Dermoid Cysts and Malignant Transformation; Probability Of Cancer Process; and Treatment of Malignant Mature Cystic Teratomas
Mature cystic teratomas, also called dermoid cysts, rarely undergo a malignant transformation, i.e. cancer process, and is commonly seen after 40-45 years of age. In the literature, its prevalence varies from 2 per thousand to 2%. The ratio of cancers caused by dermoid cyst among malignant germ cell ovarian tumors is 2.9% (1, 2).
Although all kinds of tumors can originate from all of the 3 layers (endoderm, mesoderm, ectoderm) that constitute the embryo contained by mature cystic teratoma, the MOST COMMONLY developed ones are “Squamous cell” cancers that originate from ectoderm (2, 3).
Risk factors that increase the possibility of malignant transformation in dermoid cysts: Age, tumor size and rapid growth. The patient’s age over 45 years increases the risk; and the average age of the patients diagnosed with dermoid cyst turning into cancer is 50. However, the average age is 33 in benign mature cystic teratomas (3)
Tumor diameter greater than 10 cm and rapid growth of the tumor are other important risk factors. The surgeon should definitely consider these risk factors before the surgery, and warn the patients and their relatives in this regard.
2 tumor markers can be used for the identification of squamous cell carcinoma that emerges in a mature cystic teratoma, and their increases are considered to be a risk factor. SCC antigen and CA 19.9.
Though CA 19.9 has not come into routine use (malignant dermoid cyst is so rare that carrying out a study on it is difficult), some academic studies reported that it can be used as a tumor marker (4,5).
SCC (Squamous Cell Cancer) antigen has been used for a long time with intent to review the response to the treatment, and recurrence risk of the disease, especially within the scope of the treatment of cervix (cervical) cancer. Its values really increases when there is a squamous cell carcinoma site in the dermoid cyst. Its positive predictive value is 56%, with a limit value of 2 ng/dlt. However, it becomes a significant marker as the tumor volume increases. In simple phrase, it can be used but is still not in a position that can change our approach (6).
Cancer may develop from tissues that originate from any of the 3 different embryonic layers that constitute dermoid cysts. However, there are some clinical problems with this developing malignant tumors and the approach.
Dermoid cysts often contain fat and fluid. The structure of each dermoid cyst differs from patient to patient. Some different structures such as bone and cartilage are observed, as well. It is difficult and even impossible for the pathologist to review and freeze this web of complex tissues during the operation.
During frozen surgery, the pathologist evaluates the tumoral tissue very fast, to ascertain whether it is malignant or benign, and then determines the extent of the surgery accordingly. But when it comes to dermoid cysts this is almost impossible. It is because the pathologist cannot know from what part of the tissue he/she must take a sample.
In such a case, especially if the patient is young and frozen surgery is not applicable for her, the tumor should definitely be taken out of the abdomen with a bag that we call “endobag”, in such a way as to ensure that the abdomen is kept as clean as possible; but in the meantime, the organ, i.e. the ovary should be protected; however, if the pathological result indicates a malignancy after the surgery, a staging surgery should be done in accordance with the principles of gynecologic oncology. In other words, the patient may have to be operated 2 times. Bu in a doubtful case, the decision should always be taken in favor of the ovary. It is becasue is there is no possibility to replace the ovary after its removal.
There is limited number of studies that investe, with a literature search, squamous cell carcinomas caused by dermoid cysts. Interestingly enough, the most comprehensive and objective assessments among those meta-analyses and case compilations were published by the National Taiwan University in 1996 and 2008 (7, 8).
In the series published in 1996, a total of 26 patients with squamous cell cancer developed from dermoid cysts were evaluated. In 4 of the 11 Stage Ia patients, who had no child, the ovaries were removed together with the tubes (unilateral salpingo-oophorectomy); and 2 of those patients got fregnant after the operation. The remaining 7 patients underwent a staging operation (removal of abdominal irrigation fluid, removal of the uterus and ovaries, lymphadenectomy).
The rest of Stage II and advanced-stage patients underwent a staging operation; however, the Stage III and IV patients underwent a cytoreductive surgery (i.e. removal of the all metastatic tumors).
