Case Number : Case 2672 - 02 October 2020 Posted By: Dr. Richard Carr

The tumor is some sort of an epithelioid intradermal melanocityc lesion, a little spitzoid, made me think of BAP1 inactivated melanocytic tumor. Where IHC stains performed?

Combined Nevus, DPN + common nevus. I have a question: was Beta-catenin positive? And in this case is, the CyclinD1 positivity, entirely dependent upon nuclear beta-catenin expression or could have an ominous prognostic significance?  But I don’t think this is a melanoma or something troubling... 

Not sure. ? Biphasic BAPOMA or a combined intradermal+spitz nevus- On right side there seems to be small nevoid cells with inconspicuous CYCLIN D1, on left the lesion has epithelioid/spitzoid morphology. 

Dr. Carr, what's about IHC with PRAME. You have any experience with that antibody?

agree with others-looks like a combined benign intradermal nevus with DPN

Well done. I reported this as a combined naevocellular (usually BRAF but can be other MAPK pathway lesions) and deep penetrating naevus (Beta-catenin mustation in most, APC in some - from memory). Beta-catenin was positive in the cytoplasm & nucleus in the DPN clone (I'll try to get it posted). I'm not sure if you can see a DPN without IHC beta-catenin translocated to the nucleus but it appears most cases are due to mutations in the beta-catenin gene and some have APC gene mutations. I have certainly seen a lesion recently that I thought was DPN with similar pattern for cyclin D1 which showed preserved membranous beta-catenin. DPN are grouped with "melanocytoma" i.e. lesions regarded as essentially benign (no or minimal metastatic risk) but with a small but unquantifiable risk for (further) malignant transformation. Criteria for "atypical" DPN are rather arbitrary but include increased cellular pleomorphism & greater mitotic rates (DPN have been described with scattered normal mitotic figures up to 2/mm2). I discussed the case with the ophthalmic surgeon because this was a small lesion with a narrow margin and the specimen had been examined lengthways. I advised watchful waiting since the lesion did not involve margins as far as we could see and due to the pigmentation any local recurrence should be easily identifiable. The IHC for beta-catenin is making the distinction from PEM & blue naevus with epithelioid cells more straight-forward but it appears that we find this distinction rather challenging on H&E alone in many cases. The key is to look for the naevocellular background (or blue) naevus in such lesions. You may know that blue lesions tend to have negative or weak S100 (compared to controls).

My experience with PRAME is limited and I cannot tell you the findings in DPN but will be happy to be educated but like all tests has to be used with caution. There is a recent discussion on this topic on dermpedia.

BAP lesions are hypopigmented Spitz-like, rounded, epithelioid cells, so it was not a consideration in this case but is of course another type of combined naevus / melanocytoma and needs consideration in the differential of Sptizoid lesions and naevoid melanomas.

Regarding p16 interesting that this case shows the re-assuring preserved strong mosaic pattern throughout which we are finding in keratoacanthoma and reactive epidermal & follicular hyperplasias and presumably represents an intact tumour suppression pathway.

Thanks Dr. Carr. My lab just got PRAME. I have been playing with the antibody a little bit so far but my experience is still very limited. My first impression is it does stain the nuclei of malignant melanoma, in situ and invasive. But I have seen maybe 3-4 cases so I am still learning.  

I've discussed beta-catenin & DPN with Arnaud de la Fouchardiere and it seems you can get a non-contributory beta-catenin IHC (i.e. absence of nuclear staining) in around 2% of DPN as published in the following article....

"Nuclear β-catenin expression was positive in 98/100 DPN and 2/16 of melanomas (one SSM and one nevoid melanoma with a plexiform clone) and was negative in all 30 Spitz, 26 blue, and 6 PEM lesions. In 41% DPN, β-catenin expression was positive in more than 30% nuclei. No differences were observed in cytoplasmic and nuclear cyclin D1 expression between these tumor groups, suggesting alternate, β-catenin-independent, activation pathways. We have subsequently studied nuclear β-catenin expression in a set of 13 tumors with an ambiguous diagnosis, for which DPN was part of the differential diagnosis. The three out of four patients showing canonical DPN mutation profiles were the only β-catenin-positive cases. We conclude that nuclear β-catenin expression, independently from CCND1 expression, in a dermal melanocytic tumor is an argument for its classification as DPN. In ambiguous cases and in early combined DPN lesions, this antibody can be helpful as a screening tool. β-Catenin is also potentially expressed in a subset of malignant melanomas with CTNNB1 mutations."

de la Fouchardière A, Caillot, Jacquemus J, Durieux E, Houlier A, Haddad V, Pissaloux. β-Catenin nuclear expression discriminates deep penetrating nevi from other cutaneous melanocytic tumors. Virchows Arch. 2019 May;474(5):539-550. doi: 10.1007/s00428-019-02533-9. Epub 2019 Feb 12.

https://pubmed.ncbi.nlm.nih.gov/30756182/