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Acta Med Philipp
Acta Med Philipp
AMP
Acta Medica Philippina
0001-6071
2094-9278
University of the Philippines Manila

AMP-58-15-8023
10.47895/amp.vi0.8023
Original Article
Malignant Transformation in a Mature Cystic Teratoma of the Ovary: A 5-year Descriptive Study
Billod Jimmy A. MD, MHCA 1
Manangan-Wong Rhesa Michelle MD 2
1 Department of Obstetrics and Gynecology, Baguio General Hospital and Medical Center
2 Department of Pathology, Baguio General Hospital and Medical Center
Corresponding author: Jimmy A. Billod, MD, MHCA, Department of Obstetrics and Gynecology, Baguio General Hospital and Medical Center Governors Pack Road, Baguio City 2600, Philippines. Email: jabillodmd@gmail.com. ORCiD: https://orcid.org/0000-0001-8422-0913
Oral Presentation - 27th Asia Oceana Federation of Obstetrics and Gynecology Hybrid Congress, May 23-26, 2022, Bali, Indonesia.

30 8 2024
2024
58 15 5560
© 2024 Acta Medica Philippina
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Articles are published under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.
Background and Objective

Malignant transformation (MT) in mature cystic teratoma of the ovary (MCTO) is rare. This descriptive study primarily aims to determine the prevalence rate of MT in MCTO and describe clinicopathologic features, management, and prognosis of patients who developed this rare type of tumor and likewise deliver a review in the light of recent literature.

Methods

This is a descriptive observational study of 22 patients with MT in MCTO at a Level 3 Tertiary Public Hospital in Baguio City, Philippines. The clinical and pathological records of each patient were reviewed. Descriptive statistics were used.

Results

Between January 2016 to December 2020, of the 369 cases of mature cystic teratoma, 22 cases with malignant transformation were reported with an incidence of 6%. The mean age of diagnosis was 52 years, of which 70% are aged 50 years old and above. Fifty-nine percent (13/22) and 32% (7/22) of the cases were squamous cell carcinoma and mucinous adenocarcinoma, respectively. Very rarely, malignant transformations were carcinoid tumors (1) and follicular carcinoma (1). The most common reason for consult among patients is a palpable abdominal/pelvic mass (45.5%). Around 60% percent of cases have an elevated CA-125 value with a mean level of 180 U/ml. Seventy-two percent of cases with malignant transformation measured 10 cm or more with the largest mean diameter of 13 cm. Five patients underwent fertility-sparing surgery. Fourteen had staging procedures. Twelve patients were at Stage I. Three were at Stage II. Four and three patients were at Stage III and IV, respectively. Ten patients received adjuvant platinum-based chemotherapy and nine patients warrant no treatment after surgery. The median survival time is 14 months.

Conclusion

Although not common, malignant transformation in MCT should be considered in older patients with large tumor sizes and elevated CA-125 assessed as MCT in preoperative and intraoperative assessment. This ovarian malignancy suggests an aggressive behavior but complete resection with systematic staging and indicated adjuvant platinum-based chemotherapy may improve survival.

malignant transformation of teratomas
mature cystic teratoma
ovarian cancer
squamous cell carcinoma of the ovary
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pmcINTRODUCTION

In the Philippines, ovarian cancer is the tenth most common malignancy with the fifth highest mortality rate. The 5-year prevalence of 25.05 per 100,000 (Globocan 2020) suggests ovarian cancer is a remarkable health burden in the country.1 Between 2018 and 2019, ovarian cancer remained top 6 of the causes of gynecologic admission in Baguio General Hospital and Medical Center and was the leading cause of death among gynecologic malignancies. Furthermore, ovarian cancer is the 6th most common malignancy managed in our Cancer Center for the year 2022. Over 80% of ovarian cancers are epithelial in origin, while the remaining percentage include germ cell tumors, sex cord-stromal tumors, and metastatic tumors.2

The most common germ cell tumor of the ovary is a benign mature cystic teratoma (MCT), comprising 10–25% of all ovarian neoplasms and malignant transformation, which is reported as a rare phenomenon that occurs in 1–3% of all mature cystic teratoma.3 Squamous cell carcinoma (SCCA) is MCT's most common malignant tumor (MT-MCT). Between 2013 and 2015, our clinical pathology unit recorded four cases of MT-MCT among 169 MCT cases (2.4%). Two cases of mucinous adenocarcinoma, one SCCA, and one papillary thyroid carcinoma. Last 2020, we reported on extremely rare MT-MCTs, carcinoid tumors, and papillary thyroid carcinoma.4