The rate of mean disease-free survival was 63.9 months. But the most important factor affecting this survival is the STAGE. The survival rate for Stage I and II was 100% (i.e, none of the patients was lost). 2-year disease-free survival was 30% in Stage III patients; and it reduced to 0% in Stage IV patients. In patients with advanced-stage disease, the course of disease was bad (8).
This study is important because the patients were followed-up through SCC antigen that we emphasized above; and the study showed that SCC antigen can be used for follow-up purpose especially in advanced-stage patients, if a squamous cell tumor that originated from advanced-stage mature cystic teratoma is found (8).
The research published by Chen et al (7) in 2008 was a more orderly study. As we stated before, they are extremely rare cancers; and therefore, it is difficult to do research on them.
Chen et al. did a complete literature search, and between 1976 and 2005, they found a total of 188 patients diagnosed with squamous cell carcinoma that developed in the dermoid cyst, and they were also underwent surgical staging and well evaluated in the clinical context. Only 188 cases reported from all the clinics across the world in 20 years!
The disease is typically seen in elderly patients with dermoid cyst. The average age in this group was 55 (averagely 55.0 +/- 14.4 years of age). The risk of squamous carcinoma development in large tumors is often higher. The average diameter of the dermoid cysts that leads to cancer is 13.7 +/- 5.7 cm.
The most common symptom is abdominal pain (71%). In these patients, the serum SCC antigen levels were found to be positive at the rate of 81.3%. The rate of 5-year survival was 48.4% in all stages.
The 5-year survival rate was 75.7% for stage I tumors; 33.8% for Stage II tumors; 20.6% for Sage III tumors, and 0% for stage IV tumors. All the patients were given cisplatin-based chemotherapy after surgey, and radiotherapy was also included in some cases. However, it is seen that radiotherapy has no effect on life span.
The stage of the tumor, the patient’s age, tumor size, SCC antigen levels, and the success level of the surgery are effective markers on life span. It is extremely important to ensure that there is no tumor left inside during the surgery. In addition, postoperative chemotherapy positively affects the patient’s life span (7).
In conclusion, the possibility of cancer development in dermoid cysts is extremely low. An advanced age, a great tumor diameter, and a high SCC antigen and CA 19.9 must always remind the gynecologist of the possibility of a malignant degeneration. Early-stage tumors do not adversely affect the life; and even pregnancy is possible in cases of Stage IA tumors. But unfortunately, the life span is limited and prognosis is poor in cases of advanced tumors.
References
1. Comerci J.T. Jr, Licciardi F., Bergh P.A. et al. Mature cystic teratoma: a clinicopathologic evaluation of 517 cases and review of the literature. Obstet Gynecol. 1994;84(1):22.
2. Hackethal A., Brueggmann D., Bohlmann M.K. et al. Squamous-cell carcinoma in mature cystic teratoma of the ovary: systematic review and analysis of published data. Lancet Oncol. 2008;9(12):1173.
3. Dos Santos L., Mok E., Iasonos A., Park K. et al. Squamous cell carcinoma arising in mature cystic teratoma of the ovary: a case series and review of the literature. Gynecol Oncol. 2007;105(2):321.
4. Frimer M, Seagle BL, Chudnoff S et al. Role of elevated cancer antigen 19-9 in women with mature cystic teratoma. Reprod Sci. 2014 Oct;21(10):1307-1311.
5. Coskun A, Kiran G, Ozdemir O. CA 19-9 can be a useful tumor marker in ovarian dermoid cysts. Clin Exp Obstet Gynecol. 2008;35(2):137-139.
6. Suzuki M., Kobayashi H., Sekiguchi I. et al. Clinical evaluation of squamous cell carcinoma antigen in squamous cell carcinoma arising in mature cystic teratoma of the ovary. Oncology. 1995 Jul-Aug;52(4):287-90..
7. Chen RJ, Chen KY, Chang TC. Prognosis and treatment of squamous cell carcinoma from a mature cystic teratoma of the ovary. J. Formos Med Assoc. 2008; 107(11):857-868.
8. Tseng CJ, Chou HH, Huang KG et al. Squamous cell carcinoma arising in mature cystic teratoma of the ovary. Gynecol Oncol. 1996; 63(3):364-370.