Desmoplastic myxoid tumor, SMARCB1-mutant: clinical, histopathological and molecular characterization of a pineal region tumor encountered in adolescents and adults
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Desmoplastic myxoid tumor, SMARCB1-mutant: clinical, histopathological and molecular characterization of a pineal region tumor encountered in adolescents and adults. / Thomas, Christian; Wefers, Annika; Bens, Susanne; Nemes, Karolina; Agaimy, Abbas; Oyen, Florian; Vogelgesang, Silke; Rodriguez, Fausto J; Brett, Francesca M; McLendon, Roger; Bodi, Istvan; Burel-Vandenbos, Fanny; Keyvani, Kathy; Tippelt, Stefan; Poulsen, Frantz R; Lipp, Eric S; Giannini, Caterina; Reifenberger, Guido; Kuchelmeister, Klaus; Pietsch, Torsten; Kordes, Uwe; Siebert, Reiner; Frühwald, Michael C; Johann, Pascal D; Sill, Martin; Kool, Marcel; von Deimling, Andreas; Paulus, Werner; Hasselblatt, Martin.
In: ACTA NEUROPATHOL, Vol. 139, No. 2, 02.2020, p. 277-286.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Desmoplastic myxoid tumor, SMARCB1-mutant: clinical, histopathological and molecular characterization of a pineal region tumor encountered in adolescents and adults
AU - Thomas, Christian
AU - Wefers, Annika
AU - Bens, Susanne
AU - Nemes, Karolina
AU - Agaimy, Abbas
AU - Oyen, Florian
AU - Vogelgesang, Silke
AU - Rodriguez, Fausto J
AU - Brett, Francesca M
AU - McLendon, Roger
AU - Bodi, Istvan
AU - Burel-Vandenbos, Fanny
AU - Keyvani, Kathy
AU - Tippelt, Stefan
AU - Poulsen, Frantz R
AU - Lipp, Eric S
AU - Giannini, Caterina
AU - Reifenberger, Guido
AU - Kuchelmeister, Klaus
AU - Pietsch, Torsten
AU - Kordes, Uwe
AU - Siebert, Reiner
AU - Frühwald, Michael C
AU - Johann, Pascal D
AU - Sill, Martin
AU - Kool, Marcel
AU - von Deimling, Andreas
AU - Paulus, Werner
AU - Hasselblatt, Martin
PY - 2020/2
Y1 - 2020/2
N2 - Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly occurring in infants. Mutations of the SMARCB1 gene are the characteristic genetic lesion. SMARCB1-mutant tumors in adolescents and adults are rare and may show uncommon histopathological and clinical features. Here we report seven SMARCB1-deficient intracranial tumors sharing distinct clinical, histopathological and molecular features. Median age of the four females and three males was 40 years (range 15-61 years). All tumors were located in the pineal region. Histopathologically, these tumors displayed spindled and epithelioid cells embedded in a desmoplastic stroma alternating with a variable extent of a loose myxoid matrix. All cases showed loss of nuclear SMARCB1/INI1 protein expression, expression of EMA and CD34 was frequent and the Ki67/MIB1 proliferation index was low in the majority of cases (median 3%). Three cases displayed heterozygous SMARCB1 deletions and two cases a homozygous SMARCB1 deletion. On sequencing, one tumor showed a 2 bp deletion in exon 4 (c.369_370del) and one a short duplication in exon 3 (c.237_276dup) both resulting in frameshift mutations. Most DNA methylation profiles were not classifiable using the Heidelberg Brain Tumor Classifier (version v11b4). By unsupervised t-SNE analysis and hierarchical clustering analysis, however, all tumors grouped closely together and showed similarities with ATRT-MYC. After a median observation period of 48 months, three patients were alive with stable disease, whereas one patient experienced tumor progression and three patients had succumbed to disease. In conclusion, our series represents an entity with distinct clinical, histopathological and molecular features showing epigenetic similarities with ATRT-MYC. We propose the designation desmoplastic myxoid tumor (DMT), SMARCB1-mutant, for these tumors.
AB - Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly occurring in infants. Mutations of the SMARCB1 gene are the characteristic genetic lesion. SMARCB1-mutant tumors in adolescents and adults are rare and may show uncommon histopathological and clinical features. Here we report seven SMARCB1-deficient intracranial tumors sharing distinct clinical, histopathological and molecular features. Median age of the four females and three males was 40 years (range 15-61 years). All tumors were located in the pineal region. Histopathologically, these tumors displayed spindled and epithelioid cells embedded in a desmoplastic stroma alternating with a variable extent of a loose myxoid matrix. All cases showed loss of nuclear SMARCB1/INI1 protein expression, expression of EMA and CD34 was frequent and the Ki67/MIB1 proliferation index was low in the majority of cases (median 3%). Three cases displayed heterozygous SMARCB1 deletions and two cases a homozygous SMARCB1 deletion. On sequencing, one tumor showed a 2 bp deletion in exon 4 (c.369_370del) and one a short duplication in exon 3 (c.237_276dup) both resulting in frameshift mutations. Most DNA methylation profiles were not classifiable using the Heidelberg Brain Tumor Classifier (version v11b4). By unsupervised t-SNE analysis and hierarchical clustering analysis, however, all tumors grouped closely together and showed similarities with ATRT-MYC. After a median observation period of 48 months, three patients were alive with stable disease, whereas one patient experienced tumor progression and three patients had succumbed to disease. In conclusion, our series represents an entity with distinct clinical, histopathological and molecular features showing epigenetic similarities with ATRT-MYC. We propose the designation desmoplastic myxoid tumor (DMT), SMARCB1-mutant, for these tumors.
U2 - 10.1007/s00401-019-02094-w
DO - 10.1007/s00401-019-02094-w
M3 - SCORING: Journal article
C2 - 31732806
VL - 139
SP - 277
EP - 286
JO - ACTA NEUROPATHOL
JF - ACTA NEUROPATHOL
SN - 0001-6322
IS - 2
ER -
