Difference between revisions of "BRST5:Phyllodes tumour"

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<span style="color:#0070C0">(''General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ 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'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])''</span>
+
==Primary Author(s)*==
  
−
==Primary Author(s)*==
+
Emilie Lalonde, PhD, London Health Sciences Center and Western University, London, Ontario, Canada
 +
 
 +
H. Evin Gulbahce, MD, MSCI, University of Utah, UT, USA
  
−
Put your text here<span style="color:#0070C0"> (''Name and affiliation; example:'' Jane Smith, PhD, Institute of Genomics) </span>
+
Katherine B. Geiersbach, MD, Mayo Clinic, MN, USA
  
 
__TOC__
 
__TOC__
Line 9: Line 11:
 
==Cancer Category / Type==
 
==Cancer Category / Type==
  
−
Put your text here
+
Breast cancer / Fibroepithelial Tumors of the Breast
  
 
==Cancer Sub-Classification / Subtype==
 
==Cancer Sub-Classification / Subtype==
  
−
Put your text here
+
Phyllodes Tumor 
  
 
==Definition / Description of Disease==
 
==Definition / Description of Disease==
  
−
Put your text here <span style="color:#0070C0">(''Instructions: Brief description of approximately one paragraph - include disease context relative to other WHO classification categories referring to the specific WHO book pages, diagnostic criteria if applicable, and differential diagnosis if applicable'') </span>
+
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, and 8-20% are malignant.
  
 
==Synonyms / Terminology==
 
==Synonyms / Terminology==
  
−
Put your text here <span style="color:#0070C0">(''Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.'') </span>
+
Cystosarcoma phyllodes ''(Historical)''
  
 
==Epidemiology / Prevalence==
 
==Epidemiology / Prevalence==
  
−
Put your text here
+
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==
 
==Clinical Features==
  
−
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
+
PT usually present clinically as unilateral, well circumscribed mass. Lymph node metastases are infrequent.
 
{| class="wikitable"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
−
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
+
|Unilateral, well-circumscribed mass
−
 
 
−
EXAMPLE B-symptoms (weight loss, fever, night sweats)
 
−
 
 
−
EXAMPLE Fatigue
 
−
 
 
−
EXAMPLE Lymphadenopathy (uncommon)
 
 
|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
−
|EXAMPLE Cytopenias
+
|
−
 
 
−
EXAMPLE Lymphocytosis (low level)
 
 
|}
 
|}
  
 
==Sites of Involvement==
 
==Sites of Involvement==
  
−
Put your text here <span style="color:#0070C0">(''Instruction: Indicate physical sites; Example: nodal, extranodal, bone marrow'') </span>
+
There is no specific predilection for location in the breast.
  
 
==Morphologic Features==
 
==Morphologic Features==
  
−
Put your text here
+
''Malignant'' phyllodes tumor is diagnosed when all of the following morphologic features are present <ref>{{Cite journal|last=Zhang|first=Yanhong|last2=Kleer|first2=Celina G.|date=2016-07|title=Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates|url=https://pubmed.ncbi.nlm.nih.gov/27362571|journal=Archives of Pathology & Laboratory Medicine|volume=140|issue=7|pages=665–671|doi=10.5858/arpa.2016-0042-RA|issn=1543-2165|pmid=27362571}}</ref>:
 +
 
 +
·       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==
 
==Immunophenotype==
−
 
−
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
 
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 62: Line 70:
 
!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
−
|Positive (universal)||EXAMPLE CD1
+
|Positive (universal)||CD34 (in benign PT)
 
|-
 
|-
−
|Positive (subset)||EXAMPLE CD2
+
|Positive (subset)||EGFR (97%) of Malignant PT <ref name=":3">{{Cite journal|last=Gatalica|first=Zoran|last2=Vranic|first2=Semir|last3=Ghazalpour|first3=Anatole|last4=Xiu|first4=Joanne|last5=Ocal|first5=Idris Tolgay|last6=McGill|first6=John|last7=Bender|first7=Ryan P.|last8=Discianno|first8=Erin|last9=Schlum|first9=Aaron|date=2016-01-12|title=Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast|url=https://pubmed.ncbi.nlm.nih.gov/26625196|journal=Oncotarget|volume=7|issue=2|pages=1707–1716|doi=10.18632/oncotarget.6421|issn=1949-2553|pmc=4811491|pmid=26625196}}</ref>, CD34 (majority of borderline PT, subset of malignant PT), beta-catenin (94%) of benign lesions
 