Since there are no specific clinical signs and symptoms, or radiological and laboratory markers specific to the MT-MCT, it is important to realize that malignant transformation is rarely diagnosed preoperatively and is mostly diagnosed through postoperative pathological examination.5 Thus, patients with this rare complication may not receive the optimal surgery and staging procedure for ovarian cancer. Due to its rarity, the comprehensive surgical staging of malignant ovarian germ cell tumors was derived from the epithelial ovarian carcinoma treatment guidelines, and omission of such was associated with an increased risk of disease recurrence.6 Moreover, a systematic review and meta-analysis regarding the attributable value of comprehensive surgical staging in epithelial ovarian carcinoma learned that 23% of clinically FIGO Stage I patients were upstaged after comprehensive surgical staging.7 At present, definite evidence is controversial over the procedures in MT-MCT.

It has been an observation that MT-MCT is becoming more common in our institution as we do our Surgicopathologic and Multidisciplinary Audits, hence this study. This descriptive study primarily aims to determine the prevalence rate of malignant transformations in a mature cystic teratoma of the ovary and describe clinicopathologic features, management, and prognosis of patients who developed this rare type of tumor and likewise deliver a review in the light of recent literature. In the Philippines, most articles presented were individual case reports of malignant transformations from ovarian mature cystic teratoma. The result of this study will provide a first-hand summary of our experience in managing accumulated cases and might be included in the evidence to come up with a standard protocol for managing these rare gynecologic tumors.

OBJECTIVES

General Objective

To determine the prevalence rate of malignant transformation in a mature cystic teratoma of the ovary encountered at a tertiary training institution in a span of five years from January 2016 to December 2020.

Specific Objectives

To describe the clinicopathologic characteristics of patients with malignant transformations arising from mature cystic teratoma, in terms of the following:

Mean age

Major signs and symptoms

Level of preoperative CA-125

Procedure done

The mean size of the ovarian mass

Final stage post-surgery

Adjuvant treatment after surgery

Survival of patients

METHODS

This descriptive study reviewed clinical records of patients with MT in MCTO from January 2016 to December 2020 in a Tertiary Level Public Hospital. The study population included subjects diagnosed with malignancy from ovarian mature cystic teratoma of all ages operated on for new ovarian growth in this institution. Total population sampling was used. The total number of charts and/or electronic medical records reviewed was the total number of cases with a malignant transformation from MCTO.

This review was completed primarily by the investigators in coordination with the Health Information Management Office and the Department of Anatomic Pathology. Convenience sampling was used where the available data were utilized. A list of patients with the histopathologic report of mature cystic teratoma was retrieved from the Section of Anatomic Pathology. Subsequently, patients with a diagnosis of malignant transformation arising from Mature cystic teratoma were included in this study. Data on demographics, presenting symptoms, preoperative CA125, surgical management, pathological findings, adjuvant therapy, follow-up, and treatment outcomes were obtained from the medical records (charts or Electronic Medical Records). Data needed for the study were recorded in the Data Extraction Form. Immature teratoma cases were excluded.

Data was encoded and analyzed using Microsoft Excel 16.27 (2019). Data were analyzed using descriptive statistics. Categorical variables were presented as frequency and percentages while continuous variables were presented as mean and median values. Prevalence was computed using frequency and percentage. Age, levels of CA125, and size of ovarian mass were presented as mean values. Presenting symptoms, the procedure, the final stage, and adjuvant therapy were presented in percentages. Status during follow-up was described as the median value in months.

Ethical Considerations

The study was approved by the Research Ethics Committee. There were no conceivable risks from the study that would affect patients. Confidentiality of gathered data was observed. Data collection and publication upheld the rules of the Data Privacy Act 2012.

