IGSD is becoming a more recognized inflammatory disease that most frequently presents in older men and has been shown to involve the pancreas, thyroid,9
and pituitary gland,10
with rarely described presentation in the nasal cavity and paranasal sinuses.2,3
We report an unusual case of a middle-aged woman who presented with IGSD isolated to the sphenoid sinus.
IGSD is characterized histologically by extensive infiltration of IgG4+
plasma cells and T lymphocytes, associated with fibrosis. IgG4 is the least common of the IgG subclasses to be expressed, accounting for only 3–6% of total IgG in normal serum. Concerning diagnostic criteria, IgG4-related disease is diagnosed pathologically with certain histological and immunohistological findings. There are varying criteria for the diagnosis of IGSD; however, increased numbers of IgG4+
plasma cells are required for the diagnosis and in cases with >50 IgG4+
cells/hpf the reported specificity and sensitivity are 100%.1,12,13
The serum IgG4 titer can also be used to aid in diagnosis but is elevated in only 30% of patients with IGSD and therefore not necessary for diagnosis.12
cell ratio of >40% (normal = 3–6%) can also be used with high sensitivity and specificity, 86 and 96%, respectively. Histologically, it presents with a triad of lymphoplasmacytic infiltration, sclerosis, and obliterative phlebitis.1
Our patient's surgical pathology contained a dense plasmacytic infiltrate with >150 IgG4+
cells/hpf with acute and chronic inflammation and fibrosis throughout the tissue sample (), consistent with IGSD of the sphenoid sinuses. Moteki et al.
showed IgG4-bearing plasma cell infiltrations in the mucosal tissues of patients with sinusitis associated with IgG4-related disease. IgG4-bearing plasma infiltration was indistinguishable from the control group represented by patients with common chronic rhinosinusitis, who also had IgG4-bearing plasma cell infiltrations in their nasal mucosa.14
Thus, they caution that IGSD should be diagnosed with IgG4 serum levels. However, this new entity of extrapancreatic IGSD still has to be clearly defined and plasma serum levels of IgG4 is not a diagnostic criterion. Our patient had isolated sphenoid sinus involvement with low to normal levels of serum IgG4.
Extrapancreatic IGSD lymphadenopathy is commonly seen in up to 80% of patients with IGSD.15
Lymphadenopathy occasionally is the first presenting symptom and can be mistaken for lymphoma. Lymph nodes are generally smaller in IgG4-related disease with absent constitutional symptoms such as fever and weight loss. Although lymphadenopathy is highly prevalent in autoimmune pancreatitis our patient presented without associated lymphadenopathy when evaluated by head and neck CT and MRI.
We posit that recognition of IGSD is important clinically because it has been proven to be steroid sensitive, thus potentially obviating the need for surgical management. Glucocorticoids have become the standard therapy for autoimmune pancreatitis, but the indications, dose, and duration of therapy continue to remain controversial.16
For unresponsive or recurrent IGSD, rituximab and other disease-modifying antirheumatic drugs may prove to be more efficacious.17
Although our knowledge concerning treatment in extrapancreatic organs is lacking, there is evidence that glucocorticoid treatment improves nasal sinus opacification on CT findings.14
In this instance we did not institute preoperative oral steroid because we felt the most likely diagnosis was a lymphoproliferative disorder that would require postoperative oral steroids as a part of a multidrug therapy. In hindsight, oral steroids would be a logical and justified treatment option for patients presenting with paranasal IGSD. However, this should be weighed against the risks of steroid complications. Because of the patients history of allergic rhinitis and seasonal allergies and in light of her newly diagnosed IGSD, we elected to start her on fluticasone, a nasal corticosteroid spray. Oral steroids postoperatively could also be used and were considered. Because of resolution of opacification on postoperative imaging and patent sphenoidotomy seen on nasal endoscopy (
) an oral steroid was not instituted. Albeit rare, lymphoma has arisen in IgG4-related chronic sclerosing dacryoadenitis, indicating the need for close follow-up.1,4
This case study and literature review adds to the growing literature describing IGSD disease in the head and neck. More specifically, IGSD can be found in the paranasal sinuses with preliminary data showing local control with nasal topical corticosteroids.