Cholangiocarcinoma, Primary Sclerosing Cholangitis, or IgG4-Sclerosing Cholangitis: Similar Presentations with Different Managements

In our case, we present a case of an 80-year-old male who was referred to the gastroenterologist for evaluation of a suspicious mass. CT imaging at the time had shown intrahepatic and extrahepatic biliary dilations, and the patient was thought to have a pancreatic or a common bile duct mass. A mass biopsy showed no malignancy, and further evaluation was warranted. The patient was found to have elevated IgG4 levels and was diagnosed with IgG4-sclerosing cholangitis (IgG4-SC). IgG4 has been found to create a wide array of pathologies, including autoimmune pancreatitis, dacryoadenitis, and sialadenitis. These pathologies have been grouped under an IgG4-Related Disease (IgG4-RD) category. In some cases, this IgG4-RD can present as a subclass of primary sclerosing cholangitis due to immune depositions and swelling of the CBD. Due to the strictures caused by the sclerosing cholangitis, intrahepatic and extrahepatic dilations might be found on endoscopic ultrasound (EUS). It is imperative to differentiate this from a malignant mass as the early recognition and treatment of IgG4-SC can lead to complete resolution. In this case report, we present a case of a patient who was found to have IgG4-SC and responded well to steroid treatment.

Diagnosis of IgG4-related sclerosing cholangitis

IgG4-related sclerosing cholangitis(IgG4-SC)is often associated with autoimmune pancreatitis.However,the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis(PSC),and the presence of segmental stenosis suggests cholangiocarcinoma(CC).IgG4-SC responds well to steroid therapy,whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention.Since IgG4-SC was first described,it has become a third distinct clinical entity of sclerosing cholangitis.The aim of this review was to introduce the diagnostic methods for IgG4-SC.IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical,serological,morphological,and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis.When intrapancreatic stenosis is detected,pancreatic cancer or CC should be ruled out.If multiple intrahepatic stenoses are evident,PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining.Associated inflammatory bowel disease is suggestive of PSC.If stenosis is demonstrated in the hepatic hilar region,CC should be discriminated by ultrasonography,intraductal ultrasonography,bile duct biopsy,and a higher cutoff serum IgG4 level of 182 mg/dL.

First case of IgG4-related sclerosing cholangitis associated with autoimmune hemolytic anemia

To our knowledge,patients with immunoglobulin G4-related sclerosing cholangitis(IgG4-SC)associated with autoimmune hemolytic anemia(AIHA)have not been reported previously.Many patients with IgG4-SC have autoimmune pancreatitis(AIP)and respond to steroid treatment.However,isolated cases of IgG4-SC are difficult to diagnose.We describe our experience with a patient who had IgG4-SC without AIP in whom the presence of AIHA led to diagnosis.The patient was a73-year-old man who was being treated for dementia.Liver dysfunction was diagnosed on blood tests at another hospital.Imaging studies suggested the presence of carcinoma of the hepatic hilus and primary sclerosing cholangitis,but a rapidly progressing anemia developed simultaneously.After the diagnosis of AIHA,steroid treatment was begun,and the biliary stricture improved.IgG4-SC without AIP was thus diagnosed.

IgG4-related sclerosing cholangitis and chronic sclerosing sialadenitis mimicking cholangiocarcinoma and neck malignancy

To the Editor:IgG4-related sclerosing cholangitis（IgG4-SC）has re cently been recognized as a biliary manifestation of IgG4-related disease（IgG4-RD）.Type 3 IgG4-SC pre sented biliary strictures in both the porta hepatis and the distal common bile duct（CBD）.;Its manifestation especially in the absence of autoimmune pancreatitis,is extremely rare and very similar to that of cholangiocarci noma（CC）.

