Concepts & Confusion With Regard to Non- Things that might be confused

Whitney A. High, MD, JD, MEng with non-melanoma skin cancer… Associate Professor, Dermatology & Pathology Director of Dermatopathology (Dermatology) University of Colorado School of Medicine

May 29, 2016 Newport Beach, CA

Common Entities in This What does this look like? Category

• (and dTE) • Mixed tumor of the skin • (and dTL) • • Palisading of nuclei 29 year old woman, left cheek…

Clefting immediately next to basloid islands

What ways exist to distinguish High Power H&E Examination trichoepithelioma from BCC? • The following has been proffered as “useful” in distinguishing TE/dTE from BCC:

Stain BCC Trichoepithelioma Bcl-2 Uniform & diffuse Peripheral only CK20 Negative Scattered MCs CD34 Negative Supporting stroma PHLDA1 Negative Positive

Also consider AR, CD10 (both + in TE), ST-1 (+ in BCC). Bcl-2 and CK20

Ideas that seem great in theory…

CD 34 Calcium

Basaloid neoplasm in dermis with horn cysts Horn and calcium cysts

Basaloid islands Trichilemmoma “Given that more than 7% of reported dTL reported an associated atypical basaloid proliferation, including BCC…”

P53 and Ki67 May Be of Utility in Stains To Adnexal Proliferations

“Establish General Badness” Spiradenocarcinoma/Malignant ?

46 year-old woman

Left arm

“r/o cyst”

12.5x 50x Internal “Control” Immunohistochemistry

Ki-67

• Hypercellularity • Innumerable atypical mitoses • Spontaneous necrosis P53

Comparative measures?

Pilomatrical carcinoma is a “somewhat subjective diagnosis…” – David Weedon • Pilomatrical carcinoma with KNOWN mets, the Ki67 index was ~50% • Study of pilomatrical carcinoma versus pilomatricoma, only the carcinomas P53 (+) The Actual Excision

Adipophilin (the “new” thing)

Ostler et al. Mod Pathol. 2010 Immunostains to Screen for Muir Torre

MLH-1 MSH-2 MSH-6 Screening for & sebaceoma as well.

Entities that Confuse or Confound NMSC

• TE with nevus • BCC with nevus • Dermatofibroma with induction(s) • Focal cutaneous miucinosis with induction(s) • Nevus sebaceous (with neoplasia in it)

“r/o BCC?”

Induction over DF Fibrohistiocytic cells intercalated between collagen bundles

Fibrotic and cellular (“busy”) dermis above subcutis

Entrapping of collagen (“donut sign”)

More Extreme Example Induction over FCM

Acanthotic epidermis

Other Problematic Entities Area of with Induction and Neoplasia alopecia

Basaloid processes in nevus sebaceus

Hamartomatous apocrine glands

Basaloid induction of uncertain biologic potential

Sebaceous glands Enlarged sebaceous glands Other Mistakes Made with Nonmelanoma Skin Cancer • Missing a basal due to sampling or artefactual changes • Misjudging connective tissue disease Basal cell • Misjudging pseudoepitheliomatous carcinoma hyperplasia (infections etc.) • Missing a Merkel cell carcinoma • Misjudging immunostains

Few remaining “clinging” ? basaloid cells Phone call from a client…

“Diagnosed as SCC, here in town, but he keeps getting more and more, and I can’t cut them out fast enough…”

One of the actual specimens called SCC…

“I have some ideas. Please send me the prior report, so that I can request the slides.”

“Also, please don’t do anymore surgery.” Case

A 51 year old has persistent inflammation and swelling after a surgical procedure for “SCC” of the ear. Serous, hemorrhagic and inflammatory crusting Russell body Mott cell

Mostly lymphocytes, histiocytes, plasma cells Continued inflammatory Ulcer infiltrate in the dermis

Look here!

Minute “dots” getting even larger yet, among the otherwise chronic inflammation Case

Be vigilant… avoid problems

Case Case Case Immunostains

CK20 marks 80-90% of MCC Marks ~80%* MCC, does not mark BCC

Patient • 58 year old man • History of GVHD (unknown reason) • History of multiple non-melanoma cancers on the scalp • No prior biopsies at our facility • Specimen was seconds away from s/o “SCCIS with scar” P53 CK20

Is this basal cell carcinoma?

Always, always, always remember…

SCC and SCCIS can be seen overlying or induced by MCC. Immunohistochemical Staining Immunohistochemical Staining

BerEp4 BerEp4 Cytokeratin 7

First Stage - Mohs’ (Frozen Section) Re-Excision Re-excision IHC Studies Re-excision IHC Studies

CK 7 BerEp4 CK 7 BerEp4 Her2Neu Ki-67 Her2Neu Ki-67

Breast Cancer

Back to the same old, same old.

37 year old ear. SCC, right? Mart1

Later Levels S100 Ok, ok, how about this one?

Come on.

S100 SOX10