Teratoma of the Ovary

Am J Surg Pathol. 2008 May;32(5):645-655. Abstract quote

Mucinous epithelial neoplasms arising in association with mature teratomas are a heterogeneous group of tumors, but with the exception of a single recent study, their full histologic spectrum, detailed immunophenotype, and association with classic pseudomyxoma peritonei (PMP) have not been fully studied.

The morphologic, immunohistochemical, and clinical features of 42 patients with mucinous epithelial tumors arising in association with mature ovarian teratomas were evaluated. The patients' ages ranged from 17 to 66 years (mean, 39 y). Tumor size ranged from 5.5 to greater than 200 cm. Most teratoma-associated mucinous tumors were unilateral, although 1 patient harbored bilateral mucinous tumors in association with bilateral teratomas. In all cases, the teratomatous component consisted of mature elements. Using the 2003 World Health Organization criteria for ovarian intestinal type mucinous neoplasms, 17 (40%) were classified as mucinous cystadenoma, 16 (38%) as intestinal-type mucinous epithelial neoplasm of low malignant potential (IM-LMP), 4 (10%) as intraepithelial carcinoma (IEC), and 5 (12%) as invasive mucinous carcinoma. Mucinous cystadenomas had a varied epithelial lining consisting of lower gastroenteric, gastric foveolar, or müllerian appearance. In contrast, the IM-LMP, IEC, and invasive carcinoma cases had a more uniform lower gastroenteric histology. For mucinous cystadenomas, a cytokeratin (CK) 7+/CK20- phenotype (5/13; 38%) was equally as common as a CK7-/CK20+ phenotype (5/13; 38%), with the remaining cases coexpressing both keratins (CK7+/CK20+: 3/13; 23%). In contrast, IM-LMP, IEC, and invasive adenocarcinomas more frequently had a CK7-/CK20+ phenotype (56%, 50%, and 100%, respectively). A CK7+/CK20-phenotype was rare in these later 3 morphologic groups (6%). Of the 42 total cases, 55% had pseudomyxoma ovarii and 24% had classic PMP (1 cystadenoma, 6 IM-LMP, and 3 invasive carcinomas), whereas 5% had more localized accumulations of peritoneal mucin (both IM-LMP). Pathologic evaluation of the peritoneum in these 12 cases revealed 6 with acellular mucin alone, 3 with low-grade mucinous epithelium (all 3 with ovarian IM-LMP), and 3 with high-grade mucinous carcinomatosis (all 3 with ovarian mucinous adenocarcinoma). No appendiceal lesions were identified. Follow-up was available in 48% of patients (mean, 61 mo). The only adverse outcomes occurred in the 3 patients with ovarian carcinoma and associated peritoneal carcinomatosis.

We report that a significant proportion of mucinous tumors associated with mature ovarian teratomas present with clinical PMP, which in most cases is associated with IM-LMP. PMP in this setting may harbor microscopic intra-abdominal low-grade mucinous epithelium that is histologically and immunophenotypically similar to that typically seen in appendiceal-related PMP.

Pseudomyxoma ovarii is common in this setting, particularly in tumors with IM-LMP histology, but pseudomyxoma ovarii is not predictive of PMP. Ovarian teratoma-associated benign and IM-LMP mucinous neoplasms with microscopic peritoneal low-grade mucinous epithelium do not seem to be at significant risk for intra-abdominal recurrence, but numbers are few and follow-up is limited. In contrast, teratomas with an invasive carcinomatous component and microscopic peritoneal carcinomatosis follow an aggressive clinical course.

Epidemiology
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Histopathological Features and Variants
Prognosis
Treatment
Commonly Used Terms
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EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Dermoid cyst
AGE	30-40s for mature teratomas Teens to 20s for immature teratomas

