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Review

Mature Cystic Teratoma: An Integrated Review

by
Luping Cong
1,
Sijia Wang
1,
Suet Ying Yeung
2,
Jacqueline Ho Sze Lee
2,
Jacqueline Pui Wah Chung
1 and
David Yiu Leung Chan
1,*
1
Assisted Reproductive Technology Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
2
Department of Obstetrics and Gynecology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR 999077, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(7), 6141; https://doi.org/10.3390/ijms24076141
Submission received: 28 February 2023 / Revised: 19 March 2023 / Accepted: 22 March 2023 / Published: 24 March 2023
(This article belongs to the Section Molecular Oncology)
Browse Figures
Versions Notes

Abstract

:
Ovarian dermoid cysts, also called mature cystic teratomas (MCTs), account for 69% of ovarian germ cell tumors in young women. The tumors are formed by tissues derived from three germ layers, and sebaceous materials are most commonly seen. The origin of MCTs is widely considered to be the germ cell origin, which completes meiosis I. The clinical symptoms vary widely, but 20% of tumors could be asymptomatic. The diagnosis of MCTs is usually made without difficulty by ultrasound and confirmed by histopathology post-operatively. The imaging findings have a high diagnostic value. The typical characteristics present in the sonographic images, including a dermoid plug or Rokitansky nodule, are considered strong evidence for a teratoma. Although the malignant transformation of MCTs is rare, it can occur in some cases, especially in women of advanced age. The treatment of MCTs depends on the risk of malignancy, the age of the patient, and the patient’s fertility reserve requirement. In this article, we review the epidemiology, clinical symptoms, diagnosis criteria, cellular origin, and treatment of mature cystic teratomas.

1. Introduction

Ovarian dermoid cysts, which are also called mature cystic teratomas (MCTs), are the most common ovarian germ cell tumors in young women [1]. They can occur in women of different ages, while the highest prevalence was registered among women who are at their reproductive age [1]. The patients can be asymptomatic or present with chronic pelvic pain or a pelvic mass. Acute pain occurs when there is a complication. Approximately 20% of patients are asymptomatic when the tumor is discovered. The tumors are usually found incidentally on imaging performed for other indications [2,3].
The tumors are formed by tissues derived from completely differentiated cells from three germ layers, which are ectodermal, mesodermal, and endodermal [4]. Ectodermal tissues and sebaceous material are commonly encountered and present in almost every case. 38% of tumors only contain skin and neural tissues, 30% exclusively have skin and dermal appendages, and the rest have other fully differentiated histologic tissues. A cystic echo with an echogenic nodule characterized by echogenic sebaceous material and calcifications is the most common ultrasound appearance of a mature teratoma [5,6].
The possible cause of this tumor is still unclear. The reported risk factors include late menarche and long duration of menstrual irregularities, a history of cystic teratoma, fewer pregnancies, infertility, excessive drinking, and exercise [7]. Recent studies have reported that the cellular origins of mature teratomas are diploid, which contain sets of homozygous alleles. The analysis of polymorphic markers showed a homozygous pattern in teratoma components, supporting a parthenogenetic origin from post-meiotic germ cells [8]. Karyotypic analysis frequently showed a normal karyotype, 46, XX. However, tetraploidy and structural rearrangement have also been reported [1].
The management of a mature teratoma depends on the symptoms, imaging results, and the patient’s wishes. Laparoscopy and laparotomy would be used in different cases after comparing the benefits and risks [9]. Typically, cystectomy by laparoscopy is a safe and effective option to preserve ovarian function [10]. Laparotomy and oophorectomy should be considered in women with a high malignant risk [3]. Post-operative follow-up is essential to exclude recurrence, adhesion, and malignant transformation [9]. Controversy exists about the optimum surgical procedure for the treatment of ovarian dermoid cysts, especially with small cysts. Some suggest that it is practical to conduct close follow-up instead of intervention in children and adolescents with small-size mature cystic teratomas [11].
Malignant transformation of mature cystic teratoma is a rare complication with an incidence of 1–2% and is specifically seen among postmenopausal women [12]. Squamous cell carcinoma is the most common, accounting for approximately 80–85% of malignant transformations [13].
This article will review the epidemiology, clinical presentation, imaging features, diagnosis criteria, and management of mature cystic teratomas in considerable detail and aim to provide a comprehensive understanding of one of the most common neoplasms in women before menopause.

2. Epidemiology

There are three types of ovarian teratomas: mature teratomas, immature teratomas, and monodermal teratomas [14]. Mature teratoma includes mature cystic teratoma, which is also named ovarian dermoid cysts [15]. The reported incidence is about 1.2–14.2 cases per 100,000 people per year [16]. Mature teratoma is the most common subtype of ovarian germ cell tumors, which accounts for 11% of all ovarian tumors, 69% of all germ cell tumors, and 95% of teratomas [1,17]. The predominant type of mature teratoma is cystic, and the cyst always contains skin, hair, neural tissues, and sebaceous material. Therefore, it is also called a mature cystic teratoma (MCT) or an ovarian dermoid cyst. Mature teratomas are frequently diagnosed in the reproductive years. The patients’ ages range from 13 to 76, with a median age of mid-30 [2]. Some of them are detected during a routine examination or found during pregnancy. Although the proportion of malignant germ cell tumors in children and adolescents is larger than in adults, mature teratoma is still the predominant one, consisting consists of 61% gonadal germ cell tumors (GCTs) when compared with germ cell malignancy [18,19]. Immature teratomas, which account for over 20% of malignant germ cell tumors, also commonly arise in children and women of reproductive age and become progressively less common in postmenopausal women [20]. The right-sided tumors outnumbered the left-sided tumors [2]. The reported rate for bilateral dermoid cysts is 8–15% [3].
Some studies focus on the risk factors of benign ovarian teratomas and explore whether they share the same risk factors as testicular germ cell tumors. Unexpectedly, an increased risk of benign teratoma is associated with alcohol consumption and exercise rather than exogenous hormone exposure, which indicates that further information needs to be analyzed [7].
Although most mature cystic teratomas are benign, the reported incidence of malignant transformation is 0.5% to 3% within the MCT, especially in women of advanced age [12,13]. Squamous cell carcinoma is the most common type [16,21]. Other less frequent malignant transformations include mucinous carcinoma [21], adenocarcinoma [22,23,24,25,26], melanoma [27], carcinoid [28,29,30], oligodendroglioma [31,32,33], and sarcoma [34,35,36,37].