RESULTS

Between January 2016 to December 2020, the Department of Pathology received 1,025 specimens for ovarian pathology of which 75% were benign diagnoses. Of the 369 cases of mature cystic teratoma, 22 cases with malignant transformation were reported with an incidence of 6%. Table 1 summarizes the characteristics of these 22 patients. The mean age of diagnosis was 52 years old (range 33-70 years old), of which 70 % are aged 50 years old and above. Mean Gravidity and Parity were 3. Fifty-nine percent (13/22) and 32% (7/22) of the cases with malignant transformation were squamous cell carcinoma and mucinous adenocarcinoma, respectively. A very rare malignant transformation reported was carcinoid tumor (1) and follicular carcinoma (1). The most common reason for consult among patients is a palpable abdominal/pelvic mass (45.5%). Around 60% percent of cases have an elevated CA-125 value with a mean level of 180 U/ml. Seventy-two percent of cases with malignant transformation measured 10 cm or more with a largest mean diameter of 13 cm. Ninety-five percent were unilateral. Three cases were associated with a contralateral mature cystic teratoma.

Table 1 Clinicopathologic Features of Patients with Malignant Transformation

Variables	N = 22 (%)	
Age (years)		
 30-39	3 (13.6)	
 40-49	4 (18.2)	
 50-59	12 (54.6)	
 60 and above	3 (13.6)	
	
CA 125		
 Normal (<35 mIU/ml)	6 (27.3)	
 Low normal (>35 to <100 mIU/ml)	4 (18.2)	
 High normal (>100 mIU/ml)	9 (40.9)	
 No record	3 (13.6)	
	
Reason for consult		
 Abdominal enlargement	5 (22.7)	
 Abdominal/Pelvic pain	4 (18.2)	
 Palpable mass	10 (45.5)	
 Others (incidental findings, vaginal bleeding, body weakness)	3 (13.6)	
	
Size of ovarian mass		
 <10 cm	6 (27.3)	
 10-15 cm	9 (40.9)	
 16-20 cm	6 (27.3)	
 >20 cm	1 (4.5)	
	
Procedure done		
 Salpingo-oophorectomy	5 (22.7)	
 THBSO	17 (77.3)	
 With staging	14 (63.6)	
 Without staging	8 (36.4)	
	
Final stage		
 IA	8 (36.4)	
 IB	1 (4.5)	
 IC	3 (13.6)	
 II	3 (13.6)	
 III	4 (18.2)	
 IV	3 (13.6)	
	
Adjuvant treatment given		
 Observation	9 (40.9)	
 Chemotherapy	10 (45.5)	
 None (no consent/did not follow up)	3 (13.6)	
	
Alive status since diagnosis		
 <6 months	4 (18.2)	
 6-12 months	6 (27.3)	
 >12-24 months	4 (18.2)	
 >24 months	8 (36.3)	

Twenty-two percent of patients underwent fertility-sparing surgery. Sixty-four percent had staging procedures. Twelve patients were at Stage I. Three were at Stage II. Four and three patients were at Stage III and IV, respectively. Ten patients received adjuvant platinum-based chemotherapy and nine patients warrant no treatment after surgery. Ten out of the 22 patients are deceased with a median survival time of 14 months.

DISCUSSION

Mature cystic teratoma, the most frequent germ cell tumor is benign in its pure composition, however, malignant transformation has been reported in less than 3% of cases.5,8 The most common malignant transformation is SCCA followed by adenocarcinoma as shown in the result of this study. As previously reported, carcinoid tumor, sarcoma, and papillary carcinoma are extremely rare with an estimate of 0.1 to 0.3%.4,9

The major challenge concerning these malignant transformations is that there are no specific symptoms; imaging and biochemical features to make preoperative diagnosis, hence difficult to establish definitive surgical procedures.10 Therefore, several risk factors are suggested to suspect malignant transformation. Our study showed that malignant transformation is more common in women above 50 years old, with elevated CA 125, and those with an ovarian tumor of more than 10 cm. Park et al.10 reported that risk factors for malignant transformation include elevated CA-125 levels, age over 40 years old, postmenopausal status, and large tumor size. A tumor size of ≥10 cm should be highly suspected for MT.2,11-13 A tumor size of ≥15.0 cm appeared to be associated with more aggressive disease.2 A long-standing existence of MCT without tumor removal is implied to be associated with malignant transformation. In a systematic review by Li et al.11 involving 435 cases, the mean age of diagnosis was 53.5 (range 19–87) years old, while in the report of Chiang et al.2 (TGOG Study), the median age at diagnosis was 52 years which is similar to this study. A more recent case series of 14 patients with MT-MCT from a total of 569 cases revealed that the mean age was 51.3.12 Similar to common histology of ovarian cancer, patients with MT-MCT generally present with palpable abdominal mass, abdominal distension, and abdominal pain.2,11,12

