{"id":10605,"date":"2026-02-05T15:59:21","date_gmt":"2026-02-05T14:59:21","guid":{"rendered":"https:\/\/www.hartwigmedicalfoundation.nl\/?p=10605"},"modified":"2026-02-05T16:03:58","modified_gmt":"2026-02-05T15:03:58","slug":"the-role-of-molecular-diagnostics-in-sarcomas","status":"publish","type":"post","link":"https:\/\/www.hartwigmedicalfoundation.nl\/en\/the-role-of-molecular-diagnostics-in-sarcomas\/","title":{"rendered":"The\u00a0role of\u00a0molecular\u00a0diagnostics in\u00a0sarcomas\u00a0"},"content":{"rendered":"\n

Between Science and Clinical Practice<\/strong> <\/p>\n\n\n\n

The use of molecular diagnostics in sarcoma care is receiving growing international attention. Recent studies\u00b9 show that comprehensive genomic analysis leads to a revised diagnosis or new treatment options in a subset of cases. At the same time, the prevailing expert consensus\u00b2 is that next-generation sequencing (NGS) and whole-genome sequencing (WGS) should be used as complementary, targeted tools, in situations where they are expected to add real clinical value. <\/p>\n\n\n\n

At the intersection of scientific insights and efficient clinical implementation, we spoke with two sarcoma specialists from Leiden University Medical Center (LUMC), a recognized expert center for soft tissue and bone sarcomas: Prof. Judith Bov\u00e9e, pathologist, and Prof. Hans Gelderblom, medical oncologist and Head of the Department of Medical Oncology. <\/p>\n\n\n\n

Molecular Diagnostics in daily practice<\/strong> 
For Judith Bov\u00e9e, the role of molecular diagnostics in sarcoma care is clear: it is a valuable addition to classical pathology, but microscopy still forms the basis. Sarcomas are rare and often genetically heterogeneous, which means that molecular diagnostics can be highly informative for a subset of tumors. <\/p>\n\n\n\n

\"\"
Judith Bov\u00e9e<\/figcaption><\/figure>\n\n\n\n

\u201cMolecular diagnostics are mainly used when a diagnosis cannot be established with certainty based on histology alone, or when a tumor is characterized by a specific fusion or mutation,\u201d Bov\u00e9e explains. \u201cFor some soft tissue and bone sarcomas, this really helps to achieve accurate classification\u2014for example in round cell sarcomas, where a definitive diagnosis usually cannot be established without molecular testing.  <\/p>\n\n\n\n

According to Bov\u00e9e, the use of molecular diagnostics varies by tumor type. \u201cFor some tumors, such as GIST, we perform NGS routinely; for others, we do not. Additional molecular testing is often discussed in consultation with the oncologist, particularly when there may be therapeutic implications.\u201d <\/p>\n\n\n\n

Expertise and Experience<\/strong> 
Bov\u00e9e emphasizes the importance of experience in evaluating rare tumors. \u201cIn specialized centers, pathologists see a high volume of sarcomas and testing is more targeted. There is less tendency to order tests \u2018just in case.\u2019 Outside reference centers, molecular testing may be requested more readily to compensate for diagnostic uncertainty. That is precisely where proper triage and multidisciplinary consultation are crucial. You want to test when it is necessary\u2014not simply because it is possible.\u201d <\/p>\n\n\n\n

What defines an expert? \u201cNot the absolute number of sarcoma cases a pathologist sees, but their structural involvement in sarcoma care. There are no strict numerical thresholds. Ideally, you work in a reference center, participate in multidisciplinary tumor boards, and assess sarcomas on a regular basis. Only then do you build the experience needed to diagnose these rare tumors accurately.\u201d <\/p>\n\n\n\n

Diagnostic reclassification<\/strong> 
As shown in the recent studies comprehensive genomic profiling leads to diagnostic reclassification in approximately 8\u201312% of cases. In most situations, such reclassification does not directly affect treatment, but for a small subgroup it can be clinically meaningful. <\/p>\n\n\n\n

Hans Gelderblom recognizes this pattern: \u201cFor most patients, it does not change much\u2014but for that small percentage for whom it does make a difference\u2026 well, you would not want to be the patient who misses out.\u201d <\/p>\n\n\n\n

\"Gentleman
Hans Gelderblom, photo Gerard van Bree Fotografie<\/figcaption><\/figure>\n\n\n\n

Therapeutic perspective<\/strong> 
Gelderblom stresses that molecular diagnostics become clinically meaningful only when there is an indication for systemic treatment. \u201cMany sarcomas are not treated systemically at all. They are managed locally, with surgery or radiotherapy. In those situations, extensive testing to identify therapeutic targets has limited added value.\u201d <\/p>\n\n\n\n

