DISCUSSION:
Cystic teratoma is a common benign tumor found in 10%-20%of women in their lifetime [5]. However, in rare cases, it might transform into a malignant form. The most common malignant transformation is squamous cell carcinoma, with an incidence of around 0.2%-0.8% [6]. We here discuss a case of the 80-year-old female where mature cystic teratoma has been transformed into undifferentiated carcinoma.
Any of the three germ layers, ectoderm, mesoderm, and endoderm, can be the point of development of ovarian teratoma.[7] So malignant transformation may occur from any of the three germ layers into different histological tumor types like adenocarcinoma, squamous cell carcinoma, melanoma, sarcoma, adenosquamous carcinoma, etc. The most common malignant transformation from MCT is squamous cell carcinoma, which is around 80% of all the cases of transformations.[8]
Clinically the patient with cystic teratoma usually presents with an increase in abdominal girth, abdominal pain, abdominal distension, or palpable pelvic or abdominal mass. Sometimes the patient remains asymptomatic until the complication occurs. The most common complications are ovarian torsion, rupture of the peritoneum, and invasion of the adjacent structures.[9]The gastrointestinal or urinary symptoms may arise if the tumor has invaded the adjacent organs in the pelvic cavity.[10]In our case, the patient presented with lower abdominal pain for two weeks and mild tenderness in the left iliac region on physical examination.
Preoperative identification of the malignant transformation of the mature cystic teratoma is difficult. Only 1–2% of the SCC cases can be diagnosed preoperatively [10]. Multiple criteria have been proposed to identify it. The criteria like age greater than 55, large tumor size >10 cm, and radiological signs within revascularization are most likely to represent the malignant transformation of the cystic teratoma.[11] So CT scan and MRI are essential in identifying the preoperative malignant transformation with the features like necrosis, cystic wall growth, invasion to adjacent peritoneal organs, or metastasis to the pelvic organs.[12]
Histologically, the undifferentiated tumor may show mesenchymal and epithelial differentiation features and may show the immune reactivity for markers such as cytokeratin, vimentin, and epithelial membrane antigen [13]. In the present case, the undifferentiated area of the tumor exhibited round to oval cells and did not take immunohistochemical reagents like P40, SALL 4, Synaptophysin, Desmin, vimentin, CD20 except for cytokeratin. So we consider our tumor to be an undifferentiated type with features of epithelial differentiation. However, cytokeratin and P40 were positive in the squamoid differentiated areas of carcinoma. Therefore, considering the histomorphological features and immunohistochemical findings, a final diagnosis of malignant transformation of MCT into undifferentiated carcinoma and squamous cell carcinoma was made.
The malignant transformation may be associated with the HPV infection or due to the alternation in the tumor suppressor gene like p53 and p16. [5, 14]. The malignant transformation usually has an association with the level of tumor markers. Therefore, the tumor markers like SCC antigen, CA125, CA19-9, and CEA are likely to be increased in patients with this transformation. However, the FIGO stage and tumor size do not determine the level of these markers. In our case, the level of Serum CA125 was 200 IU/mL, and CEA was 63.62 µg/L [10].
The standard treatment of malignant transformation of MCTO is radical surgery and chemotherapy. There is no fixed protocol for optimal adjuvant therapy due to the rarity of the disease. Surgical treatment is usually performed by hysterectomy with bilateral salpingo-oophorectomy, omentectomy, peritoneal biopsy, and paraaortic lymph node dissection. For chemotherapy, a wide range of therapeutic agents like anthracyclines, alkylating agents, antimetabolites, platinum agents, and vinca alkaloids are used.[12] Some scholars report the combination of Paclitaxel with alkylating agents will improve the survival of the patients with this transformation [5]. In the present case, the patient underwent surgical treatment and adjuvant chemotherapy with Paclitaxel and carboplatin 3 weekly (L1Cl completed).
The prognosis of the malignant transformation depends on factors like age >55 years, large tumor size, high cancer grade, and advanced stage of the disease. The cytoreductive surgery in combination with chemotherapy is likely to improve the prognosis. [12]