IgG4-positive Plasma Cells Research Articles

Clinical characteristics of IgG4-related retroperitoneal fibrosis in a cohort of 117 patients with idiopathic retroperitoneal fibrosis: a retrospective study.

Retroperitoneal fibrosis (RPF) is a rare condition marked by inflammation and fibrosis affecting the peritoneal and retroperitoneal soft tissues. In recent years, the identification of IgG4-related diseases has brought to light a significant association with fibrous disorders, including RPF, which were once considered independent. In this comprehensive cohort study, we performed a comparative analysis of the demographic, clinical, laboratory, histopathological, and therapeutic characteristics between patients with IgG4-related RPF and those with idiopathic retroperitoneal fibrosis (iRPF). We performed a retrospective analysis of 117 patients diagnosed with RPF at the First Affiliated Hospital of Naval Medical University between July 2007 and July 2023. Demographic, clinical, laboratory, histopathological, and therapeutic characteristics of 70 iRPF patients and 47 IgG4-related patients were systematically compared. The IgG4-related group exhibited an older age of onset, with a predominant occurrence among adult males. Significantly elevated levels of eosinophilia and IgE were observed in the IgG4-related group. Most patients across both groups displayed elevated CRP and ESR levels. Furthermore, at the time of diagnosis, the IgG4-related group had higher serum creatinine and lower levels of complement. The most prevalent clinical manifestation in both groups was flank pain. The proportion of lymphoplasmic infiltration and storiform fibrosis in IgG4-related RPF group was significantly higher. The IgG4-related RPF group had significantly higher IgG4-positive plasma cell count, IgG4/total IgG ratio, and eosinophils count than that in iRPF group. We conducted a comparative analysis of demographic, clinical, laboratory, histopathological, and therapeutic differences between the iRPF patients and the IgG4-related patients. Clarifying the distinctive characteristics of these two groups will contribute to a better understanding of the condition and facilitate the development of specific treatment strategies tailored to each group. Key Points • Identification of distinct clinical features and outcomes between IgG4-related and iRPF patients in a large retrospective study.

IgG4 in the gut: Gastrointestinal IgG4-related disease or a new subtype of inflammatory bowel disease.

IgG4-related disease (IgG4-RD) is a chronic inflammatory condition characterized by tissue infiltration with IgG4-positive plasma cells, leading to fibrosis and organ dysfunction. While primarily affecting the pancreas, bile ducts, and salivary glands, IgG4-RD can also involve the gastrointestinal tract, raising questions about its relationship with inflammatory bowel disease (IBD). Recent studies suggest that patients with IBD may exhibit histological and serological features consistent with IgG4-RD, such as a dense lymphoplasmacytic infiltration, a storiform-type of fibrosis and a prominent IgG4 immune response. This overlap represents a diagnostic challenge, as differentiating between primary IBD and IgG4-RD involving the gut is crucial for appropriate treatment. Further research is essential to delineate the prevalence of tissue and serum IgG4 expression in patients with IBD. This approach could classify subtypes of IBD, enabling advancements in non-invasive diagnosis and monitoring as well as personalized therapies. The purpose of this review is to summarize the available evidence regarding intestinal involvement in IgG4-RD and the role of both serum and tissue IgG4 in inflammatory bowel diseases IBD.

Primary intraosseous Rosai-Dorfman disease: Clinicopathological features and an assessment of a possible relationship with IgG4-related disease.

Rosai-Dorfman disease (RDD) is a rare proliferative disorder of histiocytes, and primary solitary RDD of the bone is extremely rare. Some RDDs exhibit increased immunoglobulin (Ig)G4 positive (IgG4+) plasma cell infiltration and the histopathological features of IgG4-related disease (IgG4-RD). However, the association between RDD and IgG4-RD remains unclear. Therefore, this study aimed to investigate the relationship between primary intraosseous RDD and IgG4-RD. We collected data on 11 primary intraosseous Rosai-Dorfman diseases to summarize their clinicopathological features and to investigate their relationship with IgG4-RD. The most common sites were the long bones, followed by the vertebrae. The age of onset was higher in our Chinese cohort as compared with Western patients reported in the literature, with an average age of 39.2 and a median age of 34years. Sclerosis was present in seven cases and storiform arrangement was observed in only one case. Obliterative phlebitis was not observed in any patient. The number of IgG4+ plasma cells ranged from 5 to 50 cells per high-power field, with IgG4/IgG ratios ranging from 5 to 25%. Primary intraosseous RDD may show fibrosis and increased IgG4+ plasma cell infiltration, but does not meet the criteria for IgG4-RD. We concluded that RDD did not belong to the IgG4-RD spectrum.

