The next edition of the World Health Organisation (WHO) Blue Book will see important changes to the classification of testicular germ cell tumours (GCTs), according to Prof Dan Berney, Consultant Pathologist at Barts Health NHS Trust, UK, who is co-editor of the upcoming WHO Classification of Urinary and Male Genital Tumours.
Prof Berney told the 2026 John Fitzpatrick Irish Genitourinary Cancer Conference that the next edition of the WHO series on the classification of human tumours (also known as the WHO Blue Book) will include a new classification system for tumours with somatic transformation. The classification of ‘teratoma with somatic malignancy’ will be replaced by ‘GCT with somatic changes’. This follows the publication of studies which have shown that somatic transformation does not just occur in teratomas.
The reason for this is to ensure that patients with these tumours remain under the care of genitourinary (GU) oncologists and receive appropriate treatment.
“GCTs with somatic transformation are different from GCTs, but they bear more relation to GCTs than they do to their somatic counterparts. It is important that they are not hived off into the sarcoma community. So, if you have a rhabdomyosarcoma-like transformation, these tumours should stay under the care of a GU oncologist because there is still a chance that they will be responsive to GU-type therapy, and that is probably the best way to go,” Prof Berney said.
In the new classification system, somatic type rhabdomyosarcoma will be referred to as sarcoma-like tumour of germ cell origin (rhabdomyeloblastic phenotype). Somatic type unclassified sarcoma will be referred to as the undifferentiated phenotype, and embryonic-type neuroectodermal tumours will change to embryonic-type neuroductal tumour of germ cell origin, while somatic-type enteric adenocarcinoma and squamous cell carcinoma will be referred to as enteric and squamous phenotypes. Somatic-type leukaemia/lymphomas will, in future, be called leukaemia/lymphoma-like tumour of germ cell origin. Tumours with a combination of conventional and somatic-type will be defined according to ‘components’, ie, proportion of yolk sac, seminoma, rhabdomyoblastic phenotype etc.
He pointed out that characteristic features of GCT with somatic malignancy include widespread aneuploidy, distinct epigenetic signatures, and mutations that are otherwise rare in testicular GCTs. He added that identification of somatic malignancy component could be more important than their precise histological subclassification.
The forthcoming edition of the Blue Book will also include new prognostic factors for recurrence in patients with clinical stage 1 seminoma and non-seminoma. Prof Berney said this change is important for the 20–30 per cent of patients for whom orchidectomy does not deliver cure.
After many years of debate, the new edition will include invasion of the soft tissues, particularly with the hilum, as an important prognostic factor in stage 1 seminomas.
This significant change follows the publication of a Danish study of patients with stage 1 seminoma, which was published in the Journal of Clinical Oncology in 2024. The multivariable analysis showed that while rete testis invasion is associated with a hazard ratio (HR) of 1.81 (95% CI 1.19-2.75; P=0.0058), rete testis invasion with hilar soft tissue invasion delivers a HR of 2.83 (95% CI 1.82-4.38; P<0.0001).
“Rete invasion and hilar soft tissue invasion are really strong predictors of relapse and are very important to mention in every testicular [pathology] report,” Prof Berney said.
The presence of lymphovascular invasion (LVI) was shown to confer a HR of 1.82 (95% CI 1.22-2.70; P=0.0032), while HRs for elevated b-hCG and LDH were 1.89 (95% CI 1.35-2.64; P=0.002) and 1.67 (95% CI 1.19-2.34; P=0.0031). The study concluded that patients with all four of these risk factors had a 62 per cent chance of recurrence compared to 6 per cent in patients with none of these factors.
In stage 1 non-seminomas, hilar soft tissue invasion is also a risk factor for recurrence (HR 1.70; 95% CI 1.17-2.48; P=0.0056), as is the presence of LVI (HR 3.48; 95% CI 2.38-5.10; P<0.0001). Other risk factors to be included in the list are tumour size and embryonic carcinoma predominance.
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