Primary Mucinous Tumors of the Ovary: An Interobserver
Reproducibility and Detailed Molecular Study Reveals
Significant Overlap Between Diagnostic Categories

J 2023

Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories

DUNDR, Pavel, Michaela BÁRTŮ, Tjalling BOSSE, Quang Hiep BUI, David CIBULA et. al.

Basic information

Original name

Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories

Authors

DUNDR, Pavel (203 Czech Republic, guarantor), Michaela BÁRTŮ (203 Czech Republic), Tjalling BOSSE, Quang Hiep BUI, David CIBULA (203 Czech Republic), Jana DROZENOVÁ (203 Czech Republic), Pavel FABIAN (203 Czech Republic), Oluwole FADARE, Jitka HAUSNEROVÁ (203 Czech Republic, belonging to the institution), Jan HOJNÝ (203 Czech Republic), Nikola HÁJKOVÁ (203 Czech Republic), Radek JAKŠA (203 Czech Republic), Jan LACO (203 Czech Republic), Sigurd F. LAX, Radoslav MATĚJ (203 Czech Republic), Gábor MÉHES, Romana MICHÁLKOVÁ (203 Czech Republic), Adam ŠAFANDA (203 Czech Republic), Kristýna NĚMEJCOVÁ (203 Czech Republic), Naveena SINGH, Simona STOLNICU, Marián ŠVAJDLER (203 Czech Republic), Tomáš ZIMA (203 Czech Republic), Ivana STRUŽINSKÁ (203 Czech Republic) and W Glenn MCCLUGGAGE

Edition

Modern Pathology, NEW YORK, ELSEVIER SCIENCE INC, 2023, 0893-3952

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30109 Pathology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 7.500 in 2022

RIV identification code

RIV/00216224:14110/23:00130743

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.modpat.2022.100040

UT WoS

000982550100001

Keywords in English

borderline; diagnostic agreement; mucinous tumors; next-generation sequencing; ovary; therapeutic targets

Abstract

V originále

Primary ovarian mucinous tumors represent a heterogeneous group of neoplasms, and their diagnosis may be challenging. We analyzed 124 primary ovarian mucinous tumors originally diagnosed as mucinous borderline tumors (MBTs) or mucinous carcinomas (MCs), with an emphasis on interobserver diagnostic agreement and the potential for diagnostic support by molecular profiling using a next-generation sequencing targeted panel of 727 DNA and 147 RNA genes. Fourteen experienced pathologists independently assigned a diagnosis from preset options, based on a review of a single digitized slide from each tumor. After excluding 1 outlier participant, there was a moderate agreement in diagnosing the 124 cases when divided into 3 categories (κ = 0.524, for mucinous cystadenoma vs MBT vs MC). A perfect agreement for the distinction between mucinous cystadenoma/MBT as a combined category and MC was found in only 36.3% of the cases. Differentiating between MBTs and MCs with expansile invasion was particularly problematic. After a reclassification of the tumors into near-consensus diagnostic categories on the basis of the initial participant results, a comparison of molecular findings between the MBT and MC groups did not show major and unequivocal differences between MBTs and MCs or between MCs with expansile vs infiltrative pattern of invasion. In contrast, HER2 overexpression or amplification was found only in 5.3% of MBTs and in 35.3% of all MCs and in 45% of MCs with expansile invasion. Overall, HER2 alterations, including mutations, were found in 42.2% of MCs. KRAS mutations were found in 65.5% and PIK3CA mutations in 6% of MCs. In summary, although the diagnostic criteria are well-described, diagnostic agreement among our large group of experienced gynecologic pathologists was only moderate. Diagnostic categories showed a molecular overlap. Nonetheless, molecular profiling may prove to be therapeutically beneficial in advanced-stage, recurrent, or metastatic MCs.

Links

90125, large research infrastructures

Name: BBMRI-CZ III

Citovat

DUNDR, Pavel, Michaela BÁRTŮ, Tjalling BOSSE, Quang Hiep BUI, David CIBULA, Jana DROZENOVÁ, Pavel FABIAN, Oluwole FADARE, Jitka HAUSNEROVÁ, Jan HOJNÝ, Nikola HÁJKOVÁ, Radek JAKŠA, Jan LACO, Sigurd F. LAX, Radoslav MATĚJ, Gábor MÉHES, Romana MICHÁLKOVÁ, Adam ŠAFANDA, Kristýna NĚMEJCOVÁ, Naveena SINGH, Simona STOLNICU, Marián ŠVAJDLER, Tomáš ZIMA, Ivana STRUŽINSKÁ and W Glenn MCCLUGGAGE. Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories. Modern Pathology. NEW YORK: ELSEVIER SCIENCE INC, 2023, vol. 36, No 1, p. 1-14. ISSN 0893-3952. Available from: https://dx.doi.org/10.1016/j.modpat.2022.100040.

