IgG4 Related Disease of Epididymis, Mimicking Testicular Malignancy – A Rare Entity

Immunoglobulin G4 related disease (IgG4-RD) is a systemic fibro inflammatory condition that usually presents with multiorgan involvement. We present a rare case of 54 year old male with an isolated IgG4-RD of epididymis. The patient presented with a progressive swelling of the left testicle. A clinical diagnosis of tuberculosis was made. Ultrasound scrotum showed a relatively hetero-echoic mass lesion involving the left epididymis in close proximity to the left testis. There was a focal spindle cell proliferation and an increase in number of plasma cells and keloid like collagen. Immunohistochemistry was positive for vimentin and IgG4 and negative for CD34. Serum level of IgG4 was elevated (165 mg per dL). Computed tomography of abdomen and thorax did not show any systemic involvement. HE was posted for excision of the epididymal mass. Intraoperatively, the mass was found to be densely adherent to left testicle and inseparable from it, necessitating left total orchiectomy. Histopathology and immunohistochemistry with elevated serum IgG4 levels confirmed the diagnosis of IgG4-RD of the epididymis. To the best of our knowledge, this condition is an extremely rare entity, with only very few cases of isolated IgG4-RD of epididymis reported in medical literature, with no other systemic manifestations.

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Severe IgG4-Related Disease in a Young Child: A Diagnosis Challenge

Case Reports in Pediatrics ◽

10.1155/2015/140753 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4

Author(s):

Susana Corujeira ◽

Catarina Ferraz ◽

Teresa Nunes ◽

Elsa Fonseca ◽

Luísa Guedes Vaz

Keyword(s):

Plasma Cells ◽

Elevated Serum ◽

Female Child ◽

Symptomatic Improvement ◽

Organ Involvement ◽

Immunoglobulin G4 ◽

Related Disease ◽

Lymphoplasmacytic Infiltrate ◽

Serum Igg4 ◽

Tract Infections

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome that can appear with multiple organ involvement, typically with tumor-like swelling, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, and elevated serum IgG4 concentrations. We report the case of a 22-month-old female child with failure to thrive and recurrent respiratory tract infections since 8 months of age. Physical examination was normal except for pulmonary auscultation with bilateral crackles and wheezes. Laboratory tests revealed elevated erythrocyte sedimentation rate, and elevated serum IgG and IgG4 with polyclonal hypergammaglobulinemia. Thoracic CT and MRI showed multiple mediastinal lymphadenopathies and a nodular posterior mediastinal mass in right paratracheal location with bronchial compression. Initial fine needle aspiration biopsy was compatible with reactive lymphadenopathy but after clinical worsening a thoracoscopic partial resection of the mass was performed and tissue biopsy revealed lymphoplasmacytic infiltrate and increased number of IgG4-positive plasma cells and a ratio of IgG4/IgG positive cells above 40%. Glucocorticoids therapy was started with symptomatic improvement, reduction in the size of the mass, and decrease of serum IgG4 levels after 6 weeks. There are very few reports of IgG4-RD in children. Long-term follow-up is necessary to monitor relapses and additional organ involvement.

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Evaluate the Differences in CT Features and Serum IgG4 Levels between Lymphoma and Immunoglobulin G4-Related Disease of the Orbit

Journal of Clinical Medicine ◽

10.3390/jcm9082425 ◽

2020 ◽

Vol 9 (8) ◽

pp. 2425

Author(s):

Wei-Hsin Yuan ◽

Anna Fen-Yau Li ◽

Shu-Yi Yu ◽

Ying-Yuan Chen ◽

Chia-Hung Wu ◽

...