3. Clinical Symptoms

The clinical presentation of tumors is variable. About 20% of mature teratomas are asymptomatic at the time of diagnosis and are usually detected incidentally during imaging examinations, pregnancy, or abdominal or pelvic surgery for other reasons [2,3]. Larger tumors may present with abdominal pain, symptoms of increased pelvic pressure, and a palpable mass during abdominal examination [3]. Acute abdominal pain accounts for 5–10% of all matured teratomas and is frequently caused by ovarian torsion. Patients may also experience nausea, vomiting, fever, and abnormal bleeding [3]. The spontaneous rupture rate of these tumors was reported to be 1.2% to 3.8% which may lead to chemical peritonitis [38,39]. There are several risk factors for spontaneous dermoid rupture, including prolonged pressure during pregnancy, cyst torsion with infarction, or direct trauma [38,40].
Additionally, some patients with mature teratoma may present with N-methyl-d-aspartate (NMDA) encephalitis, which is a rarely seen but severe neurological disorder [41]. Several studies showed that young women or children with ovarian teratoma could be affected by encephalitis, which leads to a wide range of neuropsychiatric symptoms such as psychosis, memory loss, and behavior disorder and subsequently develops into seizures, dyskinesias, and autonomic instability [42,43,44,45,46,47]. The majority of the teratomas are mature, while the other third are immature. It has been reported that Paraneoplastic Neurological Syndrome (PNS) often precedes the clinical manifestation of ovarian teratomas [48]. The pathogenesis underlying this process might be the presence of nerve tissue expressing the NR2 subunit of the NMDA receptor in all teratomas [43]. It is likely that the cross-presentation of the same antigen explains the relationship between ovarian teratomas and anti-NMDAR encephalitis.
The incidence of pregnancy occurring in benign cystic teratoma is about 10.5%, but no evidence demonstrates that pregnancy will increase the incidence of infection, rupture, or malignancy of this ovarian neoplasm [38]. Mature ovarian cystic teratomas have rarely been reported to secrete HCG [49]. A case report found a 41-year-old woman with a known cystic lesion on her right ovary who had an elevated serum level of human chorionic gonadotrophin (hCG), and the level of hCG resolved after cyst removal [50]. Cases have been reported of a mixed polyembryoma and immature teratoma resulting in elevated serum hCG and alpha-fetoprotein [51]. Therefore, if an elevated serum hCG is found in the presence of mature ovarian teratomas, pregnancy and other malignancies such as dysgerminomas, polyembryomas, placental site trophoblastic tumors, or choriocarcinomas should be excluded.
About 15% of MCTs incidentally found thyroid tissue within the teratomas [21], but a struma ovary is termed when thyroid tissue is the predominant element (>50%) [52]. Teratomas with thyroid tissues may present with symptoms of hyperthyroidism [53].

4. Diagnosis

Ovarian teratomas are often diagnosed during routine gynecologic examinations. Mature teratomas can be easily diagnosed by ultrasound, as the stereotypical sonographic features are uncommonly seen in malignancies. A computed tomography scan (CT scan) and a magnetic resonance imaging (MRI) scan can sometimes also help make a diagnosis. However, it is essential to recognize the presence of any malignant changes, as their identification is of paramount importance for management and prognosis.

4.1. Image Findings

Ultrasound (US) is the most commonly used imaging method to confirm ovarian dermoid cysts and is accurate enough to make a diagnosis that can be confirmed by post-operative histopathology [54]. A dermoid plug or Rokitansky nodule is considered strong evidence for a teratoma [14]. It is characterized by one or more highly echogenic nodules within the cyst [14]. Plug size varies from one to almost accounting for the entire cyst [55]. A discrete, highly echogenic focus with posterior shadowing indicating the existence of the ectopic tooth might be more specific for the diagnosis of MCTs [14]. Some other sonographic characteristics include the dermoid mesh, tips of iceberg signs, and fat-fluid level [50]. CT and MRI are alternative methods of diagnosing dermoid cysts, both of which are more sensitive to fat than ultrasound [50]. The typical image findings are summarized in Table 1.

4.2. Histological Examination

The gross, pathologic appearance of mature cystic teratomas is typical. The size of tumors varies, with a mean diameter of 7 cm, and they frequently contain well-differentiated cells from three germ layers [56]. The incidence of the three germ layers and the tissues that are commonly seen are summarized in Figure 1. Histologically, squamous epithelium lines the wall of the cyst, and the external surface is covered by the ovarian stroma [57]. In 88% of cases, tumors are unilocular with Rokitansky nodules, which contain hair, teeth, and other tissues [58,59]. The tumor cyst is filled with sebaceous material, which is liquid at body temperature and semisolid at room temperature [38]. Ectodermal tissue could be found in almost 100% of cases, such as the skin, but neural tissue is present in less than half of cases [2,38,57,58]. Fat, bone, cartilage, and muscle as mesodermal tissue are represented in over 90% of cases. Endodermal tissue is less seen compared with the previous two [38]. The cavity usually contains sebum, keratin, and floating hair [38]. 67–75% of cases have adipose tissue, and 31% of cases contain teeth [38,59].

4.3. Differential Diagnosis

Ultrasonography can be used to diagnose most mature ovarian teratomas, which are characterized by echogenic sebaceous material and calcifications [15]. However, the sonographic appearances of immature teratomas and malignant transformation are nonspecific and not enough to make a differential diagnosis. In general, these malignancies have a nonspecific clinical presentation and vary with the tumor stage [60]. Histologically, immature teratomas are usually larger, with a mean diameter of 18 cm [3]. They might be completely solid or with a few cystic components [61]. In MCTs with malignant transformation, there are septums and capsules on the surface of cysts instead of a smooth surface. The transmural growth of the Rokitansky nodule may indicate malignant changes [6]. Microscopically, immature teratomas may contain tissues from all three germ layers, but neuroepithelium is more commonly seen within the tumors when compared with their benign counterparts, and necrosis is suspected to be a sign of malignancy [56]. For the imaging findings, adhesion to neighboring structures increased wall thickness, and the presence of necrosis and hemorrhage might be a sign of malignant transformation. The tumor markers such as squamous cell carcinoma (SCC) antigen, CA 125, CA19-9, CEA, and AFP may be elevated when the malignancy exists [13,26,27,62].

5. Cellular Origin

The tissues within the tumor of MCTs, differentiated from cells from three germ layers, have attracted the interest of many researchers. Grossly, MCTs usually have one or more cysts containing sebaceous material, hair, teeth, and sometimes neural tissues [2,38,56]. Early cytogenetic analysis revealed that, although usually the karyotype of these cysts was 46, XX, they frequently differed genetically from their host [1,63], and trisomy, triploidy, and mosaicism have also been seen in some cases [64,65].
Centromere markers and enzyme analysis are the commonly used methods to study the karyotype of the tumor tissues from MCTs. Several studies have demonstrated that cells extracted from teratomas were frequently homozygous for enzyme makers who were heterozygous in host cells [64,66,67,68]. Moreover, the results of centromere marker analysis also resemble the enzyme analysis findings, which showed homozygous in the teratomas but heterozygous in host cells [64].
In 1975, Linder et al. investigated the origin of mature cystic teratomas from six cases using electrophoretic enzyme polymorphisms combined with centromeric chromosome heteromorphisms. The centromere was shown to be homozygous when it was heterozygous in host cells in all cases [67]. In 1978, Patil and colleagues studied 21 cases of benign ovarian teratomas. The centromeric markers in every teratoma were homozygous, while the distal markers were heterozygous or homozygous [69]. In 1982, Carritt et al. reported a case of multiple cysts in one patient. They found that four of the tumors had centromeric markers that were the same as those found in the host. Their results exclude the suppression of meiosis II as a mode of origin for some of these tumors, and they hypothesized that failure of meiosis I could also be the mechanism of tumorigenesis [70]. A study by Parrington et al. (1984) found that 13 out of 21 benign ovarian teratomas had homozygous centromeric markers and eight had heterozygous centromeric markers where the host was heterozygous. However, 11 of the 13 teratomas had both homozygous chromosomal and enzyme markers. Parrington et al. proposed that it might be due to the endoreduplication of a mature ovum [71]. In 1987, a study conducted by Surti U reported the first cases of tetraploidy and structural rearrangement in benign ovarian teratomas. They divided the origin of teratomas into four types, including failure of meiosis I (type 1) and meiosis II (type 2), endoreduplication of a mature ovum (type 3), and mitotic division of primitive germ cells (type 4) [72]. As many as 65.2% of the benign teratomas showed homozygous centromeric markers [1]. Later in 1999, Vortmeyer AO et al. conducted a tissue microdissection followed by genetic analysis of mature cystic teratomas of the ovary, and their results strongly supported Linder’s original hypothesis of a germ cell origin, which completes meiosis I [68]. Recently, a study conducted by Wang WC and Lai YC (2016) [73] proposed that mature teratomas in Taiwan are derived from premeiotic ovarian germ cells [73]. However, based on the evidence that both components show a homozygous pattern by molecular analysis, which strongly demonstrated a post-meiosis I oocytes origin, the reason for the discrepancy might be the host somatic cell contamination [8,74]. In summary, the studies of the origin of MCTs are listed in Table 2 chronologically.

