YAP1 融合阳性幕上室管膜瘤：PathologyOutlines 专题全文（附 10 月 8 日教科书更新）Supratentorial ependymoma, YAP1 fusion positive (with Textbook Updates, 8 October 2026)

Scope: the full PathologyOutlines Textbook Updates blog post of 8 October 2026 (five topic summaries and the featured image) and the complete topic page “Supratentorial ependymoma, YAP1 fusion positive” (all sections, 21 on-site images with legends, sample report, differential diagnosis, practice questions and answers). Externally hosted EM and FISH images are linked only. The other four topics are covered by their blog summaries.

Textbook Updates · 8 October 2026

We have posted updates of the following topics:

CNS & pituitary tumors > Gliomas, glioneuronal tumors and neuronal tumors > Ependymal tumors > Supratentorial ependymoma, YAP1 fusion positive

by Alberto Pietrantoni, M.D., Valeria Barresi, M.D., Ph.D.

Topic summary: Supratentorial ependymoma, YAP1 fusion positive is a circumscribed supratentorial glioma showing an ependymal morphology and a distinctive fusion involving the YAP1 gene. Frequently large mass involving multiple lobes or the entire hemisphere. More frequent in female patients (75%); > 60% of patients are younger than 4 years. 5 year progression free survival: 66%; better prognosis than supratentorial ependymoma, ZFTA fusion positive. Treatment: safest maximal surgical resection.

Cytopathology > Thyroid > High grade follicular cell derived nonanaplastic thyroid carcinoma

by Asma Arshia, M.B.B.S., Heather I-Hsuan Chen-Yost, M.D.

Topic summary: High grade follicular cell derived nonanaplastic thyroid carcinoma (HGFCTC) encompasses poorly differentiated thyroid carcinoma (PDTC) and high grade differentiated thyroid carcinoma (HGDTC), which are malignant thyroid neoplasms characterized by elevated mitotic activity or tumor necrosis without anaplastic cytologic features. Presents with a large, firm thyroid nodule that has grown rapidly over a period of months. Surgery and radioactive iodine are first line for treatment; however, PDTC and HGDTC are often radioactive iodine resistant.

Stains (IHC & special) > BCOR

by Nat Pernick, M.D.

Topic summary: BCOR immunohistochemistry (IHC) detects overexpression of the BCOR protein in tumors harboring BCOR genetic alterations, including BCOR gene fusions and BCOR internal tandem duplications. Positive staining: strong, diffuse nuclear reactivity. Highly sensitive marker for sarcomas with BCOR genetic abnormalities and clear cell sarcoma of the kidney, although specificity is limited by positivity in synovial sarcomas and some other tumor types. Screening tool to identify tumors that may benefit from confirmatory molecular testing.

Stains (IHC & special) > TRPS1

by Di (Andy) Ai, M.D., Ph.D., Qingqing Ding, M.D., Ph.D.

Topic summary: TRPS1 (trichorhinophalangeal syndrome type 1) is a GATA family zinc finger transcription factor involved in mammary epithelial cell growth, breast cancer development and cell survival. Nuclear staining. Used to diagnose ER positive breast cancer (> 95%), HER2 positive breast cancer (> 90%) and triple negative breast cancer (> 90%, including metaplastic and nonmetaplastic triple negative breast cancer). In immunohistochemical panel along with pancytokeratin, ER and GATA3 to diagnose metastatic carcinoma of breast origin.

Stomach > Carcinoma > Amphicrine-like carcinoma

by Ihsan Baroudi, M.D., Raul S. Gonzalez, M.D.

Topic summary: Category of rare monophasic neoplasms characterized by the coexistence of neuroendocrine and nonneuroendocrine (exocrine) epithelial differentiation within the tumor. Dual differentiation may be present either within individual tumor cells or as a tight, intimate admixture of morphologically similar tumor cells. Rare, with most data coming from single case reports. Cases often present at advanced stage and prognosis appears to be poor. Surgical resection is the main treatment, with consideration of adjuvant chemotherapy or radiotherapy.

