Anthony J Gill

Professor of Surgical Pathology & Pathologist University of Sydney

Head Cancer Diagnosis & Pathology Research Group.

Member of the Order of Australia (AM)

[Anthony J Gill @CaDxPath]

Our latest article in @AJSPjournal is now officially printed. We examine the proposed changes for the AJCC 9th edition staging of colorectal carcinoma. The proposals reset the relative balance between depth of invasion (T-stage) and nodal metastasis (N-stage); and more appropriatley recognizes the adverse effects of tumour deposits (carcinoma in soft tissue not associated with nodes)

Availalble for free download at:
https://t.co/T4iIeQOC4B

Key points:

The good:
1. The new proposal ends the stage 3A paradox (that under the old eighth edition stage 3A does much better than stage 2)
2. The new proposal appropriately recognizes tumour deposits as an additional adverse finding (not as equivalent to node mets). That is, it recognizes that patients with tumour deposits and node mets do worse than those with one or the other only.

Room for improvement?
3. However our data shows that low T-stage (T1 and T2) patients with lymph node metastase do better than those without! Perhaps this should be considered in new stage groupings.
4. This results in the new proposed stage IIB being a heterogeneous group with the excellent prognosis T1 and T2 and intermediate prognosis T3 group
5. Proposed stage group 1 and 2A both have an excellent prognosis. Perhaps these should be renamed group 1A and group 1B to emphasize the similarities between these two groups of low T-stage disease (T1 and T2 respectively but node negative) rather than the differences.

Thoughts?

[Anthony J Gill @CaDxPath]

Practice tip:
About 1% of sporadic uterine leiomyomas are fumarate hydratase deficient. But HLRCC syndrome is rare. So it is challenging to decide which people with fumarate hydratase deficient leiomyomas should be referred for genetic counselling/testing.

If multiple FH deficient leiomyomas -> refer
If FH deficient leiomyoma under 40 years ->refer

If a solitary FH deficient leiomyoma -> look in the adjacent myometrium. In my experience, scattered 2SC positive clusters of morphologically non-neoplastic cells are only ever seen in syndromic disease.

This is 2SC immunohistochemistry where I am trying to illustrate this finding. Anyone else seen this?

[C. Christofer Juhlin @DrJuhlin]

Proud to share our contribution to Modern Pathology with @CaDxPath, honoring the legacy of Dr. Virginia A. LiVolsi while highlighting an often-overlooked area of pathology - the parathyroid gland.

Open access:

https://t.co/sV0tNjb65l

[Gladell Paner, MD @GladellPaner]

It was a fantastic 2026 Grawitz Dinner Fukuoka! This was the first Grawitz Dinner at IAP and outside of North America and Europe. Thank you Prof. Toyonori Tsuzuki & team for such an amazing hospitality! A great evening for #GUPath! #IAP2026 #GUPS #ISUP #SEAUPS 🙏🏻

[NEJM @NEJM]

This randomized trial examined whether adding a multicancer early-detection blood test to usual care reduces late-stage cancer diagnoses in adults 50 to 77 years of age. Research findings from the NHS-Galleri trial are summarized in a new Quick Take video. https://t.co/u76u9DS4rl

[Allan Pereira, MD, PhD @DrAllanPereira]

🤓Ok, I think you will find this interesting:
How drugs should be named under the 'new' nomenclature:

- Trastuzumab (Herceptin) -> Trastatug
- Pembrolizumab (Keytruda) -> Pembrostotug
- Atezolizumab (Tecentriq) -> Atezostobart
- Blinatumomab (Blincyto) -> Blinatamig

Will this happen?
Well, not with older drugs, but certainly with new ones.

If you want to learn more about this naming system, check out this thread!

[Toni Choueiri, MD @DrChoueiri]

Today, an @FDA advisory panel voted 7–2, with 1 abstention, that the benefits of @GrailBio Galleri multi-cancer early detection (MCED) test outweigh its risks. A closely watched milestone for the field.

