Igg4-related disease of the ovary

DOI: 10.5146/tjpath.2020.01500 Viewed: 5341 - Downloaded : 1542 In this case report, we present probable IgG4-RD involving the bilateral ovaries in which a bilateral ovarian mass together with peritoneal and omental involvement mimicked advanced ovarian cancer. Figure 1: Axial computed tomography images of the pelvis. When the tissues were examined in frozen section, it was observed that the lesion contained intense fibrosis. Disseminated peritoneal leiomyomatosis was considered in the differential diagnosis due to the diffuse peritoneal involvement. Although a benign lesion was considered first, the final diagnosis was left to examination of the permanent sections. Macroscopic examination of the specimen showed areas of gray-white discoloration, the largest of which was 3 × 2.5 cm in diameter, on the anterior-posterior wall of the uterus and around the right and left tuba uterina. The right ovary was 3.5 cm in diameter, and the left ovary was 4 cm in diameter; the cross-sectional surfaces were irregular. Also, multiple intraabdominal serosal implants were located on the intestine and the appendix and in the right and left paracolic regions. On microscopic examination, intense fibrosis in an occasional storiform pattern was seen in both ovaries and peritoneal implants. Significant lymphoid follicles and intense lymphoplasmacytic inflammatory cell infiltration on the fibrotic ground were noteworthy. An immunohistochemical study determined the density of IgG4-positive cells. In a high power field (HPF), 40 to 50 IgG4 positive cells were found in the area of greatest density. The IgG4+/ IgG+ cell ratio was more than 40% (Figure 2AD). In conclusion, the patient was accepted as probable with IgG4-RD because of the bilateral involvement of the ovaries and the histopathological findings. Blood samples taken for IgG1, IgG2, IgG3 and IgG4 were within normal limits three weeks after the patients operation. No additional treatment was given to the patient following the operation. When diagnosing IgG4-RD, clinical, serological, and histopathological features are evaluated. IgG4-RD can affect a single organ or multiple organ systems and can be found bilaterally in organs, and an increase in the size of the affected organs or impairment of organ functions occurs [13]. Among the serological findings, the serum IgG4 concentration is expected to be >135 mg/dl; however, the serum IgG4 level did not increase in half of the reported cases [14]. Besides, the serum IgG4 level may also be high in patients with chronic diseases and certain malignancies [15]. The major histopathological findings of IgG4-RD include lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis. Lymphoplasmacytic infiltration is rich in IgG4 + plasma cells and often eosinophil leukocytes [12]. More than 10 IgG4 positive cells are present in the HPF of the biopsy samples, and the IgG4+/IgG+ cell ratio is more than 40%. If these three criteria are met, the diagnosis of IgG4-RD is definitive. Patients who meet only one of the serological or histopathological criteria and have organ symptoms probably have IgG4-RD. Patients with organ symptoms who do not meet the serological or histopathological criteria are unlikely to have IgG4-RD [13]. There are very few cases of IgG4-RD with ovarian involvement in the literature. In our case, bilateral ovarian enlargement was accompanied by peritoneal and omental implants as in the case reported by Maruyama [10]. In a case reported by Sekulic, the ovarian involvement was unilateral [11]. With these clinical findings, the preliminary diagnosis was advanced ovarian malignancy in both our case and Maruyamas case [10]. In our case, IgG4 levels were within normal limits in the blood samples taken three weeks postoperatively. In Maruyamas reported case, serum IgG4 concentration was 1,000 mg/dL on day seven postoperatively, and in Sekulics reported case, serum IgG4 concentration was not determined [10,11]. Histopathologically, intense lymphoplasmacytic infiltration was observed in all three ovarian IgG4-RD cases. In Sekulics case, the inflammation was reported to be rich in eosinophils [11]. In our case, there was intense fibrosis, whereas only Maruyama among the other two cases emphasized fibrosis [10]. We did not find phlebitis in our case, but phlebitis was seen in the other two cases [10,11]. The number of IgG4-positive cells required for the diagnosis of IgG4-RD varies with the organ involved [12]. In Maruyamas reported case, more than 90% of the plasma cells in the HPF showed positive staining immunohistochemically with IgG4 [10]. In Sekulics reported case, immunohistochemically 40 to 50 IgG4- positive cells were found per HPF, similar to our case [11]. In