2021, Volume 37, Number 1, Page(s) 063-066
IgG4-Related Disease of the Ovary
Sevda AKYOL, Fatma ÖZ ATALAY, Secil HASDEMIR, Ömer YERCI
Department of Pathology, Bursa Uludag University Faculty of Medicine, BURSA, TURKEY
Keywords: IgG4-related disease, Ovary, Fibrosis, Lymphoplasmacytic infiltration
Immunoglobulin G4-related disease is characterized by dense fibrosis, obliterative phlebitis, and lymphoplasmacytic infiltration that contains
abundant IgG4 positive plasma cells. It causes tumefactive lesions in the involved organs and is most commonly seen in the salivary glands,
pancreas, and retroperitoneum. Ovarian involvement has been reported in only two cases. In our case, a 58-year-old female patient presented
with abdominal distention and pain. Pelvic computed tomography revealed a soft tissue lesion compatible with the omental cake, several
intraabdominal implants, and bilateral adnexal fullness. A laparotomy was performed under suspicion of peritoneal carcinomatosis secondary
to bilateral adnexal mass. In the histopathologic examination, abundant lymphoplasmacytic infiltration and dense fibrosis were observed in
both ovaries and the peritoneum. In the areas of greatest density, the density of IgG4-positive plasma cells was found to range from 40 to 50 per
high-power field. The patient was accepted as suffering from probable IgG4-related disease because of the bilateral involvement of the ovaries
and the histopathological findings. In conclusion, we present this case to draw attention to the fact that IgG4-related disease can also be seen in
Immunoglobulin G4-related disease (IgG4-RD) is
characterized by dense fibrosis, obliterative phlebitis and
lymphoplasmacytic infiltration that contains abundant
IgG4-positive plasma cells 1
. IgG4-RD was first identified
in the pancreas as autoimmune pancreatitis 2
lesions similar to those of the pancreas were defined in
many organs, including the bile ducts, gallbladder, lymph
nodes, retroperitoneum, mesentery, breasts, prostate gland,
and skin 3-8
. However, IgG4-RD in the female genital
tract has been reported in very few cases 9-11
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.
A 58-year-old female patient presented with abdominal
distention and pain and underwent further investigations
after a pelvic mass was detected at an external center.
Ultrasonography (USG) revealed mass lesions on both
ovaries; the mass on the right ovary was 4 × 3.5 cm, and
the mass on the left ovary was 4.2 × 2.7 cm. The largest
metastatic nodule in the omentum was 5.4 × 4.2 cm.
Pelvic computed tomography (CT) showed a 15-cm long, 3-cm thick soft tissue lesion compatible with the
omental cake, several intraabdominal implants suggesting
increases in nodular thickness, bilateral adnexal fullness,
and pelvic peritoneal implants (Figure 1
). As a result of
these radiological findings, peritoneal carcinomatosis was
considered, and the patient underwent hysterectomy and
bilateral salpingo-oophorectomy due to the adnexal mass.
The patient’s blood values were normal, and only CA125
was high (72 U/mL) among the tumor markers.
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
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
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 patient’s
operation. No additional treatment was given to the patient
following the operation.
Click Here to Zoom
|Figure 2: A) Dense fibrosis
B) A dense parenchymal
study showing the density of
IgG4 positive cells. It ranged
from 40 to 50 IgG4 positive
cells per HPF (IHC; x400).
study showing the density
of IgG positive cells (IHC;
IgG4-RD is a relatively recently defined systemic
fibroinflammatory process 12
. It was first reported in the
pancreas in 2001 2
. Since then, it has been identified in
many organs in the body.
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
Maruyama’s case 10.
In our case, IgG4 levels were within normal limits in the
blood samples taken three weeks postoperatively. In
Maruyama’s reported case, serum IgG4 concentration
was 1,000 mg/dL on day seven postoperatively, and in
Sekulic’s reported case, serum IgG4 concentration was not
Histopathologically, intense lymphoplasmacytic infiltration
was observed in all three ovarian IgG4-RD cases.
In Sekulic’s 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 Maruyama’s reported case, more than 90% of
the plasma cells in the HPF showed positive staining
immunohistochemically with IgG4 10. In Sekulic’s
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.
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
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
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 (Küttner’s tumor). Am J Surg
8) Hennessey JV. Riedel’s 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.
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
11) Sekulic M, Sekulic SP, Movahedi-Lankarani S. IgG4-related
disease of the ovary: A first description. Int J Gynecol Pathol.
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.
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
14) Martinez-Valle F, Orozco-Galvez O, Fernandez-Codina A.
Update in ethiopathogeny, diagnosis and treatment of the IgG4
related disease. Med Clin. 2018;151:18-25.
15) Carruthers MN, Khosroshahi A, Augustin T, Deshpande V,
Stone JH. The diagnostic utility of serum IgG4 concentrations in
IgG4-related disease. Ann Rheum Dis. 2015;74:14-8.