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Immunoglobulin G4–related dacryocystitis
CASE REPORT Immunoglobulin G4–related dacryocystitis Immunoglobulin G4 (IgG4)–related dacryocystitis is a rare condition characterized by elevated serum IgG4 levels and IgG4-positive lymphoplasmacytic infiltration in the lacrimal sac.1 In the periocular region, IgG4-positive lymphoplasmacyte infiltration commonly occurs in the lacrimal gland, extraocular muscles, orbital soft tissues, and the infraorbital nerve.1 Clinicopathologic characteristics of IgG4-related dacryocystitis are not fully understood. Herein, we report the case of a patient with IgG4related dacryocystitis.
CASE REPORT This retrospective observational case report was approved by the Institutional Review Board of Aichi Medical University Hospital (No. 2016-H206) and adhered to the tenets of the 1964 Declaration of Helsinki. Written informed consent for publication of this report was obtained from the patient. A 68-year-old man presented with a 3-year history of bilateral epiphora and right rhinostenosis. He also had a history of biopsy of hypertrophic prostate performed at other institution. Immunostaining for IgG4 demonstrated intensely stained IgG4-positive plasma cells with 450 IgG4 plasma cells/high-power field (HPF). The blood test result at that time indicated an elevated serum IgG4 level (548 mg/dL; normal o105 mg/dL). These findings
corresponded with the comprehensive diagnostic criteria (2011) for IgG4-related disease.2 Systemic examinations by a rheumatologist revealed no other autoimmune diseases. At the first examination at our institution, a mass was not palpable and the skin was not erythematous in the medial canthal area. Lacrimal irrigation and probing showed bilateral nasolacrimal duct obstruction. Nasal endoscopic examination demonstrated a polyp in the right nasal cavity (Fig. 1A). Computed tomography images revealed an enlarged lacrimal sac and soft tissue involvement on both sides in the nasal cavity and the maxillary and ethmoid sinuses (Fig. 1B, C). Hematological analysis indicated an elevated serum IgG4 level (478 mg/dL). Bilateral endoscopic endonasal dacryocystorhinostomy (DCR) and sinus surgery were performed under general anaesthesia. During DCR, the anterior and posterior flaps were created from the lacrimal sac, the anterior flap was removed and was sent for histopathologic examination, whereas the posterior flap remained on the posterior osteotomy site. The nasal polyp was removed and was also sent for histopathologic examination. Histopathologic examinations of the bilateral lacrimal sac walls showed lymphoplasmacytic infiltration in the subepithelial layer (Fig. 1D). The epithelium was partially denuded around the infiltrated lesions with loss of goblet cells (Fig. 1D). Fibrosis was found around the lymphoplasmacytic infiltration, without a storiform pattern. There was no obliterative phlebitis. Immunostaining for IgG4 demonstrated
Fig. 1 — Photographs of a 68-year-old man with immunoglobulin G4 (IgG4)–related dacryocystitis. (A) A polyp (asterisk) under preoperative nasal endoscopic examination on the right side. (B) An axial computed tomographic image showing an enlarged lacrimal sac on both sides (arrows). (C) A coronal computed tomographic image showing bilateral soft tissue involvement in the nasal cavity and the maxillary and ethmoid sinuses. (D) Hematoxylin–eosin staining of the right lacrimal sac wall, showing lymphoplasmacytic infiltration with partial denudation of the epithelium (magnification, 100). (E, F) Immunostaining (brown) for immunoglobulin G4 (IgG4): (E) The right lacrimal sac wall; (F) the polyp in the right nasal cavity. Intensely stained IgG4positive plasma cells with 450 IgG4 plasma cells (magnification, 400). CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
1
Case Report intensely stained IgG4-positive plasma cells with 450 IgG4 plasma cells/HPF (Fig. 1E). Histopathologic findings of the nasal polyp corresponded to chronic sinusitis with intensely stained IgG4-positive plasma cells with 450 IgG4 plasma cells/HPF (Fig. 1F). There was no fibrosis in a storiform pattern or obliterative phlebitis. At the 1-year follow-up, the patient experienced neither epiphora nor rhinostenosis. Nasal endoscopic examinations showed a largely patent rhinostomy site and no recurrence of the sinusitis on both sides.