PROGNOSIS	CHARACTERIZATION
GENERAL
Retrospective analysis of 67 consecutive cases of pure ovarian immature teratoma. Li H, Hong W, Zhang R, Wu L, Liu L, Zhang W. Department of Gynecology-Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Zuo An Men Wai, Beijing 100021, China.	Chin Med J (Engl) 2002 Oct;115(10):1496-500 Abstract quote OBJECTIVE: To investigate the development regularity, treatment methods and prognosis of ovary immature teratoma (POIT). METHODS: Sixty-seven patients with POIT, admitted from 1958 to 1998, were retrospectively analyzed. There were 31 patients with stage I, 4 with stage II, 2 with stage III and 1 with stage IV lesions. Twenty-seven patients had recurrences and 2 had distant metastases. Unilateral adnexectomy was performed for stage I lesions. From the 1980s, this was followed by four-cycles of combination chemotherapy (VAC, PVB or BEP x 3 cycles) as post-operative adjuvant therapy. Combined chemotherapy and multiple operations were performed for advanced and recurrent lesions. RESULTS: The overall survival rate was 75% (50/67). However, there was a remarkable difference in the results from the various periods. From 1958 to 1983, the 5-year survival rate was 40% (6/15), and it was raised to 79% (26/33) from 1984 to 1993. In the period 1994 to 1998, 95% (18/19)of patients were rescued. Thirty-five patients who had early lesions (stage I and II) had a 5-year survival rate of 91.4% (32/35). Thirty-two patients with recurrent or advanced lesions had a 5-years survival rate of 56% (18/32). There were 8 patients with grade III tumors and their 5-year survival rate was only 25% (2/8). The chief prognostic factors for this disease are clinical stage, pathological grade and adequate treatment. CONCLUSION: POIT is a potentially curable disease in today's practice. It is characterized by the fact that recurrent tumors may be converted back to mature ones as time goes on. With chemotherapy, these is a good opportunity to rescue those patients with recurrent tumors. At present, treatment of POIT gives the most satisfactory results among all malignant ovarian germ cell tumor types. Tests of serum specific tumor markers (CA19-9, AFP, CA125, CEA) performed preoperatively or before chemotherapy and during follow-up have been found helpful in the evaluation of prognosis.
Pure immature teratoma of the ovary: analysis of 22 cases. Kojs Z, Urbanski K, Mitus J, Reinfuss M, Pudelek J, Walasek T. Center of Oncology, Maria Sklodowska, Curie Memorial Institute, Krakow, Poland.	Eur J Gynaecol Oncol 1997;18(6):534-6 Abstract quote Between 1970 and 1991, 22 patients with pure immature teratoma were treated at the Center of Oncology in Krakow. Sixteen (72.7%) patients had stage I, four (18.2%) stage II, and two (9.1%) stage III of disease, nine (40.9%) patients had grade 1, 11 (50%) grade 2, and two (9.1%) grade 3 tumors. Eight stage Ia, grade 1 patients were treated with surgery only, the remaining 14 (63.6%) received postoperative chemotherapy. Five-year NED (no evidence of disease) survival was achieved in 81.8% of patients. Out of 16 stage I patients, 15 (93.8%) survived 5-year NED, out of six stage II and III, three (50%) patients only survived this period. We cured all grade 1 patients, and 81.8% (9/11) grade 2; two grade 3 patients died because of tumors. We also cured all six stage Ia patients, treated with unilateral salpingo-oophorectomy (with or without chemotherapy), and all eight stage Ia grade 1 patients treated with surgery only.
Pure ovarian immature teratoma, a unique and curable disease: 10 years' experience of 32 prospectively treated patients. Bonazzi C, Peccatori F, Colombo N, Lucchini V, Cantu MG, Mangioni C. Department of Obstetrics and Gynecology, Ospedale San Gerardo, Istituto di Scienze Biomediche San Gerardo, University of Milan, Monza, Italy.	Obstet Gynecol 1994 Oct;84(4):598-604 Abstract quote OBJECTIVE: To report and evaluate a conservative and individualized treatment policy in a homogeneously selected series of patients affected by pure ovarian immature teratoma. METHODS: This prospective trial, with specific treatment policies according to stage and grade, was planned and started in 1982. The study population consisted of 32 patients affected by pure immature teratoma, with the exclusion of mixed germ cell tumors. Fertility-sparing surgery was performed whenever possible. Surgery alone, with careful follow-up, was adopted for stage I or II according to the International Federation of Gynecology and Obstetrics (FIGO) and grade 1 or 2 tumors. The other patients, with stage III or with grade 3 stage I or II tumors, or those referred at relapse, were treated with