Evaluation of fluorescence in-situ hybridization in monomorphic endometrial stromal neoplasms and their histological mimics: a review of 49 cases
Corresponding Author
Colin J R Stewart
Department of Histopathology, King Edward Memorial Hospital, Perth, WA, Australia
School of Women's and Infants Health, University of Western Australia, Perth, WA, Australia
Address for correspondence: Dr C J R Stewart, Department of Histopathology, King Edward Memorial Hospital, Bagot Road, Perth, WA 6008, Australia. e-mail: [email protected]Search for more papers by this authorYee C Leung
School of Women's and Infants Health, University of Western Australia, Perth, WA, Australia
Search for more papers by this authorAshleigh Murch
Department of Diagnostic Genomics, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, WA, Australia
Search for more papers by this authorJoanne Peverall
Department of Diagnostic Genomics, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, WA, Australia
Search for more papers by this authorCorresponding Author
Colin J R Stewart
Department of Histopathology, King Edward Memorial Hospital, Perth, WA, Australia
School of Women's and Infants Health, University of Western Australia, Perth, WA, Australia
Address for correspondence: Dr C J R Stewart, Department of Histopathology, King Edward Memorial Hospital, Bagot Road, Perth, WA 6008, Australia. e-mail: [email protected]Search for more papers by this authorYee C Leung
School of Women's and Infants Health, University of Western Australia, Perth, WA, Australia
Search for more papers by this authorAshleigh Murch
Department of Diagnostic Genomics, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, WA, Australia
Search for more papers by this authorJoanne Peverall
Department of Diagnostic Genomics, PathWest Laboratory Medicine, Queen Elizabeth II Medical Centre, Perth, WA, Australia
Search for more papers by this authorAbstract
Aims
To perform a population-based review of monomorphic endometrial stromal tumours and their histological mimics presenting over a 20-year period, including an evaluation of fluorescence in-situ hybridization (FISH) for the JAZF1 and YWHAE breakaparts.
Methods and results
Forty-nine tumours were examined, comprising 13 histological mimics and 36 endometrial stromal tumours [six stromal nodules (ESNs), 25 low-grade stromal sarcomas (ESSs), and five monomorphic undifferentiated sarcomas (mUESs)]. Nine ESSs showed variant histological patterns, including smooth muscle, sex cord-like/glandular, fibrous or rhabdoid differentiation. Three ESSs were initially misclassified as benign uterine lesions, and, conversely, three benign mimics were originally reported as ESSs. One mUES showed a prominent pseudopapillary pattern. Fluorescence in-situ hybridization demonstrated JAZF1 breakaparts in five of six ESNs and 16 of 25 ESSs; however, only three of nine ESS variants were positive. YWHAE breakaparts were present in four of five mUESs. Analysis of a subsequent metastasis in the YWHAE breakapart-negative mUES demonstrated a YWHAE deletion. None of the histological mimics was positive in FISH analysis. Diffuse cyclin D1 expression was restricted to mUESs in this series.
Conclusions
Endometrial stromal neoplasms continue to present diagnostic difficulty. Fluorescence in-situ hybridization analysis is helpful in distinguishing stromal tumours from their histological mimics and in distinguishing ESS from mUES.
References
- 1D'Angelo E, Prat J. Uterine sarcomas: a review. Gynecol. Oncol. 2010; 116; 131–139.
- 2Chiang S, Oliva E. Recent developments in uterine mesenchymal neoplasms. Histopathology 2013; 62; 124–137.
- 3Oliva E, Clement PB, Young RH. Endometrial stromal tumors: an update on a group of tumors with a protean phenotype. Adv. Anat. Pathol. 2000; 7; 257–281.
- 4Rauh-Hain JA, Del Carmen MG. Endometrial stromal sarcoma: a systematic review. Obstet. Gynecol. 2013; 122; 676–683.
- 5Dionigi A, Oliva E, Clement PB, Young RH. Endometrial stromal nodules and endometrial stromal tumors with limited infiltration: a clinicopathologic study of 50 cases. Am. J. Surg. Pathol. 2002; 26; 567–581.
- 6Kim KR, Jun SY, Park IA, Ro JY, Nam JH. Endometrial stromal tumor with limited infiltration and probable extrauterine metastasis: report of a case. Ann. Diagn. Pathol. 2005; 9; 57–60.
- 7Yilmaz A, Rush DS, Soslow RA. Endometrial stromal sarcomas with unusual histologic features: a report of 24 primary and metastatic tumors emphasizing fibroblastic and smooth muscle differentiation. Am. J. Surg. Pathol. 2002; 26; 1142–1150.
