title: Primary cutaneous perivascular epithelioid cell tumor: a clinicopathological and molecular reappraisal.
abstract: BACKGROUND
  Perivascular epithelioid cell tumor (PEComa) is a rare neoplasm of uncertain histogenesis with a mixed myomelanocytic immunophenotype, rarely arising in the skin (primary cutaneous PEComa [pcPEComa]).
  
  
  OBJECTIVE
  We analyzed the clinicopathological features of 8 pcPEComas, assayed for DNA copy number changes and for initiating mutations common in melanocytic neoplasms.
  
  
  METHODS
  pcPEComas were evaluated using immunohistochemistry, comparative genomic hybridization, and DNA sequencing.
  
  
  RESULTS
  pcPEComas were erythematous nodules, mostly in the lower extremities of women (5/8), composed of large pale-staining epithelioid cells. The patient's age range was 26 to 67 (mean 46) years. The percentages of tumors staining positively were as follows: micro-ophthalmia-associated transcription factor, NKI/C3, bcl-1, E-cadherin, and cathepsin K (100%); HMB-45, 4E-binding protein 1, and CD68 (88%); smooth muscle actin and muscle-specific actin (40%); S100 (38%); calponin (20%); desmin (13%); and melan-A, SOX10, and keratin (0%). No chromosomal copy number changes or initiating mutations were identified.
  
  
  CONCLUSIONS
  Small sample size is a limitation.
  
  
  CONCLUSIONS
  pcPEComas have a different molecular signature than extracutaneous tumors and are unrelated to tuberous sclerosis. However, the common expression of 4E-binding protein 1 points to a role of the mTOR pathway in their pathogenesis. Because pcPEComas are diagnostically challenging, we propose that micro-ophthalmia-associated transcription factor, NKIC3, smooth muscle actin, desmin, bcl-1, cathepsin K, and 4E-binding protein 1 can be used when evaluating a possible pcPEComa.
authors.affiliation: Pathology, University of California San Francisco, San Francisco, California; Dermatology, University of California San Francisco, San Francisco, California.
authors.forename: Yann
authors.initials: Y
authors.lastname: Charli-Joseph
authors.affiliation: Pathology, University of California San Francisco, San Francisco, California; Dermatology, University of California San Francisco, San Francisco, California.
authors.forename: Andrea
authors.initials: A
authors.lastname: Saggini
authors.affiliation: Pathology, University of California San Francisco, San Francisco, California.
authors.forename: Swapna
authors.initials: S
authors.lastname: Vemula
authors.affiliation: Pathology, University of California San Francisco, San Francisco, California.
authors.forename: Jingly
authors.initials: J
authors.lastname: Weier
authors.affiliation: Pathology, University of California San Francisco, San Francisco, California.
authors.forename: Sonia
authors.initials: S
authors.lastname: Mirza
authors.affiliation: Pathology, University of California San Francisco, San Francisco, California; Dermatology, University of California San Francisco, San Francisco, California; Helen A. Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. Electronic address: philip.leboit@ucsf.edu.
authors.forename: Philip E
authors.initials: PE
authors.lastname: LeBoit
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D055028:Comparative Genomic Hybridization; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D056915:DNA Copy Number Variations; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D054973:Perivascular Epithelioid Cell Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000097382:CD68 Molecule
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D056657:Cathepsin K; D018797:Cell Cycle Proteins; D019938:Cyclin D1; D003893:Desmin; D051739:Microphthalmia-Associated Transcription Factor; D010750:Phosphoproteins; C530104:CCND1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C087000:EIF4EBP1 protein, human; C497234:MITF protein, human; C534130:CTSK protein, human
keywords: array-based comparative genomic hybridization; cutaneous clear cell myomelanocytic tumor; initiating mutations; mTOR pathway; perivascular epithelioid cell tumor