Modern Rheumatology

ISSN: 1439-7595 (Print) 1439-7609 (Online) Journal homepage: http://www.tandfonline.com/loi/imor20

Immunoglobulin G4-positive lymphoplasmacytic infiltration in a sarcoidal eyelid mass Hyera Kang, Yasuhiro Takahashi, Emiko Takahashi & Hirohiko Kakizaki To cite this article: Hyera Kang, Yasuhiro Takahashi, Emiko Takahashi & Hirohiko Kakizaki (2016): Immunoglobulin G4-positive lymphoplasmacytic infiltration in a sarcoidal eyelid mass, Modern Rheumatology, DOI: 10.3109/14397595.2015.1118791 To link to this article: http://dx.doi.org/10.3109/14397595.2015.1118791

Accepted author version posted online: 13 Nov 2015. Published online: 16 Mar 2016. Submit your article to this journal

Article views: 26

View related articles

View Crossmark data

Citing articles: 2 View citing articles

Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=imor20 Download by: [The UC San Diego Library]

Date: 17 June 2017, At: 10:52

http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2016; Early Online: 1–4 ! 2016 Japan College of Rheumatology DOI: 10.3109/14397595.2015.1118791

CASE REPORT

Immunoglobulin G4-positive lymphoplasmacytic infiltration in a sarcoidal eyelid mass Hyera Kang1,2, Yasuhiro Takahashi1, Emiko Takahashi3, and Hirohiko Kakizaki1 1

Department of Ophthalmology, Aichi Medical University, Nagakute, Aichi, Japan, 2Department of Ophthalmology, University of Seonam College of Medicine, Presbyterian Medical Center, Jeonju, Korea, and 3Department of Pathology, Aichi Medical University Hospital, Nagakute, Aichi, Japan

Abstract A 62-year-old woman presented with a one month history of a hard, nonmobile subcutaneous mass along the right nasojugal fold. Hematological studies showed elevated serum immunoglobulin G4 levels. Histopathological examination of the biopsy sample disclosed immunoglobulin G4-positive lymphoplasmacytic infiltration with a storiform fibrosis, vein occlusion, and epithelioid granulomas with necrosis. Systemic review corresponded to a sarcoidosis. Without treatment, the eyelid mass did not recur six months after the excisional biopsy.

Introduction Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and sarcoidosis are distinct clinical entities. IgG4-ROD shows IgG4positive lymphoplasmacytic infiltration in the periocular region, with elevated serum IgG4 levels [1]. However, sarcoidosis causes inflammation in multiple organs with manifestation of noncaseating epithelioid granulomas [2]. IgG4-ROD and sarcoidosis are, however, both autoimmune disorders [1,2], and these entities may possibly share a common autoimmune process. There has been one report of positive IgG4 immunostaining in histopathological samples biopsied from the orbits of 5 out of 12 patients with sarcoidosis [3]. However, the detailed clinical findings such as sarcoidosis-associated conditions, results of the hematological analyses, and histopathological findings of other lesions were not reported. Here, we report detailed clinical findings from a patient with IgG4-positive lymphoplasmacytic infiltration in a sarcoidal eyelid mass, which was suspected to develop as both IgG4-ROD and sarcoidosis.

Case report This study was approved by the local ethics committee, and adhered to the tenets of the 1964 Declaration of Helsinki. The patient gave informed consent prior to inclusion in the study. A 62-year-old woman presented with a one month history of right lower eyelid swelling. She had been administered 0.1% topical betamethasone twice a day for a bilateral uveitis for two years. She was also a habitual smoker (e.g. 20 cigarettes/day, for 30 years). On initial examination, her best-corrected visual acuity was 1.2 and the intraocular pressure was 15 mmHg in both eyes. Correspondence to: Hirohiko Kakizaki, Department of Ophthalmology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan. Tel: +81 561 62 3311 (ext. 22181). Fax: +81 561 63 7255. E-mail: cosme@ d1.dion.ne.jp

Keywords Epithelioid granuloma, Immunoglobulin G4, Sarcoidosis, Storiform fibrosis, Vein occlusion History Received 29 June 2015 Accepted 5 November 2015 Published online 7 March 2016