DISCUSSION In this case report, we presented the case of a patient with IgG4-related dacryocystitis and described the detailed clinicopathologic findings. The definitive diagnosis of IgG4-related ophthalmic disease was based on the findings of IgG4-positive lymphoplasmacytes with 450 IgG4 plasma cells/HPF and elevated serum IgG4 levels.3 Although a mass was not palpable in the medial canthal area, we confirmed an enlarged lesion in the lacrimal sac on computed tomographic images based on the diagnostic criteria.3 Concomitant IgG4-related sinusitis and prostatitis further supported the diagnosis.3 Although fibrosis in a storiform pattern and obliterative phlebitis were not found in the pathologic specimens, these are sometimes lacking in ophthalmic lesions.4 Although IgG4-related lesions in the lacrimal sac/ nasolacrimal duct were previously reported in 7 patients (Table 1), some clinicopathologic findings were not available, and various diagnostic criteria of IgG4-related ophthalmic disease were used.1,5–9 Intensive lymphoplasmacytic infiltration in the subepithelial layer results in thickening of the lacrimal sac wall, which narrows the lumen of the lacrimal sac10; in addition, epithelial
denudation with loss of goblet cells promotes adhesion of the lacrimal sac walls.11 In our patient, histopathologic findings indicated IgG4-positive lymphoplasmacytic infiltration in the subepithelial layer and partial epithelial denudation with loss of goblet cells, indicative of the involvement of IgG4 immune process with development of stenosis/obstruction of the lacrimal passage. The subepithelial layer in the lacrimal passage contains the lacrimal drainage-associated lymphoid tissue (LDALT), which comprises the main immune mechanism of the lacrimal system.12 The LDALT forms a functional unit with the lacrimal gland, conjunctiva, and nasal mucosa to maintain ocular surface integrity through lymphocyte recirculation.12 IgG4-positive cells were detected in the subepithelial layer of the lacrimal passage in the current patient. Lymphocyte recirculation was possibly associated with the concurrent nasal lesions in our case, as well as with IgG4-positive staining in the lacrimal sac/nasolacrimal duct and bilateral lacrimal glands in the previously reported patient (Table 1).7 We performed endonasal endoscopic DCR in the present patient; however, steroid is commonly effective for IgG4related ophthalmic disease.2 Actually, epiphora was improved after steroid administration in 2 previously reported patients (Table 1).5,9 Steroid administration is a potentially effective treatment for only IgG4-related stenosis of the lacrimal passage without adhesions of the wall. Although the lacrimal sac generally shows the presence of lymphocytes and plasma cells in both healthy individuals and patients with common nasolacrimal duct stenosis,12 the normal population of IgG- and IgG4-bearing plasma cells in a normal and stenotic lacrimal sac is unknown. Therefore, it was unclear whether the infiltration of IgG4-positive cells in the lacrimal sac in this
Table 1—A review of the previously reported patients with involvement of immunoglobulin G4–positive lymphoplasmacytes in the lacrimal sac/nasolacrimal duct Patient No. Authors Age, y Sex Side Location Number of IgG4positive cells/HPF Other lesions
Serum IgG4 (mg/dL) Diagnosis
Treatment
1
2
Sogabe et al.1 Unknown Unknown Unknown Nasolacrimal duct Unknown
Ginat et al.5 64 M B Lacrimal sac–duct Unknown
Unknown
3
4
5
6
7
56 M L Lacrimal sac
Batra et al.6 80 F R Lacrimal sac
Marunaka et al.7 78 F R Lacrimal sac–duct
Kase et al.8 89 F R Lacrimal sac
Suzuki et al.9 58 M B Nasolacrimal duct
Unknown
Unknown
450
440
Unknown
Lung and retroperitoneum
Kidney and salivary gland
Unknown
Nil
Right parotid gland and bilateral mandibular gland
Unknown
1490
Unknown
233
Bilateral lacrimal glands and submandibular glands 558
242
243
IgG4-related nasolacrimal duct inflammation Unknown
Eosinophilic angiocentric fibrosis
Eosinophilic angiocentric fibrosis
IgG4-related sclerosing dacryocystitis
IgG4-related DLBCL IgG4-related lacrimal IgG4-related in the lacrimal sac and sac diverticulitis nasolacrimal duct nasolacrimal duct inflammation
Steroid
Steroid and rituximab
Nil
R-CHOP
Diverticulum excision Oral steroid
HPF, High-power field; M, male; F, female; B, bilateral; L, left; R, right; IgG4, immunoglobulin G4; DLBCL, diffuse large B-cell lymphoma; R-CHOP, rituximab-cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone.