IgG4-related disease with epithelioid granulomas: a case and a review of the literature.

IgG4-related disease (IgG4-RD) is a systemic, immune-mediated, fibroinflammatory disorder that affects multiple organs. Histopathologically, the supportive findings of IgG4-RD include dense lymphocytic infiltrates, obliterative phlebitis, storiform fibrosis, and elevated numbers of IgG4-positive plasma cells. However, the presence of granulomatous inflammation is generally considered highly atypical, suggesting alternative diagnoses such as sarcoidosis and lymphoma. Here, we present a case of IgG4-RD involving granulomatous lymphadenopathy. Labial salivary gland biopsy findings were consistent with IgG4-related sialadenitis. Elevated serum IgG4 levels, hypocomplementemia, and abnormal imaging findings in the kidneys and pancreas indicated an association with IgG4-RD. The patient was treated with prednisolone, which resulted in a significant improvement in the serum IgG4 and complement levels and a notable reduction in lymph node swelling. Although granulomatous inflammation is rare, integrating clinical, serological, radiological, and pathological parameters can ensure an accurate assessment within the appropriate clinicopathological context.

FDG PET/CT and MRI of IgG4-Related Disease Presenting as a Hepatic Solitary Solid Mass

Abstract A hepatic solitary solid mass mimicking malignancy was discovered through MRI and FDG PET/CT in a 76-year-old woman with abdominal pain and no abnormal tumor markers in the blood. She underwent surgery to remove the lesion. Histopathology with biopsy was highly suspicious for IgG4-related disease, although immunohistochemical staining demonstrated non–IgG4-positive plasma cells. Finally, intrahepatic IgG4-related disease was supported by elevated serum IgG4 of 141 mg/dL. IgG4-related disease could manifest as hepatic solitary solid mass without any other organ involvement, and the immunohistochemical staining of IgG4 may be negative.

Perifollicular concentric granulomas: A clue to IgG4-related lymphadenopathy.

A 69-year-old with well-controlled HIV was evaluated for persistentcough, in the context of years of fatigue and influenza A infection 6months prior. Chest CT and PET scans were notable for adenopathyconcerning for a lymphoproliferative disorder. Radiologic studies alsoshowed diffuse FDG uptake in the prostate, consistent with prostatitis.Axillary lymph node biopsy showed follicular and paracorticalhyperplasia, and few germinal centers showed perifollicular non-necrotizing granulomas. Immunohistochemical staining demonstrated apredominance of IgG4 positive plasma cells. Serum proteinelectrophoresis (SPEP) and immunosubtraction showed a board-domedpeak pattern suggestive of possible monoclonality. Serum IgG4 levelswere elevated, and the patient was diagnosed with IgG4-relateddisease (IgG4-RD). This case highlights morphologic and SPEP patternsthat can aid in supporting a diagnosis of IgG4-RD.

Sclerosing mucoepidermoid carcinoma of salivary glands.

Sclerosing mucoepidermoid carcinoma (SMEC) of the salivary glands is a rare variant of low-grade mucoepidermoid carcinoma with scanty cellular atypia characterized by marked fibrosis/sclerosis and a rich inflammatory infiltrate. Herein, we report 25 unpublished cases of SMEC, two of them with prominent eosinophilia (2/25; 8%) and three with abundant IgG4-positive plasma cells (3/25; 12%). In our series of salivary SMEC, molecular analysis using fluorescence in situ hybridization (FISH) and/or next-generation sequencing (NGS) provided evidence of MAML2 gene rearrangement in 18 cases of the 21 analyzable cases tested (86%), while this gene locus was intact in 3 cases (14%). This study focuses on the diagnostic criteria of salivary SMEC given its challenge of abundant collagenous stroma, minimal residual neoplastic areas, and inconspicuous mucous cells. Follow-up data of our cases indicate that salivary SMECs have favorable outcomes. Molecular analysis for MAML2 gene rearrangement suggests that SMECs of salivary glands represent a rare variant of conventional low-grade MECs of salivary glands. In contrast, SMECs of the thyroid gland are genetically distinct from salivary-type thyroid MECs.