|-
 
|-
−
|Negative (universal)||EXAMPLE CD3
+
|Negative (universal)||p63 and p40 (in benign and borderline PT)
 
|-
 
|-
 
|Negative (subset)||EXAMPLE CD4
 
|Negative (subset)||EXAMPLE CD4
Line 72: Line 80:
  
 
==Chromosomal Rearrangements (Gene Fusions)==
 
==Chromosomal Rearrangements (Gene Fusions)==
−
 
−
Put your text here and fill in the table
 
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 83: Line 89:
 
!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+
|7p11.2||''EGFR''
−
EXAMPLE 30% (add reference)
+
|N/A
−
|Yes
+
|
−
|No
+
|
−
|Yes
+
|
−
|EXAMPLE
+
|
−
 
+
|Intragenic deletion resulting in loss of exons 2-7, also known as EGFRvIII.
−
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
 
 
|}
 
|}
 
 
 
==Individual Region Genomic Gain / Loss / LOH==
 
==Individual Region Genomic Gain / Loss / LOH==
−
 
−
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
 
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
Line 105: Line 108:
 
!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE
+
|1
−
 
+
|Gain
−
7
+
|
−
|EXAMPLE Loss
+
|1q (whole arm)
−
|EXAMPLE
+
|No
−
 
+
|Unknown
−
chr7:1- 159,335,973 [hg38]
+
|No
−
|EXAMPLE
+
|Clinically relevant genes unknown. The frequency in benign tumors varies from 0-33% across studies.<ref name=":4">{{Cite journal|last=Laé|first=Marick|last2=La Rosa|first2=Philippe|last3=Mandel|first3=Jonas|last4=Reyal|first4=Fabien|last5=Hupé|first5=Philippe|last6=Terrier|first6=Philippe|last7=Couturier|first7=Jérôme|date=2016-12|title=Whole-genome profiling helps to classify phyllodes tumours of the breast|url=https://pubmed.ncbi.nlm.nih.gov/27207013|journal=Journal of Clinical Pathology|volume=69|issue=12|pages=1081–1087|doi=10.1136/jclinpath-2016-203684|issn=1472-4146|pmid=27207013}}</ref><ref name=":5">{{Cite journal|last=Lv|first=Shuhua|last2=Niu|first2=Yun|last3=Wei|first3=Li|last4=Liu|first4=Qingjie|last5=Wang|first5=Xiaowei|last6=Chen|first6=Yan|date=2008-12|title=Chromosomal aberrations and genetic relations in benign, borderline and malignant phyllodes tumors of the breast: a comparative genomic hybridization study|url=https://pubmed.ncbi.nlm.nih.gov/18189161|journal=Breast Cancer Research and Treatment|volume=112|issue=3|pages=411–418|doi=10.1007/s10549-007-9876-1|issn=1573-7217|pmid=18189161}}</ref><ref name=":6">{{Cite journal|last=Jones|first=A. M.|last2=Mitter|first2=R.|last3=Springall|first3=R.|last4=Graham|first4=T.|last5=Winter|first5=E.|last6=Gillett|first6=C.|last7=Hanby|first7=A. M.|last8=Tomlinson|first8=I. P. M.|last9=Sawyer|first9=E. J.|date=2008-04|title=A comprehensive genetic profile of phyllodes tumours of the breast detects important mutations, intra-tumoral genetic heterogeneity and new genetic changes on recurrence|url=https://pubmed.ncbi.nlm.nih.gov/18288784|journal=The Journal of Pathology|volume=214|issue=5|pages=533–544|doi=10.1002/path.2320|issn=0022-3417|pmid=18288784}}</ref>
−
 
