IgG4-related chronic sclerosing sialadenitis in a child with recurrent parotitis: a case report

Abstract Background IgG4-related disease (IgG4-RD) includes a group of immune-mediated diseases histologically characterized by lymphoplasmacytic infiltrate with a prevalence of IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Autoimmune pancreatitis, sialadenitis, dacryoadenitis and retroperitoneal fibrosis are the most frequent manifestations. IgG4-related sialadenitis usually affects submandibular glands and is very rare in children. Here we report the case of IgG4-related sialadenitis in a six-year-old patient previously diagnosed as juvenile recurrent parotitis. Case presentation A six-year-old patient was referred to our Centre for left parotid swelling of 4 × 3 cm, that was tender, soft in consistency, with overlying red and warm skin. His general condition was good but he was subfebrile; general examination revealed mild enlargement of left cervical lymph nodes. In the last 2 years he had had five episodes of parotitis, diagnosed by another pediatric Center as juvenile recurrent parotitis. On ultrasound examination the left parotid gland appeared enlarged, inhomogeneous, with a colliquative intraparotid lymph node and no evidence of sialolithiasis. Laboratory tests showed an increase of white blood cells and anti-VCA IgM and IgG positivity, with anti-EBNA e anti-EA I negativity. The patient was initially treated with oral antibiotics, but after 10 days the parotid became fluctuating, requiring surgical biopsy and drainage. Postoperative course was regular, with complete remission under oral antibiotic and steroid therapy. Microbiological tests, including cultures for aerobic and anaerobic bacteria, mycobacteria and Bartonella, were negative. Surprisingly, histology showed marked fibrosis and histiocytic and lymphoplasmacellular infiltrate with polyclonal plasma cells mostly expressing IgG4 immunoglobulins. Thus, the diagnosis of IgG4 related chronic sialadenitis in recurrent parotitis and recent EBV infection was made. Conclusions IgG4-related sialadenitis is very unusual in children. Histology plays a key role in diagnosis, considering that up to 30% of patients have normal serum IgG4 levels, as shown in our case. The lack of previous histological data makes it impossible to attribute our patient’s previous episodes of parotitis to IgG4-RD, though it is a very consistent possibility.

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Chronic sclerosing sialadenitis IgG4-related in a boy with recurrent parotitis: a case report

10.21203/rs.3.rs-234815/v1 ◽

2021 ◽

Author(s):

Fabio Stefano Timeus ◽

Mario Michele Calvo ◽

Anna Maria Caci ◽

Giogio Oliviero Gallone ◽

Federico Vittone

Keyword(s):

