Immature ovarian teratoma

Factfile immature teratoma of the ovary rare variant of ovarian germ cell tumor < 3% of all teratomas, < 1% of all ovarian malignacies ~20% of all germ cell tumors ~10% of the cases contralateral benign (cystic) teratoma 90% of the patients < 30 years of age, mean age 19 yrs Serum markers might be elevated (esp. AFP and HCG) 6 35 cm in diameter (average 18cm) CF: predominantly solid, fleshy, sometimes cystic

Tasks for the handling and reporting of immature ovarian teratomas Exclusion of benign solid teratoma Determining the grade of the tumor Grading based on the extent of immature tissue within the teratoma In the past tailored on immature neuroepithelium (because of this tissue is most recogniseable and increases the reproducibility) 3-tiered grading system

Grading in immature teratoma (Gonzales-Crussi) Grade 1 Occasional foci of immature tissue: <1 one low power field (x40) in a given slide no adjuvant chemotherapy required Grade 2 1-4 low power fields per slide adjuvant chemotherapy required Grade 3 > 4 low power fields in a given slide adjuvant chemotherapy required Tumor grade is the crucial feature for determining the prognosis and the necessity of adjuvant treatment sometimes a two tired grading system (low versus high grade) was suggested (O`Connor & Norris 1994)

some suthors suggest that surgical resection alone might be curative, reserving poylchemotherapy (bleomycin, etoposide and cisplatin, i.e. BEP scheme) for cases with relapse (Cushing et al . 1999)

to ensure adequate diagnosis and adequate grading of the lesion, adequate sampling is required: one block per 1-2cm of largest tumor dimension !!

Immature Tissue within Teratoma Immature ectodermal tissue Mainly neuroectodermal rosettes and tubules Immature mesenchyme Loose myxoid stroma with focal differentiation into Immature cartilage Immature fat Osteoid, rhabdomyoblasts Immature endodermal tissue Hepatic tissue Intestinal type epithel with basal vacuolisation Embryonic renal tissue with Wilms tumor it has been proposed that high-grade immature teratomas are characterised by the presence of immature neuro-epithelial structures and low-grade tumors by the presence of somite organogenesis (Cho et al. 2005) theoretically, any of the immature elements might be quantitated for grading purpose, but immature neuroepithelium is the easiest to assess (Norris et al. 1976)

Differential diagnoses of immature ovarian teratomas mature teratoma with foci of immature neuroepithel. tissue occasionally, mature teratomas might contain minute foci of immature tissue (i.e. <21mm) a study of 360 ovarian teratomas that contain immature tissue included 350 immature teratomas and only ten mature cystic teratomas with microfoci of immature tissue during a follow up of 11 months to 7 years none of the latter cases recurred this study suggests that the dx of immature teratoma is not appropriate when only minute foci of immature tissue is

present in an otherwise mature cystic teratoma (Yanai-Inbar & Scully 1987)) but, adequate sampling is required !! monodermal teratoma with malignant somatic type tumros teratoma exclusively or predominantly composed of a single type tissue, derived from 1 embryonal layer and adult type malignant tumor malignant cell type in malignant transformation is directly related to the predominant mature cell type e.g. struma ovarii can develop into a papillary thyroid carcinoma in <5% in bi- and triphasic mature teratoma, squamous cell carcinoma is the most common type of malignancy (0.5-2% and typically occurs in post-menopausal women (Hackethal et al. 2008) treatment of malignant transformation of mature teratoma is based on the cell type of the tumor MMMT admixture of primitive appearing tissues without organisation into coordinated tissue units with recognisable embryonal/fetal structures

Schedule for the differential diagnoses of immature ovarian teratomas

Germ cell tumors with teratomatous features

Immature Teratoma Mature T with foci of immaturity Monodermal T with malignant somatic type tumors

Grading important

Dermoid cyst with foci of neoroepith tissue (<21 mm) benign

Ependymoma benign PNET maligne Glioblastoma maligne

Adequate sampling is required

WHO 2003, IJGP 1987;6:203

References
Cho NH, Kim YT, Lee JH, Song C, Cho SW, Cho SH, Chi JG. Diagnostic challenge of fetal ontogeny and its application on the ovarian teratomas.Int J Gynecol Pathol. 2005 Apr;24(2):173-82. Cushing B, Giller R, Ablin A, Cohen L, Cullen J, Hawkins E, Heifetz SA, Krailo M, Lauer SJ, Marina N, Rao PV, Rescorla F, Vinocur CD, Weetman RM, Castleberry RP. Surgical resection alone is effective treatment for ovarian immature teratoma in children and adolescents: a report of the pediatric oncology group and the children's cancer group. Am J Obstet Gynecol. 1999 Aug;181(2):353-8. Deodhar KK, Suryawanshi P, Shah M, Rekhi B, Chinoy RF. Immature teratoma of the ovary: a clinicopathological study of 28 cases. Indian J Pathol Microbiol. 2011 Oct-Dec;54(4):730-5. Hackethal A, Brueggmann D, Bohlmann MK, Franke FE, Tinneberg HR, Mnstedt K. Squamous-cell carcinoma in mature cystic teratoma of the ovary: systematic review and analysis of published data. Lancet Oncol. 2008 Dec;9(12):1173-80. Heifetz SA, Cushing B, Giller R, Shuster JJ, Stolar CJ, Vinocur CD, Hawkins EP. Immature teratomas in children: pathologic considerations: a report from the combined Pediatric Oncology Group/Children's Cancer Group. Am J Surg Pathol. 1998 Sep;22(9):1115-24. McCluggage WG. Ovarian neoplasms composed of small round cells: a review. Adv Anat Pathol. 2004 Nov;11(6):288-96. Norris HJ, Zirkin HJ, Benson WL. Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases. Cancer. 1976 May;37(5):2359-72. O'Connor DM, Norris HJ. The influence of grade on the outcome of stage I ovarian immature (malignant) teratomas and the reproducibility of grading. Int J Gynecol Pathol. 1994 Oct;13(4):283-9. Rezk Y, Sheinfeld J, Chi DS. Prolonged survival following salvage surgery for chemorefractory ovarian immature teratoma: a case report and review of the literature. Gynecol Oncol. 2005 Mar;96(3):883-7. Saba L, Guerriero S, Sulcis R, Virgilio B, Melis G, Mallarini G. Mature and immature ovarian teratomas: CT, US and MR imaging characteristics. Eur J Radiol. 2009 Dec;72(3):454-63. Vicus D, Beiner ME, Clarke B, Klachook S, Le LW, Laframboise S, Mackay H. Ovarian immature teratoma: treatment and outcome in a single institutional cohort. Gynecol Oncol. 2011 Oct;123(1):50-3 Yanai-Inbar I, Scully RE. Relation of ovarian dermoid cysts and immature teratomas: an analysis of 350 cases of immature teratoma and 10 cases of dermoid cyst with microscopic foci of immature tissue. Int J Gynecol Pathol. 1987;6(3):203-12