platinum-based chemotherapy regimens. RESULTS: Thirty of 32 patients underwent fertility-sparing surgery. Ten of 32 patients received chemotherapy after surgery, either as adjuvant treatment or in the presence of visible tumor. All 32 patients are alive and disease-free, with a median follow-up from surgery of 47 months (range 11-138). In six patients, regardless of the administration of chemotherapy, the tumor either spontaneously differentiated toward mature glia or increased in volume, mimicking progression but still remaining completely mature. Five of six patients wishing to procreate had a total of seven normal pregnancies. CONCLUSIONS: Pure ovarian immature teratoma is a potentially curable disease with a unique natural history. Our data substantiate the hypothesis that low-grade and low-stage tumors do not require chemotherapy, and that a fertility-sparing surgical approach is warranted in all cases.
Malignant germ cell tumors of the ovary: 20-year report of LAC-USC Women's Hospital. Curtin JP, Morrow CP, D'Ablaing G, Schlaerth JB. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and Department of Pathology, University of Southern California School of Medicine, Los Angeles, California, USA.	Int J Gynecol Cancer 1994 Jan;4(1):29-35 Abstract quote Thirty-six patients with malignant germ cell tumors (GCT) of the ovary were treated during the period from 1971 to 1990. Twenty-five of these patients underwent initial surgery at this institution; 11 were referred after initial surgery. Endodermal sinus tumor (EST) was the most common subtype (N = 13), followed by immature teratoma (IMT) N = 11), dysgerminoma (N = 9), and mixed germ cell tumor (N = 3). Eight of nine patients with dysgerminoma and 14 of 27 patients with non-dysgerminomatous germ cell tumors had stage I disease. Surgical staging resulted in a change of stage in 10 of 31 patients; seven were upstaged, and three were downstaged. Thirty-five of 36 patients are alive with no evidence of disease at a median follow-up of 47 months (range 12-210 months). Two of nine patients with dysgerminoma received postoperative radiotherapy; two additional patients required radiotherapy for recurrence. Twenty-five of 27 patients with non-dysgerminomatous tumors were treated with combination chemotherapy. Second-look laparotomy was done in 18 patients, four of whom had positive results. Three of the four patients with positive second-look laparotomy results remain free of disease after salvage chemotherapy; the fourth patient died of progressive grade 3 IMT. Nineteen of 27 patients undergoing fertility-preserving surgery have resumed normal menses, and four of these have delivered normal infants. The other eight patients remain on oral contraceptives. We conclude that surgical staging provided important information in this study of 36 patients with ovarian germ cell malignancies. As noted by many previous reports, combination chemotherapy (developed during the past 20 years) has dramatically improved prognosis for this group of patients. Second-look laparotomy (SLL), especially for patients with advanced disease, was able to identify patients requiring additional therapy. Most patients with this disease can retain their normal, uninvolved ovary with preservation of normal menstrual and reproductive function.
CHROMOSOME KARYOTYPE
Histologic grade and karyotype of immature teratoma of the ovary. Ihara T, Ohama K, Satoh H, Fujii T, Nomura K, Fujiwara A.	Cancer 1984 Dec 15;54(12):2988-94 Abstract quote Seven cases of ovarian "pure" immature teratoma were encountered in patients 10 to 38 years of age, six cases being in Stage Ia and one case in Stage IIc. The primary tumors and recurrent growth observed in one case were histologically graded from 0 to 3 according to the criteria of Norris et al. Karyotypes of the tumors and the patients were determined using culture and banding techniques. The only nonsurviving case was in Stage IIc. Four primary tumors belonging to grades 0, 1, and 2 showed a normal 46,XX female karyotype and the patients are alive and healthy. Three grade 3 tumors showed various types of karyotype abnormalities (48,XX,+14,+21; 47,XX,+20; 47,XXX). One patient died, one is alive after experiencing a recurrent tumor, and one has only been followed for 22 months. All seven patients had a normal 46,XX female chromosome constitution. Evidence to date indicates that karyotype of ovarian immature teratoma is either normal female 46,XX or a slight deviation from normal. It is postulated that in ovarian immature teratoma normal 46,XX karyotype is an indicator of favorable prognosis, whereas deviations in karyotype suggest a possibility of poor prognosis.