Plasma Cells ◽

White Blood Cells ◽

Anaerobic Bacteria ◽

Final Diagnosis ◽

Low Grade ◽

Obliterative Phlebitis ◽

Cervical Lymph Nodes ◽

Chronic Sclerosing Sialadenitis ◽

Igg4 Related Disease ◽

Serum Igg4

Abstract BackgroundIgG4-related diseases are a group of immune-mediated diseases characterized by a lymphoplasmacytic infiltrate with a prevalence of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis. Autoimmune pancreatitis, sialadenitis, dacryoadenitis and retroperitoneal fibrosis are the most frequent manifestations. IgG4-related sialadenitis usually affects submandibular glands and is very rare in children. We report here a case of an unexpected diagnosis of IgG4-related sialoadenitis in a boy previously diagnosed as affected by juvenile recurrent parotitis.Case presentationA six-year old boy presented to our centre with left parotid swelling about 4x3 cm, tender, soft in consistency, with the overlying skin red and warm. He had low-grade fever and a mild enlargement of left cervical lymph nodes. In the last two years he had five episodes of parotitis and a diagnosis of juvenile recurrent parotitis.. The general conditions were good, and the remainder of the physical examination was normal. At the ultrasonography left parotid was enlarged, inhomogeneous, with a colliquated intraparotid lymph node and no evidence of sialolithiasis. Laboratory tests were normal, except for an increase of white blood cells and positivity for IgM and IgG anti-VCA, with anti-EBNA e anti-EA I negative. The patient was treated with cephalosporins and azitromycin, but after 10 days the parotid became fluctuating and the patient underwent to drainage and biopsy of the gland. He was discharged after 3 days of observation, without any complications, and treated with a further course of cefpodoxime and betametasone, with a good clinical response.Investigations for aerobic and anaerobic bacteria, mycobacteria and Bartonella on the pus were negative. Histology showed marked fibrosis and histiocytic and lymphoplasmacellular infiltration. The plasma cells were polyclonal and mostly expressed IgG4 subclass immunoglobulins. The final diagnosis was chronic sclerosing sialadenitis IgG4-related in recurrent parotitis and recent EBV infection. ConclusionsThe interest of this case comes from the rarity of IgG4-related sialadenitis in children. It is not possible to argue with certainty that the previous episodes of parotitis were manifestations of a IgG4-related disease, due to the lack of histological data. Serum IgG4 in our patient were normal, as described in literature in 30% of cases.

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Needle biopsy compared with surgical biopsy: pitfalls of small biopsy in histologial diagnosis of IgG4-related disease

Arthritis Research & Therapy ◽

10.1186/s13075-021-02432-y ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Yanying Liu ◽

Fei Yang ◽

Xiying Chi ◽

Yuxin Zhang ◽

Jiangnan Fu ◽

...

Keyword(s):

Needle Biopsy ◽

Plasma Cells ◽

Classification Criteria ◽

Histological Diagnosis ◽

Obliterative Phlebitis ◽

Surgical Biopsy ◽

Related Disease ◽

Igg4 Related Disease ◽

Significant Difference ◽

Storiform Fibrosis

Abstract Objective The growing utilization of needle biopsy has challenged the current pathology consensus of IgG4-related disease (IgG4-RD). The aims of this study were to identify the histological characteristics of needle biopsy and surgical specimens and evaluate the ability of needle biopsy in histological diagnosis of IgG4-RD. Methods Biopsies from patients who were referred to as IgG4-RD by the 2019 ACR/EULAR IgG4-RD classification criteria in Peking University People’s Hospital from 2012 to 2019 were re-evaluated. Typical histological features and diagnostic categories were compared between needle biopsy and surgical biopsy. Results In total, 69 patients met the 2019 ACR/EULAR classification criteria and 72 biopsies of them were re-evaluated. All cases showed lymphoplasmacytic infiltrate, while storiform fibrosis and obliterative phlebitis were only present in 35 (48.6%) and 23 (31.9%) specimens, respectively. Storiform fibrosis was more likely to be seen in retroperitoneum lesion (P = 0.033). Surgical biopsy showed significantly higher IgG4+ plasma cells/high-power field (IgG4/HPF) count (P < 0.01) and higher proportion of IgG4/HPF > 10 (P < 0.01). No significant difference was observed with regard to the ratio of IgG4+ plasma cells/IgG+ plasma cells (IgG4/IgG) (P = 0.399), storiform fibrosis (P = 0.739), and obliterative phletibis (P = 0.153). According to the 2011 comprehensive diagnostic criteria, patients who performed a needle biopsy were less likely to be probable IgG4-RD (P = 0.045). Based on the 2011 pathology consensus, needle biopsy was less likely to be diagnosed as IgG4-RD (P < 0.01), especially to be highly suggestive IgG4-RD (P < 0.01). Only 1/18 (5.6%) needle salivary specimens fulfilled the cutoff of IgG4/HPF > 100, which was significantly less than 15/23 (65.2%) of surgical ones (P < 0.01). Conclusions Needle biopsy shows an inferiority in detecting IgG4/HPF count but not in IgG4/IgG ratio, storiform fibrosis, and obliterative phlebitis. Compared with surgical samples, needle biopsy is less likely to obtain a histological diagnosis of IgG4-RD. A different IgG4/HPF threshold for needle biopsy of the salivary glands may be considered.

