evaluate the adequacy of specimen, clinical characteristics, endoscopy and histologic findings of colorectal biopsies from IBD and non-IBD patients.Method: This cross-sectional study included 49 IBD and 49 non-IBD cases registered in the archives of Anatomical Pathology Department, Cipto Mangunkusumo National Referral Hospital Jakarta in 2019. The samples were evaluated for adequacy of specimen, clinical, endoscopy and histologic findings.Results: Most samples were adult with a slight female predominance. All request forms contained the clinical working diagnosis but only 26.5% and 20.4% of them provided clinical history and endoscopy findings. During histology evaluation, 59.2% of the specimen was considered sub-optimal. The most common histologic findings in both IBD and non-IBD groups were diffuse lymphoplasmacytic infiltration in the lamina propria and crypt distortion. Fibrosis/collagen deposition was found in 38.8% of IBD population compared to 12.2% of non-IBD population (p=0.003). Most IBD cases (55.1%) were categorized as active phase IBD.Conclusion: Since the most common histologic findings in IBD patients were also found in non-IBD patients, IBD diagnosis based on histopathology alone is highly inadvisable. However, there were also lack of clinical data and endoscopy findings in most of colorectal biopsies sent for IBD evaluation. Along with overlapping and unspecific morphology and suboptimal events during histological evaluation, all of this complicated the diagnosis of IBD. Hence multidisciplinary approach is required for a better IBD diagnosis and treatment.

Immunoglobulin G4-Related Orbital Disease with Bilateral Optic Perineuritis and Maxillary Nerves Involvement: A Case Report.

Immunoglobulin G4-related optic neuropathy caused by optic perineuritis is a rare complication of immunoglobulin G4-related disease (IgG4-RD). Herein, we report a 38-year-old Asian man with history of sinusitis who presented with painless blurred vision and proptosis for over 6 months. Examination with the Hertel exophthalmometer revealed 21.5 mm on both eyes. Magnetic resonance imaging revealed a doughnut sign encircling the right optic nerve, bilateral tram-track signs on both optic nerves, enlarged bilateral maxillary nerves with perineural spreading to the infraorbital nerves, hypertrophy of extraocular muscles, and pansinusitis. Visual evoked potentials displayed bilateral delayed P100 latency, indicating bilateral optic neuropathy. Biopsy with functional endoscopic sinus surgery demonstrated diffuse dense lymphoplasmacytic infiltrate and fibrosis. IgG4-positive plasma cells exceeded 50 cells per high-power field while the overall IgG4/IgG ratio was above 40%. Serological studies unveiled extremely high serum concentrations of IgG4 (2650 mg/dL), and the calculated serum IgG4/IgG ratio was 100%. These comprehensive features supported the diagnosis of IgG4-RD with bilateral optic perineuritis, branches of trigeminal nerve involvement, and pansinusitis. The visual acuity improved slightly following the initiation of treatment with corticosteroids, but it became worse again during the tapering course. Following another course of corticosteroids followed by subsequent immunosuppressant treatment with azathioprine, vision in both eyes ultimately improved during the 2-year follow-up period.

