Abstract
Primary soft tissue myoepithelial tumours (METs) are rare. Recent studies have shown EWSR1 rearrangement in certain METs. We present clinicopathological, immunohistochemical and molecular features of 14 primary soft tissue METs. Fourteen tumours, five benign and nine malignant, occurred in 12 men and two women, with an age range of 18–60 years (mean, 39.2); in upper extremities, four (29 %); chest wall, three (21 %); paraspinal region, three (21 %); pelvis, two (14 %) and lower extremities, two (14 %). Tumour size varied from 2 to 21.6 cm (mean, 8.7). Microscopically, most tumours were at least focally circumscribed. Morphological heterogeneity was noted, commonest patterns being cord-like and diffuse arrangement of polygonal cells in a myxoid stroma. By immunohistochemistry, tumours were positive for epithelial membrane antigen (EMA) (10/12, 83 %), cytokeratin (CK)/MNF116 (3/12, 25 %), p63 (7/10, 70 %), CD10 (4/6, 67 %), calponin (6/6, 100 %), S-100P (11/13, 85 %), glial fibrillary acidic protein (GFAP) (6/12, 50 %), smooth muscle actin (SMA) (3/9, 33 %), INI1/SMARCB1 (6/10, 60 %), brachyury (0/11), CD34 (0/5) and vimentin (4/4, 100 %), implying 93 % positivity for at least one epithelial marker. EWSR1 gene rearrangement was detected in 3/6 (50 %) METs (one benign and two malignant) and in an eccrine porocarcinoma which was included for reasons of comparison. Outcome details were available for six patients all surgically treated; three tumours (two malignant and one benign) resected with unknown marginal status recurred; two patients died and a single patient with myoepithelial carcinoma, who underwent a wide excision, is disease-free. This study illustrates the wide morphological spectrum of soft tissue METs, including benign and malignant subtypes. EMA and S-100P are optimal markers that should be supplemented with broad spectrum keratins, such as AE1/AE3, along with p63, GFAP and calponin in case of need but the results must be correlated with morphological features. Brachyury is useful in separating parachordoma/myoepithelioma from chordoma. EWSR1 rearrangement mostly occurs in METs that are deep-seated, irrespective of benign or malignant behaviour. Most malignant METs are INI1 negative.
Similar content being viewed by others
References
Kilpatrick SE, Limon J (2002) Mixed tumor/myoepithelioma/parachordoma. In: Fletcher CDM, Unni K, Mertens F (eds) World Health Organization classification of tumors. IARC, Lyon, pp 198–199
Kilpatrick SE, Hitchcock MG, Kraus MD, Calonje E, Fletcher CD (1997) Mixed tumors and myoepitheliomas of soft tissue: a clinicopathologic study of 19 cases with a unifying concept. Am J Surg Pathol 21:13–22
Michal M, Miettinen M (1999) Myoepitheliomas of the skin and soft tissues. Virchows Arch 434:393–400, Report of 12 cases
Bisceglia M, Cardone M, Fantasia L, Cenacchi G, Pasquinelli G (2001) Mixed tumors, myoepitheliomas, and oncocytomas of the soft tissues are likely members of the same family: a clinicopathologic and ultrastructural study. Ultrastruct Pathol 25:399–418
Hornick JL, Fletcher CD (2003) Myoepithelial tumors of soft tissue: a clinicopathologic and immunohistochemical study of 101 cases with evaluation of prognostic parameters. Am J Surg Pathol 27:1183–1196
Hornick JL, Fletcher CD (2004) Cutaneous myoepithelioma: a clinicopathologic and immunohistochemical study of 14 cases. Hum Pathol 35:14–24
Stojsić Z, Brasanac D, Bacetić D, Janković R, Drndarević N (2006) Soft tissue myoepithelial carcinoma. Vojnosanit Pregl 63:611–614