- 8Massand RP, Euscher ED, Deavers MT, Malpica A. Endometrioid stromal sarcoma: a clinicopathologic study of 63 cases. Am. J. Surg. Pathol. 2013; 37; 1635–1647.
- 9Park JY, Sung CO, Jang S-J, Song SY, Han JH, Kim K-R. Pulmonary metastatic nodules of uterine low-grade endometrial stromal sarcoma: histopathological and immunohistochemical analysis of 10 cases. Histopathology 2013; 63; 833–840.
- 10Sandberg AA. The cytogenetics and molecular biology of endometrial stromal sarcoma. Cytogenet. Genome Res. 2007; 118; 182–189.
- 11Chiang S, Oliva E. Cytogenetic and molecular aberrations in endometrial stromal tumors. Hum. Pathol. 2011; 42; 609–617.
- 12Huang HY, Ladanyi M, Soslow RA. Molecular detection of JAZF1–JJAZ1 gene fusion in endometrial stromal neoplasm with classic and variant histology: evidence for genetic heterogeneity. Am. J. Surg. Pathol. 2004; 28; 224–232.
- 13Hrzenjak A, Moinfar F, Tavassoli FA et al. JAZF1/JJAZ1 gene fusion in endometrial stromal sarcomas: molecular analysis by reverse transcriptase-polymerase chain reaction optimised for paraffin-embedded tissue. J. Mol. Diagn. 2005; 7; 388–395.
- 14Chiang S, Ali R, Melnyk N et al. Frequency of known gene rearrangements in endometrial stromal tumors. Am. J. Surg. Pathol. 2011; 35; 1364–1372.
- 15Jakate K, Azimi F, Ali RH et al. Endometrial sarcomas: an immunohistochemical and JAZF1 re-arrangement study in low-grade and undifferentiated tumors. Mod. Pathol. 2013; 26; 95–105.
- 16Micci F, Panagopoulos I, Bjerkehagen B, Heim S. Consistent rearrangement of chromosomal band 6p21 with generation of fusion genes JAZF1/PHF1 and EPC1/PHF1 in endometrial stromal sarcoma. Cancer Res. 2006; 66; 107–112.
- 17D'Angelo E, Ali RH, Espinosa I et al. Endometrial stromal sarcomas with sex cord differentiation are associated with PHF1 rearrangement. Am. J. Surg. Pathol. 2013; 37; 514–521.
- 18Panagopoulos I, Thorsen J, Gorunova L et al. Fusion of ZC3H7B and BCOR genes in endometrial stromal sarcomas carrying an X:22 translocation. Genes Chromosom. Cancer 2013; 52; 610–618.
- 19Dewaele B, Przybyl J, Quattrone A et al. Identification of a novel, recurrent MBTD1–CXorf67 fusion in low-grade endometrial stromal sarcoma. Int. J. Cancer 2014; 134; 1112–1122.
- 20Gabre-Medhin S, Nord KH, Moller E et al. Recurrent rearrangement of the PHF1 gene in ossifying fibromyxoid tumors. Am. J. Pathol. 2012; 181; 1069–1077.
- 21Graham RP, Weiss SW, Sukov WR et al. PHF1 rearrangements in ossifying fibromyxoid tumors of soft parts: a fluorescence in situ hybridization study of 41 cases with emphasis on the malignant variant. Am. J. Surg. Pathol. 2013; 37; 1751–1755.
- 22Antonescu CR, Sung YS, Chen CL et al. Novel ZC3H7B–BCOR, MEAF6–PHF1, and EPC1–PHF1 fusions in ossifying fibromyxoid tumors—molecular characterization shows genetic overlap with endometrial stromal sarcoma. Genes Chromosom. Cancer 2014; 53; 183–193.
- 23Schoolmeester JK, Sukov WR, Maleszewski JJ et al. JAZF1 rearrangement in a mesenchymal tumor of nonendometrial stromal origin: report of an unusual ossifying sarcoma of the heart demonstrating JAZF1/PHF1 fusion. Am. J. Surg. Pathol. 2013; 37; 938–942.
- 24Lee C-H, Marino-Enriquez A, Ou W et al. The clinicopathologic features of YWHAE–FAM22 endometrial stromal sarcomas: a histologically high-grade and clinically aggressive tumor. Am. J. Surg. Pathol. 2012; 36; 641–653.