A slit-lamp examination revealed pigmented cells on the right lens, but no keratoprecipitates, possibly due to the 0.1% topical betamethasone administration [2]. The gonioscopic examination did not show a peripheral anterior synechia or an iris nodule. The funduscopic examination showed snowball-like vitreous opacities (Figure 1a) and mild vasculitis in both eyes. The extraocular muscle motility was normal and the patient did not notice diplopia. A hard, nonmobile subcutaneous mass was palpable along the right nasojugal fold (Figure 1b). Orbital computed tomographic (CT) images revealed a subcutaneous mass on the right side and swollen bilateral medial rectus muscles anteriorly (Figure 1c). Hematological analysis indicated an elevated serum IgG4 level (206 mg/dL; normal,5105 mg/dL). Serum IgG (1623.2 mg/dL; normal, 870–1700 mg/dL), IgE levels (30.4 IU/L; normal,5173 IU/L), serum calcium levels (9.5 mg/dL; normal, 8.7–10.3 mg/dL), angiotensin converting enzyme (13.2 U/L; normal,521.4 U/L), rheumatoid factor (53.0 IU/mL; normal,515 IU/mL), anti-nuclear antibody (51:40; normal,51:40), anti-DNA antibody (52.0 IU/L; normal,56.0 IU/L), and soluble interleukin-2 receptor (443 U/mL; normal, 145–519 U/mL) were within normal limits. The subcutaneous mass was completely removed under local anesthesia. Histopathological examination of the biopsy sample revealed a lymphoplasmacytic infiltration with follicular formation, marked fibrosis, vein occlusion, and epithelioid granulomas (Figure 1d and e). Fibrotic lesions partly showed a storiform pattern (Figure 1f). Although necrosis and accumulation of neutrophils accompanied some of the epithelioid granulomas, Ziehl–Neelsen, periodic acid Schiff, and Grocott staining did not show bacteria or fungal bodies. Immunostaining for IgG and IgG4 demonstrated intensely stained IgG4-positive lymphoplasmacytes surrounding the granulomas, with450 IgG4 plasma cells per highpower field (magnification 400; Figure 1g). The JH gene rearrangement was negative. Systemic review revealed mild enlargement of the mediastinal and bilateral hilar lymph nodes on chest CT images (Figure 2a–c) and skin nodules of the right hand and the right lower limb.

2

H. Kang et al.

Mod Rheumatol, 2016; Early Online: 1–4

Figure 1. Ophthalmic findings. (a) Slit-lamp examination using a non-contact lens in the left eye showing a snowball-like vitreous opacity (arrow). (b) A facial photograph showing a subcutaneous mass located along the right nasojugal fold (arrow). (c) An axial orbital computed tomography (CT) image showing a subcutaneous mass on the right side (yellow arrow). Medial rectus muscles are enlarged at the insertion to the globe on both sides (blue arrows) but the extraocular muscle motility in the patient was normal and the patient did not notice diplopia. (d–g) Histopathological findings of the biopsy sample from the eyelid. (d) An epithelioid granuloma (arrow) [hematoxylin and eosin (H&E) stain; magnification 200]. (e) Follicular formation with fibrosis (H&E stain; magnification 100). (f) Storiform fibrosis (H&E stain; magnification 200). (g) Immunoglobulin G4 (IgG4) positive lymphoplasmacytic infiltration (immunostaining for IgG4; magnification 400).

DOI: 10.3109/14397595.2015.1118791

IgG4-ROD and sarcoidosis

3

Figure 2. Systemic findings. (a–c) Axial chest CT images showing mild enlargement of the mediastinal (green arrows) and bilateral hilar lymph nodes (yellow arrows). (d, e) Histopathological findings of the biopsy sample from the skin nodule. (d) Noncaseating epithelioid granulomas (arrows) (H&E stain; magnification 200). (e) Negative IgG4 staining (immunostaining for IgG4; magnification 200).

Biopsy samples of the hilar lymph nodes and the skin nodules showed noncaseating epithelioid granulomas (Figure 2d). Immunostaining for IgG and IgG4 revealed a few stained IgG4positive cells (Figure 2e). Bronchoalveolar lavage (BAL) showed an increase in the ratio of the cluster of differentiation (CD) 4/CD8 (7.90; normal range in smokers, 0.40–1.00). There was no evidence of acid-fast bacterial infection in the BAL fluid. The cardiac echography and urinalysis revealed no remarkable changes. In the absence of treatment, the eyelid mass did not recur during the six months after the biopsy. The patient continued to apply 0.1% topical betamethasone twice a day for the uveitis, and was treated with 0.05% betamethasone ointment for skin nodules in the hand and leg.

Discussion We present a patient with an eyelid mass histopathologically showing IgG4-positive lymphoplasmacytic infiltration and epithelioid granulomas. Based on the findings of the hypertrophic lesion

in the eyelid, IgG4-positive lymphoplasmacytes with 450 IgG4 plasma cells per high-power field, and elevated serum IgG4 levels, this patient was judged as ‘‘definitive’’ IgG4-ROD according to the diagnostic criteria of IgG4-ROD [1]. Although not common, the eyelid is one of the target organs in IgG4-ROD [1]. As for sarcoidosis, the histopathological findings of the hilar lymph nodes and the skin nodules corresponded to the histological diagnostic criteria of sarcoidosis proposed by the Japan Society of Sarcoidosis and other Granulomatous Disorders in 2015 [4]. Although epithelioid granulomas with necrosis in the eyelid mass are not typical for sarcoidosis, there was no evidence of bacterial or fungal infection in the eyelid mass [2]. In addition, bilateral enlargement of the hilar lymph nodes, an elevated CD4/CD8 ratio in the BAL fluid, and uveitis satisfied the clinical diagnostic criteria of sarcoidosis [4]. A previous study proposed a subgroup of sarcoidosis patients with positive IgG4 staining [3]. However, storiform fibrosis and occluded veins, as well as positive IgG4 staining shown in this patient, are histopathological characteristics of IgG4-related disease

