Case report
A case of IgG4-related syndrome presenting with a fibroma molle-like nodule Kazutoshi Harada, MD, PhD, Miyuki Yamaguchi, MD, PhD, Tatsuyoshi Kawamura, MD, Naotaka Shibagaki, MD, PhD, and Shinji Shimada, MD, PhD
PhD,
Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan Correspondence Kazutoshi Harada,
MD, PhD
1110 Shimogato, Chuo Yamanashi 409-3898, Japan E-mail: [email protected]
Conflicts of interest: None.
Case report A 76-year-old man presented with a nodule on the upper part of his left arm. He had first noticed the nodule two months previously. His medical history included renal dysfunction of unknown etiology. On physical examination, a slightly reddish, elastic, soft nodule was apparent on the upper part of the left arm (Fig. 1a). The area surrounding the nodule exhibited redness; however, the patient did not report pain or itching. A diagnosis of soft fibroma was made, and the nodule was totally resected. Histological examination of the nodule showed a dense infiltration of inflammatory cells in the dermis (Fig. 1b). The inflammatory lesion surrounded by fibrosis predominantly consisted of plasma cells with a few histiocytes and lymphocytes (Fig. 1c). The infiltrated plasma cells did not show nuclear atypia and light chain restriction. Immunohistochemistry against human immunoglobulin G4 (IgG4) detected plasma cells expressing IgG4 at the site of the lesion (Fig. 2). The average number of IgG4-positive plasma cells was 64 per high-power field, and the average IgG4+ : IgG+ cells ratio was 74.6%. A full blood cell count showed mild anemia. Mild renal dysfunction (blood urea nitrogen, 33.8 mg/dl; creatinine, 1.33 mg/dl) was detected by biochemical examination of the blood. Serum Ig levels were: IgG, 2800 mg/dl; IgA, 536 mg/dl; IgM, 89 mg/dl; and IgE, 4372 IU/ml. Serum IgG4 was increased to 320 mg/dl (normal range: 4– 108 mg/dl). Computed tomography did not show mass lesions suspicious for IgG4-related syndrome in the panª 2014 The International Society of Dermatology
creas, bile duct, liver, kidneys, or retroperitoneal area. Because the patient was suspected of having renal dysfunction attributable to IgG4-related syndrome, he was referred to the nephrology department for renal biopsy; however, he refused the examination. On the basis of these findings, we diagnosed this case as IgG4-related syndrome accompanied by a skin nodule. Discussion Immunoglobulin G4-related syndrome was defined only recently.1 It is characterized by the involvement of a wide variety of tissues, including the pancreas, liver, kidneys, and lacrimal glands, and by lymphoplasmacytic infiltrates and fibrosis, elevated serum IgG4 titer, and increased IgG4-positive plasma cells in tissues. Several cases of this syndrome that include cutaneous manifestations have been reported.2–5 These cases involved acquired reactive perforating collagenosis, multiple red papules, indurated plaques, erythematous nodules, and indurated subcutaneous nodules. By contrast, the present patient demonstrated an elastic, soft, slightly reddish, multilobular nodule on the arm. To the best of our knowledge, this is the first case of IgG4-related syndrome to manifest as a fibroma molle-like nodule. Previously reported patients with IgG4-related syndrome that included a cutaneous manifestation were affected by Mikulicz’s disease, which is included in IgG4-related syndrome. However, the present patient showed renal dysfunction presumably caused by IgG4-related syndrome and developed a soft, International Journal of Dermatology 2015, 54, e163–e165
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Case report
A fibroma molle-like nodule in IgG4-related syndrome
Harada et al.
(a)
(b)
Figure 1 (a) Clinical examination reveals a slightly reddish, multilobular, elastic, soft nodule on the left upper arm of a 76-year-old man. Histopathology shows (b) nodular infiltration of inflammatory cells surrounded by fibrosis, and (c) dense infiltration of plasma cells without cell atypia. [Hematoxylin and eosin stain; original magnification (b) 940, (c) 9200]
(c)
(a)
(b)
(c)
Figure 2 Immunohistochemistry shows the infiltration of plasma cells expressing immunoglobulin G4 (IgG4). (a) Massive infiltration of plasma cells expressing IgG (red). Nuclear counterstaining with DAPI is shown in blue. (b) Immunohistochemical staining for IgG4 (green). (c) Merged image showing the co-localization of whole IgG and IgG4. (Original magnification: [a-c] 9400)
fibroma-like nodule. These findings may suggest that skin symptoms differ between patients with Mikulicz’s disease and those with other types of IgG4-related syndrome, such as autoimmune pancreatitis and retroperitoneal fibrosis. Recently, this syndrome was classified into five groups according to the location of lesions.6 With further clinical investigation, cutaneous manifestations of IgG4related syndrome may be divided into several subclasses according to which organs are affected. The solitary skin lesion reported here was composed of plasmacytes; therefore, primary cutaneous plasmacytoma should be International Journal of Dermatology 2015, 54, e163–e165
excluded. Primary cutaneous plasmacytoma is a rare cutaneous B cell lymphoma caused by malignant proliferations of plasma cells in skin without an underlying multiple myeloma.7 Histologically, primary cutaneous plasmacytoma is characterized by a diffuse or nodular infiltrate of plasma cells, with cell atypia. In the present case, histological analysis showed dense infiltration of plasma cells without nuclear atypia and no light chain restriction on immunohistochemistry. Hence, we diagnosed the nodule as a skin manifestation of IgG4-related syndrome. ª 2014 The International Society of Dermatology
Harada et al.
