The edition · Pathology
A negative p16 does not rule out HPV-associated cervical carcinoma
A case series finds non-diffuse p16 in 5.5% of cervical squamous carcinomas, some with high-risk HPV and MTAP co-deletion. Also: HRD profiling in serous carcinoma at scale, phyllodes classification compared, and a newly described BAP1-linked vulvovaginal tumour.
The edition in brief
In a single-institution series of 201 cervical squamous cell carcinomas, 11 (5.5%) showed negative or focal p16: four with high-risk HPV, six HPV-independent and one with low-risk HPV. Three of the four high-risk HPV cases with complete p16 loss also lost MTAP, suggesting p16/MTAP co-deletion, and this was seen in precursor lesions too. The authors recommend pairing p16 with HPV testing or prior HPV results. The Italian PROMETHEUS study ran comprehensive genomic profiling with an HRD assay on 295 high-grade serous carcinomas, with 96.6% technical success, BRCA1 or BRCA2 variants in 23%, a genomic instability score of 42 or more in 46.7%, and germline variants in 32 of 46 patients referred for counselling. A Histopathology series of 58 borderline or malignant phyllodes tumours found stromal mitoses of 30 or more per 10 HPF and malignant heterologous elements independently linked to metastasis; the Tan system matched WHO 2019 in 97%, while the Refined Criteria upgraded half of borderline tumours without better prediction. A four-case series describes a vulvovaginal epithelioid mesenchymal neoplasm with deciduoid morphology, two with germline BAP1 variants. The pearl covers sampling phyllodes tumours.
HRD profiling in serous ovarian carcinoma works at scale, and finds germline carriers
Choose high-tumour-content blocks for HRD testing in high-grade serous carcinoma, and route tumour BRCA findings to genetic counselling.
Phyllodes tumours: mitoses and heterologous elements predict metastasis better than new criteria
Report stromal mitoses and malignant heterologous elements explicitly in phyllodes tumours, and stay with WHO 2019 grading.
A deciduoid vulvovaginal tumour that can signal BAP1 predisposition
Stain for BAP1 in deciduoid epithelioid vulvovaginal tumours, and recommend genetic referral if it is lost.
Sample phyllodes tumours generously
Sample phyllodes tumours extensively and from their most active areas before assigning a grade.
Negative p16 in cervical squamous carcinoma: check HPV before calling it HPV-independent
When p16 is negative or focal in cervical squamous carcinoma, confirm HPV status before reporting it as HPV-independent.
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