2
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
Case Report patient was specific for an IgG4-related condition or just an inflammatory response to a common nasolacrimal duct stenosis. Future studies are needed to clarify the difference in immunohistochemical findings between IgG4-related dacryocystitis and other conditions. IgG4-related disease possibly shares a common autoimmune process with other autoimmune diseases such as thyroid eye disease, sarcoidosis, and granulomatosis with polyangiitis.13–15 Although a rheumatologic examination revealed no other autoimmune diseases in this patient, it is necessary to detect other coincident autoimmune diseases when specimens of lacrimal sac walls show IgG4-positive cell infiltration. In conclusion, the patients’ clinicopathologic findings indicated involvement of IgG4 immune process in the LDALT with development of the dacryocystitis and subsequent obstruction of the lacrimal passage. Yasuhiro Takahashi, MD, PhD,* Emiko Takahashi, MD, PhD,† Kunihiro Nishimura, MD, PhD,‡ Hirohiko Kakizaki, MD, PhD* * Department of Oculoplastic, Orbital and Lacrimal Surgery, Aichi Medical University Hospital, Nagakute, Japan; † Department of Pathology, Aichi Medical University Hospital, Nagakute, Japan; ‡Department of Otolaryngology, Aichi Medical University, Nagakute, Japan.
Correspondence to: Yasuhiro Takahashi, MD, PhD: yasuhiro_tak@ yahoo.co.jp REFERENCES 1. Sogabe Y, Ohshima K, Azumi A, et al. Location and frequency of lesions in patients with IgG4-related ophthalic diseases. Graefes Arch Clin Exp Ophthalmol. 2014;252:531-8.
2. Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012;22:21-30. 3. Goto H, Takahira M, Azumi A. Japanese Study Group for IgG4Related Ophthalmic Disease. Diagnostic criteria for IgG4-related ophthalmic disease. Jpn J Ophthalmol. 2015;59:1-7. 4. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181-92. 5. Ginat DT, Freitag SK, Kieff D, et al. Radiographic patterns of orbital involvement in IgG4-related disease. Ophthal Plast Reconstr Surg. 2013;29:261-6. 6. Batra R, Mudhar HS, Sandramouli S. A unique case of IgG4 sclerosing dacryocystitis. Ophthal Plast Reconstr Surg. 2012;28:e70-2. 7. Marunaka H, Orita Y, Tachibana T, et al. Diffuse large B-cell lymphoma of the lacrimal sac arising from a patient with IgG4related disease. Mod Rheumatol. 2016;16:1-5. 8. Kase S, Suzuki Y, Shinohara T, Kase M. IgG4-related lacrimal sac diverticulitis. Orbit. 2014;33:217-9. 9. Suzuki M, Mizumachi T, Morita S, Kubota K, Iizuka K. A case of immunoglobulin 4-related disease with bilateral mass-forming lesions in the nasolacrimal ducts. J Clin Rheumatol. 2011;17 2077–10. 10. Linberg JV, McCormick SA. Primary acquired nasolacrimal duct obstruction: a clinicopathologic report and biopsy technique. Ophthalmology. 1986;93:1055-63. 11. Mito H, Takahashi Y, Nakano T, Asamoto K, Ikeda H, Kakizaki H. Consecutive microscopic anatomical characteristics of the lacrimal sac and nasolacrimal duct: cases with or without inflammation. Invest Ophthalmol Vis Sci. 2014;55:5233-7. 12. Ali MJ, Mulay K, Pujari A, Naik MN. Derangements of lacrimal drainage-associated lymphoid tissue (LDALT) in human chronic dacryocystitis. Ocul Immunol Inflamm. 2013;21:417-23. 13. Wong AJ, Plank SR, Choi D, et al. IgG4 immunostaining and its implications in orbital inflammatory disease. PLoS One. 2014;9: e109847. 14. Takahashi Y, Takahashi E, Hiromatsu Y, Kakizaki H. Immunoglobulin G4-positive staining of orbital lesions in thyroid eye disease: report of two cases. Mod Rheumatol. 2016;4:1-4. 15. Kang H, Takahashi Y, Takahashi E, Kakizaki H. Immunoglobulin G4-positive lymphoplasmacytic infiltration in a sarcoidal eyelid mass. Mod Rheumatol. 2016;16:1-4. Can J Ophthalmol 2017;]:]]]–]]] 0008-4182/17/$-see front matter & 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2017.02.008
