DOI: https://doi.org/10.21203/rs.3.rs-2861607/v1
Background: Malignant transformation of ovarian mature cystic teratoma rarely develops, especially when multiple malignant components simultaneously occur.
Case presentation:A 47-year-old woman presented with a 12-month history of intermittent abdominal distension and pain along with bloody stool for 3 weeks. Abdominal computed tomography revealed a cystic mass in the right ovary adjacent to the colon. Additionally, fluids were observed in the colon cavity . Colonoscopy showed a protuberant mass on the surface of the sigmoid colon covered with blood . Considering the large size of the colonic mass and the undetermined diagnosis of the mass, the patient underwent laparoscopic partial colectomy, hysterectomy, and bilateral appendage resection.Grossly, the ovarian cyst was connected to the colon wall, and the cut surface of the colon tumor was cystic and contained mucus. Histopathological examination revealed that the surface of colonic lesions was the granulation tissue, and the lower part was composed of fibrous stroma and mucinous cyst. The cyst wall was covered with columnar cells and contained abundant intracellular mucin. No nuclear atypia was observed. The lesions penetrated the entire intestinal wall and connected with ovarian cysts. Mucus, lipids, and hair could be observed in the ovarian cyst cavity. Histopathological examination showed that the cyst wall was lined with stratified squamous epithelium, and the sebaceous glands could be observed in the fibrous stroma of the cyst wall. Thyroid follicular components could be found in the surrounding area, and some cells were arranged in a chrysanthemum-like cluster . Under high magnification, the nuclei of these cells were characterized as pepper-salt-like . In another area, the typical papillary structure of papillary thyroid carcinoma and the formation of multiple cysts containing mucus were observed; some of which were lined with columnar epithelium containing goblet cells . Under high magnification, the nuclei of these papillae were crowded, ground glass-like, with nuclear grooves. Notably, no malignant tumor components were observed in the colon wall and colon polyps, which are only composed of benign mucinous epithelium. Based on these findings, the patient was suspected of ovarian mature cystic teratoma, which contained mucinous cysts, carcinoids, goiters, and papillary thyroid carcinoma. Moreover, mucinous cysts involved the colon wall and formed a polypoid appearance. At the time of this writing, 6 months had passed since treatment completion, without clinical or histological evidence of recurrence.
Conclusion: Herein, we present a rare case of malignant ovarian mature cystic teratoma, including mucinous cysts, goiters, papillary thyroid carcinoma, and carcinoids. The tumor remarkably invaded the intestinal wall and formed a benign polypoid appearance, suggesting the occurrence of this rare tumor type should be considered when intestinal polyps are found during gastrointestinal endoscopy.
Malignant transformation is a rare complication of mature cystic teratoma, occurring in approximately 2% of cases [1]. Ovarian mature cystic teratoma can be accompanied by goiter, papillary thyroid carcinoma [2], and carcinoid [3]; however, the simultaneous occurrence of three components is particularly rare [4, 5]. Ovarian cancer can invade the colon, often manifested as bowel obstruction, anemia, perforation, vague abdominal discomfort, and rarely bowel intussusception or fistulization [6]. Ovarian mucinous neoplasms may occur with mature ovarian teratomas, and a significant proportion of these neoplasms present with pseudomyxoma peritonei and mucinous carcinoma [7]. Here, we present a case of mature ovarian teratoma in which mucinous cysts, carcinoids, goiters, and papillary thyroid carcinoma were also observed in the tumor. The invasion of an ovarian tumor to the rectum that formed a benign polypoid appearance makes this case more special.