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IgG4-Related Sclerosing Cholangitis: Rarely Diagnosed, but not a Rare Disease

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2021/1959832 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Sylvia Drazilova ◽

Eduard Veseliny ◽

Patricia Denisa Lenartova ◽

Dagmar Drazilova ◽

Jakub Gazda ◽

...

Keyword(s):

Diagnostic Criteria ◽

Sclerosing Cholangitis ◽

Plasma Cells ◽

Histological Finding ◽

Good Prognosis ◽

High Serum ◽

Obliterative Phlebitis ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Storiform Fibrosis

IgG4-related sclerosing cholangitis, a biliary manifestation of an IgG4-related disease, belongs to the spectrum of sclerosing cholangiopathies which result in biliary stenosis. It presents with signs of cholestasis and during differential diagnosis it should be distinguished from cholangiocarcinoma or from other forms of sclerosing cholangitis (primary and secondary sclerosing cholangitis). Despite increasing information and recently established diagnostic criteria, IgG4-related sclerosing cholangitis remains underdiagnosed in routine clinical practice. The diagnosis is based on a combination of the clinical picture, laboratory parameters, histological findings, and a cholangiogram. Increased serum IgG4 levels are nonspecific but are indeed a part of the diagnostic criteria proposed by the Japan Biliary Association and the HISORt criteria for IgG4-SC. High serum IgG4 retains clinical utility depending on the magnitude of elevation. Approximately 90% of patients have concomitant autoimmune pancreatitis, while 10% present with isolated biliary involvement only. About 26% of patients have other organ involvement, such as IgG4-related dacryoadenitis/sialadenitis, IgG4-related retroperitoneal fibrosis, or IgG4-related renal lesions. A full-blown histological finding characterized by IgG4-enriched lymphoplasmacytic infiltrates, obliterative phlebitis, and storiform fibrosis is difficult to capture in practice because of its subepithelial localization. However, the histological yield is increased by immunohistochemistry, with evidence of IgG4-positive plasma cells. Based on a cholangiogram, IgG-4 related sclerosing cholangitis is classified into four subtypes according to the localization of stenoses. The first-line treatment is corticosteroids. The aim of the initial treatment is to induce clinical and laboratory remission and cholangiogram normalization. Even though 30% of patients have a recurrent course, in the literature data, there is no consensus on chronic immunosuppressive maintenance therapy. The disease has a good prognosis when diagnosed early.

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Immunoglobulin G4 Sclerosing Cholangitis: An Unusual Cause of Obstructive Jaundice—Case Report and Literature Review

Case Reports in Rheumatology ◽

10.1155/2018/9602373 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5

Author(s):

Pragya Shrestha ◽

Brian Le ◽

Brent Wagner ◽

William Pompella ◽

Paras Karmacharya

Keyword(s):

Sclerosing Cholangitis ◽

Plasma Cells ◽

Systemic Disease ◽

Clinical Manifestations ◽

Disease Process ◽

High Serum ◽

Diagnostic Challenge ◽

Obliterative Phlebitis ◽

Immunoglobulin G4 ◽

Serum Igg4

IgG4-related sclerosing cholangitis (IgG4-SC) is one of the most common extra-pancreatic manifestation of IgG4-related disease (IgG4-RD) and is clinically distinct from primary sclerosing cholangitis (PSC). IgG4-RD is an increasingly recognized immune-mediated fibroinflammatory systemic disease, mostly affecting middle-aged and older male populations that can affect multiple organs. The presence of extra-biliary clinical manifestations of IgG4-RD, such as parotid and lacrimal swelling, lymphadenopathy, autoimmune pancreatitis, and retroperitoneal fibrosis, if present could provide important clues to diagnosis. High serum IgG4 levels, characteristic radiological (e.g., sausage-shaped pancreas or periaortitis) or biopsy findings (high percentage of IgG4+ plasma cells, lymphoplasmacytic infiltrate, storiform fibrosis, or obliterative phlebitis) in the setting of these features is diagnostic of this disease process. However, isolated IgG4-SC might be a diagnostic challenge, and the distinction is important as management of this disorder is vastly different from other causes of cholangitis such as PSC. Systemic corticosteroid therapy is the mainstay of therapy.

