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Mature Cystic Teratoma of Ovary with Abnormally High Levels of Ca19-9: A Case Report

Teratoma maduro cístico do ovário com níveis aberrantes de Ca19-9: caso clínico

Abstract

Mature cystic teratomas, or dermoid tumors, are the most common benign ovarian neoplasms in young women. Malignant transformation is rare, and occurs in less than 2% of the cases. The heterogeneous histological composition of these tumors may be responsible for the occasional elevation of various tumor markers, such as Ca19-9 and Ca125. We describe one case of mature cystic teratoma in a 50-year old woman with the second highest level of Ca19-9 (8922.76 UI/mL) described in the literature. We concluded that abnormal levels of Ca19-9 are not necessarily associated with ovarian malignancy, and may lead to unnecessary medical intervention and patient anxiety. Therefore, the clinical features, imaging studies and antigen testing should be interpreted carefully, and should not limit the surgical approach.

Keywords:
Ca19-9; tumor markers; mature cystic teratoma; ovarian teratoma; dermoid cyst

Resumo

Os teratomas maduros císticos do ovário, ou tumores dermoides, são as neoplasias benignas mais frequentes em mulheres jovens. A sua transformação maligna é rara, e ocorre emmenos de 2% dos casos. A composição histológica heterogénea destes tumores pode ser responsável pela ocasional elevação de marcadores tumorais, como o Ca19-9 e o Ca125. Descrevemos umcaso de teratoma maduro cístico do ovário numa paciente de 50 anos com o segundo valor mais elevado de Ca19-9 (8922,76 UI/mL) descrito na literatura. Concluímos que níveis anormalmente elevados de Ca19-9 não estão necessariamente associados a tumores malignos, e podem conduzir a intervenções médicas desnecessárias e contribuir para o aumento da ansiedade da paciente. Portanto, as características clínicas, os estudos imagiológicos e os marcadores tumorais devem ser interpretados cuidadosamente, e não devem limitar o tipo de conduta cirúrgica.

Palavras-chave:
Ca19-9; marcadores tumorais; teratoma maduro cístico; teratoma ovárico; quisto dermoide

Introduction

Mature cystic teratoma (MCT), or dermoid tumor, was described for the first time 300 years ago, and is the most common ovarian tumor in adolescents and young women.11 Park CH, Jung MH, Ji YI. Risk factors for malignant transformation of mature cystic teratoma. Obstet Gynecol Sci 2015;58(6): 475-480 It accounts for 10–25% of all ovarian neoplasms, and 60% of all benign ovarian tumors.22 Atabekoglu C, Bozaci EA, Tezcan S. Elevated carbohydrate antigen 19-9 in a dermoid cyst. Int J Gynaecol Obstet 2005;91(3):262-263 33 Ulkumen BA, Goker A, Pala HG, Ordu S. Abnormal elevated Ca 19- 9 in the dermoid cyst: a sign of the ovarian torsion? Case Rep Obstet Gynecol 2013;20(13):860-505 Although most women presenting MCT are asymptomatic, ∼ 20% can have complications such as torsion, rupture, infection and malignant transformation (0,17–3% of cases).44 Madaan M, Puri M, Sharma R, Kaur H, Trivedi SS. Unusually high levels of Ca19-9 associated with mature cystic teratoma of the ovary. Case Rep Obstet Gynecol 2014;2014:187910 55 Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19:230-235 MCTs are composed of one or more of the three well differentiated tissues derived from the ectoderm, mesoderm and/or endoderm germ layers. This heterogeneous composition may be responsible for the occasional elevation of various tumor markers, such as cancer antigen (Ca) 19–9 and Ca125.66 DedeM, Gungor S, YenenMC, Alanbay I, Duru NK, Hasimi A. CA19- 9may have clinical significance in mature cystic teratomas of the ovary. Int J Gynecol Cancer 2006;16(1):189-193 7. Ito K. CA19-9 in mature cystic teratoma. Tohoku J Exp Med 1994; 172(2):133-138

