IgG4-positive Cells Research Articles

Granulomatosis with polyangiitis with lacrimal gland enlargement and pancreatic swelling: case report and literature review.

A 62-year-old man had bilateral eyelid swelling for 4 months. Two months before admission, he developed fatigue and lost 5 kg of bodyweight. Further examination revealed elevated serum C-reactive protein, normal angiotensin-converting enzyme, elevated proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA), and normal IgG4 concentration. Chest X-ray and computed tomography showed no enlarged hilar lymph nodes, but positron emission tomography-computed tomography showed fluorodeoxyglucose accumulation in both lacrimal glands, in lung nodules, and in the pancreas. Tissue biopsies of the lacrimal glands and pulmonary nodules showed granuloma with giant cells, but no IgG4-positive cells or fibrosis. Pancreatic tissue showed no findings of autoimmune pancreatitis. In the 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis, the total score was 10 points. Final comprehensive diagnosis was granulomatosis with polyangiitis, based on the negative results of differential diseases, such as IgG4-related diseases and sarcoidosis. Prednisolone 60 mg/day was started on day 8, and rituximab 500 mg/body/week on day 12. After beginning treatment, general malaise and lacrimal gland enlargement were resolved, PR3-ANCA and C-reactive protein became negative, and the nodular shadow in the lungs disappeared. This is the first report of granulomatosis with polyangiitis presenting both lacrimal gland and pancreatic lesions.

The 2023 revised diagnostic criteria for IgG4-related dacryoadenitis and sialadenitis.

For the diagnosis of IgG4-related dacryoadenitis and sialadenitis, either revised comprehensive diagnostic criteria or organ-specific diagnostic criteria for IgG4-related dacryoadenitis and sialadenitis in 2008 were applied; however, the collected knowledge for IgG4-related dacryoadenitis and sialadenitis required us to revise the criteria for IgG4-related dacryoadenitis and sialadenitis. The board member of Japanese Study Group for IgG4-related Dacryoadenitis and Sialadenitis revised the diagnostic criteria for IgG4-related dacryoadenitis and sialadenitis. We collected the clinical questions to be revised and performed a review of the literature. When the data were insufficient, additional data collection was performed. After the revision, public comments were collected. The three major points were revised. 1. Asymmetric or under two pairs of dacryoadenitis and sialoadenitis were included as IgG4-related dacryoadenitis and sialadenitis. 2. The thresholds of IgG4-positive cell infiltration were adjusted to an IgG4+/IgG+ ratio >0.4 and IgG4+ cells >10 per high power field. 3. The labial salivary gland biopsy was allowed to diagnose IgG4-related dacryoadenitis and sialadenitis. The revised diagnostic criteria for IgG4-related dacryoadenitis and sialadenitis solved several issues with the previous criteria. It will improve the early diagnosis of IgG4-related dacryoadenitis and sialadenitis, especially in situations without enough resources for a biopsy.

Mass Forming Autoimmune Pancreatitis, Misdiagnosed as Pancreatic Cancer: Case Report

Autoimmune pancreatitis is characterized by infiltration of the pancreas parenchyma by immunoglobulin G4 (IgG4)-positive plasma cells, chronic inflammation, and fibrosis. It can affect the entire body depending on the subtype. Distinguishing mass-forming type autoimmune pancreatitis from pancreatic cancer can often be challenging. A 60-year-old male presented to our outpatient clinic with abdominal discomfort. Computed tomography revealed a 4.8 cm mass in the pancreatic head obstructing the common bile duct. Endoscopic ultrasound-guided fine needle biopsy and endoscopic retrograde cholangiopancreatography with biliary drainage were performed. Pathological examination revealed no malignant cells, but more than 20 IgG4-positive cells were observed. Following two weeks of steroid treatment, the patient’s symptoms improved, and follow-up imaging showed a reduction in the size of the pancreatic head mass. Herein, we report a case of mass-forming autoimmune pancreatitis initially misdiagnosed as pancreatic cancer.