Featured Image

Topic full text: Supratentorial ependymoma, YAP1 fusion positive

Authors: Alberto Pietrantoni, M.D., Valeria Barresi, M.D., Ph.D. · Editorial Board Member: Jared T. Ahrendsen, M.D., Ph.D. · Deputy Editor-in-Chief: Chunyu Cai, M.D., Ph.D. · Last author update: 1 October 2026 · Last staff update: 1 October 2026

Definition / general

• Supratentorial ependymoma, YAP1 fusion positive is a circumscribed supratentorial glioma showing an ependymal morphology and a distinctive fusion involving the YAP1 gene

Essential features

• Supratentorial by definition
• Glial neoplasm with perivascular pseudorosettes or ependymal canals, with an ependymal immunophenotype (GFAP+, Olig2-, EMA+)
• Rearrangement of the YAP1 gene
• It can be graded as WHO CNS grade 2 or 3 on morphological grounds

ICD coding

• ICD-O: 9396/3 - supratentorial ependymoma, YAP1 fusion positive
• ICD-11: 2A00.0Y & XH1511 - other specified gliomas of brain & ependymoma, NOS

Epidemiology

• More frequent in female patients (75%) than male patients (Cancer Cell 2015;27:728)
• Median age: 11 months (range: 1 month - 51 years) (Cancer Cell 2015;27:728, Clin Neuroradiol 2024;34:939)
• Over 60% of patients are younger than 4 years (Cancer Cell 2015;27:728)
• YAP1 fusion found in 10 - 11% of supratentorial ependymomas (Cancer Cell 2015;27:728)

Sites

• By definition it affects the supratentorial compartment (Brain Pathol 2019;29:205)
• Frequently large mass involving multiple lobes or the entire hemisphere (Clin Neuroradiol 2024;34:939)
• YAP1 fusion has also been reported in rare ependymomas of the posterior fossa or the spinal region (Acta Neuropathol Commun 2024;12:158, Brain Pathol 2022;32:e13020)

Pathophysiology

• Rearrangement of the yes associated protein 1 (YAP1) gene is the main driver alteration
• YAP1 is a Hippo pathway transcriptional coactivator that regulates tissue homeostasis, cell fate and proliferation (Nat Commun 2019;10:3914)
• YAP1 is a proto-oncogene and exerts its function through interaction with the family of TEAD transcription factors and nuclear factor I (Nat Commun 2019;10:3914)
• YAP1 overexpression leads to formation of ependymoma-like tumors in animal models (Nat Commun 2020;11:2380)
• CDKN2A / CDKN2B homozygous deletion and copy number variations are usually absent (Cancer Cell 2015;27:728)

Etiology

• Unknown

Clinical features

• Usual features of supratentorial mass forming lesions (Brain Sci 2021;11:301, Ann Transl Med 2017;5:269)
  • Increased intracranial pressure
  • Headache
  • Seizures
  • Focal neurological deficits
  • Behavioral changes

Diagnosis

• Combination of location, histological and immunohistochemical findings and evidence of a YAP1 fusion (Neuro Oncol 2021;23:1231)
• Essential diagnostic criteria according to WHO CNS 2021
  • Supratentorial tumor with morphological and immunohistochemical features of ependymoma
  • Gene fusion involving YAP1
• Desirable diagnostic criteria
  • DNA methylation profile aligned with supratentorial ependymoma, YAP1 fusion positive
  • No immunoreactivity for p65 (RELA) or L1-CAM
  • PAS positive eosinophilic granular bodies
• Reference: Neuro Oncol 2021;23:1231

Radiology description

• MRI findings (Brain Pathol 2019;29:205, Clin Neuroradiol 2024;34:939)
  • Cystic and solid mass forming lesion
  • Intraparenchymal, intraventricular or paraventricular
  • Solid component can display multinodular pattern and hemorrhage
  • Mostly isointense on T1 and T2 weighted sequences
  • Variable peritumoral edema
  • Calcifications can be present, better highlighted with CT
  • Heterogeneous contrast enhancement

Radiology images

Contributed by Fabio Martino Doniselli, M.D., Ph.D.

Prognostic factors

• 5 year overall survival: 100% (Cancer Cell 2015;27:728)
• 5 year progression free survival: 66% (Cancer Cell 2015;27:728)
• Better prognosis than supratentorial ependymoma, ZFTA fusion positive (Cancer Cell 2015;27:728)
• Gross total or near total resection favorably affects prognosis (Neurosurgery 2019;85:41)
• Histological WHO grade (see Microscopic description) shows weak or no correlation with prognosis (J Negat Results Biomed 2011;10:7, Cancer Cell 2015;27:728)

Case reports & case series

• Infant girl with a left frontoparietal mass (BMJ Case Rep 2024;17:e261022)
• Case series of 15 pediatric patients younger than 3 years at diagnosis (Brain Pathol 2019;29:205)
• 26 year old man with a left frontal mass (Neuropathology 2021;41:133)
• 35 year old man with a left frontal mass (Brain Tumor Pathol 2022;39:240)

Treatment

• Safest maximal surgical resection (Neuro Oncol 2018;20:445)
• Postsurgical conformal radiation therapy depending on patient's age and presence or absence of tumor residue (Neuro Oncol 2018;20:445)
• Chemotherapy is still investigational and has been administered as exclusive therapy in children and in adults with recurring ependymoma when further surgery and radiation are no longer feasible (Neuro Oncol 2018;20:445)

