#dermpathJC August 2017 Summary:

#dermpathJC August 2017:

Thursday, August 24th, 9pm EST

Article discussed: BerEp4, cytokeratin 14, and cytokeratin 17 immunohistochemical staining aid in differentiation of basaloid squamous cell carcinoma from basal cell carcinoma with squamous metaplasia.

Authors: Linskey KRGimbel DCZukerberg LRDuncan LMSadow PMNazarian RM.

Archives of Pathology and Laboratory Medicine, November 2013, Volume 137, Issue 11, Pages 1591-8.

Free access at: http://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2012-0424-OA.

Special thanks to Dr. Katy Veprauskas (@LinskeyKaty) for providing the summary below.

Journal Club Summary


  • Basaloid squamous cell carcinoma (bSCC) of the skin and aerodigestive tract shows histologic overlap with primary and metastatic basal cell carcinoma with squamous differentiation (metatypical BCC, or BCCm).
  • BerEp4 has proved to be a helpful diagnostic aid owing to its positivity in basal cell carcinoma, however is limited due to its lack of strong staining in areas of squamous differentiation.
  • Squamous cell carcinoma tends toward more aggressive clinical behavior compared with basal cell carcinoma, therefore additional markers are needed to help facilitate diagnosis.

Aim of study:

  • To test immunohistochemical markers CK14 and CK17, along with BerEp4, to determine their utility in the distinction between bSCC and BCCm.


  • A total of 25 bSCC (8 cutaneous, 12 aerodigestive tract, 5 lymph node metastases) and 43 cases of BCCm (39 cutaneous, 4 lymph node metastases) were stained with BerEp4, CK17 and CK14.
  • The mean percentage of staining was significantly higher in BCCm compared with bSCC (BerEp4, P = .006; CK17, P < .001; CK17, P < .001).
  • The percentage of diffuse staining was also significantly higher in BCCm compared with bSCC (58% of BCCm cases displayed diffuse staining for all markers compared with no cases (0%) of bSCC).
  • Nearly all BCCm showed diffuse staining for CK17 and CK14 (98%), compared with 8% of bSCC.
  • Areas of squamous differentiation in BCCm often did not show staining with BerEp4.
  • Sensitivity, specificity, negative and positive predictive values are shown in Table 2.



  • BerEp4 alone is unreliable for differentiation between BCCm and bSCC, and the addition of CK14 or CK17 will augment the sensitivity and negative predictive value of BerEp4 staining in the diagnosis.


  • Small sample size.
  • Single center study.
  • Conflicting reports in prior literature due to different antibodies used and different definitions of BCCm.

Twitter Journal Club Discussion Summary:

  • Some (but not all) participants have noted occasional lack of reliable BerEp4 staining of BCC
  • Most participants do not have CK14 or CK17 in their lab, but they may be available as send out stains
  • Basaloid SCC of the skin was discussed as being a rare but important entity that we would not want to miss; potential extrapolation of study results to other SCC which do not meet Wain criteria but may be moderately differentiated or have other basaloid features
  • Discussed the distinction between aerodigestive tract bSCC and HPV-related oropharyngeal SCCs; bSCC is considered a separate entity which is not HPV related (all tested negative for p16 in our study) with a worse prognosis than HPV-related OPSCC.
  • Other immunostains that participants cited as helpful in the BCC vs SCC differential include MOC31 which stains BCC and UEA-1 which stains SCC (https://www.ncbi.nlm.nih.gov/pubmed/25702956); GATA3 also mentioned but may not be as helpful (supposed to stain BCC > SCC, but may also stain adnexal tumors which may enter the differential, and can also show some staining in SCC).

Thanks to all who participated! See you in September!

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