Myoepitheliomas and mixed tumors were only recently recognized to occur primarily in soft tissue, and only small case numbers have been described. To characterize these tumors further and to evaluate prognostic parameters, 101 myoepithelial tumors of soft tissue were retrieved from the authors' consult files. Hematoxylin and eosin sections were reexamined, immunohistochemistry was performed, and clinical details were obtained from referring physicians. Fifty-three patients were male and 48 female (mean age 38 years; range 3–83 years). Tumor size ranged from 0.7 to 20 cm (mean 4.7 cm). Most tumors arose in the extremities and limb girdles: 41 in the lower limbs, 35 in the upper limbs, 15 in the head and neck, and 10 in the trunk. Fifty-four tumors were situated in subcutis and 37 in deep soft tissue (depth unstated in 10). Most cases were grossly well circumscribed; 43 showed microscopically infiltrative margins. Histologically, most tumors were lobulated, composed of cords or nests of epithelioid, ovoid, or spindled cells with a variably reticular architecture and a chondromyxoid or collagenous/hyalinized stroma. Eight cases showed a predominantly solid proliferation of spindled or plasmacytoid cells; 17 demonstrated ductular differentiation (mixed tumors). Cartilage was present in 6 cases, 6 contained bone, and 4 others contained both. Mitoses ranged from 0 to 68 per 10 high power fields (mean 4.7 per 10 high power fields). Tumors with benign cytomorphology or mild cytologic atypia (low-grade) were classified as myoepithelioma or mixed tumor, whereas tumors with moderate to severe atypia (high-grade) were classified as myoepithelial carcinoma (epithelioid or spindled cells with vesicular or coarse chromatin, prominent, often large nucleoli, or nuclear pleomorphism) or malignant mixed tumor (cytologically malignant cartilage or bone). Sixty-one cases were myoepitheliomas or mixed tumors, and 40 were myoepithelial carcinomas or malignant mixed tumors. By immunohistochemistry, all cases with available material were reactive for epithelial markers (keratins and/or epithelial membrane antigen): 90 of 97 (93%) expressed keratins (most often AE1/AE3 or PAN-K), 84 of 97 (87%) S-100 protein, 44 of 51 (86%) calponin, 52 of 83 (63%) epithelial membrane antigen, 40 of 87 (46%) glial fibrillary acidic protein, 27 of 75 (36%) smooth muscle actin, 15 of 66 (23%) p63, and 7 of 51 (14%) desmin. Follow-up was available for 64 patients. Among 33 cases with benign or low-grade cytology (mean follow-up 36 months; range 4–168 months), 6 recurred locally (18%) and none metastasized. No clinical or histologic features correlated with recurrence. Among 31 cytologically malignant cases (mean follow-up 50 months; range 4–252 months), 13 recurred locally (42%) and 10 metastasized (32%); so far, 4 patients have died of metastatic tumor. This study expands the spectrum of myoepithelial tumors of soft tissue to include myoepithelial carcinomas and malignant mixed tumors, which pursue an aggressive clinical course. Although the majority of morphologically benign or low-grade myoepithelial neoplasms of soft tissue behave in a benign fashion, there is an approximate 20% risk for local recurrence.
Well-characterized in salivary glands, myoepitheliomas, and mixed tumors (“pleomorphic adenomas”) were only recently recognized to occur primarily in soft tissue. 23,26 Because fewer than 40 soft tissue myoepithelial tumors have been reported so far, their characterization to date has been limited. Perhaps the greatest impediment to their recognition at this site is the plasticity of myoepithelial cells and the resultant broad morphologic spectrum of myoepithelial tumors. In salivary glands, the uncommon diagnosis of myoepithelioma was initially reserved for those tumors composed of spindle cells or plasmacytoid (hyaline) cells demonstrating a solid growth pattern. 4,38 With the recognition that neoplastic myoepithelial cells in mixed tumors can display a wide range of histologic features, 11 however, this category has been expanded more recently to include those tumors with myxoid or hyalinized stroma, reticular or trabecular architecture, and epithelioid or clear myoepithelial cells. 1,13,39,42 It remains debatable whether focal epithelial (ductal) differentiation or chondroid matrix is allowable in a myoepithelioma 9 or should result in the diagnosis of mixed tumor (“pleomorphic adenoma”). These changing definitions illustrate the considerable heterogeneity and overlap in the histologic appearances of mixed tumors and myoepitheliomas; many investigators now think that these tumors lie on a morphologic continuum. 4,11,41 Given the benign clinical behavior of most mixed tumors and myoepitheliomas of salivary glands, the distinction is perhaps semantic. A more significant clinical problem has been the difficulty in establishing criteria for malignancy in myoepitheliomas. In salivary gland lesions, invasion beyond the tumor capsule into adjacent salivary gland or soft tissue is the most widely accepted criterion, although cytologic atypia and mitotic rate have also been reported to be useful, without there being firm guidelines for reaching a diagnosis of myoepithelial carcinoma (malignant myoepithelioma). 12,27,28,36 The reported small series of soft tissue myoepitheliomas and mixed tumors have described occasional tumors that recurred or metastasized 23,26; criteria for malignancy, however, have yet to be established. To evaluate clinical and histologic prognostic parameters, this study examined 101 myoepithelial tumors arising primarily in soft tissue.
From the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Received for publication January 22, 2003; accepted April 9, 2003.
Address correspondence and reprint requests to Christopher D. M. Fletcher, MD, FRCPath, Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115; e-mail: firstname.lastname@example.org