Gross description

• Circumscribed lesion
• Necrotic and calcified areas can be present

Frozen section description

• Classic ependymoma features (J Neurosurg Spine 2018;30:133)
  • Proliferation of fibrillary glial looking monomorphic to moderately pleomorphic cells
  • Perivascular pseudorosettes are frequently seen
  • Necrosis, microvascular proliferation and mitotic activity can be present

Microscopic (histologic) description

• Sharp demarcation from surrounding parenchyma, although microscopic infiltration can be seen (Brain Pathol 2019;29:205)
• Moderate or high cellular density (Brain Pathol 2019;29:205)
• Perivascular pseudorosettes are a common finding (Brain Pathol 2019;29:205)
• True ependymal rosettes are rarely reported (Brain Pathol 2019;29:205)
• Monomorphic small to medium size nuclei, with round or polygonal shape and dense chromatin (Brain Pathol 2019;29:205)
• Eosinophilic cytoplasm with mostly indistinct borders; well demarcated, granular eosinophilic cytoplasm may be seen focally (Brain Pathol 2019;29:205)
• Small clusters of small gemistocyte-like cells are occasionally observed (Brain Pathol 2019;29:205)
• Eosinophilic granular bodies and calcifications can be seen (Brain Pathol 2019;29:205)
• Variable mitotic index (Brain Pathol 2019;29:205)
• Marked nuclear pleomorphism, microvascular proliferation and necrosis can be present (Brain Pathol 2019;29:205)
• Grading
  • CNS WHO grade 2 or 3 (no standardized grading system)
  • Features suggesting grade 3: brisk mitotic activity, necrosis, microvascular proliferation, anaplasia
  • Controversial prognostic relevance of grading (J Negat Results Biomed 2011;10:7, Cancer Cell 2015;27:728)

Microscopic (histologic) images

Contributed by Alberto Pietrantoni, M.D.

Cytology description

• Cytology of cerebrospinal fluid usually performed for staging purposes
• Smears performed during intraoperative examination
• Cytology findings (Cytopathology 2024;35:556)
  • Fibrillary glial cells with plump cytoplasmic processes
  • Round, monomorphic to moderately pleomorphic nuclei, with salt and pepper chromatin
  • Intraoperative smears show moderate cellularity, frequently with aggregates of cells around blood vessels (perivascular pseudorosettes)
  • True ependymal rosettes are rarely seen
  • Vessels are sometimes hyalinized

Positive stains

• GFAP: variable intensity; stronger expression within perivascular pseudorosettes (Brain Pathol 2019;29:205)
• EMA: cytoplasmic paranuclear dot-like or ring-like positivity (Brain Pathol 2019;29:205)
• MAP2: variable expression (Brain Pathol 2019;29:205)
• S100, CD56, podoplanin (D2-40): positive, although not specific (Clin Neuropathol 2009;28:373)
• Synaptophysin, cytokeratins: may be positive in scattered cells; more extensive expression in rare cases (Appl Immunohistochem Mol Morphol 2000;8:25)
• PAS: positive in eosinophilic granular bodies (Brain Pathol 2019;29:205)
• Ki67 labeling index: variable (Brain Pathol 2019;29:205)

Negative stains

• Olig2: generally negative; rare isolated cells may be positive (Brain Pathol 2019;29:205)
• L1-CAM, p65 (Brain Pathol 2019;29:205)
• Neurofilament (Brain Pathol 2019;29:205)

Electron microscopy description

• Ependymal differentiation can be confirmed by the presence of abortive cilia on ultrastructural examination (Brain Pathol 2019;29:205)

Electron microscopy images

Images hosted on other servers:

Abortive cilia

Molecular / cytogenetics description

• YAP1 rearrangement with MAMLD1 being the most common partner (Brain Pathol 2019;29:205, Cancer Cell 2015;27:728)
• Other less common fusion partner genes: MAML2, FAM118B (Cancer Cell 2015;27:728, Brain Tumor Pathol 2022;39:240)
• Case with ZFTA::YAP1 fusion has been reported, which defies current classification criteria (Acta Neuropathol Commun 2026;14:183)
• Relatively stable genome (low frequency of copy number variations) (Cancer Cell 2015;27:728)
• Supratentorial ependymoma, YAP1 fusion positive has its own DNA methylation profile (Cancer Cell 2015;27:728)
• Case of supratentorial ependymoma with a TEAD::NCOA2 fusion and no YAP1 rearrangement was reported to have the same DNA methylation profile as supratentorial ependymoma, YAP1 fusion positive (Acta Neuropathol 2025;149:14)

