title: PHLDA1 (TDAG51) is a follicular stem cell marker and differentiates between morphoeic basal cell carcinoma and desmoplastic trichoepithelioma.
abstract: BACKGROUND
  Morphoeic basal cell carcinoma (BCC) and desmoplastic trichoepithelioma can often be difficult to differentiate on routine sections and few reliable immunohistochemical markers are currently available. Recent cDNA microarray studies revealed the pleckstrin homology-like domain, family A, member 1 protein (PHLDA1) as a highly reliable marker of the hair follicle stem cells. Given the differentiation of trichoepithelioma along the follicular lineage and the proposed role of PHLDA1 as a follicular stem cell marker, we examined the staining pattern of PHLDA1 in the desmoplastic variant of trichoepithelioma and in its differential diagnostic conundrum, morphoeic BCC.
  
  
  OBJECTIVE
  To describe the expression pattern of PHLDA1 in morphoeic BCC and desmoplastic trichoepithelioma.
  
  
  METHODS
  Evaluation of the staining pattern for PHLDA1 was performed using standard immunohistochemical techniques. For comparison reasons, we analysed staining for PHLDA1 in normal skin structures with particular reference to the hair follicle.
  
  
  RESULTS
  With the exception of one case, all 16 desmoplastic trichoepitheliomas were immunoreactive with more than 80% of the cells stained, whereas all 14 morphoeic BCCs were PHLDA1-negative with the exception of ulcerated tumours. In the latter, the tumour islands close to the ulcer were PHLDA1-positive whereas the deeper located tumour portions remained immunonegative. PHLDA 1 was prominently expressed in the hair follicle bulge of terminal and vellus hair follicles.
  
  
  CONCLUSIONS
  The hair follicle bulge marker PHLDA1 differentiates between desmoplastic trichoepitheliomas and nonulcerated examples of morphoeic BCCs. We suggest incorporating PHLDA1 in the diagnostic work-up of difficult to differentiate basaloid tumours.
authors.affiliation: Department of Dermatology, A61, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA. klaus.sellheyer@gmail.com
authors.forename: K
authors.initials: K
authors.lastname: Sellheyer
authors.forename: D
authors.initials: D
authors.lastname: Krahl
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002280:Basal Cell Carcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D018859:Hair Follicle / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008544:Melanocytes / Q000378:metabolism; D008875:Middle Aged; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells; D013545:Sweat Glands / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C491923:PHLDA1 protein, human; D014157:Transcription Factors