+
|-
−
chr7
+
|7
 +
|Amplification
 +
|
 +
|7p11.2
 +
|No
 +
|No
 +
|No
 +
|Relevant gene: ''EGFR.'' Amplified (and/or with structural rearrangement, most commonly loss of exons 2-7, also known as EGFRvIII) in 33% of borderline and malignant tumors <ref name=":3" /><ref name=":0">{{Cite journal|last=Tan|first=Jing|last2=Ong|first2=Choon Kiat|last3=Lim|first3=Weng Khong|last4=Ng|first4=Cedric Chuan Young|last5=Thike|first5=Aye Aye|last6=Ng|first6=Ley Moy|last7=Rajasegaran|first7=Vikneswari|last8=Myint|first8=Swe Swe|last9=Nagarajan|first9=Sanjanaa|date=2015-11|title=Genomic landscapes of breast fibroepithelial tumors|url=https://pubmed.ncbi.nlm.nih.gov/26437033|journal=Nature Genetics|volume=47|issue=11|pages=1341–1345|doi=10.1038/ng.3409|issn=1546-1718|pmid=26437033}}</ref>
 +
|-
 +
|7
 +
|Gain
 +
|
 +
|7q
 +
|No
 +
|Unknown
 +
|No
 +
|Clinically relevant gene(s) unknown. Observed in 39-57% of malignant tumors, 7-13% of borderline tumors; not seen in benign tumors <ref name=":6" />.
 +
|-
 +
|8
 +
|Gain
 +
|
 +
|8q
 +
|No
 +
|Unknown
 +
|No
 +
|Clinically relevant gene(s) unknown. Associated with higher grade tumors <ref name=":4" /><ref name=":6" />. Significantly more common in malignant versus borderline tumors <ref name=":4" />.
 +
|-
 +
|9
 +
|Deletion
 +
|
 +
|9p21.3
 +
|No
 
|Yes
 
|Yes
 +
|No
 +
|Relevant genes: ''CDKN2A''/ ''CDKN2B.'' Borderline and malignant tumors; associated with recurrent disease <ref name=":2">{{Cite journal|last=Tsang|first=Julia Y.|last2=Shao|first2=Yan|last3=Poon|first3=Ivan K.|last4=Ni|first4=Yun-Bi|last5=Kwan|first5=Johnny S.|last6=Chow|first6=Chit|last7=Shea|first7=Ka-Ho|last8=Tse|first8=Gary M.|date=2022-10|title=Analysis of recurrent molecular alterations in phyllodes tumour of breast: insights into prognosis and pathogenesis|url=https://pubmed.ncbi.nlm.nih.gov/35691725|journal=Pathology|volume=54|issue=6|pages=678–685|doi=10.1016/j.pathol.2022.03.008|issn=1465-3931|pmid=35691725}}</ref>.
 +
|-
 +
|10
 +
|Deletion
 +
|
 +
|10q23.31
 +
|No
 
|Yes
 
|Yes
 
|No
 
|No
−
|EXAMPLE
+
|Relevant gene: ''PTEN'' may be enriched in borderline and malignant tumors <ref name=":2" /><ref name=":5" /><ref name=":6" /><ref name=":1">{{Cite journal|last=Kim|first=Ji-Yeon|last2=Yu|first2=Jong Han|last3=Nam|first3=Seok Jin|last4=Kim|first4=Seok Won|last5=Lee|first5=Se Kyung|last6=Park|first6=Woong-Yang|last7=Noh|first7=Dong-Young|last8=Nam|first8=Do-Hyun|last9=Park|first9=Yeon Hee|date=2018-02|title=Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast|url=https://pubmed.ncbi.nlm.nih.gov/29145046|journal=Translational Oncology|volume=11|issue=1|pages=18–23|doi=10.1016/j.tranon.2017.10.002|issn=1936-5233|pmc=5684533|pmid=29145046}}</ref><ref name=":4" />.
−
 
