Malignant Transformation of an Ovarian Mature Cystic Teratoma to a Malignant Melanoma

Abstract

Ovarian mature cystic teratomas comprise tissue derived from all three germ layers and constitute 10–20% of all ovarian neoplasms. Malignant transformation of mature cystic teratomas (MCT) is very rare with an incidence of 0.17–2%. The most frequently reported malignancies include squamous cell carcinoma and adenocarcinoma. Herein, we describe a case of a 56-year-old female who presented with abdominal pain and underwent total abdominal hysterectomy with bilateral oophorectomy and omentectomy for a ruptured dermoid cyst. Histological examination showed nests of pleomorphic cells with prominent nucleoli and melanin pigment in the background of a mature cystic teratoma. These cells showed immunoreactivity for Melan-A and HMB-45, thus confirming the diagnosis of malignant transformation of a mature cystic teratoma to a malignant melanoma.

Introduction

Mature teratomas constitute 10–20% of all ovarian neoplasms. Malignant transformation is very rare with an incidence of 0.17–2% [1] and transformation to a primary malignant melanoma is extremely rare. The prognosis of malignant transformation of the MCT is very poor [2]. Very few cases of malignant transformation of a mature cystic teratoma to a malignant melanoma have been reported to date [3, 4].

Herein, we describe a case of a primary malignant melanoma arising from a ruptured ovarian mature cystic teratoma and associated with omental and bowel deposits.

Case Report

A 56-year-old female, post-menopausal for 16 years, presented with lower abdominal pain for 2 months, and abdominal distension. There was no vaginal discharge or post-menopausal bleeding. Physical examination revealed diffuse fullness present over the lower abdomen corresponding to 18-week uterus size. On vaginal examination, a separate mobile cystic mass was felt in the left fornix. Right fornix, bilateral parametrium, and rectal mucosa were free. On ultrasound, the left adnexa showed a cystic anechoic mass lesion of size 85 × 78 mm and the left ovary was not visualized separately.

A computed tomography scan revealed an ill-defined large heterogenous lesion measuring 9.8 × 9.5 cm with areas of fat attenuation and calcification in the left adnexa suggestive of teratoma (Fig. 1a).

Fig. 1.

Radiological and gross findings. a Computed tomography showed an ill-defined large heterogenous lesion measuring 9.8 × 9.5 cm with areas of fat attenuation and calcification in the left adnexa suggestive of teratoma. b, c Gross findings showed a mass filled with pultaceous material and two small blackish nodules attached to the inner surface of the cyst wall. d, e The attached omentum showed numerous blackish nodules scattered all over. f The uterus and cervix are grossly unremarkable

On gross examination, the tumor was globular, gray-white, and cystic mass filled with pultaceous material. The external surface was pearly white. Two small blackish nodules were identified measuring 2 cm and 1 cm in diameter attached to the inner surface of the cyst wall. The uterus and cervix were grossly unremarkable (Fig. 1b–f).

Microscopy showed keratinized stratified squamous epithelium with pilosebaceous unit, cartilage, and keratin flakes. Occasional focus also showed bone and thyroid follicles. The blackish nodule was composed of nests and lobules of epithelioid to spindle-shaped cells with pleomorphic hyperchromatic nuclei, coarse irregular chromatin, prominent eosinophilic nucleoli, atypical mitotic figures, and dusty pigmented cytoplasm. Although the histomorphological characteristics and melanin pigment clearly suggested melanoma, a provisional diagnosis of melanoma developing within a teratoma was made and confirmed on immunohistochemistry, which was positive for HMB-45, s-100, SOX-10, and Melan-A. Omental and bowel deposits also showed metastatic melanoma deposits (Fig. 2).

Fig. 2.

Histomorphological and immunohistochemical findings. a Hematoxylin and eosin–stained sections exhibited a cyst lined by stratified squamous epithelium with pilosebaceous unit. b Occasional areas of thyroid follicles filled with colloid were also observed (marked with a red arrow). c Bony fragments (marked with a green arrow) along with focus of the tumor exhibiting pigment deposition. d The cyst wall along with the presence of a tumor composed of pleomorphic spindle-shaped cells with extensive pigment deposition (inset shows high power view of sebaceous gland with foci of malignant melanoma). e Microphotograph of the tumor composed of spindle-shaped cells with oval to elongated nuclei and scant eosinophilic cytoplasm with melanin pigment deposition. f, g, h Immunohistochemistry demonstrated positive expression for SOX10 (f), S-100 (g), and Melan-A (h) (× 40, × 100 magnification)

The patient was subsequently assessed to exclude the possibility of melanoma at any other site—skin and gastrointestinal tract. She was given adjuvant immunotherapy with high-dose interferon (IFN)-α. Currently, she is under close surveillance with no evidence of any recurrence/residual disease.

Discussion

Teratoma is the most common germ cell tumor of the ovary, comprising 10–20% of all ovarian neoplasms. It is composed of tissue derived from all three germ layers, that is, the endoderm, mesoderm, and ectoderm [5]. Mature cystic teratoma mainly occurs in young females. Malignant transformation can occur at any age; however, it most commonly occurs in menopausal women [2], although it is a very rare phenomenon.

Malignant transformation of the MCT to squamous cell carcinoma, basal cell carcinoma, sebaceous tumors, adenocarcinoma, sarcoma, malignant melanoma, and neuroectodermal tumor has been reported to date [6]. Among these, squamous cell carcinoma is the most common malignant tumor arising from teratoma while malignant melanoma is extremely rare. Very few cases of malignant transformation of mature cystic teratoma into melanoma have been reported to date [3, 4]. Table 1 summarizes the clinicopathological features of previously reported cases.

Table 1.