- 25Isphording A, Ali RH, Irving J et al. YWHAE–FAM22 endometrial stromal sarcoma: diagnosis by reverse transcription-polymerase chain reaction in formalin-fixed, paraffin-embedded tumor. Hum. Pathol. 2013; 44; 837–843.
- 26Kurihara S, Oda Y, Ohishi Y et al. Endometrial stromal sarcomas and related high-grade sarcomas: immunohistochemical and molecular genetic study of 31 cases. Am. J. Surg. Pathol. 2008; 32; 1228–1238.
- 27Croce S, Hostein I, Ribeiro A et al. YWHAE rearrangement identified by FISH and RT-PCR in endometrial stromal sarcomas: genetic and pathological correlations. Mod. Pathol. 2013; 26; 1390–1400.
- 28Lee C-H, Ali RH, Rouzbahman M et al. Cyclin D1 as a diagnostic immunomarker for endometrial stromal sarcoma with YWHAE–FAM22 rearrangement. Am. J. Surg. Pathol. 2012; 36; 1562–1570.
- 29Kurihara S, Oda Y, Ohishi Y et al. Coincident expression of beta-catenin and cyclin D1 in endometrial stromal tumors and related high-grade sarcomas. Mod. Pathol. 2010; 23; 225–234.
- 30Hutton SM, Webster LR, Nielsen S, Leung Y, Stewart CJR. Immunohistochemical expression and prognostic significance of oestrogen receptor-alpha, oestrogen receptor-beta and progesterone receptor in stage 1 adult-type granulosa cell tumour of the ovary. Pathology 2012; 44; 611–616.
- 31Stewart CJR, Crook ML, Little L, Louwen K. Correlation between invasive pattern and immunophenotypic alterations in endocervical adenocarcinoma. Histopathology 2011; 58; 720–728.
- 32Stewart CJR, Baker E, Beaton C, Crook M, Peverall J, Wallace S. Detection of Y-chromosome in gonadal tumours using fluorescence in situ hybridization: diagnostic value in intersex conditions including older patients with clinically unsuspected androgen insensitivity syndrome. Histopathology 2008; 52; 175–182.
- 33Oliva E, Clement PB, Young RH, Scully RE. Mixed endometrial stromal and smooth muscle tumors of the uterus: a clinicopathologic study of 15 cases. Am. J. Surg. Pathol. 1998; 22; 997–1005.
- 34Lazar A, Abruzzo LV, Pollock RE, Lee S, Czerniak B. Molecular diagnosis of sarcomas: chromosomal translocations in sarcomas. Arch. Pathol. Lab. Med. 2006; 130; 1199–1207.
- 35Tanas MR, Goldblum JR. Fluorescence in situ hybridisation in the diagnosis of soft tissue neoplasms: a review. Adv. Anat. Pathol. 2009; 16; 383–391.
- 36Sato K, Ueda Y, Sugaya J, Ozaki M, Hisaoka M, Katsuda S. Extrauterine endometrial stromal sarcoma with JAZF1/JJAZ1 fusion confirmed by RT-PCR and interphase FISH presenting as an inguinal tumor. Virchows Arch. 2007; 450; 349–353.
- 37Amador-Ortiz C, Roma AA, Huettner PC, Becker N, Pfeifer JD. JAZF1 and JJAZ1 gene fusion in primary extrauterine endometrial stromal sarcoma. Hum. Pathol. 2011; 42; 939–946.
- 38Tavassoli FA, Devilee P. World health organization classification of tumours pathology and genetics of tumours of the breast and female genital organs. Lyon: IARC Press, 2003.
- 39Gu W, Lupski JR. CNV and nervous system diseases—what's new? Cytogenet. Genome Res. 2008; 123; 54–64.
- 40Nagamani SC, Zhang F, Shchelochkov OA et al. Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment. J. Med. Genet. 2009; 46; 825–833.
- 41O'Meara E, Stack D, Lee CH et al. Characterization of the chromosomal translocation t(10;17)(q22;p13) in clear cell sarcoma of kidney. J. Pathol. 2012; 227; 72–80.
- 42Suzuki S, Tanioka F, Minato H et al. Breakages at YWHAE, FAM22A, and FAM22B loci in uterine angiosarcoma: a case report with immunohistochemical and genetic analysis. Pathol. Res. Pract. 2014; 210; 130–134.
- 43McCluggage WG, Young RH. Endometrial stromal sarcomas with true papillae and pseudopapillae. Int. J. Gynecol. Pathol. 2008; 27; 555–561.
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