Table 1 Key clinical characteristics, histopathology, and molecular pathology of three DICER1-associated sarcomas
Demographics | Clinical characteristics | Histopathology | Molecular pathology | Outcomes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patients | Age at diagnosis | Gender | Site of sarcoma | Other DICER1-associated conditions | Family history | Gross features | Rhabdomyoblastic differentiationa | Anaplasia | Chondroid/myxoid differentiation | Bone/osteoid formation | Immunohistochemical stains | Initial diagnosisb | DICER1 mutation(s) | Other genetic alterations | Final diagnosis | |||
Positive | Negative | Somatic | Germline | |||||||||||||||
Patient 1 | 5 | F | Ovary | None | Mother: benign thyroid nodules Paternal grandmother: thyroid cancer Paternal great uncle: Brain tumor (DOD) | Oophorectomy specimen: fragments of torsed and ruptured ovarian tissue, measuring 8 × 6 × 4.8 cm in aggregate | Present | Present | Present | Present | Desmin myogenin SALL4 | AE1/AE3 inhibin A calretinin INI1 (retained) GFAP NKX2.2 SOX10 | High-grade pleomorphic sarcoma | c.2223_2230del; p.S742T*16 c.5425G>A;p.G1809R | c.2223_2230del; p.S742T*16 | None | DICER1-associated ovarian sarcoma | Alive; radiographic remission 13-months off therapy |
Patient 2 | 16 | F | Peritoneum | Papillary thyroid microcarcinoma | None | Oophorectomy and peritoneal mass specimens: unknown Autopsy: multiple tumor nodules, measuring 3.5–4.8 cm in peritoneum and omentum. Extensive abdominal, sub-diaphragmatic, and mediastinal lymphadenopathy was also identified. | Present | Present | Present | Present | Peritoneal mass: desmin Myogenin MyoD1 p53: 20% of the SRBC Autopsy: desmin S100 (partial) | Peritoneal mass: calretinin CD10 Cytokeratin 7 EMA Inhibin A WT1 Autopsy (post chemotherapy): myogenin WT1 CK7 CD34 CD10 CD68 | Outside hospital: mature cystic teratoma Re-review at our institution: adenosarcoma with rhabdomyosarcomatous overgrowth | c.3682C>T;p.Q1228* c.5428G>T;p.D1810Y | Not tested | NRAS:vc.181C>A; p.Q61K | DICER1-associated peritoneal sarcoma | DOD |
Patient 3 | 4 | M | Brain | None | Maternal aunt: unknown cancer | Hemicraniectomy specimen: tumor tissue fragments measuring 2.3 × 2.1 × 0.9 cm in aggregate | Present | Present | Present | Absent | Desmin Myogenin MyoD1 (focal) TLE1 BCOR and CD99 (patchy, weak) Ki67 > 95% | INI-1 (retained) BRG1 (retained) SMA AE1/AE3 GFAP EMA Synaptophysin Olig2 S100 | Primitive embryonal tumor with embryonal rhabdomyosarcomatous elements | c.5439G>C;p.E1813D | Not tested | GLI2c IGFR1c TSC2c LOH 11p15.5 Loss 14q32.12 Gain 8q11.21 | DICER1-associated primary intracranial sarcoma | DOD |
