The edition · Pathology
Mismatch repair staining is worth adding for three sarcoma types, a case series argues
Deficiency was found in about 1 in 20 uterine leiomyosarcomas and some pleomorphic sarcomas, with Lynch syndrome and immunotherapy at stake. A living guideline keeps salivary tests for oral cancer out of routine use, and self-collected swabs matched clinician samples for detecting CIN2+.
The edition in brief
A US series of 39 mismatch repair-deficient sarcomas found deficiency in 1.2% of 1,531 sequenced sarcomas overall, but more often in uterine leiomyosarcoma (5.6%), undifferentiated or unclassified pleomorphic sarcoma (2.3%) and pleomorphic rhabdomyosarcoma; eight tumours were the first cancer in patients with Lynch syndrome, and some responded completely to checkpoint inhibitors. The authors propose routine MMR immunohistochemistry for these types and any sarcoma with a Lynch history; this is a proposal from a retrospective series, not a guideline. A US living guideline on early detection of oral squamous cell carcinoma limits commercial salivary adjunct tests to research, and keeps a clinical oral examination for all adults and biopsy or referral for persistent mucosal lesions. An Australian VALHUDES evaluation in 400 colposcopy attenders found self-collected vaginal swabs as sensitive as practitioner cervical samples for CIN2+ on two PCR HPV assays, with lower specificity. A Canadian laboratory used an amplicon NGS panel to call glioma copy number changes, matching FISH in a 39-case validation and cutting FISH requests by 90% in practice. A UK breast screening EQA review found expert agreement below 80% in 5.7% of cases, mostly atypical and papillary lesions. The pearl covers MLH1 loss and methylation testing.
Salivary tests for oral cancer stay in research; examination and biopsy stay the standard
Keep salivary adjunct tests for oral cancer out of routine use; examine every adult's mouth and biopsy persistent lesions.
Self-collected vaginal swabs matched clinician cervical samples for CIN2+ on two PCR HPV tests
Self-collected vaginal swabs can be used with validated PCR HPV assays, with capacity planned for more positive results.
An NGS panel called glioma copy number changes in agreement with FISH and cut FISH by 90%
Consider validating copy number calling on your NGS panel for glioma, keeping reflex FISH for equivocal results.
Expert breast pathologists disagreed on about 1 in 18 EQA cases, mostly atypical and papillary lesions
Treat atypical and papillary breast lesions at category boundaries as cases for a second opinion and explicit wording of uncertainty.
MLH1 and PMS2 loss needs a methylation or BRAF check before a Lynch referral
Add methylation or BRAF testing to MLH1 and PMS2 loss before suggesting Lynch syndrome, and refer other loss patterns to genetics.
About 1 in 20 uterine leiomyosarcomas were mismatch repair deficient in a large sequencing database
Consider adding MMR immunohistochemistry to uterine leiomyosarcoma, pleomorphic rhabdomyosarcoma and undifferentiated pleomorphic sarcoma.
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