The edition · Pathology
A three-stain panel caught 89% of lung carcinoid relapses; the WHO classification caught 11%
On preoperative biopsies, OTP, CD44 and Ki-67 outperformed the WHO 2021 classification on prognosis and more than doubled inter-observer agreement. Folate receptor alpha helps separate serous tubal intraepithelial carcinoma from its mimics, and small cell carcinoma of the bladder splits into two phenotypes with different antibody-drug conjugate targets.
The edition in brief
Three immunohistochemistry papers this morning, each about the same underlying problem: morphology alone is not reproducible enough for the decisions being asked of it. In 98 resected lung neuroendocrine tumours from the Dutch pathology registry with a median 83 months of follow-up, a panel of OTP, CD44 and Ki-67 applied to preoperative biopsies identified 17 of 19 relapses as high risk. The WHO 2021 classification, applied to the same biopsies by three revising pathologists, identified 2 of 19. Negative predictive value was 0.96 against 0.82, and inter-observer agreement was κ 0.673 for the panel against 0.276 for WHO. Biopsy-to-resection concordance was also better. In 408 tubal epithelial samples from 262 patients, folate receptor alpha was high in 73.2% of serous tubal intraepithelial carcinomas and 76.7% of high-grade serous carcinomas, but predominantly low or absent in serous tubal intraepithelial lesions and earlier changes. It is proposed as an adjunct alongside morphology, p53 and Ki-67 rather than as a standalone discriminator, and about a quarter of carcinomas will not express it. A multi-institutional cohort of 88 small cell carcinomas of the bladder was stratified by dominant transcription factor into ASCL1, NEUROD1, POU2F3 and YAP1-driven groups. These collapse into high and low neuroendocrine phenotypes with different therapeutic biomarker profiles: DLL3 and SLFN11 enriched in high-neuroendocrine tumours, membranous Nectin-4 higher in low-neuroendocrine ones, with NECTIN4 amplification in 21.9%.
Folate receptor alpha as an adjunct when the tubal lesion sits between STIL and STIC
Where morphology and p53 leave the STIL-versus-STIC question open, a high folate receptor alpha score is supportive evidence for carcinoma — but a low score settles nothing.
Small cell carcinoma of the bladder splits into two phenotypes with different drug targets
In small cell carcinoma of the bladder, the transcription factor phenotype predicts which therapeutic targets are present — and argues against assuming Nectin-4 is available.
When a classification's kappa is 0.28, the grade is partly a property of the signatory
Report what the specimen can support, and say plainly when a grade must wait for the resection.
OTP, CD44 and Ki-67 on the biopsy identified 17 of 19 lung carcinoid relapses; WHO identified 2
On a lung carcinoid biopsy where extent of resection is being decided, add OTP, CD44 and Ki-67 — and report the risk profile alongside the WHO category rather than instead of it.
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