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A Retrospectively Diagnosed Case of IgG4-Related Tubulointerstitial Nephritis Showing Good Renal Outcome and Pathological Progress

Case Reports in Nephrology ◽

10.1155/2013/953214 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7

Author(s):

Qiong Wu ◽

Raima Nakazawa ◽

Hisae Tanaka ◽

Masayuki Endoh ◽

Masafumi Fukagawa

Keyword(s):

Diabetic Nephropathy ◽

Lymph Node ◽

Plasma Cells ◽

Tubulointerstitial Nephritis ◽

Lymph Node Involvement ◽

Renal Outcome ◽

Creatinine Concentration ◽

Chronic Sialadenitis ◽

Serum Igg4 ◽

Node Involvement

A 74-year-old man was hospitalized for diabetic nephropathy evaluation and assessment of the effect of treatment on his tubulointerstitial nephritis (TIN). When he was 62 years old, he developed polyarthralgia and had superficial lymph node swelling, mildly increased serum creatinine concentration, hypergammaglobulinemia, hypocomplementemia, high serum IL-2R level, and positive titer of antinuclear antibody. Several tissues were biopsied. Mild chronic sialadenitis and reactive lymphadenitis were identified. Renal specimen showed mild glomerular ischemia, extensive storiform fibrosis, and abundant infiltrating monocytes and plasma cells. He was treated with oral prednisolone and cyclophosphamide. After the treatment, most of his clinical parameters quickly returned to within the reference range. However, he developed diabetes mellitus soon after steroid therapy. At the time of rebiopsy, a high level of serum IgG4 was detected. The second renal biopsy showed diabetic nephropathy without any tubulointerstitial damage. The first biopsied tissues were retrospectively investigated. Large numbers of IgG4-positive plasma cells were detected in the kidneys and lymph nodes. A retrospective diagnosis of IgG4-related TIN with lymph node involvement was made. In conclusion, this paper describes a retrospectively diagnosed case of IgG4-related TIN with lymph node involvement, showing good clinical and pathological prognosis.

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IgG4-Related Disease in a Urachal Tumor

Case Reports in Urology ◽

10.1155/2014/275850 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3

Author(s):

Travis W. Dum ◽

Da Zhang ◽

Eugene K. Lee

Keyword(s):

Plasma Cells ◽

Elevated Serum ◽

Needle Aspiration ◽

Lung Lesion ◽

High Rate ◽

Mediastinal Lymphadenopathy ◽

Obliterative Phlebitis ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4

IgG4-related disease is a newly recognized fibroinflammatory disorder that has the ability to affect nearly every organ system. It is characterized by tumefactive lesions and fibrosis and closely mimics neoplasms. Only one case of IgG4-related bladder mass has been reported in the literature, but there are no reports of IgG4-related disease in a urachal mass. Herein, we report a 26-year-old male who initially presented with symptoms of recurrent UTI. Work-up revealed a 6 cm urachal tumor, a 1.4 cm pulmonary lesion, and mediastinal lymphadenopathy; all metabolically active on PET scan and suspicious for urachal adenocarcinoma. Lung lesion fine needle aspiration and TURBT pathology revealed inflammation but no evidence of malignancy. The patient underwent a partial cystectomy and umbilectomy with pathology demonstrating dense plasmacytic cells, a high rate of immunohistochemistry staining positive for IgG4 plasma cells, a storiform pattern of fibrosis, and an obliterative phlebitis. Furthermore, the patient had an elevated serum IgG4 level of 227 mg/dL (range 2.4–121 mg/dL). IgG4-related disease is a newly recognized fibroinflammatory disorder that can mimic neoplastic processes and a high index of suspicion and accurate tissue pathology is necessary for an accurate diagnosis.