IgG4-связанное заболевание с вовлечением тканей глазницы у пятилетнего ребенка

Case study IgG4-related disease involving the tissues of the orbit in a five-year-old child Yu.V. Kotova, E.E. Grishina, E.I. Kondratieva, G.I. Fokanova, I.M. Tarabanko Moscow Regional Research Institute of Childhood, Mytishchi, Moscow Region, Russian Federation M.F. Vladimirsky Moscow Regional Research Institute, Moscow, Russian Federation Purpose. To demonstrate a rare clinical case of IgG4-related disease in the practice of a rheumatologist, a pediatrician and an ophthalmologist. Material and methods. A 5-year-old child had a lesion in the left orbit, manifested by left-sided exophthalmos, medial displacement of the left eye, and limited outward eye mobility. He underwent an orbitotomy with histological and immunohistochemical examination of the biopsy specimen in the ophthalmology department of M.F. Vladimirsky Moscow Regional Research Institute. A diagnosis of IgG4-related disease involving the left orbital tissue was made. Results. In the rheumatology department of the Moscow Regional Research Clinical Institute of Childhood, the boy received pulse therapy with glucocorticoids. When trying to reduce the dose of glucocorticoids, exophthalmos and swelling of the eyelids on the left increased again. Cyclophosphamide therapy was ineffective. In addition to oral Prednisolone, Rituximab, a drug from the group of synthetic chimeric monoclonal antibodies, was prescribed. A stabilization of the process in the left orbit and an improvement in the general condition of the child ocurred. The duration of remission is 2 years. Discussion. IgG4-related disease is characterized by lymphoplasmacytic infiltration of tissues with a predominance of IgG4-positive cells and subsequent formation of fibrosis. Ophthalmological manifestations of IgG4-related disease are most often characterized by damage to the tissues of the orbit and lacrimal gland. Usually develops in middle-aged people; it is rare in pediatric practice. Conclusion. Patients with IgG4-related disease can be encountered in the practice of a rheumatologist, pediatrician and ophthalmologist. If diagnosis and treatment are not urgent, the disease is prone to progression, which leads to disability of the patient. The main treatment method is long-term use of glucocorticoids. In case of steroid resistance or steroid dependence, early use of immunosuppressive drugs or monoclonal antibodies could be considered. Key words: immunoglobulin G4-related disease, autoimmune orbital myositis, pediatric rheumatology, immunosuppressive therapy

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.

Common Characteristics of Sinonasal Inflammation Associated with IgG4-Related Disease and Other Chronic Inflammatory Diseases: A Retrospective Observational Study

Plain Language SummaryImmunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4 levels and tissue IgG4-positive cells. A part of IgG4-RD patients has sinonasal lesions. Because other inflammatory diseases also have features common to IgG4-RD, accurate knowledge of IgG4-RD is required. However, very little is known about IgG4-related rhinosinusitis. This study retrospectively analyzed clinicopathological features of IgG4-related rhinosinusitis and compared IgG4-related rhinosinusitis with other inflammatory diseases. Seven patients with sinonasal lesions and high serum IgG4 levels were retrospectively reviewed. Six of 7 patients were diagnosed with IgG4-RD, while one was diagnosed with granulomatosis with polyangiitis (GPA). In the 6 patients with IgG4-RD, intranasal findings showed nasal polyps in 3 patients (50%) and computed tomography showed ethmoid sinus involvement in 5 patients (83%), which shared common features with eosinophilic sinusitis (ECRS). However, no patients showed histopathological eosinophil infiltration. Although the patient with GPA revealed tissue infiltration of IgG4-positive cells in the nasal biopsy, the patient also had saddle nose and positivity of myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA), which indicated GPA. We diagnosed the patient with GPA, which is a known mimicker of IgG4-RD. In this study, the patients with IgG4-related rhinosinusitis had clinical and pathological characteristics similar to those of ECRS and GPA. IgG4-related rhinosinusitis should be diagnosed based on not only tissue infiltration of IgG4-positive cells but also systemic findings including nasal findings and serum ANCA levels. IgG4-RD should be ruled out in patients with eosinophilia without histopathological eosinophil infiltration.

