A Case of IgG4-related Disease With Bone Marrow Involvement: Bone Marrow Findings and Flow Cytometric Immunophenotyping of Plasma Cells

IgG4-related disease (IgG4-RD) is a multi-organ chronic inflammatory process caused by infiltration of IgG4-positive plasma cells in one or more organs. Intracranial involvement has only recently become better recognized. Our case series adds to the growing literature on the varying presentations of intracranial IgG4 by describing the clinical and imaging findings of three patients who presented to our institution with intracranial involvement. Our first patient presented with a mass-forming IgG4 pachymeningitis mimicking a sphenoid wing meningioma, which is to our knowledge the largest mass-forming pachymeningitis published in the literature. Our second case depicts another presentation of extensive IgG4 pachymeningitis involving both cavernous sinuses and surrounding Meckel’s caves. The third case describes a patient with presumed lymphocytic hypophysitis, which was later determined to be IgG4-related hypophysitis with concomitant pachymeningitis and perineural spread along the optic nerves. The delayed diagnoses in our cases illustrates the diagnostic challenge that clinicians face in differentiating intracranial IgG4-RD from other infiltrative diseases such as sarcoidosis, granulomatous disease, tuberculosis and lymphoma. Earlier consideration of IgG4-related hypophysitis and hypertrophic pachymeningitis in the differential diagnosis can prevent significant morbidity including unnecessary surgical intervention and organ failure secondary to extensive fibrosis.

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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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P039 The diagnostic utility of bone marrow flow-cytometric immunophenotyping for the differential diagnosis of chronic idiopathic neutropenia from myelodysplastic syndromes

Leukemia Research ◽

10.1016/s0145-2126(09)70119-5 ◽

2009 ◽

Vol 33 ◽

pp. S80-S81

Author(s):

H. Papadaki ◽

H. Koutala ◽

M. Velegraki ◽

K. Pyrovolaki ◽

I. Mavroudi ◽

...

Keyword(s):

Bone Marrow ◽

Differential Diagnosis ◽

Myelodysplastic Syndromes ◽

Diagnostic Utility ◽

Flow Cytometric Immunophenotyping ◽

Flow Cytometric ◽

Chronic Idiopathic Neutropenia

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Follicular Lymphoma in Staging Bone Marrow Specimens: Correlation of Histologic Findings With the Results of Flow Cytometry Immunophenotypic Analysis

Archives of Pathology & Laboratory Medicine ◽

10.5858/2007-131-282-flisbm ◽

2007 ◽

Vol 131 (2) ◽

pp. 282-287

Author(s):

Dan Iancu ◽

Suyang Hao ◽

Pei Lin ◽

S. Keith Anderson ◽

Jeffrey L. Jorgensen ◽

...

Keyword(s):

Bone Marrow ◽

Follicular Lymphoma ◽

B Cell ◽

Bone Marrow Biopsy ◽

Cell Population ◽

Color Flow ◽

Flow Cytometric Immunophenotyping ◽

Histologic Evidence ◽

Flow Cytometric ◽

Biopsy Specimens

Abstract Context.—Bone marrow (BM) examination is part of the staging workup of lymphoma patients. Few studies have compared BM histologic findings with results of flow cytometric immunophenotyping analysis in follicular lymphoma (FL) patients. Objective.—To correlate histologic findings with immunophenotypic data in staging BM biopsy and aspiration specimens of FL patients. Design.—Bone marrow biopsy specimens of untreated FL patients were reviewed. Histologic findings were correlated with 3-color flow cytometric immunophenotyping results on corresponding BM aspirates. Results.—Bone marrow biopsy specimens (with or without aspirates) of 114 patients with histologic evidence of FL in BM were reviewed. There were 76 bilateral and 38 unilateral biopsies performed, resulting in 190 specimens: 187 involved by FL and 3 negative (in patients with a positive contralateral specimen). The extent of BM involvement was <5% in 32 (17.1%), ≥5% and ≤25% in 102 (54.6%), >25% and ≤50% in 27 (14.4%), and >50% in 26 (13.9%) specimens. The pattern of involvement was purely paratrabecular in 81 (43.3%), mixed in 80 (42.8%), and purely nonparatrabecular in 26 (13.9%). Immunophenotyping was only performed unilaterally, on BM aspirates of 92 patients, and was positive for a monoclonal B-cell population in 53 (57.6%) patients. Immunophenotyping was more often negative when biopsy specimens showed FL with a purely paratrabecular pattern. For comparison, we assessed 163 FL patients without histologic evidence of FL in BM also analyzed by flow cytometric immunophenotyping. A monoclonal B-cell population was identified in 5 patients (3%). Conclusions.—Our data suggest that 3-color flow cytometric immunophenotyping adds little information to the evaluation of staging BM specimens of FL patients.

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Ossifying fibrous epulis as an IgG4-related disease of the oral cavity: a case report and literature review

BMC Oral Health ◽

10.1186/s12903-022-02041-4 ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Yoshiko Ike ◽

Takahiro Shimizu ◽

Masaru Ogawa ◽

Takahiro Yamaguchi ◽

Keisuke Suzuki ◽

...