And if you haven’t seen it yet, the NHS-Galleri randomized trial was published yesterday in @NEJM:
https://t.co/XrYZ8DZ1r5

[GRAIL @GrailBio]

Today GRAIL announced a favorable vote from an FDA Advisory Committee for the approval of the Premarket Approval application of the Galleri multi-cancer early detection test (MCED).

The Committee considered Galleri’s safety, effectiveness, and overall benefit-risk profile for screening for the early detection of multiple types of cancer in adults aged 50 years and older.

Read more: https://t.co/Hm97ydCD8y

#MCED #Galleri #CancerScreening

[Matthew Herper @matthewherper]

I’m following the FDA advisory committee on $GRAL’s Galleri blood test for detecting multiple types of cancer today and will be posting my thoughts here. So far, we’ve seen only company presentations, usually the dullest part of an advisory panel.

But there have been some interesting tidbits. First, Grail is leaning heavily into simply the idea that they detect more cancers and can localize them, not getting into larger questions about the benefit to patients from doing so. See this slide. Speaking as part of Grail’s presentation, Mylynda Massart, a family medicine at UPMC, argued that the test can fit will with existing cancer screening and is something that many patients are eager to use.

The panelists, in their first questions, expressed skepticism. One asked if the incredible, white-glove treatment that Grail gives doctors now can really scale. Another responded a Grail comment: “You’re carefully choosing your words. It is curative intent but you do not have outcome data.” Another panelist asked why the control arm of Grail’s randomized clinical trial in the UK was not included in the briefing document; the primary outcome of that trial was not included, either. Grail and FDA said that based on the agreement they came to with the FDA. Another panelist asked why so many patients from Grail’s other big study were not included in the briefing material; Grail said that had to do with when the data were submitted.

What’s interesting is that the FDA seems to be telling the panel to limit the scope of its discussion. An FDA official said that both follow-ups and outcome data were beyond the scope of the claim being considered.

[Eric Topol @EricTopol]

The GRAIL NHS Galleri randomized trial with over 142,000 participants was published today @NEJM
"In this trial, we did not observe a lower incidence rate of stage III or IV cancers [the primary endpoint] across 12 prespecified cancers after three screening rounds with multicancer early-detection testing plus usual care than with usual care alone."
https://t.co/QGxc00VztA

[Markus Eckstein @Markuseckstein3]

Our NECTIN4 scoring system for predicting enfortumab vedotin response in urothelial carcinoma is just published. 🔬

The short version: NECTIN4 is not a failed biomarker. It has been measured in the wrong compartment.

📊 179 EV-treated mUC patients, multicenter, FISH plus IHC, benchmarked against EV-301 EPAR data.

Why the field thought NECTIN4 was ubiquitous 🧠

In EV-301 the median H-score was 250, with 82.6% ≥150. That near-universal expression underpinned the biomarker-unselected label.

In our cohort, membranous H-score alone was 160. Cytoplasmic was 200. Combined, 260, with 78.2% ≥150, almost exactly mirroring EV-301.

So the trial numbers most likely reflect membranous plus cytoplasmic staining. That single methodological choice is why NECTIN4 looked like it was everywhere. 🎯

And it matters, because only one compartment predicts anything:

✅ Membranous 2+/3+ vs 0/1+: ORR 55.1% vs 25.5% (p<0.001), mPFS 7.1 vs 2.9 months (HR 0.45), mOS 12.3 vs 6.9 months (HR 0.57).
❌ Cytoplasmic: ORR 49.6% vs 39.5% (p=0.4). No PFS or OS signal.
❌ Bulk NECTIN4 mRNA, which cannot resolve localisation: no association either.
Adding cytoplasmic staining inflates positivity and dilutes prediction. Negativity rate drops from 12% to 3.4%. More positives, less information. 📉
The scoring system 🔬

Four tiers (0, 1+, 2+, 3+) adapted from the ASCO/CAP HER2 gastric algorithm, chosen deliberately because it accounts for incomplete membranous staining, the same framework that carried T-DXd to tumour-agnostic approval.

Blinded interobserver testing, 44 cases, three raters, two with no prior NECTIN4 experience:
📈 Fleiss' κ 0.749 across all four tiers.
📈 Fleiss' κ 0.874 for the clinically relevant 0/1+ vs 2+/3+ cutoff. Almost perfect agreement.