Lee JR, Georgi DE, Wang BY (2007) Malignant myoepithelial tumor of soft tissue: a report of two cases of the lower extremity and a review of the literature. Ann Diagn Pathol 11:190–198
Kas K, Voz ML, Roijer E, Astrom AK, Meyen E, Stenman G, Van de Ven WJ (1997) Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in pleomorphic adenomas with t(3;8)(p21;q12) translocations. Nat Genet 15:170–174
Martins C, Fonseca I, Roque L, Pereira T, Ribeiro C, Bullerdiek J, Soares J (2005) PLAG1 gene alterations in salivary gland pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: a combined study using chromosome banding, in situ hybridization and immunocytochemistry. Mod Pathol 18:1048–1055
Hallor KH, Teixeira MR, Fletcher CD, Bizarro S, Staaf J, Domanski HA, von Steyern FV, Panagopoulos I, Mandahl N, Mertens F (2008) Heterogeneous genetic profiles in soft tissue myoepitheliomas. Mod Pathol 21:1311–1319
Brandal P, Panagopoulos I, Bjerkehagen B, Gorunova L, Skjeldal S, Micci F, Heim S (2008) Detection of a t(1;22)(q23;q12) translocation leading to an EWSR1–PBX1 fusion gene in a myoepithelioma. Genes Chromosomes Cancer 47:558–5564
Brandal P, Panagopoulos I, Bjerkehagen B, Heim S (2009) t(19;22)(q13;q12) Translocation leading to the novel fusion gene EWSR1–ZNF444 in soft tissue myoepithelial carcinoma. Genes Chromosomes Cancer 48:1051–1056
Antonescu CR, Zhang L, Chang NE, Pawel BR, Travis W, Katabi N, Edelman M, Rosenberg AE, Nielsen GP, Dal Cin P, Fletcher CD (2010) EWSR1–POU5F1 fusion in soft tissue myoepithelial tumors. A molecular analysis of sixty-six cases, including soft tissue, bone, and visceral lesions, showing common involvement of the EWSR1 gene. Genes Chromosomes Cancer 49:1114–1124
Flucke U, Palmedo G, Blankenhorn N, Slootweg PJ, Kutzner H, Mentzel T (2011) EWSR1 gene rearrangement occurs in a subset of cutaneous myoepithelial tumors: a study of 18 cases. Mod Pathol 24:1444–1450
Flucke U, Mentzel T, Verdijk MA, Slootweg PJ, Creytens DH, Suurmeijer AJ, Tops BB (2012) EWSR1-ATF1 chimeric transcript in a myoepithelial tumor of soft tissue: a case report. Hum Pathol 43:764–768
Rekhi B, Amare P, Gulia A, Baisane C, Patil A, Agarwal S, Puri A, Jambhekar NA (2011) Primary intraosseous myoepithelioma arising in the iliac bone and displaying trisomies of 11, 15, 17 with del (16q) and del (22q11)—a rare case report with review of literature. Path Res Pract 207:780–785
Aparicio MA, López-Barea F, Cruz JJ, Macías MDCG, Hernández T, de Alava E (2012) Soft tissue myoepithelial carcinoma without EWSR1 gene rearrangement and poor outcome. A case report. Rev Esp Patol 45:58–63
Bridge RS, Rajaram V, Dehner LP, Pfeifer JD, Perry A (2006) Molecular diagnosis of Ewing sarcoma/primitive neuroectodermal tumor in routinely processed tissue: a comparison of two FISH strategies and RT-PCR in malignant round cell tumors. Mod Pathol 19:1–8
Flucke U, Hulsebos TJ, van Krieken JH, Mentzel T (2010) Myxoid epithelioid sarcoma: a diagnostic challenge. A report on six cases Histopathology 57:753–759
Flucke U, Tops BB, Verdijk MA, van Cleef PJ, van Zwam PH, Slootweg PJ, Bovée JV, Riedl RG, Creytens DH, Suurmeijer AJ, Mentzel T (2012) NR4A3 rearrangement reliably distinguishes between the clinicopathologically overlapping entities myoepithelial carcinoma of soft tissue and cellular extraskeletal myxoid chondrosarcoma. Virchows Arch 460:621–628
McHugh JB, Visscher DW, Barnes EL (2009) Update on selected salivary gland neoplasms. Arch Pathol Lab Med 133:1763–1774
