RHEUMATOLOGY
Letters to the Editor Rheumatology 2015;54:11241125 doi:10.1093/rheumatology/kev024 Advance Access publication 25 March 2015
SIR, IgG4-related disease is a disorder of uncertain aetiology characterized by tumour-like lesions at multiple sites, increased serum IgG4 and a rapid response to corticosteroid treatment [1, 2]. It can involve almost any organ, but uterine involvement has not been reported to the best of our knowledge. In the present report we describe a case of IgG4-related disease that involved the uterus. A 68-year-old woman with no history of allergic disease had been prescribed oral antihistamines and low-dose betamethasone (0.25 mg/day) at a local clinic for persistent cough, erythema on bilateral forearms and peripheral blood eosinophilia (540/mm3). The cough initially improved, but later returned, whereas the erythema and eosinophilia resolved. After 2 months the patient was referred to our hospital due to shortness of breath and bilateral pleural effusions. Vital signs were unremarkable; percutaneous oxygen saturation was 94% while breathing room air. No adventitious breath sounds were audible and dull percussions were noted on both sides of the chest. There was no evidence of erythema or oedema. Blood examination revealed normal serum CRP levels. Thoracentesis demonstrated bilateral exudative pleural effusions, but microbiological analyses of these fluids yielded negative results. The pleural effusion cytology showed neutrophils, lymphocytes and macrophages, but no malignant cells. Tests for serum tumour markers, IL-6 and autoantibodies were all negative. Tuberculosis infection was excluded on the basis of a negative IFN-g release assay. Contrast-enhanced whole-body CT performed as a screening study showed bilateral pleural effusions, thickening of the soft tissue around the descending aorta (Fig. 1A) and an enlarged heterogeneously enhancing uterus (Fig. 1B). Left thoracoscopic pleural biopsy was performed under local anaesthesia. Histopathological examination revealed pleuritis with plasma cell infiltration, but the aetiology was not determined. CT-guided needle biopsy from the periaortic lesion was not performed to avoid risk. Gynaecological referral was made due to the uterine enlargement in this post-menopausal woman. Transvaginal endometrial cytology revealed atypical cells, but subsequent endometrial biopsy specimens did not contribute to the diagnosis. Uptake of [18F]fluorodeoxyglucose as measured by PET was observed in the bilateral pleura, periaortic region and uterus (Fig. 1C). The patient agreed to a total hysterectomy for definitive diagnosis, of which differential
! The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Tasmania Library on May 21, 2015
L ET T E R
A rare case of IgG4-related disease involving the uterus
diagnoses included malignancy, particularly lymphoma and sarcoma. Histopathologically the muscle layer of the uterine corpus showed fibrosis with lymphoid follicles that consisted of lymphocytes, plasma cells and eosinophils (Fig. 1D), accompanied by focal obstructive phlebitis. On immunostaining, plasma cells were positive for IgG and IgG4 (Fig. 1E), and the IgG4:IgG ratio was >60%. Furthermore, immunostaining with k and antibodies supported no evidence of lymphoma. Serum IgG4 was elevated [307 mg/dl (normal 10 published cases of IgG4-related disease with pleural involvement [1, 3, 4]. Non-infectious periaortitis is known to be a subtype of this disease [1]. Nonetheless, the simultaneous and isolated presentation of involvement of pleurae, periaortic lesions and uterus may be rare. In the present case, the muscle layer of the uterus showed fibrosis and infiltration of lymphocytes, eosinophils and IgG4-positive plasma cells. These pathological findings are consistent with previously described characteristics of IgG4-related disease [1, 2]. Uterine pseudotumours may be important differential diagnoses [5], including epithelial and stromal metaplasia, pseudolymphoma, inflammatory myofibroblastic tumour, adenomyosis and post-therapy surgical changes. Of these, inflammatory myofibroblastic tumour is frequently associated with IgG4-related disease in other organs such as the liver [6] and lung [4]. The pathological characteristics of inflammatory myofibroblastic tumours resemble those of IgG4-realated disease, hence it is assumed that some past cases of uterine IgG4-related disease were diagnosed as uterine inflammatory myofibroblastic tumour. Transvaginal endometrial cytology and biopsy did not yield the diagnosis in the present case. For the diagnosis of IgG4-related disease of the pancreas, the usefulness of endoscopic US-guided fine-needle aspiration has been increasingly recognized for obtaining adequate tissue samples [7]. Thus it is possible that transvaginal USguided needle aspiration may be useful for diagnosing IgG4-related disease involving the uterus.
