The edition · Pathology
In-house HRD profiling worked in 97% of serous carcinomas
A real-world programme of comprehensive genomic profiling for high-grade serous carcinoma succeeded in almost every sample and fed germline referral; FGFR2/3-altered cholangiocarcinoma looks like its own subtype; and central review of lung neuroendocrine tumours is far less standard than assumed.
The edition in brief
The PROMETHEUS study at an Italian cancer institute ran comprehensive genomic profiling with homologous recombination deficiency scoring on 295 consecutive high-grade serous carcinomas; it succeeded in 96.6%, found BRCA1 or BRCA2 mutations in about 23%, a high genomic instability score in 47%, and other potentially actionable alterations in 15%, and a high score was linked to better survival. A retrospective series of 90 intrahepatic cholangiocarcinomas found FGFR2/3-altered tumours were all small-duct type, younger, larger, mostly non-mucinous and TP53/KRAS-poor, with better disease-specific survival on univariate but not multivariate analysis. A systematic review of 359 studies on pulmonary carcinoid and large cell neuroendocrine carcinoma found central pathology review in under a third, with median disagreement of 17% where reported. An expert group has proposed a four-tier TESST classification of testicular sex cord-stromal tumours that moves away from ovarian analogies.
A proposed TESST classification for testicular sex cord-stromal tumours
Keep reporting to WHO for now, but use the TESST tiers to separate entities with distinct behaviour from mere morphological patterns.
FGFR2/3-altered intrahepatic cholangiocarcinoma: a distinct small-duct subtype
Small-duct, non-mucinous intrahepatic cholangiocarcinoma should prompt fusion-capable molecular testing for FGFR2.
Central review of lung neuroendocrine tumours: used rarely, reported loosely
Treat lung neuroendocrine grading on small biopsies as provisional, and seek a second opinion when the category changes treatment.
Protect the block before molecular testing
Fixation, decalcification and block selection decide whether a molecular test succeeds.
Comprehensive HRD profiling for high-grade serous carcinoma works at scale
Comprehensive HRD profiling at diagnosis for high-grade serous carcinoma is feasible at scale; pair it with a clear route to germline testing.
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