terms of histopathological features, multiple myeloma, lymphoproliferative diseases, spindle cell mesenchymal neoplasms, multicentric Castleman disease, and infections should be considered in the differential diagnosis of IgG4- RD. Therefore, when examining a sample with IgG4-RDlike histology, its clinical history should be considered. The evaluation of IgG4-RD in frozen section may also be difficult due to pronounced fibrosis. Disseminated peritoneal leiomyomatosis can be considered in the differential diagnosis in frozen evaluation. In our case, luteinized thecoma associated with sclerosing peritonitis was also included in the differential diagnosis due to the bilateral ovarian and peritoneal involvement. However, the absence of luteinized cells and the presence of intense lymphoplasmacytic inflammation with storiform fibrosis ruled out this disease. In conclusion, we reported the third case of ovarian IgG4- RD. In histopathological examinations, IgG4-RD, although very rare, should be considered in the differential diagnosis, particularly if marked lymphoplasmacytic inflammation with storiform fibrosis is observed in ovary. IgG4-RD responds well to prednisone therapy, which increases the importance of a correct diagnosis. Correct diagnosis also prevents unnecessary surgical interventions. CONFLICT of INTEREST The authors declare no conflict of interest. AUTHORSHIP CONTRIBUTIONS All authors contributed to titles such as concept, design, data collection or processing, analysis or interpretation, literature review, writing, approval. 1) Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med. 2012;366:539-51. 2) Hamano H, Kawa S, Horiuchi A,Unno H, Furuya N, Akamatsu T, Fukushima M, Nikaido T, Nakayama K, Usuda N, Kiyosawa K. High Serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344:732-8. 3) Zen Y, Harada K, Sasaki M, Sato Y, Tsuneyama K, Haratake J, Kurumaya H, Katayanagi K, Masuda S, Niwa H, Morimoto H, Miwa A, Uchiyama A, Portmann BC, Nakanuma Y. IgG4-related sclerosing cholangitis with and without hepatic inflammatory pseudotumor, and sclerosing pancreatitis-associated sclerosing cholangitis: Do they belong to a spectrum of sclerosing pancreatitis? Am J Surg Pathol. 2004;28:1193-203. 4) Cheuk W, Yuen HK, Chu SY, Chiu EK, Lam LK, Chan JK. Lymphadenopathy of IgG4 related sclerosing disease. Am J Surg Pathol. 2008;32:671-81. 5) Zen Y, Onodera M, Inoue D, Kitao A, Matsui O, Nohara T, Namiki M, Kasashima S, Kawashima A, Matsumoto Y, Katayanagi K, Murata T, Ishizawa S, Hosaka N, Kuriki K, Nakanuma Y. Retroperitoneal fibrosis: A clinicopathologic study with respect to immunoglobulin G4. Am J SurgPathol. 2009;33:1833-9. 6) Chen TS, Montgomery EA. Are tumefactive lesions classified as sclerosing mesenteritis a subset of IgG4-related sclerosing disorders? J Clin Pathol. 2008;6:1093-7. 7) Kitagawa S, Zen Y, Harada K, Sasaki M, Sato Y, Minato H, Watanabe K, Kurumaya H, Katayanagi K, Masuda S, Niwa H, Tsuneyama K, Saito K, Haratake J, Takagawa K, Nakanuma Y. Abundant IgG4- positive plasma cell infiltration characterizes chronic sclerosing sialadenitis (Küttners tumor). Am J Surg Pathol. 2005;29:783-91. 8) Hennessey JV. Riedels thyroiditis: A clinical review. J Clin Endocrinol Metab. 2011;96:3031-41. 9) Ohkubo H, Miyazaki M, Oguri T, Arakawa A, Kobashi Y, Niimi A. A rare case of IgG4-related disease involving the uterus. Rheumatology. 2015;54:1124-5. 10) Maruyama S, Sato Y, Taga A, Emoto I, Shirase T, Haga H. Immunoglobulin G4-related disease presenting as bilateral ovarian masses and mimicking advanced ovarian cancer. J Obstet Gynaecol Res.2016;42:103-8. 11) Sekulic M, Sekulic SP, Movahedi-Lankarani S. IgG4-related disease of the ovary: A first description. Int J Gynecol Pathol. 2016;36:190-4. 12) Deshpande V, Zen Y, Chan JK, Yi EE, Sato Y, Yoshino T, Klöppel G, Heathcote JG, Khosroshahi A, Ferry JA, Aalberse RC, Bloch DB, Brugge WR, Bateman AC, Carruthers MN, Chari ST, Cheuk W, Cornell LD, Fernandez-Del Castillo C, Forcione DG, Hamilos DL, Kamisawa T, Kasashima S, Kawa S, Kawano M, Lauwers GY, Masaki Y, Nakanuma Y, Notohara K, Okazaki K, Ryu JK, Saeki T, Sahani DV, Smyrk TC, Stone JR, Takahira M, Webster GJ, Yamamoto M, Zamboni G, Umehara H, Stone JH. Consensus statement on the pathology of IgG4-related disease. Mod Pathol. 2012;25:1181-92. 13) Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, Matsui S, Yoshino T, Nakamura S, Kawa S, Hamano H, Kamisawa T, Shimosegawa T, Shimatsu A, Nakamura S, Ito T, Notohara K, Sumida T, Tanaka Y, Mimori T, Chiba T, Mishima M, Hibi T, Tsubouchi H, Inui K, Ohara H. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD). Modern Rheumatology.2011;22:1,21-30. Keywords : IgG4-related disease, Ovary, Fibrosis, Lymphoplasmacytic infiltration