Deconstructing IgG4-related disease involvement of midline structures: Comparison to common mimickers.
OBJECTIVE
A series of destructive and tumefactive lesions of the midline structures have been recently added to the spectrum of IgG4-related disease (IgG4-RD). We examined the clinical, serological, endoscopic, radiological, and histological features that might be of utility in distinguishing IgG4-RD from other forms of inflammatory conditions with the potential to involve the sinonasal area and the oral cavity.


METHODS
We studied 11 consecutive patients with erosive and/or tumefactive lesions of the midline structures referred to our tertiary care center. All patients underwent serum IgG4 measurement, flow cytometry for circulating plasmablast counts, nasal endoscopy, radiological studies, and histological evaluation of tissue specimens. The histological studies included immunostaining studies to assess the number of IgG4 + plasma cells/HPF for calculation of the IgG4+/IgG + plasma cell ratio.


RESULTS
Five patients with granulomatosis with polyangiitis (GPA), three with cocaine-induced midline destructive lesions (CIMDL), and three with IgG4-RD were studied. We found no clinical, endoscopic, or radiological findings specific for IgG4-RD. Increased serum IgG4 and plasmablasts levels were not specific for IgG4-RD. Rather, all 11 patients had elevated blood plasmablast concentrations, and several patients with GPA and CIMDL had elevated serum IgG4 levels. Storiform fibrosis and an IgG4+/IgG + plasma cell ratio >20% on histological examination, however, were observed only in patients with IgG4-RD.


CONCLUSIONS
Histological examination of bioptic samples from the sinonasal area and oral cavity represents the mainstay for the diagnosis of IgG4-RD involvement of the midline structures.
a Unit of Medicine and Clinical Immunology, Ospedale San Raffaele , Milan , Italy.|b Unit of Medicine and Clinical Immunology, Università Vita-Salute San Raffaele , Milan , Italy.
Marco
M
Lanzillotta
a Unit of Medicine and Clinical Immunology, Ospedale San Raffaele , Milan , Italy.|b Unit of Medicine and Clinical Immunology, Università Vita-Salute San Raffaele , Milan , Italy.
Corrado
C
Campochiaro
b Unit of Medicine and Clinical Immunology, Università Vita-Salute San Raffaele , Milan , Italy.|c Department of Otorhinolaryngology , IRCCS San Raffaele Scientific Institute , Milan , Italy.
Matteo
M
Trimarchi
d Pathology Unit, IRCCS San Raffaele Scientific Institute , Milan , Italy.
Gianluigi
G
Arrigoni
e Neuroradiology Unit, IRCCS San Raffaele Scientific Institute , Milan , Italy.
Simonetta
S
Gerevini
f Immunohematology and Transfusion Medicine Unit , IRCCS San Raffaele Scientific Institute , Milan , Italy.
Raffaella
R
Milani
a Unit of Medicine and Clinical Immunology, Ospedale San Raffaele , Milan , Italy.
Enrica
E
Bozzolo
b Unit of Medicine and Clinical Immunology, Università Vita-Salute San Raffaele , Milan , Italy.|c Department of Otorhinolaryngology , IRCCS San Raffaele Scientific Institute , Milan , Italy.
Matteo
M
Biafora
b Unit of Medicine and Clinical Immunology, Università Vita-Salute San Raffaele , Milan , Italy.|e Neuroradiology Unit, IRCCS San Raffaele Scientific Institute , Milan , Italy.
Elena
E
Venturini
g San Raffaele Telethon Institute for Gene Therapy (TIGET) , Milan , Italy.|h Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute , Milan , Italy , and.
Maria Pia
MP
Cicalese
i Division of Rheumatology, Allergy, and Immunology , Massachusetts General Hospital, Harvard Medical School , Boston , MA , USA.
John H
JH
Stone
a Unit of Medicine and Clinical Immunology, Ospedale San Raffaele , Milan , Italy.|b Unit of Medicine and Clinical Immunology, Università Vita-Salute San Raffaele , Milan , Italy.
Maria Grazia
MG
Sabbadini
a Unit of Medicine and Clinical Immunology, Ospedale San Raffaele , Milan , Italy.|b Unit of Medicine and Clinical Immunology, Università Vita-Salute San Raffaele , Milan , Italy.
Emanuel
http://orcid.org/0000-0002-9192-4270
E
Della-Torre
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005434:Flow Cytometry; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007159:Immunologic Tests; D008297:Male; D008875:Middle Aged; D061270:Nasal Septal Perforation / Q000097:blood / Q000276:immunology* / Q000473:pathology; D010950:Plasma Cells / Q000276:immunology*; D055815:Young Adult
D007074:Immunoglobulin G
Cocaine; Granulomatosis with polyangiitis; IgG4; IgG4-related disease; Midline destructive lesion