As previously published, some reported that SCC transformation in MCTO may be associated with high-risk human papillomavirus (HPV) infection, and alterations in the tumor proteins, p53, and p16 may be involved in the process of malignant transformation.2,14 Conversely, the recent next-generation sequencing analysis reported that no SCC was positive for HPV. The most frequently altered genes in SCC were TP53 in 80% of cases, while PIK3CA and CDKN2A in 52% and 44% of cases, respectively. In addition, a mutation in TP53 was associated with improved overall survival.15,16 KRAS proto-oncogene mutation is implicated in mucinous adenocarcinoma transformations.17 Inherited multiple endocrine neoplasia type 1 (MEN-1) and p53 are rarely reported in carcinoid tumors.18 No molecular markers have been reported for thyroid carcinomas arising within MCT without struma ovarii.19 This potential molecular abnormality was not conducted among the patients in the study.

The gross pathologic appearance of benign ovarian teratoma is characteristic. However, for a concealed malignancy, the following features are suggested to consider: nodularity, papillary or solid growths, adhesions to the pelvic wall and peritoneum, presence of ascites, areas of necrosis, and hemorrhages, together with the presence of risk factors would aid the physician to suspect malignancy.10 It is important to do a meticulous gross examination intraoperatively. A rush frozen section (RFS) may be indicated in some instances, especially in patients who wish to retain fertility to provide a provisional intraoperative pathologic diagnosis to guide extent of surgery. The sensitivity, specificity, and overall accuracy of RFS on malignant ovarian masses are 86%, 100%, and 97%, respectively. However, it must be emphasized that RFS on germ cell tumors has a 13% discordant rate.20

Definitive diagnosis of MT-MCT is primarily based on histopathologic studies. Immunohistochemical biomarkers may play an active or complementary role in the accurate classification. Reports presented that SCCA in MCTO was positive staining for pancytokeratin, p63, and Ki67, and alteration in p53.21,22 For extremely rare cases such as carcinoid tumors and papillary thyroid transformations, neuroendocrine markers (chromogranin, synaptophysin, and CD56) and thyroid biomarkers (HBME-1, galectin-3, thyroglobulin, and Thyroid Peroxidase) are excellent immuno-histochemistry stains, respectively. 9,23-25

The optimal management of these malignant transformations is uncertain because of their rarity, and there is no gold standard and direct comparisons between treatment approaches. The rarity suggests a low likelihood of future prospective studies to determine the best treatment options.5 Due to mostly low tumoral behavior, complete resection is the main mode of treatment. All of our patients underwent complete resection of the ovarian mass by salpingo-oophorectomy with or without hysterectomy. Furthermore, the treatment modalities for malignancy in mature ovarian teratoma depend on the stage of the disease and fertility desire. Conservative treatment is often offered to younger patients who wish to retain their fertility and it consists of unilateral salpingo-oophorectomy or cystectomy without adjuvant therapy. Conservation of ovarian tissue on the affected side is acceptable.5,26 For perimenopausal and postmenopausal women, bilateral salpingo-oophorectomy and hysterectomy should be performed. Complete cytoreduction surgery and lymphadenectomy improve the treatment outcome.10,11

The advantages of adjuvant radiotherapy or chemotherapy stated in the retrospective study of Gainford et al.27 have never been prospectively reviewed. For Stage 1 tumors, additional therapy is debatable for they have a fairly good prognosis. Likewise, no universally accepted regimens or dosages for more advanced diseases exist. However, cisplatin-based chemotherapy for patients with more advanced cancer provided improved survival. Other authors suggest that chemotherapy with alkylating agents is related to better prognosis in patients with SCC transformation in MCTO.28 A systematic review endorses individualized and integrated treatment based on platinum-based chemotherapy.2 In our institution, a carboplatin-paclitaxel chemotherapy regimen was mostly utilized, similar to the accounts of the previous reports.8,12,29 A 30-year-old woman reported attaining remission for 45 months after radical cytoreduction with combination chemotherapy, consisting of carboplatin, paclitaxel, and bevacizumab, followed by maintenance therapy with bevacizumab.30