 
−
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
 
 
|-
 
|-
−
|EXAMPLE
+
|13
−
 
+
|Deletion
−
8
+
|
−
|EXAMPLE Gain
+
|13q14.2
−
|EXAMPLE
 
−
 
 
−
chr8:1-145,138,636 [hg38]
 
−
|EXAMPLE
 
−
 
 
−
chr8
 
 
|No
 
|No
 
|No
 
|No
 
|No
 
|No
−
|EXAMPLE
+
|Relevant gene: ''RB1.'' Mostly borderline or malignant tumors <ref name=":5" /><ref name=":6" /><ref name=":4" />. Focal deletions support the minimal cytoband 13q14.2 including RB1 <ref name=":6" /><ref name=":4" />
−
 
 
−
Common recurrent secondary finding for t(8;21) (add reference).
 
 
|}
 
|}
 
==Characteristic Chromosomal Patterns==
 
==Characteristic Chromosomal Patterns==
−
 
−
Put your text here <span style="color:#0070C0">(''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'')</span>
 
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE
+
|<span style="color:#0070C0">N/A</span>
−
 
+
|
−
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)==
 
==Gene Mutations (SNV / INDEL)==
  
−
Put your text here and fill in the table <span style="color:#0070C0">(''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.'') </span>
+
Prevalence estimates are drawn from the COSMIC database (url: https://cancer.sanger.ac.uk/cosmic) and from literature cited in the table.
  
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE: TP53; Variable LOF mutations
+
|''EGFR''
−
 
+
|Oncogene
−
EXAMPLE:
+
|6-8%
−
 
+
|No
−
EGFR; Exon 20 mutations
+
|No
−
 
+
|No
−
EXAMPLE: BRAF; Activating mutations
+
|No
−
|EXAMPLE: TSG
+
|Yes (off-label/ clinical trials)
−
|EXAMPLE: 20% (COSMIC)
+
|More common in malignant tumors <ref name=":2" />
−
 
+
|-
−
EXAMPLE: 30% (add Reference)
+
|''FLNA''
−
|EXAMPLE: IDH1 R123H
+
|Oncogene
−
|EXAMPLE: EGFR amplification
+
|19-35% <ref name=":0" /><ref name=":2" />
 +
|No
 +
|No
 +
|No
 +
|No
 +
|No
 +
|No significant difference between benign, borderline, and malignant tumors.
 +
|-
 +
|''KMT2D'' (previously MLL2)
 +
|Tumor suppressor gene
 +
|13-15% <ref name=":0" /><ref name=":2" /><ref name=":7">{{Cite journal|last=Yeong|first=Joe|last2=Thike|first2=Aye Aye|last3=Young Ng|first3=Cedric Chuan|last4=Md Nasir|first4=Nur Diyana|last5=Loh|first5=Kiley|last6=Teh|first6=Bin Tean|last7=Tan|first7=Puay Hoon|date=2017-12|title=A genetic mutation panel for differentiating malignant phyllodes tumour from metaplastic breast carcinoma|url=https://pubmed.ncbi.nlm.nih.gov/29066183|journal=Pathology|volume=49|issue=7|pages=786–789|doi=10.1016/j.pathol.2017.07.011|issn=1465-3931|pmid=29066183}}</ref>
 +
|No
 +
|No
 +
|No
 +
|No
 +
|No
 +
|Histone methyltransferase gene; inactivation results in aberrant transcription regulation. No significant difference between benign, borderline, and malignant tumors.
 +
|-
 +
|''MED12''
 +
|Oncogene
 +
|53-73% <ref name=":0" /><ref name=":2" /><ref>{{Cite journal|last=Cani|first=Andi K.|last2=Hovelson|first2=Daniel H.|last3=McDaniel|first3=Andrew S.|last4=Sadis|first4=Seth|last5=Haller|first5=Michaela J.|last6=Yadati|first6=Venkata|last7=Amin|first7=Anmol M.|last8=Bratley|first8=Jarred|last9=Bandla|first9=Santhoshi|date=2015-04|title=Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic Targets in Phyllodes Tumors|url=https://pubmed.ncbi.nlm.nih.gov/25593300|journal=Molecular cancer research: MCR|volume=13|issue=4|pages=613–619|doi=10.1158/1541-7786.MCR-14-0578|issn=1557-3125|pmc=4936398|pmid=25593300}}</ref>
 +
|''RARA'', ''TERT'' promoter, ''SETD2'', ''EGFR''
 +
|N/A
 +
|Yes
 +
|No
 +
|Unknown
 +
|No significant difference between benign, borderline, and malignant tumors. G44 residue is a hotspot.
 +
<br />
 +
|-
 +
|''NF1''
 +
|Tumor suppressor gene
 +
|8-10% <ref name=":2" /><ref name=":7" />
 +
|No
 +
|No
 +
|No
 +
|No
 +
|No
 