A Comprehensive Review of IgG4 Related Disease Unraveling the Role of B and T Lymphocytes in the Pathogenesis of the Disease

IgG4-RD is a chronic fibro inflammatory disease characterized by a significant elevation of serum IgG4 concentration and marked infiltration of IgG4-positive plasma cells in the affected organs. A dense lymphoplasmacytic infiltrate and the formation of ectopic lymphoid structures are characteristic histopathological findings in an IgG4-RD lesions. These findings strongly suggest the preferential involvement of T and B lymphocytes in the development of this disease. We want to sum up the last evidences regarding the IgG4-RD with a focus on the role of the involvement of CD4+T-cell subsets and B lymphocytes.

EUS-guided fine-needle biopsy versus fine-needle aspiration for histopathological evidence for type 1 autoimmune pancreatitis: A single-center retrospective study in China.

EUS is recommended for guiding pancreatic tissue acquisition in suspected autoimmune pancreatitis (AIP) cases. However, there is a lack of comparative research on the effectiveness between EUS-guided fine-needle aspiration (EUS-FNA) and EUS-guided fine-needle biopsy (EUS-FNB) for diagnosing AIP in China. This study aimed to evaluate the diagnostic accuracy of EUS-guided tissue acquisition (EUS-TA) specifically for type 1 AIP. Between 2010 and 2023, individuals with AIP who received EUS-TA at Changhai Hospital were included in the study. A total of 173 patients diagnosed with AIP who underwent EUS-TA were included in the final analysis. Of these, 104 patients (60.1%) received EUS-FNA, and 69 patients (39.9%) underwent EUS-FNB. Sufficient pancreatic tissue samples (>5 cells/high-power field) were obtained in 164 of 173 patients (94.8%), with success rates of 94.2% for EUS-FNA and 95.7% for EUS-FNB (P > 0.05). EUS-FNB exhibited higher rates of reliable level 1 histopathological findings (40.9% vs. 16.3%, P < 0.001) and reliable level 2 histopathological findings (33.3% vs. 12.2%, P < 0.001) compared with EUS-FNA. Furthermore, a higher occurrence of IgG4-positive plasma cell infiltration (>10 cells/high-power field) was observed with EUS-FNB compared with EUS-FNA (74.2% vs. 27.9%, P < 0.001). The multivariate logistic analysis also revealed that EUS-FNA was less effective in obtaining reliable evidence compared with EUS-FNB, as evident in both level 2 (P = 0.002; odds ratio, 0.21; 95% confidence interval, 0.08-0.56) and level 1 (P = 0.001; odds ratio, 0.19; 95% confidence interval, 0.08-0.49) histopathological evidence. EUS-FNB demonstrates higher rates of level 1 and level 2 histopathological findings, as well as more abundant IgG4-positive plasma cell infiltration, compared with EUS-FNA.

A rare case of IgG4-related aortitis in the thoracic aorta mimicking an intramural hematoma: navigating the diagnostic labyrinth

A 54-year-old female presented with recurrent abdominal pain and new onset chest pain. Chest computed-tomography angiogram detected a thoracic aortic aneurysm with suspected Type A intramural hematoma (IMH) versus aortitis. Initially, conservative management was pursued while awaiting a definitive diagnosis. Differential workup was negative, while additional imaging modalities favored IMH, prompting expedited surgical intervention. During ascending aortic and hemiarch replacement, severe aortitis was unexpectedly discovered without evidence of IMH. Histopathological examination of the aortic specimens identified transmural aortic inflammation with lymphoplasmacytic infiltrate and irregular fibrosis. Numerous IgG4-positive plasma cells were present with IgG4/IgG ratio of 40–50% suggesting IgG4-related disease (IgG4-RD). Subsequent analysis revealed B cells positive for clonal IgH gene rearrangement, and bone marrow biopsy then revealed the same clonal B cells. She was ultimately diagnosed with CLL, the most common phenotype of monoclonal B-cell lymphocytosis, thought to account for the IgG4-predominant plasma cells causing aortitis. Although rare, this case highlights the importance of considering IgG4-related disease (IgG4-RD) as a cause of aortitis when assessing symptomatic patients with aortic pathologies, emphasizing the complexities involved in diagnosing due to a variety of imaging presentation, differentiating, and managing large-vessel vasculitides. Moreover, it underscores the importance of Multidisciplinary Aortic Team care and the use of multiple diagnostic modalities in evaluating ambiguous aortic pathologies.

