BRST5:Tall cell carcinoma with reversed polarity

Breast Tumours (WHO Classification, 5th ed.)

Primary Author(s)*

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

WHO Classification of Disease

Structure	Disease
Book	Breast Tumours (5th ed.)
Category	Epithelial tumours of the breast
Family	Rare and salivary gland-type tumours: Introduction
Type	Tall cell carcinoma with reversed polarity
Subtype(s)	N/A

WHO Essential and Desirable Genetic Diagnostic Criteria

WHO Essential Criteria (Genetics)*
WHO Desirable Criteria (Genetics)*	IDH2 mutation
Other Classification

*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.

Related Terminology

Acceptable
Not Recommended

Gene Rearrangements

Driver Gene	Fusion(s) and Common Partner Genes	Molecular Pathogenesis	Typical Chromosomal Alteration(s)	Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes

Individual Region Genomic Gain/Loss/LOH

Chr #	Gain, Loss, Amp, LOH	Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]	Relevant Gene(s)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes

Characteristic Chromosomal or Other Global Mutational Patterns

Chromosomal Pattern	Molecular Pathogenesis	Prevalence - Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes

Gene Mutations (SNV/INDEL)

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 [https://BioRender.com, accessed on 11/4/2025].

Gene	Genetic Alteration	Tumor Suppressor Gene, Oncogene, Other	Prevalence - Common >20%, Recurrent 5-20% or Rare <5% (Disease)	Diagnostic, Prognostic, and Therapeutic Significance - D, P, T	Established Clinical Significance Per Guidelines - Yes or No (Source)	Clinical Relevance Details/Other Notes
IDH2	codon 172 mutations	Oncogene	Common	D	Yes (WHO)	Majority are R172S, R172T; others include R172G, R172W, R172I
PIK3CA		Oncogene	Common	T	Yes (NCCN)	Co-mutated with IDH2; hotspots include H1047R, E542K, E545K

Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Genes and Main Pathways Involved

Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
IDH2	Carbon metabolism; carboxylic acid (Krebs) cycle	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.
PIK3CA	PI3K/AKT/mTOR pathway	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.

Genetic Diagnostic Testing Methods

Next generation sequencing (NGS); immunohistochemistry with monoclonal antibodies against IDH2 mutant codon R172S (monoclonal antibody clone 11C8B1 is reactive against R172S or R172T); 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

None

Links

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

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 Associate Editor 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.

Prior Author(s):

References

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*Citation of this Page: “Tall cell carcinoma with reversed polarity”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 04/16/2025, https://ccga.io/index.php/BRST5:Tall cell carcinoma with reversed polarity.