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Novel SRF-ICA1L Fusions in Cellular Myoid Neoplasms With Potential For Malignant Behavior.
Am J Surg Pathol 2020; 44(1):55-60AJ

Abstract

Pericytic tumors comprise a histologic continuum of neoplasms with perivascular myoid differentiation, which includes glomus tumors, myopericytoma, myofibroma, and angioleiomyoma. Despite their morphologic overlap, recent data suggest a dichotomy in their genetic signatures, including recurrent NOTCH gene fusions in glomus tumors and PDGFRB mutations in myofibromas and myopericytomas. Moreover, SRF-RELA fusions have been described in a subset of cellular variants of myofibroma and myopericytoma showing myogenic differentiation. Triggered by an index case of an unclassified cellular myoid tumor showing a novel SRF-ICA1L fusion we have investigated our files for cases showing similar histology and screened them using a combined approach of targeted RNA sequencing and fluorescence in situ hybridization. A fusion between SRF exon 4 and ICA1L exon 10 or 11 was identified in a total of 4 spindle cell tumors with similar clinicopathologic features. Clinically, the tumors were deep-seated and originated in the trunk or proximal lower extremity of adult patients (age range: 23 to 55 y). Histologically, the tumors were composed of cellular fascicles of monomorphic eosinophilic spindle cells showing increased mitotic activity, harboring densely hyalinized stroma, often with focal areas of necrosis. All 4 tumors had similar immunoprofiles with positivity for smooth muscle actin, calponin, and smooth muscle myosin heavy chain. Tumors were negative for desmin and caldesmon, markers often seen in SRF-RELA-positive tumors with similar morphology. Follow-up information was available in 3 patients. Two patients had no evidence of disease, 2 and 5 years after surgical resection. One patient, a 35-year-old male patient with a 19 cm deep-seated tumor with brisk mitotic activity (>20 mitoses in 10 HPF), developed lung metastases 7 years after initial diagnosis. In summary, we report a series of 4 cellular myoid tumors with novel SRF-ICA1L gene fusions, characterized by bland spindle cell fascicular growth, expression of specific smooth muscle markers, elevated mitotic activity, marked stromal hyalinization, focal coagulative necrosis, and potential for malignant behavior. Given the morphologic overlap with related cellular myopericytic tumors with SRF-RELA fusions, it is likely that SRF-ICA1L fusions define a similar subset of neoplasms composed of immature smooth muscle cells.

Authors+Show Affiliations

Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31478943

Citation

Suurmeijer, Albert J., et al. "Novel SRF-ICA1L Fusions in Cellular Myoid Neoplasms With Potential for Malignant Behavior." The American Journal of Surgical Pathology, vol. 44, no. 1, 2020, pp. 55-60.
Suurmeijer AJ, Dickson BC, Swanson D, et al. Novel SRF-ICA1L Fusions in Cellular Myoid Neoplasms With Potential For Malignant Behavior. Am J Surg Pathol. 2020;44(1):55-60.
Suurmeijer, A. J., Dickson, B. C., Swanson, D., Sung, Y. S., Zhang, L., & Antonescu, C. R. (2020). Novel SRF-ICA1L Fusions in Cellular Myoid Neoplasms With Potential For Malignant Behavior. The American Journal of Surgical Pathology, 44(1), pp. 55-60. doi:10.1097/PAS.0000000000001336.
Suurmeijer AJ, et al. Novel SRF-ICA1L Fusions in Cellular Myoid Neoplasms With Potential for Malignant Behavior. Am J Surg Pathol. 2020;44(1):55-60. PubMed PMID: 31478943.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel SRF-ICA1L Fusions in Cellular Myoid Neoplasms With Potential For Malignant Behavior. AU - Suurmeijer,Albert J, AU - Dickson,Brendan C, AU - Swanson,David, AU - Sung,Yun-Shao, AU - Zhang,Lei, AU - Antonescu,Cristina R, PY - 2021/01/01/pmc-release PY - 2019/9/4/pubmed PY - 2019/9/4/medline PY - 2019/9/4/entrez SP - 55 EP - 60 JF - The American journal of surgical pathology JO - Am. J. Surg. Pathol. VL - 44 IS - 1 N2 - Pericytic tumors comprise a histologic continuum of neoplasms with perivascular myoid differentiation, which includes glomus tumors, myopericytoma, myofibroma, and angioleiomyoma. Despite their morphologic overlap, recent data suggest a dichotomy in their genetic signatures, including recurrent NOTCH gene fusions in glomus tumors and PDGFRB mutations in myofibromas and myopericytomas. Moreover, SRF-RELA fusions have been described in a subset of cellular variants of myofibroma and myopericytoma showing myogenic differentiation. Triggered by an index case of an unclassified cellular myoid tumor showing a novel SRF-ICA1L fusion we have investigated our files for cases showing similar histology and screened them using a combined approach of targeted RNA sequencing and fluorescence in situ hybridization. A fusion between SRF exon 4 and ICA1L exon 10 or 11 was identified in a total of 4 spindle cell tumors with similar clinicopathologic features. Clinically, the tumors were deep-seated and originated in the trunk or proximal lower extremity of adult patients (age range: 23 to 55 y). Histologically, the tumors were composed of cellular fascicles of monomorphic eosinophilic spindle cells showing increased mitotic activity, harboring densely hyalinized stroma, often with focal areas of necrosis. All 4 tumors had similar immunoprofiles with positivity for smooth muscle actin, calponin, and smooth muscle myosin heavy chain. Tumors were negative for desmin and caldesmon, markers often seen in SRF-RELA-positive tumors with similar morphology. Follow-up information was available in 3 patients. Two patients had no evidence of disease, 2 and 5 years after surgical resection. One patient, a 35-year-old male patient with a 19 cm deep-seated tumor with brisk mitotic activity (>20 mitoses in 10 HPF), developed lung metastases 7 years after initial diagnosis. In summary, we report a series of 4 cellular myoid tumors with novel SRF-ICA1L gene fusions, characterized by bland spindle cell fascicular growth, expression of specific smooth muscle markers, elevated mitotic activity, marked stromal hyalinization, focal coagulative necrosis, and potential for malignant behavior. Given the morphologic overlap with related cellular myopericytic tumors with SRF-RELA fusions, it is likely that SRF-ICA1L fusions define a similar subset of neoplasms composed of immature smooth muscle cells. SN - 1532-0979 UR - https://www.unboundmedicine.com/medline/citation/31478943/Novel_SRF-ICA1L_Fusions_in_Cellular_Myoid_Neoplasms_With_Potential_For_Malignant_Behavior L2 - http://dx.doi.org/10.1097/PAS.0000000000001336 DB - PRIME DP - Unbound Medicine ER -