6. Treatment

The management of a mature teratoma is influenced by the risk of malignancy, the age of the patient, and the fertility reserve requirement. Surgical removal is an effective treatment for ovarian dermoid cysts. Chemotherapy and targeted drug therapy are considered when there is any malignant change or when it is combined with other ovarian cancers.

6.1. Mature Cystic Teratomas

Surgical removal is an effective treatment for ovarian dermoid cysts. The surgeries were classified as ovary-sparing surgery (OSS) or oophorectomy, either laparoscopic or via laparotomy [75]. Recently, the increasing use of laparoscopy in gynecologic surgery required a reexamination of the management of MCTs [9]. Compared with traditional laparotomy, the potential benefits of laparoscopy include a reduction in post-operative pain, blood loss, and a shorter hospital stay [76]. However, laparoscopy has been criticized for being associated with a higher risk of intraperitoneal cyst rupture that increases the risk of chemical peritonitis and adhesion formation, and an erroneous diagnosis may cause the iatrogenic spill of malignant cells [77,78]. The published rupture and spillage rates with laparoscopic surgery vary widely, from 0% to 100% [10].
Generally, cystectomies are performed only to remove the cysts so that they can preserve the rest of the ovarian function; however, follow-up is necessary to exclude recurrence, which occurs in 4% to 5% of cases [9]. It is considered that teratomas with a diameter of around 5 cm in premenopausal women require surgical resection, but a smaller tumor will also warrant removal in the postmenopausal woman because of the higher risk of malignant transformation [79]. Oophorectomy is the standard treatment in postmenopausal women and should be considered in perimenopausal women with multiple teratomas in one ovary and women with a large cystic teratoma destroying large normal ovarian tissue [80]. Since MCTs are the most common ovarian germ cell tumors in children and adolescents, it is important to make the best compromise between the preservation of fertility and the prevention of recurrences [75]. In children, the low malignancy rate leads to increased consideration of ovarian sparing surgery (OSS) as a better option for MCTs [81]. OSS should always be considered in the following cases: no evidence of lymphadenopathy or liver/lung metastasis, normal levels of tumor markers, absence of calcifications, or specific radiological findings [75]. Ovarian masses in postmenopausal women, even those with imaging findings of MCT, should be carefully evaluated if they are accompanied by any malignant changes because of the early stage of the tumor. No clinical, radiological, or biological sign is specific. Therefore, resection of any ovarian mass, even if asymptomatic, is required [13,82].

6.2. Malignant Transformations

Mature cystic teratoma is the most common type of ovarian germ cell neoplasm, but occasionally it can undergo malignant transformations, especially in postmenopausal women over 40 years old [82,83]. Although imaging examinations can diagnose MCTs with considerable accuracy, tissue examination is necessary to exclude any malignancy [11]. The majority of malignant transformations are squamous-cell carcinomas, while the remainders are carcinoid tumors, adenocarcinomas, melanoma [27], oligodendroglioma [31,32,33], and sarcoma [16,34,35,36,37,83,84,85]. The treatments for these malignant transformations are the same as for ovarian carcinoma, including surgical removal and chemotherapy. Radiotherapy did not show benefits for prognosis [16,21,84]. The treatment options for malignant transformations are summarized in Figure 2.
For young patients who wish to maintain their fertility, the malignant transformed dermoid cysts limited to the ovarian capsule without local or distant invasion can be treated by conservative treatment by conducting unilateral adnexectomy with multiple peritoneal biopsies [85,86]. In cases of elderly patients, the treatment is the same for any ovarian cancer, including total hysterectomy with bilateral adnexectomy, omentectomy, and lymphadenectomy [79,86]. The best adjuvant therapy for squamous cell carcinomas derived from MCTs has not been determined, but cisplatin is commonly used [84,86,87,88]. Alkylating drugs were also found to be associated with significant increases in survival in tumors at stages beyond Ia in Hackethal’s study in 2008 [16]. Paclitaxel and carboplatin are used in patients with adenocarcinoma [22]. Dacarbazine (DTIC) monotherapy or combination therapy, including nitrosourea and cisplatin, may be administered as adjuvant therapies for patients with melanoma [27]. Cisplatin and adriamycin were used in patients with sarcoma [34]. Patients with other ovarian germ cell tumors can achieve complete remission after BEP treatment, which is the combination of bleomycin, etoposide, and cisplatin (Platinol) [89,90].
Target cancer therapy as precision medicine is to target specific genes and proteins in tumor cells to stop their growth and survival. For germ cell tumors (GCTs), this aim is challenging since it varies in histological subtypes and the low number of relapse cases [95]. However, there are several target cancer therapy drugs for ovarian cancers that could be taken into consideration when there is malignancy accompanied by MCTs. Angiogenesis inhibitors are used to prevent the growth and spread of cancers. Bevacizumab has been proven to be effective against epithelial ovarian cancer [91]. Poly(ADP)-ribose polymerase (PARP) inhibitors, such as Olaparib, Rucaparib, and Niraparib, may result in the accumulation of DNA damage and result in selective cell death, particularly if a BRCA mutation is detected in cancer cells [92]. Antibody-drug conjugates (ADC) are chemotherapy drugs linked with antibodies. Many epithelial ovarian cancer cells have high expression levels of the surface folate receptor-alpha (FR-alpha) protein. In this situation, ADC can attach to the FR-alpha protein and deliver chemotherapy drugs to cancer cells [93]. Changes in neurotrophic tyrosine receptor kinases (NTRK) genes, specifically the NTRK 1-3 gene fusions, appear in a few ovarian cancers. Targeted drugs such as Larotrectinib and Entrectinib can combine with the NTRK receptor on the cell surface and subsequently inhibit the activation of downstream pathways, which can prevent cancer cell proliferation and induce apoptosis [94]. However, in some refractory tumors, drug resistance is one of the main reasons for tumor relapse and metastasis. The mechanisms of drug resistance are various, mainly including muli-drug resistance, apoptosis suppression, altering drug metabolism, epigenetic and drug targets, enhancing DNA repair, and gene amplification [96].

