The Power of Digital Pathology

Conversation with Prof Dr Daniel Baumhoer

In early 2024, Prof Daniel Baumhoer joined the Basel Research Centre for Child Health (BRCCH) as the first professor as part of the organisation’s transition to a digital health hub in Basel. Prof Dr Baumhoer will lead the Malignant and Bone and Soft Tissue Pathologies capacity-building platform. This resource will complement and support the work of the six appointed professors who will form the core of the new BRCCH. He is currently the Deputy Medical Director of the Institute of Medical Genetics and Pathology and Head of the Bone Tumour Reference Centre (BTRC) and DÖSAK (Swiss Austrian German Working Group on Maxillofacial Tumours) Registry at the University Hospital Basel.

Prof Dr Baumhoer grew up in Germany and attended medical school at the Georg-August University of Göttingen. He moved to Basel in 2004 to train in pathology and passed the pathology board exam in 2009. In 2014, he took over as the lead of the BTRC and DÖSAK registry, both at the University Hospital Basel providing second opinions on difficult-to-classify bone and soft tissue and maxillofacial tumours. Each year, the registries receive between 800 and 1,000 consultation requests from around the world.

“The Bone Tumor Reference Centre is something quite unique, I think, worldwide,” says Prof Dr Baumhoer. “Since it was founded in 1972, we have collected more than 22,000 bone tumours, mostly from children and adolescents, but also from adults.”

Since many of these tumours are rare, this large sample set provides an ideal setting to study these lesions and gain experience in their morphological and genetic spectrum. The team also uses elaborate molecular profiling techniques to analyse tissue samples. Available patient follow-up information makes this repository a powerful tool to drive innovative paediatric health research and informatics.

“I'm really looking forward to meeting the other experts within the BRCCH to foster collaboration and use the unique BTRC dataset to better understand the underlying pathogenesis of bone and soft tissue tumours,” shares Prof Dr Baumhoer.

Expediting Diagnosis Using Digital Pathology

Within the University Hospital Basel, Prof Dr Baumhoer has also been leading the transition to digital pathology. This process involves scanning histologic slides, which can then be assessed digitally. Integrating these digital slides into the hospital’s repository, which also contains radiologic images of patients, enables a more integrated approach as pathology findings can be provided to and assessed by all clinicians. Digital histology slides can also be easily shared and discussed with other experts, even internationally.

“From a scientific point of view, digital pathology makes it possible to share cases more easily, to use new techniques and algorithms to evaluate histologic patterns and to create a more holistic digital diagnostic approach by integrating other modalities, including radiology,” concludes Prof Dr Baumhoer.

One of the current challenges for the BTRC is that physical paraffin blocks of tissue must be sent to the registry in Basel by mail, a lengthy process prone to delays, sometimes customs-related. For patients waiting to start treatment, this is valuable time they can’t afford to waste. Digital pathology could help shorten this timeline by allowing clinicians to send histology images digitally. The physical tissue blocks will only be required for molecular testing.

“Using digital pathology would make these interactions more effective,” suggests Prof Dr Baumhoer. “I envision that there will be a lot more consultation cases in the future, but it will be easier and faster to assess and sign them out using digital pathology.”

The team has made great progress in transitioning to digital pathology at the University Hospital Basel over the last three years. All consult bone and soft tissue tumours are currently being digitised. It is expected that this platform will start being integrated into the routine diagnostic workflow in the coming months. Once digital pathology is implemented, it opens opportunities to incorporate automation for diagnostics into pathology workflows, accelerating the diagnostic process and getting information to clinicians and patients faster.

Diagnosing Bone and Soft Tissue Tumours Using Molecular Analysis

Outside of his clinical practice, Prof Dr Baumhoer studies the molecular profiles of bone and soft tissue tumours to better understand their pathogenesis. He started his career by investigating osteosarcoma, a highly aggressive type of bone cancer that is most common in adolescents and young adults. Different subtypes of osteosarcoma can be characterised by genetic pathway alterations, which could have therapeutic implications. With only 30 to 35 cases of this cancer type in Switzerland each year, it was challenging for Prof Dr Baumhoer to collect sufficient amounts of tissue samples needed to perform genetic profiling, a process that took several years. However, the results were worth the wait.

“We did a lot of sequencing on these samples and we found distinct genetic signatures which could be the basis of new and innovative treatment approaches,” illustrates Prof Dr Baumhoer.

His team was the first to define a specific genetic profile in osteosarcoma associated with deficiencies in DNA repair resembling breast and ovarian cancers with BRCA mutations (so-called BRCAness). To study how these tumours genetically evolve over time, Prof Dr Baumhoer sequentially investigated osteosarcoma samples from patients before and after treatment and following recurrence or metastatic spread.

“Most of the studies we conducted in recent years are included in the World Health Organisation (WHO) classification of tumours,” emphasises Prof Dr Baumhoer. “So, the results are diagnostically relevant.”

One example is the most common benign bone tumour called non-ossifying fibroma. This tumour affects 40 per cent of the population during skeletal growth and maturation. Since the vast majority of these lesions are incidental findings that undergo spontaneous regression, they were thought to be developmentally derived disorders and not regarded as true neoplasms. However, Prof Dr Baumhoer’s team was the first to show that, despite being completely benign, non-ossifying fibromas have recurrent mutations in common cancer pathways that can be used to confirm the diagnosis molecularly.

“It is really important to me to understand more about the molecular pathogenesis of bone tumours,” says Prof Dr Baumhoer. “If we identify recurrent driver gene alterations, these can be used to confirm a diagnosis, but potentially also to enable targeted treatment approaches. Understanding the mechanism of how tumours develop is a first and mandatory step to finding new and effective ways to treat patients.”

Prof Dr Baumhoer is now investigating the DNA methylation profiles of bone and soft tissue tumours. DNA methylation is involved in gene regulation and cellular differentiation. As a result, tumour cells often carry specific methylation patterns that differ between tumour subtypes, and also between normal and cancerous cells. By analysing the DNA of bone and soft tissue tumours, Prof Dr Baumhoer hopes to identify specific methylation patterns that could be used to better differentiate between tumour subtypes. Using new and innovative sequencing technologies, tumour classification could be possible in a few hours rather than the several days to weeks that molecular tests currently take.

“Identifying reliable diagnostic methylation signatures would have a huge impact on patient care since the treating clinicians could immediately start therapy without further delay,” proposes Prof Dr Baumhoer.

Welcoming Prof Dr Baumhoer to the BRCCH

As the first professor to join the BRCCH as a digital health hub, Prof Dr Baumhoer is enthusiastic about collaborating with other experts in paediatric digital health, bringing together his experience, data and diagnostic infrastructure.

“There will be experts in genetics and sequencing, in digitisation, and I think it will be very fruitful if different experts from different angles, but with the same aim, come together and join forces,” expresses Prof Dr Baumhoer. “I really hope we can develop innovative new ideas and projects together.”