8301 A Rare Case of IgG4-Related Hypophysitis

Abstract Disclosure: P. Kesavan Chary: None. J.M. Silverstein: None. Background: IgG4-related disease (IgG4-RD) is an immune-mediated condition that presents as systemic inflammation and fibrosis of tissues, often affecting multiple organs. Isolated IgG4-related Hypophysitis is rare and characterized by lymphoplasmacytic infiltration of the pituitary gland by IgG4-positive plasma cells. A combination of clinical, serologic, radiologic, and histopathologic findings is used for diagnosis of IgG4-RD and approximately two-thirds of all patients have elevated serum IgG4 levels. We report a case of isolated IgG4-related Hypophysitis in a middle-aged woman serologically negative for IgG4-related disease. Case Report: A 52 year old female with history of steroid dependent severe persistent asthma, allergic rhinitis, and chronic sinusitis presented with one month of headache, polyuria, and polydipsia. MRI Brain demonstrated an enlarged, rounded pituitary gland 16 x 11 x 9 mm, with homogeneous enhancement, extension into the suprasellar cistern, and mild thickening of the infundibulum suspected to represent a pituitary adenoma. Lab evaluation revealed mild hyperprolactinemia (prolactin 83.2, normal 4.8-23.3 ng/mL) and secondary adrenal insufficiency based on an abnormal high-dose cosyntropin stimulation test in the setting of a low adrenocorticotrophic hormone (ACTH) level (&amp;lt;2.0 pg/mL). Remaining pituitary hormone levels were normal. Inpatient work-up for polyuria and polydipsia showed a low urine specific gravity of 1.003. An overnight water deprivation test was performed. Baseline urine osmolality (UOsm) was 95 mOsm/kg and serum sodium was 144 mmol/L; after 3 hours of water deprivation, serum Osm increased to 301 mOsm/kg (275-300 mOsm/kg) and UOsm only to 215 mOsm/kg, while her sodium increased to 145 mmol/L. Results were felt to be consistent with AVP deficiency (Central Diabetes Insipidus) and the patient was started on desmopressin. Because of the presence of AVP deficiency, further work-up was done to evaluate for an infiltrative process or malignancy. ANA, RPR, ESR, CRP, CBC, ACE level, T-SPOT, and IgG subclasses were unremarkable. Further imaging studies yielded a negative nuclear bone scan and PET/CT scan. For diagnostic purposes, the patient underwent biopsy via an endoscopic endonasal transsphenoidal approach. Pathology showed the presence of &amp;gt;10 IgG4+ plasma cells in a single high-power field, consistent with a diagnosis of IgG4-related Hypophysitis. Conclusion: Isolated IgG4-related Hypophysitis is the least common clinical presentation of IgG4-RD, which is itself a rare and relatively newly recognized condition. IgG4-related Hypophysitis should be suspected in patients presenting with AVP deficiency and pituitary stalk enlargement with an otherwise negative work up. Presentation: 6/2/2024

6797 Pituitary Apoplexy as initial Presentation of IgG4-Related hypophysitis

Abstract Disclosure: M. Alameri: None. A. Alnuaimi: None. Introduction: IgG4-related hypophysitis is a rare disease due to IgG4 lymphoplasmacytic infiltration of the pituitary gland. It can either be isolated or part of a multisystemic disease. We report a rare case of pituitary apoplexy as first manifestation of IgG4-RD. Case report: A 27-year-old previously healthy male presented to emergency department with severe headache, nausea, vomiting and visual impairment. CT brain showed a large sellar suprasellar mass of 3cm with thick rim enhancement. Blood test showed evidence of central adrenal insufficiency, central hypothyroidism and secondary hypogonadism. Patient was started on hormone replacement therapy for central adrenal insufficiency and central hypothyroidism. Pituitary magnetic resonance imaging (MRI) demonstrated a 3.1 x 2.4 x 2.4 cm well-defined large sellar suprasellar mass with thick rim enhancement with intrinsic heterogeneous T2 signal with hypointense T1 signal on fat-suppressed post contrast imaging consistent with necrotic haemorrhagic suggestive of pituitary apoplexy and background of hypophysitis. Upward displacement of optic chiasm was noted without involvement of cavernous sinus. The patient was initially treated with high-dose steroids aiming for reduction of the pituitary mass. However, eventually, he underwent transsphenoidal surgery due to alternated level of consciousness. Pituitary histopathology showed that vast majority of the tissue is necrotic. A small fragment of viable anterior pituitary tissue is present, which measures up to 5.5 mm in greatest dimension which exhibited marked chronic inflammation, predominantly comprised of small lymphocytes. Plasma cells were present and staining with IgG/IgG4 revealed two high-power fields with clusters of approximately 25 and 50 IgG4 positive plasma cells, respectively. Blood test showed elevated blood IgG4 levels of &amp;gt;2.60 g/L (normal reference range 0.03-2.01 g/L). Case was discussed at Endocrine MDT meeting which agreed that blood tests result along with histopathology findings were in keeping with IgG4-Related hypophysitis as per the Mayo Clinic, Leporati and Japan-Korea proposed criteria. Because blood IgG4 levels were elevated, a systemic evaluation was performed. No evidence of other systemic disease found. High dose steroid therapy was initiated, which reduced remnant inflammatory sellar changes. Discussion and conclusion: IgG4-related pituitary disease should be considered as differential diagnosis in unusual presentations of pituitary apoplexy in the context of sellar suprasellar hypophysitis. Presentation: 6/2/2024

