Case Number : Case 2417 - 4 October 2019 Posted By: Dr. Richard Carr

Asymmetrical growth, with a partially lentiginous component in a elderly fit well with melanoma ( or with a very high grade dysplastic melanocytes tumor). IHC stains are consistent with melanoma ( I don't know much about PRAME ).

Favor Melanoma, horizontal growth. 

Melanoma.

This is case courtesy of a UK based dermatologist and dermatopathologist who will provide the feedback. I am pleased to let you all know that they have been invited on to the team and will provide regular cases for Spot Diagnosis. I first met him as a senior dermatology trainee around 15 years ago. He approached me to provide some dermpath experience. I quickly realised an extra-ordinary potential and wanted to encourage his interest. Within a 2 year period he had seen all of my skin, soft tissue, lymphoreticular and a good slice of the general slide collection (circa 4,000 slides at that point), sat in on sign-out of nearly all my routine diagnostic skin work (I would batch the reporting to coincide with his twice weekly visits) and gained the RCPath diploma in Dermatopathology, set at expert referral practice (at the the first attempt). He has worked in central hospitals as a consultant dermatologist with interest in lymphoma and also a part-post at a paediatric centre. In 2008 he attended the ISDP meeting in Graz. The meeting was so inspiring that this led to a change of career path to combine his exemplary clinical dermatology skills with diagnostic dermatopathology and we managed to secure a part-time appointment as a consultant dermatopathologist in our pathology network initially based with me in Warwick. Once he had gained considerable expertise as a dermatopathologist true to his nature of being a highly rounded individual he chose for family and personal reasons to opt for a post in the rural Devonshire town of Dorchester (Thomas Hardy country) where he consults in clinical dermatology and dermatopathology as well as maintaining an interest in a research laboratory (The Poundury Cancer Institute). He already has multiple publications in dermatology and dermatopathology and we are currently collaborating on work to further understand the biology of follicular SCC and keratoacanthoma. He is an excellent lecturer. He is lucky to have a remarkable wife (a consultant dermatologist) and two lovely daughters. He is currently studying to be a yoga teacher.  It is with great pleasure I hand this case over to my friend and colleague Dr Saleem Taibjee. 

I think it would be nice if we received many more comments on the case as a welcoming gesture to Dr Taibjee.

Dear Dermpath Pro colleagues

Thank you to Richard for the kind introduction.

I very much welcome feedback about any cases I post. Some will be straightforward, but others will be more contentious and hopefully we all benefit from the dialogue and discussions.

This first case is probably in the latter group, and I am interested that 2 of the participants have favoured melanoma.

My own favoured diagnosis, however, was benign or at worst dysplastic, and I was reassured that Richard had thought so too when reviewing the case when I had originally shared it with him.

My reasoning is that the lesion is small and well demarcated.. although there is inflammation and a phenotypic change (e.g. image 6, more epithelioid junctional component to the left vs smaller naevocytes to the right within the dermis), even the more epithelioid 'clone' has fairly bland nuclear cytology and there is no significant Pagetoid spread.

The bottom line is that were no clear-cut criteria for malignancy, and this is the flavour of report I issued in this case. Of course, the risk here is small, the lesion is predominantly junctional and unlikely to have any metastatic risk, hence in my view it is preferable to take a more pragmatic approach and avoid labelling the patient with melanoma, even if expressing some uncertainty.

Although the beta-catenin image is not showing this well, there did appear to be some nuclear positivity in the more epithelioid component, which as we know may indicate a deep penetrating naevus like clone/molecular pathway to account for the phenotypic heterogeneity. Of course, that would require substantiating on a molecular level.

For those unfamiliar with PRAME, I first became aware of this when Klaus Busam eloquently presented some preliminary findings in London last year. The relevant publication is Lezcano C, et al. PRAME Expression in Melanocytic Tumors. Am J Surg Pathol 2018;42:1456-65.

We have now acquired PRAME immunohistochemistry in our local laboratory, and in the initial few cases I have employed it in, it usually gives a clear signal of either positive or negative, and it does indeed seem to be promising as an adjunctive diagnostic tool to help discrimate benign from malignant melanocytic lesions in certain settings, or assist in determining margins. In that regard, PRAME is negative in this particular case (it usually shows crisp nuclear staining when positive), which is additionally reassuring.

Best wishes

Saleem

 Favouring inflamed junctional clonal naevus, ,DPN-type (rather the DN or MM)

H&Ex6, IHCx3