Keyword(s):

Elevated Serum ◽

Hounsfield Unit ◽

Immunoglobulin G4 ◽

Related Disease ◽

Serum Igg4 ◽

Orbital Lymphoma ◽

Serum Igg Levels ◽

Igg Level ◽

Ct Features ◽

Higher Sensitivity

Background: Benign immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD)—characterized as tumors mimicking malignant orbital lymphoma (OL)—responds well to steroids, instead of chemotherapy, radiotherapy and/or surgery of OL. The objective of this study was to report the differences in computed tomography (CT) features and- serum IgG4 levels of IgG4-ROD and OL. Methods: This study retrieved records for patients with OL and IgG4-ROD from a pathology database during an eight-year-and-five-month period. We assessed the differences between 16 OL patients with 27 lesions and nine IgG4-ROD patients with 20 lesions according to prebiopsy CT features of lesions and prebiopsy serum IgG4 levels and immunoglobulin G (IgG) levels This study also established the receiver-operating curves (ROC) of precontrast and postcontrast CT Hounsfield unit scales (CTHU), serum IgG4 levels, serum IgG levels and their ratios. Results: Significantly related to IgG4-ROD (all p < 0.05) were the presence of lesions with regular borders, presence of multiple lesions—involving both lacrimal glands on CT scans—higher median values of postcontrast CTHU, postcontrast CTHU/precontrast CTHU ratios, serum IgG4 levels and serum IgG4/IgG level ratios. Compared to postcontrast CTHU, serum IgG4 levels had a larger area under the ROC curve (0.847 [95% confidence interval (CI): 0.674–1.000, p = 0.005] vs. 0.766 [95% CI: 0.615–0.917, p = 0.002]), higher sensitivity (0.889 [95% CI: 0.518–0.997] vs. 0.75 [95% CI: 0.509–0.913]), higher specificity (0.813 [95% CI: 0.544–0.960] vs. 0.778 [95% CI: 0.578–0.914]) and a higher cutoff value (≥132.5 mg/dL [milligrams per deciliter] vs. ≥89.5). Conclusions: IgG4-ROD showed distinct CT features and elevated serum IgG4 (≥132.5 mg/dL), which could help distinguish IgG4-ROD from OL.

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Immunoglobulin G4-related disease - diagnostic dilemma and importance of clinical judgement: a case report

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20204922 ◽

2020 ◽

Vol 8 (11) ◽

pp. 4144

Author(s):

Jagadeesh Chandrasekaran ◽

Phani Krishna Machiraju

Keyword(s):

Early Recognition ◽

Elevated Serum ◽

Antineutrophil Cytoplasmic Antibodies ◽

Inflammatory Disorder ◽

Imaging Features ◽

Immunoglobulin G4 ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

The Right

Immunoglobulin G4 (IgG4)-related disease is a multi-organ, immune-mediated, fibro-inflammatory disorder characterized by tumefactive masses in the affected organs. Incidence and prevalence of IgG4-related disease (RD) are not clearly known and have slight male preponderance. It often involves multiple organs at the time of presentation or over the course of disease mimicking malignancy, Sjogren's syndrome, antineutrophil cytoplasmic antibodies associated vasculitis, infections. A thorough workup is needed to rule out these mimickers. A 33-year-old gentleman presented to us with history of progressive swelling in the right peri-orbital region for four years. On evaluation, abdominal imaging was notable for the sausage-shaped pancreas and hypoenchancing nodules in bilateral kidneys. Histological examination of right lacrimal gland revealed lymphoplasmacytic infiltrate and storiform fibrosis. Serum IgG4 levels were normal, and immunostaining was negative. A diagnosis of IgG4-RD was suggested because of multi-organ involvement, classical radiological and histopathological features. Awareness about IgG4-RD, an under-recognized entity is essential, as it is treatable, and early recognition may help in a favourable outcome. Appropriate use of clinicopathological, serological and imaging features in the right clinical context may help in accurate diagnosis. Elevated serum IgG4 levels and biopsy are not mandatory for the diagnosis.

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Immunoglobulin G4-related hypertrophic pachymeningitis

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000568 ◽

2019 ◽

Vol 6 (4) ◽

pp. e568 ◽

Cited By ~ 6

Author(s):

Michaël Levraut ◽

Mikaël Cohen ◽

Saskia Bresch ◽

Caroline Giordana ◽

Fanny Burel-Vandenbos ◽

...