|
 
|
 +
|-
 +
|''PIK3CA''
 +
|Oncogene
 +
|9-11% <ref name=":2" /><ref name=":7" />
 +
|No
 +
|No
 +
|No
 +
|No
 +
|No
 +
|More common in malignant tumors <ref name=":2" />.
 +
|-
 +
|''RARA''
 +
|Oncogene
 +
|23-37% <ref name=":2" /><ref name=":7" />
 +
|''MED12''
 +
|No
 +
|No
 +
|Yes
 +
|No
 
|
 
|
 +
|-
 +
|''RB1''
 +
|Tumor suppressor gene
 +
|10-15% <ref name=":2" /><ref name=":7" />
 +
|No
 +
|No
 +
|No
 +
|No
 +
|No
 
|
 
|
−
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
+
|-
−
<br />
+
|''SETD2''
 +
|Other
 +
|15-22% <ref name=":2" /><ref name=":7" />
 +
|No
 +
|No
 +
|No
 +
|No
 +
|No
 +
|Histone methyltransferase gene; inactivation results in aberrant transcription regulation.
 +
|-
 +
|''TERT'' promoter
 +
|Oncogene
 +
|~60% <ref name=":2" /><ref name=":7" />
 +
|No
 +
|No
 +
|No
 +
|No
 +
|No
 +
|No significant difference between benign, borderline, and malignant tumors <ref name=":2" />
 +
|-
 +
|''TP53''
 +
|Tumor suppressor gene
 +
|15%
 +
|No
 +
|No
 +
|No
 +
|No
 +
|No
 +
|More common in malignant tumors <ref name=":2" />. Germline TP53 pathogenic mutations have been associated with PT <ref>{{Cite journal|last=Rosenberger|first=Laura H.|last2=Thomas|first2=Samantha M.|last3=Nimbkar|first3=Suniti N.|last4=Hieken|first4=Tina J.|last5=Ludwig|first5=Kandice K.|last6=Jacobs|first6=Lisa K.|last7=Miller|first7=Megan E.|last8=Gallagher|first8=Kristalyn K.|last9=Wong|first9=Jasmine|date=2020-10|title=Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing|url=https://pubmed.ncbi.nlm.nih.gov/32504368|journal=Annals of Surgical Oncology|volume=27|issue=10|pages=3633–3640|doi=10.1245/s10434-020-08480-z|issn=1534-4681|pmc=9945652|pmid=32504368}}</ref>.
 
|}
 
|}
 
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.
 
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.
Line 219: Line 337:
 
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
  
−
Put your text here
+
Next-generation sequencing (NGS) panel including genes listed in Gene Mutations table at a minimum. Standard somatic breast cancer panels are not appropriate for phyllodes tumors due to differences in mutational profiles.
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Chromosomal microarray for CNV detection can be considered if NGS panel does not call CNVs. Detection of CNVs can help differentiate between fibroadenomas and phyllodes tumors. FISH for EGFR amplification can also be considered in the absence of chromosome microarray or appropriate NGS assay.
  