Immunohistological analysis reveals IgG1-dominant immunophenotype of tubulointerstitial nephritis unassociated with IgG4-related diseases

PurposeTubulointerstitial nephritis (TIN) has various etiologies, including IgG4-related disease (IgG4-RD), autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and others. IgG4-positive plasma cell infiltration can occasionally be found in TIN unrelated to IgG4-RD. Therefore, there may be problems with usage of IgG4 immunostaining to differentiate between TIN with and TIN without IgG4-RD. This study aimed to compare the proportion of plasma cells that are positive for each IgG subclass and to clarify the predominant IgG subclass trends and clinical characteristics associated with IgG4-RD and non-IgG4-related interstitial nephritis.MethodsThe study enrolled 44 cases of TIN: 6 of IgG4-RD, 8 of autoimmune disease, 9 of AAV, and 21 of unknown disease group. In addition to clinical characteristics, IgG subclass composition of interstitial plasma cells was evaluated among 4 groups by immunohistochemistry.ResultsIgG1 was the predominant IgG subclass in TIN unrelated to IgG4-RD. In the IgG4-RD group, the IgG subclass rate was high in both IgG1 and IgG4. The rate of average IgG4-positive cells was significantly lower in the autoimmune disease group and unknown disease group compared with the IgG4-RD group.ConclusionThe present study revealed IgG1-dominant immune profiles of TIN unrelated to IgG4-RD. Further investigation is required to elucidate the clinicopathological differences between IgG1-dominant and IgG4-dominant groups in IgG4-RD.

Diagnostic challenges of the idiopathic plasmacytic lymphadenopathy (IPL) subtype of idiopathic multicentric Castleman disease (iMCD): Factors to differentiate from IgG4-related disease

Aims and methodsIdiopathic multicentric Castleman disease (iMCD) is currently considered to be classified into three clinical subtypes, including idiopathic plasmacytic lymphadenopathy (IPL), thrombocytopaenia, anasarca, fever, reticulin fibrosis/renal dysfunction, organomegaly (TAFRO)...

Eosinophilic Gastroenteritis with Ascites, Elevated Serum IgG4, and Hypereosinophilic Syndrome: A Manifestation of IgG4-related Disease?

A 76-year-old woman with persistent diarrhea was referred to our hospital. She had purpura, peripheral eosinophilia (18,177/μL), and an elevated serum IgG4 level (819 mg/dL). Abdominal computed tomography revealed massive ascites and bowel edema. A skin biopsy of the purpura revealed leukocytoclastic vasculitis with prominent eosinophilic infiltration. Biopsies of the gastrointestinal mucosa revealed dense eosinophilic infiltration, indicating eosinophilic gastroenteritis (EG) associated with the hypereosinophilic syndrome. The number of IgG4-positive cells increased in the duodenal mucosa; however, the diagnostic criteria for IgG4-related disease (IgG4-RD) were not met. Whether or not EG with ascites is a manifestation of IgG4-RD warrants further investigation.

The assessment of 18F-FDG PET/CT in IgG4-related disease: Case report and review of the literature

Immunoglobulin G4-related disease (IgG4-RD) is easily misdiagnosed. We report a case of IgG4-RD, whose main complaint was swollen eyelids, revealed by 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) and confirmed by pathological analysis from the submaxillary nodes. A 49-year-old woman complained about a bilateral swollen eyelid with blurred vision for 2 years. An enlarged submandibular lymph node was found during a physical examination. Head-enhanced magnetic resonance imaging (MRI) showed that the nasopharyngeal soft tissues were thickened, and the bilateral cervical lymph nodes were enlarged. A nasopharyngoscopy and tissue biopsy indicated chronic inflammation. 18F-FDG PET/CT was taken to eliminate malignant tumor metastasis, and the results suggest autoimmune disease. A biopsy of submandibular lymphatic nodes was taken, and the immunohistochemical staining showed IgG4-positive cells. Finally, IgG4-RD was diagnosed with elevated serum IgG4. The diagnosis of IgG4-RD is based on a comprehensive judgment of clinical symptoms, serum IgG4 levels, imaging studies, and pathological evidence. Ophthalmologists should be aware of the general conditions of patients who complain of unexplained ocular swelling, and 18F-FDG PEC/CT is strongly recommended. Compared with histopathologic examination, 18F-FDG PEC/CT can display changes in morphology and metabolism in involved organs and is noninvasive. It can be helpful in detecting, diagnosing, characterizing, and monitoring the response of the IgG4-RD.

