Unilateral sclerosing dacryoadenitis
Figure 1-1. A 27-year-old female, otherwise well, presented with 4 weeks increasing left upper lid swelling with mild ache, and a hard tender mass in the left lacrimal gland.
Figure 1-2. CT scans show a grossly enlarged lacrimal gland with flattening of the globe.
Figure 1-3. MRI shows a discrete lacrimal gland lesion, which enhances with gadolinium.
Figure 1-4. Biopsy showed a hard, pale mass in the lacrimal gland, which on H and E section on low power, showed masses of lymphoplasmacytic infiltrate separated by bands of fibrosis.
Figure 1-5. On higher power, the lymphoplasmacytic infiltrate also separated portions of relatively normal glandular structures with some reactive follicle formation.
Figure 1-6. Immunohistochemical staining for CD20+ lymphocytes showed many within areas of lymphoplasmacytic infiltrate and follicle formation.
Figure 1-7. Immunostaining for CD3, a T-cell marker, shows numerous T-cells.
Figure 1-8. Immunostaining for IgG4 shows large numbers of IgG4+ plasma cells up to 96/high power field.
Figure 1-9. Immunostaining for IgG shows smaller numbers of IgG+ plasma cells (but more diffuse background staining, of no significance) and a ratio of IgG4+/IgG+ plasma cells of 137%. Serum IgG4 levels were normal. CT chest, abdomen and pelvis were normal. She responded well to a course of oral steroids.
Bilateral lacrimal and salivary gland disease
Figure 2-1. A 58-year-old man presented in late 2012. A year before, an enlarged left submandibular gland was removed and diagnosed as bilateral lacrimal and salivary gland disease (formerly known as Mickulicz disease). An enlarged right submandibular gland was removed 3 months before presentation. There was a long history of rhinosinusitis, endoscopic sinus surgery a year earlier, and a 3-year history of asthma. For 9 months he had noted swelling in both upper lids and mild ptosis. The lacrimal glands were palpably enlarged and firm.
Figure 2-2. Both parotid glands were enlarged, the left more than right.
Figure 2-3. An axial CT scan showed bilateral, symmetrically enlarged lacrimal glands. Serum IgG4 levels were markedly elevated, and he had a mild eosinophilia and ESR of 29. Biopsy of one lacrimal gland showed firm, pale tissue, with atrophic gland, dense fibrosis and reactive lymphoid follicles, 90 IgG4+ plasma cells/hpf, and an IgG4+/IgG+ plasma cell ratio of 150%. Review of the salivary glands showed similar pathology. He was started on 40 mg of prednisolone with a good clinical response, but when reduced below 7.5 mg, symptoms recurred. Introducing Azathioprine with low-dose prednisolone got a good and well-maintained response.
Bilateral, asymmetric lacrimal gland and orbital fat disease, rhinosinusitis, and sclerosing cholangitis
Figure 3-1. A 41-year-old man presented mid 2009 with 5 months of swelling in the left lacrimal gland and chronic rhinosinusitis. He had recently developed grossly deranged liver function tests and was found to have autoimmune sclerosing cholangitis and a grossly elevated serum IgG4 levels.
Figure 3-2. Coronal and axial CT scans show pansinusitis and poorly defined enlarged lacrimal glands with an infiltrative process spilling over into the orbital fat. The second coronal CT scan shows possible enlargement of the infraorbital nerve. Biopsy of the left lacrimal gland showed chronic sclerosing dacryoadenitis with large numbers of IgG4+ plasma cells and a ratio of IgG4+/IgG+ plasma cells of 41%. He was treated with oral steroids, with improvement in his orbital and nasal symptoms and normalization of liver function tests, but relapse on tapering of the oral steroids, treated with Azathioprine and low dose steroids.
Mickulicz pattern evolved to extraocular muscle disease, enlarged infraorbital nerves, and sinus disease
Figure 4-1. A 37-year-old man presented in 1991 with bilateral lacrimal and submandibular gland enlargement.
Figure 4-2. An axial CT scan showed the enlarged lacrimal glands, which on biopsy showed reactive lymphoid hyperplasia. He responded to a short course of oral steroids and was lost to follow-up.
