Do MDS Diagnoses Require Second Opinions?

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Investigators have identified a need for strong coordination between clinicians and skilled pathologists to ensure accurate, timely diagnosis of myelodysplastic syndromes (MDS). The study findings were recently published by Gorak et al in Blood Advances.


MDS—a collection of chronic hematologic malignancies most commonly occurring in patients aged 60 years and older—has widely varying prognoses and a tendency to evolve into acute myeloid leukemia. MDS can be difficult to diagnose and is misdiagnosed in about four of every 100,000 patients per year, putting patients at an increased risk for treatment errors and potentially harmful consequences.

Local pathologists typically make the initial diagnosis using the World Health Organization’s classifications for MDS. Their diagnosis is then reviewed by central pathologists who examine bone marrow specimens, clinical data, and laboratory results and either confirm or refute the diagnosis.

“We found that expert pathologists had major disagreements with local pathologists’ diagnoses in about 20% of overall cases,” explained senior study author Mikkael Sekeres, MD, Chief of the Division of Hematology at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine. “Some patients were told they had cancer when they didn’t or the opposite: that they did not have cancer when, in fact, they did. More importantly, we showed that misdiagnosed patients received the wrong initial treatment almost 10% of the time,” he stressed.  

Study Methods and Results

In the new study, the investigators analyzed the data of 918 patients diagnosed with or suspected to have MDS who were scheduled for bone marrow biopsies and who were enrolled in the National Heart, Lung, and Blood Institute’s (NHLBI) National MDS Natural History Study—which was designed to build a specimen biorepository and improve the understanding of MDS. The investigators compared local and centrally reviewed diagnoses to quantify rates and degrees of clinically meaningful differences among MDS categories. They also determined whether misdiagnoses affected the provided therapy.

The investigators discovered that about one-third of the cases received diagnostic reclassification after central pathologists reviewed the initial diagnoses and one-fifth of them were reclassified. Additionally, 15% of the disagreements between local and central pathologists were the result of site miscoding errors by research coordinators—which call into question the accuracy of national cancer registries that include patients with MDS. In cases involving disagreements, the treatment rates were lower compared with cases in which the local and central pathologists agreed. Misdiagnoses resulted in patients receiving inappropriate therapy in 7% of the cases.


“Our findings highlight the vital importance of seeking expert opinions from National Cancer Institute–designated cancer centers, especially with rare [hematologic malignancies] such as MDS,” underscored Dr. Sekeres.

The investigators noted that community-based oncologists and pathologists often have more experience diagnosing common cancers such as breast cancer than rarer ones such as MDS. “They may miss subtleties that would cause them to question the verity of rarer diagnoses,” Dr. Sekeres suggested.

The investigators emphasized that their findings may have major implications for national registries and the Surveillance, Epidemiology, and End Results program.

“Our findings help to explain discrepancies in regional and national database reporting of MDS incidence rates, subtypes, and outcomes. Diagnostic disagreements, coding errors, and evolving diagnostic guidelines call into question the accuracy of current population-based data,” Dr. Sekeres revealed. “[Hematologic malignancies] require second opinions from highly specialized clinicians coordinating with highly skilled pathologists to ensure patients are accurately diagnosed and get the right treatment in a timely manner,” he concluded.

Disclosure: For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.