Large cell calcifying Sertoli cell tumour: molecular and immunohistochemical assessment of a series comprising non-metastasising and metastasising neoplasms.

Large cell calcifying Sertoli cell tumour (LCCSCT) is a type of testicular sex cord-stromal tumour that may occur sporadically or in the context of Carney complex and other genetic syndromes. A subset is clinically malignant, and the molecular mechanisms that drive such aggressive behaviour remain unknown. METHODS AND RESULTS: We analysed 21 samples from 20 patients with LCCSCT (12 non-metastasising and eight metastasising) using PRKAR1A immunohistochemistry (IHC) and next-generation sequencing. All tumours except two (cases 17 and 20, both metastasising) demonstrated loss of PRKAR1A expression. Among 11 cases with interpretable sequencing results, all harboured pathogenic single nucleotide variants of PRKAR1A. Evidence of loss of heterozygosity (LOH) of PRKAR1A was present in all tumours with interpretable zygosity data, but the mechanisms of LOH were different for non-metastasising and metastasising tumours. Non-metastasising tumours demonstrated only copy-neutral LOH, while metastasising tumours demonstrated a spectrum of mechanisms of LOH, including copy-loss LOH, two concurrent mutations or copy-neutral LOH. Relevant molecular findings in non-metastasising LCCSCT were limited to PRKAR1A variants. In contrast, all metastasising LCCSCTs with interpretable data harboured additional pathogenic variants, including (but not restricted to) BRCA2 mutations with evidence of LOH and bi-allelic CDKN2A/B deletions. Three patients harboured PRKAR1A variants of inferred germline origin, including one with Carney complex and two without known syndromic features. CONCLUSIONS: This study further confirms that PRKAR1A IHC is a useful diagnostic tool for both non-metastasising and metastasising tumours and suggests that molecular analyses can be helpful to identify non-metastasising tumours with malignant potential in selected patients. Importantly, these results highlight that germline assessment could be beneficial for all patients presenting with LCCSCT.

Financial implications of biparametric prostate MRI.

BACKGROUND: Multiparametric magnetic resonance imaging (MP-MRI) targeted biopsy has been shown to identify more clinically-significant cancers and reduce the detection of clinically-insignificant disease when compared to systematic biopsy; however, the wide-spread accessibility of MP-MRI is limited. A potential strategy for reducing the cost, study time, and contrast-associated risks associated with MP-MRI is elimination of the dynamic contrast-enhanced (DCE) sequence, relying instead on biparametric MRI (BP-MRI). BP-MRI has been shown to have a diagnostic accuracy and cancer detection rate that are equivalent to those of MP-MRI. METHODS: We modeled the potential cost of BP-MRI compared to MP-MRI to determine what cost savings would occur if DCE was eliminated from these studies. RESULTS: When controlled for a 45 min time window that allows for one full MP-MRI or three full BP-MRI studies, the BP-MRI 45 min gross profit is $1531.32. This is an increase in gross profit of $892.58 for the 45 min time window or $10,710.98 in a 9-h business day when performing BP-MRI compared to MP-MRI for prostate cancer detection. CONCLUSIONS: BP-MRI has the potential to result in substantial cost benefit and increased access to MRI in the diagnostic workflow and risk-stratification of men being evaluated for prostate cancer when compared to conventional MP-MRI.