References 1 Sato Y, Notohara K, Kojima M, et al. IgG4-related disease: historical overview and pathology of hematological disorders. Pathol Int 2010; 60: 247–258. 2 Hattori T, Miyanaga T, Tago O, et al. Isolated cutaneous manifestation of IgG4-related disease. J Clin Pathol 2012; 65: 815–818. 3 Hamaguchi Y, Fujimoto M, Matsushita Y, et al. IgG4-related skin disease, a mimic of angiolymphoid hyperplasia with eosinophilia. Dermatology 2011; 223: 301–305. 4 Shiomi T, Yoshida Y, Horie Y, et al. Acquired reactive perforating collagenosis with the histological features of
ª 2014 The International Society of Dermatology
A fibroma molle-like nodule in IgG4-related syndrome
Case report
IgG4-related sclerosing disease in a patient with Mikuliczs disease. Pathol Int 2009; 59: 326–331. 5 Cheuk W, Lee KC, Chong LY, et al. IgG4-related sclerosing disease: a potential new etiology of cutaneous pseudolymphoma. Am J Surg Pathol 2009; 33: 1713– 1719. 6 Zen Y, Nakanuma Y. IgG4-related disease: a crosssectional study of 114 cases. Am J Surg Pathol 2010; 34: 1812–1819. 7 Kazakov DV, Belousova IE, Muller B, et al. Primary cutaneous plasmacytoma: a clinicopathological study of two cases with a longterm follow-up and review of the literature. J Cutan Pathol 2002; 29: 244–248.
International Journal of Dermatology 2015, 54, e163–e165
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A case of IgG4-related syndrome presenting with a fibroma molle-like nodule Kazutoshi Harada, MD, PhD, Miyuki Yamaguchi, MD, PhD, Tatsuyoshi Kawamura, MD, Naotaka Shibagaki, MD, PhD, and Shinji Shimada, MD, PhD
PhD,
Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan Correspondence Kazutoshi Harada,
MD, PhD
1110 Shimogato, Chuo Yamanashi 409-3898, Japan E-mail: [email protected]
Conflicts of interest: None.
Case report A 76-year-old man presented with a nodule on the upper part of his left arm. He had first noticed the nodule two months previously. His medical history included renal dysfunction of unknown etiology. On physical examination, a slightly reddish, elastic, soft nodule was apparent on the upper part of the left arm (Fig. 1a). The area surrounding the nodule exhibited redness; however, the patient did not report pain or itching. A diagnosis of soft fibroma was made, and the nodule was totally resected. Histological examination of the nodule showed a dense infiltration of inflammatory cells in the dermis (Fig. 1b). The inflammatory lesion surrounded by fibrosis predominantly consisted of plasma cells with a few histiocytes and lymphocytes (Fig. 1c). The infiltrated plasma cells did not show nuclear atypia and light chain restriction. Immunohistochemistry against human immunoglobulin G4 (IgG4) detected plasma cells expressing IgG4 at the site of the lesion (Fig. 2). The average number of IgG4-positive plasma cells was 64 per high-power field, and the average IgG4+ : IgG+ cells ratio was 74.6%. A full blood cell count showed mild anemia. Mild renal dysfunction (blood urea nitrogen, 33.8 mg/dl; creatinine, 1.33 mg/dl) was detected by biochemical examination of the blood. Serum Ig levels were: IgG, 2800 mg/dl; IgA, 536 mg/dl; IgM, 89 mg/dl; and IgE, 4372 IU/ml. Serum IgG4 was increased to 320 mg/dl (normal range: 4– 108 mg/dl). Computed tomography did not show mass lesions suspicious for IgG4-related syndrome in the panª 2014 The International Society of Dermatology
creas, bile duct, liver, kidneys, or retroperitoneal area. Because the patient was suspected of having renal dysfunction attributable to IgG4-related syndrome, he was referred to the nephrology department for renal biopsy; however, he refused the examination. On the basis of these findings, we diagnosed this case as IgG4-related syndrome accompanied by a skin nodule. Discussion Immunoglobulin G4-related syndrome was defined only recently.1 It is characterized by the involvement of a wide variety of tissues, including the pancreas, liver, kidneys, and lacrimal glands, and by lymphoplasmacytic infiltrates and fibrosis, elevated serum IgG4 titer, and increased IgG4-positive plasma cells in tissues. Several cases of this syndrome that include cutaneous manifestations have been reported.2–5 These cases involved acquired reactive perforating collagenosis, multiple red papules, indurated plaques, erythematous nodules, and indurated subcutaneous nodules. By contrast, the present patient demonstrated an elastic, soft, slightly reddish, multilobular nodule on the arm. To the best of our knowledge, this is the first case of IgG4-related syndrome to manifest as a fibroma molle-like nodule. Previously reported patients with IgG4-related syndrome that included a cutaneous manifestation were affected by Mikulicz’s disease, which is included in IgG4-related syndrome. However, the present patient showed renal dysfunction presumably caused by IgG4-related syndrome and developed a soft, International Journal of Dermatology 2015, 54, e163–e165
e163
e164
Case report
A fibroma molle-like nodule in IgG4-related syndrome
Harada et al.
