1. Ovarian Teratoma Ryan M. Mitchell, MD, PhD 9/30/2010

2. “r/o bowel obstruction” cc: 4 day h/o increasing abdominal pain and distention HPI: abd pain and distention x 4 days, mildly improved sitting upright, no association with eating; vomiting x several episodes (non-bilious) -> some improvement; last BM 3 days prior; able to run ½ mile earlier same day; intermittent abd discomfort 1 mo. prior with possible distention Note: MVC 1 week prior to presentation PMH: intussusception at 5 mo s/p open reduction FHx: prostate ca-maternal grandfather, breast ca-maternal grandmother, ear “teratoma”-grandfather SHx: lives with parents and older sibs, no smokers ROS: no fevers, weight has fluctuated, no night sweats, otherwise negative

3. PE: Vitals: WNL HEENT: WNL CV: WNL Pulm: WNL Abd: firm, distended, dull to percussion, hypoactive bowel sounds, midly tender to palpation diffusely Ext: WNL

4. KUB: several distended small bowel loops, calcifications in pelvis suspicious for teratoma CT: pelvic and abdominal mass, possible large immature teratoma arising most likely from left ovary Labs: hCG < 1, AFP < 0.9 (nl <12), CA 19-9 (148 (nl < 55), CA 125 192 (<35), CEA 3.8 (nl < 5)

6. Cytology: negative for malignant cells

7. Ovarian Tumors Surface epithelial Sex cord-stroma Germ cell Dysgerminoma-non-differentiated Yolk sac tumor-extraembryonic differentiation Embryonal carcinoma-primitive differentiation Choriocarcinoma- trophoblast lineage Teratoma-variable differentiation toward somatic tissues

8. OGCT Signs and Symptoms Abdominal enlargement, pain (50-85%) -ascites (20%) -median size of teratoma is 6-16 cm Precocious puberty, abnormal vaginal bleeding (10%) Ovarian torsion (5%) Tumor markers: β -hCG, AFP, LDH Malignancy more common in Asian/Pacific Islanders and Hispanics compared to Caucasians

9. Teratomas Origin: totipotential primordial germ cells that partially differentiate toward somatic tissues, or aberrant migration Pediatric teratomas: sacrococcygeal (50%), ovary (25-30%), medistinum (7%), H&N (6%), CNS (5%), testis (3-5%) Mature (benign): 50% of ovarian neoplasms in children, 20% in adults Cystic or solid Mature cystic teratoma (95%) – dermoid cyst Ectoderm, mesoderm, endoderm Malignant transformation in 0.2-2% (squamous cell ca from ectoderm) Immature (malignant): 1% Monodermal Struma ovarii, carcinoid Benign > 95%, may be hyperthyroid

10. Imaging Mature cystic teratoma Cystic lesion with echogenic tubercle/raised protuberance projecting ino cystic cavity Shadowing echodensity on U/S teeth Fat in cystic lumen-most specific Malignant degeneration More solid with transmural extension Immature teratoma Larger and more solid compared to MCT Coarse calcifications

11. Mature Teratoma Usually cystic, but rarely solid ~9/100,000 women-years Slow growing: 1.8 mm/yr (?) Never skeletal muscle tissue Bilateral in 10-15% of cases Fetiform teratoma: resembles a malformed fetus  homozygous at loci where host is heterozygous  Parthenogenesis? Tx: complete resection-cystectomy vs. oophorectomy http://library.med.utah.edu/WebPath/FEMHTML/FEM060.html

12. Mature Teratoma Malignant degeneration: Largely reflects predominance of ectodermal tissue treat according to transformed histology treat according to transformed histology Most commonly squamous cell carcinoma Risk factors: increasing age, larger size, rate of growth, elevated CA 125 Surgical debulking similar to GCTs and epithelial tumors Adjuvant therapy with alkylating agents Also basal cell ca, melanoma, thyroid cancer, others

13. Immature Teratoma aka teratoblastoma, embryonal teratoma, malignant teratoma Annual incidence is ~0.13/100,000 person-years Usually younger than pts with mature cystic teratoma Usually solid Variable differentiation -> histologic grading based on amount of immature neural tissue Serum tumor markers: + AFP, + LDH, - hCG Preop: CT chest, abd, pelvis

14. Immature Teratoma/Malignant GCTs Frozen sections if unsure of malignancy Laparotomy, inspection of peritoneal surfaces, diaphragm, omentum, contralateral ovary Biopsy of multiple surfaces and any suspicious lesions Cytology of ascitic fluid or peritoneal washings Cytology of ascitic fluid or peritoneal washings Cytoreductive therapy: maximal tumor reduction vs. morbidity (non-randomized trials) Salpingoophorectomy Preservation of normal appearing uterus, fallopian tube and ovary LN involvement Sampling of pelvic and para-aortic, not lymphadenectomy Second look laparotomy: best for incompletely resected teratoma

15. Immature Teratoma/Malignant GCTs Surgical resection and adjuvant bleomycin, etoposide, cisplatin/carboplatin (prospective trials) Possible exception: Grade 1 Stage 1 (9 pt longitudinal study) 80% fertility after chemo 5 yr survival: grade 1: 95%, grade 2: 80%, grade 3: 60-70% Prognosis: - stage, histologic grade, elevation of serum markers, LN involvement Cryopreservation of fertilized eggs or oocytes Follow-up: clinical exam, radiographic, tumor marker serologies

16. Staging of Malignant OGCTs International Federation of Obstetrics and Gynecology (FIGO) classification I: confined to ovaries IA: one ovary, intact capsule, ovarian surface not involved, negative peritoneal cytology IB: bilateral IC: rupture, malignant cells in ascites or peritoneal washings II: extension into pelvic tissues III: spread beyond pelvis or to regional LNs, confined to abdomen IV: distant mets or involvement of liver parenchyma

17. Future Directions Optimization of chemotherapy regimen Use of tumor biomarkers for diagnosis, risk stratification, prognosis, treatment response Optimization of follow-up surveillance Preservation of fertility

18. References Escobar MA, Rossman etal. Fetus-in-fetu: report of a case and a review of the literature. J Pediatr Surg. 2008 May;43(5):943-6. Pectasides D, Pectasides E, et al. Germ cell tumors of the ovary. Cancer Treat Rev. 2008 Aug;34(5):427-41. Epub 2008 Apr 18. Guillem V, and Poveda, A. Germ Cell Tumors of the Ovary. Clin. Transl Oncol 2007:9, 237- 243. Tangjit S, Manusirivitthava S, et al. Squamous cell carcinoma arising from dermoid cyst: Case reports and review of literature. Int J Gynecol Cancer. 2003 Jul-Aug;13(4):558-63. Gershenson DM, et al; Gynecologic Oncology Group. Reproductive and sexual function after platinum-based chemotherapy in long term ovarian germ cell tumor urvivors; a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Jul 1;25(19):2792-7. Weiss JR, Burgess JR, Kaplan KJ. Fetiform Teratoma (Homonculus). Arch Path Lab Med. 2006;130:1552-1556. Saba L, Guerriero S, et al. Mature and Immature Ovarian Teratomas: CT, US, and MR Imaging Characteristics. Eur J Rad. 2009;72:454-463. Hackethal A, Brueggmann D, Squamous-cell carcinoma in mature cystic teratoma of the ovary: systematic review and analysis of published data. Lancet Onc. 2008;9:1173-1180. McKenney JK, Heerema-McKenney A, Rouse RV. Extragonadal germ cell tumors: a review with emphasis on pathologic features, clinical prognostic variables and differential diagnostic considerations. dv Anat Pathol. 2007 Mar;14(2):69-92.