Case Number : Case 1481-26 February Posted By: Guest

Nipple fibrino-emorragic ulceration, with reactive atypical epithelia cells ( do not look like pagetoid...). Radiation induced ulcer of the nipple?

I liked Vincenzo's suggestion.

Luminal expression of Cam5.2 and CK7, isn't it?

Those are Toker cells highlighted by the IHQ, it would be interesting to include HER2neu and or polyclonal CEA as those markers are positive in Paget's (I dont think there is need of doing them in this case).

Yes it could be radiation induced ulcer/dermatits if the clinical fits, that is a good suggestion

I agree with Vincenzo's suggestion of radiation induced ulceration. However, it is a tricky case. Both Toker cells and Paget's show a similar immunoprofile (CK7+). Rarely Toker cells, can be Her2 neu+ (and Paget's can be negative), and can also express ER, and can show atypia!  CD138 can be helpful, along with p53 (positive in Paget's), and negative in Toker cells. I haven't personally used CD138. The age group is right for Paget's disease. Need correlation with radiology. Did she have history of radiation? I would be cautious, and recommend rebiopsy, after the ulcer heals. 

Yes, Toker cells and Paget's show similar immunoprolfie, but morphologically this is not Paget's. Also CAM 5.2 doe not show any positivity in the area of ulceration (1st image), only scattered cells in the adjacent epidermis; so would go with Toker cells.

The cause of the ulcer is uncertain in these images…radiation induced ulcer may fit, provided there is a history. Cant seen any radiation fibroblasts or typical vascular changes though!

This is a very difficult case.  I gave you the exact information that came with the request but subsequent enquiry revealed there was a previous history of contralateral mastectomy for extensive DCIS and ipsilateral WLE for DCIS with radiotherapy that caused "significant radiation burns". These two punch biopsies were initially reported as showing ulceration with abundant foreign material within the exudate. No evidence of neoplasia.

At MDM review discussion mild spongiosis was noted. She was treated with potent topical steroids. On review at 3 months the area was larger and remained suspicious given the past medical history.  Patient was very reluctant to undergo another biopsy but finally acquiesced and I received the specimen which showed florid Paget's disease.  I then reviewed the prior biopsies which in my opinion showed unexplained ulceration, quite striking and suspicious cellular atypia leading me to suspect subtle Paget's disease.  The immunostains showed a few clusters and individual cells but the majority of atypical cells appeared to be compatible with reactive keratinocytes.  In my opinion the initial biopsies should have been reported as showing ulceration of undetermined cause i.e. non-diagnostic and additional levels & immunostains performed. I suspect this is Paget's and not just Toker cell's but it is hard to be definitive.

Learning Points:

As a general rule be very suspicious of nipple biopsies and have a low threshold for deeper levels and immunostains, try to be fully cognizant of the complete clinical history.

Nice case. Thanks Dr Carr!