Keyword(s):

Steroid Therapy ◽

Case Reports ◽

Treatment Algorithm ◽

Elevated Serum ◽

Case Series ◽

Hypertrophic Pachymeningitis ◽

Immunoglobulin G4 ◽

Systemic Involvement ◽

Meningeal Involvement ◽

Serum Igg4

ObjectiveMeningeal involvement in Immunoglobulin G (IgG)-4-related disease is rare and only described in case reports and series. Because a review into the disease is lacking, we present 2 cases followed by a literature review of IgG4-related hypertrophic pachymeningitis (IgG4-HP).MethodsTwo IgG4-HP cases were reported, one involving the spinal cord and responding to surgical management and a second involving the brain and responding to Rituximab therapy. We then review clinical cases and case-series of histologically proven IgG4-HP that were published in the PubMed-NCBI database.ResultsForty-two case reports and 5 case-series were studied (60 patients, 20 women). The median age was 53. Eighteen patients had systemic involvement and 24 had single-organ IgG4-HP. Fifty-five percent of patients had an elevated serum IgG4. Treatment was surgical in 20/53 cases. Steroid therapy and immunosuppressors were effective in 85% and more than 90% of the cases, respectively. The rate of disease relapse was 42.1% after steroid therapy was discontinued.Discussion/conclusionIgG4-HP is characterized by the lack of extra-neurologic organ-involvement and systemic signs. Histopathologic studies should be performed as it is crucial for diagnosis because serum markers are rarely informative. 18F-FDG positon tomography can be useful to characterize systemic forms. There is no specific CSF marker for IgG4-HP and the diagnostic value of CSF IgG4 levels needs to be studied with larger samples. We provide a treatment algorithm for IgG4-HP. Such treatment strategies rely on early surgery, steroids, and early immunosuppressive therapy to prevent neurologic complications.

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Immunoglobulin G4-related sclerosing cholangitis mimicking cholangiocarcinoma: a case report and literature review

Journal of International Medical Research ◽

10.1177/0300060520959214 ◽

2020 ◽

Vol 48 (10) ◽

pp. 030006052095921

Author(s):

Cheng Xu ◽

Yongmei Han

Keyword(s):

Sclerosing Cholangitis ◽

Plasma Cells ◽

Elevated Serum ◽

Clinical Manifestations ◽

Immunoglobulin G4 ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

History Of ◽

The Common

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a novel clinical disease that is characterized by elevated serum IgG4 concentrations and tumefaction or tissue infiltrated by IgG4+ plasma cells. The clinical manifestations of IgG4-RD depend on the type of tissues affected. IgG4-related sclerosing cholangitis is a type of IgG4-RD. We report a patient who initially visited a local hospital with a 5-month history of jaundice. He was found to have a mass in the upper part of the common bile duct that mimicked cholangiocarcinoma. He underwent surgery in our hospital and was later diagnosed with IgG4-related sclerosing cholangitis. We administered prednisolone 40 mg once a day for treatment. Taking into account the possible side effects of moderate-dose hormone therapy, we also administered teprenone, potassium chloride, and calcium carbonate. The patient did not have any recurrence of symptoms or adverse drug reactions during follow-up.

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Urologic manifestations of IgG4-related disease

Revista Mexicana de Urología ◽

10.48193/rmu.v80i5.610 ◽

2020 ◽

Vol 80 (5) ◽

pp. 1-10

Author(s):

Benjamin Enrique Montaño Roca ◽

Davide Vanacore ◽

Gustavo Gallegos Sánchez ◽

César Eduardo Rosales Velázquez ◽

Guillermo Enrique Ruvalcaba Oceguera ◽

...