7. Conclusions

Mature cystic teratomas are one of the most common ovarian tumors among young women. These tumors are composed of tissues that are derived from ectoderm, mesoderm, or endodermal layers. Clinical presentations are associated with tumor size and complications. Image examination is extremely helpful in diagnosis and management. The treatment for MCTs should be based on the clinical symptoms, the risk of malignancy, the patient’s age, and the requirement for fertility preservation. Better knowledge of the epidemiology, clinical, and imaging features of mature cystic teratomas can be helpful in making an accurate diagnosis and subsequently guiding clinicians to make the most appropriate treatment plan. Meanwhile, the next generation sequencing brought light to explore new drugs for those refractory tumors. However, the biggest challenge is the low malignant transformation rate in MCTs and the high cure rate after surgery. Therefore, international cooperation is necessary for basic research and clinical trials.

Author Contributions

Conceptualization, L.C. and D.Y.L.C.; writing—original draft preparation, L.C., S.W., S.Y.Y., and J.H.S.L.; writing—review and editing, J.P.W.C. and D.Y.L.C. All authors have read and agreed to the published version of the manuscript.

Funding

This research is partially supported by Health and Medical Research Fund (HMRF) Hong Kong (07183826), and the Hong Kong Research Matching Grant (Ref. 8601386).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Surti, U.; Hoffner, L.; Chakravarti, A.; Ferrell, R. Genetics and biology of human ovarian teratomas. I. Cytogenetic analysis and mechanism of origin. Am. J. Hum. Genet. 1990, 47, 635. [Google Scholar] [PubMed]
  2. Ayhan, A.; Bukulmez, O.; Genc, C.; Karamursel, B.S.; Ayhan, A. Mature cystic teratomas of the ovary: Case series from one institution over 34 years. Eur. J. Obstet. Gynecol. Reprod. Biol. 2000, 88, 153–157. [Google Scholar] [CrossRef] [PubMed]
  3. Saleh, M.; Bhosale, P.; Menias, C.O.; Ramalingam, P.; Jensen, C.; Iyer, R.; Ganeshan, D. Ovarian teratomas: Clinical features, imaging findings and management. Abdom. Radiol. 2021, 46, 2293–2307. [Google Scholar] [CrossRef]
  4. Chen, V.W.; Ruiz, B.; Killeen, J.L.; Coté, T.R.; Wu, X.C.; Correa, C.N.; Howe, H.L. Pathology and classification of ovarian tumors. Cancer Interdiscip. Int. J. Am. Cancer Soc. 2003, 97, 2631–2642. [Google Scholar] [CrossRef] [PubMed]
  5. Quinn, S.F.; Erickson, S.; Black, W.C. Cystic ovarian teratomas: The sonographic appearance of the dermoid plug. Radiology 1985, 155, 477–478. [Google Scholar] [CrossRef]
  6. Saba, L.; Guerriero, S.; Sulcis, R.; Virgilio, B.; Melis, G.; Mallarini, G. Mature and immature ovarian teratomas: CT, US and MR imaging characteristics. Eur. J. Radiol. 2009, 72, 454–463. [Google Scholar] [CrossRef]
  7. Westhoff, C.; Pike, M.; Vessey, M. Benign ovarian teratomas: A population-based case-control study. Br. J. Cancer 1988, 58, 93–98. [Google Scholar] [CrossRef] [Green Version]
  8. Fujii, K.; Yamashita, Y.; Yamamoto, T.; Takahashi, K.; Hashimoto, K.; Miyata, T.; Kawai, K.; Kikkawa, F.; Toyokuni, S.; Nagasaka, T. Ovarian mucinous tumors arising from mature cystic teratomas—A molecular genetic approach for understanding the cellular origin. Hum. Pathol. 2014, 45, 717–724. [Google Scholar] [CrossRef]
  9. Templeman, C.L.; Fallat, M.E.; Lam, A.M.; Perlman, S.E.; Hertweck, S.P.; O’Connor, D.M. Managing Mature Cystic Teratomas of the Ovary. Obstet. Gynecol. Surv. 2000, 55, 738–745. [Google Scholar] [CrossRef]
  10. Savasi, I.; Lacy, J.A.; Gerstle, J.T.; Stephens, D.; Kives, S.; Allen, L. Management of Ovarian Dermoid Cysts in the Pediatric and Adolescent Population. J. Pediatr. Adolesc. Gynecol. 2009, 22, 360–364. [Google Scholar] [CrossRef]
  11. O’Neill, K.E.; Cooper, A.R. The Approach to Ovarian Dermoids in Adolescents and Young Women. J. Pediatr. Adolesc. Gynecol. 2011, 24, 176–180. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  12. Kido, A.; Togashi, K.; Konishi, I.; Kataoka, M.L.; Koyama, T.; Ueda, H.; Fujii, S.; Konishi, J. Dermoid cysts of the ovary with malignant transformation: MR appearance. Am. J. Roentgenol. 1999, 172, 445–449. [Google Scholar] [CrossRef]
  13. Christopherson, W.; Councell, R. Malignant degeneration of a mature ovarian teratoma. Int. J. Gynecol. Obstet. 1989, 30, 379–384. [Google Scholar] [CrossRef]
  14. Hertzberg, B.S.; Kliewer, M.A. Sonography of benign cystic teratoma of the ovary: Pitfalls in diagnosis. Am. J. Roentgenol. 1996, 167, 1127–1133. [Google Scholar] [CrossRef] [PubMed]
  15. Outwater, E.K.; Siegelman, E.S.; Hunt, J.L. Ovarian Teratomas: Tumor Types and Imaging Characteristics. Radiographics 2001, 21, 475–490. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Hackethal, A.; Brueggmann, D.; Bohlmann, M.K.; Franke, F.E.; Tinneberg, H.-R.; Münstedt, K. Squamous-cell carcinoma in mature cystic teratoma of the ovary: Systematic review and analysis of published data. Lancet Oncol. 2008, 9, 1173–1180. [Google Scholar] [CrossRef]
  17. Pekar-Zlotin, M.; Rabinovich, I.; Goldrat, I.; Vaknin, Z.; Gidoni, Y.; Zur-Naaman, H.; Maymon, R.; Smorgick, N. Ovarian Dermoid Cysts Associated with Paraneoplastic Syndrome N-methyl-D-aspartic Acid Receptor Antibodies Encephalitis. J. Minim. Invasive Gynecol. 2021, 28, 1190–1193. [Google Scholar] [CrossRef]
  18. De Silva, K.; Kanumakala, S.; Grover, S.; Chow, C.; Warne, G. Ovarian Lesions in Children and Adolescents—An 11-year Review. J. Pediatr. Endocrinol. Metab. 2004, 17, 951–957. [Google Scholar] [CrossRef]
