IgG4-Related Midline Destructive Lesion: Expanding the spectrum of organ involvement in IgG4-related disease

Background/Purpose: Midline destructive lesion (MDL) is a fibroinflammatory condition involving the nose, paranasal sinuses, and palate with relentless erosion through contiguous facial structures. A variety of historical terms, including “lethal midline granuloma”, have been used to describe MDL. The characteristic lesion is an ulcerative process that occurs in the nose and palate associated with epithelium and cartilage loss, leading ultimately to functional deformity. MDL may occur in a variety of inflammatory, neoplastic, and infectious disorders, but the diagnosis remains elusive in a significant proportion of idiopathic cases. We report three patients with MDL whose cases were marked by clinical, serological, and histopathological features diagnostic of IgG4-related disease (IgG4-RD). Methods: We evaluated three patients with MDL involving the soft palate and uvula. Two patients also had nasal septal perforations. We investigated the clinical and radiological features of each case, performed flow cytometry on peripheral blood to determine the concentration of IgG4+ plasmablasts, and reviewed the histopathology, performing immunostaining for IgG and IgG4. Results: The three patients, one man and two women, were aged 54, 38, and 27, respectively. All three patients were heavy, current tobacco smokers. One patient had a remote history of intranasal cocaine use but had not used cocaine for six years before the onset of her palatal and nasal symptoms. Onset of symptoms was subacute in all patients and, in view of the extent of the tissue destruction, the lesions appeared (in retrospect) to have occurred with remarkably little symptomatology. The processes began as small ulcers in the soft palate that evolved slowly into palatal perforations. The onset and progression of nasal septal perforation was equally subacute and subclinical. Two patients had obtained prostheses to plug their soft palate defects, facilitate speech, and prevent nasal regurgitation of liquids and food. The third patient had remnants of food within her nasal cavity. Physical examination demonstrated a hypernasal speech quality and florid palatal and nasal septal lesions. The uvulae were absent in all three cases. There were no obvious sites of disease beyond the soft palate and nasal cavity, but diagnostic imaging is awaited presently in one patient. Infections, malignancies, and autoimmune disorders were excluded by extensive serological, microbiological, and histopathological examinations. The serum IgG4 concentrations were normal in all three patients (96, 119, and 11 mg/dL, respectively; normal < 121 mg/dL)(the third patient had been treated with rituximab). However, all three patients had substantial elevations of IgG4+ plasmablast in blood, with concentrations of 85,200/ml, 3835/ml, and 7351/ml, respectively (normal < 300/ml). Pathology in all three cases showed typical histopathological features of IgG4-RD: a diffuse lymphoplasmacytic infiltrate with an abundance of IgG4-positive plasma cells, a mild to moderate tissue eosinophilia, storiform fibrosis, and obliterative phlebitis. Conclusions: IgG4-RD is a cause of midline destructive lesions involving the soft palate, uvula, and nasal septum.