Immunoglobulin G4-Related Hypertrophic Pachymeningitis Presenting with Multiple Lower Cranial Nerve Palsies

Immunoglobulin G4-related disease (IgG4-RD) is a multi-organ condition that infrequently exhibits neurological involvement. Here, we describe a case of IgG4-related hypertrophic pachymeningitis with multiple lower cranial nerve palsies. A 65-year-old man presented with a 5-month history of hoarseness and dysphagia. A neurologic examination revealed multiple lower cranial nerve palsies. Brain magnetic resonance imaging indicated diffuse dural involvement along the left tentorium and temporal fossa. Serum IgG and IgG4 levels were found to be elevated. Ethmoid polyp biopsy revealed chronic inflammation with moderate lymphoplasmacytic and some eosinophilic infiltration. Up to 60 IgG4-positive cells were observed per high-power field, and the measured IgG4/IgG ratio was approximately 10% to 20%. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography indicated abnormally high FDG uptake in the left posterior fossa, tentorium, and left temporal fossa, with additional involvement of the lung, iliac artery, and renal artery. Based on these findings, we diagnosed the patient with IgG4-related hypertrophic pachymeningitis and successfully treated the condition with steroids and rituximab. IgG4-RD should be differentiated from distinct conditions presenting with multiple cranial nerve palsies accompanied by pachymeningitis.

A rare case of inflammatory myofibroblast tumor of the stomach successfully treated by inverted laparoscopic and endoscopic cooperative surgery

BackgroundAn Inflammatory myofibroblastic tumor (IMT) is a rare intermediate malignancy characterized by myofibroblast proliferation and inflammatory cell infiltration. Various organs are the primary sites of origin. However, primary tumors originating in the stomach tend to be extremely rare, making the diagnosis difficult. Herein, we present a case of IMT originating in the stomach that was effectively managed using inverted laparoscopic endoscopic cooperative surgery (LECS).Case presentationA 47-year-old male who was admitted to the hospital because of a submucosal tumor that was discovered during upper gastrointestinal endoscopy. The diameter of the tumor was approximately 20 mm. A KIT-negative gastrointestinal stromal tumor was suspected based on the biopsy findings. Therefore, partial resection of the stomach was performed using inverted laparoscopic and endoscopic cooperative surgery. Histopathological examination revealed collagen fiber proliferation from the submucosal layer to the muscular layer, accompanied by infiltration of spindle-shaped cells, lymphocytes, and numerous inflammatory cells. Immunohistochemistry results were positive for SMA and negative for CD34, desmin, and c-kit. IgG4-positive cells were observed with an IgG4/IgG ratio > 50%, and specific nuclei were positive for ALK. Therefore, IMT was diagnosed. This condition may be difficult to diagnose both before and after surgery because of its rarity and submucosal tumor-like morphology.ConclusionWhen a submucosal tumor originating in the stomach is observed, IMT should be considered. Partial resection of the stomach with LECS and immunohistochemical diagnosis may be useful.

Single-cell mass cytometric analysis of peripheral immunity and multiplex plasma marker profiling of non-small cell lung cancer patients receiving PD-1 targeting immune checkpoint inhibitors in comparison with platinum-based chemotherapy.