 
==Familial Forms==
 
==Familial Forms==
  
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Patients with Li-Fraumeni syndrome (germline ''TP53'' pathogenic variant) are at increased risk for phyllodes tumor (NCCN breast cancer guidelines).  However, phyllodes tumor is not listed as a syndrome-associated tumor in the Genetic/Familial High-Risk Assessment guidelines.
  
 
==Additional Information==
 
==Additional Information==
  
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Due to the rare incidence of phyllodes tumors, most genomic studies are limited in number, and studies including patient follow-up information are very rare. Thus, the true mutation rate for rare events may vary compared to the numbers presented. In addition, very few studies have evaluated the prognostic outcome of genomic abnormalities. Additional studies are needed to better characterize the landscape and clinical significance of genomic abnormalities in phyllodes tumors.
  
 
==Links==
 
==Links==
  
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https://www.pathologyoutlines.com/topic/breastphyllodesgeneral.html
  
 
==References==
 
==References==
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#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.
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==Notes==
 
==Notes==
 
<nowiki>*</nowiki>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.
 
<nowiki>*</nowiki>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.

Latest revision as of 16:32, 12 July 2024

Primary Author(s)*

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

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

Katherine B. Geiersbach, 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, and 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 Unilateral, well-circumscribed mass
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
7p11.2 EGFR N/A Intragenic deletion resulting in loss of exons 2-7, also known as EGFRvIII.

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
1 Gain 1q (whole arm) No Unknown No Clinically relevant genes unknown. The frequency in benign tumors varies from 0-33% across studies.[3][4][5]
7 Amplification 7p11.2 No No No Relevant gene: EGFR. Amplified (and/or with structural rearrangement, most commonly loss of exons 2-7, also known as EGFRvIII) in 33% of borderline and malignant tumors [2][6]
7 Gain 7q No Unknown No Clinically relevant gene(s) unknown. Observed in 39-57% of malignant tumors, 7-13% of borderline tumors; not seen in benign tumors [5].
8 Gain 8q No Unknown No Clinically relevant gene(s) unknown. Associated with higher grade tumors [3][5]. Significantly more common in malignant versus borderline tumors [3].
9 Deletion 9p21.3 No Yes No Relevant genes: CDKN2A/ CDKN2B. Borderline and malignant tumors; associated with recurrent disease [7].
10 Deletion 10q23.31 No Yes No Relevant gene: PTEN may be enriched in borderline and malignant tumors [7][4][5][8][3].
13 Deletion 13q14.2 No No No Relevant gene: RB1. Mostly borderline or malignant tumors [4][5][3]. Focal deletions support the minimal cytoband 13q14.2 including RB1 [5][3]

Characteristic Chromosomal Patterns

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
N/A

Gene Mutations (SNV / INDEL)

Prevalence estimates are drawn from the COSMIC database (url: https://cancer.sanger.ac.uk/cosmic) and from literature cited in the table.

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
EGFR Oncogene 6-8% No No No No Yes (off-label/ clinical trials) More common in malignant tumors [7]
FLNA Oncogene 19-35% [6][7] No No No No No No significant difference between benign, borderline, and malignant tumors.
KMT2D (previously MLL2) Tumor suppressor gene 13-15% [6][7][9] No No No No No Histone methyltransferase gene; inactivation results in aberrant transcription regulation. No significant difference between benign, borderline, and malignant tumors.
MED12 Oncogene 53-73% [6][7][10] RARA, TERT promoter, SETD2, EGFR N/A Yes No Unknown No significant difference between benign, borderline, and malignant tumors. G44 residue is a hotspot.


NF1 Tumor suppressor gene 8-10% [7][9] No No No No No
PIK3CA Oncogene 9-11% [7][9] No No No No No More common in malignant tumors [7].
RARA Oncogene 23-37% [7][9] MED12 No No Yes No
RB1 Tumor suppressor gene 10-15% [7][9] No No No No No
SETD2 Other 15-22% [7][9] No No No No No Histone methyltransferase gene; inactivation results in aberrant transcription regulation.
TERT promoter Oncogene ~60% [7][9] No No No No No No significant difference between benign, borderline, and malignant tumors [7]
TP53 Tumor suppressor gene 15% No No No No No More common in malignant tumors [7]. Germline TP53 pathogenic mutations have been associated with PT [11].