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The Cellular and Molecular Bases of Allergy, Inflammation and Tissue Fibrosis in Patients with IgG4-related Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21145082 ◽

2020 ◽

Vol 21 (14) ◽

pp. 5082

Author(s):

Song-Chou Hsieh ◽

Chieh-Yu Shen ◽

Hsien-Tzung Liao ◽

Ming-Han Chen ◽

Cheng-Han Wu ◽

...

Keyword(s):

Plasma Cells ◽

Elevated Serum ◽

Clinical Manifestations ◽

Malignant Neoplasms ◽

Th2 Response ◽

Obliterative Phlebitis ◽

Inflammatory Reactions ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4

IgG4-related disease (IgG4-RD) is a spectrum of complex fibroinflammatory disorder with protean manifestations mimicking malignant neoplasms, infectious or non-infectious inflammatory process. The histopathologic features of IgG4-RD include lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis together with increased in situ infiltration of IgG4 bearing-plasma cells which account for more than 40% of all IgG-producing B cells. IgG4-RD can also be diagnosed based on an elevated serum IgG4 level of more than 110 mg/dL (normal < 86.5 mg/mL in adult) in conjunction with protean clinical manifestations in various organs such as pancreato–hepatobiliary inflammation with/without salivary/lacrimal gland enlargement. In the present review, we briefly discuss the role of genetic predisposition, environmental factors and candidate autoantibodies in the pathogenesis of IgG4-RD. Then, we discuss in detail the immunological paradox of IgG4 antibody, the mechanism of modified Th2 response for IgG4 rather than IgE antibody production and the controversial issues in the allergic reactions of IgG4-RD. Finally, we extensively review the implications of different immune-related cells, cytokines/chemokines/growth factors and Toll-like as well as NOD-like receptors in the pathogenesis of tissue fibro-inflammatory reactions. Our proposals for the future investigations and prospective therapeutic strategies for IgG4-RD are shown in the last part.

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IgG4-related disease: an atypical presentation of steroid-responsive renal mass

BMJ Case Reports ◽

10.1136/bcr-2020-240611 ◽

2021 ◽

Vol 14 (5) ◽

pp. e240611

Author(s):

Shu Hui Ng ◽

Jing Shin Tay ◽

Ee Ling Lai

Keyword(s):

Renal Mass ◽

Plasma Cells ◽

Normal Serum ◽

Obliterative Phlebitis ◽

Related Disease ◽

First Line Therapy ◽

Igg4 Related Disease ◽

Serum Igg ◽

Storiform Fibrosis ◽

Lymphoplasmacytic Infiltration

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disease characterised by dense lymphoplasmacytic infiltration rich in IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Serum IgG4 levels are typically elevated but half of the patients had normal serum IgG4 levels. IgG4-RD represents a spectrum of diseases that involve various organs such as the pancreas, liver, kidneys, and salivary glands often manifesting as diffuse organ enlargement or a mass-like lesion mimicking cancer. An increased incidence of malignancy among patients with IgG4-RD has been reported. Thus, differentiating malignancy from IgG4-RD manifestation is important as the treatment differs. Glucocorticoids are considered first-line therapy and should be started early to prevent fibrosis. Patients usually have an excellent clinical response to steroids, and poor steroid response is indicative of an alternative diagnoses such as malignancy. This case report describes a case of IgG4-RD with renal mass in a young man that resolved with glucocorticoid therapy alone.

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Multiple pleural nodules diagnosed as IgG4-related disease: a case report

Surgical Case Reports ◽

10.1186/s40792-021-01166-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yoshihito Iijima ◽

Shun Iwai ◽

Nozomu Motono ◽

Katsuo Usuda ◽

Akihiro Shioya ◽

...

