BRST5:Phyllodes tumour

From Compendium of Cancer Genome Aberrations
Revision as of 22:27, 11 December 2023 by Kgeiersbach (talk | contribs)
Jump to navigation Jump to search

EGFR(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

H. Evin Gulbahce, MD, MSCI, University of Utah, UT, USA

Emilie Lalonde, PhD, London Health Sciences Center and Western University, London, Ontario, Canada

Patricija Zot, MD, Mayo Clinic, MN, USA

Cancer Category / Type

Breast cancer / Fibroepithelial Tumors of the Breast

Cancer Sub-Classification / Subtype

Phyllodes Tumor

Definition / Description of Disease

Phyllodes Tumor (PT) is a rare fibroepithelial neoplasm. Phyllodes tumors are subclassified as benign, borderline, or malignant based on a combination of several histologic features including stromal cellularity, atypia, mitotic activity, tumor border, and stromal overgrowth. The majority (60-75%) are benign, 15-25% are borderline, 8-20% are malignant.

Synonyms / Terminology

Cystosarcoma phyllodes (Historical)

Epidemiology / Prevalence

Rare, less than 1% of all breast tumors and 2.5% of all fibroepithelial neoplasms. The incidence is higher, ~7% of breast tumors, among Asian women. Phyllodes tumor is more common in older women (in their 50s), in contrast to fibroadenomas which are more common in younger women (in their 20s).

Clinical Features

PT usually present clinically as unilateral, well circumscribed mass. Lymph node metastases are infrequent.

Signs and Symptoms
Laboratory Findings

Sites of Involvement

There is no specific predilection for location in the breast.

Morphologic Features

Malignant phyllodes tumor is diagnosed when all of the following morphologic features are present [1]:

·       Marked stromal nuclear pleomorphism

·       Stromal overgrowth (absence of epithelial elements in one low-power microscopic field)

·       Increased mitoses (>=10 mitoses/10 high power fields (hpf))

·       Increased stromal cellularity

·       Permeative tumor border

Or, when malignant heterologous elements are present (with the exception of well-differentiated liposarcoma).

Borderline phyllodes tumor is diagnosed when one or more of the above adverse histologic features are present but histologic criteria fall short of malignant PT.

Benign phyllodes tumor has well defined borders, shows mild stromal cellularity, does not show atypia, and has a mitotic count <5/10 hpf

Immunophenotype

Finding Marker
Positive (universal) CD34 (in benign PT)
Positive (subset) EGFR (97%) of Malignant PT [2], CD34 (majority of borderline PT, subset of malignant PT), beta-catenin (94%) of benign lesions
Negative (universal) p63 and p40 (in benign and borderline PT)
Negative (subset) EXAMPLE CD4

Chromosomal Rearrangements (Gene Fusions)

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
NA

Individual Region Genomic Gain / Loss / LOH

Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EGFR Amplification 7p11.2 No No No Borderline and malignant tumors [3] [4]
RB1 Deletion 13q14.2 No No No Mostly borderline or malignant tumors [5][3][6]
PTEN Deletion 10q23.31 No Yes No Malignant tumors; less common [5][6]
CDKN2A/ CDKN2B Deletion 9p21.3 No Yes No Borderline and malignant tumors; associated with recurrent disease [6]

Characteristic Chromosomal Patterns

Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis)

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE

Co-deletion of 1p and 18q

Yes No No EXAMPLE:

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

Gene Mutations (SNV / INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.)

Gene; Genetic Alteration Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) Prevalence (COSMIC / TCGA / Other) Concomitant Mutations Mutually Exclusive Mutations Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
MED12 Gain of function; G44 residue is a hotspot 73%, 67% (PMID:25593300, 26437033) Often co-occurring RARA, TERT promoter, SETD2, EGFR mutations Yes No Unknown All (Benign, borderline, and malignant) grades


TERT promoter
RARA
EGFR
TP53
PIK3CA
KMT2D (synonym MLL2)
ZNF703
SETD2
FLNA
RB1
NF1

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

Put your text here

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table.)

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE:  KMT2C and ARID1A; Inactivating mutations EXAMPLE:  Histone modification, chromatin remodeling EXAMPLE:  Abnormal gene expression program

Genetic Diagnostic Testing Methods

Put your text here

Familial Forms

Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)

Additional Information

Put your text here

Links

Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page (Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "http://www." portion.)

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)

  1. Zhang, Yanhong; et al. (2016-07). "Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates". Archives of Pathology & Laboratory Medicine. 140 (7): 665–671. doi:10.5858/arpa.2016-0042-RA. ISSN 1543-2165. PMID 27362571. Check date values in: |date= (help)
  2. Gatalica, Zoran; et al. (2016-01-12). "Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast". Oncotarget. 7 (2): 1707–1716. doi:10.18632/oncotarget.6421. ISSN 1949-2553. PMC 4811491. PMID 26625196.
  3. 3.0 3.1 Tan, Jing; et al. (2015-11). "Genomic landscapes of breast fibroepithelial tumors". Nature Genetics. 47 (11): 1341–1345. doi:10.1038/ng.3409. ISSN 1546-1718. PMID 26437033. Check date values in: |date= (help)
  4. Gatalica, Zoran; et al. (2016-01-12). "Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast". Oncotarget. 7 (2): 1707–1716. doi:10.18632/oncotarget.6421. ISSN 1949-2553. PMC 4811491. PMID 26625196.
  5. 5.0 5.1 Kim, Ji-Yeon; et al. (2018-02). "Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast". Translational Oncology. 11 (1): 18–23. doi:10.1016/j.tranon.2017.10.002. ISSN 1936-5233. PMC 5684533. PMID 29145046. Check date values in: |date= (help)
  6. 6.0 6.1 6.2 Tsang, Julia Y.; et al. (2022-10). "Analysis of recurrent molecular alterations in phyllodes tumour of breast: insights into prognosis and pathogenesis". Pathology. 54 (6): 678–685. doi:10.1016/j.pathol.2022.03.008. ISSN 1465-3931. PMID 35691725 Check |pmid= value (help). Check date values in: |date= (help)

EXAMPLE Book

  1. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.

Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.