title: Giant Basal Cell Carcinomas Express Neuroactive Mediators and Show a High Growth Rate: A Case-Control Study and Meta-Analysis of Etiopathogenic and Prognostic Factors.
abstract: BACKGROUND
  Giant basal cell carcinomas (GBCCs), (BCC ≥ 5 cm), are often painless, destructive tumors resulting from poorly understood patient neglect.
  
  
  OBJECTIVE
  To elucidate etiopathogenic factors distinguishing GBCC from basal cell carcinoma (BCC) and identify predictors for disease-specific death (DSD).
  
  
  METHODS
  Case-control study examining clinicopathologic and neuroactive factors (β-endorphin, met-enkephalin, serotonin, adrenocorticotropic hormone, and neurofilament expression) in GBCC and BCC. Systematic literature review to determine DSD predictors.
  
  
  RESULTS
  Thirteen GBCCs (11 patients) were compared with 26 BCCs (25 patients). GBCC significantly differed in size, disease duration, and outcomes; patients were significantly more likely to live alone, lack concern, and have alcoholism. GBCC significantly exhibited infiltrative/morpheic phenotypes, perineural invasion, ulceration, and faster growth. All neuromediators were similarly expressed. Adenoid phenotype was significantly more common in GBCC. Adenoid tumors expressed significantly more β-endorphin (60% vs. 18%, P = 0.01) and serotonin (30% vs. 4%, P = 0.02). In meta-analysis (n ≤ 311: median age 68 years, disease duration 90 months, tumor diameter 8 cm, 18.4% disease-specific mortality), independent DSD predictors included tumor diameter (cm) (hazard ratio (HR): 1.12, P = 0.003), bone invasion (HR: 4.19, P = 0.015), brain invasion (HR: 8.23, P = 0.001), and distant metastases (HR: 14.48, P = 0.000).
  
  
  CONCLUSIONS
  GBCC etiopathogenesis is multifactorial (ie, tumor biology, psychosocial factors). BCC production of paracrine neuromediators deserves further study.
authors.affiliation: *Albany Medical College, Albany, NY; †Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; ‡VA Boston Healthcare System Geriatric Research, Education and Clinical Center, Boston, MA; §Department of Dermatology, University of Alabama at Birmingham, VA Medical Center, Birmingham, AL; ¶Western Pathology, Inc., San Luis Obispo, CA; ‖Department of Plastic Surgery, Albany Medical College, Albany, NY; **Loyola Stritch School of Medicine, Maywood, IL; and ††Department of Pathology, Albany Medical College, Albany, NY.
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Yazdani Abyaneh
authors.forename: Peter
authors.initials: P
authors.lastname: Engel
authors.forename: Andrzej
authors.initials: A
authors.lastname: Slominski
authors.forename: Bruce
authors.initials: B
authors.lastname: Ragsdale
authors.forename: Richard
authors.initials: R
authors.lastname: Agag
authors.forename: Daniel
authors.initials: D
authors.lastname: Cramer
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Carlson
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000032:analysis / Q000096:biosynthesis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D016022:Case-Control Studies; D004744:Enkephalin, Methionine / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012701:Serotonin / Q000032:analysis / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000523:psychology; D055815:Young Adult; D001615:beta-Endorphin / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D012701:Serotonin; D004744:Enkephalin, Methionine; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone