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Distinct biphasic histomorphological pattern in gastrointestinal stromal tumours (GISTs) with common primary mutations but divergent molecular cytogenetic progression
Author(s) -
Agaimy Abbas,
Haller Florian,
Gunawan Bastian,
Wünsch Peter H,
Füzesi László
Publication year - 2009
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2008.03214.x
Subject(s) - pathology , biology , gist , epithelioid cell , comparative genomic hybridization , immunohistochemistry , stromal cell , chromosome instability , mitotic index , cancer research , medicine , chromosome , mitosis , gene , genetics
Aims: 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. Methods and 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.