(a)
(b)
Figure 1 (a) Clinical examination reveals a slightly reddish, multilobular, elastic, soft nodule on the left upper arm of a 76-year-old man. Histopathology shows (b) nodular infiltration of inflammatory cells surrounded by fibrosis, and (c) dense infiltration of plasma cells without cell atypia. [Hematoxylin and eosin stain; original magnification (b) 940, (c) 9200]
(c)
(a)
(b)
(c)
Figure 2 Immunohistochemistry shows the infiltration of plasma cells expressing immunoglobulin G4 (IgG4). (a) Massive infiltration of plasma cells expressing IgG (red). Nuclear counterstaining with DAPI is shown in blue. (b) Immunohistochemical staining for IgG4 (green). (c) Merged image showing the co-localization of whole IgG and IgG4. (Original magnification: [a-c] 9400)
fibroma-like nodule. These findings may suggest that skin symptoms differ between patients with Mikulicz’s disease and those with other types of IgG4-related syndrome, such as autoimmune pancreatitis and retroperitoneal fibrosis. Recently, this syndrome was classified into five groups according to the location of lesions.6 With further clinical investigation, cutaneous manifestations of IgG4related syndrome may be divided into several subclasses according to which organs are affected. The solitary skin lesion reported here was composed of plasmacytes; therefore, primary cutaneous plasmacytoma should be International Journal of Dermatology 2015, 54, e163–e165
excluded. Primary cutaneous plasmacytoma is a rare cutaneous B cell lymphoma caused by malignant proliferations of plasma cells in skin without an underlying multiple myeloma.7 Histologically, primary cutaneous plasmacytoma is characterized by a diffuse or nodular infiltrate of plasma cells, with cell atypia. In the present case, histological analysis showed dense infiltration of plasma cells without nuclear atypia and no light chain restriction on immunohistochemistry. Hence, we diagnosed the nodule as a skin manifestation of IgG4-related syndrome. ª 2014 The International Society of Dermatology
Harada et al.
References 1 Sato Y, Notohara K, Kojima M, et al. IgG4-related disease: historical overview and pathology of hematological disorders. Pathol Int 2010; 60: 247–258. 2 Hattori T, Miyanaga T, Tago O, et al. Isolated cutaneous manifestation of IgG4-related disease. J Clin Pathol 2012; 65: 815–818. 3 Hamaguchi Y, Fujimoto M, Matsushita Y, et al. IgG4-related skin disease, a mimic of angiolymphoid hyperplasia with eosinophilia. Dermatology 2011; 223: 301–305. 4 Shiomi T, Yoshida Y, Horie Y, et al. Acquired reactive perforating collagenosis with the histological features of
ª 2014 The International Society of Dermatology
A fibroma molle-like nodule in IgG4-related syndrome
Case report
IgG4-related sclerosing disease in a patient with Mikuliczs disease. Pathol Int 2009; 59: 326–331. 5 Cheuk W, Lee KC, Chong LY, et al. IgG4-related sclerosing disease: a potential new etiology of cutaneous pseudolymphoma. Am J Surg Pathol 2009; 33: 1713– 1719. 6 Zen Y, Nakanuma Y. IgG4-related disease: a crosssectional study of 114 cases. Am J Surg Pathol 2010; 34: 1812–1819. 7 Kazakov DV, Belousova IE, Muller B, et al. Primary cutaneous plasmacytoma: a clinicopathological study of two cases with a longterm follow-up and review of the literature. J Cutan Pathol 2002; 29: 244–248.
International Journal of Dermatology 2015, 54, e163–e165
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