Cancer antigen 19–9 (also called sialylated Lewis(a) antigen) is located in the cell membrane, and undergoes various alterations during the process of cell differentiation and/or malignant transformation.77 Ito K. CA19-9 in mature cystic teratoma. Tohoku J Exp Med 1994; 172(2):133-138 It is most frequently raised in patients with malignancies of the pancreas, biliary tract, colon, esophagus and liver, but it can also be elevated in benign conditions, and has been suggested recently as a potential marker for the diagnosis of ovarian MCT.55 Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19:230-235

To the extent of our knowledge, we describe a case of MCT with the second highest level of the serum Ca19–9 described in literature.88 Kataoka T, Watanabe Y, Hoshiai H. Retrospective evaluation of tumor markers in ovarian mature cystic teratoma and ovarian endometrioma. J Obstet Gynaecol Res 2012;38(8):1071-1076

Case Presentation

A 50-year-old, premenopausal healthy woman, G1P1 (caesarean section), presented to our hospital with abdominal cramping and right abdominal pain with one week of evolution and recent worsening. Her medical history included chronic hypertension without any other clinically relevant history. Physical examination revealed a large and firm left pelvic mass occupying the left adnexal area, and the pouch of Douglas displacing the uterus to the right side. A pelvic ultrasound showed an adnexal mass with 74 × 63 mm with echogenic areas suggestive of MCT of the left ovary. The patient's complete blood count and reactive protein-C were within the normal range. She was admitted to our service due to severe abdominal pain, and with the aim of performing further imaging and laboratory tests to clarify the origin of the mass. A pelvic magnetic resonance imaging (MRI) scan showed a multiloculated left pelvic mass with 95 × 70 × 67 mm with areas of fat density and proteinaceous content (Fig. 1). A computed tomography (CT) scan revealed the same mature mass with 107 × 77 mm with abundant fat content (Fig. 2). Tumor markers were within the normal parameters (Ca15.3–9.2 UI/mL; α-fetoprotein – 0.76 ng/mL; β human chorionic gonadotropin – < 1.2 mUI/mL; and Ca125–14.1 UI/mL), except for Ca19–9, which was markedly raised (8922.76 UI/mL). Upper gastrointestinal endoscopy and total colonoscopy did not show signs of gastrointestinal malignancy.

Fig. 1
T2-weighted magnetic resonance image — Multiloculated left pelvic mass with 95 × 70 × 67 mm with areas of fat density and proteinaceous content.

Fig. 2
CT scan image — Left adnexal mass with 102 × 77 mm with heterogeneous content and abundant fat component.

As we strongly believe that experienced imagiologists can reliably make the diagnosis of MCT based on MRI and CT scans, and after the exclusion of a gastrointestinal malignancy, we decided to perform an exploratory laparotomy with peritoneal lavage. During the procedure we found a 10 cm solid mass replacing the left ovary. The intraoperative histologic diagnosis revealed a mature cystic teratoma. We performed a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Extensive histologic sectioning confirmed this diagnosis. The postoperative period was uneventful, and Ca19–9 returned to its normal levels.