Letters to the Editor
FIG. 1 Radiological and pathological findings of IgG4-related disease involving the uterus
B
D
E
C
Contrast-enhanced whole-body CT showing (A) bilateral pleural effusions and thickening of the soft tissue around the descending thoracic aorta (arrow) and (B) an enlarged heterogeneously enhancing uterus (arrow). (C) Uptake of [18F]fluorodeoxyglucose as measured by PET is observed in the bilateral pleura, periaortic lesion and uterus. (D) Histopathologically the myometrium shows fibrosis with infiltration of lymphocytes, plasma cells and eosinophils. (E) On immunostaining, numerous IgG4-positive plasma cells are seen. In conclusion, we demonstrate that IgG4-related disease can involve the uterus. Additional case descriptions are required to better characterize the pathological and clinical features of uterine IgG4-related disease. Rheumatology key message .
References
It is important to recognize that IgG4-related disease can involve the uterus.
Funding: No specific funding was received from any funding bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: The authors have declared no conflicts of interest. 1
2
Hirotsugu Ohkubo , Mikinori Miyazaki , Tetsuya Oguri1, Atsushi Arakawa3, Yoichiro Kobashi4 and Akio Niimi1 1 Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 2Department of Pulmonary Medicine, Nagoya Memorial Hospital, Nagoya, 3Department of Obstetrics and Gynaecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, and 4 Department of Pathology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara, Japan Accepted 3 February 2015 Correspondence to: Hirotsugu Ohkubo, Department of
www.rheumatology.oxfordjournals.org
Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 4678601, Japan. E-mail: [email protected]
1 Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012;366:53951. 2 Deshpande V, Zen Y, Chan JK et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol 2012;25:118192. 3 Sekiguchi H, Horie R, Utz JP, Ryu JH. IgG4-related systemic disease presenting with lung entrapment and constrictive pericarditis. Chest 2012;142:7813. 4 Zen Y, Inoue D, Kitao A et al. IgG4- related lung and pleural disease: a clinicopathologic study of 21 cases. Am J Surg Pathol 2009;33:188693. 5 Simionescu C, Ma˘rga˘ritescu C, Stepan A, Ciurea R, Cernea N. Uterine pseudotumors. Rom J Morphol Embryol 2011;52:74358. 6 Zen Y, Fujii T, Sato Y, Masuda S, Nakanuma Y. Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4-related disease. Mod Pathol 2007;20:88494. 7 Kanno A, Ishida K, Hamada S et al. Diagnosis of autoimmune pancreatitis by EUS-FNA by using a 22-gauge needle based on the International Consensus Diagnostic Criteria. Gastrointest Endosc 2012;76:594602.
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Letters to the Editor Rheumatology 2015;54:11241125 doi:10.1093/rheumatology/kev024 Advance Access publication 25 March 2015
SIR, IgG4-related disease is a disorder of uncertain aetiology characterized by tumour-like lesions at multiple sites, increased serum IgG4 and a rapid response to corticosteroid treatment [1, 2]. It can involve almost any organ, but uterine involvement has not been reported to the best of our knowledge. In the present report we describe a case of IgG4-related disease that involved the uterus. A 68-year-old woman with no history of allergic disease had been prescribed oral antihistamines and low-dose betamethasone (0.25 mg/day) at a local clinic for persistent cough, erythema on bilateral forearms and peripheral blood eosinophilia (540/mm3). The cough initially improved, but later returned, whereas the erythema and eosinophilia resolved. After 2 months the patient was referred to our hospital due to shortness of breath and bilateral pleural effusions. Vital signs were unremarkable; percutaneous oxygen saturation was 94% while breathing room air. No adventitious breath sounds were audible and dull percussions were noted on both sides of the chest. There was no evidence of erythema or oedema. Blood examination revealed normal serum CRP levels. Thoracentesis demonstrated bilateral exudative pleural effusions, but microbiological analyses of these fluids yielded negative results. The pleural effusion cytology showed neutrophils, lymphocytes and macrophages, but no malignant cells. Tests for serum tumour markers, IL-6 and autoantibodies were all negative. Tuberculosis infection was excluded on the basis of a negative IFN-g release assay. Contrast-enhanced whole-body CT performed as a screening study showed bilateral pleural effusions, thickening of the soft tissue around the descending aorta (Fig. 1A) and an enlarged heterogeneously enhancing uterus (Fig. 1B). Left thoracoscopic pleural biopsy was performed under local anaesthesia. Histopathological examination revealed pleuritis with plasma cell infiltration, but the aetiology was not determined. CT-guided needle biopsy from the periaortic lesion was not performed to avoid risk. Gynaecological referral was made due to the uterine enlargement in this post-menopausal woman. Transvaginal endometrial cytology revealed atypical cells, but subsequent endometrial biopsy specimens did not contribute to the diagnosis. Uptake of [18F]fluorodeoxyglucose as measured by PET was observed in the bilateral pleura, periaortic region and uterus (Fig. 1C). The patient agreed to a total hysterectomy for definitive diagnosis, of which differential
