Endocrine Abstracts

Background: Improved diagnostic precision is achieved with the addition of transcription factor (TF) analysis to characterise pituitary tumours. Clinicopathological studies have demonstrated a reduction in the prevalence of true null cell tumours (NC) and a rise in plurihormonal (PH) tumours, in comparison to methods based on hormone staining. There remains a high degree of heterogeneity in epidemiological and clinical patterns seen in studies. We hypothesise that variations in methodological and diagnostic criteria contribute to inconsistencies observed. We therefore reviewed methodological approaches to pituitary tumour diagnosis in recent studies.

Methods: A PubMed search was conducted with keywords “pituitary tumour” (and variations in nomenclature), “classification”, “transcription factor” and “clinicopathological”. Abstracts of studies involving pituitary tumours, published in English between 2015 to February 2023 were screened for relevance. Studies were excluded if they did not assess for presence or absence of all 3 TF or if analyses were limited to tumour subsets only. Case reports and review articles were excluded. Remaining studies were evaluated for their methodology, type of antibody and scoring strategy. Outcomes were number of NC and PH tumours.

Results: Of the 13 studies included in this review, 9 were conducted retrospectively using stored tissue blocks. Threshold definitions for positive identification of tumour types varied from 5% tumour cells positive to 80%. Mean storage time of oldest specimens used in retrospective studies was 17.1±6.8 years at time of publication. There was a positive linear correlation between number of tumours classified as NC and the age of tissue used for analysis (R²=0.71, P=0.03). Five studies with clinical data reported that 33-100% of NC tumours showed radiological invasion. In the non-functioning tumour category, the percentage of individual tumour subtypes varied substantially across all studies: 6.9±4.7% silent PIT1, 17.4±7.9% silent corticotroph tumours, 67.1±10.1% gonadotroph tumours, 5.5±4.5% NC tumours and 3.2±3.0% silent PH tumours. Studies that used a cut-off of 5% or 10% tumour cells to define TF positivity were able to diagnose PH tumours. When a high cut-off of 80% was applied, PH tumours were not identified.

Conclusion: Higher proportion of NC tumour classification is seen with older tumour specimens, possibly representing false negative staining. Positivity cut-off influences the ability to detect PH tumours. We highlight the need for large prospective studies and a standardised approach to assessment of transcription factor expression before developing guidelines for clinical management based on TF analysis.