Cutaneous myoepithelioma (CM) is a rare tumor among the primary skin neoplasms. We present the case of a patient with a diagnosis of CM in the right hypothenar region. Histological study showed a proliferation of myoepithelial cells with a solid, reticular growth pattern in a chondromyxoid stroma. The tumor cells were positive for CK AE, S-100, EMA, and p63.
Proliferation of myoepithelial cells can lead to the formation of benign or malignant neoplasms. Cutaneous myoepitheliomas are recently described rare tumors originating in the skin, usually in the dermis. They can appear at virtually any age, most commonly in the upper and lower limbs. CM diagnosis can be challenging due to its different morphological presentations. Similarly, CMs have different immunohistochemical reactivity profiles, thus correct diagnosis depends on an adequate analysis. In general, cutaneous myoepithelioma cells show immunoreactivity for epithelial and myoepithelial markers. They are usually positive for EMA (epithelial membrane antigen), S-100 protein, and low molecular weight keratins. Reactivity is variable for glial fibrillary acidic protein (GFAP) and p63. Certain neoplastic cells maintain reactivity for EMA but are negative for keratins, while others may lose reactivity to myoepithelial markers like SMA (smooth muscle actin), and in rare cases, some can be negative for S-100 but positive for SOX-10. A syncytial variant of CM has been described with a different immunophenotype from that of the classical variant. These lesions have a good prognosis when resection is complete and the margins are negative.
A 51-year-old male patient presented with a painless, progressively growing mass in the hypothenar region of the right hand with a one-year evolution. The lesion was completely resected. A pseudo capsulated dermal nodule of
Cutaneous Myoepithelioma in the hypothenar region of the right hand. (a) A proliferation of myoepithelial cells with a solid and reticular growth pattern without cell atypia [insert HE 40X] in a chondromyxoid stroma. (b) The tumor cells show diffuse expression to cytokeratin AE1/AE3. (c) EMA focal expression. (d) Coexpression of S-100 protein. (e) p63 focal expression.
Myoepithelial cells are specialized basal cells that derive from the ectoderm. They are found in different tissues, including the sweat glands, salivary glands, mammary glands, and the respiratory tract [
Myoepithelial neoplasms are a group of rare but well characterized tumors that includes, among others, salivary, skin, and soft tissue tumors [
Cutaneous myoepitheliomas occur more frequently in men, as is also the case with chondroid syringomas [
Clinically, CM usually presents as a painless nodule of variable size and gradually progressing growth that generally causes no problems or discomfort. This description coincided with our patient’s clinical presentation and with that described by Kanemaru et al. regarding a cutaneous myoepithelioma on the right arm of a Japanese male patient [
Macroscopically, CM shows up as a well-defined, usually whitish-gray or yellowish lobular lesion with a smooth surface and no capsule. It varies in size, although it is usually smaller than CMC, and can range from 0.5 to 2.5 cm, averaging at 0.7 cm [
Histologically, CMs appear as well-defined nodular, multinodular, or lobular neoplasms with no capsule that usually show infiltration. A minority of cases are exophytic lesions with an epidermal collarette. In the present case, a peripheral connective sheath was observed, even though the lesion was not exophytic. The superficial subcutaneous tissue is compromised in around 25% of cases [
In CMs, tumor cells show coexpression of epithelial markers and S-100 protein, as in our case. Most show positivity for cytokeratins (pan-keratin, AE1/AE3, Cam5.2), while positivity for EMA has been variably reported in from 19% to 79% of cases. S-100 protein is also positive in most cases (72%–100%). The reactivity for GFAP is lower, and can be positive in up to half of cases. Myogenic marker expression is variable. Calponin is positive in 86% to 100% of cases, while SMA is positive in only 36% to 64%. This type of tumor usually does not express desmin, although a few positive cases have been reported for this marker (0%–20%). P63 is positive in up to 70% of cases, and SOX-10 is present in 82%. This last marker is especially useful in cases that are negative for S-100 protein [
Main characteristics of the classic and syncytial variants of cutaneous myoepithelioma
Cutaneous myoepithelioma—classical variant | Cutaneous myoepithelioma—syncytial variant | |
---|---|---|
Growth pattern | Trabecular, reticular, plexiform (rare) | In sheets, solid, and syncytial |
Cytology | Mixed: epithelioid, fusiform, clear, or plasmocytoid cells | Ovoid, fusiform, or histiocytoid |
Stroma | Chondromyxoid, myxoid, or hyaline | Sparse; presence of adipose metaplasia seems to be more frequent than in the classical variant |
Immunohistochemistry | ||
Calponin | (+) 86%–100% | (+) >85% |
SMA | (+) in up to 60% of cases | (+) 70% |