A 47-year-old woman presented with a 12-month history of intermittent abdominal distension and pain along with bloody stool for 3 weeks. The patient’s symptoms started 12 month prior and had worsened over the last 3 week.She had no previous medical history. He had no history of food or drug allergy and no family history of gastrointestinal tumors.The temperature of the patient was 36.7°C, heart rate was 97 beats per minute, breathing rate was 16 beats per minute, and blood pressure was 132/77 mmHg. Examination of the chest and lung showed no abnormalities.Laboratory findings showed Significantly elevated CA-125 (cancer antigen 125) (124 U/ml) and normal findings across the rest of tumor makers(CEA/CA19-9/CA153).Abdominal computed tomography showed a large solid-cystic intra-abdominal mass (sized 77 × 51 mm), adjacent to the colon, originating from the right ovary, omental thickening in the vicinity of the tumor. Additionally, fluids were observed in the colon cavity. There was no obvious abnormality in the uterus and left ovary. (Fig. 1A). Colonoscopy showed a protuberant mass on the surface of the sigmoid colon covered with blood (Fig. 1B). The lesion was then biopsied. Microscopically, granulation tissues, and inflammatory exudates were observed; however, no tumor cell component was found. Considering the large size of the colonic mass and the undetermined diagnosis of the mass, the patient underwent laparoscopic partial colectomy, hysterectomy, and bilateral appendage resection. Laparoscopic exploration revealed that the right ovarian tumor with dense adhesion to a segment of the sigmoid colon, and suspicious cancer implants were found in the omentum. No obvious cancer tissue was found on the surface of the liver, uterus, and left appendage. The total operation time is about four hours. The patient lost approximately 1000 ml of blood during the operation. Hand sewn colonic anastomosis was used for colon anastomosis. There were no obvious complications during and after the operation.Grossly, the ovarian cyst was connected to the colon wall, and the cut surface of the colon tumor was cystic and contained mucus. Histopathological examination revealed that the surface of colonic lesions was the granulation tissue, and the lower part was composed of fibrous stroma and mucinous cyst. The cyst wall was covered with columnar cells and contained abundant intracellular mucin. No nuclear atypia was observed (Fig. 1C). The lesions penetrated the entire intestinal wall and connected with ovarian cysts (Fig. 1D). Mucus, lipids, and hair could be observed in the ovarian cyst cavity. Histopathological examination showed that the cyst wall was lined with stratified squamous epithelium, and the sebaceous glands could be observed in the fibrous stroma of the cyst wall. Thyroid follicular components could be found in the surrounding area, and some cells were arranged in a chrysanthemum-like cluster (Fig. 1E). Under high magnification, the nuclei of these cells were characterized as pepper-salt-like (Fig. 1F). In another area, the typical papillary structure of papillary thyroid carcinoma and the formation of multiple cysts containing mucus were observed; some of which were lined with columnar epithelium containing goblet cells (Fig. 1G). Under high magnification, the nuclei of these papillae were crowded, ground glass-like, with nuclear grooves (Fig. 1H). Notably, no malignant tumor components were observed in the colon wall and colon polyps, which are only composed of benign mucinous epithelium. Immunohistochemical staining was performed to analyze the expression of TTF1(catalogue number:8G7G3/1),TG(catalogue number:OTI8F2),Syn(catalogue number:UMAB112),CgA(catalogue number:LK2H10),Ki67(catalogue number:UMAB107) and CK(catalogue number:AE1/AE3) (supplier:ZSGB-BIO).Tissue sections were incubated at 70°C for 1 h, followed by incubation with 100% xylene for 10 min, 100% ethanol twice for 5 min each, and then 95%, 90%, and 80% ethanol for 2 min each. The slides were washed and repaired under high pressure. After setting up and running the automatic immunohistochemical stainer program, slides were counterstained, differentiated, subjected to anti-blue staining, dehydrated, and cleared. Slides were finally observed under a microscope. Fibrous connective tissue within the tissue was used as a negative control.Immunohistochemical results showed that those papillary thyroid carcinomas were positive for TTF1(Thyroid follicular epithelial marker) and TG(Thyroid follicular epithelial marker) (Fig. 2A-B) and the cells arranged in a chrysanthemum-like cluster were positive for Syn(Neuroendocrine marker) and CgA (Neuroendocrine marker) (Fig. 2C-D). Ki67 showed that approximately 20% of the papillary carcinoma cells were positive (Fig. 2E). CK(Epithelial marker) immunohistochemical staining was diffusely positive (Fig. 2F).Based on these findings, the patient was suspected of ovarian mature cystic teratoma, which contained mucinous cysts, carcinoids, goiters, and papillary thyroid carcinoma. Moreover, mucinous cysts involved the colon wall and formed a polypoid appearance. The patient underwent laparoscopic partial colectomy, hysterectomy, and bilateral appendage resection.At the time of this writing, 6 months had passed since treatment completion, without clinical or histological evidence of recurrence.
Malignant transformation may occur in a small number of ovarian mature cystic teratomas, occurring in approximately 2% of cases; however, one study reported that the incidence was 4% [15]. The age range of patients with malignant mature cystic teratoma reported in the literature is 19–88 years, which commonly occurs in postmenopausal women [16]. Most cases of malignant transformation are in the form of squamous cell carcinoma. However, thyroid carcinoma, which may occur with struma ovarii, and carcinoid tumors, is one of the less commonly reported malignancies. A single mature cystic teratoma containing multiple types of malignant transformation is even rarer [4, 5]. A study on the malignant transformation of ovarian mature cystic teratoma from three gynecological centers in Italy showed that nine (39.1%) patients were histologically diagnosed with squamous cell carcinoma, five (21.7%) with thyroid carcinoma, six (26.1%) with carcinoid, one (4.3%) with papillary renal carcinoma, one (4.3%) with medulloblastoma and one (4.3%) with intestinal-type mucinous adenocarcinoma. The clinical outcome of early-stage malignancies associated with mature ovarian teratomas is excellent at post-treatment [8].