Prognosis is primarily dependent on the stage of the disease, with stage I patients having a relatively good prognosis, but the outcome is very poor when the disease has spread beyond the ovary.2 Malignant tumors evolving from ovarian teratomas sometimes present with locally invasive disease or with distant metastases.5 The prevalent sites of metastasis are contiguous pelvic structures, including the contralateral ovary and hematologic dissemination may occur in the lungs, bone, liver, and brain, however, metastasis is rare. Other important predictors of prognosis include tumor grade, vascular involvement, cyst wall invasion, tumor infiltration, capsular rupture, and adhesions.12,31 There is no standardized approach to post-treatment surveillance, however, routine physical examination and radiographic imaging are warranted.

CONCLUSION

MT-MCTO is rare and a challenging complication. The preoperative diagnosis of this transformation is difficult, and the definitive diagnosis would be achieved post-operatively as there are no specific symptoms; imaging and biochemical features to make suspicion, hence difficult to establish definitive surgical procedures. The following risk factors would indicate malignant transformation developing from MCTO: advanced age, elevated CA-125 value, and large tumor size. Histopathologic examination of multiple tissue sections and immunohistochemical staining aid in definitive diagnosis.

This study illustrates the aggressive behavior of this ovarian malignancy and the optimal treatment strategy remains the main challenge, but optimal removal of the tumor and complete surgical staging with indicated adjuvant chemotherapy may render improvement of prognosis. Thus, patients with these characteristics need to be referred to a higher center that can provide appropriate diagnosis and management, which includes complete resection with surgical staging and adjuvant treatment.

Despite the limitation of being a small sample size retrospective single institutional study, this report shows the importance of adequate preoperative workup of an ovarian mass, correct surgical and pathological diagnosis, and judicious referral to the oncology center. Prospective and multicenter collaborative studies are needed to provide satisfactory evidence to establish consensus management, and to strengthen and validate the recommendations provided by various guidelines.

Statement of Authorship

Both authors certified fulfillment of ICMJE authorship criteria.

Author Disclosure

Both authors declared no conflicts of interest.

