Does Immunohistochemistry Add to Morphology in Differentiating Trichoepithelioma, Desmoplastic Trichoepithelioma, Morpheaform Basal Cell Carcinoma, and Microcystic Adnexal Carcinoma?

Appl Immunohistochem Mol Morphol. 2022 Apr 1;30(4):273-277. doi: 10.1097/PAI.0000000000001002.


Background: The distinction among cutaneous basaloid neoplasms such as trichoepithelioma (TE), desmoplastic trichoepithelioma (DTE), morpheaform basal cell carcinoma (MBCC), and microcystic adnexal carcinoma (MAC) can be difficult, especially in superficial biopsies. As the treatment plan of each entity is different, accurate characterization is important for appropriate management. While TE and DTE are benign neoplasms with indolent behavior, MBCC and MAC are typically locally aggressive. The expression of several recently described immunohistochemical (IHC) markers, including p40, IMP3, and ProEx C, has not been adequately established in cutaneous neoplasms. We explored the potential utility of a broad IHC panel, including previously reported and novel markers to differentiate TE, DTE, MBCC, and MAC.

Design: A total of 35 archival cases [TE (n=14), DTE (n=9), MBCC (n=6), and MAC (n=6)] were stained with 9 IHC markers: p40, IMP3, ProEx C, p16, CK20, Ki-67, androgen receptor, D2-40, and beta-catenin. Tumors with >5% immunoreactivity were scored as positive. The intensity was scored on a scale from 1+ to 3+. The pattern of positivity- nuclear, cytoplasmic, membranous, or in combination; peripheral or central distribution with lesion was also recorded.

Results: CK20 (in contrast to prior studies) and IMP3 were negative in all cases. Likewise, with the exception of one case of TE, androgen receptor showed no immunoreactivity in all categories. No significant difference was observed in the expression of beta-catenin, p16, ProEx C, and p40 among the four groups of cutaneous neoplasms. The mean Ki-67 labeling index for MBCC (8%) was slightly higher than DTE (3%). Interestingly, the proliferation index for TE (15%) was significantly higher than that of MBCC. All six cases of MAC and 36% of TEs expressed D2-40; neither the MBCC nor DE cases showed D2-40immunoreactivity. Also, we confirmed the previously published observation of scattered CK20 positive Merkel cells in the epidermis of all cases of DTE; whereas, no Merkel cells were identified in MBCC and MAC cases.

Conclusions: Except Ki-67, our IHC panel showed no significant added diagnostic utility of IHC in discriminating among TE, DTE, MBCC, and MAC. Among the four cutaneous neoplasms, DTE and MBCC show a small but discernible difference in Ki-67.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Carcinoma, Basal Cell* / pathology
  • Diagnosis, Differential
  • Humans
  • Immunohistochemistry*
  • Ki-67 Antigen
  • Neoplasms, Adnexal and Skin Appendage / diagnosis
  • Neoplasms, Basal Cell* / diagnosis
  • Receptors, Androgen
  • Skin Neoplasms* / diagnosis
  • Skin Neoplasms* / pathology
  • beta Catenin


  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Receptors, Androgen
  • beta Catenin

Supplementary concepts

  • Microcystic adnexal carcinoma