TREATMENT	CHARACTERIZATION
GENERAL
Immature teratoma of the ovary. Koulos JP, Hoffman JS, Steinhoff MM. Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington 06032.	Gynecol Oncol 1989 Jul;34(1):46-9 Abstract quote Twenty-five cases of patients with pure immature teratoma of the ovary, accrued from the Connecticut Tumor Registry from 1969 to 1984, were reviewed. Two patients had grade 1 tumors, twelve had grade 2 tumors, and eleven had grade 3 tumors. The majority of patients (23) were stage I at the time of initial surgery. Twenty-one of the twenty-three patients were treated with some form of unilateral adnexal surgery with or without adjuvant combination chemotherapy (VAC). Two of the twenty-three patients were treated with total abdominal hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO) with the addition of either VAC chemotherapy or radiation therapy. Recurrence occurred in two patients, both of whom had grade 3 tumors and were subsequently treated with surgical resection plus VAC chemotherapy. One patient, who recurred after initial therapy with unilateral salpingo-oophorectomy (USO) plus VAC chemotherapy, was successfully treated with surgical resection and further chemotherapy. Two patients were stage III at the time of initial surgery, one of whom was treated with USO plus adjuvant combination chemotherapy and radio-therapy. The other patient was treated with TAH/BSO plus VAC chemotherapy. In our series, no patient died from immature teratoma (one patient died from advanced breast carcinoma). It is reasonable to withhold chemotherapy from patients with stage I, grade 1 and 2, immature teratoma which may be treated initially with conservative surgery. The risk of recurrence in patients with grade 3 tumors warrants the addition of further chemotherapy.
CHEMOTHERAPY
Pure malignant immature teratoma of the ovary: the role of chemotherapy and second-look surgery. Culine S, Lhomme C, Kattan J, Michel G, Duvillard P, Droz JP. Department of Medicine, Department of Surgery, Department of Pathology, Institut Gustave Roussy, Villejuif; and Department of Medical Oncology, Centre Leon Berard, Lyon, France.	Int J Gynecol Cancer 1995 Nov;5(6):432-437 Abstract quote Fifteen patients with pure malignant immature teratoma of the ovary were treated at the Institut Gustave Roussy over a 17-year period. Chemotherapy was delivered as primary postoperative therapy in 11 patients. Four other patients received chemotherapy as part of their salvage treatment for recurrent disease. A second-look laparotomy was performed in eight patients. Histological findings were: no tumor in three patients, mature teratoma in four patients, and immature grade 1 teratoma in one patient. The latter five patients had persistent radiologic abnormalities at the end of chemotherapy. Twelve patients remain free of disease 24-228 months from initiation of chemotherapy. Two children were delivered from the two patients who attempted pregnancy. All three patients who died of progressive disease had a grade 3 immature teratoma. We conclude that the treatment of pure immature teratoma of the ovary should include primary conservative surgery and cisplatin-based chemotherapy. Second-look surgery is mandatory in patients with persistant radiologic abnormalities at the completion of chemotherapy.
SURGERY
Recent management of malignant ovarian germ cell tumors: a study of 34 cases. Linasmita V, Srisupundit S, Wilailak S, Tangtrakul S, Israngura N, Bullangpoti S. Department of Obstetrics and Gynecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.	J Obstet Gynaecol Res 1999 Oct;25(5):315-20 Abstract quote OBJECTIVE: To review the outcome of the treatment in patients with malignant ovarian Germ cell tumors with respect to survival and surgical management at a single institution during 1990-1996. METHODS: Thirty-four patients with malignant ovarian Germ cell tumors were studied retrospectively for their surgical management. Fourteen patients had pure dysgerminoma, 11 endodermal sinus tumor, 6 immature teratoma, and 3 mixed Germ cell tumors. Nine patients had stage IA, 8 stage IC, 2 stage IIC, 8 stage III, 3 stage IV, and 4 referred patients with recurrent diseases. RESULTS: Nineteen patients underwent primary conservative surgery, 11 had primary nonconservative surgery. Twenty-two patients were treated with chemotherapy (BEP or EP or PVB regimen). Five patients with pure dysgerminoma received adjuvant radiotherapy. Persistent remission was achieved in 26 patients. Two patients (7.4%) had recurrence after remission. Seven patients had died of the diseases. Patients with complete clinical remission did not undergo second-look surgery. The overall survival was 78.8%, 100% for immature teratoma, 84.6% for pure dysgerminoma, 72.8% for endodermal sinus tumor, and 33.3% for mixed Germ cell tumors, with median follow-up time 31 (3-93) months. CONCLUSION: Patients with limited diseases regardless of histologic types can be safely managed by unilateral salpingo-oophorectomy followed by, if indicated, 3-4 courses of cisplatin-based chemotherapy. For advanced diseases, conservative surgery is advisable in patients with endodermal sinus tumor.
Is there a role for second-look laparotomy in the management of malignant germ cell tumors of the ovary? Experience at Institut Gustave Roussy. Culine S, Lhomme C, Michel G, Leclere J, Duvillard P, Droz JP. Department of Medicine, Institut Gustave Roussy, Villejuif, France.	J Surg Oncol 1996 May;62(1):40-5 Abstract quote The last two decades have seen great improvements in the management of patients with germ-cell tumors of the ovary. The initial treatment approach includes conservative surgery and cisplatin-based chemotherapy in most cases. At completion of chemotherapy, the role of second-look surgery remains questionable. We retrospectively analyzed the long-term outcome (median follow-up, 8 years) of 40 patients who received various chemotherapy regimens after primary surgery and focused on the role of second-look surgery. A second-look laparotomy was performed at completion of chemotherapy in 22 patients. Histological findings were no tumor in 13; mature teratoma in 5; immature teratoma in 1; active disease in 3. Six of the latter nine patients had persistent radiologic abnormalities after chemotherapy. All three patients with active disease had elevated serum tumor markers. Five out of the six patients with residual teratoma lesions had a teratoma component in the primary tumor. According to histological findings at second-look surgery, the number of patients without long-term evidence of disease is 12, 5, 1 and 0, respectively. Eighteen patients were not subjected to second-look surgery. One of them had clearly progressive disease and the other 17 experienced a clinical complete response at completion of chemotherapy. All patients but one are alive without evidence of disease. We conclude that second-look surgery is not necessary in patients with elevated serum tumor marker levels and in those patients with neither radiologic abnormality nor teratoma element in the primary tumor. However, we recommend a second-look procedure for the small subset of patients with a teratoma component in the primary tumor and persistent radiologic abnormalities along with normal serum tumor markers at the end of chemotherapy.