  19. Evers, M.; Rechnitzer, C.; Graem, N.; Wehner, P.S.; Schroeder, H.; Rosthoej, S.; Mosbech, C.H.; Hoei-Hansen, C.E.; Sehested, A.; Treger, T.D.; et al. Epidemiological study of paediatric germ cell tumours revealed the incidence and distribution that was expected, but a low mortality rate. Acta Paediatr. 2017, 106, 779–785. [Google Scholar] [CrossRef]
  20. Coleman, R.L.; Westin, S.N.; Ramirez, P.T.; Salvo, G.; Gershenson, D.M. Malignant diseases of the ovary, fallopian tube, and peritoneum. In Comprehensive Gynecology; Elsevier: Amsterdam, The Netherlands, 2021; p. 707. [Google Scholar] [CrossRef]
  21. Gadducci, A.; Pistolesi, S.; Guerrieri, M.E.; Cosio, S.; Carbone, F.G.; Naccarato, A.G. Malignant Transformation in Mature Cystic Teratomas of the Ovary: Case Reports and Review of the Literature. Anticancer. Res. 2018, 38, 3669–3675. [Google Scholar] [CrossRef]
  22. Belaid, I.; Khechine, W.; Ben Abdelkader, A.; Bedioui, A.; Ezzairi, F.; Chabchoub, I.; Boujnah, R.; Tlili, T.; Hochlaf, M.; Ben Fatma, L.; et al. Adenocarcinoma of intestinal type arising in mature cystic teratoma of ovary: A diagnostic dilemma. Clin. Case Rep. 2020, 8, 644–647. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Li, Y.; Zhang, R.; Pan, D.; Huang, B.; Weng, M.; Nie, X. KRAS mutation in adenocarcinoma of the gastrointestinal type arising from a mature cystic teratoma of the ovary. J. Ovarian Res. 2014, 7, 85. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Ueda, G.; Fujita, M.; Ogawa, H.; Sawada, M.; Inoue, M.; Tanizawa, O. Adenocarcinoma in a Benign Cystic Teratoma of the Ovary: Report of a Case with a Long Survival Period. Gynecol. Oncol. 1993, 48, 259–263. [Google Scholar] [CrossRef] [PubMed]
  25. Song, Y.J.; Ryu, S.Y.; Choi, S.C.; Lee, E.D.; Lee, K.H.; Cho, S.Y. Adenocarcinoma arising from the respiratory ciliated epithelium in a benign cystic teratoma of the ovary. Arch. Gynecol. Obstet. 2009, 280, 659–662. [Google Scholar] [CrossRef] [PubMed]
  26. Fishman, A.; Edelstein, E.; Altaras, M.; Beyth, Y.; Bernheim, J. Adenocarcinoma Arising from the Gastrointestinal Epithelium in Benign Cystic Teratoma of the Ovary. Gynecol. Oncol. 1998, 70, 418–420. [Google Scholar] [CrossRef]
  27. Choi, W.K.; Lee, D.H.; Cho, D.H.; Jang, K.Y.; Kim, K.M. Primary malignant melanoma arising from ruptured ovarian mature cystic teratoma with elevated serum CA 19–9: A case report and review of literature. BMC Women’s Health 2019, 19, 149. [Google Scholar] [CrossRef] [PubMed]
  28. Zhang, W.; Chen, Q. Primary ovarian carcinoid arising in associated mature cystic teratoma. BMC Women’s Health 2022, 22, 76. [Google Scholar] [CrossRef]
  29. Tosuner, Z.; Sönmez, F.C.; Arici, D.S.; Dansuk, R. Carcinoid tumor arising in a mature cystic teratoma: A case report. Oncol. Lett. 2015, 9, 2236–2238. [Google Scholar] [CrossRef] [Green Version]
  30. Kim, J.-Y. A carcinoid tumor arising from a mature cystic teratoma in a 25-year-old patient: A case study. World J. Surg. Oncol. 2016, 14, 120. [Google Scholar] [CrossRef] [Green Version]
  31. Ünal, B.; Güleç, F.; Sedele, M. Oligodendroglioma Arising in Mature Cystic Teratoma. Case Rep. Oncol. Med. 2014, 2014, 745462. [Google Scholar] [CrossRef]
  32. Zannoni, G.F.; Fadda, G.; Scambia, G.; Capelli, A.; Carbone, A. Oligodendroglioma arising within a mature cystic ovarian teratoma: Case report and review of the literature. Acta Obstet. Gynecol. Scand. 2002, 81, 896–897. [Google Scholar] [CrossRef] [PubMed]
  33. Serrano-Arévalo, M.L.; Lino-Silva, L.S.; Malagón, H.R.D. Oligodendroglial cell proliferation arising in an ovarian mature cystic teratoma. Clinicopathological, inmunohistochemical, and ultrastructural study of a case that may represent an oligodendroglioma. Ultrastruct. Pathol. 2017, 41, 62–66. [Google Scholar] [CrossRef] [PubMed]
  34. Ngwalle, K.; Hirakawa, T.; Tsuneyoshi, M.; Enjoji, M. Osteosarcoma arising in a benign dermoid cyst of the ovary. Gynecol. Oncol. 1990, 37, 143–147. [Google Scholar] [CrossRef]
  35. Kefeli, M.; Kandemir, B.; Akpolat, I.; Yildirim, A.; Kokcu, A. Rhabdomyosarcoma Arising in a Mature Cystic Teratoma With Contralateral Serous Carcinoma: Case Report and Review of the Literature. Int. J. Gynecol. Pathol. 2009, 28, 372–375. [Google Scholar] [CrossRef] [PubMed]
  36. Desouki, M.M.; Fadare, O.; Chamberlain, B.K.; Shakir, N.; Kanbour-Shakir, A. Malignancy associated with ovarian teratomas: Frequency, histotypes, and diagnostic accuracy of intraoperative consultation. Ann. Diagn. Pathol. 2015, 19, 103–106. [Google Scholar] [CrossRef]
  37. Trabzonlu, L.; Durmaz, G.; Vural, C.; Muezzinoglu, B.; Corakci, A. Malignant tumors associated with ovarian mature teratoma: A single institution experience. Pathol. Res. Pract. 2017, 213, 518–521. [Google Scholar] [CrossRef]
  38. Caruso, P.A.; Marsh, M.R.; Minkowitz, S.; Karten, G. An intense clinicopathologic study of 305 teratomas of the ovary. Cancer 1971, 27, 343–348. [Google Scholar] [CrossRef] [PubMed]
  39. Jha, S.; Goel, G.; Sinha, H.H.; Anant, M.; Agarwal, M. Effects of Intraoperatively Ruptured Ovarian Dermoid Cysts. J. Gynecol. Surg. 2022, 38, 221–225. [Google Scholar] [CrossRef]
  40. Tanaka, Y.; Hori, H.; Gorai, I. Chemical peritonitis caused by an iatrogenic rupture of mature cystic teratoma of the ovary during labor: A report of a case didactic to all the maternity health care workers. J. Matern. Neonatal Med. 2011, 24, 388–390. [Google Scholar] [CrossRef]
  41. Dalmau, J.; Gleichman, A.J.; Hughes, E.G.; Rossi, J.E.; Peng, X.; Lai, M.; Dessain, S.K.; Rosenfeld, M.R.; Balice-Gordon, R.; Lynch, D.R. Anti-NMDA-receptor encephalitis: Case series and analysis of the effects of antibodies. Lancet Neurol. 2008, 7, 1091–1098. [Google Scholar] [CrossRef] [Green Version]
