Regardless of Richard,s cocktail of P16,P53, and Ki67 ; I guess the configuration is excellent for KA.

The silhouette fits well a KA diagnosis. But there are some conflicting details: 1) squamous cells don’t appear pale enough; 2)the external border at the left isn normal appearing; 3) I don’t see ( but not sure of course ) elastic material entrapped; 4) ther’s an acantholytic trend between basal/parabasal layer and overlying epidermis. 

Moreover I think there’s a keratin granuloma, but I don’t know what it means. Waiting the Richard’s comment. 

Looks like KA to me. Eager for Dr. Carr's comments. 

null type p16 and p53 not fitting with KA

Well done Nadine did you by any chance attend Friday's marathon?

KA is a CLIN-H&E/EVG-IHC diagnosis according to my new work. See below

CLINICAL: 80% of KA are on the intermittently sun-exposed limb. Chronically sun-damaged scalp almost never. M:F approx. 1:1, median age ~75 years compared with ~80 for SCC.

HISTO: No single criterion but. I've been using 17 to classify KA-like lesions.

This lesion falls down on so many levels one can make a sure diagnosis of follicular SCC.

I forgot (perhaps i'm getting lazy!) - Desmoplasia 0! Have to say most folliclar SCC (and therefore most cutaneous SCC) don't give rise to desmoplasia ?something to do with the origin from folliclar cells which are not conflicted with the stroma! Just a theory. You should consider ?CLL in such cases but I think this case had plenty of plasma cells so not likely but no harm in making an enquiry about the lymphocyte count with the clinician.

On a serious note. If you list out the 17 features and make sure you check each your less likely to miss a feature that is absent ("The dog that did not bark in the night" solving the crime, Sherlock Holmes)

Thanks Richard, very educative comment!!! My specialty thesis was the KA, but I’m starting to learn now this lesion, thanks to you.

Keratin granulomas are great for regressing KA but not specific. Crateriform (follicular) SCC can show extensive regression and it's caught me out unfortunately into making an incorrect diagnosis myself of a crateriform SCC with extensive regression that metastasied and I'd favoured a KA (it was p16 null on review with the metastasis - basically it was a wrong diagnosis and no metastasising typical KA). 

Dear sir

Then this article, it must have been really follicular SCC

Squamous Cell Carcinoma Arising in Keratoacanthoma: A Neglected Phenomenon in the Elderly

Weedon, David D MD, FRCPA; Malo, Jonathan BSc (Physiol); Brooks, David B Biomed Sci; Williamson, Richard MBBS, FRCPA

Dear krishnakumar - if you use my criteria above all three cases illustrated by Weedon in 2010 paper are more than likely just FSCC with KA-like PEH (I have many examples). I have seen many more examples of the latter than really convincing KA with malignant area (although I do have one or two very convincing examples) and even then it's possible the KA developed on or near an AK lesion and not necessarily the other way round! He (Weedon) is a great great man and so was Ackerman, and so are Mckee, Requena (25% of KA lesions have malignant transformation - although also sun-exposed and more elderly) and many many more all great but did not recognise that most SCC on sun-exposed, hair bearing skin are follicular (infundibular-tricholemmal). Interestingly Weedon cautioned about KA in >90 years (13% malignant transformation). Welcome to the new paradigm: KA in NOT SCC and most SCC are on sun-exposed hair bearing skin are follicular (infundibular-tricholemmal) tumours, 80% head and neck, severely sun-damaged and hair bearing skin (where all the tiny vellus hair germs sit surrounded entirely by solar elastosis). Also epidermal keratinocytes have natures sun-hat (melanin) that those little vellus germs don't have (after all nature decided that in evolution it is not too concerned with balding men >60 years who did not survive in pre-history). Seems our modern society is happy to throw enormous research and money at melanoma, that affects younger humans, a tumour that frequently can mimic a benign lesion (and highly challenging uncertain lesions we call MELTUMP). When we admit uncertainty on CLIN-H&E we regularly apply IHC and molecular techniques to help clarify the issue. In KA v's KA-like SCC at least as challenging (as illustrated above) we have not got off the starting blocks and somehow lost our way and any resemblance of scientific rigour. Simple logic (above) dictates most skin SCC are derived from the follicular vellus germs. We only reported 4% of invasive SCC arising from bowenoid dysplasia in an audit in 2013 and in my experience most SCC don't have associated AK or BAK.  The p16, p53, Ki67 work merely confirmed my suspicions beyond reasonable doubt (that KA are not SCC) but it required a meticulous study over more than 15 years culminating in the extraordinary conclusion that the "eyes cannot see what the brain does not know" even for the greats in dermatopathology! Also diagnostic criteria (as above) and exemplified by Ackerman's approach have not been systematically applied to KA. Researches used a hotch potch of criteria (not used by Weedon) some okay but many severely lacking and more typical of FSCC! We have so much more to learn but when we "don't know" we should say so, not make a pretence we can tell benign from cancer in difficult cases of uncertainty. When we make a diagnostic mistake (even if it is understandable at the time of diagnosis and only revealed by a metastasis / bad outcome) we should learn from it and develop better criteria & understanding in the future. This is called scientific research according to Karl Popper. Unfortunately pseudo-science pervades most areas of modern life. At least covid gave me a little more time to work this out! Would you believe there are those who believe strongly Covid does not exist but is a conspiracy - does this sound familiar? Now to challenge the traditional concepts - it may need the true and the good of Dermpathpro users to spread the message person by person and maybe one day we will develop a better understanding and even work out the molecular biology as to why KA (a cancer according to the WHO) regresses, develop a cure for cancer and perhaps those people that sort it will take the trip to Stokholm mentioned in Philip LeBoit's editorial around 20 years ago in Am. J. Dermpath.