IgG4-related disease: A common manifestation in an uncommon genus

Background: IgG4-related disease (IgG4-RD) is a recently described clinicopathological condition with a wide range of clinical manifestations: a dense lymphoplasmacytic infiltrate rich in IgG4positive plasma cells, fibrosis arranged in a storiform pattern, obliterative phlebitis, and, elevated serum IgG4 concentrations. Treatment involves corticosteroids and rituximab for the most severe cases. Case Presentation: Here we present two cases, two white females (ages 26 years and 50 years) IgG 4-RD with low back, flank pain, and retroperitoneal mass, with a compressive effect on the kidney and ureter and causing hydronephrosis. Biopsy of mass revealed infiltrates with IgG4 plasma cells, consistent with the diagnosis of IgG4 disease. The patients were treated with steroids, and rituximab showed significant improvement. Conclusion: Retroperitoneal fibrosis (RPF), a rarest cause of back pain in young adults, should be suspected in patients with back pain, renal dysfunction, and other associated symptoms. It is important to identify this particular cause as it is treatable and may be easily missed. The workup includes kidney function assessment and abdominal imaging using computet tomography (CT) or magnetic resonance imaging (MRI). Biopsy of the mass helps identify malignancy.

Imaging Findings in Cardiovascular Involvements of IgG4 Related Disease: A Systematic Review Study.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by IgG4-positive plasma cell infiltration that can affect multiple organs, including the cardiovascular system. The diagnosis of IgG4-RD relies on a combination of clinical, serological, radiological, and pathological findings. However, due to the varied and insidious clinical presentations, normal IgG4 levels in a significant percentage of patients, and frequent multi-organ involvement, imaging plays a crucial role in the diagnosis of IgG4-RD. The aim of study is to comprehensively examine the imaging findings in IgG4-related cardiovascular disease for accurate diagnosis and appropriate treatment. A systematic search was conducted across electronic databases, PubMed, Scopus, and Web of Sciences, until 1 September 2023, following PRISMA guidelines by searching major databases for studies reporting detailed cardiovascular imaging findings in IgG4-RD. The search yielded 68 studies (60 case reports, 5 case series, 2 cross-sectional, 1 case-control) with 120 cases of cardiovascular IgG4-RD. Most of the cases were male, averaging 62.8 years. The common initial symptoms were dyspnea and chest pain. The most common imaging finding was vasculopathy, including vessel wall thickening, periarteritits, periaortitis, aortitis, stenosis, ectasia, aneurysm formation, intramural hemorrhage, fistula formation, and dissection, followed by pericardial involvement and mediastinal masses. Case series and cross-sectional studies also showed vasculopathy being the most common finding on various imaging modalities, including angiography and PET/CT, highlighting the complex pathology of IgG4-RD. This study evaluated current IgG4-RD articles, revealing a higher prevalence in men and vasculopathy as the most common cardiovascular complication.