Keyword(s):

Plasma Cells ◽

Elevated Serum ◽

Aged Patients ◽

Related Disease ◽

Igg4 Related Disease ◽

Lymphoplasmacytic Infiltrate ◽

Urinary Tract Symptoms ◽

Serum Igg4 ◽

Inflammatory Pseudotumors ◽

Clinically Significant

IgG4-related disease (IgG4-RD) is a clinical entity characterized by elevated serum IgG4 and tumor-like inflammation, with tissue infiltration by IgG4 and plasma cells. IgG4-RD is rare, but clinically significant, and its urologic manifestations have been reported in the literature. The present review covers a broad spectrum, describing the pathologies related to the area of urology. In 2003, Terumi Kamisawa was the first to recognize IgG4-RD, characterized by multiorgan lesions in patients with autoimmune pancreatitis and classified as an inflammatory and fibrotic entity with a dense lymphoplasmacytic infiltrate, positive for IgG4.(1–3) It presents in middle-aged patients, between 59-68 years of age, with no clear distribution by sex, (4–6) and has different clinical presentations. The main urologic manifestations are inflammatory pseudotumors and lower urinary tract symptoms. The present article offers a clear, general overview of the disease, encompassing its pathophysiology, diagnosis, and treatment, from the perspective of urology.

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IgG4-Related Lymphadenopathy

International Journal of Rheumatology ◽

10.1155/2012/572539 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 47

Author(s):

Yasuharu Sato ◽

Tadashi Yoshino

Keyword(s):

Lymph Node ◽

Plasma Cells ◽

Elevated Serum ◽

Serum Levels ◽

Lymph Node Involvement ◽

Lymph Node Biopsy ◽

Immunoglobulin G4 ◽

Reactive Protein ◽

Serum Igg4 ◽

Node Involvement

Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity, with at least 5 histological subtypes. Indeed, lymph node biopsy may be performed under the suspicion that the lymphadenopathy is a malignant lymphoma or other lymphoproliferative disorder. The diagnosis of IgG4-RD is characterized by both elevated serum IgG4 (>135?mg/dL) and histopathological features, including a dense lymphoplasmacytic infiltrate rich in IgG4+plasma cells (IgG4+/IgG+plasma cell ratio >40%). However, patients with hyper-interleukin (IL-) 6 syndromes such as multicentric Castleman’s disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. Owing to these factors, IgG4-RD cannot be differentiated from hyper-IL-6 syndromes on the basis of histological findings alone. Laboratory analyses are crucial to differentiate between the 2 diseases. Hyper-IL-6 syndromes are characterized by elevated serum levels of IgG, IgA, IgM, and C-reactive protein (CRP); thrombocytosis; anemia; hypoalbuminemia; hypocholesterolemia. In contrast, IgG4-RD does not share any of these characteristics. Therefore, the diagnosis of IgG4-RD requires not only pathological findings but also clinical and laboratory analyses.

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IgG4-Related Disease: A Multispecialty Condition

Case Reports in Rheumatology ◽

10.1155/2014/723493 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3

Author(s):

Iuri Usêda Santana ◽

Emanuela Pimenta da Fonseca ◽

Mittermayer Barreto Santiago

Keyword(s):

Plasma Cells ◽

Elevated Serum ◽

Diffuse Abdominal Pain ◽

Related Disease ◽

Igg4 Related Disease ◽

Lymphoplasmacytic Infiltrate ◽

Serum Igg4 ◽

Polyclonal Hypergammaglobulinemia ◽

History Of ◽

Systemic Condition

IgG4-related disease (IgG4-RD) is a recently recognized group of conditions, characterized by tumor-like swelling of involved organs, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, variable degrees of fibrosis, and elevated serum IgG4 concentrations. Currently IgG4-RD is recognized as a systemic condition that can affect several organs and tissues. Herein we report the case of a 34-year-old male patient who was admitted to our hospital with diffuse abdominal pain, weight loss, and painful stiffness in his neck. He had a history of tumoral mass of the left maxillary region, right palpebral ptosis with protrusion of the eyeball, and chronic dry cough for about 6 years. Laboratory tests revealed polyclonal hypergammaglobulinemia and increased serum IgG4 levels. Immunohistochemical staining of the maxillary biopsy was compatible with IgG4-RD. He had an excellent response to corticosteroid therapy. This case highlights that IgG4-RD should be included in the differential diagnosis with multisystem diseases.

