Atypical teratoid / rhabdoid tumor

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Classification according to ICD-10
C72 Malignant neoplasm of the brain
ICD-O 9508/3
WHO grade IV
ICD-10 online (WHO version 2019)
Magnetic resonance imaging of a large atypical teratoid / rhabdoid tumor in an infant.

As atypical teratoider / rhabdoid tumor , often called ATRT or AT / RT abbreviated, is a rare brain tumor from the group of embryonic tumors called. The extremely malignant tumor is classified according to the WHO classification of tumors of the central nervous system as grade IV and occurs predominantly in small children.

Epidemiology

Atypical teratoid / rhabdoid tumors make up around 2% of all brain tumors in children, with the majority affecting children in the first few years of life. In adults, the occurrence has only been described in isolated cases.

Sporadic cases in which no connection with a hereditary disease can be identified predominate. Familial accumulation occurs in the so-called rhabdoid predisposition syndrome .

Symptoms

Atypical teratoid / rhabdoid tumors can be located in the posterior fossa, but also occur in the area of ​​the cerebral hemispheres. The clinical symptoms depend on the location of the tumor and the age of the child and are usually characterized by the rapid growth of the tumor. Drowsiness, nausea, and vomiting are common but non-specific symptoms.

Neuropathology

Histology of an ATRT with numerous rhabdoid tumor cells. Hematoxylin-eosin stained section.

Name-giving and typical for the fine tissue ( histological ) properties are relatively large tumor cells that have protruding nuclear bodies ( nucleoli ) and inclusions in their cell body, so-called rhabdoid tumor cells. Their cell structure is reminiscent of a malignant soft tissue tumor, the rhabdomyosarcoma . Mitotic activity, cell density and nuclear polymorphism are increased. Tumor necrosis is common. The tumor grows unstructured or in papillary structures, which can make it difficult to differentiate it from plexus carcinoma . On the other hand, in addition to sections with rhaboid tumor cells, there are also small cell sections whose histology is similar to that of other embryonic tumors such as medulloblastoma .

Pathogenesis

Immunohistochemistry for INI1, the product of the SMARCB1 gene, which is typically defective in ATRT. Note the lack of brown staining of the cell nuclei of the tumor cells in comparison to the strong brown colored cell nuclei of the blood vessels involved (internal positive control ).

Genetic changes that affect the SMARCB1 gene on chromosome 22q11.2 and lead to a reduced expression of its gene product, the INI1 protein, are characteristic. A germline mutation in the SMARCB1 gene can be detected in around a third of patients . This finding is associated with a younger age of onset and an even more unfavorable prognosis.

The immunohistochemical proof of a lack of INI1 protein expression can be used diagnostically in the majority of cases to differentiate it from other tumors. However, since ATRT can rarely also occur in connection with genetic changes in SMARCA4 (BRG1), a gene that codes for a further subdivision of the SWI / SNF chromatin remodeling complex , detection of a preserved INI1 expression makes the diagnosis of ATRT although less likely, it by no means rules them out.

Treatment and prognosis

Complete surgical removal often cannot be achieved. As part of the further treatment, which usually takes place in the context of clinical studies, adjuvant chemotherapy and (as part of an individual treatment concept depending on the age of the child) possibly also include radiation .

Even after surgical removal and initially a good response to chemotherapy, the further course is often characterized by renewed tumor growth. Two years after diagnosis, 83% of the affected small children died in a clinical study despite intensive therapeutic efforts. Children over three years of age have a slightly better prognosis, which is possibly due to the radiation (which can only be carried out in this age group due to the side effects). For this reason, proton therapy has established itself as a treatment option in the treatment of AT / RT in recent years , as this is particularly gentle on children and can thus reduce long-term side effects of radiation therapy.

Through an intensive and aggressive combination treatment, a two-year survival rate of 70% was achieved in a clinical study carried out at American clinics.

literature

  • Rorke, Biegel: Atypical teratoid / rhabdoid tumor. In: Paul Kleihues, Webster K. Cavenee (Ed.): World Health Organization classification of tumors. Volume 1: Pathology and genetics of tumors of the nervous system. IARC Press, Lyon 2000, ISBN 92-832-2409-4 .

Individual evidence

  1. ↑ D. Strother: Atypical teratoid rhabdoid tumors of childhood: diagnosis, treatment and challenges. In: Expert Rev Anticancer Ther . 2005; 5 (5), PMID 16221059 , pp. 907-915. (Review article)
  2. ↑ Makuria et al .: Atypical teratoid rhabdoid tumor (AT / RT) in adults: review of four cases. In: J Neurooncol. 2008; 88 (3), PMID 18369529 , pp. 321-330.
  3. ↑ Sévenet et al.: Constitutional mutations of the hSNF5 / INI1 gene predispose to a variety of cancers. In: Am J Hum Genet. 1999; 65 (5), PMID 10521299 , pp. 1342-1348.
  4. ↑ CS Bruggers, SB Bleyl, T. Pysher et al .: Clinicopathologic comparison of familial versus sporadic atypical teratoid / rhabdoid tumors (AT / RT) of the central nervous system . In: Pediatr Blood Cancer . September 2010, doi : 10.1002 / pbc.22757 , PMID 20848638 .
  5. ↑ Judkins include: INI1 protein expression distinguishes atypical teratoid / rhabdoid tumor from choroid plexus carcinoma. In: J Neuropathol Exp Neurol . 2005; 64 (5), PMID 15892296 , pp. 391-397.
  6. ^ Haberler et al: Immunohistochemical analysis of INI1 protein in malignant pediatric CNS tumors: Lack of INI1 in atypical teratoid / rhabdoid tumors and in a fraction of primitive neuroectodermal tumors without rhabdoid phenotype. In: Am J Surg Pathol . 2006; 30 (11), PMID 17063089 , pp. 1462-1468.
  7. ^ R. Schneppenheim, MC Frühwald, S. Gesk, M. Hasselblatt, A. Jeibmann, U. Kordes, M. Kreuz, I. Leuschner, JI Martin Subero, T. Obser, F. Oyen, I. Vater, R. Siebert: Germline nonsense mutation and somatic inactivation of SMARCA4 / BRG1 in a family with rhabdoid tumor predisposition syndrome. In: Am. J. Hum. Genet. 86, 2010, PMID 20137775 , pp. 279–284, PMC 282019 (free full text).
  8. ^ SM Pfister, A. Korshunov, M. Kool, M. Hasselblatt, C. Eberhart, MD Taylor: Molecular diagnostics of CNS embryonal tumors . In: Acta Neuropathol. tape 120 , no. 5 , November 2010, p. 553-566 , doi : 10.1007 / s00401-010-0751-5 , PMID 20882288 .
  9. ↑ Tekautz et al.: Atypical teratoid / rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy. In: J Clin Oncol . 2005; 23 (7), PMID 15735125 , pp. 1491-1499.
  10. ↑ Proton therapy for brain tumors at the WPE | WPE-UK.de. In: West German Proton Therapy Center Essen (WPE). Retrieved on August 5, 2019 (German).
  11. ↑ B. Timmermann: Radiation therapy for cancer in childhood - effect, opportunities and possible risks. In: https://www.kinderkrebsstiftung.de . German Children's Cancer Foundation, August 29, 2018, accessed on August 5, 2019 (German).
  12. ↑ Chi et al .: Intensive Multimodality Treatment for Children With Newly Diagnosed CNS Atypical Teratoid Rhabdoid Tumor. In: J Clin Oncol. 2009; 27 (3), PMID 19064966 , pp. 385-389.

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