A CASE OF IGG4-RELATED INTERSTITIAL LUNG DISEASE MANIFESTING AS RECURRENT NECROTIZING PNEUMONIA

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: IgG4-related disease is a newly recognized fibroinflammatory disorder characterized by enlargement of one or more organs with classic histopathologic findings of diffuse lymphoplasmacytic infiltration and IgG4+ plasma cells. Presentation relies on the primary organ affected. Pulmonary disease can be especially difficult to characterize, as its course may mimic various lung pathologies. In this case report, we describe a case of IgG4-related interstitial lung disease (ILD) that manifested as recurrent necrotizing pneumonia. CASE PRESENTATION: A 33-year old female with past medical history of recent Group B Streptococcal bacteremia with aortic valve endocarditis was admitted for severe aortic insufficiency, necessitating aortic valve replacement. She developed hypoxic respiratory failure requiring ventilation support and treatment for pneumonia. After discharge, she was soon readmitted for right sided necrotizing pneumonia. Initial bronchoscopy positive for Streptococcus Viridians and Lactobacillus with repeat bronchoscopy after antibiotics showing normal flora. Patient was ultimately readmitted for left sided chest pain and hypoxia. Initial workup showed elevated inflammatory markers and CT chest with right-sided, multifocal pneumonia with cavitations. Microbiology and immunologic studies unremarkable. The patient did not improve on 1 month of antibiotics so underwent a lung biopsy revealing for interstitial fibrosis, inflammatory lymphoplasmacytic infiltrate, and positive IgG4 staining with elevated serum IgG4 levels- diagnostic for IgG4-related ILD. The patient was started on PO prednisone with complete resolution on most recent follow-up 2 months later. DISCUSSION: IgG4-related disease was first recognized in 2003 and is now understood as a spectrum of related diseases. In particular, the prevalence of pulmonary involvement remains uncertain, and neither diagnostic criteria nor treatment have officially been established. Review of previous cases reveals diverse presentations sharing features of other lung pathologies including pneumonias, cancer, and granulomatous diseases. The current report describes IgG4-related ILD manifesting as recurrent necrotizing pneumonia confirmed via characteristic lung pathology and an elevated serum IgG4 level of 235 mg/dL. Treatment relied on previous cases describing good prognosis from corticosteroids; specifically, prednisone 0.6 mg/kg with plans for slow taper. Patient was successfully weaned from oxygen support without further addition of DMARDs. CONCLUSIONS: IgG4-related disease encompasses a spectrum of fibroinflammatory disorders that can affect multiple organ systems, including the lungs. Given the evolving nature of IgG4-related ILD, diagnosis can be especially difficult given the multitude of presentations mimicking other infectious, neoplastic, and inflammatory disease processes. Larger studies could further understanding of this complex disease. Reference #1: Stone, John H., et al. “Mechanisms of Disease: IgG4-Related Disease.” The New England Journal of Medicine, 9 Feb. 2012. Reference #2: Chen, Chiu-Fan et al. “IgG4-related lung disease presenting as interstitial lung disease with bronchiolitis: A case report.” Medicine vol. 96,49 (2017): e9140. doi:10.1097/MD.0000000000009140 Reference #3: Umehara, Hisanori, et al. “Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD).” Modern Rheumatology, vol. 22, no. 1, 2 Jan. 2014, pp. 21-30. Abstract. DISCLOSURES: no disclosure on file for Duc Ho; No relevant relationships by Larry Jankelowitz, source=Web Response No relevant relationships by Ramier Lehne, source=Web Response

Clinical case of membranous nephropathy in a patient with IgG4-related disease

IgG4-related disease (IgG4-RD) currently is considered as a chronic fibroinflammatory immune-mediated multisystemic condition of unidentified etiology, which can imitate a wide range of malignant, infectious, rheumatologic, and other diseases. It can affect almost any organ system in the body synchronously or sequentially, but the most often affected are the pancreas, hepatobiliary tract, periorbital structures, salivary glands, kidneys, and lymph nodes. The most frequent renal manifestations of IgG4-RD is IgG4-related tubulointerstitial nephritis. Membranous nephropathy is the most common glomerular disease accompanied by IgG4-RD. Regardless of the organ localization, patients with IgG4-RD are characterized by elevated serum IgG4, but this laboratory abnormality is not specific and can be changed in other diseases. In all suspected cases of IgG4-RD the diagnosis should be confirmed by histological examination. Characteristic pathologic features include diffuse or focal lymphoplasmacytic infiltration with prominent IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. Patients with IgG4- RD usually have an excellent clinical response to glucocorticoids, but relapse rates after steroid withdrawal are high, which may require additional use of immunosuppressants or rituximab. Due to the low prevalence and multitude of clinical manifestations the disease often remains underdiagnosed on time. This case report describes middle-aged patients with a history of chronic recurrent pancreatitis complicated by the nephrotic syndrome. Kidney biopsy showed membranous nephropathy and diagnosis IgG4-RD with multiorgan involvement was made. Partial remission was achieved on corticosteroid therapy. The presented case clearly demonstrates the difficulties of diagnosis and treatment of IgG4-RD. IgG4-related membranous nephropathy should be included in the differential diagnosis for patients with nephrotic syndrome accompanied by multiorgan dysfunction.

