Second Diagnostic Opinions in Sarcoma Linked to Improved Survival Outcomes

Discrepancy and discordance between the first and second diagnostic opinions in patients with bone and soft tissue sarcoma (STS) reduced 5-year overall and specific disease survival in patients, according to a recent systematic review published in Pathology.¹

STS is a rare cancer that originates as an abnormal growth of cells in the body’s soft tissues, like fat, muscle, nerves, fibrous tissue, blood vessels, or deep skin tissue. There are more than 50 subtypes of STS, some of which are more prevalent in children than adults and vice versa; others, or intermediate STS, may spread to nearby tissues and organs but not other distant parts of the body.² Given there are numerous subtypes of STS, its global classification as a cancer is continuously updated. The World Health Organization classification of tumors of bone and soft tissue was updated in 2020 and recognized an additional 20 subtypes of cancer. Therefore, accurate diagnosis is imperative for patient treatment management and survival outcomes. In this systematic review, researchers assessed multiple studies for discrepancies between the first and second differential diagnoses and the value of a second opinion in patients with bone and soft tissue sarcomas.¹

The study authors compiled 1668 studies from the Ovid Medline, Ovid Embase, and Cochrane Central databases from 1990 to February 2024. Of the 1668 studies, only 27 were included in the final analysis. The study lengths ranged from 1 month to 10 years, and the number of cases ranged from 2 to 2425. All studies contained some variation of a second opinion consisting of an additional diagnostic assessment compared with the initial diagnosis.

There was a lack of variability in definition, making direct comparisons across studies difficult. However, the second opinion documented in each study was conducted by another expert pathologist, but the reason for it remains unclear and varies across studies. The reasons ranged from standard of practice to diagnostic difficulty to assessment before treatment or solely for the study.

The value of a second opinion in patients with STS is supported by the Australian and New Zealand Sarcoma Association (ANZSA) guidelines established to optimize treatment management of sarcoma. Although a second opinion was documented in each study, the physician’s experience was not reported, and many were not performed by a subspecialist pathologist with sarcoma expertise.

The definition of discordance also varied across studies, as some focused on diagnosis discordance, whereas others focused on changes in the management of prognosis. Discordance was measured in major or minor designation in 66.7% of studies, whereas 44.4% defined major discordance as a change in diagnosis that altered disease management or prognosis.

Minor discordances were often discrepancies in histological subtype or changes that did not affect a patient’s diagnosis or treatment management.

There were 5 studies that reported major discordance rates exceeding 20%, all of which included either voluntarily referred cases, mandatory second opinions, or reviews for study purposes. The studies with the highest discordance rates were more likely to have included voluntary referrals for diagnostic assistance. Researchers also found that there were higher rates of discrepancy by tumor type, specifically gastrointestinal stromal tumors, low-grade fibromyxoid sarcoma, and angiomatoid fibrohistiocytic sarcoma.

Only 1 study reported the impact of diagnostic discrepancies on survival. Of the 397 patients in that study, only 46 were patients with STS. The 5-year overall and disease-specific survival was significantly less in patients with a major change in diagnosis (59.2% vs 70.2%; P = .02) when compared with those who had no change in diagnosis (72.9% vs 81.2%; P = .02).

This study was limited in variability by the study’s definitions of major and minor discordance. Many of the studies were retrospective, and there was a lack of standardization in the definition of a second opinion.

“Given the potential benefits of reduced diagnostic discrepancy and improved clinical management…the recommendation from the ANZSA guidelines working group is to seek diagnostic confirmation for all bone and soft tissue sarcomas through an expert second opinion,” the study authors concluded. “

References:

1. Vu Jennifder, Petrucco C, Vargos C, et al. The value of a second expert opinion in histopathological diagnosis of bone and soft tissue sarcoma: a systematic review. Pathology. 2026;58(1):1-7. doi:10.1016/j.pathol.2025.09.005

2. What is a soft tissue sarcoma? American Cancer Society. November 23, 2021. Accessed February 17, 2026. https://www.cancer.org/cancer/types/soft-tissue-sarcoma/about/soft-tissue-sarcoma