Discussion

Mature cystic teratomas are ovarian germ cell tumors believed to arise from the primordial germ cells by failure of meiosis II or from a pro-meiotic cell in which meiosis has failed. These tumors are composed of tissues originated in all germ cell layers, and therefore various malignancies may rise in any of these layers.11 Park CH, Jung MH, Ji YI. Risk factors for malignant transformation of mature cystic teratoma. Obstet Gynecol Sci 2015;58(6): 475-480 Considering these histological features, it is not surprising that Ca19–9 and Ca125 can be raised in patients presenting MCT.55 Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19:230-235 99 Ustunyurt E, Gungor T, Iskender C, Ustunyurt BO, Bilge U, Mollamahmutoglu L. Tumor markers in mature cystic teratomas of the ovary. Arch Gynecol Obstet 2009;279(2):145-147 The rate of elevation of tumor markers Ca19–9 and Ca125 in MCTs has been reported to range from 39.6 to 59% and 13.5 to 25% respectively.55 Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19:230-235 1010 Suh DS, Moon SH, Kim SC, Joo JK, Park WY, Kim KH. Significant simultaneous changes in serum CA19-9 and CA125 due to prolonged torsion of mature cystic teratoma of the ovary. World J Surg Oncol 2014;12:353 However, markedly raised levels of Ca19–9 (greater than 1,000 mUI/mL) are almost always observed in the advanced stage of malignancy.1111 Pyeon SY, Park JY, Ki KD, Lee JM. Abnormally high level of CA-19-9 in a benign ovarian cyst. Obstet Gynecol Sci 2015;58(6):530-532 Nevertheless, Ustunyurt et al suggest that Ca19–9 is a potential marker for the diagnosis of MCT.99 Ustunyurt E, Gungor T, Iskender C, Ustunyurt BO, Bilge U, Mollamahmutoglu L. Tumor markers in mature cystic teratomas of the ovary. Arch Gynecol Obstet 2009;279(2):145-147

The diagnosis of these tumors is not difficult in the majority of cases. Computed tomography and MRI imaging present high sensitivity for fat and calcification, which represent the most common features of MCTs.1212 Saba L, Guerriero S, Sulcis R, Virgilio B, Melis G, Mallarini G. Mature and immature ovarian teratomas: CT, US andMR imaging characteristics. Eur J Radiol 2009;72(3):454-463 Despite the specific characteristics of dermoid tumors in pelvic imaging studies, making a definitive diagnosis is sometimes difficult, and ∼ 30% of them are not apparent in the pelvic ultrasound.55 Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19:230-235 Some intrinsic sonographic features of cystic teratomas can act as confounding factors, and more than 80% of these tumors present an echo pattern that can suggest malignancy, creating difficulties to differentiate a benign mass from an ovarian malignancy.1212 Saba L, Guerriero S, Sulcis R, Virgilio B, Melis G, Mallarini G. Mature and immature ovarian teratomas: CT, US andMR imaging characteristics. Eur J Radiol 2009;72(3):454-463 Furthermore, other common findings, such as their large diameters and occasionally raised tumor markers, make the differential diagnosis even more difficult.55 Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19:230-235 We must also keep in mind that the malignant transformation of MCT, most frequently in invasive squamous cell carcinoma, but also in adenocarcinoma, sarcoma, carcinoid, thyroid carcinoma and melanoma, although rare (less than 2% of cases), can also be associated with the elevation of tumor markers, such as Ca19–9.1313 Parithivel K, Jagannathan JP, Krajewski K, et al. Ovarian squamous cell carcinoma arising from mature cystic teratoma. Cancer Imaging 2011;11:67-69 1414 Kudva R, Ayachit GS, Ayachit A. Malignant melanoma arising in an ovarian mature cystic teratoma - a rare entity. J Clin Diagn Res 2015;9(4):ED14-ED16 Nevertheless, when the nature of a pelvic mass cannot be determined by imaging study alone, Ca19–9 testing might be a helpful tool to assist MCT diagnosis.55 Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19:230-235