Desmin | (-) 80%–100% | (-) 80%–100% |
EMA | (+) 42% | (+) 100% |
Cytokeratins (pankeratin, AE1/AE3, Cam5.2) | Diffuse and intense positivity in most cases (93%–100%) | Focal positivity in a few cases (12%) |
S-100 | (+) 72%–100% | (+) 86%–100% |
GFAP | (+) variable, 27%–54% | (+) 42% |
p63 | (+) variable, 7%–45% | (+) 54% |
Molecular alteration | EWSR1 gene rearrangement. Identified fusion genes include PBX1, PBX3, POU5F1, ZNF444, DUX4, ATF1, NR4A3, CREB1. | EWSR1 gene rearrangement. The fusion genes are different from the classical variant. |
Rearrangements of the
In the context of a morphology suggestive of myoepithelial neoplasia, a CM diagnosis requires a complete immunohistochemical study. It is clear that these tumors are characterized by the wide range of histological patterns and immunophenotypes they can show, which sometimes complicates differential diagnosis with other skin neoplasms such as epithelioid fibrous histiocytoma, early juvenile xanthogranuloma (without lipidization), Spitz nevus, epithelioid sarcoma, and ossifying fibromyxoid tumor. Differential diagnosis will depend on the CM’s predominant histological pattern (see Table
Differential diagnosis of cutaneous myoepithelioma
Tumor | Age of presentation | Most frequent location | Form of the lesion | Histology | Cytology | Immunohistochemistry | Molecular alteration |
---|---|---|---|---|---|---|---|
For CM with sheets of epithelioid, ovoid, or histiocytoid cells and solid growth pattern | |||||||
Benign epithelioid fibrous Histiocytoma | Adults, second to fifth decades | Lower limbs and trunk | Exophytic, polypoid | Highly vascularized stroma with scattered inflammatory cells. Trapping of collagen bundles at the periphery of the lesion. | Epithelioid cells, often binucleated | S-100 (-), keratin (-), EMA (+/-), SMA (-/+), calponin (-) | AKL gene rearrangement. Identified fusion genes include SQSTM1, VCL, DCTN1, ETV6, PPFIBP1 and SPECC1L |
Spitz nevus | Frequent in children; 65% of all cases occur in adolescents and young adults | Head and neck, trunk and lower limbs | Semispherical nodule | Solid pattern with cellular nests. Kamino bodies. | Epithelioid melanocytes with prominent nucleoli | S-100 (+), HMB45 (+), Melan-A (+), keratin (-), EMA (-), GFAP (-) | Alteration of the HRAS gene has been reported |
Epithelioid sarcoma | Young adults | Distal portion of the extremities | Exophytic | Multinodular, very evident and diffuse infiltration with no myxoid or hyalinized stroma | Epithelioid to fusiform | Keratin (+), EMA (+), S-100 (-), GFAP (-) | Deletions of SMARCB1; gain of chromosomes 11, 1, 6, and 9 have been reported |
For CM composed predominantly of spindle cells | |||||||
Pilar leiomyoma | Young adults; may be congenital | Limbs and trunk | Nodule (usually painful) | Cellular bundles ramifying between collagen fiber bundles | Fusiform | Desmin (+), S-100 (-), GFAP (-), keratin (+/-), EMA (+/-) | Not reported |
For CM showing reticular pattern and myxoid matrix | |||||||
Ossifying fibromyxoid tumor | Adults, fifth decade of life | Lower and upper limbs | Exophytic | Lobular o multinodular | Round or ovoid | S-100 (+), desmin (+), keratins (+/-), GFAP (+/-) | PHF1 gene rearrangement |
Extraskeletal myxoid chondrosarcoma | Adults, peak in the sixth decade | Limbs, especially the groin and gluteal region | Exophytic | Lobular or multinodular; reticular or trabecular pattern. Greater cellularity towards the periphery of the nodules. | Fusiform to epithelioid | Keratins (-), p63 (-), GFAP (-), SMA (-), EMA (-/+), S-100 (-/+) | Translocation t (9; 22) (q22; q12)–NR4A3-EWSR1. |
The clinical course of myoepithelioma does not always correlate with their histological characteristics. Most metastatic skin and soft tissue myoepitheliomas showed cellular atypia, high mitotic rate, and infiltrating margins, but a small number of cases without these characteristics showed unusual malignant behavior [
We present this case to highlight the need to consider myoepithelioma within the tumors of hand. The correct histological diagnosis in a very rare location ensures adequate management and follows up.
The article was in accordance with the local ethics committee (Ethics Committee, Hospital Metropolitano, Quito, Ecuador). The patient agreed that her stored material was enclosed and that her clinical data were anonymously used.
Written informed consents for publication of their clinical details and/or clinical images were obtained from the patient. A copy of the consent forms is available for review by the editor of this journal.
The authors declare that there is no conflict of interest regarding the publication of this paper.
NM and LR performed the histological examination and diagnosis cutaneous myoepithelioma in the hand. DG and IR conducted a thorough literature review and the differential diagnosis, and DG was the major contributor in writing the manuscript. All authors read and approved the final manuscript.
The authors wish to thank Fany Rocha (secretary) for their valuable support.