Funding Source

None.
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REFERENCES

1 Velayo CL, Reforma KN, Sicam RVG, Diwa MH, Sy ADR, Tantengco OAG. Clinical performance of a multivariate index assay in detecting early-stage ovarian cancer in Filipino women. Int J Environ Res Public Health. 2022 Aug;19 (16 ):9896. doi: 10.3390/ijerph19169896. PMID: 36011527; .36011527
2 Chiang AJ, Chen MY, Weng CS, Lin H, Lu CH, Wang PH, et al . Malignant transformation of ovarian mature cystic teratoma into squamous cell carcinoma: a Taiwanese Gynecologic Oncology Group (TGOG) study. J Gynecol Oncol. 2017 Sep;28 (5 ):e69. doi: 10.3802/jgo.2017.28.e69. PMID: 28657230; PMCID: .28657230
3 Kim JY. A carcinoid tumor arising from a mature cystic teratoma in a 25-year-old patient: a case study. World J Surg Oncol. 2016 Apr; 14 :120.doi: 10.1186/s12957-016-0867-8. PMID: 27098182; PMCID: .27098182
4 Billod JA, Suare JG, Natavio KMA. Carcinoid tumor and papillary thyroid carcinoma arising from ovarian mature cystic teratoma: two cases of an extraordinary malignant transformation. Int J Reprod Contracept Obstet Gynecol. 2021 Apr;10 (4 ):1686-90. doi: 10.18203/2320-1770.ijrcog20211159.
5 Dane C, Ekmez M, Karaca A, Ak A, Dane B. Follicular variant of papillary thyroid carcinoma arising from a dermoid cyst: a rare malignancy in a young women and review of literature. Taiwan J Obstet Gynecol. 2012 Sep;51 (3 ):421-5. doi: 10.1016/j.tjog.2012.07.019. PMID: 23040929.23040929
6 Medica-Franco H, Colonna-Marquez LE. Non-epithelial ovarian carcinoma: What is the optimal staging surgery? Chin Clin Oncol. 2020 Aug;9 (4 ):50. doi: 10.21037/cco-20-18. PMID: 32692188.32692188
7 van de Vorst REWM, Hoogendam JP, van der Aa M, Witteveen PO, Zweemer RP, Gerestein CG. The attributive value of comprehensive surgical staging in clinically early-stage epithelial ovarian carcinoma: A systematic review and meta-analysis. Gynecol Oncol. 2021 Jun;161 (3 ):876-83. doi: 10.1016/j.ygyno.2021.04.007. PMID: 33849726.33849726
8 Tehranian A, Ghahghaei-Nezamabadi A, Seifollahi A, Kasraei S, Dehghani-Nejad H, Maleki-Hajiagha A. Ovarian mature cystic teratoma with malignant transformation: two case reports. J Med Case Rep. 2021 Jan;15 (1 ):23. doi: 10.1186/s13256-020-02594-4. PMID: 33499917; PMCID: 33499917
9 Souaf I, El Fatemi H, Bennani A, Leila C, Nawale H, Tawfik H, et al . Papillary carcinoma derived from ovarian mature cystic teratoma: a new case report and literature review. Case Rep Clin Med. 2014 Apr;3 (4 ):197-202. doi: 10.4236/crcm.2014.34046.
10 Park CH, Jung MH, Ji YI. Risk factors for malignant transformation of mature cystic teratoma. Obstet Gynecol Sci. 2015 Nov;58 (6 ):475-80. doi: 10.5468/ogs.2015.58.6.475. PMID: 26623411; PMCID: .26623411
11 Li C, Zhang Q, Zhang S, Dong R, Sun C, Qiu C, et al . Squamous cell carcinoma transformation in mature cystic teratoma of the ovary: a systematic review. BMC Cancer. 2019 Mar;19 (1 ):217. doi: 10.1186/s12885-019-5393-y. PMID: 30866852; PMCID: .30866852
12 Qin L, Zhao T, Liu X, Wang H, Gu X, Chen D, et al . Malignant transformation arising from mature ovarian cystic teratoma: a case series. Medicine (Baltimore). 2021 Apr;100 (13 ):e24726. doi: 10.1097/MD.0000000000024726. PMID: 33787574; PMCID: .33787574
13 Yamanaka Y, Tateiwa Y, Miyamoto H, Umemoto Y, Takeuchi Y, Katayama K, et al . Preoperative diagnosis of malignant transformation in mature cystic teratoma of the ovary. Eur J Gynaecol Oncol. 2005;26 (4 ):391–2. PMID: 16122185.16122185
14 Chiang AJ, Chen DR, Cheng JT, Chang TH. Detection of human papillomavirus in squamous cell carcinoma arising from dermoid cysts. Taiwan J Obstet Gynecol. 2015 Oct;54 (5 ):559–66. doi: 10.1016/j.tjog.2015.08.008. PMID: 26522111.26522111
15 Chun Y. Neuroendocrine tumors of the female reproductive tract: a literature review. J Pathol Transl Med. 2015 Oct;49 (6 ):450–61. doi: 10.4132/jptm.2015.09.20. PMID: 26459408; PMCID: .26459408
