title: Distinct biphasic histomorphological pattern in gastrointestinal stromal tumours (GISTs) with common primary mutations but divergent molecular cytogenetic progression.
abstract: OBJECTIVE
  The morphological diversity of gastrointestinal stromal tumours (GISTs) is well appreciated. The aim of this study was to shed light on the molecular pathogenesis of GISTs displaying a distinct biphasic histomorphological pattern, which is poorly understood.
  
  
  RESULTS
  Six biphasic gastric GISTs (four high, one intermediate and one low risk for aggressive behaviour) were studied by histological, immunohistochemical, molecular and comparative genomic hybridization methods. The different tumour components were designated as primary and secondary compartments, based on cellularity and mitotic index. In addition, metastases from two patients were analysed separately. According to the classification of Miettinen et al., four biphasic histomorphological patterns were seen: (i) sclerosing spindle cell/dyscohesive or paraganglioma-like epithelioid (n = 2); (ii) sarcomatous spindle cell/pleomorphic sarcomatous spindle cell (n = 1); (iii) sarcomatous spindle cell/sarcomatous epithelioid (n = 2); and (iv) sclerosing epithelioid/hypercellular epithelioid/sarcomatous epithelioid (n = 1) morphology. In each case, both tumour compartments revealed the same KIT (n = 5) or platelet-derived growth factor receptor-alpha (n = 1) mutation, as well as common chromosomal imbalances reflecting their common clonal origin. Additional chromosomal imbalances were detected in the secondary tumour compartments and their respective metastases.
  
  
  CONCLUSIONS
  Our results indicate that the intratumoral phenotypic diversity in GIST reflects histomorphological progression, which is associated with higher chromosomal instability, irrespective of the primary mutation.
authors.affiliation: Institute of Pathology, Nürnberg Clinic Centre, Nürnberg, Germany. abbas.agaimy@uk-erlangen.de
authors.forename: Abbas
authors.initials: A
authors.lastname: Agaimy
authors.forename: Florian
authors.initials: F
authors.lastname: Haller
authors.forename: Bastian
authors.initials: B
authors.lastname: Gunawan
authors.forename: Peter H
authors.initials: PH
authors.lastname: Wünsch
authors.forename: László
authors.initials: L
authors.lastname: Füzesi
mesh_terms: D000368:Aged; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation