Mature cystic teratoma or dermoid cyst is the most common ovarian germ cell neoplasm and most common childhood ovarian tumor comprising approximately 25% of all ovarian tumors [9
]. They have a very wide age range but usually occur during the reproductive years. Approximately 90% are unilateral and with a variable size of 5-10cm. Microscopically, they are usually unilocular cysts containing tissue from all three germ cells with teeth, bone, and neural tissue being found [9
]. Secondary malignancies may develop in any of the tissues derived from the three germ layers-the ectoderm, meso-derm and endoderm. A nodular prominence is usually present in the wall of the cyst at the junction between the teratoma and normal ovarian tissue and this has been called a Rokitansky protuberance [10
]. The greatest cellular variety is found in this area and hence should be thoroughly sampled to rule out malignant components.
Malignant transformation within a mature dermoid cyst is a rare event, less than 2% of all such lesions. Approximately 1% of mature cystic teratomas have malignant somatic-type tissue elements [11
]. Risk factors for malignancy in a mature cystic teratoma include age over 45 years, tumor diameter greater than 10cm, and rapid growth [11
]. The most common malignancy has been reported as squamous cell carcinoma followed by carcinoid tumor and transitional cell carcinoma. In their publication, Al-Rayyan et al concluded that regardless of the type of malignancy, the tumor size, the extent of the disease and the patient's age were the major factors governing the survival in these patients. They recommended maintaining a higher suspicion of malignancy in managing dermoid cysts occurring in patients over the age of 45 years, especially if rapidly growing or very large tumors greater than 10cm [11
]. In addition, Kelly and Scully with their detailed report of cases of malignancy arising in dermoid cyst felt that thickening of the cyst wall and adherence to surrounding structures should also raise high index of suspicion for malignancy in a dermoid cyst [3
]. The best outcome for their patients was when the tumor was completely excised and staging and treatment planning at the initial surgery or as soon as possible after the diagnosis. Squamous cell carcinoma if confined to the ovary had better outcome than if there were peritoneal extension [11
]. When malignant transformation has occurred within a teratoma, treatment is usually tailored toward the transformed histology [11
]. Recent studies indicated that a combination of adjuvant chemotherapy and radiotherapy might improve survival in these patients. Irrespective of the tumor type, or the size of tumor, they concluded that the prognosis is better if tumor was limited to one ovary and with an intact capsule [9
]. Burgess et a I also reported the importance of exploring both ovaries as the incidence of teratoma has a bilateral proclivity [12
Stromal tumors arising from the mesodermal germ cells of a mature dermoid cyst are rarer than their epithelial counterparts but have been reported [5
]. The incidence of osteosarcoma alone arising from a mature dermoid cyst to date consists of four cases (). Ngwalle et al described the typical case occurring in a postmenopausal woman with an osteosarcoma arising in benign dermoid cyst [5
]. The same age range has been observed for other soft tissue osteosarcomas which also exclusively affected adults older than 50 years [13
]. This is not the same for osteosarcomas of the bone, a tumor of growing individuals with a peak incidence in the second decade of life [5
]. The prognosis in all of the cases of osteosarcoma in dermoid cyst was poor, which is similar to osteosarcoma of soft tissue. In Ngwalle et al's case, it seemed to have a better prognosis and the postulation could have been due to the limited involvement of the ovary and low stage at the time of surgery [5
Reported osteosarcomas in dermoid cyst
A combination of different malignancies arising in the same dermoid cyst or the incidence of more than one malignancy arising from one ovary is exceptionally rare. But different combinations have been reported in the literature () Hanada et al described the multiple malignancy arising from a dermoid cyst of the ovary namely squamous cell carcinoma and myxoid fibrous histiocytoma in 1981 [2
]. In 1996, a case report of carcinosarcoma arising in the dermoid cyst of the ovary by Arora and Haldane comprising of adenocarcinoma and leiomyosarcoma was reported [1
]. To date, to the best of our knowledge, a unique combination of squamous cell carcinoma and osteosarcoma arising in mature dermoid cyst of the ovary has never been reported before. The treatment of multiple malignancies arising from dermoid cyst consists of aggressive cancer surgery followed with combination chemotherapy and radiotherapy. The prognosis is dismal and the patients usually succumb to their disease within months [1
Clinical and histological features and outcome of patients reported with multiple malignancies in dermoid cyst
The distinction between “pure” malignant mixed mesodermal (carcinosarcoma) tumors of the ovary versus collision tumors arising in a benign dermoid cyst versus a squamous cell carcinoma with sarcomatous transformation is of academic interest. Carcinosarcoma is diagnosed when both the carcinoma and sarcoma are present without any benign teratoma tissue [14
]. The coexistence of two malignancies in the background of benign teratomatous tissue especially in a postmenopausal woman eliminates this diagnosis. In our case, benign epithelium, squamous cell and osteosarcoma were clearly coexistent in the dermoid cyst. No immature elements were identified despite through examination and multiple sections of the specimen, ruling out to some extent the possibility of these tumors arising in an immature teratoma. Also immature teratomas usually occur in younger age group and typically the malignant transformation occurs chiefly in postmenopausal women.
Collision tumors occur when two different malignancies arise metachronously in the same organ at two separate areas and usually have a common point of meeting or contact but for the most part are separate from each other. In the present case, there was no such area of common contact point despite extensive sampling. There were no areas of two separate well defined point of origin with a common meeting point.
Pathogenesis of malignant transformation of one somatic cell type to another is not clearly. In our patient, the mature dermoid cyst most likely has undergone the transformation of the totipotential germ cells toward the formation of squamous cell carcinoma that might have later dedifferentiated into osteosarcoma.