The effect of platinum-based chemotherapy (Chem.) and second- or multiple- line immune checkpoint PD-1 blocking therapy by Nivolumab or Pembrolizumab (ICI) was assayed in the peripheral blood of non-small cell lung cancer (NSCLC) patients. Flow cytometry was used to detect NSCLC-related antigen binding IgG antibodies. The Luminex MagPix multiplex bead-based cytokine/chemokine detecting system was used to quantitatively measure 17 soluble markers in the plasma samples. Single-cell mass cytometry was applied for the immunophenotyping of peripheral leukocytes. The incubation of patient derived plasma with human NSCLC tumor cell lines, such as A549, H1975, and H1650, detected NSCLC-specific antibodies reaching a maximum of up to 32% reactive IgG-positive NSCLC cells. The following markers were detected in significantly higher concentration in the plasma of Chem. group versus healthy non-smoker and smoker controls: BTLA, CD27, CD28, CD40, CD80, CD86, GITRL, ICOS, LAG-3, PD-1, PD-L1, and TLR-2. The following markers were detected in significantly higher concentration in the plasma of ICI group versus healthy non-smoker and smoker controls: CD27, CD28, CD40, GITRL, LAG-3, PD-1, PD-L1, and TLR-2. We showed the induction of CD69 and IL-2R on CD4+ CD25+ T-cells upon chemotherapy; the exhaustion of one CD8+ T-cell population was detected by the loss of CD127 and a decrease in CD27. CD19+CD20+, CD79B+, or activated B-cell subtypes showed CD69 increase and downregulation of BTLA, CD27, and IL-2R in NSCLC patients following chemotherapy or ICI. Peripheral immunophenotype caused by chemotherapy or PD-1 blocking was shown in the context of advanced NSCLC.

The role of IgG4-positive plasma cell population in classic Hodgkin lymphoma.

The effect of IgG4, which constitutes the least of the IgG subclasses, on the pathogenesis and prognosis of lymphoma or solid tumors is one of the research topics of interest in recent years. The role of IgG4, which has been reported to suppress antitumor immunity, in classic Hodgkin's lymphoma (cHL), which is recognized by its pathognomonic microenvironment, is not yet clearly known.The aim of this study was to determine IgG4-positive plasma cell density in the cHL microenvironment and to compare it with histopathological and clinical parameters. In addition, the role of the increase in IgG4-positive cells in the development of relapse after treatment was also investigated.A retrospective cross-sectional study.Ninety-four patients with the initial diagnosis of cHL who had no comorbidity or no treatment history and forty-one reactive lymph nodes with follicular hyperplasia findings were included in the study. Three hot-spot areas were identified with reference to the IgG4 sections. Mean IgG4-positive plasmacyte counts and IgG4/IgG ratios were determined and compared with histopathological characteristics.The mean IgG4 + plasma cell count was 33.57 in cHL cases and 47.04 in the control group (p = 0.233). IgG4/IgG ratio was significantly higher in cHL compared with the control group (0.27 vs. 0.21, p = 0.021). The IgG4/IgG ratio was found to be higher in younger patients with classic Hodgkin lymphoma, with a low correlation (p = 0.028, r = - 0.226). There was no relationship with gender, lymph node location, histological subtype, EBV positivity and bone marrow infiltration. It was observed that IgG4/IgG ratio was higher in early-stage patients (p = 0.022). No significant IgG4 + cell increase was detected in the initial diagnosis and relapse slides of six patients who developed relapse after standard treatment, resulting in a cure.Novel therapeutic modalities targeting microenvironmental components have been reported to show dramatic effects, particularly in relapsed or refractory patients. Detailed characterization of the cHL inflammatory milieu will be useful for the identification of alternative targets. IgG4 subclass antibodies, which have been described to have anti-inflammatory effects, may have prognostic significance in a proportion of cHL patients.

