USP6 (17p13), Aneurysmal Bone Cyst and Nodular Fasciitis, FISH
Supporting the diagnosis of aneurysmal bone cyst or nodular fasciitis
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Aneurysmal bone cyst (ABC) is a multicystic and expansile bone tumor of uncertain line of differentiation. USP6 fusion genes are detectable in approximately 70% of primary ABC and not in other conditions that may simulate ABC histologically, including giant cell tumor of bone, osteosarcoma, osteoblastoma, brown tumor, cherubism, and vascular neoplasms.Nodular fasciitis (NF) is a self-limited mesenchymal lesion of myofibroblastic differentiation. NF rapid growth, rich cellularity, and brisk mitotic activity may lead to a misdiagnosis of sarcoma. USP6 fusions are detectable in 90% of NF but not in other conditions that may simulate NF, including dermatofibroma, cellular fibrous histiocytoma, fibromatosis, and a large variety of sarcomas.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
0-9% rearranged cells
An interpretive report will be provided.
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for the USP6 FISH probe (positive result).
A positive result is consistent with rearrangement of the USP6 gene locus on 17p13 and supports the diagnosis of aneurysmal bone cyst (ABC) or nodular fasciitis (NF). A negative result is consistent with no rearrangement of the USP6 gene locus on 17p13. However, this result does not exclude the diagnosis of ABC or NF. Rearrangement varies in individual tumors and among different cells in the same tumor.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Reliable results are dependent on adequate specimen collection and processing. This test has been validated on formalin-fixed, paraffin-embedded tissues; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause FISH failure.
Clinical diagnosis and/or therapy should not be based solely on this assay. The results should be considered in conjunction with clinical information, histologic analysis, and/or additional diagnostic tests.
In a study by Oliveira et al, 52 primary aneurysmal bone cyst (ABC) specimens were tested by FISH for USP6 locus rearrangements.(2) Thirty-six (69%) ABC showed rearrangement of the USP6 locus.(2) Subsequently, a blinded investigation was performed on 14 ABC, 48 nodular fasciitis (NF), and 39 control tissues. All samples were identified and diagnosed by a soft tissue pathology expert. Two technologists scored 100 cells each. USP6 was found to be rearranged in 11 of 14 (77%) ABC specimens; similar to what is reported in the literature.(1,2) Out of the 11 ABC specimens positive for USP6, 3 (30%) showed CDH11-USP6 rearrangement and 2 (20%) showed COL1A1-USP6 rearrangements, all of which have been reported in the literature.(1,2) USP6 was found rearranged in NF in 44 of 48 (92%) lesions tested. No rearrangement was seen in any of the control tissues.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Oliveira AM, Hsi B, Weremowicz S, et al: USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst. Cancer Res 2004 Mar 15;64(6):1920-1923
2. Oliveira AM, Perez-Atayde AR, Inwards CY, et al: USP6 and CDH11 oncogenes identify the neoplastic cell in primary aneurysmal bone cysts and are absent in so-called secondary aneurysmal bone cysts. Am J Pathol 2004 Nov;165(5):1773-1780
3. Fletcher CDM, Unni KK, Mertens F: World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. IARC Press, Lyon, France, 2005, pp 48-49
4. Erickson-Johnson MR, Chou MM, Evers BR, et al: Fusion of Non-Muscle Myosin MYH9 to USP6 Oncogene in Nodular Fasciitis, USCAP Abstract #39, 2011