  42. Zaborowski, M.P.; Spaczynski, M.; Nowak-Markwitz, E.; Michalak, S. Paraneoplastic neurological syndromes associated with ovarian tumors. J. Cancer Res. Clin. Oncol. 2015, 141, 99–108. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  43. Dalmau, J.; Tüzün, E.; Wu, H.; Masjuan, J.; Rossi, J.E.; Voloschin, A.; Baehring, J.M.; Shimazaki, H.; Koide, R.; King, D. Paraneoplastic anti–N-methyl-D-aspartate receptor encephalitis associated with ovarian teratoma. Ann. Neurol. 2007, 61, 25–36. [Google Scholar] [CrossRef] [Green Version]
  44. Dai, Y.; Zhang, J.; Ren, H.; Zhou, X.; Chen, J.; Cui, L.; Lang, J.; Guan, H.; Sun, D. Surgical outcomes in patients with anti-N-methyl D-aspartate receptor encephalitis with ovarian teratoma. Am. J. Obstet. Gynecol. 2019, 221, 485.e1–485.e10. [Google Scholar] [CrossRef]
  45. Zhang, L.; Lu, Y.; Xu, L.; Liu, L.; Wu, X.; Zhang, Y.; Zhu, G.; Hong, Z. Anti-N-methyl-D-aspartate receptor encephalitis with accompanying ovarian teratoma in female patients from East China: Clinical features, treatment, and prognostic outcomes. Seizure 2020, 75, 55–62. [Google Scholar] [CrossRef]
  46. Chiu, H.-C.; Su, Y.-C.; Huang, S.-C.; Chiang, H.-L.; Huang, P.-S. Anti-NMDAR encephalitis with ovarian teratomas: Review of the literature and two case reports. Taiwan. J. Obstet. Gynecol. 2019, 58, 313–317. [Google Scholar] [CrossRef]
  47. Yu, M.; Li, S.; Cheng, J.; Zhou, L.; Jiang, Z.; Di, W. Ovarian teratoma-associated anti-NMDAR encephalitis: A single-institute series of six patients from China. Arch. Gynecol. Obstet. 2021, 303, 1283–1294. [Google Scholar] [CrossRef]
  48. Wu, C.-Y.; Wu, J.-D.; Chen, C.-C. The Association of Ovarian Teratoma and Anti-N-Methyl-D-Aspartate Receptor Encephalitis: An Updated Integrative Review. Int. J. Mol. Sci. 2021, 22, 10911. [Google Scholar] [CrossRef]
  49. Dawley, B.; Acuna, A.; Grasu, B. Ectopic production of HCG by a benign ovarian mature cystic teratoma simulating an extra-uterine pregnancy: A case report. West Va. Med. J. 2012, 108, 15–18. [Google Scholar]
  50. Kite, L.; Uppal, T. Ultrasound of ovarian dermoids—Sonographic findings of a dermoid cyst in a 41-year-old woman with an elevated serum hCG. Australas. J. Ultrasound Med. 2011, 14, 19–21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  51. Takemori, M.; Nishimura, R.; Yamasaki, M.; Kawabe, Y.; Hasegawa, K. Ovarian Mixed Germ Cell Tumor Composed of Polyembryoma and Immature Teratoma. Gynecol. Oncol. 1998, 69, 260–263. [Google Scholar] [CrossRef]
  52. Bin Park, S.; Kim, J.K.; Kim, K.-R.; Cho, K.-S. Imaging Findings of Complications and Unusual Manifestations of Ovarian Teratomas. RadioGraphics 2008, 28, 969–983. [Google Scholar] [CrossRef] [PubMed]
  53. Devaney, K.; Snyder, R.; Norris, H.J.; Tavassoli, F.A. Proliferative and histologically malignant struma ovarii: A clinicopathologic study of 54 cases. Int. J. Gynecol. Pathol. Off. J. Int. Soc. Gynecol. Pathol. 1993, 12, 333–343. [Google Scholar] [CrossRef] [PubMed]
  54. Tan, P.; Willatt, J.; Lindsell, D. The ability of ultrasound to detect gynaecological neoplasms and their ultrasound morphological features. Australas. Radiol. 2007, 51, 260–266. [Google Scholar] [CrossRef] [PubMed]
  55. Sheth, S.; Fishman, E.; Buck, J.; Hamper, U.; Sanders, R. The variable sonographic appearances of ovarian teratomas: Correlation with CT. Am. J. Roentgenol. 1988, 151, 331–334. [Google Scholar] [CrossRef] [PubMed]
  56. Soslow, R.A.; Tornos, C. Diagnostic Pathology of Ovarian Tumors; Springer Science & Business Media: Berlin/Heidelberg, Germany, 2011. [Google Scholar]
  57. Blackwell, W.J.; Dockerty, M.B.; Masson, J.C.; Mussey, R.D. Dermoid Cysts of the Ovary: Their Clinical and Pathologic Significance. Am. J. Obstet. Gynecol. 1946, 51, 151–172. [Google Scholar] [CrossRef] [PubMed]
  58. Friedman, A.; Pyatt, R.; Hartman, D.; Downey, E.; Olson, W. CT of benign cystic teratomas. Am. J. Roentgenol. 1982, 138, 659–665. [Google Scholar] [CrossRef]
  59. MATZ, M.H. Benign cystic teratomas of the ovary. Obstet. Gynecol. Surv. 1961, 16, 591–605. [Google Scholar] [CrossRef]
  60. Tangjitgamol, S.; Manusirivithaya, S.; Sheanakul, C.; Leelahakorn, S.; Thawaramara, T.; Jesadapatarakul, S. Squamous cell carcinoma arising from dermoid cyst: Case reports and review of literature. Int. J. Gynecol. Cancer 2003, 13. [Google Scholar] [CrossRef]
  61. Yanai-Inbar, I.; Scully, R.E. Relation of ovarian dermoid cysts and immature teratomas: An analysis of 350 cases of immature teratoma and 10 cases of dermoid cyst with microscopic foci of immature tissue. Int. J. Gynecol. Pathol. Off. J. Int. Soc. Gynecol. Pathol. 1987, 6, 203–212. [Google Scholar] [CrossRef]
  62. Atwi, D.; Kamal, M.; Quinton, M.; Hassell, L.A. Malignant transformation of mature cystic teratoma of the ovary. J. Obstet. Gynaecol. Res. 2022, 48, 3068–3076. [Google Scholar] [CrossRef]
  63. Corfman, P.A.; Richart, R.M. Chromosome Number and Morphology of Benign Ovarian Cystic Teratomas. N. Engl. J. Med. 1964, 271, 1241–1244. [Google Scholar] [CrossRef] [PubMed]
  64. Eppig, J.J.; Kozak, L.P.; Eicher, E.M.; Stevens, L.C. Ovarian Teratomas in Mice are Derived from Oocytes That Have Completed the First Meiotic Division. In Genetic Mosaics and Chimeras in Mammals; Springer: Berlin/Heidelberg, Germany, 1978; pp. 33–37. [Google Scholar] [CrossRef]
  65. Ohama, K. Androgenesis and Parthenogenesis in Humans. Hum. Genet. 1987, 245–249. [Google Scholar] [CrossRef]
  66. Linder, D.; Power, J. Further evidence for post -meiotic origin of teratomas in the human female. Ann. Hum. Genet. 1970, 34, 21–30. [Google Scholar] [CrossRef] [PubMed]
  67. Linder, D.; McCaw, B.K.; Hecht, F. Parthenogenic Origin of Benign Ovarian Teratomas. N. Engl. J. Med. 1975, 292, 63–66. [Google Scholar] [CrossRef] [PubMed]
