Changes

BRST5:Tall Cell Carcinoma with Reversed Polarity (view source)

Revision as of 12:26, 13 October 2023

33 bytes removed , 12:26, 13 October 2023

no edit summary

Line 19: Line 19:

==Synonyms / Terminology==

−

* Breast tumor resembling tall cell variant of papillary thyroid carcinoma

+

*Breast tumor resembling tall cell variant of papillary thyroid carcinoma

−

* Solid papillary breast carcinoma resembling the tall cell variant of papillary thyroid neoplasms (Historical)

+

*Solid papillary breast carcinoma resembling the tall cell variant of papillary thyroid neoplasms (Historical)

−

* Breast cancer with altered nuclear polarity (Historical)

+

*Breast cancer with altered nuclear polarity (Historical)

−

* Solid papillary carcinoma with reverse polarity (Historical)

+

*Solid papillary carcinoma with reverse polarity (Historical)

−

* Tall cell variant of papillary breast carcinoma (Historical)

+

*Tall cell variant of papillary breast carcinoma (Historical)

==Epidemiology / Prevalence==

Line 47: Line 47:

==Morphologic Features==

−

* Circumscribed nests of cells, many of which have fibrovascular cores. Foamy histiocytes are often present within the fibrovascular cores.

+

*Circumscribed nests of cells, many of which have fibrovascular cores. Foamy histiocytes are often present within the fibrovascular cores.

−

* Occasionally true papillae and cyst-like structures with colloid-like material are identified.

+

*Occasionally true papillae and cyst-like structures with colloid-like material are identified.

−

* Epithelial cells are tall, may have nuclear grooves and intranuclear cytoplasmic inclusions.

+

*Epithelial cells are tall, may have nuclear grooves and intranuclear cytoplasmic inclusions.

−

* The most characteristic feature is the presence of nuclei in the apical rather than basal pole of the cells hence the “reverse polarity”.

+

*The most characteristic feature is the presence of nuclei in the apical rather than basal pole of the cells hence the “reverse polarity”.

==Immunophenotype<ref name=":0">{{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 name=":1">{{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=":2">{{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 name=":3">{{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><ref name=":4">{{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>==

−

* Most carcinomas do not express estrogen or progesterone receptors (ER, PR). Those that tend to show staining of only a small fraction of the cells.

+

*Most carcinomas do not express estrogen or progesterone receptors (ER, PR). Those that tend to show staining of only a small fraction of the cells.

−

* No cases reported to be HER2 positive (3+) or amplified by ISH.

+

*No cases reported to be HER2 positive (3+) or amplified by ISH.

−

* Proliferative index (Ki67) has been less than 20%.

+

*Proliferative index (Ki67) has been less than 20%.

{| class="wikitable sortable"

Line 62: Line 62:

!Finding!!Marker

|-

−

|Positive (universal)||Cytokeratin 7, cytokeratin 5/6

+

|Positive (universal)||Cytokeratin 7, cytokeratin 5/6

|-

−

|Positive (subset)||GCDFP-15, GATA3, IDH1/2 mutant, calretinin

+

|Positive (subset)||GCDFP-15, GATA3, IDH1/2 mutant, calretinin

|-

−

|Negative (universal)||HER2 (ERBB2) expression or amplification; TTF-1, thyroglobulin, myoepithelial markers (p63, myosin)

+

|Negative (universal)||HER2 (ERBB2) expression or amplification; TTF-1, thyroglobulin, myoepithelial markers (p63, myosin)

|-

|Negative (subset)||

Line 96: Line 96:

!Therapeutic Significance (Yes, No or Unknown)

!Notes

−

|-

−

|

−

|

−

|

−

|

−

|

−

|

−

|

−

|

|-

|

Line 170: Line 161:

!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

|-

−

|''IDH2'' codon 172 mutations (majority are R172S, R172T; other mutations include R172G, R172W, R172I)

+

|''IDH2'' codon 172 mutations (majority are R172S, R172T; other mutations include R172G, R172W, R172I)

−

|Carbon metabolism: citrate cycle

+

|Carbon metabolism: citrate 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.

+

|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'' mutations: H1047R most common

+

|''PIK3CA'' mutations: H1047R most common

−

|PI3K/AKT/mTOR pathway

+

|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.

+

|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.

|-

|

Line 205: Line 196:

==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.

+

Kgeiersbach

Editors, Reviewers

50

edits