Keyword(s):

Plasma Cells ◽

Histopathological Examination ◽

Fibrous Tissue ◽

Positron Emission Tomography Imaging ◽

Surgical Biopsy ◽

Immunoglobulin G4 ◽

Related Disease ◽

Igg4 Related Disease ◽

Positron Emission ◽

Serum Igg4

Abstract Background Immunoglobulin G4 (IgG4)-related diseases are characterized by abnormal IgG4 levels, swelling, and marked infiltration and fibrosis of the lymphocytes and IgG4-positive plasma cells, causing hypertrophic lesions or nodules. The cause is currently not well understood. IgG4-related diseases involving lesions limited to the pleura are extremely rare. Herein, we report an IgG4-related disease presenting with multiple pleural nodules confirmed by thoracoscopic surgical biopsy. Case presentation A 74 year-old man was referred to our department for definitive diagnosis of multiple pleural nodules after 1 year of follow-up. Computed tomography of the chest revealed multiple pleural nodules, while 2-deoxy-2-( 18F)-fluorodeoxyglucose positron emission tomography imaging exhibited tracer accumulation in the nodules. A thoracoscopic surgical biopsy was performed. Histopathological examination revealed hyalinized fibrous tissue with a high degree of plasma cell-based inflammatory cell infiltration. Immunohistochemically, IgG4-positive cells were conspicuous, accounting for 70.5% of the plasma cells. The postoperative serum IgG4 concentration was 289 mg/dL. We diagnosed the patient with an IgG4-related disease with multiple pleural nodules. The postoperative course was good, and the patient is currently being followed up. Conclusion IgG4-related disease should be considered in cases presenting with multiple pleural nodules.

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IgG4-related gastric disease with plasma cell-rich obliterative arteritis accompanied by early-stage gastric cancer: a case report

Surgical Case Reports ◽

10.1186/s40792-021-01126-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Masayoshi Obatake ◽

Koichi Sato ◽

Shigehiko Yagi ◽

Hiromi Ohtani ◽

Katsumi Kito

Keyword(s):

Gastric Cancer ◽

Plasma Cell ◽

Early Stage ◽

Vascular Lesions ◽

Gastric Disease ◽

Inflammatory Disorder ◽

Obliterative Phlebitis ◽

Regional Lymph Node Dissection ◽

Serum Igg4 ◽

Storiform Fibrosis

Abstract Background Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated inflammatory disorder that can involve multiple organs. It is characterized by IgG4-positive plasma cell-rich storiform fibrosis and obliterative phlebitis associated with a high serum IgG4 level. There are few reports of gastric IgG4-RD, especially those detected prior to systemic or other organ involvement. Case presentation: A 70-year-old man was diagnosed with type 0–IIc gastric cancer at the anterior wall of the gastric corpus by upper gastrointestinal endoscopy. In addition, a submucosal tumor (SMT) 7 mm in diameter was found at the greater curvature of the angulus. Laparoscopic distal gastrectomy with regional lymph node dissection was performed. Pathology revealed a poorly differentiated adenocarcinoma in the type 0–IIc lesion and storiform fibrosis with infiltration of a large number of IgG4-positive plasma cells in the SMT. Postoperative laboratory testing showed elevation of serum IgG4 levels; thus, we diagnosed the SMT as IgG4-RD. Intriguingly, the gastric IgG4-RD lesion demonstrated IgG4-positive plasma cell-rich arteritis as well as typical obstructive phlebitis. The patient has been followed for 2 years after surgery without recurrence of cancer, but skin lesions of IgG4-RD have appeared. Conclusion We report a rare case of IgG4-RD presenting as a gastric SMT, accompanied by early-stage gastric cancer. Our case may support a newly proposed relationship between IgG4-RD and malignancies. The gastric IgG4-RD lesion showed arteritis as well as obliterative phlebitis, potentially providing novel insight into IgG4-related vascular lesions.

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