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
3
CASE REPORT This retrospective observational case report was approved by the Institutional Review Board of Aichi Medical University Hospital (No. 2016-H206) and adhered to the tenets of the 1964 Declaration of Helsinki. Written informed consent for publication of this report was obtained from the patient. A 68-year-old man presented with a 3-year history of bilateral epiphora and right rhinostenosis. He also had a history of biopsy of hypertrophic prostate performed at other institution. Immunostaining for IgG4 demonstrated intensely stained IgG4-positive plasma cells with 450 IgG4 plasma cells/high-power field (HPF). The blood test result at that time indicated an elevated serum IgG4 level (548 mg/dL; normal o105 mg/dL). These findings
corresponded with the comprehensive diagnostic criteria (2011) for IgG4-related disease.2 Systemic examinations by a rheumatologist revealed no other autoimmune diseases. At the first examination at our institution, a mass was not palpable and the skin was not erythematous in the medial canthal area. Lacrimal irrigation and probing showed bilateral nasolacrimal duct obstruction. Nasal endoscopic examination demonstrated a polyp in the right nasal cavity (Fig. 1A). Computed tomography images revealed an enlarged lacrimal sac and soft tissue involvement on both sides in the nasal cavity and the maxillary and ethmoid sinuses (Fig. 1B, C). Hematological analysis indicated an elevated serum IgG4 level (478 mg/dL). Bilateral endoscopic endonasal dacryocystorhinostomy (DCR) and sinus surgery were performed under general anaesthesia. During DCR, the anterior and posterior flaps were created from the lacrimal sac, the anterior flap was removed and was sent for histopathologic examination, whereas the posterior flap remained on the posterior osteotomy site. The nasal polyp was removed and was also sent for histopathologic examination. Histopathologic examinations of the bilateral lacrimal sac walls showed lymphoplasmacytic infiltration in the subepithelial layer (Fig. 1D). The epithelium was partially denuded around the infiltrated lesions with loss of goblet cells (Fig. 1D). Fibrosis was found around the lymphoplasmacytic infiltration, without a storiform pattern. There was no obliterative phlebitis. Immunostaining for IgG4 demonstrated
Fig. 1 — Photographs of a 68-year-old man with immunoglobulin G4 (IgG4)–related dacryocystitis. (A) A polyp (asterisk) under preoperative nasal endoscopic examination on the right side. (B) An axial computed tomographic image showing an enlarged lacrimal sac on both sides (arrows). (C) A coronal computed tomographic image showing bilateral soft tissue involvement in the nasal cavity and the maxillary and ethmoid sinuses. (D) Hematoxylin–eosin staining of the right lacrimal sac wall, showing lymphoplasmacytic infiltration with partial denudation of the epithelium (magnification, 100). (E, F) Immunostaining (brown) for immunoglobulin G4 (IgG4): (E) The right lacrimal sac wall; (F) the polyp in the right nasal cavity. Intensely stained IgG4positive plasma cells with 450 IgG4 plasma cells (magnification, 400). CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
1
Case Report intensely stained IgG4-positive plasma cells with 450 IgG4 plasma cells/HPF (Fig. 1E). Histopathologic findings of the nasal polyp corresponded to chronic sinusitis with intensely stained IgG4-positive plasma cells with 450 IgG4 plasma cells/HPF (Fig. 1F). There was no fibrosis in a storiform pattern or obliterative phlebitis. At the 1-year follow-up, the patient experienced neither epiphora nor rhinostenosis. Nasal endoscopic examinations showed a largely patent rhinostomy site and no recurrence of the sinusitis on both sides.