Keyword(s):

Oral Cavity ◽

Lymph Nodes ◽

Plasma Cells ◽

Maxillofacial Surgery ◽

The Body ◽

Pathological Diagnosis ◽

Cervical Lymph Nodes ◽

Related Disease ◽

Igg4 Related Disease ◽

Organ Manifestations

Abstract Background Fibrous sclerosing tumours and hypertrophic lesions in IgG4-related disease (IgG4-RD) are formed in various organs throughout the body, but disease in the oral region is not included among individual organ manifestations. We report a case of ossifying fibrous epulis that developed from the gingiva, as an instance of IgG4-RD. Case presentation A 60-year-old Japanese man visited the Department of Oral and Maxillofacial Surgery, Gunma University Hospital, with a chief complaint of swelling of the left mandibular gingiva. A 65 mm × 45 mm pedunculated tumour was observed. The bilateral submandibular lymph nodes were enlarged. The intraoperative pathological diagnosis of the enlarged cervical lymph nodes was inflammation. Based on this diagnosis, surgical excision was limited to the intraoral tumour, which was subsequently pathologically diagnosed as ossifying fibrous epulis. Histopathologically, the ossifying fibrous epulis exhibited increased levels of fibroblasts and collagen fibres, as well as infiltration by numerous plasma cells. The IgG4/IgG cell ratio was > 40%. Serologic analysis revealed hyper-IgG4-emia (> 135 mg/dL). The patient met the comprehensive clinical diagnosis criteria and the American College of Rheumatology and European League Against Rheumatism classification criteria for IgG4-RD. Based on these criteria, we diagnosed the ossifying fibrous epulis in our patient as an IgG4-related disease. A pathological diagnosis of IgG4-related lymphadenopathy was established for the cervical lymph nodes. Concomitant clinical findings were consistent with type II IgG4-related lymphadenopathy. Conclusions A routine serological test may be needed in cases with marked fibrous changes (such as epulis) in the oral cavity and plasma cells, accompanied by tumour formation, to determine the possibility of individual-organ manifestations of IgG4-related disease.

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Clinical and immunological variants of ANCA-associated systemic vasculitis: a look at the phenomenon of IgG4 overproduction. Literature review and own observations

Rheumatology Science and Practice ◽

10.47360/1995-4484-2020-550-559 ◽

2020 ◽

Vol 58 (5) ◽

pp. 550-559

Author(s):

T. V. Beketova ◽

N. V. Kokosadze

Keyword(s):

Clinical Case ◽

Plasma Cells ◽

Systemic Vasculitis ◽

Clinical Manifestations ◽

Definite Diagnosis ◽

Related Disease ◽

Epitope Specificity ◽

Igg4 Related Disease ◽

Choice Of Treatment ◽

Combined Data

Systemic vasculitis (SV) associated with anti-neutrophilic cytoplasmic antibodies is a multifactorial process characterized by the variability of the epitope specificity of anti-neutrophilic cytoplasmic antibodies and the diversity of clinical phenotypes of the disease. In recent years, there has been an increasing interest in the combination of AAV and the phenomenon of IgG4 hyperproduction, which varies widely within AAV, from anti-neutrophilic cytoplasmic antibodies products of IgG4 subclass of undetermined significance, the presence of IgG4 positive plasma cells in the foci of immunoinflammatory lesions in patients with a definite diagnosis of AAV, to the typical clinical manifestations of an IgG4-related disease (IgG4-RD). We introduce own clinical case and analyze the combined data of the literature, which included 35 cases of a combination of AAV and IgG4-related pathology, indicating existing differences in the clinical manifestations of classical IgG4-RD and when combined with AAV. The currently accumulated data allows us to discuss the allocation of a specific clinical and immunological variant of AAV with IgG4 hyperproduction, characterized by a combination of clinical manifestations of AAV and clinical and / or histological signs of IgG4-related pathology. It is important to emphasize that the allocation of phenotypes of AAV in the future may be important for the personalized choice of treatment tactics for patients.

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Sudden Cardiac Death Due to Coronary Artery Involvement by IgG4-Related Disease: A Rare, Serious Complication of a Rare Disease

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2012-0614-cr ◽

2014 ◽

Vol 138 (6) ◽

pp. 833-836 ◽

Cited By ~ 31

Author(s):

Nimesh R. Patel ◽

Mary L. Anzalone ◽

L. Maximilian Buja ◽

M. Tarek Elghetany

Keyword(s):

Sudden Cardiac Death ◽

Coronary Arteries ◽

Cardiac Death ◽

Plasma Cells ◽

Severe Stenosis ◽

Immunoglobulin G4 ◽

Emergency Center ◽

Related Disease ◽

Igg4 Related Disease ◽

Systemic Disorder

Immunoglobulin G4–related disease (IgG4-RD) is a systemic disorder characterized by multiorgan fibrosis with IgG4-producing plasma cells, increased IgG4 serum concentration, and responsiveness to steroid therapy. Involvement of the pancreas, salivary glands, orbit, aorta, and other sites has been well documented in the literature; however, there have been limited reports of cases involving the coronary arteries. We report the case of a 53-year-old Hispanic man who was brought to the emergency center and diagnosed with sudden cardiac death. Autopsy was subsequently performed, revealing multiorgan involvement by IgG4-RD, including involvement of the coronary arteries. The inflammation and fibrosis, in combination with concomitant atherosclerotic disease, resulted in severe stenosis of the coronary arteries. Two of the coronary arteries were further occluded by thrombosis. These factors led to cardiac hypoperfusion, myocardial infarction and, ultimately, sudden cardiac death. Fatal involvement of the coronary arteries has not been previously reported, raising a new concern for a severe complication of IgG4-RD.

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