Reproducible, teachable in a short training session, deployable in routine practice.

Genomics on top 🧬
NECTIN4 amplification in 25.1% (45/179). ORR 76.2% vs 36.6%. mPFS 12.2 vs 3.9 months (HR 0.40). mOS 30.1 vs 8.5 months (HR 0.33). At 24 months, 58.8% of amplified patients were alive versus 19.0%.
And IHC prescreens for it: 80% of amplified tumours are 3+, under 5% of 0/1+ tumours carry an amplification. Restricting FISH to 2+/3+ captures 97.8% of amplified cases while sparing 29.1% of patients any molecular testing. ⚡

The integrated three-tier model:

1️⃣ Amplified: ORR 76.2%, mOS 30.1 mo
2️⃣ Non-amplified, membranous high: ORR 42.9%, mOS 8.8 mo
3️⃣ Non-amplified, membranous low: ORR 26.1%, mOS 6.9 mo

Both remained independent in multivariable models. C-index for OS improves from 0.557 to 0.621 when amplification and membranous expression are combined. Neither marker alone does what the two do together.

Where I think this lands 🎯

I do not (!) read this as an argument for testing every patient . With EV+P as first-line standard and few alternatives, a negative result rarely changes what you do today and shouldn't change it right now given the high EVP efficacy.

But that is an argument about the therapeutic landscape, not about the biology. And the landscape is changing fast: HER2 ADCs, TROP2, HER3/EGFR, NECTIN4 radioligands and T-cell engagers. The moment two viable options compete for the same patient, the question stops being "does the target matter" and becomes "which target first."
Notably, unlike the HER2-low paradigm, EV-301 showed an attenuated treatment effect in NECTIN4-low disease, PFS HR around 0.9 with confidence intervals crossing 1 (check out Figure 1 of the paper).
⚠️Prospective validation is running: EVOKE (DRKS00034745).

Immense thanks to @niklas_kluemper and Jonas Saal, to Thomas Büttner, Sebastian Rauch and Fabienne Lange, and to every centre and biobank that contributed. This was a genuinely collaborative effort within the fantastic GUARDIANS and BRIDGE Consortium. 🙏

🔗 https://t.co/CuQR9LJe6k

@Uroweb @AmerUrological @ASCO @PathSoc @OncoAlert @Histo_Journal @andreanecchi @emanuele_crupi @danieleraggi83 @raffcolo @Dr_Aggen @DrRosenbergMSK @h_alahmadie @PGrivasMDPhD @shilpaonc @drenriquegrande @amerseburger @brookmans76 @DrYukselUrun @onkowissen @imedverse @UroDocAsh @urotoday @EUplatinum @JCO_ASCO @CCR_AACR @niklas_kluemper @DrRosenbergMSK @Dr_Aggen @Uromigos @tompowles1 @shilpaonc @PGrivasMDPhD

#Uropathology #urothelial #BladderCancer #NECTIN4 #pathtwitter

[Yakup Ergün @dr_yakupergun]

All 22 patients who became ctDNA-positive during adjuvant surveillance developed distant recurrence. The median lead time was 346 days—but in one patient, it reached 1,937 days, or approximately 5.3 years.

Technically impressive and prognostically compelling. Yet such a long lead time raises an important question: without an established intervention, how can we use this early molecular information without simply prolonging uncertainty and anxiety?

When does lead time translate into clinical benefit?

https://t.co/4CCiCOHYf2

[Anirban Maitra @Aiims1742]

Final version of @NeehaZaidi paper on Mutant KRAS Vaccine for #PancreaticCancer interception in high risk cohorts out in @CD_AACR.
https://t.co/6GTEnTTTDY
Notable data is detection of KRAS antigen targeted T cells 1 year post vaccine - annual boosters as a prevention strategy?

[Anirban Maitra @Aiims1742]

An update on the @Merck @moderna_tx mRNA vaccine trial from @JaniceM10 @Perlmutter_CC and @DrLaPook @CBSNews
@nyugrossman @nyulangone @JohnPLeonardMD
https://t.co/pmLmd7DpPf

[Anthony J Gill @CaDxPath]

The State Funeral for Profesor Richard Scolyer will be held on Monday 13 July 2026 at the Sydney Opera House.