The spread of ovarian cancer to the colorectum may occur in four different ways: hematogenous metastasis, lymphatic metastasis, direct invasion, and peritoneal dissemination [9]. Haraoka et al. in an autopsy series reported that colorectal metastases present with an ovarian origin in approximately 6.0% of cases and represent approximately 30.5% of all ovarian cancers [10]. However, these reports are all related to malignant ovarian tumors, and reports of benign ovarian mucinous cysts involving the colon are particularly rare. According to reports, the dissemination of malignantly transformed ovarian mature cystic teratoma is different from other germ-cell-derived tumors. Tumor dissemination through direct invasion and peritoneal implantation usually does not metastasize to the lymph nodes [15, 16]. The formation of fistulas and invasion into the neighboring organs are extremely rare complications for ovarian mature cystic teratomas. The invasion of malignant cells into neighboring organs due to malignant transformation of the tumor is reported as the cause of fistula formation into the neighboring organs. A review of 17 cases revealed that fistula formation due to malignant transformation comprised only 4 cases (23.5%), with inflammation as the actual cause in the majority of cases (13 cases, 76.5%)[21]. In our case, various malignant components appeared in ovarian mature cystic teratoma; however, only benign mucus epithelium was observed in the area that invaded the colon, and no typical malignant components were observed.
Non-neoplastic polyps of the colon include hyperplastic, hamartomatous (juvenile polyps, Peutz-Jeghers polyps), inflammatory, and mucosal polyps. Neoplastic polyps show epithelial dysplasia by the definition and include adenomas and carcinomas [11]. In a few cases, some special intestinal diseases may also have a polypoid appearance, such as inflammatory bowel disease and Colitis cystica profunda [12, 13]. Our case showed that the ovarian tumor invaded the intestinal wall, forming a polypoid appearance. A biopsy of the polyp surface only found some granulation tissues and necroses, which is not helpful for the diagnosis. The main body of intestinal polyps is mainly composed of some benign mucus epithelium, fibrous stroma, and smooth muscle. This particular case of ovarian tumor invading the intestinal wall caused a polypoid appearance in the intestinal cavity, which suggests that this special situation should be considered when finding intestinal polyps during the gastrointestinal endoscopic biopsy.
Ovarian mature cystic teratoma with malignant transformation is rare and has a poor outcome. Early detection and complete surgical resection of the tumor, along with an early FIGO stage, are crucial to patient survival. The limited number of cases for analysis makes definite conclusions regarding the appropriate adjuvant chemotherapy for this disease difficult [14]. The treatment method is excision of the uterus and bilateral appendages [17, 18]. Because the tumor is usually unilateral, a more conservative surgical treatment plan may be as effective as for cases that have not penetrated the capsule and are not involved in the adjacent tissues. If the tumor has metastasized outside the ovary and adjacent tissues, a more radical approach is recommended, including removal of the tumor and affected tissues or organs. Some reports also confirmed that tumors are not sensitive to chemotherapy [15]. Although some patients have received chemotherapy and multidisciplinary management, the recurrence rate and mortality rate are still high[19].However, according to a recently published systematic review, early hysterectomy and platinum chemotherapy appear to be associated with better survival[20].Our patient underwent laparoscopic partial colectomy, hysterectomy, and bilateral appendage resection. The patient did not receive chemotherapy and radiotherapy, and at 6 months post-treatment, no evidence of recurrence or metastasis was found.
In this report, a rare case of ovarian mature cystic teratoma with malignant transformation is presented with mucinous cysts, carcinoids, goiters, and papillary thyroid carcinoma components. Notably, ovarian tumors invade the colon, which forms a benign polypoid appearance in the intestinal cavity, which suggests that the possibility of this rare tumor type should be considered when intestinal polyps were detected during gastrointestinal endoscopy.
Acknowledgements
Not applicable.
Funding
Jilin Provincial Science and Technology Development Plan Project 20190201222JC.
Author information
Authors and Affiliations
Department of Pathology, Lequn Branch,The First Hospital of Jilin University, Changchun, Jilin, China, 130021
Jixuan Liu,Jinsong Ni and Yafang Liu
Author contributions
Jixuan Liu and Yafang Liu contributed to the manuscript design and drafting, and reviewed the literature; Jixuan Liu and Nicui contributed to analysis and interpretation of the imaging and pathology findings, and revision of the manuscript; Jixuan Liu and Jinsong Ni was responsible for language editing of article;All authors issued final approval for the version to be submitted.
Availability of data and materials
All data generated or analyzed during this study are included in this published article.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Patients were not involved in the design, or conduct, or reporting, or dissemination plans of this research. The patient's written consent for publication was obtained.
Competing interests
The authors declare having no conflicts of interest.
|
Marker
|
papillary thyroid carcinomas
|
the cells arranged in a chrysanthemum-like cluster(carcinoids)
|
goiters
|
mucinous cysts
|
|---|---|---|---|---|
|
TTF1
|
+
|
-
|
+
|
-
|
|
TG
|
+
|
-
|
+
|
-
|
|
Syn
|
-
|
+
|
-
|
-
|
|
CgA
|
-
|
+
|
-
|
-
|
|
Ki67
|
+ 20%
|
+ 5%
|
+༜2%
|
+༜2%
|
|
CK
|
+
|
+
|
+
|
+
|
| TTF1: Thyriod transcription factor-1,TG: thyroglobulin,Syn: Synaptophysin,CgA: Chromogranin A, | ||||
| Ki67: Anti-Ki67 antibody, CK:Cytokeratin. | ||||