Diagnosis of Neonatal Alloimmune Thrombocytopenia: Determination of the Specificity of Antiplatelet Alloantibodies in the Maternal Blood Plasma Using a Molecular and Genetic Method

Background: Thrombocytopenia occurs in 1-5 % of newborns (platelet count < 150 × 109/L). Low platelet count of 50 × 109/L leads to the hemorrhagic syndrome, with one of its causes being neonatal alloimmune thrombocytopenia resulting from incompatibility between the mother and the fetus with human platelet antigens (HPA) inherited from the father and absent in the mother, which leads to the formation of maternal antibodies. Anti-HPA-1a, anti-HPA-5b, anti-HPA-3a, and anti-HPA-3b antibodies are clinically significant as they destroy fetal/neonatal platelets causing severe complications (intracranial hemorrhage in 20 % of cases and prenatal or postnatal death in 10 % of cases). Adequate diagnosis is a key to a successful treatment approach, which largely depends on the thrombocytopenia cause. Objective: To determine the alloimmune nature of neonatal thrombocytopenia and the specificity of antibodies in the mother’s blood. Materials and methods: We studied blood samples of parents (21 pairs) of newborns with thrombocytopenia in Saint Petersburg, Russian Federation. We used flow cytometry to determine alloantibodies in the maternal plasma after incubation with paternal platelets and staining with Goat F(ab’)2 Anti-Human IgG-FITC and CD41-PE monoclonal antibodies. Allosensitization index was calculated as the percentage of IgG-positive cells to the number of cells fixing anti-CD41 antibodies. At the value of ≥ 15 %, antiplatelet alloantibodies were considered present in a sample. We used a molecular detection system of the FluoVista analyzer (Inno-Train, Germany) for genetic testing with allele-specific primers. Alleles of genes encoding the expression of HPA-1, HPA-2, HPA-3, HPA-4, HPA-5, HPA-6, HPA-9, and HPA-15 antigens were determined by a real-time polymerase chain reaction using a set of HPA-FluoGene reagents (Inno-Train, Germany). Genomic DNA was isolated using the DNA-sorb-B set (AmpliSens, Russian Federation). Results: We found that 8 of 21 (38 %) mothers had antibodies against paternal platelets. During genotyping in mother/father pairs, incompatible combinations of platelet antigens were revealed: HPA-1b/HPA-1a in 9 pairs (HPA-1a antigen absent on the maternal platelets and present on the paternal platelets), of which 5 mothers (55%) had antibodies with a probable specificity to anti-HPA-1a; HPA-1a/HPA-1b incompatibility in 4 pairs, with 2 (50 %) mothers having antibodies with an anti-HPA-1b specificity. HPA-3a/HPA-3b incompatibility was observed in 4 pairs, with antibodies (probably anti-HPA3b) in 1 mother (25%). HPA-2a/HPA-2b, HPA-5a/HPA-5b, HPA-15a/HPA-15b, HPA-15b/HPA-15a incompatibilities were detected (1 case each in 21 pairs), with no antibodies found in mothers. The probable specificity of the antibodies was distributed as follows: 62 % for anti-HPA-1a, 25% for anti-HPA-1b, and 13 % for anti-HPA-3a. Conclusions: We confirmed the immune nature of neonatal thrombocytopenia and determined the probable specificity of maternal alloantibodies in 8 of 21 cases.

Frequency, clinical picture, diagnosis, and differential diagnosis of the pathology of the digestive tract (esophagus, stomach, and bowel) in IgG4-related disease (autoimmune pancreatitis)

