Evidence map›Paper›PMID 32461623›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2020

CYLD-mutant cylindroma-like basaloid carcinoma of the anus: a genetically and morphologically distinct class of HPV-related anal carcinoma.

Erik A Williams, Meagan Montesion, Radwa Sharaf, James Corines, Parth J Patel, Brendan J Gillespie, Dean C Pavlick, Ethan S Sokol, Brian M Alexander, Kevin Jon Williams and 6 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
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

11 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. CYLD in health and disease.Disease models & mechanisms · 2023
    Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
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

16 authors at 6 institutions in 1 country.

Erik A WilliamsFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA. erwilliams@foundationmedicine.com.ORCID http://orcid.org/0000-0002-9190-2450
Meagan MontesionFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.ORCID http://orcid.org/0000-0001-9155-556X
Radwa SharafFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.
James CorinesDepartment of Pathology, State University of New York Upstate Medical University, 766 Irving Avenue, Syracuse, NY, 13210, USA.
Parth J PatelDepartment of Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA.
Brendan J GillespieFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.
Dean C PavlickFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.
Ethan S SokolFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.
Brian M AlexanderFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.
Kevin Jon WilliamsDepartment of Physiology and Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA.
Julia A ElvinFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.
Jeffrey S RossFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.
Shakti H RamkissoonFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.
Amanda C HemmerichFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.
Julie Y TseFoundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA.
Mark C MochelDepartments of Pathology and Dermatology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA.ORCID http://orcid.org/0000-0001-7306-8813
Foundation Medicine (United States)SUNY Upstate Medical University · USTemple University · USTech Foundation · USTufts University · USVirginia Commonwealth University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rare reports of anal carcinoma (AC) describe histologic resemblance to cutaneous cylindroma, but mutations in the tumor suppressor CYLD, the gene responsible for familial and sporadic cylindromas, have not been systematically investigated in AC. Here, we investigate CYLD-mutant AC, focusing on molecular correlates of distinct histopathology. Comprehensive genomic profiling (hybrid-capture-based DNA sequencing) was performed on 574 ACs, of which 75 unique cases (13%) harbored a CYLD mutation. Clinical data, pathology reports, and histopathology were reviewed for each CYLD-mutant case. The spectrum of CYLD mutations included truncating (n = 50; 67%), homozygous deletion (n = 10; 13%), missense (n = 16; 21%), and splice-site (n = 3; 4%) events. Compared with CYLD-wildtype AC (n = 499), CYLD-mutant ACs were significantly enriched for females (88% vs. 67%, p = 0.0001), slightly younger (median age 59 vs. 61 years, p = 0.047), and included near-universal detection of high-risk HPV sequences (97% vs. 88%, p = 0.014), predominantly HPV16 (96%). The CYLD-mutant cohort also showed significantly lower tumor mutational burden (TMB; median 2.6 vs. 5.2 mut/Mb, p < 0.00001) and less frequent alterations in PIK3CA (13% vs. 31%, p = 0.0015). On histopathologic examination, 73% of CYLD-mutant AC (55/75 cases) showed a striking cylindroma-like histomorphology, composed of aggregates of basaloid cells surrounded by thickened basement membranes and containing characteristic hyaline globules, while only 8% of CYLD-wildtype tumors (n = 34/409) contained cylindroma-like hyaline globules (p < 0.0001). CYLD-mutant carcinomas with cylindroma-like histomorphology (n = 55) showed significantly lower TMB compared with CYLD-mutant cases showing basaloid histology without the distinctive hyaline globules (n = 14) (median 1.7 vs. 4.4 mut/Mb, p = 0.0058). Only five CYLD-mutant cases (7%) showed nonbasaloid conventional squamous cell carcinoma histology (median TMB = 5.2 mut/Mb), and a single CYLD-mutant case showed transitional cell carcinoma-like histology. Within our cohort of ACs, CYLD mutations characterize a surprisingly large subset (13%), with distinct clinical and genomic features and, predominantly, a striking cylindroma-like histopathology, representing a genotype-phenotype correlation which may assist in classification of AC.

Indexed as

MutationAdultAgedAged, 80 and overAlphapapillomavirusAnus NeoplasmsBiomarkers, TumorCarcinoma, Adenoid CysticCell Transformation, ViralDeubiquitinating Enzyme CYLDDNA Mutational AnalysisFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedBiomarkers, TumorCYLD protein, humanDeubiquitinating Enzyme CYLDRNA Splice Sites

Identifiers

PMID32461623
PMCPMC7685972
OpenAlexW3032310548

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.