Figure 4-3. In 2001, he returned with 2–3 years of increasing bilateral proptosis and lid swelling.
Figure 4-4. CT scans now showed enlarged extraocular muscles, disease in the lacrimal glands and superior orbits, and definite enlargement of the infraorbital nerves and canals. Biopsies from the orbit showed reactive lymphoid hyperplasia again. He responded to oral steroids, but moved overseas and was again lost to follow-up. In 2007 these biopsies were reviewed, and he had IgG4+ plasma cells of 150/hpf and an IgG4+/IgG+ plasma cell ratio of 300%.
Lacrimal gland swelling, cervical lymphadenopathy, asthma, chronic rhinosinusitis, enlarged infraorbital nerves, developed diffuse large B-cell lymphoma and died from lymphoma
Figure 5-1. A 51-year-old man first presented in 1991 with a year of left lacrimal gland swelling, cervical lymphadenopathy, asthma, chronic sinusitis, and an urticarial skin rash. He had been diagnosed with Sjogren's disease, but had negative serology. Biopsy of the left lacrimal gland was diagnosed as reactive lymphoid hyperplasia. He responded well to oral steroids and chlorambucil.
Figure 5-2. CT scans showed lacrimal gland disease with some mild enlargement of some EOMs, rhinosinusitis and changes from previous sinus surgery, and grossly enlarged infraorbital nerves and canals on each side. He returned in 2008 with increasing bilateral proptosis. He was rebiopsied and found to have large numbers of IgG4+ plasma cells. He was treated with oral prednisolone and methotrexate with a good response. Two years later, he developed diffuse large B-cell lymphoma, and 18 months later, died from his disease.
Enlarged lacrimal glands and frontal and infraorbital nerves, cervical lymphadenopathy, enlarged parotid glands and submandibular glands, primary biliary cirrhosis, developed left perioptic nerve disease, on rebiopsy, marginal zone lymphoma of MALT type
Figure 6-1. A 52-year-old woman presented in 2008 with a 1-year history of bilateral lacrimal gland enlargement, cervical lymphadenopathy, and salivary gland enlargement. She had a history of primary biliary cirrhosis, and atypical Sjogren's syndrome with negative serology. MRI scans showed an enlarged left frontal nerve, which was biopsied and showed a dense lymphoplasmacytic infiltrate and features of IgG4-RD.
Figure 6-2. A sagittal CT scan showed the frontal nerve enlargement extending through the superior orbital fissure into the cavernous sinus. The left lacrimal gland and frontal nerve were biopsied. They showed reactive lymphoid hyperplasia with large numbers of IgG4+ plasma cells, a ratio of IgG4+/IgG+ plasma cells of 80%, and a markedly elevated serum IgG4 level. She was treated with low-dose prednisolone and hydroxychloroquine by her rheumatologist with minimal response.
Figure 6-3. Two years later, she developed worsening vision in her left eye, and a repeat MRI showed disease surrounding the optic nerve and extending through the superior orbital fissure into the cavernous sinus.
Figure 6-4. A coronal MRI showed more enlargement of the left frontal nerves than of the right, and enlargement of the left infraorbital nerve and canal. A rebiopsy showed transformation to marginal zone lymphoma of MALT type. She was treated with low-dose orbital irradiation with improvement in vision and proptosis.
Sclerosing orbital, lacrimal system and nasal disease, formerly known as Eosinophilic Angiocentric Fibrosis
Figure 7-1. A 25-year-old man presented in 2008 with 6 months of left epiphora and proptosis, with a lacrimal mucocele. There was a hard inferomedial orbital mass.
Figure 7-2. CT scans showed a large dense mass involving the inferomedial orbit compressing and displacing the globe. A biopsy diagnosed eosinophilic angiocentric fibrosis. He then underwent a DCR with repeat biopsy of the orbit and thickened nasal mucosa. There was dense fibrosis with large numbers of IgG4+ plasma cells and a mild increase in serum IgG4. He was commenced on oral steroids and methotrexate with stabilization of disease. Rituximab is being considered if his disease worsens.