# Myoepithelioma of the Hand: A Systematic Review
## 4 Discussion
### Immunohistochemistryistochemistry  
Histologic examination is crucial to make our diagnosis. Different cell morphologies within myoepitheliomas show varying immunoreactivity to smooth muscle markers. Spindle cells exhibit the strongest immunoreactivity, followed by epithelioid cells, with plasmacytoid and clear cells showing less or no activity [30].  
Myoepithelioma cells typically express cytokeratin (AE1/AE3, CK 5/6, Cam 5.2, CK-7 and CK-14) and vimentin (positive in neoplastic myoepithelial cells but negative in normal myoepithelial cells).  
Neoplastic transformation can modify the typical smooth muscle phenotype of myoepithelial cells, showing positivity for the following markers [31]: S-100 (positive in neoplastic myoepithelial cells but not in normal myoepithelial cells), calponin (the most sensitive myogenic marker [31,32], smooth muscle actin (SMA), muscle-specific actin (MSA), smooth muscle myosin, P63 protein, glial fibrillary acidic protein (GFAP), and SOX10 (expressed in 80% of myoepitheliomas but are only a third of myoepithelial carcinomas [33]. E-cadherin is also expressed in myoepitheliomas [34]. Myoepithelial cells are typically negative for carcinoembryonic antigen (CEA), indicating no tubular differentiation [34].  
As myoepitheliomas can show focal areas similar to parachordomas, it is becoming a common idea that parachordoma should be considered in the same spectrum of myoepithelioma of soft tissue, as also described in the new WHO classification [1]. One element that differentiates myoepitheliomas from parachordomas is that the latter is GFAP- and SMA-negative. Nevertheless, since very few cases of parachordomas have been described, we cannot consider this distinction.  
From our review, it emerges that the consistently positive immunohistochemical markers in myoepitheliomas include AE1/AE3, S-100, vimentin, calponin, and EMA. These markers are essential for identifying the neoplasm and may vary depending on the cell morphology present.  
Histologic examination is the primary method to assess malignancy.  
Malignancy should be suspected in presence of an infiltrative growth pattern. In a study of 101 myoepithelial tumors of soft tissue [28], the only parameter related to recurrence and metastasis was the presence of at least moderate cytological atypia, defined as nuclear pleomorphism, vesicular or coarse chromatin, and/or prominent nucleoli. It must be pointed out that, when occurring in pediatric population, myoepithelial tumors are more prone to be malignant. When exclusively talking about cutaneous myoepithelioma, the main features of malignancy are represented by cytological atypia and high mitotic rate and the presence of infiltrative borders, but occasional cases showed no histological features of malignancy [35].  
When talking about mitotic rate, there is no cutoff although [PERSON] et al. [32] reported that finding \(>\)7 mitoses per 10 HPF was diagnostic of malignancy. Despite being quite reliable, cytologic atypia is not pathognomic of malignancy as some low-grade myoepithelial carcinomas behave aggressively [29], and the single most useful criterion remains the invasive growth pattern. Nevertheless, this is not reliable in soft tissues, as nearly half of the cases described by [PERSON] et al. [28] showed microscopically infiltrative margins, and this feature was associated with neither recurrence nor metastasis. Although experience is limited, the presence of at least moderate cytologic atypia should be sufficient to classify the neoplasm as myoepithelial carcinoma with risk for aggressive behavior and propensity for metastasis.  
Regarding cytogenetic and genomic findings, genomic fusions are prominent features. The most common genomic fusions are ESWR1-POU5F1 and ESWR1-PBX3. Chromosomal translocations and complex chromosomal aberrations are frequent, but specific patterns may vary from tumor to tumor. Chromosomal aberrations are especially frequent in the case of malignant behavior [12,28].