Pathology and Molecular Biology of Teratomas in Childhood and Adolescence

Abstract

The biologic behaviour of teratomas depends on various interdependent clinical and epidemiologic variables such as the age at diagnosis, sex, tumor site, histology which all correlate to different cytogenetic and molecular biologic aberrations. Thus, testicular teratomas of infancy are generally benign. Accordingly, prepubertal teratomas show no cytogenetic or molecular genetic aberrations. In contrast, postpubertal testicular teratomas can present as clinically malignant tumors and may show complex cytogenetic aberrations such as the isochromosome 12p, which is pathognomonic of malignant germ cell tumors. Notably, teratomas of both age groups show an at least partial erasure of the genomic imprinting, correlating with their origin from primordial germ cells. The Kiel Pediatric Tumor Registry includes 541 teratoma specimens, and among these, the most frequent tumor sites (in descending order) are: the sacrococcygeal region (33.8 %), the ovaries (31.2 %) and the testes (10.5 %). Rare localizations include the mediastinum, the retroperitoneum, the head and neck region as well as the central nervous system. The WHO classification of germ cell tumors distinguishes mature and immature teratomas as well as teratomas with malignant transformation. In immature teratomas, primitive neuroectodermal structures predominate. According to the grading system (Gonzalez-Crussi, 1982), mature teratomas (G0) are more frequent (54.5 %) than immature teratomas (G1-G3, 45.5 %). Only 7.8 % of all teratomas show the highest grade of immaturity (G3). The frequency of additional microscopic foci of malignant yolk sac tumor correlates with the grade of immaturity. In sacrococcygeal teratomas, the yolk sac tumor microfoci may give rise to a malignant relapse after incomplete resection. The rare teratomas with malignant transformation contain components with "conventional" somatic type malignancy such as leukaemia, carcinoma or sarcoma. Here, molecular genetic analysis has demonstrated the origin of the somatic malignancy from a malignant transformation within the germ cell tumor with retention of the cytogenetic changes characteristic of malignant germ cell tumors.

Sacrococcygeal teratomas: clinico-pathological characteristics and isochromosome 12p status

“…Germ cell tumors arise primarily within the gonads, but a significant minority can also be found in extragonadal midline locations, including the sacrum, presacral space, coccyx, mediastinum, retroperitoneum, and pineal/ intracranial space. 1 The biological behavior and prognosis of extragonadal teratomas have been interpreted analogously to the tumors in the ovaries and testes, using criteria such as age, size, the presence of immature elements, and concurrent somatic malignant transformation of any of its elements. Whereas ovarian teratomas are typically cystic, composed of mature elements and almost uniformly benign, postpubertal testicular tumors are considered to nearly always 2 carry a potential for malignant behavior, even when composed entirely of mature elements.…”

Role of regeneration in tissue repairing and therapies

“…Metastatic testicular teratomas also occur which form a palpable mass in the testis. Similarly, mature cystic teratoma [24,25] and squammouns cell carcinoma occurs in the ovary of young patients [26,27] mainly during childhood and adolescence [28]. Besides, extra gonadial [29] and sacrococcygeal heart are rare forms of teratomas [30].…”

Klinische Forschung und Behandlung in der Pädiatrie

“…Dar ü ber hinaus defi nieren die kooperierenden Fachdisziplinen selbst zunehmend mehr die speziellen Anforderungen und Leistungsprofi le [19,23] und bauen fachspezifi sche Register durch die zentrale Dokumentation von Behandlungsdaten und Nachsorgeergebnissen auf [3] . Dagegen ist das Kieler Kindertumorregister im Rahmen der Referenzbegutachtung im Laufe von mehreren Jahrzehnten entstanden, wie am Beispiel der Teratome erkennbar ist [10] . Es erarbeitet in Kooperation mit der entsprechenden Therapieoptimierungsstudie Risikostratifi kationen [7] , ermittelt Inzidenzen f ü r sehr seltene Krankheitszust ä nde, wie z.…”

“…B. die maligne Transformation von Teratomen [1] . Hierauf aufbauend werden molekularbiologische und molekulargenetische Untersuchungen zur Tumorpathogenese durchgef ü hrt [10] . Die Nutzung derartiger Register f ü r besondere Aufgaben bedarf jedoch einer Struktur, wie sie f ü r das epidemiologische Kinderkrebsregister f ü r die (Langzeit-) Nachsorge und Erfassung von Sp ä tfolgen erst k ü rzlich beschrieben worden ist [4] .…”

“…G ö bel U, Gortner L. Klinische Forschung und Behandlung … Klin P ä diatr 2008; 220: 2 -4 nach den in Deutschland etablierten Protokollen behandelt und in diesen registriert [3,7,10] ; zus ä tzlich bestehen direkte internationale Kooperationen zwischen Referenzeinrichtungen [10] . …”