A 35 year old man presents with fullness around his left eye. On examination, there is protosis . A CT scan shows a mass in the orbit, involving the lacrimal gland and the adjacent soft tissue and lateral rectus muscle. The mass is biopsied.
Figure 1-low power
Figure 2-higher power of figure 1
Figure 3-IgG4 immunohistochemistry stain.
1. What is the diagnosis?
2. What is the histological differential diagnosis?
3. What other investigations would you recommend in this case.
1. The diagnosis is IgG4-related sclerosing disease of the orbit.
2. There is quite a broad histological differential diagnosis, for orbital pathology that has a sclerosing and inflammatory components. The following differential merits consideration:
Vasculitis (sclerosing phase).
Adult onset xanthogranuloma.
Erdheim Chester disease.
End stage thyroid eye disease.
Metastatic tumours (especially breast carcinoma and carcinoids).
Sclerotic reaction around a primary lacrimal gland tumour.
Sclerotic reaction around a MALToma.
Extrameduallry myeloid tumour.
Reaction around a ruptured dermoid cyst.
Reactions to vascular hamartomas.
Reactions to implants.
3. A serum IgG4 level
IgG4 related sclerosing disease is often a multi-system, probable autoimmune process that shows a good response to steroids. Sites reported to be affected include, the pancreas, biliary tract, gall bladder, liver, salivary glands, retroperitoneum, kidney, breast, lung, thyroid, prostate, lymph nodes, orbit and lacrimal gland. Autoimmune pancreatitis is the prototypic lesion. Patients can have an elevated serum IgG4 level.
In the orbital cavity, the lacrimal gland and orbital soft tissues can be affected. It is likely that most cases of so called cases of idiopathic orbital inflammation or idiopathic sclerosing inflammation of the orbit or lacrimal gland represent IgG4 related sclerosing disease.
When it affects the lacrimal gland, the main features are acinar atrophy, interstitial lymphocytes and plasma cells, reactive lymphoid follicles and variable degrees of sclerosis, depending on the age of the lesion. Similar features are found in orbital soft tissue.
In this case, the biopsy features sclerosis with aggregates of plasma cells, lymphocytes and some eosinophils. Figure 3 shows most of the plasma cells express IgG4. The percentage of tissue plasma cells expressing IgG4 was around 80% in this case (when compared to the total number of IgG positive plasma cells).
Recently, 3 cases of B-cell non-Hodgkins lymphoma have been reported on a backdrop of IgG4 sclerosing disease of the orbit.
Cheuk W, Yuen HK, Chan AC, Shih LY, Kuo TT, Ma MW, Lo YF, Chan WK, Chan JK.Ocular adnexal lymphoma associated with IgG4+ chronic sclerosing dacryoadenitis: a previously undescribed complication of IgG4-related sclerosing disease. Am J Surg Pathol. 2008 Aug;32(8):1159-67
Takahira M, Kawano M, Zen Y, Minato H, Yamada K, Sugiyama K.IgG4-Related Chronic Sclerosing Dacryoadenitis. Arch Ophthalmol. 2007 Nov;125(11):1575-8.
Cheuk W, Yuen HK, Chan JK.Chronic sclerosing dacryoadenitis: part of the spectrum of IgG4-related Sclerosing disease? Am J Surg Pathol. 2007 Apr;31(4):643-5.