Kane SV, Bagwan IN (2010) Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 51 cases in a tertiary cancer center. Arch Otolaryngol Head Neck Surg 136:702–712
Tirabosco R, Mangham DC, Rosenberg AE, Vujovic S, Bousdras K, Pizzolitto S et al (2008) Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue. Am J Surg Pathol 32:572–580
Jambhekar NA, Rekhi B, Dikshit R, Agarwal M, Puri A (2010) Revisiting chordoma with brachyury, a “new age” marker—analysis of a validation study on 51 cases. Arch Pathol Lab Med 134:1181–1187
Fisher C, Miettinen M (1997) Parachordoma: a clinicopathologic and immunohistochemical study of four cases of an unusual soft tissue neoplasm. Ann Diagn Pathol 1:3–10
Folpe A, Agoff SN, Willis J, Weiss SW (1999) Parachordoma is immunohistochemically and cytogenetically distinct from axial chordoma and extraskeletal myxoid chondrosarcoma. Am J Surg Pathol 23:1059–1067
Rekhi B, Gorad BD, Chinoy RF (2008) Clinicopathological features with outcomes of a series of conventional and proximal-type epithelioid sarcomas, diagnosed over a period of 10 years at a tertiary cancer hospital in India. Virchows Arch 453:141–153
Hornick JL, Dal Cin P, Fletcher CD (2009) Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol 33:542–550
Bahrami A, Dalton JD, Krane JF, Flether CDM (2012) A subset of cutaneous and soft tissue mixed tumors is genetically linked to their salivary gland counterpart. Genes Chromosomes Cancer 51:140–148
Matsuyama A, Hisaoka M, Hashimoto H (2012) PLAG1 expression in mesenchymal tumors: an immunohistochemical study with special emphasis on the pathogenetical distinction between soft tissue myoepithelioma and pleomorphic adenoma of the salivary gland. Pathol Intl 62:1–7
Kumar R, Rekhi B, Shirazi N, Gawde D, Pais A, Aamre P, Jambhekar NA (2008) Spectrum of cytomorphological features, including literature review, of an extraskeletal myxoid chondrosarcoma with t (9; 22) (q22; q11.2) translocation in one case. Diagn Cytopathol 36:868–875
Noguchi H, Mitsuhashi T, Seki K, Tochigi N, Tsuji M, Shimoda T, Hasegawa T (2010) Fluorescence in situ hybridization analysis of extraskeletal myxoid chondrosarcomas using EWSR1 and NR4A3 probes. Hum Pathol 41:336–342
Romeo S, Dei Tos AP (2010) Soft tissue tumors associated with EWSR1 translocation. Virchows Arch 456:219–234
Jin Y, Jin C, Mertens F, Persson B, Jonsson N (1998) Characterization of a malignant eccrine poroma by cytogenetic and fluorescence in situ hybridization techniques. Cancer Genet Cytogenet 102:100–103
Hollmann TJ, Hornick JL (2011) INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol 35:e47–e63
Kohashi K, Oda Y, Yamamoto H, Tamiya S, Oshiro Y, Izumi T, Taguchi T, Tsuneyoshi M (2008) SMARCB1/INI1 protein expression in round cell soft tissue sarcomas associated with chromosomal translocations involving EWS: a special reference to SMARCB1/INI1 negative variant extraskeletal myxoid chondrosarcoma. Am J Surg Pathol 32:1168–1174
Acknowledgments
The support of Immunohistochemistry laboratory of our Department is acknowledged. We thank Smita Mumbarkar, Jyoti Bodke and Ragni Mohite from molecular pathology laboratory, ACTREC, Khargar, Navi Mumbai for performing cytogentic test (FISH).
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rekhi, B., Sable, M. & Jambhekar, N.A. Histopathological, immunohistochemical and molecular spectrum of myoepithelial tumours of soft tissues. Virchows Arch 461, 687–697 (2012). https://doi.org/10.1007/s00428-012-1335-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-012-1335-7