Gastric IgG4-related disease presenting as a mass lesion and masquerading as a gastrointestinal stromal tumor.

IgG4-related disease of the stomach is a rare disorder, and only a few cases have been reported. We present two cases that were identified over a 2-month period in our center. Two male patients aged 52 and 48 years presented with mass lesion in the stomach, which were clinically thought to be gastrointestinal stromal tumor, and they underwent excision of the lesion. Microscopic examination revealed marked fibrosis, which was storiform in one case, associated with diffuse lymphoplasmacytic infiltration and an increase in IgG4-positive plasma cells on immunohistochemistry. Serum IgG4 level was markedly elevated. Although rare, IgG4-related disease should be considered in the differential diagnosis of gastric submucosal mass lesions.

IgG4-related disease of the thyroid gland requiring emergent total thyroidectomy: A case report

IgG4-related disease of the thyroid gland is a recently recognised subtype of thyroiditis, often with rapid progression requiring surgical treatment. Here, we report a 47-year-old Malay woman presenting with progressively painless neck swelling over three years, with subclinical hypothyroidism. CT scan revealed diffuse thyroid enlargement (up to 13 cm) with retrosternal extension and without regional lymphadenopathy. Fine needle aspiration of the thyroid showed limited well-visualised follicular epithelial cells with widespread Hurthle cell change and scanty background colloid, but no evidence of lymphocytosis. The cytologic features fell into the category of ‘atypia of undetermined significance’. Subsequently, the patient developed hypercapnic respiratory failure secondary to extrinsic upper airway compression by the thyroid mass and underwent emergent total thyroidectomy. Histology of the thyroid showed diffuse dense lymphoplasmacytic infiltrate with fibrosis and focal obliterative phlebitis. Follicular cells exhibited reactive nuclear features and some Hurthle cell change. IgG4+ plasma cells were over 40/high power field while overall IgG4/IgG ratio was above 50%. Post-surgery, the patient was found to have markedly elevated serum IgG4 concentration but PET/CT did not show significant increased fludeoxyglucose uptake in other areas. Her recovery was complicated by a ventilator-associated pneumonia with empyema, limiting early use of corticosteroids on treatment of IgG4-related disease.

Gastrointestinal manifestation of immunoglobulin G4-related disease: clarification through a multicenter survey.

Several reports on immunoglobulin (Ig)G4-related disease (IgG4-RD) with gastrointestinal involvement (IgG4-related gastrointestinal disease; IgG4-GID) have been published, although this entity has not been fully established clinicopathologically. Thus, we carried out a multicenter survey. Patients with possible IgG4-GID who underwent resection were collected. Histologic slides were reevaluated, and eight cases with diffuse lymphoplasmacytic infiltration but without numerous neutrophils, granulations or epithelioid granulomas were further analyzed. Overall, the IgG4 counts (87-345/high-power field) and IgG4/IgG-positive ratio were high (44-115%). The demographic findings included advanced age among the patients (55-80years) and male preponderance (six cases). Six lesions (five gastric, one esophageal), consisting of lymphoplasmacytic infiltration with neural involvement in the muscularis propria and/or bottom-heavy plasmacytosis in the gastric mucosa, were histologically regarded as highly suggestive of IgG4-RD. Storiform fibrosis and obliterative phlebitis were found in two cases, and the former gave rise to a 7-cm-sized inflammatory pseudotumor (IPT) in one case. Ulceration and carcinoma co-existed in three and two lesions, respectively. All the patients had other organ involvement (OOI), and serum IgG4 levels were markedly elevated (four of five patients). The remaining two cases with gastric IPTs featuring reactive nodular fibrous pseudotumor or nodular lymphoid hyperplasia were regarded as possible cases of IgG4-RD because of the histologic findings and lack of OOI. IgG4-GID is found in the setting of IgG4-RD, often with ulceration or cancer. Characteristic histologic findings are observed in the muscularis propria and gastric mucosa. Cases with IPT may be heterogeneous, and there may be mimickers of IgG4-GID.

The Pathology of IgG4-Related Disease in the Bile Duct and Pancreas.

