Case Number : Case 2997 - 31 December 2021 Posted By: Dr. Richard Carr

lobules of atypical squamoid cells surrounded by dense lymphocytic cells or vague granuloma with surrounding lymphocytes

Not clear on morphology

may be lymphoepithelial tumor

I was thinking of a lymphoepithelial carcinoma, too, ?primary.

Perhaps lymphoepithelial-like carcinoma would be a more appropriate definition. 

Happy new year everybody!

Looks like lymphoepithelioid Ca. I would like to see an EBER stain

p16 immunohistochemistry is usually negative in lymphoepithelial carcinoma since P 16 is positive should we do testing for HPV where 16 is positive

Yes this is a lymphoepithelioma-like carcinoma. I suspect many are from the adnexa (probably follicular stem cells mainly) because, as is typical,  there no surface tumour. Do you have a reference regarding p16 and LELC as I'm not familiar with any studies off the top my head although I didn't google it specifically. I do know that p16 diffuse positive >90% of the cells is quite uncommon generally but often seen in Bowenoid epidermal dysplasia (whether HPV or non-HPV associated) and very uncommon in follicular SCC and non-bowens associated SCC. My understanding is that high p16 in the setting of high risk HPV is accumulation of wild type protein. We allow staining up to 90% that we suspect is wild type and reactive in KA but nearly always retains more variation in intensity mild/moderate/strong mosaic which might even be the case in this tumour. p16 can also appear high when there is a clear cut highly aberrant (null or diffuse moderate/strong) p53 as in this case. So my semi-educated guess of the molecular in a case like this is a mutation of a p53 that has abnormally sequestered due to longer half-like and a preserved but up-regulated p16 as a secondary response to the loss of p53 function. We don't know if the presumed mutations in p53 are bi-allelic, theoretically a normal allele could compensate but I'd guess it is likely, judging by the p16 over-expression p53 function has been lost i.e. the 2nd allele lost, mutated or methylated, or the 1st allele with a dominant mutation that stops the normal p53 function from the other allele. Sadly IHC and genetics are rather complex to correlate without very detailed studies. However like most carcinomas on the severely sun-damaged skin we do have highly aberrant patterns for one if not both IHC markers in this case.