Some retrospective studies have been conducted in the last years with the objective of associating the elevation of serum Ca19–9 with specific clinical features of MCTs. Dede et al66 DedeM, Gungor S, YenenMC, Alanbay I, Duru NK, Hasimi A. CA19- 9may have clinical significance in mature cystic teratomas of the ovary. Int J Gynecol Cancer 2006;16(1):189-193 7. Ito K. CA19-9 in mature cystic teratoma. Tohoku J Exp Med 1994; 172(2):133-138 retrospectively evaluated 80 cases of MCTs and concluded that patients with elevated Ca19–9 levels have greater tumor sizes, though the difference was statistically not significant. Another work from Cho et al55 Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19:230-235 reviewed the clinical features of 239 patients with pathologically confirmed MCTs, and demonstrated a significant correlation between Ca19–9 level, tumor size and fat component. However, Frimer et al1515 Frimer M, Seagle BLL, Chudnoff S, Goldberg GL, Shahabi S. Role of elevated cancer antigen 19-9 in women with mature cystic teratoma. Reprod Sci 2014;21(10):1307-1311 failed to demonstrate any relationship between Ca19–9 and any meaningful clinical parameters. Ulkumen et al33 Ulkumen BA, Goker A, Pala HG, Ordu S. Abnormal elevated Ca 19- 9 in the dermoid cyst: a sign of the ovarian torsion? Case Rep Obstet Gynecol 2013;20(13):860-505 suggest that the correlation between high serum antigen levels and tumor size is due to leakage from the cyst wall into the bloodstream, as a result of the rupture of its weakened wall caused by the large diameter of the lesion. The rise in tumor marker concentration may also be related to ovarian torsion and to the extent of the necrosis of the ovary.33 Ulkumen BA, Goker A, Pala HG, Ordu S. Abnormal elevated Ca 19- 9 in the dermoid cyst: a sign of the ovarian torsion? Case Rep Obstet Gynecol 2013;20(13):860-505 Only a few reports have suggested that this antigen might have been stimulated by the inflammatory change due to the ischemic reaction after the torsion, and might predict the extent of tissue necrosis.1010 Suh DS, Moon SH, Kim SC, Joo JK, Park WY, Kim KH. Significant simultaneous changes in serum CA19-9 and CA125 due to prolonged torsion of mature cystic teratoma of the ovary. World J Surg Oncol 2014;12:353 Cancer antigen 19–9 can be a particularly good marker for the evaluation of ovarian torsion and the extensity of ovarian necrosis, whose early detection is of great importance.33 Ulkumen BA, Goker A, Pala HG, Ordu S. Abnormal elevated Ca 19- 9 in the dermoid cyst: a sign of the ovarian torsion? Case Rep Obstet Gynecol 2013;20(13):860-505 55 Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19:230-235

The published studies have demonstrated that malignant transformation is not related to serum Ca19–9 elevation, and that its high levels in women with MCT of the ovary are not associated with malignant transformation.1010 Suh DS, Moon SH, Kim SC, Joo JK, Park WY, Kim KH. Significant simultaneous changes in serum CA19-9 and CA125 due to prolonged torsion of mature cystic teratoma of the ovary. World J Surg Oncol 2014;12:353

Some authors support the combined use of Ca19–9 and Ca125 as a useful tool for determining the nature of a pelvic mass with associated high levels of the serum Ca19–9.55 Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19:230-235 1010 Suh DS, Moon SH, Kim SC, Joo JK, Park WY, Kim KH. Significant simultaneous changes in serum CA19-9 and CA125 due to prolonged torsion of mature cystic teratoma of the ovary. World J Surg Oncol 2014;12:353 1515 Frimer M, Seagle BLL, Chudnoff S, Goldberg GL, Shahabi S. Role of elevated cancer antigen 19-9 in women with mature cystic teratoma. Reprod Sci 2014;21(10):1307-1311 Furthermore, Ca19–9 levels can be used as a marker for postoperative follow-up in benign diseases, and as a marker for recurrence of mature cystic teratomas.44 Madaan M, Puri M, Sharma R, Kaur H, Trivedi SS. Unusually high levels of Ca19-9 associated with mature cystic teratoma of the ovary. Case Rep Obstet Gynecol 2014;2014:187910 77 Ito K. CA19-9 in mature cystic teratoma. Tohoku J Exp Med 1994; 172(2):133-138

In conclusion, abnormal levels of Ca19–9 are not necessarily associated with ovarian malignancy, and may lead to unnecessary medical intervention and patient anxiety. We described one case of unilateral MCT with the second highest concentration of Ca19–9 (8922.76 UI/mL) published in literature, with no signs of torsion or necrosis.