Immunoglobulin G4-related disease (IgG4-RD) in the pancreatobiliary system manifests as sclerosing cholangitis (SC), hepatic inflammatory pseudotumors, and type 1 autoimmune pancreatitis (AIP). The pathology of IgG4-RD involves an inflammatory process and fibrogenic pathway, the combination of which damages the affected organs. Fibroinflammatory injury is characterized by three microscopic findings: a diffuse lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, obliterative phlebitis, and storiform fibrosis. Although the diagnosis of IgG4-related pancreatocholangitis is relatively straightforward in surgical specimens, the current clinical requirement is to diagnose patients using biopsy samples, which remains challenging. Histological differential diagnoses include primary SC, follicular cholangitis/pancreatitis, SC with granulocytic epithelial lesions, and type 2 AIP. Although the massive infiltration of IgG4-positive plasma cells is a histological hallmark of IgG4-RD, many other immune cells (e.g., Th2 lymphocytes, regulatory T cells, and M2 macrophages) appear to be strongly involved in orchestral immune reactions.

Schwannomas gastrointestinales: revisión de la literatura a propósito de 5 casos en intestino

Less than 300 cases of gastrointestinal schwannoma have been reported to date. They occur most commonly in the stomach, being rare in the small bowel and rectum, and show characteristic clinical, histological, immunohistochemical and molecular features.We reviewed five cases of gastrointestinal schwannoma diagnosed between 2005 and 2015 in our hospital (Hospital Clínico San Carlos, Madrid).The patients were four women and one man, with a median age of 74 years. Three tumours were located in the caecum, one in the jejunum and one in the ileum. Tumour size ranged from 0.5 to 4.5cm. Microscopically, all were composed of monotonous benign-appearing spindle cells, without well-formed palisades or Verocay bodies. In all cases, except one, peripheral cuff-like lymphoid aggregates and/or diffuse lymphoplasmacytic infiltrate were present. S100 was diffusely positive and Ki-67 index was lower than 10%. None of the patients had recurrences or metastases.

Graves' Disease Patients with Persistent Hyperthyroidism and Diffuse Lymphoplasmacytic Infiltration in the Thyroid Show No Histopathological Compatibility with IgG4-Related Disease.

BackgroundIgG4-related disease is a novel disease entity characterized by diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells and fibrosis into multiple organs. There is still controversy over whether some thyroid diseases are actually IgG4-related disease. The objective of this study was to elucidate the clinicopathological features of Graves’ disease with diffuse lymphoplasmacytic infiltration in the thyroid.Patients and MethodsAmong 1,484 Graves’ disease patients who underwent thyroidectomy, we examined their histopathological findings including the degree of lymphoplasmacytic and fibrotic infiltration and levels of IgG4-positive plasma cells in the thyroid. Their clinical pictures were defined by laboratory and ultrasonographic evaluation.ResultsA total of 11 patients (0.74%) showed diffuse lymphoplasmacytic infiltration in the stroma of the thyroid gland. Meanwhile, other patients showed variable lymphoid infiltration ranging from absent to focally dense but no aggregation of plasma cells in the thyroid gland. Based on the diagnostic criteria of IgG4-related disease, 5 of the 11 subjects had specifically increased levels of IgG4-positive plasma cells in the thyroid. Fibrotic infiltration was present in only 1 patient developing hypothyroidism after anti-thyroid drug treatment for 4 years, but not in the other 10 patients with persistent hyperthyroidism. Obliterative phlebitis was not identified in any of the 11 subjects. Thyroid ultrasound examination showed 1 patient developing hypothyroidism who had diffuse hypoechogenicity, but the other hyperthyroid patients had a coarse echo texture.ConclusionsIn our study, Graves’ disease patients with persistent hyperthyroidism who had diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells in the thyroid showed no concomitant fibrosis or obliterative phlebitis.