Thanks for clarifying this sir, what's your thoughts on Voriconazole induced atypical squamoproliferative lesions and this where there was a dilemma whether it was KA or SCC and they excised it

Do you suggest use of p16 and p53 sir routinely

New Onset of Keratoacanthomas After Vismodegib Treatment for Locally Advanced Basal Cell Carcinomas: A Report of 2 Cases

Dear Krishnakumar,

Great reference. They'd need to be tested against the criteria above and IHC (yes on ALL KA!).

They look good for KA note the first case is on non-sun-exposed skin and the second under the brow ridge intermittently sun-exposed skin.

Some of the lesions have beta HPV (I'd guess similar to what was found in BRAFi Rx for melanomas.

But was is your opinion....?

Warm regards

Richard

On 23/11/2020 at 12:09, Dr. Richard Carr said:

Well done Nadine did you by any chance attend Friday's marathon?

KA is a CLIN-H&E/EVG-IHC diagnosis according to my new work. See below

CLINICAL: 80% of KA are on the intermittently sun-exposed limb. Chronically sun-damaged scalp almost never. M:F approx. 1:1, median age ~75 years compared with ~80 for SCC.

HISTO: No single criterion but. I've been using 17 to classify KA-like lesions.

This lesion falls down on so many levels one can make a sure diagnosis of follicular SCC.

I'll check my "score" from the database for it and get back to you but the main features I assess are outlined below (this is certainly still at an experimental stage but a typical KA comes in at or below 10% (i.e.score 3.4 / 34 if you can score all criteria in a completely excised lesion such as this. I'd guess this case would score >35% (i.e. 12/34) which is my approximate cut-off for a confident diagnosis of FSCC (I've just totted it up based on the images at 16.5!). My scores: Symmetry 0.5; Lips 1; Crater 0; Base 1; Verticality 2; Depth 2; parakeratosis / dyskeratosis: 1.5; Abscesses 2; Necrosis 0; Thickened prolifeartive zone: 1; Acantholysis 0.5; Mucin 0; Lichenoid reaction 1 (not producting much effect i.e. civatte/colloid bodies or much squamatisation); Regression: 2 (minimal); Entrapment 2 (Nil seen here). So it looks like some of you need to learn how to diagnose KA - but to be fair nearly all of the worlds histopathologists also will need to sharpen their diagnostic skills because our work indicates KA are not SCC all typical lesions having a benign IHC profile thus far. Both p16 and p53 are null but with such a lesion it's icing on the horn! Oh in KA the horn is more laminar orthokeratotic superficially and does not usually poke out above the lips as here. So a horn clinically on sun-damated head and neck skin would be almost impossible for a typical KA.  You can practically r/o KA on the damaged scalp of an elderly male BTW. Symmetry: 2 = Poor; 1 = roughly; 0 = Good

Lateral Lips: 2 = Minimal; 1 = poor/asymmetrical 0 = symmetrical well formed

Crater:  2=Minimal; 1 = poorly formed; 0 = Yes nicely formed

Even Rounded base: 2 = No; 1 = partial; 0 = Yes

Vertical growth > Lateral: 2 = striking (>1:1); 1 = equivocal (>1:2); 0 = No (≤1:2)

Depth relative to sweat Glands: Below = 2;  at or above = 0

Dyskeratosis & Parakeratosis: Prom = 2; Focal = 1; Minimal = 0

Intra-epithelial neutrophil microabscesses: 2 = min; 1 = focal; 0 = Prom

Necrosis (RAC): 2 = extensive; 1 focal; 0 = minimal

Thick basaloid peripheries: 2 = Prominent; 1 = Equivocal 0 = No

Good even maturation to keratin throughout: 2 = Poor; 1 = variable; 0 = yes

Acantholysis: 2 = Prom; 1 = focal; 0 = Minimal

Follicular Mucin: 2 = Prom; 1 = focal; 0 = Minimal: n/a = 1

Lichenoid reaction/colloid bodies: 2 = Minimal; 1 = patchy; 0 = striking

Stromal desmoplasia between nests (RAC): 2 = prom. 1 = mild; 0 = minimal

Regression (RAC); 2 minimal; 1 = <50%; 0 = >50%

Intra-epithelial elastic/collagen trapping (EVG): No = 2; 1 = focal; Prom = 0

 

 

 

Thanks a ton Dr. Carr for giving these set of criteria to resolve KA vs FSCC. You have been telling us about the p16, p53 and Ki67 staining patterns as well helpful in distinction, have you devised any scoring system for IHC as well. These discussion you are having has made me interested in this entity a lot more. I am asking for too much, but cold you please also provide the various types of IHC patterns for us to have a comprehensive set of parameters.

Regards!

I'm in the process of writing up paper and the patterns for publication. I'll continue to share cases and the range of patterns but a complete null is by for the most common for p16 in SCC. Warm regards

R

21 hours ago, Dr. Richard Carr said:

I'm in the process of writing up paper and the patterns for publication. I'll continue to share cases and the range of patterns but a complete null is by for the most common for p16 in SCC. Warm regards

R

Thank you Dr. Carr. Looking forward to publication.

Yes attended Fridays marathon, thanks Richard for your teaching it made alot of sense.