Evidence map›Paper›PMID 42166008›Full record

ArticleVirchows Archiv : an international journal of pathology2026

Clinicopathologic characterization of renal tumors with Folliculin (FLCN) biallelic inactivation.

Stephanie E Siegmund, Sara E Wobker, Lara R Harik, Maria Tretiakova, Shivani Kandukuri, Kiril Trpkov, Fiona Maclean, Igor Odintsov, Michel Alchoueiry, Manju Aron and 8 more

Abstract readMulticenter Study
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In one paragraph

Article in Virchows Archiv : an international journal of pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Stephanie E SiegmundDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Sara E WobkerThe Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Lara R HarikDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Maria TretiakovaDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.
Shivani KandukuriDepartment of Pathology, University of California at Irvine Medical Center, Irvine, CA, USA.
Kiril TrpkovDiagnostic and Molecular Pathology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Fiona MacleanFaculty of Medicine, Health and Human Sciences, Douglass Hanly Moir Pathology, Macquarie University, Sydney, NSW, Australia.
Igor OdintsovDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Michel AlchoueiryDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Manju AronDepartment of Pathology, Keck School of Medicine of USC, Los Angeles, CA, USA.
Maria M PickenDepartment of Pathology, Loyola University Medical Center, Maywood, IL, USA.
Jonathon MahlowDepartment of Pathology, Huntsman Cancer Institute - University of Utah, Salt Lake City, Utah, USA.
Adebowale J AdeniranThe Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Peter A HumphreyThe Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Holger MochDepartment of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.
Harrison TsaiDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Elizabeth P HenskeDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Michelle S HirschDepartment of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. mhirsch1@bwh.harvard.edu.ORCID http://orcid.org/0000-0002-8767-8564

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder caused by germline inactivation of the folliculin gene (FLCN). Approximately 25% of BHD syndrome patients are diagnosed with renal tumors, which can be multifocal and/or bilateral. These tumors have been reported to span a broad histologic spectrum; however, the majority exhibit a distinctive histology characterized by intermingled cytologic features similar to that seen in oncocytoma and chromophobe renal cell carcinoma. Accordingly, such tumors were previously termed 'hybrid oncocytic chromophobe tumor' (HOCT). To date, most studies have characterized tumors arising in BHD syndrome patients without molecular confirmation of FLCN biallelic inactivation; accordingly, the clinicopathologic characterization of molecularly confirmed FLCN biallelic inactivated tumors remains limited. This study evaluates a multi-institutional cohort of 18 renal tumors from different individuals, including integrated histologic, immunohistochemical, and targeted next-generation sequencing analyses. While all patients exhibited clinical characteristics raising suspicion for BHD syndrome, germline status was not available in 5 patients. Nevertheless, molecular analysis demonstrated findings supportive of FLCN biallelic inactivation in all patients, and there were no other candidate driver alterations or recurrent molecular findings. Histologically, most tumors showed 'conventional' histology consisting of solid or nested growth with a characteristic mosaic population of eosinophilic and clear cells and low-grade nuclear features, including frequent perinuclear halos and binucleation. Two cases showed 'non-conventional' histology including tubulocystic and tubulopapillary architecture. Immunohistochemistry revealed consistent GPNMB expression and a distinctive mosaic staining pattern for KRT7, L1CAM, and GATA3, aiding distinction from other eosinophilic renal neoplasms. Follow-up was available for 17 patients (median 37 months, range 1-110 months). Both patients with non-conventional morphology demonstrated advanced stage at presentation, including one with metastatic disease. Collectively, these findings define one of the largest molecularly-confirmed cohorts of FLCN biallelic inactivated tumors to date and support recognition of FLCN-driven tumors as a distinct, molecularly defined entity.

Indexed as

Biomarkers, TumorBirt-Hogg-Dube SyndromeKidney NeoplasmsProto-Oncogene ProteinsTumor Suppressor ProteinsAdultAgedFemaleHumansImmunohistochemistryMaleMiddle AgedBiomarkers, TumorFLCN protein, humanProto-Oncogene ProteinsTumor Suppressor ProteinsBiallelic inactivationBirt Hogg DubeFolliculin (FLCN)GPNMBImmunohistochemistryKidneyNext generation sequencingRenal

Identifiers

PMID42166008

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.