16 Cooke SL, Ennis D, Evers L, Dowson S, Chan MY, Paul J, et al . The driver mutational landscape of ovarian squamous cell carcinomas arising in mature cystic teratoma. Clin Cancer Res. 2017 Dec;23 (24 ): 7633–40. doi: 10.1158/1078-0432.CCR-17-1789. PMID: 28954785.28954785
17 Pintea M. Mucinous cystadenoma arising in a mature cystic teratoma in a 25-year-old patient. Case Rep Obstet Gynecol. 2014;2014 :649521. doi: 10.1155/2014/649521. PMID: 24891964; PMCID: .24891964
18 Kamilaris CDC, Stratakis CA. Multiple endocrine neoplasia type 1 (MEN1): An update and the significance of early genetic and clinical diagnosis. Front Endocrinol (Lausanne). 2019 Jun;10 :339. doi: 10.3389/fendo.2019.00339. PMID: 31263451; PMCID: 31263451
19 Pineyro MM, Pereda J, Schou P, de los Santos K, de la Peña S, Caserta B, et al . Papillary thyroid microcarcinoma arising within a mature ovarian teratoma: case report and review of the literature. Clin Med Insights Endocrinol Diabetes. 2017 Jun;10 :1179551417712521. doi: 10.1177/1179551417712521. PMID: 28615984; PMCID: .28615984
20 Billod JA, Domingo EJ, Geraldino NT. Diagnostic accuracy of intraoperative frozen section in the diagnosis of ovarian neoplasms in a tertiary training hospital: a 10-year retrospective report. Philipp J Gynecol Oncol. 2016;13 :1-14.
21 Feng X, Xu L. Rare case of squamous cell carcinoma arising in a recurrent ovarian mature cystic teratoma of a young woman: A case report and review of the literature. Medicine (Baltimore). 2018 May;97 (20 ):e10802. doi: 10.1097/MD.0000000000010802. PMID: 29768376; PMCID: .29768376
22 Liu H, Lin F. Application of immunohistochemistry in thyroid pathology. Arch Pathol Lab Med. 2015 Jan;139 (1 ):67-82. doi: 10.5858/arpa.2014-0056-RA. PMID: 2554914525549145
23 Szczepanek-Parulska E, Pioch A, Cyranska-Chyrek E, Wolinski K, Jarmołowska-Jurczyszyn D, Janicka-Jedynska M, et al . The role of immunohistochemical examination in diagnosis of papillary thyroid cancer in struma ovarii. Folia Histochem Cytobiol. 2019;57 (1 ): 35–42. doi: 10.5603/FHC.a2019.0004. PMID: 30924920.30924920
24 Devi P, Aghighi M, Mikhail N. Papillary thyroid carcinoma in struma ovarii. Cureus. 2020 Apr;12 (4 ):e7582. doi: 10.7759/cureus.7582. PMID: 32391231; PMCID: .32391231
25 Salman WD, Singh M, Twaij Z. A case of papillary thyroid carcinoma in struma ovarii and review of the literature. Patholog Res Int. 2010 Aug;2010 :352476. doi: 10.4061/2010/352476. PMID: 21151690; PMCID: 21151690
26 Guney N, Sayilgan T, Derin D, Ozcan D. Primary carcinoid tumor arising in a mature cystic teratoma of the ovary: a case report. Eur J Gynaecol Oncol. 2009;30 (2 ):223-5. PMID: 19480263.19480263
27 Gainford MC, Tinker A, Carter J, Petru E, Nicklin J, Quinn M, et al . Malignant transformation within ovarian dermoid cysts: An audit of treatment received and patient outcomes. An Australia New Zealand Gynecological Oncology Group (ANZGOG) and Gynecologic Cancer Intergroup (CGIG) Study. Int J Gynecol Cancer. 2010 Jan; 20 (1 ):75-81. doi: 10.1111/IGC.0b013e3181c7fccf. PMID: 20130506.20130506
28 Hackethal A, Brueggmann D, Bohlmann MK, Franke FE, Tinneberg HR, Munstedt K. Squamous-cell carcinoma in mature cystic teratoma of the ovary: systematic review and analysis of published data. Lancet Oncol. 2008 Dec;9 (12 ):1173–80. doi: 10.1016/S1470-2045(08)70306-1. PMID: 19038764.19038764
29 Gadducci A, Guerrieri ME, Cosio S. Squamous cell carcinoma arising from mature cystic teratoma of the ovary: a challenging question for gynecologic oncologists. Crit Rev Oncol Hematol. 2019 Jan; 133 :92-8. doi: 10.1016/j.critrevonc.2018.10.005. PMID: 30661663.30661663
30 Fukase M, Ohta T, Watanabe N, Suzuki Y, Seino M, Sudo T, et al . Squamous cell carcinoma arising from a mature cystic teratoma of the ovary: successful treatment with carboplatin, paclitaxel, and bevacizumab. Gynecol Oncol Rep 2020 Aug;34 :100632. doi: 10.1016/j.gore.2020.100632. PMID: 32964091; PMCID: .32964091
31 Rim S-Y, Kim S-M, Choi H-S. Malignant transformation of ovarian mature cystic teratoma. Int J Gynecol Cancer. 2006 Jan-Feb;16 (1 ):140–4. doi: 10.1111/j.1525-1438.2006.00285.x. PMID: 16445624.16445624
