PMID- 25857825 OWN - NLM STAT- MEDLINE DCOM- 20160406 LR - 20230210 IS - 1530-0285 (Electronic) IS - 0893-3952 (Linking) VI - 28 IP - 7 DP - 2015 Jul TI - ALK rearrangement and overexpression in epithelioid fibrous histiocytoma. PG - 904-12 LID - 10.1038/modpathol.2015.49 [doi] AB - Epithelioid benign fibrous histiocytoma, also known as 'epithelioid cell histiocytoma,' has traditionally been considered a morphologic variant of cutaneous fibrous histiocytoma (dermatofibroma). In addition to its characteristic epithelioid cytomorphology, several phenotypic differences suggest that epithelioid fibrous histiocytoma may differ biologically from other variants. Recently, ALK rearrangement was described in two cases of epithelioid fibrous histiocytoma and separately in two cases reported as 'atypical' fibrous histiocytoma (with epithelioid features), with corresponding ALK expression detectable by immunohistochemistry. The goals of this study were to determine the frequency of ALK expression by immunohistochemistry in epithelioid fibrous histiocytoma, to determine its value for the diagnosis of epithelioid fibrous histiocytoma among variants and other histologic mimics, and to evaluate ALK gene rearrangement in epithelioid fibrous histiocytoma. ALK protein expression was evaluated in whole tissue sections from 33 epithelioid fibrous histiocytomas, 41 other cases of fibrous histiocytoma (11 conventional and 10 each cellular, atypical, and aneurysmal types), 10 cutaneous syncytial myoepitheliomas, and 5 atypical fibroxanthomas, using a mouse anti-ALK monoclonal antibody. Fluorescence in situ hybridization (FISH) was performed using break-apart probes. In total, 29/33 (88%) cases of epithelioid fibrous histiocytoma showed diffuse cytoplasmic ALK expression. Staining was moderate to strong in intensity in all cases except one, which showed diffuse weak expression. All other tumor types were negative for ALK expression. FISH demonstrated ALK rearrangement in all ALK-immunoreactive cases evaluated (n=13), and not in one ALK expression-negative epithelioid fibrous histiocytoma successfully examined. In conclusion, the majority of epithelioid fibrous histiocytomas demonstrate ALK expression and ALK gene rearrangement. ALK expression is not seen in other variants of fibrous histiocytoma, providing a useful diagnostic tool to distinguish epithelioid fibrous histiocytoma from most histologic mimics. The expression of ALK suggests that epithelioid fibrous histiocytoma is a biologically distinct tumor type, unrelated to conventional fibrous histiocytoma and histologic variants. FAU - Doyle, Leona A AU - Doyle LA AD - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Marino-Enriquez, Adrian AU - Marino-Enriquez A AD - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Fletcher, Christopher D M AU - Fletcher CD AD - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Hornick, Jason L AU - Hornick JL AD - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. LA - eng PT - Journal Article DEP - 20150410 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Alk protein, mouse) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Anaplastic Lymphoma Kinase MH - Diagnosis, Differential MH - Epithelioid Cells/*metabolism/pathology MH - Gene Expression Regulation, Neoplastic MH - *Gene Rearrangement MH - Histiocytoma, Benign Fibrous/*diagnosis/genetics/metabolism/pathology MH - Humans MH - Receptor Protein-Tyrosine Kinases/*genetics/metabolism MH - Skin Neoplasms/*diagnosis/genetics/metabolism/pathology EDAT- 2015/04/11 06:00 MHDA- 2016/04/07 06:00 CRDT- 2015/04/11 06:00 PHST- 2015/01/15 00:00 [received] PHST- 2015/03/06 00:00 [revised] PHST- 2015/03/07 00:00 [accepted] PHST- 2015/04/11 06:00 [entrez] PHST- 2015/04/11 06:00 [pubmed] PHST- 2016/04/07 06:00 [medline] AID - S0893-3952(22)01399-0 [pii] AID - 10.1038/modpathol.2015.49 [doi] PST - ppublish SO - Mod Pathol. 2015 Jul;28(7):904-12. doi: 10.1038/modpathol.2015.49. Epub 2015 Apr 10.