IgG4-related sclerosing cholangitis in the absence of autoimmune pancreatitis mimicking extrahepatic cholangiocarcinoma

Aims. IgG4-related sclerosing cholangitis in extrahepatic bile ducts in the absence of autoimmune pancreatitis (AIP) is rare and is poorly studied. Herein, we present the clinicopathological features of four cases of IgG4-related sclerosing cholangitis. Methods and results. The clinicopathological features of IgG4-related sclerosing cholangitis were compared with those of IgG4-related sclerosing cholangitis with AIP (n = 7), extrahepatic cholangiocarcinoma (n = 29), primary sclerosing cholangitis (n = 40), and secondary sclerosing cholangitis (n = 12). Several histomorphologic features distinguish IgG4-related sclerosing cholangitis, including a marked degree of bile duct injury, a higher percentage of lymphoid follicle formation, a higher percentage of perineuritis, and a more diffuse and dense lymphoplasmacytic infiltrate. All four cases of IgG4-related sclerosing cholangitis occurred exclusively in males. Of these cases, none had IgG4 serology checked preoperatively, and all had a preoperative diagnosis of extrahepatic cholangiocarcinoma. Clinical follow-up was available in 2 patients with a mean time of 11 months. Follow-up confirmed the benign course of the disease as the patients showed no evidence of relapse. IgG4-related conditions, including sclerosing cholecystitis and retroperitoneal fibrosis, were noted in three patients. Conclusions. IgG4-related sclerosing cholangitis in the absence of AIP presents as a distinct and under-recognized disease that mimics extrahepatic cholangiocarcinoma clinically. Awareness of this entity is essential to avoid erroneously diagnosing malignancy. The current threshold of 10 IgG4-positive plasma cells/high-power field (HPF) in the biopsy is not specific enough to exclude cholangiocarcinoma. Therefore, we suggest the diagnostic cut-off to be 50 IgG4-positive plasma cells/HPF in the biopsy.

Evaluation of Gastric Lesions Based on Helicobacter pylori and Helicobacter-Like Organisms (HLOs) in Cats; A Histopathological and Bacteriological Study.

Background:The lesions induced by Helicobacter pylori in a candidate animal model should always be examined thoroughly. The resemblance of these lesions to those observed in humans can indicate whether the usage of this model will contribute to the understanding of the various pathogenic mechanisms involved in the development of human H. pylori-associated diseases.Objectives:The aim of this study was to perform a histopathological and bacteriological evaluation of gastric lesions based on H. pylori and Helicobacter-like organisms (HLOs) in cats.Materials and Methods:The present study was carried out on 28 cat’s (13 male and 15 female cases) gastric mucosae, which were tested by bacteriological and histopathological methods. Biochemical tests such as catalase, oxidase and urease were utilized in addition to Gram and Giemsa staining.Results:This research demonstrated that solely one case of H. pylori was isolated by gastric mucosal culture. Microscopically, the infected stomachs by HLOs comprised a mild to severe diffuse lymphoplasmacytic infiltration into the subglandular and gastric mucosa. Lymphoid follicles were also marked, particularly within pyloric tissues and mostly in displaced mucosal glands. For 75% of the gastritis cases, both HLOs and rapid urease tests were positive, whereas 83% of cases were more than one-year-old with gastritis. Furthermore, 75% of cats indicated gastritis, though 25% encompassed no gastritis; hence 20% had negative results for the rapid urease test and 25% for the Giemsa staining test. Such results may indicate that cats without gastritis were considered as free of HLOs pathogenic bacteria.Conclusions:These results suggest that most cases of gastritis were located in the antral region. Additionally, the isolation of H. pylori from domestic cats raises the possibility of zoonotic characteristics for the slightly pathogen; therefore transmission occurs from cats to human and vice versa.

Comparison of histopathological features of pancreatic carcinoma and type 1 autoimmune pancreatitis

Type 1 autoimmune pancreatitis (AIP-1) is an immunoglobulin G (IgG)-4-related disease (IgG4-RD), characterized by elevated serum immunoglobulin G4 (IgG4) and infiltration by IgG4(+) plasma cells. Pancreatic carcinoma (PC) sometimes shows infiltration by IgG4(+) plasma cells, but details have been unclear. We compared pathological findings and expression of IgG4 and IgG in fibroses in 18 PC patients to those from 9 AIP-1 patients. Fibroses were divided into areas of ductal adenocarcinoma (DA) and obstructive pancreatitis (OP). Serum IgG4 levels were lower than the cut-off value in all PC patients with no IgG4-RD. Diffuse lymphoplasmacytic infiltration and eosinophil infiltration were characteristic of fibroses in PC. Though AIP-1 samples often had storiform fibrosis even in biopsies, PC did not show storiform fibrosis. Ratios of IgG4(+) plasma cells/IgG(+) plasma cells (IgG4/IgG ratios) in DA and OP were significantly lower than in AIP-1. However, high-density IgG4(+) plasma cell foci were detected in PC fibroses, particularly around peripheral nerves, vessels, and lymphoid follicles; between lobules and invasion fronts; and within neutrophilic abscesses. In conclusion, the IgG4/IgG ratio is useful in distinguishing PC from AIP-1, and should be evaluated in three or more areas, as PC can show localized high-density IgG4(+) plasma cell areas.