! The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: [email protected]
Downloaded from http://rheumatology.oxfordjournals.org/ at University of Tasmania Library on May 21, 2015
L ET T E R
A rare case of IgG4-related disease involving the uterus
diagnoses included malignancy, particularly lymphoma and sarcoma. Histopathologically the muscle layer of the uterine corpus showed fibrosis with lymphoid follicles that consisted of lymphocytes, plasma cells and eosinophils (Fig. 1D), accompanied by focal obstructive phlebitis. On immunostaining, plasma cells were positive for IgG and IgG4 (Fig. 1E), and the IgG4:IgG ratio was >60%. Furthermore, immunostaining with k and antibodies supported no evidence of lymphoma. Serum IgG4 was elevated [307 mg/dl (normal 10 published cases of IgG4-related disease with pleural involvement [1, 3, 4]. Non-infectious periaortitis is known to be a subtype of this disease [1]. Nonetheless, the simultaneous and isolated presentation of involvement of pleurae, periaortic lesions and uterus may be rare. In the present case, the muscle layer of the uterus showed fibrosis and infiltration of lymphocytes, eosinophils and IgG4-positive plasma cells. These pathological findings are consistent with previously described characteristics of IgG4-related disease [1, 2]. Uterine pseudotumours may be important differential diagnoses [5], including epithelial and stromal metaplasia, pseudolymphoma, inflammatory myofibroblastic tumour, adenomyosis and post-therapy surgical changes. Of these, inflammatory myofibroblastic tumour is frequently associated with IgG4-related disease in other organs such as the liver [6] and lung [4]. The pathological characteristics of inflammatory myofibroblastic tumours resemble those of IgG4-realated disease, hence it is assumed that some past cases of uterine IgG4-related disease were diagnosed as uterine inflammatory myofibroblastic tumour. Transvaginal endometrial cytology and biopsy did not yield the diagnosis in the present case. For the diagnosis of IgG4-related disease of the pancreas, the usefulness of endoscopic US-guided fine-needle aspiration has been increasingly recognized for obtaining adequate tissue samples [7]. Thus it is possible that transvaginal USguided needle aspiration may be useful for diagnosing IgG4-related disease involving the uterus.
Letters to the Editor
FIG. 1 Radiological and pathological findings of IgG4-related disease involving the uterus
B
D
E
C
Contrast-enhanced whole-body CT showing (A) bilateral pleural effusions and thickening of the soft tissue around the descending thoracic aorta (arrow) and (B) an enlarged heterogeneously enhancing uterus (arrow). (C) Uptake of [18F]fluorodeoxyglucose as measured by PET is observed in the bilateral pleura, periaortic lesion and uterus. (D) Histopathologically the myometrium shows fibrosis with infiltration of lymphocytes, plasma cells and eosinophils. (E) On immunostaining, numerous IgG4-positive plasma cells are seen. In conclusion, we demonstrate that IgG4-related disease can involve the uterus. Additional case descriptions are required to better characterize the pathological and clinical features of uterine IgG4-related disease. Rheumatology key message .
References
It is important to recognize that IgG4-related disease can involve the uterus.
Funding: No specific funding was received from any funding bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article. Disclosure statement: The authors have declared no conflicts of interest. 1
2
Hirotsugu Ohkubo , Mikinori Miyazaki , Tetsuya Oguri1, Atsushi Arakawa3, Yoichiro Kobashi4 and Akio Niimi1 1 Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 2Department of Pulmonary Medicine, Nagoya Memorial Hospital, Nagoya, 3Department of Obstetrics and Gynaecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, and 4 Department of Pathology, Tenri Hospital, 200 Mishima-cho, Tenri, Nara, Japan Accepted 3 February 2015 Correspondence to: Hirotsugu Ohkubo, Department of
www.rheumatology.oxfordjournals.org
Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 4678601, Japan. E-mail: [email protected]
1 Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012;366:53951. 2 Deshpande V, Zen Y, Chan JK et al. Consensus statement on the pathology of IgG4-related disease. Mod Pathol 2012;25:118192. 3 Sekiguchi H, Horie R, Utz JP, Ryu JH. IgG4-related systemic disease presenting with lung entrapment and constrictive pericarditis. Chest 2012;142:7813. 4 Zen Y, Inoue D, Kitao A et al. IgG4- related lung and pleural disease: a clinicopathologic study of 21 cases. Am J Surg Pathol 2009;33:188693. 5 Simionescu C, Ma˘rga˘ritescu C, Stepan A, Ciurea R, Cernea N. Uterine pseudotumors. Rom J Morphol Embryol 2011;52:74358. 6 Zen Y, Fujii T, Sato Y, Masuda S, Nakanuma Y. Pathological classification of hepatic inflammatory pseudotumor with respect to IgG4-related disease. Mod Pathol 2007;20:88494. 7 Kanno A, Ishida K, Hamada S et al. Diagnosis of autoimmune pancreatitis by EUS-FNA by using a 22-gauge needle based on the International Consensus Diagnostic Criteria. Gastrointest Endosc 2012;76:594602.
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