7 Germ Cell Tumors Dysgerminoma Endodermal sinus tumor Teratoma ImmatureMatureStruma ovariiCarcinoidChoriocarcinomaEmbryonal carcinomaPolyembryomaMixed GCTCombo GCT/StromalGonadoblastomaOtherCarcinoid develops in mature teratomas, usually in older women. Can have malignant potential, but generally have an indolent course and rarely metastasize.
9 Dysgerminoma Lance Armstrong Incidence 10-15% bilaterality 1-2% of ovarian tumors3-5% of ovarian malignancies40% of all GCTPeak incidence age 1967% stage IA10-15% bilaterality20% in “normal appearing” opposite ovary
10 DysgerminomaLarge, white to grey, fleshy, lobulated masses.
11 DysgerminomaNo or very little areas of hemorrhage or necrosis – if these are present, think about a mixed germ cell tumor.
12 Dysgerminoma Presentation Tumor markers Survival Solid, lobulated, and can be large15% associated with mature cystic teratomaAssociated with gonadal dysgenesis and gonadoblastomaHigh growth fraction, lymphatic spreadTumor markersLDH, placental alkaline phosphataseSurvivalOverall =86%Stage I =90%
13 Dysgerminoma Fertility-sparing surgery Radiosensitive Chemotherapy 85% of patients are younger than 35 yoConsider uterine preservation (IVF)RadiosensitiveChemotherapyCombination, dose-intense regimen
14 Dysgerminoma Large, round, ovoid or polygonal cells Nest and cords of primitive appearing germ cellsLymphatic space invasion is common
15 Dysgerminoma Incidence Survival Stage IA 70% 92% 10-year Stage IB 10% >90%5-yearStage II, III15%Stage IV5%80%
16 Endodermal Sinus Tumor Presentation20% of all GCTMedian age 19 yoAbdominal pain, large mass10-30 cm commonVery rapid growth, intra-abdominal and hematological spreadTumor marker: AFP, α1 antitrypsinSynonymsYolk sac tumorSurvivalOverall survival =70%Stage I =90%
17 Endodermal Sinus Tumor Solid tumor with hemorrhage and gelatinous necrosis on cut surfaceMicroscopyHyaline globulesReticular PatternSchiller-Duval bodiesSingle blood vessel surrounded by neoplastic cells
21 Immature Teratoma Presentation 20% of all GCT75% in first 2 decades of life12-15% bilateral60-70% are Stage IRarely produce tumor markers: αFP and CA-125Grade is determined by % immature neural tissueStage IA grade 1 → no adjuvant therapySurvivalOverall =63%Stage I =75%
22 Immature TeratomaSolid with cystic areas. Cut surface is soft fleshy or encephaloid.
24 Immature Teratoma Grade Scully Norris 1 2 3 Well differentiated Well differentiatedAll mature; rare mitoses1Well differentiated; rare embryonal tissueSome immature and neuroepithelium2Moderate embryonal; atypia and mitosesImmature neuroepithelium ≤ 3 lpf3Large embryonal; atypia and mitosesImmature neuroepithelium in ≥ 4 lpf
25 Significance of Grading GradeNumberTumor Deaths1224 (18%)2249 (37%)3107 (70%)
26 Mature Teratoma 5-25% of all ovarian tumors 10-20% bilateralMost common ovarian tumor of young womenSonographyComplex, cystic and solidFat/fluid or hair/fluid level, calcificationsHigh MI score1-2% with malignant degenerationRokitansky’s protuberanceSquamous cell cancers possible
31 Specialized Teratomas Struma ovarii2-3% of all teratomas25-35% have symptoms of hyperthyroidismUsually benign, but may undergo malignant transformationCarcinoid tumorsAssociated with GI or respiratory epitheliumPrimary ovarian tumors are rare (N=50)Often older postmenopausal women1/3 have carcinoid syndrome from serotoninSymptoms resolve with excision5-hydroxyindoleacetic acid in urine
32 Struma OvariiFollicles contain vividly eosinophilic, acellular colloidVariation in follicular size is typicalCan have rich vascularity
34 Choriocarcinoma Presentation Tumor marker Uncommon, aggressive tumor Often part of mixed GCTConsider met from gestational chorioCAMean age 20 yo, children commonHalf of premenarchal → precocious pubertyTumor markerhCG
36 Embryonal Carcinoma Presentation Tumor markers: hCG, αFP Survival Mean age < 30 yoOnly 4% of GCT and often part of mixed tumor60% Stage IAPoorly differentiated germ cell tumorAggressive, intra-abdominal spread and mets commonTumor markers: hCG, αFPSurvivalOverall =40%Stage I =75%
37 Embryonal Carcinoma Large, primitive cells Papillary or gland-like formation, occasionalSheets and ribbons
38 Polyembryona Best classified as a mixed tumor Never found in pure formFewer than 50 casesAll under age 40Resembles embryonal carcinomaEmbryo days 13-15Treated like other mixed GCTTumor markers: hCG, αFP
40 Gonadoblastoma Combined Germ Cell / Sex Cord Stromal Tumor PresentationAge 1-38Small tumorsPhenotypic ♀ with virilization90% have Y chromosome22% from streak gonadsBilaterality 30-50%Check chromosomes for dysgenic gonadsBSO if Y presentIf testicular feminization syndrome, await puberty before BSO
41 Gonadoblastoma Large germ cells, clear cytoplasm Nests of primordial germ cells surrounded by specialized stromal cellsAssociated sex cord stromal cellsGonadoblastomaDysgerminoma
47 Granulosa Cell Tumor Presentation Estrogen excess and the endometrium Adult (95%) and juvenile typesSolid and/or cystic- variableEstrogen, occasional androgen80% palpable on examinationHemoperitoneum in 15%80-90% Stage ILow grade, late relapseEstrogen excess and the endometrium25% proliferative55% hyperplastic13% adenocarcinoma
55 Germ Cell and Stromal Tumors of the Ovary Treatment SummaryGerm Cell and Stromal Tumorsof the Ovary
56 Endodermal sinus tumor Embryonal carcinoma Malignant teratoma DysgerminomaUSO staging if possibleBEP x 3 cycles if stage II-IVEndodermal sinus tumorDebulk but preserve fertilityBEP x 3-4 cyclesEmbryonal carcinomaAs aboveMalignant teratomaBEP or VACx 3-4 cyclesGranulosa cell tumorUSO if youngo/w TAH/BSOGnRH agonists for advanced ds.Sertoli-leydig cell
57 Summary Common in young women Tumor markers Treatment Fertility-sparing surgeryChemosensitive→ BEP for 3-6 cyclesRadiosensitiveNo adjuvant chemo for:Stage I pure dysgerminomaStage IA grade 1 immature teratoma