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

Next-generation sequencing (NGS) panel including genes listed in Gene Mutations table at a minimum. Standard somatic breast cancer panels are not appropriate for phyllodes tumors due to differences in mutational profiles.

Chromosomal microarray for CNV detection can be considered if NGS panel does not call CNVs. Detection of CNVs can help differentiate between fibroadenomas and phyllodes tumors. FISH for EGFR amplification can also be considered in the absence of chromosome microarray or appropriate NGS assay.

Familial Forms

Patients with Li-Fraumeni syndrome (germline TP53 pathogenic variant) are at increased risk for phyllodes tumor (NCCN breast cancer guidelines).  However, phyllodes tumor is not listed as a syndrome-associated tumor in the Genetic/Familial High-Risk Assessment guidelines.

Additional Information

Due to the rare incidence of phyllodes tumors, most genomic studies are limited in number, and studies including patient follow-up information are very rare. Thus, the true mutation rate for rare events may vary compared to the numbers presented. In addition, very few studies have evaluated the prognostic outcome of genomic abnormalities. Additional studies are needed to better characterize the landscape and clinical significance of genomic abnormalities in phyllodes tumors.

Links

https://www.pathologyoutlines.com/topic/breastphyllodesgeneral.html

References

  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. ↑ 2.0 2.1 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 3.2 3.3 3.4 3.5 Laé, Marick; et al. (2016-12). "Whole-genome profiling helps to classify phyllodes tumours of the breast". Journal of Clinical Pathology. 69 (12): 1081–1087. doi:10.1136/jclinpath-2016-203684. ISSN 1472-4146. PMID 27207013. Check date values in: |date= (help)
  4. ↑ 4.0 4.1 4.2 Lv, Shuhua; et al. (2008-12). "Chromosomal aberrations and genetic relations in benign, borderline and malignant phyllodes tumors of the breast: a comparative genomic hybridization study". Breast Cancer Research and Treatment. 112 (3): 411–418. doi:10.1007/s10549-007-9876-1. ISSN 1573-7217. PMID 18189161. Check date values in: |date= (help)
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Jones, A. M.; et al. (2008-04). "A comprehensive genetic profile of phyllodes tumours of the breast detects important mutations, intra-tumoral genetic heterogeneity and new genetic changes on recurrence". The Journal of Pathology. 214 (5): 533–544. doi:10.1002/path.2320. ISSN 0022-3417. PMID 18288784. Check date values in: |date= (help)
  6. ↑ 6.0 6.1 6.2 6.3 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)
  7. ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 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)
  8. ↑ 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)
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Yeong, Joe; et al. (2017-12). "A genetic mutation panel for differentiating malignant phyllodes tumour from metaplastic breast carcinoma". Pathology. 49 (7): 786–789. doi:10.1016/j.pathol.2017.07.011. ISSN 1465-3931. PMID 29066183. Check date values in: |date= (help)
  10. ↑ Cani, Andi K.; et al. (2015-04). "Next-Gen Sequencing Exposes Frequent MED12 Mutations and Actionable Therapeutic Targets in Phyllodes Tumors". Molecular cancer research: MCR. 13 (4): 613–619. doi:10.1158/1541-7786.MCR-14-0578. ISSN 1557-3125. PMC 4936398. PMID 25593300. Check date values in: |date= (help)
  11. ↑ Rosenberger, Laura H.; et al. (2020-10). "Germline Genetic Mutations in a Multi-center Contemporary Cohort of 550 Phyllodes Tumors: An Opportunity for Expanded Multi-gene Panel Testing". Annals of Surgical Oncology. 27 (10): 3633–3640. doi:10.1245/s10434-020-08480-z. ISSN 1534-4681. PMC 9945652 Check |pmc= value (help). PMID 32504368 Check |pmid= value (help). Check date values in: |date= (help)

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.

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