DISCUSSION In this case report, we presented the case of a patient with IgG4-related dacryocystitis and described the detailed clinicopathologic findings. The definitive diagnosis of IgG4-related ophthalmic disease was based on the findings of IgG4-positive lymphoplasmacytes with 450 IgG4 plasma cells/HPF and elevated serum IgG4 levels.3 Although a mass was not palpable in the medial canthal area, we confirmed an enlarged lesion in the lacrimal sac on computed tomographic images based on the diagnostic criteria.3 Concomitant IgG4-related sinusitis and prostatitis further supported the diagnosis.3 Although fibrosis in a storiform pattern and obliterative phlebitis were not found in the pathologic specimens, these are sometimes lacking in ophthalmic lesions.4 Although IgG4-related lesions in the lacrimal sac/ nasolacrimal duct were previously reported in 7 patients (Table 1), some clinicopathologic findings were not available, and various diagnostic criteria of IgG4-related ophthalmic disease were used.1,5–9 Intensive lymphoplasmacytic infiltration in the subepithelial layer results in thickening of the lacrimal sac wall, which narrows the lumen of the lacrimal sac10; in addition, epithelial
denudation with loss of goblet cells promotes adhesion of the lacrimal sac walls.11 In our patient, histopathologic findings indicated IgG4-positive lymphoplasmacytic infiltration in the subepithelial layer and partial epithelial denudation with loss of goblet cells, indicative of the involvement of IgG4 immune process with development of stenosis/obstruction of the lacrimal passage. The subepithelial layer in the lacrimal passage contains the lacrimal drainage-associated lymphoid tissue (LDALT), which comprises the main immune mechanism of the lacrimal system.12 The LDALT forms a functional unit with the lacrimal gland, conjunctiva, and nasal mucosa to maintain ocular surface integrity through lymphocyte recirculation.12 IgG4-positive cells were detected in the subepithelial layer of the lacrimal passage in the current patient. Lymphocyte recirculation was possibly associated with the concurrent nasal lesions in our case, as well as with IgG4-positive staining in the lacrimal sac/nasolacrimal duct and bilateral lacrimal glands in the previously reported patient (Table 1).7 We performed endonasal endoscopic DCR in the present patient; however, steroid is commonly effective for IgG4related ophthalmic disease.2 Actually, epiphora was improved after steroid administration in 2 previously reported patients (Table 1).5,9 Steroid administration is a potentially effective treatment for only IgG4-related stenosis of the lacrimal passage without adhesions of the wall. Although the lacrimal sac generally shows the presence of lymphocytes and plasma cells in both healthy individuals and patients with common nasolacrimal duct stenosis,12 the normal population of IgG- and IgG4-bearing plasma cells in a normal and stenotic lacrimal sac is unknown. Therefore, it was unclear whether the infiltration of IgG4-positive cells in the lacrimal sac in this
Table 1—A review of the previously reported patients with involvement of immunoglobulin G4–positive lymphoplasmacytes in the lacrimal sac/nasolacrimal duct Patient No. Authors Age, y Sex Side Location Number of IgG4positive cells/HPF Other lesions
Serum IgG4 (mg/dL) Diagnosis
Treatment
1
2
Sogabe et al.1 Unknown Unknown Unknown Nasolacrimal duct Unknown
Ginat et al.5 64 M B Lacrimal sac–duct Unknown
Unknown
3
4
5
6
7
56 M L Lacrimal sac
Batra et al.6 80 F R Lacrimal sac
Marunaka et al.7 78 F R Lacrimal sac–duct
Kase et al.8 89 F R Lacrimal sac
Suzuki et al.9 58 M B Nasolacrimal duct
Unknown
Unknown
450
440
Unknown
Lung and retroperitoneum
Kidney and salivary gland
Unknown
Nil
Right parotid gland and bilateral mandibular gland
Unknown
1490
Unknown
233
Bilateral lacrimal glands and submandibular glands 558
242
243
IgG4-related nasolacrimal duct inflammation Unknown
Eosinophilic angiocentric fibrosis
Eosinophilic angiocentric fibrosis
IgG4-related sclerosing dacryocystitis
IgG4-related DLBCL IgG4-related lacrimal IgG4-related in the lacrimal sac and sac diverticulitis nasolacrimal duct nasolacrimal duct inflammation
Steroid
Steroid and rituximab
Nil
R-CHOP
Diverticulum excision Oral steroid
HPF, High-power field; M, male; F, female; B, bilateral; L, left; R, right; IgG4, immunoglobulin G4; DLBCL, diffuse large B-cell lymphoma; R-CHOP, rituximab-cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone.
