Compendium of Cancer Genome Aberrations

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BRST5:Tall cell carcinoma with reversed polarity (view source)

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{{DISPLAYTITLE:Tall cell carcinoma with reversed polarity}}
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[[BRST5:Table_of_Contents|Breast Tumours (WHO Classification, 5th ed.)]]
 
==Primary Author(s)*==
 
==Primary Author(s)*==
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H. Evin Gulbahce, MD, MSCI, University of Utah, UT, USA <span style="color:#0070C0"> </span>
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==WHO Classification of Disease==
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Put your text here
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__TOC__
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==Cancer Category/Type==
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==Cancer Sub-Classification / Subtype==
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==Definition / Description of Disease==
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Put your text here
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==Synonyms / Terminology==
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==Epidemiology / Prevalence==
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Put your text here
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==Clinical Features==
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Put your text here and fill in the table
   
{| class="wikitable"
 
{| class="wikitable"
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|'''Signs and Symptoms'''
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!Structure
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|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
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!Disease
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|-
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EXAMPLE B-symptoms (weight loss, fever, night sweats)
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|Book
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|Breast Tumours (5th ed.)
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EXAMPLE Fatigue
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|-
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|Category
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EXAMPLE Lymphadenopathy (uncommon)
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|Epithelial tumours of the breast
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|-
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|Family
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|Rare and salivary gland-type tumours: Introduction
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|-
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|Type
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|Tall cell carcinoma with reversed polarity
 
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|-
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|'''Laboratory Findings'''
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|Subtype(s)
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|EXAMPLE Cytopenias
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|N/A
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EXAMPLE Lymphocytosis (low level)
   
|}
 
|}
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==Sites of Involvement==
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==WHO Essential and Desirable Genetic Diagnostic Criteria==
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{| class="wikitable"
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Put your text here
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|WHO Essential Criteria (Genetics)*
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==Morphologic Features==
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Put your text here
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==Immunophenotype==
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Put your text here and fill in the table
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{| class="wikitable sortable"
   
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!Finding!!Marker
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|WHO Desirable Criteria (Genetics)*
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|''IDH2'' mutation
 
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|Positive (universal)||EXAMPLE CD1
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|Other Classification
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|
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|}
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<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
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==Related Terminology==
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{| class="wikitable"
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|Acceptable
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|
 
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|Positive (subset)||EXAMPLE CD2
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|Not Recommended
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|-
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|
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|Negative (universal)||EXAMPLE CD3
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|-
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|Negative (subset)||EXAMPLE CD4
   
|}
 
|}
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==Chromosomal Rearrangements (Gene Fusions)==
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==Gene Rearrangements==
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<br />
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Put your text here and fill in the table
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{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
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!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
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!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
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!Diagnostic Significance (Yes, No or Unknown)
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!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
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!Prognostic Significance (Yes, No or Unknown)
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!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
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!Therapeutic Significance (Yes, No or Unknown)
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!Established Clinical Significance Per Guidelines - Yes or No (Source)
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!Notes
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!Clinical Relevance Details/Other Notes
 
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|-
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|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
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|
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EXAMPLE 30% (add reference)
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|
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|Yes
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|No
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|
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|Yes
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|
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|EXAMPLE
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|
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|
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|
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|}
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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).
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|}
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==Individual Region Genomic Gain/Loss/LOH==
 
==Individual Region Genomic Gain/Loss/LOH==
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<br />
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Put your text here and fill in the table
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{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
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!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
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!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
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!Diagnostic Significance (Yes, No or Unknown)
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!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
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!Prognostic Significance (Yes, No or Unknown)
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!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
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!Therapeutic Significance (Yes, No or Unknown)
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!'''Clinical Relevance Details/Other Notes'''
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!Notes
   
|-
 
|-
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|EXAMPLE
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|
−
 
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|
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7
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|
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|EXAMPLE Loss
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|
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|EXAMPLE
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|
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|
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chr7:1- 159,335,973 [hg38]
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|
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|EXAMPLE
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chr7
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|Yes
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|Yes
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|No
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|EXAMPLE
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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).
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|-
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|EXAMPLE
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8
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|EXAMPLE Gain
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|EXAMPLE
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chr8:1-145,138,636 [hg38]
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|EXAMPLE
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chr8
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|No
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|No
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|No
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|EXAMPLE
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Common recurrent secondary finding for t(8;21) (add reference).
   
|}
 
|}
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==Characteristic Chromosomal Patterns==
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Put your text here
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==Characteristic Chromosomal or Other Global Mutational Patterns==
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<br />
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Chromosomal Pattern
 
!Chromosomal Pattern
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!Diagnostic Significance (Yes, No or Unknown)
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!Molecular Pathogenesis
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!Prognostic Significance (Yes, No or Unknown)
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!'''Prevalence -'''
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!Therapeutic Significance (Yes, No or Unknown)
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'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
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!Notes
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!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
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!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
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!'''Clinical Relevance Details/Other Notes'''
 
