DICER1-associated central nervous system sarcoma in children: comprehensive clinicopathologic and genetic analysis of a newly described rare tumor

被引：53

作者：

Kamihara, Junne ^{[1
]}

Paulson, Vera ^{[2
,14
]}

Breen, Micheal A. ^{[3
]}

Laetsch, Theodore W. ^{[4
]}

Rakheja, Dinesh ^{[5
]}

Shulman, David S. ^{[1
]}

Schoettler, Michelle L. ^{[1
]}

Clinton, Catherine M. ^{[6
]}

Ward, Abigail ^{[6
]}

Reidy, Deirdre ^{[6
]}

Pinches, R. Seth ^{[7
]}

Weiser, Daniel A. ^{[8
]}

Mullen, Elizabeth A. ^{[1
]}

Schienda, Jaclyn ^{[6
]}

Meyers, Paul A. ^{[9
]}

DuBois, Steven G. ^{[1
]}

Nowak, Jonathan A. ^{[10
]}

Foulkes, William D. ^{[11
]}

Schultz, Kris Ann P. ^{[12
,13
]}

Janeway, Katherine A. ^{[1
]}

Vargas, Sara O. ^{[2
]}

Church, Alanna J. ^{[2
]}

机构：

[1] Harvard Med Sch, Dept Pediat Oncol, Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA 02115 USA

[2] Harvard Med Sch, Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA

[3] Harvard Med Sch, Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA

[4] Univ Texas SouthWestern Med Ctr & Childrens Hlth, Dept Pediat, Dallas, TX USA

[5] Univ Texas Southwestern Med Ctr Dallas, Dept Pathol, Dallas, TX USA

[6] Dana Farber Boston Childrens Canc & Blood Disorde, Dept Pediat Oncol, Boston, MA USA

[7] Boston Childrens Hosp, Dept Pathol, Boston, MA USA

[8] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Pediat, New York, NY USA

[9] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY USA

[10] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[11] McGill Univ, Dept Human Genet, Hlth Ctr, Jewish Gen Hosp, Montreal, PQ, Canada

[12] Childrens Minnesota, Canc & Blood Disorders, Minneapolis, MN USA

[13] Childrens Minnesota, Int Pleuropulm Blastoma Registry DICER1, Minneapolis, MN USA

[14] Univ Washington, Med Ctr, Dept Lab Med, Seattle, WA 98195 USA

来源：

MODERN PATHOLOGY | 2020年 / 33卷 / 10期

关键词：

JOINT-CONSENSUS-RECOMMENDATION; GENERATION SEQUENCING ASSAY; SOMATIC DICER1 MUTATIONS; PLEUROPULMONARY BLASTOMA; GERM-LINE; VARIANTS; ASSOCIATION; VALIDATION; GUIDELINES; STANDARDS;

D O I：

10.1038/s41379-020-0516-1

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

The spectrum of neoplasms associated with DICER1 variants continues to expand, with the recent addition of primary "DICER1-associated central nervous system sarcoma" (DCS). DCS is a high-grade malignancy predominantly affecting pediatric patients. Six pediatric DCS were identified through a combination of clinical diagnostic studies, archival inquiry, and interinstitutional collaboration. Clinical, histologic, immunohistologic, and molecular features were examined. Genomic findings in the 6 DCS were compared with those in 14 additional DICER1-associated tumors sequenced with the same assay. The six patients presented at ages 3-15 years with CNS tumors located in the temporal (n = 2), parietal (n = 1), fronto-parietal (n = 1), and frontal (n = 2) lobes. All underwent surgical resection. Histologic examination demonstrated high-grade malignant spindle cell tumors with pleuropulmonary blastoma-like embryonic "organoid" features and focal rhabdomyoblastic differentiation; immature cartilage was seen in one case. Immunohistochemically, there was patchy desmin and myogenin staining, and patchy loss of H3K27me3, and within eosinophilic cytoplasmic globules, alfa-fetoprotein staining. Biallelic DICER1 variants were identified in all cases, with germline variants in two of five patients tested. DCS demonstrated genomic alterations enriched for Ras pathway activation and TP53 inactivation. Tumor mutational burden was significantly higher in the 6 DCS tumors than in 14 other DICER1-associated tumors examined (mean 12.9 vs. 6.8 mutations/Mb, p = 0.035). Postoperative care included radiation (n = 5) and chemotherapy (n = 3); at the last follow-up, three patients were alive without DCS, and three had died of disease. Our analysis expands the clinical, histologic, immunohistological, and molecular spectrum of DCS, identifying distinctive features that can aid in the diagnosis, multidisciplinary evaluation, and treatment of DCS.

引用

页码：1910 / 1921

页数：12

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