When systemic therapy is indicated, molecular information comes into play. \u201cIt is truly a case-by-case decision. You consider the patient\u2019s fitness, whether treatment is realistic, and we always discuss this in a multidisciplinary tumor board. The key question is: do you expect to find something that is relevant for this specific patient? Does it fit the clinical picture?\u201d <\/p>\n\n\n\n

In the Netherlands, a dedicated reimbursement framework exists for broader diagnostics, including extensive NGS panels and WGS, allowing clinicians to look beyond standard panel testing. Precisely because these decisions are so patient-specific, Gelderblom advocates for centralized care. \u201cIn advanced sarcoma cases, these discussions should take place in an expert MDO, together with the pathologist. That allows for a well-informed assessment of whether molecular diagnostics are meaningful and helps avoid unnecessary delays.\u201d <\/p>\n\n\n\n

Molecular diagnostics can also facilitate access to clinical trials or reimbursement. \u201cIn certain angiosarcomas, particularly those with a high mutational burden, molecular results can support eligibility for a trial or help secure reimbursement for treatment,\u201d Gelderblom adds. <\/p>\n\n\n\n

Tissue requirements<\/strong> 
A practical limitation for the broader use of WGS is the availability of suitable tissue. Not all hospitals can process fresh or frozen material, which is required for certain diagnostic approaches. Reference centers usually have this well organized, whereas this can be more challenging elsewhere. According to both experts, this underscores the importance of centralization and uniformity of care. <\/p>\n\n\n\n

The importance of turnaround time<\/strong> 
Both Bov\u00e9e and Gelderblom emphasize the importance of turnaround time\u2014not only for clinicians, but especially for patients. Immunohistochemistry results are often available within a day; targeted NGS panels (DNA and\/or RNA) typically take several days to just over a week, while WGS requires approximately (max) two weeks. <\/p>\n\n\n\n

Gelderblom explains: \u201cIt is essential to avoid diagnostic procedures themselves delaying care. For many patients, every day of waiting feels like an eternity, and for clinicians, even a week can determine whether therapy can be initiated. That is why treatment is sometimes started based on histology and clinical presentation, with molecular results becoming available at a later stage.\u201d  <\/p>\n\n\n\n

In the Netherlands, turnaround times for NGS and WGS are gradually improving. In addition, new sequencing technologies are being explored that may further accelerate diagnostics in the future. While this is not yet fully embedded in routine practice, the development in this area is clearly progressing.  <\/p>\n\n\n\n

Data: Valuable, but fragmented<\/strong> 
The potential to learn from data is substantial, but current practice remains fragmented. Bov\u00e9e points to technical and legal barriers: \u201cMolecular results are recorded in PALGA, but not yet standardized everywhere, although significant efforts are being made. Linking WGS data with pathology findings and clinical outcomes is challenging. In practice, data integration remains a major obstacle.\u201d <\/p>\n\n\n\n

Gelderblom observes the same issue from the clinical perspective: \u201cFor over a decade, we have struggled with the lack of comprehensive national registries. Genomics, pathology, and clinical outcomes are still insufficiently connected, making systematic learning difficult.\u201d <\/p>\n\n\n\n

Both conclude that nationwide, uniform integration of these data sources is still lacking, despite being essential for improving care. <\/p>\n\n\n\n

Looking Ahead: smarter, faster, and better integrated<\/strong> 
When asked to describe their ideal scenario five years from now, Bov\u00e9e and Gelderblom envision a similar direction. They see the greatest potential in faster generation of results, ensuring that relevant information becomes available earlier in the care pathway. <\/p>\n\n\n\n

Gelderblom also highlights organizational improvements: \u201cAll high-grade sarcomas should be discussed immediately in an expert MDO, with appropriate consent for diagnostics and research obtained upfront. That would make the entire process much more efficient.\u201d <\/p>\n\n\n\n

According to both experts, progress does not lie in testing more or broader by default, but in smarter, faster, and better integrated diagnostic strategies,<\/strong> with molecular diagnostics serving as a valuable complement to both diagnosis and treatment selection. <\/p>\n\n\n\n

\u00b9 Introduction and Impact of Routine Whole Genome Sequencing in the Diagnosis and Management of Sarcoma.<\/em> British Journal of Cancer, 2024. 
Comprehensive Genomic Profiling Alters Clinical Diagnoses in a Significant Fraction of Tumors Suspicious of Sarcoma.<\/em> Clinical Cancer Research, 2024. 
Clinical Impact of Prospective Whole Genome Sequencing in Sarcoma Patients.<\/em> Cancers, 2022. <\/p>\n\n\n\n

\u00b2 Guidelines for Next-Generation Sequencing in Sarcoma Diagnosis and Treatment.<\/em> JAMA Oncology, 2025. <\/p>\n\n\n\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

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