Review of primary sclerosing cholangitis with increased IgG4 levels

Primary sclerosing cholangitis(PSC) is a chronic progressive liver disease. Subtypes of PSC have been described, most recently PSC with elevated serum and/or tissue IgG4 subclass. We aim to summarise the clinical phenotype,disease associations, differential diagnosis, response to therapy and pathogenic mechanisms underlying PSC-high IgG4 subtype. We reviewed Pub Med,MEDLINE and Embase with the search terms "primary sclerosing cholangitis","IgG4", and "IgG4-related sclerosing cholangitis(IgG4-SC)". Elevated serum IgG4 are found in up-to one-quarter, and abundant IgG4-plasma cell infiltrates in the liver and bile ducts are found in up-to one-fifth of PSC patients. This group have a distinct clinical phenotype, with some studies reporting a more aggressive course of liver and associated inflammatory bowel disease, compared to PSCnormal IgG4 and the disease mimic IgG4-SC. Distinguishing PSC-high IgG4 from IgG4-SC remains challenging, requiring careful assessment of clinical features,organ involvement and tissue morphology. Calculation of serum IgG4:IgG1 ratios and use of a novel IgG4:IgG RNA ratio have been reported to have excellent specificity to distinguish IgG4-SC and PSC-high IgG4 but require validation in larger cohorts. A role for corticosteroid therapy in PSC-high IgG4 remains unanswered, with concerns of increased toxicity and lack of outcome data. The immunological drivers underlying prominent IgG4 antibodies in PSC are incompletely defined. An association with PSC-high IgG4 and HLA class-II haplotypes(B*07, DRB1*15), T-helper2 and T-regulatory cytokines(IL4, IL10,IL13) and chemokines(CCL1, CCR8) have been described. PSC-high IgG4 have a distinct clinical phenotype and need careful discrimination from IgG4-SC,although response to immunosuppressive treatments and long-term outcome remains unresolved. The presence of IgG4 likely represents chronic activation to persistent antigenic exposure in genetically predisposed individuals.

Cholangiocarcinoma developed in a patient with IgG4-related disease

A 77-year-old man with jaundice and a pancreatic head tumor was referred to our hospital in August2006.The initial laboratory tests,computed tomography(CT)scan,magnetic resonance imaging(MRI),and endoscopic retrograde cholangiopancreatography suggested IgG4-related cholangitis and autoimmune pancreatitis.Oral prednisolone(PSL)was then administered.This treatment reduced the size of the pancreatic parenchyma,and the lower common bile duct(CBD)returned to its normal size.Thus,the oral PSL was gradually tapered to a maintenance dose.In February 2010,a CT scan and MRI showed segmental wall thickening and stenosis of the middle CBD,the progression of which led to extrahepatic obstructive jaundice.We suspected the emergence of a cholangiocarcinoma rather than the exacerbation of the IgG4-related sclerosing cholangitis because the stricture of the CBD was short and localized.Then,a percutaneous transhepatic biliary drainage was performed.The biopsy specimens obtained via the percutaneous transhepatic tract indicated an abnormal glandular formation,suggesting the presence of a moderate,well-differencated adenocarcinoma.The gross examination,microscopic examination and immunohistochemical analysis of the pancreaticoduodenectomy specimen suggested that a cholangiocarcinoma developed from the IgG4-related sclerosing cholangitis.

The protean manifestations of central nervous system IgG4-related hypertrophic pachymeningitis:a report of two cases

Background:IgG4-related hypertrophic pachymeningitis is a relative newly recognized and rare manifestation of IgG4-related disease,an immune-mediated fibroinflammatory tumefactive disorder.Fewer than 80 patients have been reported in the literature,and it can mimic common neurosurgical conditions.We describe the clinical presentation of two patients that were initially considered to have a subdural collection,tuberculous meningitis,and a cervical spinal meningioma,but were eventually diagnosed with this disease.Case presentation:Two ethnic Chinese men,86 and 62 years old,experienced a 4-week history of headache.Both patients had a history of autoimmune disease,namely glomerulonephritis and Grave’s disease,respectively.Magnetic resonance brain imaging revealed diffuse dural thickening with the latter patient exhibiting homogeneous and intense gadolinium-contrast enhancement.Since the 86-year-old patient also had progressive bilateral visual loss,giant cell arteritis was suspected and a 2-week course of glucocorticoid therapy was prescribed,but his symptoms failed to improve.The 62-year-old patient also had accompanying low-grade fever and was treated empirically as having tuberculous meningitis although there were no confirmatory microbiological findings.This patient further developed right hemiparesis,and additional imaging revealed a C4/5 intradural-extramedullary contrast-enhancing lesion resembling a meningioma causing cord compression.Both patients underwent neurosurgical intervention with the former undergoing a dural biopsy and the latter having the cervical lesion resected.The final diagnosis was IgG4-related hypertrophic pachymeningitis with the hallmark histological features of lymphoplasmacytic infiltration of IgG4+plasma cells,storiform fibrosis,and obliterative phlebitis.In addition,their serum IgG4 levels were elevated(i.e.,>135 mg/dL).Both patients received at least 6 months of glucocorticoid therapy while the latter also had azathioprine.Their symptoms improved significantly and recurrent lesions were not detected on follow-up imaging.Conclusions:A high index of suspicion for this condition is suggested when a male patient with a history of autoimmune disease and compatible radiological findings,experiences subacute headache that is disproportionate to the degree of dural involvement.Neurosurgeons should consider early meningeal biopsy to establish a definitive histological diagnosis in order for early effective immunosuppressive treatment to be initiated and to avoid unnecessary morbidity.