@article{2281361,
   author = {Dundr, Pavel and Bártů, Michaela and Bosse, Tjalling and Bui, Quang Hiep and Cibula, David and Drozenová, Jana and Fabian, Pavel and Fadare, Oluwole and Hausnerová, Jitka and Hojný, Jan and Hájková, Nikola and Jakša, Radek and Laco, Jan and Lax, Sigurd F. and Matěj, Radoslav and Méhes, Gábor and Michálková, Romana and Šafanda, Adam and Němejcová, Kristýna and Singh, Naveena and Stolnicu, Simona and Švajdler, Marián and Zima, Tomáš and Stružinská, Ivana and McCluggage, W Glenn},
   article_location = {NEW YORK},
   article_number = {1},
   doi = {http://dx.doi.org/10.1016/j.modpat.2022.100040},
   keywords = {borderline; diagnostic agreement; mucinous tumors; next-generation sequencing; ovary; therapeutic targets},
   language = {eng},
   issn = {0893-3952},
   journal = {Modern Pathology},
   title = {Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories},
   url = {https://www.sciencedirect.com/science/article/pii/S0893395222000400},
   volume = {36},
   year = {2023}
}

TY  - JOUR
ID  - 2281361
AU  - Dundr, Pavel - Bártů, Michaela - Bosse, Tjalling - Bui, Quang Hiep - Cibula, David - Drozenová, Jana - Fabian, Pavel - Fadare, Oluwole - Hausnerová, Jitka - Hojný, Jan - Hájková, Nikola - Jakša, Radek - Laco, Jan - Lax, Sigurd F. - Matěj, Radoslav - Méhes, Gábor - Michálková, Romana - Šafanda, Adam - Němejcová, Kristýna - Singh, Naveena - Stolnicu, Simona - Švajdler, Marián - Zima, Tomáš - Stružinská, Ivana - McCluggage, W Glenn
PY  - 2023
TI  - Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories
JF  - Modern Pathology
VL  - 36
IS  - 1
SP  - 1-14
EP  - 1-14
PB  - ELSEVIER SCIENCE INC
SN  - 08933952
KW  - borderline
KW  - diagnostic agreement
KW  - mucinous tumors
KW  - next-generation sequencing
KW  - ovary
KW  - therapeutic targets
UR  - https://www.sciencedirect.com/science/article/pii/S0893395222000400
N2  - Primary ovarian mucinous tumors represent a heterogeneous group of neoplasms, and their diagnosis may be challenging. We analyzed 124 primary ovarian mucinous tumors originally diagnosed as mucinous borderline tumors (MBTs) or mucinous carcinomas (MCs), with an emphasis on interobserver diagnostic agreement and the potential for diagnostic support by molecular profiling using a next-generation sequencing targeted panel of 727 DNA and 147 RNA genes. Fourteen experienced pathologists independently assigned a diagnosis from preset options, based on a review of a single digitized slide from each tumor. After excluding 1 outlier participant, there was a moderate agreement in diagnosing the 124 cases when divided into 3 categories (κ = 0.524, for mucinous cystadenoma vs MBT vs MC). A perfect agreement for the distinction between mucinous cystadenoma/MBT as a combined category and MC was found in only 36.3% of the cases. Differentiating between MBTs and MCs with expansile invasion was particularly problematic. After a reclassification of the tumors into near-consensus diagnostic categories on the basis of the initial participant results, a comparison of molecular findings between the MBT and MC groups did not show major and unequivocal differences between MBTs and MCs or between MCs with expansile vs infiltrative pattern of invasion. In contrast, HER2 overexpression or amplification was found only in 5.3% of MBTs and in 35.3% of all MCs and in 45% of MCs with expansile invasion. Overall, HER2 alterations, including mutations, were found in 42.2% of MCs. KRAS mutations were found in 65.5% and PIK3CA mutations in 6% of MCs. In summary, although the diagnostic criteria are well-described, diagnostic agreement among our large group of experienced gynecologic pathologists was only moderate. Diagnostic categories showed a molecular overlap. Nonetheless, molecular profiling may prove to be therapeutically beneficial in advanced-stage, recurrent, or metastatic MCs.
ER  -

DUNDR, Pavel, Michaela BÁRTŮ, Tjalling BOSSE, Quang Hiep BUI, David CIBULA, Jana DROZENOVÁ, Pavel FABIAN, Oluwole FADARE, Jitka HAUSNEROVÁ, Jan HOJNÝ, Nikola HÁJKOVÁ, Radek JAKŠA, Jan LACO, Sigurd F. LAX, Radoslav MATĚJ, Gábor MÉHES, Romana MICHÁLKOVÁ, Adam ŠAFANDA, Kristýna NĚMEJCOVÁ, Naveena SINGH, Simona STOLNICU, Marián ŠVAJDLER, Tomáš ZIMA, Ivana STRUŽINSKÁ and W Glenn MCCLUGGAGE. Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories. \textit{Modern Pathology}. NEW YORK: ELSEVIER SCIENCE INC, 2023, vol.~36, No~1, p.~1-14. ISSN~0893-3952. Available from: https://dx.doi.org/10.1016/j.modpat.2022.100040.

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