Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
IgG4-Related Disease in the Head and Neck
Introduction
Background
IgG4-related disease (IgG4-RD) is a relatively recently recognized fibroinflammatory condition of unknown etiology characterized by elevated serum IgG4, plasmacytic infiltration, multifocal tumefactive fibrosis, and clinical improvement by steroid therapy.
The association between autoimmune (sclerosing) pancreatitis and elevated serum IgG4 was first described by Hamano et al. in 2001, but it wasn't until 2003 that the systemic nature of IgG4-RD was discovered. After the pancreas, the head and neck is thought to be the second most common site of involvement by IgG-RD. Recent years have been marked by a cascade of research implicating IgG4-RD in multiple previously established conditions. In the head and neck these include hypertrophic pachymeningitis (HP) in the skull base, Küttner tumor (2005), Mikulicz disease (2006), fibrous subtype of Hashimoto (2009), Riedel thyroiditis (2010), and a subset of idiopathic orbital inflammatory disease (2007).
Epidemiology
IgG4-RD was originally described in Japan, and 74% to 86.6% of all reported cases are Japanese. However, it has likely been underreported in the western world, with IgG4-RD now described in nearly all ethnic groups across all continents. A recent review of cases at a North American institution showed 80% to be of Caucasian ethnicity.
Including all subsites, IgG4-RD in the head and neck has an almost 1 : 1 gender ratio, which is in contrast to systemic manifestations of IgG4-RD that favor males with a reported ratio of 1.3 to 3.2 : 1. The average age at presentation is 60.4 years, although there are case reports of IgG4-RD in children.
The most common subsites within the head and neck are the salivary glands and the orbits. Discrepancy exists in the literature as to which is more common. One study reviewing 799 cases of systemic IgG4-RD found that salivary gland involvement was more common (40% vs. 29%), whereas another study reviewing 730 cases of IgG4-RD with only head and neck manifestations found that orbital involvement was more common (22% vs. 53%). Less common subsites in the head and neck include thyroid, dura, pituitary hypophysis, temporal bones, paranasal sinuses, cervical lymph nodes, and larynx ( Fig. 40.1 ).
Histopathology
Histologically, IgG4-RD is characterized by a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. It remains unclear whether IgG4-RD is of autoimmune, allergic, or other etiology and IgG4 plasma cells in tissue, the hallmark of the disease, may be pathogenic or simply a response to an unknown inflammatory process. Elevated serum IgG4 is often detected, but nearly 50% of biopsy proven and clinically active systemic IgG4-RD may have normal serum IgG4 levels. Two different diagnostic criteria have been proposed.
Boston Criteria
According to the international symposium on IgG4-RD in Boston (2011), two-thirds of histologic features are diagnostic of “highly suggestive of IgG4-RD.” With fewer criteria, “probable IgG4-RD” can still be diagnosed if other serologic or radiographic evidence of IgG4-RD are present. Exceptions for “highly suggestive” are made for dacryoadenitis (one-third of histologic features), and oral mucosa and lymph nodes (reliant on IgG4 cell number and ratio).
- 1.
Dense lymphoplasmacytic infiltrate
- 2.
Fibrosis, usually storiform in character
- 3.
Obliterative phlebitis
Japanese Criteria
According to the Japanese criteria (2012), characteristic diffuse or localized swelling or masses in single or multiple organs ( Table 40.1 ), in addition to both criteria, is diagnostic of “definite IgG4-RD.” Combined with only one criterion it is diagnostic of “possible IgG4-RD.”
- 1.
Elevated serum IgG4
- 2.
Marked lymphocyte and plasmacyte infiltration, fibrosis, and elevated IgG4/IgG cell ratio on histology
TABLE 40.1
Reported Manifestations of IgG4-Related Disease Throughout the Body
| Intracranial | Hypertrophic pachymeningitis |
| Hypophysitis | |
| Parenchymal disease | |
| Head and neck | Mikulicz disease |
| Küttner tumor | |
| Orbital inflammatory pseudotumor | |
| Riedel thyroiditis | |
| Fibrotic subtype Hashimoto thyroiditis | |
| Chest | Pulmonary pseudotumor |
| Interstitial pneumonia | |
| Pericarditis | |
| Fibrosing mediastinitis | |
| Inflammatory aortitis/dissection | |
| Abdomen/pelvis | Autoimmune pancreatitis |
| Sclerosing cholangitis | |
| Cholecystitis | |
| Retroperitoneal fibrosis | |
| Liver pseudotumor | |
| Tubulointerstitial nephritis | |
| Inflammatory aortitis/dissection | |
| Prostatitis | |
| Testicular involvement | |
| Other | Cutaneous pseudolymphoma |
| Lymphadenopathy |
Temporal Evolution: Overview
In general, IgG4-RD is characterized by relapsing-remitting, but slowly progressive, mass-like and fibrotic soft-tissue lesions, which can be focal or diffuse and typically are described as firm if palpable. The diagnosis is often delayed by months to years, likely due to the often-painless nature, relative sparing of glandular function, and lack of systemic symptoms until late in the disease. However, a minority of patients will present with fulminant disease at the outset. Once the abnormality is recognized, diagnostic delay is common, often arising from confusion with neoplastic processes due to the mass-like appearance of the lesion on imaging and clinical exam.
IgG4-RD characteristically exhibits rapid response to steroids and other immunosuppressive regimens, but this is not specific and should not be used to differentiate IgG4-RD from other pathologies. Although as many as 32% to 40% of cases will show relapse or treatment failure with initial therapy, full remission with medical treatment has been reported in up to 90% of cases. Despite this, surgery is common, either to treat local mass-effect or due to suspicion of neoplasm.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here