Isolated Multifocal Sclerosing Thyroiditis: Case Report

Multifocal fibrosclerosis is a very rare fibroproliferative syndrome involving multiple organ systems. In our report we present the case of multifocal sclerosing thyroiditis characterized by multiple fibroelastic foci similar to breast “radial scar”, which can be misdiagnosed as multifocal papillary carcinoma. The diagnosis of multifocal sclerosing thyroiditis, in according with Armed Forces Institute of Pathology (AFIP) textbook on thyroid tumors, was made only after histological and himmunohistochemical examination. We consider the multifocal sclerosing thyroiditis as the first stage of multifocal IgG4-related sclerosing disease for the presence of IgG4 within fibrosclerotic tissue of thyroid. Total body CT-scan and plamatic IgG4 levels must be investigated in order to exclude or confirm the presence of systemic disease.

Cholangitis:Diagnosis,Treatment and Prognosis

Cholangitis is a serious life-threatening situation affecting the hepatobiliary system.This review provides an update regarding the clinical and pathological features of various forms of cholangitis.A comprehensive search was performed in the PubMed,Scopus,and Web of Knowledge databases.It was found that the etiology and pathogenesis of cholangitis are heterogeneous.Cholangitis can be categorized as primary sclerosing(PSC),secondary(acute)cholangitis,and a recently characterized form,known as IgG4-associated cholangitis(IAC).Roles of genetic and acquired factors have been noted in development of various forms of cholangitis.PSC commonly follows a chronic and progressive course that may terminate in hepatobiliary neoplasms.In particular,PSC commonly has been associated with inflammatory bowel disease.Bacterial infections are known as the most common cause for AC.On the other hand,IAC has been commonly encountered along with pancreatitis.Imaging evaluation of the hepatobiliary system has emerged as a crucial tool in the management of cholangitis.Endoscopic retrograde cholangiography,magnetic resonance cholangiopancreatography and endoscopic ultrasonography comprise three of the modalities that are frequently exploited as both diagnostic and therapeutic tools.Biliary drainage procedures using these methods is necessary for controlling the progression of cholangitis.Promising results have been reported for the role of antibiotic treatment in management of AC and PSC;however,immunosuppressive drugs have also rendered clinical responses in IAC.With respect to the high rate of complications,surgical interventions in patients with cholangitis are generally restricted to those patients in whom other therapeutic approaches have failed.

Indolent lung opacity: Ten years follow-up of pulmonary inflammatory pseudo-tumor

Inflammatory pseudotumor(IPT) has always been considered a diagnostic challenge. Its rarity and resemblance to other more common pathological entities imposes that neither clinical nor radiological characteristics can lead to a definitive diagnosis. The surgical excision of the lesion is the ultimate approach for accurate diagnosis and cure. Moreover the true nature of IPT, its origin as a neoplastic entity or an overreactive inflammatory reaction to an unknown trigger, has been a long debated matter. Surgery remains the treatment of choice. IPT is mostly an indolent disease with minimal morbidity and mortality. Local invasion and metastasis predict a poor prognosis. We hereby present a unique case of pulmonary IPT that was surgically excised, but recurred contralaterally, shortly thereafter. Despite no medical or surgical treatment for ten years, the lesion has remained stable in size, with neither symptoms nor extra-pulmonary manifestations.

Present state of endoscopic ultrasonography-guided fine needle aspiration for the diagnosis of autoimmune pancreatitis type 1

Autoimmune pancreatitis(AIP)is defined as pancreatitis caused by irregular narrowing of the pancreatic duct accompanied by pancreatic swelling,fibrosis and lymphocyte infiltration,events that are related to autoimmune mechanisms.The 2010 International Consensus Diagnostic Criteria for AIP defined pancreatitis as“type 1”when increased levels of serum IgG4 were present and other organs were involved;lymphoplasmacytic sclerosing pancreatitis was the main histological characteristic.Apart from surgery,endoscopic ultrasonographyguided fine needle aspiration(EUS-FNA)is the only method for the histological diagnosis of AIP;however,this method is difficult.The use of larger-diameter FNA needles and trucut biopsy did not improve the diagnostic performance of EUS-FNA,but it has improved gradually.In this review,we look back at past efforts to improve the diagnostic performance of EUS-FNA and reveal the present state of EUS-FNA for the histological diagnosis of AIP type 1.