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|-
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|EXAMPLE
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|
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|
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|
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|
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|
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|
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|}
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Co-deletion of 1p and 18q
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|Yes
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|No
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|No
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|EXAMPLE:
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See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
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|}
   
==Gene Mutations (SNV/INDEL)==
 
==Gene Mutations (SNV/INDEL)==
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[[File:IDH2 with protein domain and hotspots.png|left|thumb|769x769px|Diagram of the ''IDH2'' gene (NM_002168) showing the mutational hotspot R172 within the isocitrate dehydrogenase functional domain. Missense mutations at codon 172 result in a substitution for arginine (R) with a different amino acid. Image prepared with the aid of ProteinPaint {26711108} and BioRender software <nowiki>[https://BioRender.com, accessed on 11/4/2025]</nowiki>.]]
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Put your text here and fill in the table
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<br />
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{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
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!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
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!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''
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!'''Diagnostic Significance (Yes, No or Unknown)'''
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'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
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!Prognostic Significance (Yes, No or Unknown)
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!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''
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!Therapeutic Significance (Yes, No or Unknown)
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!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
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!Notes
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!'''Clinical Relevance Details/Other Notes'''
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|-
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|''IDH2''
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|codon 172 mutations
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|Oncogene
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|Common
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|D
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|Yes (WHO)
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|Majority are R172S, R172T; others include R172G, R172W, R172I<ref>{{Cite journal|last=Alsadoun|first=Nadjla|last2=MacGrogan|first2=Gaëtan|last3=Truntzer|first3=Caroline|last4=Lacroix-Triki|first4=Magali|last5=Bedgedjian|first5=Isabelle|last6=Koeb|first6=Marie-Hélène|last7=El Alam|first7=Elsy|last8=Medioni|first8=Dan|last9=Parent|first9=Michel|date=2018-09|title=Solid papillary carcinoma with reverse polarity of the breast harbors specific morphologic, immunohistochemical and molecular profile in comparison with other benign or malignant papillary lesions of the breast: a comparative study of 9 additional cases|url=https://pubmed.ncbi.nlm.nih.gov/29785016|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=31|issue=9|pages=1367–1380|doi=10.1038/s41379-018-0047-1|issn=1530-0285|pmid=29785016}}</ref><ref>{{Cite journal|last=Chiang|first=Sarah|last2=Weigelt|first2=Britta|last3=Wen|first3=Huei-Chi|last4=Pareja|first4=Fresia|last5=Raghavendra|first5=Ashwini|last6=Martelotto|first6=Luciano G.|last7=Burke|first7=Kathleen A.|last8=Basili|first8=Thais|last9=Li|first9=Anqi|date=2016-12-15|title=IDH2 Mutations Define a Unique Subtype of Breast Cancer with Altered Nuclear Polarity|url=https://pubmed.ncbi.nlm.nih.gov/27913435|journal=Cancer Research|volume=76|issue=24|pages=7118–7129|doi=10.1158/0008-5472.CAN-16-0298|issn=1538-7445|pmc=5502804|pmid=27913435}}</ref><ref name=":0">{{Cite journal|last=Lozada|first=John R.|last2=Basili|first2=Thais|last3=Pareja|first3=Fresia|last4=Alemar|first4=Barbara|last5=Paula|first5=Arnaud Da Cruz|last6=Gularte-Merida|first6=Rodrigo|last7=Giri|first7=Dilip D.|last8=Querzoli|first8=Patricia|last9=Cserni|first9=Gabor|date=2018-08|title=Solid papillary breast carcinomas resembling the tall cell variant of papillary thyroid neoplasms (solid papillary carcinomas with reverse polarity) harbour recurrent mutations affecting IDH2 and PIK3CA: a validation cohort|url=https://pubmed.ncbi.nlm.nih.gov/29603332|journal=Histopathology|volume=73|issue=2|pages=339–344|doi=10.1111/his.13522|issn=1365-2559|pmc=6783257|pmid=29603332}}</ref><ref>{{Cite journal|last=Zhong|first=Elaine|last2=Scognamiglio|first2=Theresa|last3=D'Alfonso|first3=Timothy|last4=Song|first4=Wei|last5=Tran|first5=Hung|last6=Baek|first6=Inji|last7=Hoda|first7=Syed A.|date=2019-04|title=Breast Tumor Resembling the Tall Cell Variant of Papillary Thyroid Carcinoma: Molecular Characterization by Next-Generation Sequencing and Histopathological Comparison With Tall Cell Papillary Carcinoma of Thyroid|url=https://pubmed.ncbi.nlm.nih.gov/30227763|journal=International Journal of Surgical Pathology|volume=27|issue=2|pages=134–141|doi=10.1177/1066896918800779|issn=1940-2465|pmid=30227763}}</ref>
 