2
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
Case Report patient was specific for an IgG4-related condition or just an inflammatory response to a common nasolacrimal duct stenosis. Future studies are needed to clarify the difference in immunohistochemical findings between IgG4-related dacryocystitis and other conditions. IgG4-related disease possibly shares a common autoimmune process with other autoimmune diseases such as thyroid eye disease, sarcoidosis, and granulomatosis with polyangiitis.13–15 Although a rheumatologic examination revealed no other autoimmune diseases in this patient, it is necessary to detect other coincident autoimmune diseases when specimens of lacrimal sac walls show IgG4-positive cell infiltration. In conclusion, the patients’ clinicopathologic findings indicated involvement of IgG4 immune process in the LDALT with development of the dacryocystitis and subsequent obstruction of the lacrimal passage. Yasuhiro Takahashi, MD, PhD,* Emiko Takahashi, MD, PhD,† Kunihiro Nishimura, MD, PhD,‡ Hirohiko Kakizaki, MD, PhD* * Department of Oculoplastic, Orbital and Lacrimal Surgery, Aichi Medical University Hospital, Nagakute, Japan; † Department of Pathology, Aichi Medical University Hospital, Nagakute, Japan; ‡Department of Otolaryngology, Aichi Medical University, Nagakute, Japan.
Correspondence to: Yasuhiro Takahashi, MD, PhD: yasuhiro_tak@ yahoo.co.jp REFERENCES 1. Sogabe Y, Ohshima K, Azumi A, et al. Location and frequency of lesions in patients with IgG4-related ophthalic diseases. Graefes Arch Clin Exp Ophthalmol. 2014;252:531-8.
2. Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012;22:21-30. 3. Goto H, Takahira M, Azumi A. Japanese Study Group for IgG4Related Ophthalmic Disease. Diagnostic criteria for IgG4-related ophthalmic disease. Jpn J Ophthalmol. 2015;59:1-7. 4. Deshpande V, Zen Y, Chan JK, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181-92. 5. Ginat DT, Freitag SK, Kieff D, et al. Radiographic patterns of orbital involvement in IgG4-related disease. Ophthal Plast Reconstr Surg. 2013;29:261-6. 6. Batra R, Mudhar HS, Sandramouli S. A unique case of IgG4 sclerosing dacryocystitis. Ophthal Plast Reconstr Surg. 2012;28:e70-2. 7. Marunaka H, Orita Y, Tachibana T, et al. Diffuse large B-cell lymphoma of the lacrimal sac arising from a patient with IgG4related disease. Mod Rheumatol. 2016;16:1-5. 8. Kase S, Suzuki Y, Shinohara T, Kase M. IgG4-related lacrimal sac diverticulitis. Orbit. 2014;33:217-9. 9. Suzuki M, Mizumachi T, Morita S, Kubota K, Iizuka K. A case of immunoglobulin 4-related disease with bilateral mass-forming lesions in the nasolacrimal ducts. J Clin Rheumatol. 2011;17 2077–10. 10. Linberg JV, McCormick SA. Primary acquired nasolacrimal duct obstruction: a clinicopathologic report and biopsy technique. Ophthalmology. 1986;93:1055-63. 11. Mito H, Takahashi Y, Nakano T, Asamoto K, Ikeda H, Kakizaki H. Consecutive microscopic anatomical characteristics of the lacrimal sac and nasolacrimal duct: cases with or without inflammation. Invest Ophthalmol Vis Sci. 2014;55:5233-7. 12. Ali MJ, Mulay K, Pujari A, Naik MN. Derangements of lacrimal drainage-associated lymphoid tissue (LDALT) in human chronic dacryocystitis. Ocul Immunol Inflamm. 2013;21:417-23. 13. Wong AJ, Plank SR, Choi D, et al. IgG4 immunostaining and its implications in orbital inflammatory disease. PLoS One. 2014;9: e109847. 14. Takahashi Y, Takahashi E, Hiromatsu Y, Kakizaki H. Immunoglobulin G4-positive staining of orbital lesions in thyroid eye disease: report of two cases. Mod Rheumatol. 2016;4:1-4. 15. Kang H, Takahashi Y, Takahashi E, Kakizaki H. Immunoglobulin G4-positive lymphoplasmacytic infiltration in a sarcoidal eyelid mass. Mod Rheumatol. 2016;16:1-4. Can J Ophthalmol 2017;]:]]]–]]] 0008-4182/17/$-see front matter & 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2017.02.008
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2017
3