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Long-term effects of intensive B cell depletion therapy in severe cases of IgG4-related disease with renal involvement

Immunologic Research ◽

10.1007/s12026-020-09163-3 ◽

2020 ◽

Vol 68 (6) ◽

pp. 340-352

Author(s):

Giacomo Quattrocchio ◽

Antonella Barreca ◽

Andrea Demarchi ◽

Roberta Fenoglio ◽

Michela Ferro ◽

...

Keyword(s):

B Cells ◽

B Lymphocyte ◽

Plasma Cells ◽

Renal Involvement ◽

Elevated Serum ◽

Long Term Effects ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Storiform Fibrosis

AbstractIgG4-related disease (IgG4-RD) is an immune-mediated disorder often showing elevated serum IgG4 concentrations, dense T and B lymphocyte infiltration, and IgG4-positive plasma cells and storiform fibrosis. We prospectively evaluated for 4 years 5 patients with histologically proven IgG4-RD of whom 3 had tubulointerstitial nephritis (TIN) and 2 had retroperitoneal fibrosis (RPF). They received an intensive B depletion therapy with rituximab. The estimated glomerular filtration rate of TIN patients after 1 year increased from 9 to 24 ml/min per 1.73 m2. IgG/IgG4 dropped from 3236/665 to 706/51 mg/dl, C3/C4 went up from 49/6 to 99/27 mg/dl, and the IgG4-RD responder index fell from 10 to 1. CD20+ B cells decreased from 8.7 to 0.5%. A striking drop in interstitial plasma cell infiltrate as well as normalization of IgG4/IgG-positive plasma cells was observed at repeat biopsy. Both clinical and immunological improvement persisted over a 4-year follow-up. Treating these patients who were affected by aggressive IgG4-RD with renal involvement in an effort to induce a prolonged B cells depletion with IgG4 and cytokine production decrease resulted in a considerable rise in eGFR, with IgG4-RD RI normalization and a noteworthy improvement in clinical and histological features. Furthermore, the TIN subgroup was shown not to need for any maintenance therapy.

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The Utility of Serum IgG4 Concentrations as a Biomarker

International Journal of Rheumatology ◽

10.1155/2012/198314 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 24

Author(s):

Shigeyuki Kawa ◽

Tetsuya Ito ◽

Takayuki Watanabe ◽

Masahiro Maruyama ◽

Hideaki Hamano ◽

...

Keyword(s):

Autoimmune Pancreatitis ◽

Plasma Cells ◽

High Serum ◽

Wall Thickening ◽

Systemic Involvement ◽

Related Disease ◽

Igg4 Related Disease ◽

Serum Igg4 ◽

Long Term Follow Up ◽

Characteristic Features

IgG4-related disease is a new disease entity involving IgG4 in its clinical presentation and having 6 characteristic features: (1) systemic involvement; (2) solitary or multiple lesions showing diffuse or localized swelling, masses, nodules, and/or wall thickening on imaging; (3) high serum IgG4 concentration >135 mg/dL; (4) abundant infiltration of lymphoplasmacytes and IgG4-bearing plasma cells; (5) a positive response to corticosteroid therapy; and (6) complications of other IgG4-related diseases. To date, most IgG4-related diseases have been recognized as extrapancreatic lesions of autoimmune pancreatitis. This paper will discuss the utility of IgG4 as a biomarker of IgG4-related diseases, including in the diagnosis of autoimmune pancreatitis and its differentiation from pancreatic cancer, in the prediction of relapse, in the long-term follow-up of patients with autoimmune pancreatitis and normal or elevated IgG4 concentrations, and in patients with autoimmune pancreatitis and extrapancreatic lesions, as well as the role of IgG4 in the pathogenesis of IgG4-related disease.

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