|-
 
|-
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|EXAMPLE: TP53; Variable LOF mutations
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|''PIK3CA''
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EXAMPLE:
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EGFR; Exon 20 mutations
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EXAMPLE: BRAF; Activating mutations
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|EXAMPLE: TSG
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|EXAMPLE: 20% (COSMIC)
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EXAMPLE: 30% (add Reference)
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|EXAMPLE: IDH1 R123H
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|EXAMPLE: EGFR amplification
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|
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|
   
|
 
|
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|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
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|Oncogene
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<br />
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|Common
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|}
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|T
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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.
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|Yes (NCCN)
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|Co-mutated with ''IDH2''; hotspots include H1047R, E542K, E545K<ref name=":0" />
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|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
    
==Epigenomic Alterations==
 
==Epigenomic Alterations==
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Put your text here
      
==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
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<br />
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Put your text here and fill in the table
   
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
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|-
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|EXAMPLE: BRAF and MAP2K1; Activating mutations
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|''IDH2''
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|EXAMPLE: MAPK signaling
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|Carbon metabolism; carboxylic acid (Krebs) cycle
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|EXAMPLE: Increased cell growth and proliferation
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|Increased conversion of α-ketoglutarate (α-KG) to the oncometabolite ''R''-2-hydroxylglutarate (''R''-2-HG). Increased levels of 2-HG result in hypermethylation of epigenetic targets and a subsequent block in cellular differentiation. Due to widespread hypermethylation, there is increased H3K27me3 nuclear immunoreactivity in tumors harboring ''IDH2'' R172 mutations.
 
|-
 
|-
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|EXAMPLE: CDKN2A; Inactivating mutations
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|''PIK3CA''
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|EXAMPLE: Cell cycle regulation
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|PI3K/AKT/mTOR pathway
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|EXAMPLE: Unregulated cell division
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|Three most common PIK3CA mutations are H1047R, E542K, and E545K; PIK3CA mutations induce hyperactivation of the alpha isoform of the catalytic subunit (p110α) of class IA PI3K kinase. Mutations are often co-occurring with other drivers in ER-positive breast cancers and are associated with endocrine resistance. PIK3CA mutations are targetable with the PI3K inhibitor alpelisib in ER positive breast cancers; however, tall cell carcinoma with reverse polarity is usually ER negative.
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|-
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|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
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|EXAMPLE:  Histone modification, chromatin remodeling
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|EXAMPLE:  Abnormal gene expression program
   
|}
 
|}
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==Genetic Diagnostic Testing Methods==
     −
Put your text here
      +
==Genetic Diagnostic Testing Methods==
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Next generation sequencing (NGS); immunohistochemistry with monoclonal antibodies against ''IDH2'' mutant codon R172S (monoclonal antibody clone 11C8B1 is reactive against R172S or R172T)<ref>{{Cite journal|last=Pareja|first=Fresia|last2=da Silva|first2=Edaise M.|last3=Frosina|first3=Denise|last4=Geyer|first4=Felipe C.|last5=Lozada|first5=John R.|last6=Basili|first6=Thais|last7=Da Cruz Paula|first7=Arnaud|last8=Zhong|first8=Elaine|last9=Derakhshan|first9=Fatemeh|date=2020-06|title=Immunohistochemical analysis of IDH2 R172 hotspot mutations in breast papillary neoplasms: applications in the diagnosis of tall cell carcinoma with reverse polarity|url=https://pubmed.ncbi.nlm.nih.gov/31896809|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=33|issue=6|pages=1056–1064|doi=10.1038/s41379-019-0442-2|issn=1530-0285|pmc=7286791|pmid=31896809}}</ref>; pyrosequencing; Sanger sequencing; PCR with allele detection (examples include PCR with melting curve analysis, or PCR with use of allele-specific probes); allele-specific PCR; single base extension.  
 
==Familial Forms==
 
==Familial Forms==
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None
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==Additional Information==
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<br />
 +
==Links==
 +
<nowiki>https://www.pathologyoutlines.com/topic/breastmalignantspcrp.html</nowiki>
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Put your text here
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<br />
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==Notes==
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==Additional Information==
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Put your text here
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<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 [[Leadership|''<u>Associate Editor</u>'']] or other CCGA representative.  When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
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==Links==
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Prior Author(s):
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Put your text placeholder here (use "Link" icon at top of page)
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<br />
 
==References==
 
==References==
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(use "Cite" icon at top of page)
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<references />
     −
'''EXAMPLE Book'''
  −
#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==
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(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. 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. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span>
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<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.
+
<references />
 +
<nowiki>*</nowiki>''Citation of this Page'': “Tall cell carcinoma with reversed polarity”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/BRST5:Tall cell carcinoma with reversed polarity</nowiki>.
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[[Category:BRST5]]
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[[Category:DISEASE]]
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[[Category:Diseases T]]
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