Germ cell tumours UK SH. Ivo Leuschner. Kiel Pediatric Tumor Registry, Institute of Pathology University Hospital of Schleswig-Holstein Campus Kiel
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1 Germ cell tumours Ivo Leuschner Kiel Pediatric Tumor Registry, Institute of Pathology University Hospital of Schleswig-Holstein Campus Kiel UK SH
2 Old histogenetic Concept of Germ cell tumours Pluripotent (primordial) germ cell Gonadoblastoma totipotent (embryonal) cell Seminoma/ Germinoma/ Dysgerminoma? embryonal carcinoma extraembryonal structures immature teratoma mature teratoma? Yolk sac tumor Chorio carcinoma mixed malignant Germ cell tumour
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4 Type 1 Germ cell tumors Age: Infants, children Histology: Teratoma (mature/immature) and Yolk sac tumor Sites: Saccrococcygeal, testis, ovary, mediastinum, neck, brain (rarely) Genetics: Teratoma (diploid), Yolk sac tumor (aneuploid) Gains on chromosomes 1q, 12(p13), 20q Losses on chromosomes 1p, 4, 6q
5 Teratoma Most common type of germ cell tumor (51,3% of germ cell tumors in the Kiel Pediatric Tumor Registry) Usually all three types of germ cell layers Degree of maturity depends on amount of immature elements: Grading by Gonzalez-Crussi (1982) Grade 0 (mature) - Grade 3 (immature) Norris (1976); Thurlbeck (1960)
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12 Teratoma Degree of maturity depends on amount of immature elements: Grading by Gonzalez-Crussi (1982) Grade 0 (mature) Grade 1 (<10 percent) Grade 2 (10 50 percent Grade 3 (> 50 percent) Norris (1976); Thurlbeck (1960)
13 Immature teratoma of the mediastinmum
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15 Pathology Department Hanoi October 2012
16 Yolk sac tumours Second most common type of germ cell tumours (18,3% of cases in the KTR) large morphological variability: Pseudo papillary polyvesicular ( vitelline ) mikrocystic endometriod hepatoid parietal mesenchyma-like
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19 Endometriod variant of YST
20 Solid variant of YST
21 Hepatoid variant of YST: AFP staining
22 Yolk sac tumours Immunohistochemsitry: Cytokeratin-positive AFP-positive Glypikan 2-positive SALL4-positive
23 AFP
24 AFP
25 AFP
26 Glypikan 3
27 Yolk sac tumour microfoci in teratoma In about 28% of pediatric teratomas the microfoci of YST are initially not seen (Heifetz, 1998) Recurrences with YST components are often found in cases with incomplete resection Nevertheless: Recurrences with YST components can also occur in initially mature teratomas
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30 Yolk sac tumour microfoci in teratoma Identification of YST microfoci very important If the serum AFP level is elevated in children above 6-9 months of age, a YST coponent should be suspected
31 AFP
32 AFP
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34 Type 2 Germ cell tumors Age: Testis: above 14 years Ovary: probablby above 4 years Medtastinum: Adolescents Brain: Children Histology: Seminoma/Dysgerminoma/Germinoma Non-seminomatous: Teratoma, embryonal carcinoma, Yolk sac tumor, choriocarcinoma -> all are malignant Genetics: mostly aneuploid Gains on chromosomes X, 7, 8, 12p, 21 Losses on chromosomes Y, 1p, 11, 13, 18
35 Seminoma/Dysgerminoma/Germinoma As pure tumours more infrequent as other germ cell tumours (9,7% of cases in the KTR) mostly in the ovary or CNS
36 Seminoma/Dysgerminoma/Germinoma
37 PLAP
38 CD 117
39 oct 3/4
40 IGCNU in about 90 percent
41 Embryonal Carcinoma and choriocarcinoma As pure tumors rare in children (2,1% bzw. 0,6% of cases in the KTR) Embryonal Carcinoma components can occur in mediastinal and testikular mixed germ cell tumours in adolescents beta-hcg-positive giant cells cells can cause mild elevation of serum beta-hcg
42 CD 30
43 beta-hcg
44 beta-hcg
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46 Malignant transformation in germ cell tumours Very rare in children Some cases with neuroblastoma, Wilms tumor, plexus carcinoma, etc. have been reported In adults a PNET-like malignant transformation can occurr
47 GCT with malignant (somatic) transformation: PNET-like
48 Type 4 Germ cell tumors Age: Ovary: Children/Adults?? Testis: young boys Histology: Mature Teratome ( Dermoid cyst ) Genetics: euploid/near euploid
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50 Genetics of Germ cell tumours Adult malignant GCT: Gain on chromosome 12, Isochromosome 12 (not in ovarian mature teratomas ( Dermoid cysts )) YST children: Gain on chromosome 1q and 20q Loss on chromosome 1p and 6q (LOH) Maybe also seen in immature teratoma Pure mature teratoma children: No molecular changes yet found
51 Summary Germ cell tumors in children are different from adult germ cell tumors in morphology in biology in molecular genetics
52 Thank you for your attention!
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