A Case of IgG4-Related Lung Disease Presenting as Interstitial Lung Disease.

Intrathoracic involvement of immunoglobulin G4 (IgG4)-related disease has recently been reported. However, a subset of the disease presenting as interstitial lung disease is rare. Here, we report a case of a 35-year-old man with IgG4-related lung disease with manifestations similar to those of interstitial lung disease. Chest computed tomography showed diffuse ground glass opacities and rapidly progressive pleural and subpleural fibrosis in both upper lobes. Histological findings showed diffuse interstitial lymphoplasmacytic infiltration with an increased number of IgG4-positive plasma cells. Serum levels of IgG and IgG4 were also increased. The patient was diagnosed with IgG4-related lung disease, treated with anti-inflammatory agents, and showed improvement. Lung involvement of IgG4-related disease can present as interstitial lung disease and, therefore, should be differentiated when evaluating interstitial lung disease.

Cerebrospinal Fluid Analysis in Immunoglobulin G4-related Hypertrophic Pachymeningitis

To the Editor: Immunoglobulin G4-related disease (IgG4-RD) is characterized by fibrous swelling of affected organs, elevations in serum IgG4 concentrations, and responsiveness to glucocorticoid treatment1. Affected tissues display similar histological features: diffuse lymphoplasmacytic infiltration by numerous IgG4-positive plasma cells, occasional eosinophils, storiform fibrosis, and obliterative phlebitis2. IgG4-related hypertrophic pachymeningitis (IgG4-HP) has been identified as a characteristic central nervous system (CNS) manifestation of IgG4-RD, but comprehensive cerebrospinal fluid (CSF) analyses are substantially lacking3,4. Recently, we demonstrated an intrathecal IgG and IgG4 synthesis in the CSF of a patient with IgG4-HP and suggested IgG4 Indices as safe potential diagnostic tools for IgG4-HP5. Here, we describe 2 new cases of IgG4-HP with CSF evaluation at diagnosis and in response to treatment. In case 1, March 2007, a 56-year-old man was admitted with a 1-year history of right frontal headache. Magnetic resonance imaging (MRI) showed right frontal pachymeningitis. Granulomatous meningeal inflammation was suspected and oral prednisone (1 mg/kg body weight/day) was started with clinical and radiological improvement. Prednisone was discontinued after 8 months, but in July 2008 the headache recurred. Blood and CSF analyses are shown in Table 1. MRI evidenced a right frontotemporal progression of the pachymeningitis (Figure 1A). A meningeal biopsy … Address correspondence to Dr. E. Della-Torre, Department of Medicine and Clinical Immunology, San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. E-mail: dellatorre.emanuel{at}hsr.it

Immunoglobulin G4-Related Disease of the Heart Causing Aortic Regurgitation and Heart Block

Immunoglobulin (Ig) G4-related disease is a novel disease entity characterized by diffuse lymphoplasmacytic infiltrates and the presence of abundant IgG4-positive plasma cells in extensive fibrosis, frequently associated with tumorous swelling lesion and elevated serum IgG4 concentrations. Immunoglobulin G4-related disease has been described in almost every organ system but rarely affects the heart. We describe a rare case of IgG4-related disease of the heart causing aortic regurgitation and heart block in a 59-year-old woman. The excised lesion revealed a high ratio of IgG4-positive to IgG-positive plasma cells, providing a definite diagnosis of IgG4-related disease. The aortic valve was replaced using Manouguian technique, resulting in a favorable outcome.