Despite the publication of European guidelines for the diagnosis and treatment of IgG4-related disease (IgG4-RD), this problem is very complicated from a practical point of view. There are many publications about autoimmune pancreatitis and liver and biliary tract lesions in IgG4-RD, but the data on the digestive tract lesions are not sufficient. Gastrointestinal manifestations of IgG4-RD are considered to be rare or very rare.
 IgG4-RD presenting as esophageal lesions is rare condition. Only single clinical cases are available. I. Obiorah et al. reported the highest number of cases of IgG4-related esophagitis (8 cases). Interestingly, 7/8 cases reported by I. Obiorah et al. were males (age range: 18 to 79 years), and most patients had dysphagia as the most prominent symptom, with erosions and strictures at endoscopy. Histologically, all patients had a lymphoplasmacytic infiltrate and storiform fibrosis, while obliterative phlebitis was observed in 3/8 patients. Hence, 2 of the 3 major histological “Boston criteria” of IgG4-RD were fulfilled in all patients. Besides, all patients had at least 50 IgG4-positive cells per HPF (range: 50–110), and IgG4/IgG ratios of at least 50% (range: 50–90%). Of I. Obiorah’s patients, s-IgG4 had only been measured in three — all of whom had values in the normal range. Esophageal strictures were identified in three patients, two patients had achalasia.
 Based on K. Notohara’s series and the other published cases, it can be concluded that gastric IgG4-RD often (but not always) seems to be clinically asymptomatic, that s-IgG4 is elevated in a considerable number of cases, and histologically, that at least two of the Boston criteria often are found. The recommended cut-off of 50 IgG4-positive cells and IgG4/IgG ratios of >40% was often fulfilled in the reported cases of IgG4-RD.
 There are few reports of IgG4-RD involving the duodenum, duodenal papilla, ileum with small bowel obstruction caused by pseudotumor or sclerosing disease of the small bowel with luminal narrowing.
 There are case reports of IgG4-RD with lesion of ileocecal area with an obstructing ileocecal mass and appendix, mimicking Crohn’s disease, appendicitis or appendiceal tumor. IgG4-related inflammatory bowel disease may — rarely — also be one of manifestations of IgG4-RD.
 Treatment should be conducted in accordance with European guidelines.

Urticaria with Immunoglobulin G4-Related Disease: An Association or Coincidence?

Immunoglobulin (Ig) G4-related disease is a recently described fibro-inflammatory disease with diverse clinical manifestations but consistent and characteristic histopathological features across multiple organ systems and skin, leading to tissue sclerosis and ultimately organ failure if not treated adequately. Here, we report a case of 56-year-old male patient presenting with urticarial lesions and generalized itching for 4 months. Routine investigations showed elevated 24-h urine protein, absolute eosinophil count, serum IgE, reversed albumin: globulin ratio, and “M” spike on serum electrophoresis. Renal biopsy showed storiform fibrosis, diffuse dense inflammatory cells (plasma cells and eosinophils), and IgG4-positive cells on immunohistochemistry which was histologically highly suggestive of IgG4-related chronic tubulointerstitial nephritis. Quick response was seen with oral corticosteroids.

IgG4-related disease with kidney and lymph nodes involvement: a case-based review.

IgG4-related disease (IgG4-RD), a rare immune-mediated chronic fibro-inflammatory condition, has various initial symptoms, thus posing diagnostic and therapeutic challenges. Here, we report a case of IgG4-RD in a 35-year-old man with initial clinical symptoms of facial edema and recent onset of proteinuria. It took more than 1year from the onset of clinical symptoms to diagnosis. Pathological examination of renal biopsy revealed significant renal interstitial lymphoid tissue hyperplasia simulating growth pattern of lymphoma. Immunohistochemical (IHC) staining results showed that CD4 + T lymphocyte hyperplasia was dominant. There was no significant deletion of CD2/CD3/CD5/CD7. No monoclone was detected in TCR gene rearrangement. IHC staining showed that the number of IgG4-positive cells was greater than 100/HPF. The ratio of IgG4/IgG was greater than 40%. Combined with clinically examinations, IgG4-related tubulointerstitial nephritis was considered. Further cervical lymph node biopsy results suggested IgG4-related lymphadenopathy. He received methylprednisolone 40mg/day intravenously for 10days, leading to normal results of laboratory tests and clinical manifestations. The patient had a good prognosis without recurrence during 14months of follow-up. This case report can be used as a reference for early diagnosis and treatment of such patients in the future.

Breast MALT Lymphoma: A Clinical, Histomorphologic, and Immunophenotypic Evaluation.