4

H. Kang et al.

[5]. In addition, the serum IgG4 level was elevated in this patient. This patient was, therefore, diagnosed with both IgG4-ROD and sarcoidosis, rather than being part of the sarcoidosis subgroup. The relationship between other IgG4-related diseases and sarcoidosis has been previously examined. Although previous studies demonstrated pulmonary lesions resembling sarcoidosis in autoimmune pancreatitis [6] and Mikulicz’s disease [7], histopathological examinations revealed no evidence of noncaseating epithelioid granuloma. A previous case report showed the association between autoimmune pancreatitis and sarcoidosis; however, this report did not present evidence of IgG4 positive cell infiltration in the biopsy specimen from the pancreas [8]. As a previous study showed no evidence of IgG4 positive cell infiltration in cardiac or lymph node specimens and an elevated serum IgG4 level in patients with cardiac or non-cardiac sarcoidosis [9], this report concluded that sarcoidosis does not belong to or overlap with IgG4-related diseases. In the future, further studies related to this condition are necessary to confirm the characteristics of patients with clinical expression of both an IgG4-related disease and sarcoidosis. The IgG4 positive lymphoplasmacytic infiltration was evident only in the eyelid mass. Immunopathogenesis of sarcoidosis involves a number of chemical mediators [2], which attract lymphocytes to the inflammatory lesions. In addition, the necrotic tissue observed only in the eyelid mass also releases chemical mediators, resulting in aggravation of the inflammatory responses [10]. These mediators may have promoted the accumulation of IgG4 positive lymphoplasmacytes in the eyelid mass. Marked fibrosis in the eyelid mass in our patient was a different histopathological finding than typical IgG4-ROD, which usually shows less fibrosis in biopsy samples [1]. More severe fibrosis may have been caused by the combination of inflammatory responses from both the IgG4 positive lymphoplasmacytic infiltration and sarcoidosis [3]. Although we did not administer a steroid for the eyelid mass after the removal, such fibrous lesions may be recalcitrant to steroid therapy. In conclusion, we describe a patient with IgG4 positive lymphoplasmacytic infiltration in a sarcoidal eyelid mass. Based on the histopathological and clinical findings, this patient may develop both IgG4-ROD and sarcoidosis, rather than belonging to the subgroup of sarcoidosis patients with positive IgG4 staining. Considering the histopathological findings, the inflammatory process of sarcoidosis and necrosis may have facilitated the accumulation of IgG4 positive lymphoplasmacytes around the epithelioid granulomas of the patient.

Mod Rheumatol, 2016; Early Online: 1–4

Acknowledgments The authors wish to acknowledge Dr. Masayuki Yamaji from the Department of Thoracic Surgery, Aichi Medical University, for his advice on radiographic image interpretation.

Ethics approval This study was approved by the local ethics committee (number: 2015-024) and adhered to the tenets of the 1964 Declaration of Helsinki. The patients gave informed consent prior to inclusion in the study. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Conflict of interest Authors do not have conflicts of interest.

References 1. 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. 2. ATS/ERS/WASOG Committee. Statement on sarcoidosis. Am J Respir Crit Care Med. 1999;160:736–55. 3. Wong AJ, Plank SR, Choi D, Harrington CA, Troxell ML, Houghton DC, et al. IgG4 immunostaining and its implications in orbital inflammatory disease. PLoS One. 2014;9:e109847. 4. Japan Society of Sarcoidosis and other Granulomatous Disorders. http://www.jssog.com/www/top/shindan/shindan2-1new.html. 5. Deshpande V, Zen Y, Chan JKC, Yi EE, Sato Y, Yoshino T, et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181–92. 6. Tsushima K, Tanabe T, Yamamoto H, Koizumi T, Kawa S, Hamano T, et al. Pulmonary involvement of autoimmune pancreatitis. Eur J Clin Invest. 2009;39:714–22. 7. Matsui S, Taki H, Shinoda K, Suzuki K, Hayashi R, Tobe K, et al. Respiratory involvement in IgG4-related Mikulicz’s disease. Mod Rheumatol. 2012;22:31–9 8. Michel L, Clairand R, Ne´el A, Masseau A, Frampas E, Hamidou M. Association of IgG4-related disease and sarcoidosis. Thorax. 2011;66:920–1. 9. Terasaki F, Tsuji M, Kizawa S, Fujita S, Kanzaki Y, Kitaura Y, et al. Sarcoidosis does not belong to or overlap with immunoglobulin G4related diseases based on an assessment of serum immunoglobulin G4 levels in cardiac and noncardiac sarcoidosis. Hum Pathol. 2012;43:818–25. 10. Lu S. Burn wound healing. In: Yang Z, ed. Chinese burn surgery. Dordrecht: Springer; 2015: 209.

Immunoglobulin G4-positive lymphoplasmacytic infiltration in a sarcoidal eyelid mass.

A 62-year-old woman presented with a one month history of a hard, nonmobile subcutaneous mass along the right nasojugal fold. Hematological studies sh...
566B Sizes 0 Downloads 9 Views