Evidence map›Paper›PMID 41848733›Full record

ArticleJAMA network open2026

An AI Approach to Differentiating Lung Squamous Cell Carcinoma From Metastases of Other Origins.

Mark G Evans, Jennifer R Ribeiro, Todd Maney, Anthony Helmstetter, Jennifer Johnson, Anthony N Karnezis, Casey Bales, George W Sledge, David Spetzler, Ari Vanderwalde and 7 more

Abstract read
In one paragraph

Article in JAMA network open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

17 authors.

Mark G EvansCaris Life Sciences, Phoenix, Arizona.
Jennifer R RibeiroCaris Life Sciences, Phoenix, Arizona.
Todd ManeyCaris Life Sciences, Phoenix, Arizona.
Anthony HelmstetterCaris Life Sciences, Phoenix, Arizona.
Jennifer JohnsonDepartments of Medical Oncology and Otolaryngology, Thomas Jefferson University, Philadelphia, Pennsylvania.
Anthony N KarnezisUC Davis Health, Sacramento, California.
Casey BalesCaris Life Sciences, Phoenix, Arizona.
George W SledgeCaris Life Sciences, Phoenix, Arizona.
David SpetzlerCaris Life Sciences, Phoenix, Arizona.
Ari VanderwaldeCaris Life Sciences, Phoenix, Arizona.
Matthew OberleyCaris Life Sciences, Phoenix, Arizona.
Balazs HalmosDepartments of Oncology and Medicine, Albert Einstein College of Medicine, Bronx, New York.
Hossein BorghaeiFox Chase Cancer Center, Philadelphia, Pennsylvania.
Farah AbdullaCaris Life Sciences, Phoenix, Arizona.
David BryantCaris Life Sciences, Phoenix, Arizona.
Fred R HirschTisch Cancer Institute at Mount Sinai, New York, New York.
Hassan GhaniCaris Life Sciences, Phoenix, Arizona.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Importance: Distinguishing primary lung squamous cell carcinoma (SCC) from squamous metastases to the lung is a clinical challenge due to histopathologic similarities. Accurate diagnosis is essential to guide treatment decisions. Objective: To assess the utility of an artificial intelligence (AI) approach that includes evaluation of key orthogonal evidence in distinguishing primary lung SCCs from metastatic tumors of other tissue origins. Design, Setting, and Participants: This cross-sectional study used GPSai, a tissue-of-origin AI model run automatically on each sample submitted for molecular profiling, to flag potential misdiagnoses among research-eligible cases submitted as lung SCC. Molecularly profiled cases within the Caris Life Sciences clinicogenomic database from January 1, 2024, to January 31, 2025, were queried. All cases were reviewed by board-certified pathologists. Main Outcomes and Measures: The primary outcome was the rate of misdiagnosis among presumed lung SCCs confirmed by pathologist review and orthogonal evidence, which included clinical history and clinical findings, GATA3 and uroplakin II immunohistochemistry for urothelial carcinoma, UV variant signature for cutaneous SCC, CD5 and CD117 (c-KIT) immunohistochemistry for thymic carcinoma, and human papillomavirus positivity for orogenital SCC (eg, head and neck, cervical). Results: Through a combination of AI and orthogonal evidence, 123 (3.1%) misdiagnoses were confirmed among 3958 cases submitted as presumed lung SCC (patients misdiagnosed: median [range] age, 71 [39 to >89]; 76.4% male). The cohort included 50 cutaneous SCCs (40.7%), 33 orogenital SCCs (26.8%) (including 25 head and neck [75.8%]), 20 urothelial carcinomas (16.3%), 15 thymic carcinomas (12.2%), 4 NUT carcinomas (3.3%), and 1 prostate SCC (0.8%). Ninety-two of the 123 patients (74.8%) had clinical history or findings consistent with the new diagnosis. Eighty-eight cases (71.5%) had differences in guideline-preferred first-line systemic therapies following the diagnosis change. Conclusions and Relevance: In this cross-sectional study of patients diagnosed with lung SCC, a meaningful number of patients experienced misdiagnosis, which was identified using a multipronged AI-assisted approach. Diagnosis changes prompted by AI and orthogonal evidence may assist clinicians in prognostication and therapy selection.

Indexed as

Artificial IntelligenceCarcinoma, Squamous CellLung NeoplasmsAgedCross-Sectional StudiesDiagnosis, DifferentialDiagnostic ErrorsFemaleHumansMaleMiddle Aged

Identifiers

PMID41848733
PMCPMC13000640

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.