Introduction. Primary breast extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is rare and understudied. Embryonically, mammary glands are developed as specialized skin appendages. It is possible that overlapping features exist between breast MALT lymphoma and primary cutaneous marginal zone lymphoma. Methods. We studied 5 primary and 6 secondary breast MALT lymphomas diagnosed in our institution during a 20-year period. Clinical and pathologic features of these lymphomas were analyzed and compared. Results. Most primary and secondary breast MALT lymphomas had similar clinical presentations as unilateral breast lesions without axillary lymphadenopathy. However, primary lymphomas tended to be diagnosed in older patients (median: 77 years old) than secondary lymphomas (median: 60 years old). Thyroid abnormality was a common finding in both primary (3/5) and secondary (5/6) lymphomas. Hashimoto's thyroiditis was diagnosed in one primary lymphoma. No distinct histopathologic findings were found in primary lymphomas. Features for primary cutaneous marginal zone lymphoma, including overexpression of IgG and IgG4 and high IgG4/IgG ratio, were absent in all primary but present in one secondary lymphoma with cutaneous origin. This secondary lymphoma also had expansion of CD30-positive cells. Conclusion. Primary breast MALT lymphoma does not share the distinctive features of primary cutaneous marginal zone lymphoma that set it apart from other extranodal marginal zone lymphomas. Having increased IgG- and IgG4-positive cells with a high IgG/IgG4 ratio in breast MALT lymphoma may indicate cutaneous origin. CD30 overexpression may be a feature seen in marginal zone lymphoma of cutaneous origin, which needs further studies to prove.

A rare case of Riedel's thyroiditis: Immunoglobulin G4-related thyroid disease

Abstract Introduction Riedel's thyroiditis is a rare thyroiditis in which normal thyroid tissue is replaced by dense fibrous connective tissue. Its etiology is not fully known. An autoimmune process is thought to exist. In this disease group, lymphoplasmocytic tissue infiltration, mostly consisting of IgG4 (+) plasma cells and small lymphocytes, is seen accompanying fibrosis. In our case, we presented a very rare case of Reidel's thyroiditis. Clinical Case We report the case of a 46-year-old woman who came to the general surgery department with an enlargement at the base of her neck. Among the patient's complaints were dysphonia, a feeling of pressure and pain in the neck. She had no history of thyroid disease. Laboratory findings; TSH 0.06 uIU/ml (0.27–4.2), fT3 2.69 pg/mL (2.3–4.5), fT4 1.81 ng/dl (0.93–1.70), crp 73.6 mg/l (0.0–5.0), sedimentation 90 mm/h (0–20), leukocytes 11.74 10^3/ul (4.49–12.68), absolute neutrophil count 9.22 10 ^3/ul (1.9–7.9). Trucut biopsy was performed with the preliminary diagnosis of malignancy due to the history of a mass growing in a short time on the neck of the patient. Pathology result; “Intense fibrosis increase, severe lymphoplasmacytic cell infiltration rich in IgG4 positive cells. Thyroid follicle epithelial cells with ck7, panck, pax8, thyroglobulin, ttf1 positive and cea, ck20, alk negative Intense plasma cells with CD38 have polyclonal staining with kappa and lambda, and IgG4/IgG ratio > 50%. In the background, cd3, pax5 and bcl2 and T cell-rich reactive inflammatory cells are accompanied. Obliterative vascular structures were noted in rust and elastic histochemical stains, and storiform fibrosis was observed in places on the ground. When histopathological and immunohistochemical findings are evaluated together, it is primarily compatible with IgG4-related disease/reidel thyroiditis.'' She was then referred to the endocrinology department. The serum IgG4 level was found to be above normal. She was started on steroid treatment with 64 mg daily methylprednisolone. A weekly control plan was made. In these controls, the steroid dose was gradually reduced. In the follow-up one week later, it was observed that the patient's CRP and sedimentation returned to normal values. There was also a decrease in enlargement in the neck area. In the third month of the treatment, the patient didn't want to continue the treatment. She did not visit our clinic for the next 3 months. Then, she came for the control after three months without treatment. Biochemistry and thyroid function tests were normal. The swelling in the neck area of the patient was completely gone. Conclusion Reidel's thyroiditis is a very rare disease with publications on the basis of case reports in the literature. Therefore, there are no broad-spectrum clinical studies. Clarity on treatment approaches was also not provided. We also benefited from case reports while managing our patient's treatment. We believe that our case will contribute to the literature for the same purpose.