Although several studies have been published, a correlation between the clinical features of MCT and the elevation of serum tumor markers has not yet been established. We believe that an isolated increase of serum Ca19–9 is not rare, and is not associated with malignant transformation. Therefore, the clinical features, imaging studies and antigen testing should be interpreted carefully, and should not limit a minimally invasive surgical approach.

References

  • 1
    Park CH, Jung MH, Ji YI. Risk factors for malignant transformation of mature cystic teratoma. Obstet Gynecol Sci 2015;58(6): 475-480
  • 2
    Atabekoglu C, Bozaci EA, Tezcan S. Elevated carbohydrate antigen 19-9 in a dermoid cyst. Int J Gynaecol Obstet 2005;91(3):262-263
  • 3
    Ulkumen BA, Goker A, Pala HG, Ordu S. Abnormal elevated Ca 19- 9 in the dermoid cyst: a sign of the ovarian torsion? Case Rep Obstet Gynecol 2013;20(13):860-505
  • 4
    Madaan M, Puri M, Sharma R, Kaur H, Trivedi SS. Unusually high levels of Ca19-9 associated with mature cystic teratoma of the ovary. Case Rep Obstet Gynecol 2014;2014:187910
  • 5
    Cho HY, Kim K, Jeon YT, Kim YB, No JH. CA19-9 elevation in ovarian mature cystic teratoma: discrimination from ovarian cancer - CA19-9 level in teratoma. Med Sci Monit 2013; 19:230-235
  • 6
    DedeM, Gungor S, YenenMC, Alanbay I, Duru NK, Hasimi A. CA19- 9may have clinical significance in mature cystic teratomas of the ovary. Int J Gynecol Cancer 2006;16(1):189-193 7. Ito K. CA19-9 in mature cystic teratoma. Tohoku J Exp Med 1994; 172(2):133-138
  • 7
    Ito K. CA19-9 in mature cystic teratoma. Tohoku J Exp Med 1994; 172(2):133-138
  • 8
    Kataoka T, Watanabe Y, Hoshiai H. Retrospective evaluation of tumor markers in ovarian mature cystic teratoma and ovarian endometrioma. J Obstet Gynaecol Res 2012;38(8):1071-1076
  • 9
    Ustunyurt E, Gungor T, Iskender C, Ustunyurt BO, Bilge U, Mollamahmutoglu L. Tumor markers in mature cystic teratomas of the ovary. Arch Gynecol Obstet 2009;279(2):145-147
  • 10
    Suh DS, Moon SH, Kim SC, Joo JK, Park WY, Kim KH. Significant simultaneous changes in serum CA19-9 and CA125 due to prolonged torsion of mature cystic teratoma of the ovary. World J Surg Oncol 2014;12:353
  • 11
    Pyeon SY, Park JY, Ki KD, Lee JM. Abnormally high level of CA-19-9 in a benign ovarian cyst. Obstet Gynecol Sci 2015;58(6):530-532
  • 12
    Saba L, Guerriero S, Sulcis R, Virgilio B, Melis G, Mallarini G. Mature and immature ovarian teratomas: CT, US andMR imaging characteristics. Eur J Radiol 2009;72(3):454-463
  • 13
    Parithivel K, Jagannathan JP, Krajewski K, et al. Ovarian squamous cell carcinoma arising from mature cystic teratoma. Cancer Imaging 2011;11:67-69
  • 14
    Kudva R, Ayachit GS, Ayachit A. Malignant melanoma arising in an ovarian mature cystic teratoma - a rare entity. J Clin Diagn Res 2015;9(4):ED14-ED16
  • 15
    Frimer M, Seagle BLL, Chudnoff S, Goldberg GL, Shahabi S. Role of elevated cancer antigen 19-9 in women with mature cystic teratoma. Reprod Sci 2014;21(10):1307-1311

Publication Dates

  • Publication in this collection
    July 2016

History

  • Received
    02 Mar 2016
  • Accepted
    10 June 2016
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