  68. Vortmeyer, A.O.; Devouassoux-Shisheboran, M.; Li, G.; Mohr, V.; Tavassoli, F.; Zhuang, Z. Microdissection-Based Analysis of Mature Ovarian Teratoma. Am. J. Pathol. 1999, 154, 987–991. [Google Scholar] [CrossRef] [Green Version]
  69. Patil, S.R.; EW, L. Human benign ovarian teratomas: Chromosomal and electrophoretic enzyme studies. Birth Defects Orig Artic Ser. 1978, 14, 297–301. [Google Scholar] [PubMed]
  70. Carritt, B.; Parrington, J.M.; Welch, H.M.; Povey, S. Diverse origins of multiple ovarian teratomas in a single individual. Proc. Natl. Acad. Sci. USA 1982, 79, 7400–7404. [Google Scholar] [CrossRef] [Green Version]
  71. Parrington, J.M.; West, L.; Povey, S. The origin of ovarian teratomas. J. Med. Genet. 1984, 21, 4–12. [Google Scholar] [CrossRef] [Green Version]
  72. Surti, U.; Deka, R.; Hoffner, L.; Majumber, P.; Chakravarti, A.; Ferrel, R. Human ovarian teratomas: Origin and gene mapping using cytogenetic and DNA markers. Am. J. Hum. Genet. 1988, 43, A34. [Google Scholar]
  73. Wang, W.-C.; Lai, Y.-C. Genetic analysis results of mature cystic teratomas of the ovary in Taiwan disagree with the previous origin theory of this tumor. Hum. Pathol. 2016, 52, 128–135. [Google Scholar] [CrossRef]
  74. Kerr, S.E.; Flotte, A.B.; McFalls, M.J.; Vrana, J.A.; Halling, K.C.; Bell, D.A. Matching Maternal Isodisomy in Mucinous Carcinomas and Associated Ovarian Teratomas Provides Evidence of Germ Cell Derivation for Some Mucinous Ovarian Tumors. Am. J. Surg. Pathol. 2013, 37, 1229–1235. [Google Scholar] [CrossRef] [PubMed]
  75. Spinelli, C.; Strambi, S.; Masoni, B.; Ghionzoli, M.; Bertocchini, A.; Sanna, B.; Morganti, R.; Messina, M.; Molinaro, F.; Tursini, S.; et al. Surgical management of ovarian teratomas in childhood: A multicentric study on 110 cases and a literature review. Gynecol. Endocrinol. 2021, 37, 950–954. [Google Scholar] [CrossRef] [PubMed]
  76. Lin, P.; Falcone, T.; Tulandi, T. Excision of ovarian dermoid cyst by laparoscopy and by laparotomy. Am. J. Obstet. Gynecol. 1995, 173, 769–771. [Google Scholar] [CrossRef]
  77. Zanetta, G.; Ferrari, L.; Mignini-Renzini, M.; Vignali, M.; Fadini, R. Laparoscopic excision of ovarian dermoid cysts with controlled intraoperative spillage. Safety and effectiveness. J Reprod Med. 1999, 44, 815–820. [Google Scholar]
  78. Childress, K.J.; Santos, X.M.; Perez-Milicua, G.; Hakim, J.; Adeyemi-Fowode, O.; Bercaw-Pratt, J.L.; Dietrich, J.E. Intraoperative rupture of ovarian dermoid cysts in the pediatric and adolescent population: Should this change your surgical management? J. Pediatr. Adolesc. Gynecol. 2017, 30, 636–640. [Google Scholar] [CrossRef] [PubMed]
  79. Caspi, B.; Appelman, Z.; Rabinerson, D.; Zalel, Y.; Tulandi, T.; Shoham, Z. The growth pattern of ovarian dermoid cysts: A prospective study in premenopausal and postmenopausal women. Fertil. Steril. 1997, 68, 501–505. [Google Scholar] [CrossRef]
  80. Howard, F. Surgical management of benign cystic teratoma. Laparoscopy vs. laparotomy. J. Reprod. Med. 1995, 40, 495–499. [Google Scholar]
  81. Spinelli, C.; Strambi, S.; Liloia, C.; Bertocchini, A.; Messineo, A. Update on the surgical management of ovarian neoplasms in children and adolescents: Analysis on 32 cases. Gynecol. Endocrinol. 2016, 32, 787–791. [Google Scholar] [CrossRef]
  82. Mahtate, M.; Talib, S.; Slaoui, A.; Zeraidi, N.; Lakhdar, A.; Rhrab, B.; Baydada, A. Malignant Degeneration of a Mature Ovarian Teratoma. Case Rep. Obstet. Gynecol. 2021, 2021, 5527467. [Google Scholar] [CrossRef]
  83. Dos Santos, L.; Mok, E.; Iasonos, A.; Park, K.; Soslow, R.; Aghajanian, C.; Alektiar, K.; Barakat, R.R.; Abu-Rustum, N.R. Squamous cell carcinoma arising in mature cystic teratoma of the ovary: A case series and review of the literature. Gynecol. Oncol. 2007, 105, 321–324. [Google Scholar] [CrossRef]
  84. Chen, R.-J.; Chen, K.-Y.; Chang, T.-C.; Sheu, B.-C.; Chow, S.-N.; Huang, S.-C. Prognosis and treatment of squamous cell carcinoma from a mature cystic teratoma of the ovary. J. Formos. Med. Assoc. 2008, 107, 857–868. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  85. Rim, S.-Y.; Kim, S.-M.; Choi, H.-S. Malignant transformation of ovarian mature cystic teratoma. Int. J. Gynecol. Cancer 2006, 16, 140–144. [Google Scholar] [CrossRef]
  86. Gadducci, A.; Guerrieri, M.E.; Cosio, S. Squamous cell carcinoma arising from mature cystic teratoma of the ovary: A challenging question for gynecologic oncologists. Crit. Rev. Oncol. 2019, 133, 92–98. [Google Scholar] [CrossRef] [PubMed]
  87. Chiang, A.-J.; La, V.; Peng, J.; Yu, K.-J.; Teng, N.N. Squamous Cell Carcinoma Arising From Mature Cystic Teratoma of the Ovary. Int. J. Gynecol. Cancer 2011, 21, 466–474. [Google Scholar] [CrossRef]
  88. Fukase, M.; Ohta, T.; Watanabe, N.; Suzuki, Y.; Seino, M.; Sudo, T.; Nagase, S. Squamous cell carcinoma arising from a mature cystic teratoma of the ovary: Successful treatment with carboplatin, paclitaxel, and bevacizumab. Gynecol. Oncol. Rep. 2020, 34, 100632. [Google Scholar] [CrossRef] [PubMed]
  89. Fenner, M.H.; Beutel, G.; Grünwald, V. Targeted therapies for patients with germ cell tumors. Expert Opin. Investig. Drugs 2008, 17, 511–522. [Google Scholar] [CrossRef]
  90. Ribeiro, G.; Hughesdon, P.; Wiltshaw, E. Squamous carcinoma arising in dermoid cysts and associated with hypercalcemia: A clinicopathologic study of six cases. Gynecol. Oncol. 1988, 29, 222–230. [Google Scholar] [CrossRef]
  91. Burger, R.A.; Brady, M.F.; Bookman, M.A.; Fleming, G.F.; Monk, B.J.; Huang, H.; Mannel, R.S.; Homesley, H.D.; Fowler, J.; Greer, B.E. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N. Engl. J. Med. 2011, 365, 2473–2483. [Google Scholar] [CrossRef] [Green Version]
