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Peer-reviewedCC BY 4.0Histopathology

Additional sectioning and AI‐assisted diagnosis reveal underdiagnosis of serous (pre)malignancies in fallopian tube specimen from BRCA1/2 carriers

  • Anouk B Bouwmeester1
  • Tamar A Gootzen2
  • Marielle Nobbenhuis3
  • Vilius Rudaitis4
  • Caroline B van den Berg5
  • Heleen J van Beekhuizen5
  • Luthy SM Alcalá6
  • Dineke PM Smedts7
  • Nicole CM Visser8
  • Viola Verhoef9
  • Trudy GN Jonges10
  • Ronald P Zweemer11
6 more authors
  • Alicia Leon‐Catillo12
  • Carlijn Lems1
  • Joanne A de Hullu2
  • Jeroen AWM van der Laak1
  • Miranda P Steenbeek2,13
  • Michiel Simons1
13 affiliations
  1. 1Department of Pathology Radboudumc Nijmegen the Netherlands
  2. 2Department of Gynecology and Obstetrics Radboudumc Nijmegen the Netherlands
  3. 3Department of Gynecological Oncology The Royal Marsden NHS Foundation Trust London UK
  4. 4Faculty of Medicine, Clinic of Obstetrics and Gynecology Vilnius University Vilnius Lithuania
  5. 5Department of Gynecology and Obstetrics ErasmusMC Rotterdam the Netherlands
  6. 6Department of Pathology Amphia hospital Breda the Netherlands
  7. 7Department of Gynecology and Obstetrics Amphia hospital Breda the Netherlands
  8. 8Department of Pathology PAMM Eindhoven the Netherlands
  9. 9Department of Gynecology and Obstetrics Maxima Medical Center Veldhoven the Netherlands
  10. 10Department of Pathology University Medical Center Utrecht Utrecht the Netherlands
  11. 11Department of Gynecological Oncology University Medical Center Utrecht Utrecht the Netherlands
  12. 12Department of Pathology Antoni van Leeuwenhoek Amsterdam the Netherlands
  13. 13Department of Gynecology and Obstetrics Catharina Hospital Eindhoven the Netherlands
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Abstract

Aim: Germline BRCA1/2 pathogenic variant carriers are at increased risk for high‐grade serous carcinoma (HGSC) and are therefore advised to have a risk‐reducing salpingo‐oophorectomy (RRSO) around the age of 40. A risk of 0.9% to develop peritoneal HGSC (pHGSC) remains, which increases up to 27.5% when serous tubal intraepithelial carcinoma (STIC) is detected at RRSO. The relationship between the detection of STIC and the occurrence of pHGSC is still poorly understood. Here, we investigated the role of tissue sampling by examining deeper sections of the tubal tissue of RRSO specimens.

Methods: Four groups of patients were included: (1) STIC without pHGSC (n = 5); (2) STIC with pHGSC (n = 4); (3) no STIC and no pHGSC (n = 5); and (4) no STIC and pHGSC (n = 5). Follow‐up time was 10 years or until the development of pHGSC. Deeper sections were cut at 150 μm intervals. A deep learning model was used to support STIC detection.

Results: A focus of isolated STIC or HGSC was found in the deeper sections of all patients who developed pHGSC, while these patients did not have STIC or HGSC at the initial diagnosis. No patients with STIC and pHGSC showed HGSC in the deeper sections. We observed that five STICs presented as serous tubal intraepithelial lesions (STILs) in adjacent slides based on low Ki‐67 expression.

Conclusions: Our findings underscore the hypothesis that pHGSC originates in the fallopian tube and confirm that invasiveness is not necessary for disease progression of STIC towards pHGSC. Furthermore, deeper sections might be of additional value when STIL is diagnosed.

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Cite

BibTeXRIS
BibTeX
@article{bouwmeester2026additional,
  title = {{Additional sectioning and AI‐assisted diagnosis reveal underdiagnosis of serous (pre)malignancies in fallopian tube specimen from BRCA1/2 carriers}},
  author = {Anouk B Bouwmeester and Tamar A Gootzen and Marielle Nobbenhuis and Vilius Rudaitis and Caroline B van den Berg and Heleen J van Beekhuizen and Luthy SM Alcalá and Dineke PM Smedts and Nicole CM Visser and Viola Verhoef and Trudy GN Jonges and Ronald P Zweemer and Alicia Leon‐Catillo and Carlijn Lems and Joanne A de Hullu and Jeroen AWM van der Laak and Miranda P Steenbeek and Michiel Simons},
  journal = {Histopathology},
  year = {2026},
  month = aug,
  doi = {10.1111/his.70249},
  url = {https://doi.org/10.1111/his.70249},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Additional sectioning and AI‐assisted diagnosis reveal underdiagnosis of serous (pre)malignancies in fallopian tube specimen from BRCA1/2 carriers
AU  - Anouk B Bouwmeester
AU  - Tamar A Gootzen
AU  - Marielle Nobbenhuis
AU  - Vilius Rudaitis
AU  - Caroline B van den Berg
AU  - Heleen J van Beekhuizen
AU  - Luthy SM Alcalá
AU  - Dineke PM Smedts
AU  - Nicole CM Visser
AU  - Viola Verhoef
AU  - Trudy GN Jonges
AU  - Ronald P Zweemer
AU  - Alicia Leon‐Catillo
AU  - Carlijn Lems
AU  - Joanne A de Hullu
AU  - Jeroen AWM van der Laak
AU  - Miranda P Steenbeek
AU  - Michiel Simons
PY  - 2026
DA  - 2026/08/12
JO  - Histopathology
DO  - 10.1111/his.70249
UR  - https://doi.org/10.1111/his.70249
AB  - Aim: Germline BRCA1/2 pathogenic variant carriers are at increased risk for high‐grade serous carcinoma (HGSC) and are therefore advised to have a risk‐reducing salpingo‐oophorectomy (RRSO) around the age of 40. A risk of 0.9% to develop peritoneal HGSC (pHGSC) remains, which increases up to 27.5% when serous tubal intraepithelial carcinoma (STIC) is detected at RRSO. The relationship between the detection of STIC and the occurrence of pHGSC is still poorly understood. Here, we investigated the role of tissue sampling by examining deeper sections of the tubal tissue of RRSO specimens.  Methods: Four groups of patients were included: (1) STIC without pHGSC (n = 5); (2) STIC with pHGSC (n = 4); (3) no STIC and no pHGSC (n = 5); and (4) no STIC and pHGSC (n = 5). Follow‐up time was 10 years or until the development of pHGSC. Deeper sections were cut at 150 μm intervals. A deep learning model was used to support STIC detection.  Results: A focus of isolated STIC or HGSC was found in the deeper sections of all patients who developed pHGSC, while these patients did not have STIC or HGSC at the initial diagnosis. No patients with STIC and pHGSC showed HGSC in the deeper sections. We observed that five STICs presented as serous tubal intraepithelial lesions (STILs) in adjacent slides based on low Ki‐67 expression.  Conclusions: Our findings underscore the hypothesis that pHGSC originates in the fallopian tube and confirm that invasiveness is not necessary for disease progression of STIC towards pHGSC. Furthermore, deeper sections might be of additional value when STIL is diagnosed.
SN  - 0309-0167
SN  - 1365-2559
ER  -