Characteristics of previously reported cases of malignant melanoma arising in a mature cystic teratoma

Authors	Age (years)	Clinical presentation	Radiological findings	Histopathological diagnosis	Treatment
Lee et al. [12]	71	Palpable mass in the lower abdomen, generalized weakness, weight loss	CT—15 cm sized septate cystic mass with multiple internal fatty components in the pelvic cavity. MRI of the pelvic mass were suggestive of ovarian mature cystic teratoma	Primary malignant melanoma of the ovary arising in a cystic teratoma	BSO, followed by 2 cycles of chemotherapy
Godoy et al. [13]	64	Large left adnexal mass and ascites	CT—right-sided pleural effusion, an ovarian mass and ascites	Primary malignant melanoma of the ovary arising in a cystic teratoma	BSO, hysterectomy, omentectomy, resection of diffuse tumoral implant followed by chemotherapy
Hyun et al. [14]	75	Pelvic mass	USG—pelvic mass measuring 17 × 11 cm with mixed echogenicity and a thin septation CT—multi-lobulated 19 × 15 cm cystic mass with calcification and fat, suggesting a teratoma	Primary malignant melanoma of the ovary arising in a cystic teratoma	BSO, partial omentum followed by chemotherapy and immunotherapy
Lee et al. [15]	38	2 month history of lower abdominal pain	CT—12 × 13 cm left adnexal mass	Primary malignant melanoma of the ovary arising in a cystic teratoma	Left salpingo-oophorectomy
Genc et al. [16]	54	Pain and swelling in the lower abdomen for 5 months	USG and CT—a multilocular right ovarian cyst measuring 18 cm	Primary malignant melanoma of the ovary arising in a cystic teratoma	TAH, LSO followed by immunotherapy and radiotherapy
Kudva et al. [1]	56	Gradually enlarging palpable abdominal mass over 1 year, loss of appetite, abdominal distension and early satiety	USG—a mixed echogenicity solid-cystic abdominopelvic mass with thin septations CT—a large multiloculated solid-cystic abdominopelvic mass (19.6 × 13.9 × 16.2 cm) with areas of fat attenuation and fat fluid levels suggestive of teratoma	Primary malignant melanoma of the ovary arising in a cystic teratoma	TAH, BSO, omentectomy followed by chemotherapy
Brudie et al. [4]	35	Undergoing evaluation for infertility	Pelvic ultrasound demonstrated a pelvic mass versus fibroid	Primary malignant melanoma of the ovary arising in a cystic teratoma	RSO, sampling of right pelvic and aortic lymphadenectomy, omental biopsy, intra-peritoneal biopsies

BSO bilateral salpingo-oophorectomy, TAH total abdominal hysterectomy, RSO right salpingo-oophorectomy, LSO left salpingo-oophorectomy, CT computed tomography, MRI magnetic resonance imaging, USG ultrasound

Raised CA19-9 levels were found to be associated with mature cystic teratoma and have been proposed as a diagnostic tool. CA19-9 is a modified Lewis blood group antigen expressed on the surface of cancer cells. Ovarian mature teratomas constitute cells derived from every stratum germinativum, so CA19-9 levels are usually raised in these patients [7].

Grossly, these tumors are cystic and show the presence of nodules or plaques within the cyst wall. On cut shows the presence of pultaceous material mixed with hair, teeth, and cartilage. The rupture of teratoma into the abdominal cavity is difficult to diagnose as these patients complain of mild and non-specific lower abdominal pain and abdominal distension [8].

Microscopic features of ovarian malignant melanoma are similar to those of melanomas originating from the skin. They are most commonly composed of diffuse solid nodules, nests, and pseudopapillary patterns of tumor cells. These cells show pleomorphic hyperchromatic nuclei, coarse irregular chromatin, prominent eosinophilic nucleoli, atypical mitotic figures, and dusty pigmented cytoplasm [9]. For the confirmatory diagnosis, immunohistochemistry is done for melanocytic markers such as S-100, Melan-A, SOX-10, and HMB45.

It is very crucial to distinguish primary malignant melanoma from metastatic ovarian melanoma because a large number of cases are metastatic.

Boughton et al. [10] and Cronje et al. [11] performed a study in which they used certain criteria to diagnose primary malignant melanoma arising from teratoma. These criteria included the following:

• i.There should be no evidence of a primary tumor at other sites.
• ii.Correlation between the age and symptoms of patients.
• iii.Malignant melanoma is present in unilateral ovarian teratoma.
• iv.Well-demonstrated junctional activity, although this junctional activity is not an essential finding for diagnosis.

Ovarian malignant melanoma is treated by hysterectomy with salpingo-oophorectomy and pelvic clearance followed by chemotherapy and radiotherapy. Dacarbazine (DTIC), nitrosourea, and cisplatin are used as chemotherapy drugs as well as in relapse cases [4].

Malignant melanoma arising from ovarian teratoma is extremely rare and has very poor prognosis. The patient should be thoroughly evaluated for other primary site tumors before making the diagnosis of teratoma with malignant transformation to malignant melanoma.

Author Contribution

RR, SA, NN, PP, and SZ were responsible for reporting and diagnosing the case. RR and SA were major contributors to the writing of the manuscript while NN, PP, and SZ were responsible for the article review and editing. All authors read and approved the final manuscript.

Availability of Data and Material

That data is available from the corresponding author on request.

Declarations

This paper has been prepared by the abovementioned authors and reviewed and agreed upon for submission. The requirements for authorship as stated above in this document have been met, and that each author believes that the manuscript represents honest work.

Ethics Approval and Consent to Participate

Informed patient consent was taken. The study was done in accordance with the Declaration of Helsinki of 1975.

Consent for Publication

Informed written patient consent was taken before publication of the article.

Conflict of Interest

The authors declare no competing interests.