  92. Liu, J.F.; Konstantinopoulos, P.A.; Matulonis, U.A. PARP inhibitors in ovarian cancer: Current status and future promise. Gynecol. Oncol. 2014, 133, 362–369. [Google Scholar] [CrossRef]
  93. O’Malley, D.M.; Matulonis, U.A.; Birrer, M.J.; Castro, C.M.; Gilbert, L.; Vergote, I.; Martin, L.P.; Mantia-Smaldone, G.M.; Martin, A.G.; Bratos, R.; et al. Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. Gynecol. Oncol. 2020, 157, 379–385. [Google Scholar] [CrossRef]
  94. Harbin, L.M.; Gallion, H.H.; Allison, D.B.; Kolesar, J.M. Next Generation Sequencing and Molecular Biomarkers in Ovarian Cancer—An Opportunity for Targeted Therapy. Diagnostics 2022, 12, 842. [Google Scholar] [CrossRef] [PubMed]
  95. Galvez-Carvajal, L.; Sanchez-Muñoz, A.; Ribelles, N.; Saez, M.; Baena, J.; Ruiz, S.; Ithurbisquy, C.; Alba, E. Targeted treatment approaches in refractory germ cell tumors. Crit. Rev. Oncol. Hematol. 2019, 143, 130–138. [Google Scholar] [CrossRef] [PubMed]
  96. Mansoori, B.; Mohammadi, A.; Davudian, S.; Shirjang, S.; Baradaran, B. The Different Mechanisms of Cancer Drug Resistance: A Brief Review. Adv. Pharm. Bull. 2017, 7, 339–348. [Google Scholar] [CrossRef] [PubMed]
Ijms 24 06141 g001 550
Figure 1. The incidence of three germ layers and the tissues in MCTs.
Figure 1. The incidence of three germ layers and the tissues in MCTs.
Ijms 24 06141 g001
Ijms 24 06141 g002 550
Figure 2. Treatment options for malignant transformations [3,21,22,27,34,35,79,85,86,87,88,89,90,91,92,93,94].
Figure 2. Treatment options for malignant transformations [3,21,22,27,34,35,79,85,86,87,88,89,90,91,92,93,94].
Ijms 24 06141 g002
Table
Table 1. Typical image findings of MCTs [3,6,14,15,55].
Table 1. Typical image findings of MCTs [3,6,14,15,55].
Pathologic EquivalentImage Findings
USRokitansky noduleEchogenic tubercle with cystic echo
Hair and watery fluidThin band-like echoes
Presence of sebumDense echo pattern
Sebum layered on serous fluidFat–fluid level
Desquamative materialFloating intracystic spheres
CTFat intralesionalSubstance’s density is −20 HU or lower inside a cyst
Rokitansky noduleRounded (or bridge) structure, clearly linked to the cyst wall, projecting inside the cyst
Or
Irregular mural thickening containing dense structures (calcified structures) and\or areas of fatty
MRISebaceous materialT1 hyperintense and T2 hypointense
Squamous materialT1 hypointense and T2 hyperintense
HairT2 hypointense
ToothLow-signal-intensity central calcifications
US: Ultrasound; CT: Computed tomography; MRI: Magnetic resonance imaging.
Table
Table 2. The studies of the cellular origin of MCTs.
Table 2. The studies of the cellular origin of MCTs.
ReferencesMaterialsMarkersMain ResultsConclusion
Linder D et al. [66] 197039 MCTs from 33 patientsAllelic isozymes: G6PD, PGM1, PGM3, 6PGD6 of 12 tumors at PGM1 locus were heterozygous in host but homozygous in tumorsMCTs are from post-meiotic origin
Linder D et al. [67] 19755 MCTs from 5 patientsQ-banding, G-banding, C-banding; PGM1, PGM3, 6PGD, etc.2 of 3 tumors at PGM1 locus, and 1 of 2 tumors at PGM3 locus were heterozygous in host but homozygous in tumorsMCTs arise from single germ cell after first meiosis
Eppig JJ et al. [64] 197723 teratomas from strain LT/SV miceGpi-121 of 23 tumors at Gpi-1 locus were heterozygous in host but homozygous in tumorsTumors are origin from post-meiotic oocytes
Carritt B et al. [70] 19827 benign ovarian teratomas in one patientC-banding, PGM1, PGD, UMPK, ME24 of 7 teratomas showed heterozygous on c-banding resultsExclude the suppression of meiosis II as amode of origin for some of these tumors.
Parrington JM et al. [71] 198421 benign ovarian teratomas from 14 patientsC-banding, Q-banding; 13 enzyme markers (PGD, PGM1, PGM3, etc.)52% of teratomas had homozygous centromeres and enzymesMany of this group are thought to arise from duplication of a mature ovum
Surti U [1] 1990102 benign mature teratomas from patientsQ-banding, C-bandingFirst reported tetraploidy and structural rearrangement in teratomas; 65% of teratomas have homozygous centromere65% of tumors arose from single germ cell after first meiosis or failure of second meiosis or endoreduplication of mature ovum; the rest arose by failure of first meiosis or mitotic division of premeiotic germ cell
Vootmeyer AO [68] 19997 mature ovarian teratomasMicrodissection; PCR using microsatellite markersMarkers showed homozygous in majority tumorsTumors arose from post-meiotic germ cell
Wang WC [73] 20169 MCTs15 STR analysis; Methylation analysisMost of the STR loci in tumors showed heterozygousExclude the parthenogenetic origin of MCTs
MCTs: Mature cystic teratomas; G6PD: glucose-6-phosphate dehydrogenase; PGM1: Phosphoglucomutase 1; PGM3: Phosphoglucomutase 3; 6PGD: 6-phosphogluconate dehydrogenase; Gpi-1: Glucose-6-phosphate isomerase 1; UMPK: Uridine monophosphate kinase; PCR: Polymerase chain reaction; STR: Short tandem repeat.
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Cong, L.; Wang, S.; Yeung, S.Y.; Lee, J.H.S.; Chung, J.P.W.; Chan, D.Y.L. Mature Cystic Teratoma: An Integrated Review. Int. J. Mol. Sci. 2023, 24, 6141. https://doi.org/10.3390/ijms24076141

AMA Style

Cong L, Wang S, Yeung SY, Lee JHS, Chung JPW, Chan DYL. Mature Cystic Teratoma: An Integrated Review. International Journal of Molecular Sciences. 2023; 24(7):6141. https://doi.org/10.3390/ijms24076141

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Cong, Luping, Sijia Wang, Suet Ying Yeung, Jacqueline Ho Sze Lee, Jacqueline Pui Wah Chung, and David Yiu Leung Chan. 2023. "Mature Cystic Teratoma: An Integrated Review" International Journal of Molecular Sciences 24, no. 7: 6141. https://doi.org/10.3390/ijms24076141

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