title: Fumarate hydratase immunohistochemical staining may help to identify patients with multiple cutaneous and uterine leiomyomatosis (MCUL) and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome.
abstract: OBJECTIVE
  Multiple cutaneous and uterine leiomyomatosis (MCUL) also named as hereditary leiomyomatosis and renal cancer syndrome (HLRCC) is an autosomal dominant disorder caused by heterozygotic germline mutations in fumarate hydratase (FH) with incomplete penetrance and clinically challenging to diagnose. To test immunohistochemistry for FH as a potential marker for the detection of FH-deficiency.
  
  
  RESULTS
  We have tested 42 smooth muscle neoplasms, 13 lesions of patients with suspicious or confirmed HLRCC, 20 sporadic piloleiomyomas, two angioleiomyomas and 7 leiomyosarcomas. FH staining grades from 1 to 3. Ten of the 13 lesions from the patients with HLRCC syndrome showed negative FH staining. Most sporadic piloleiomyomas presented grade 3 FH staining although five cases presented grade 1 FH staining. Sensitivity of FH staining in our series is 83.3% but specificity is 75%.
  
  
  CONCLUSIONS
  This staining could indicate a high risk of HLRCC in most of the confirmed cases but it could also suggest the presence of a syndrome in up to 25% of sporadic cases. HLRCC syndrome should be rule out in FH negative piloleiomyomas after complete anamnesis if multiple lesions or positive familiar history is found.
authors.affiliation: Department of Dermatology, Hospital Infanta Cristina, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Llamas-Velasco
authors.forename: L
authors.initials: L
authors.lastname: Requena
authors.forename: H
authors.initials: H
authors.lastname: Kutzner
authors.forename: L
authors.initials: L
authors.lastname: Schärer
authors.forename: A
authors.initials: A
authors.lastname: Rütten
authors.forename: M
authors.initials: M
authors.lastname: Hantschke
authors.forename: B E
authors.initials: BE
authors.lastname: Paredes
authors.forename: T
authors.initials: T
authors.lastname: Mentzel
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005649:Fumarate Hydratase / Q000032:analysis* / Q000172:deficiency*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D018231:Leiomyomatosis / Q000175:diagnosis*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis*; D008875:Middle Aged; D009123:Muscle Hypotonia / Q000175:diagnosis*; D009386:Neoplastic Syndromes, Hereditary; D011596:Psychomotor Disorders / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis*; D014594:Uterine Neoplasms / Q000175:diagnosis*
chemical_list: D005649:Fumarate Hydratase
keywords: fumarase; immunocytochemistry; piloleiomyoma