Idiopathic hyalinizing fibrosclerosis: A systemic steroid-resistant condition distinct from IgG4-related disease

Since the concept of IgG4-related disease (IgG4-RD) was proposed, that diagnosis has been considered in idiopathic fibroinflammatory diseases in various organs, particularly in cases with multi-organ involvement. We have recently encountered three cases of fibrosing disease of uncertain etiology with shared microscopic appearances. Case 1 (56-year-old man) had an irregular mass at the base of mesentery. Case 2 (29-year-old woman) presented with obstructive jaundice due to an ill-defined mass at the hepatic hilum and two lung nodules. Case 3 (53-year-old man) had multiple solid nodules in the mediastinum, peritoneum, retroperitoneum, and mesentery; he also had diffuse irregular narrowing of the intra- and extra-hepatic bile ducts in keeping with sclerosing cholangitis. Serum IgG4 concentrations were not elevated. Biopsies from the nodular lesions showed extensive hyalinizing fibrosis with an only focal lymphoplasmacytic infiltrate. Thick collagenous bundles are arranged in an irregular or partly whorl pattern. Typical storiform fibrosis or obliterative phlebitis was not observed. The number of IgG4-positive plasma cells was <10 cells/high-power field; the ratio of IgG4/IgG-positive plasma cells was <30%. After the histological diagnosis of sclerosing mesenteritis, pulmonary hyalinizing granuloma, and mediastinal fibrosis was made, they were treated with a trial of steroids, but none showed a significant response. In conclusion, a hyalinizing fibrotic condition can occur at various anatomical sites. They have shared microscopic findings, and are steroid-resistant. Although the clinical presentation may mimic IgG4-RD, the two conditions are likely distinct. We would propose a diagnostic term of ‘idiopathic hyalinizing fibrosclerosis’ for this under-recognized, rare, systemic condition.

Effects of Corticosteroid Treatment on Olfactory Dysfunction in LATY136F Knock-In Mice.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory condition affecting multiple organs, including the pancreas, salivary glands, lungs, kidneys, skin, and lymph nodes. Clinically, it is characterized by elevated serum IgG and IgG4 levels and tissue infiltration by IgG4-positive plasma cells, lymphocytes, fibrosis, and phlebitis obliterans. IgG4-RD is linked to increased Th2-dominant cytokines, contributing to eosinophilia, elevated serum IgG4, and fibrosis. A notable feature is its good response to corticosteroid therapy. To investigate the effects of corticosteroid treatment on olfactory dysfunction in LATY136F knock-in mice, which exhibited increased production of Th2-type IgG1 (the murine homolog of human IgG4) and developed multiorgan tissue lesions similar to those observed in IgG4-RD patients. LATY136F knock-in mice (n=24) were divided into groups that received prednisolone or saline at different ages. Olfactory function was assessed using a behavioral test with cycloheximide. Histological and immunohistochemical analyses were performed to evaluate the olfactory epithelium thickness as well as the presence of mature and immature olfactory neurons. Corticosteroid-treated mice exhibited significantly improved olfactory function compared to the controls. Histological analysis revealed a significant increase in olfactory epithelium thickness and mature (olfactory marker protein-positive) and immature (growth-associated protein 43-positive) olfactory neurons in the treated groups compared with the control group. Corticosteroid treatment effectively improved olfactory dysfunction and promoted olfactory epithelium regeneration in LATY136F knock-in mice, suggesting the potential therapeutic benefits of corticosteroid treatment for patients with IgG4-RD experiencing olfactory dysfunction. However, further research on topical nasal steroid therapy in untreated patients is warranted. The results support further investigation into topical nasal steroid therapies for treating olfactory dysfunction in untreated patients, potentially influencing clinical practice and patient management strategies for IgG4-RD globally.

IgG4-Rich Lesions Associated With Intranasal Drug Use Can Mimic IgG4-Related Disease.

Manifestations of immunoglobulin G4-related disease (IgG4-RD) occur in several organ systems and anatomic locations, including the nasal cavity and paranasal sinuses. Other processes affecting the sinonasal tract, such as chronic rhinosinusitis, aspirin-exacerbated respiratory disease, and nasal polyposis, also involve IgG4. To characterize an association between IgG4 and nasal lesions arising in the clinical context of intranasal drug use. The cases of 3 patients (2 with histories of intranasal cocaine abuse, and 1 with intranasal heroin abuse) were evaluated. Clinical features of each case were compiled from the electronic medical record. Histologic morphology of surgical specimens was examined. Immunohistochemical staining was performed to assess involvement of/association with IgG4. Clinical features of these lesions included diffuse necrotic fibrinous debris, scarring, and endoscopically evident inflammation. Tissue sections showed acutely and chronically inflamed respiratory-type mucosa with abundant IgG4-positive plasma cells. Although these cases share some aspects in common with IgG4-RD, other definitive characteristics are absent, and notable differences exist. This series provides the first demonstration of increased IgG4 expression in nasal lesions associated with intranasal drug use. Despite some similarities, the pathologic processes and IgG4-rich infiltrates in these 3 cases seem to represent a different phenomenon that is not IgG4-RD. Although these lesions contain abundant IgG4-positive cells, they should not be mistaken for or conflated with IgG4-RD.

Primary sclerosing cholangitis with IgG4-positive plasma cells in bile duct biopsies - Frequency and characterization.

Patients diagnosed with primary sclerosing cholangitis (PSC) but with characteristics of immunoglobulin G4 (IgG4)-associated cholangitis (IAC) have been described. IAC often presents with biliary IgG4-positive plasma cell (IgG4+ PC) infiltration and responds to corticosteroids. In PSC, the frequencies or implications of biliary IgG4+ PC are unknown. We aimed to characterize the phenomenon of biliary IgG4+ PC in patients with an established PSC diagnosis. Bile duct biopsies from 191 surveillance or therapeutic endoscopic retrograde cholangiography of 58 PSC patients were retrospectively analyzed for IgG4+ PC infiltration. Patients with ≥10 IgG4+ PC per high-power field (HPF) were identified and characterized by clinical parameters, including serum IgG4 and cholangiographic presentations. Altogether 39.7% of the PSC patients showed ≥10 IgG4+ PC/HPF in bile duct biopsies. Patients with biliary IgG4+ PC infiltration were significantly younger at diagnosis of PSC (P = 0.023). There was no association between biliary IgG4+ PC infiltration and transplant-free survival (P = 0.618). Patients with IgG4+ PC infiltration in bile duct biopsies showed significantly higher baseline (P = 0.002) and maximum (P = 0.001) serum IgG4 compared to those without. Biliary IgG4+ PC infiltration was associated with high-grade bile duct strictures (P = 0.05). IgG4-positive plasma cell infiltrations were found multifocally in 72.7% of this subgroup of PSC patients. IgG4+ PC ≥10/HPF can be found abundantly in bile duct biopsies in PSC. Histological findings correlated with serum IgG4, age, and high-grade bile duct strictures. IgG4+ PC was located multifocally, hinting at a systemic biliary phenotype.

Dermatological Manifestations of IgG4-Related Disease: Insights into the Immunopathogenesis and Clinical Spectrum

This review aims to provide insights into the immunopathogenesis and clinical spectrum of dermatological manifestations in IgG4-related disease (IgG4-RD), a systemic fibroinflammatory disorder characterized by tissue infiltration of IgG4-positive plasma cells. Through comprehensive immunohistochemical analyses of skin biopsies from patients with IgG4-RD-associated cutaneous lesions, researchers endeavor to understand the role of IgG4- mediated immune responses, cytokine signaling, and fibrotic pathways in driving skin inflammation and fibrosis. Moreover, this research seeks to characterize the clinical presentation and treatment response of IgG4-RD-related dermatological manifestations to immunomodulatory therapies. Understanding the complex immunopathogenic mechanisms underlying IgG4-RD-related skin lesions may contribute to the refinement of diagnostic criteria and therapeutic strategies for managing this emerging autoimmune condition. Future research directions could include exploring novel biomarkers, identifying potential therapeutic targets, and investigating the long-term outcomes of dermatological involvement in IgG4-RD.

Tubulointerstitial nephritis with storiform fibrosis in a patient with angioimmunoblastic T-cell lymphoma.

We present a case of an angioimmunoblastic T-cell lymphoma (AITL) and tubulointerstitial nephritis with storiform fibrosis in a 76-year-old man. The patient exhibited lymphadenopathy, polyclonal hypergammaglobulinemia, and renal dysfunction and was diagnosed with AITL on the basis of lymph node biopsy findings. The serum IgG4 level was highly elevated. Renal biopsy revealed IgG4-positive plasma cells and storiform fibrosis without infiltration of AITL, and the findings indicated IgG4-related kidney disease (IgG4-RKD). Following THPCOP therapy for AITL, the renal function improved. While diagnosing IgG4-RKD in a patient with AITL poses challenges, follicular helper T cell involvement appeared crucial in AITL and renal tubulointerstitial lesions in this case.