The details are available at:

State Memorial Service for Professor Richard Scolyer AO https://t.co/SmJGBvCv8u

[Anthony J Gill @CaDxPath]

The State Funeral for Profesor Richard Scolyer will be held on Monday 13 July 2026 at the Sydney Opera House.

The details are available at:

State Memorial Service for Professor Richard Scolyer AO https://t.co/SmJGBvCv8u

[Dr Rishabh Jain @DrRishabhOnco]

The ctDNA hype cycle is over.

ASCO’s first ctDNA guideline tells us where liquid biopsy actually changes practice. 🧬

✅ Use ctDNA when:
• Tissue is unavailable or unsafe
• Results are needed urgently
• Drug approvals allow/require liquid biopsy

⚠️ Negative ctDNA does NOT exclude actionable disease.
Tissue confirmation remains critical.

Practice-changing trials cited by ASCO:

🔹 DYNAMIC
Stage II colon cancer
Less chemotherapy, same outcomes.

🔹 PADA-1
ESR1-guided switch to fulvestrant + palbociclib improved PFS.

🔹 SERENA-6
ctDNA-detected ESR1 mutations enabled earlier intervention and significantly prolonged PFS.

🔹 IMvigor011
MRD-positive bladder cancer benefited from adjuvant atezolizumab.

❌ ctDNA should not replace imaging, pathology, or standard staging.

Bottom line:

The question is no longer:
“Can we detect it in blood?”

The question is:
“Will acting on it improve outcomes?”

That’s the bar ASCO has set. 🎯

#Oncology #ctDNA #LiquidBiopsy #ASCO #PrecisionMedicine
@OncoAlert @ASCO @JCOPO_ASCO

[Anthony J Gill @CaDxPath]

Our latest article in @AJSPjournal is now officially printed. We examine the proposed changes for the AJCC 9th edition staging of colorectal carcinoma. The proposals reset the relative balance between depth of invasion (T-stage) and nodal metastasis (N-stage); and more appropriatley recognizes the adverse effects of tumour deposits (carcinoma in soft tissue not associated with nodes)

Availalble for free download at:
https://t.co/T4iIeQOC4B

Key points:

The good:
1. The new proposal ends the stage 3A paradox (that under the old eighth edition stage 3A does much better than stage 2)
2. The new proposal appropriately recognizes tumour deposits as an additional adverse finding (not as equivalent to node mets). That is, it recognizes that patients with tumour deposits and node mets do worse than those with one or the other only.

Room for improvement?
3. However our data shows that low T-stage (T1 and T2) patients with lymph node metastase do better than those without! Perhaps this should be considered in new stage groupings.
4. This results in the new proposed stage IIB being a heterogeneous group with the excellent prognosis T1 and T2 and intermediate prognosis T3 group
5. Proposed stage group 1 and 2A both have an excellent prognosis. Perhaps these should be renamed group 1A and group 1B to emphasize the similarities between these two groups of low T-stage disease (T1 and T2 respectively but node negative) rather than the differences.

Thoughts?

[Anthony J Gill @CaDxPath]

Ever year I put out this summary of the impact factors of the pathology journals that I most value reading. The new impact factors have just been released, and there are some interesting trends. Of course there is much more to journal selection than the impact factor . . . to me the main thing is targetting the audience that you most want to read your article. For example some articles are best read by national audiences, others by internatonal readership . . . some by subspeciality pathologists, others by general diagnostic surgical pathologists, still others by basic scientists interested in pathology.

[Anthony J Gill @CaDxPath]

Ever year I put out this summary of the impact factors of the pathology journals that I most value reading. The new impact factors have just been released, and there are some interesting trends. Of course there is much more to journal selection than the impact factor . . . to me the main thing is targetting the audience that you most want to read your article. For example some articles are best read by national audiences, others by internatonal readership . . . some by subspeciality pathologists, others by general diagnostic surgical pathologists, still others by basic scientists interested in pathology.