The histological diagnosis of IgG4‐related disease on small biopsies: challenges and pitfalls

Abstract

Aims The pathological diagnosis of IgG4‐related disease (IgG4‐RD) relies on histology, IgG4‐positive cells, and an increased IgG4/IgG ratio. Small biopsies from patients with a presumptive diagnosis of IgG4‐RD often fail to meet consensus histological criteria. The aims of this study were to evaluate consecutive small biopsies from patients with a presumptive diagnosis of IgG4‐RD, and to assess the significance of the pathological findings. Methods and results We evaluated 55 small biopsies from patients with a presumptive diagnosis of IgG4‐RD. The retrospective cohort comprised 71 patients with IgG4‐RD and 57 mimics. We performed immunohistochemistry (IHC) and in‐situ hybridisation (ISH) for IgG4 and IgG. Twenty‐six patients from the prospective cohort met the histological criteria for IgG4‐RD (definite); 29 patients lacked one or more pathological features (borderline). Twenty biopsies (36%) lacked both storiform fibrosis and obliterative phlebitis, and nine (16%) lacked an increase in the number of IgG4‐positive plasma cells. Ninety‐three per cent of patients showed an IgG4/total IgG ratio of >40% (>30% by ISH). There were no differences in the incidence of multiorgan disease (P = 0.9), serum IgG4 levels (P = 0.6) and response to therapy between the definite and borderline groups. A strong correlation (Pearson 0.77) between the IHC and ISH platforms was noted with regard to the IgG4/total IgG ratio. Conclusion Patients with a presumptive diagnosis of IgG4‐RD but lacking the characteristic pathological features of this disease appear to be clinically similar to those who meet the current pathological criteria. An elevated IgG4/total IgG ratio is the most sensitive pathological feature, and ISH provides a robust quantification platform. We recommend evaluating tumefactive lymphoplasmacytic infiltrates with an increased IgG4/IgG ratio, regardless of histological features, for IgG4‐RD.

IgG4‐positive plasma cells in Hashimoto thyroiditis: IgG4‐related disease or inflammation‐related IgG4‐positivity?

“…The patchy distribution of IgG4 positive cells in the tissue causes the challenge for the analysis (34). Importantly, HPF adjustment is needed to be able to compare the results of various studies (34).…”

“…The patchy distribution of IgG4 positive cells in the tissue causes the challenge for the analysis (34). Importantly, HPF adjustment is needed to be able to compare the results of various studies (34). In addition, the non‐specific presence of IgG4‐positive cells in various conditions such as inflammation and lymphoproliferative disorders was reported (10‐15, 34) and the presence of both IgG4‐positive cells and at least two histopathological features is required (32).…”

“…Importantly, HPF adjustment is needed to be able to compare the results of various studies (34). In addition, the non‐specific presence of IgG4‐positive cells in various conditions such as inflammation and lymphoproliferative disorders was reported (10‐15, 34) and the presence of both IgG4‐positive cells and at least two histopathological features is required (32). IgG4‐RD histopathological features are viewed non‐specific when individually present, but they possess collectively a strong evidence (32, 35).…”

Retroperitoneal Fibrosis and its Differential Diagnoses: The Role of Radiological Imaging

“…B. Cristian et al postulieren, dass bildmorphologische Verfahren in ihrer Genauigkeit nicht ausreichen, eine maligne Genese der RPF auszuschließen [6]. Andere Autoren berichten Gegensätzliches und präsentieren signifikante Zusammenhänge zwischen bildmorphologischen Kriterien (Ausdehnung oberhalb der Nierenstilgefäße, retroperitoneale Ausbreitung mit Abhebung der Bauchaorta, zusätzlicher Nachweis vergrößerter Lymphknoten) und funktionellen Parametern (sehr hohe Tracer-Anreicherung bei atypischer Verteilung in der FDG-PET/CT) als Kriterien für eine maligne Genese der RPF [3,7,8]. Es bleibt also unklar, ob die histopathologische Sicherung in jedem Fall nötig ist; bei atypischer Lokalisation, klinischen oder diagnostischen Hinweisen auf eine maligne Genese und/oder bei fehlendem Ansprechen der Fibrose auf eine medikamentöse Therapie sollte die Gewinnung einer Histologie jedoch dringend angestrebt werden.…”

Inflammatory Myofibroblastic Tumour of the Submandibular Gland

“…Although they occur primarily in the lung and orbits, they have been reported to occur in various tissues and organs throughout the body [1]. IMTs provide a diagnostic challenge as biopsies tend to be inconclusive and a diagnostic tissue specimen is required for histological confirmation [2]. Almost any area can be affected by IMTs, but they are most commonly found in the lung and orbits, with head and neck IMTs only representing approximately 14-18% of all cases.…”