Molecular / cytogenetics images

Images hosted on other servers:

YAP1 rearrangement on FISH

Sample pathology report

• Brain, temporal lobe, excision:
  • Supratentorial ependymoma, YAP1 fusion positive, CNS WHO grade 3 (see comment)
  • Comment: Circumscribed proliferation of glial cells, with small round nuclei, perivascular pseudorosettes and scattered eosinophilic granular bodies. The mitotic index is 5 mitoses/mm². Necrosis and microvascular proliferation are present. Tumor cells express GFAP and EMA. Olig2 and L1-CAM are negative. Ki67 proliferation index is 20% in hotspot areas. FISH analysis identified a rearrangement of the YAP1 gene. No rearrangement of the ZFTA gene was found.

Differential diagnosis

• Supratentorial ependymoma, ZFTA fusion positive:
  • Usually no eosinophilic granular bodies
  • L1-CAM+
  • p65+ if ZFTA is fused with RELA
  • No YAP1 rearrangement
  • ZFTA rearrangement
  • Very rare cases of supratentorial ependymomas with ZFTA::YAP1 fusion (Acta Neuropathol Commun 2026;14:183)
• Angiocentric glioma:
  • No contrast enhancement
  • Diffuse growth, syncytial and spindle cells
  • No YAP1 rearrangement
  • MYB rearrangement (MYB::QKI fusion most frequently)
• Astroblastoma, MN1 altered:
  • Astroblastic pseudorosettes, vascular and pericellular hyalinization
  • Olig2 at least focally positive
  • No YAP1 rearrangement
  • MN1 rearrangement
• CNS tumor with BCOR internal tandem duplication:
  • Perivascular pseudorosettes are GFAP negative
  • Diffuse BCOR positivity
  • No YAP1 rearrangement
  • Internal tandem duplication of exon 15 of BCOR
• Rosette forming glioneuronal tumor:
  • Biphasic tumor, with a glial and a neurocytic component and neurocytic rosettes
  • Olig2+, EMA-
  • No YAP1 rearrangement
  • FGFR1 hotspot mutation
• Embryonal tumor with multilayered rosettes:
  • Rosettes are multilayered
  • Mostly negative for glial markers; neuronal markers positive in neuropil-like matrix
  • LIN28A+
  • No YAP1 rearrangement
  • Alterations of C19MC or DICER1

Additional references

• WHO Classification of Tumours Editorial Board: Central Nervous System Tumours, 5th Edition, 2022

Practice question #1

The image shown above is a recurring feature of an intraventricular, circumscribed, supratentorial brain tumor in a pediatric patient. No significant mitotic activity, necrosis or microvascular proliferation is observed. The tumor has a sharp demarcation from surrounding brain parenchyma. The tumor is positive for GFAP and EMA and negative for Olig2 and L1-CAM. Which of the following genes is most likely to be altered in such a tumor?

1. CDKN2A / CDKN2B
2. EWSR1
3. STAT6
4. YAP1
5. ZFTA

Practice answer #1

D.YAP1. The image shows a perivascular disposition of mostly monomorphic cells, with a perivascular anucleate zone. This feature, alongside the reported immunophenotype and clinical information, may indicate a supratentorial ependymoma, which can exhibit rearrangement of the YAP1 or ZFTA genes. Answer E is incorrect because in this case, ZFTA rearrangement is less likely given the negativity for L1-CAM. Therefore, supratentorial ependymoma, YAP1 fusion positive is the most likely diagnosis out of the given options. Answer A is incorrect because CDKN2A / CDKN2B can be deleted in ependymomas but they are usually preserved in YAP1 fusion positive ependymomas. Answers B and C are incorrect because EWSR1 and STAT6 are altered in mesenchymal tumors (like Ewing sarcoma and solitary fibrous tumor, respectively), which do not seem to be compatible with the case.

Reference: Supratentorial ependymoma, YAP1 fusion positive

Practice question #2

Which of the following is a molecular alteration that should be searched for in pediatric supratentorial ependymomas?

1. BRAF mutation
2. EGFR amplification
3. FGFR1 mutation
4. IDH mutation
5. YAP1 fusion

Practice answer #2

E.YAP1 fusion. YAP1 fusion is reported in supratentorial ependymomas and it defines a subtype of these tumors. Answers A, B, C and D are incorrect because the other options are molecular features that characterize other CNS neoplasms: BRAF and FGFR1 mutations for various low grade gliomas and glioneuronal tumors, EGFR amplification for high grade gliomas including glioblastoma, IDH wild type and IDH1 / IDH2 mutation for IDH mutant astrocytoma and oligodendroglioma.

Reference: Supratentorial ependymoma, YAP1 fusion positive