More than one vascular marker should be used due to the heterogeneous expression of vascular markers. However, in absence of such a clinical history, the lesion should be extensively examined by available IHC stains. It is obvious to think about angiosarcoma in a malignant spindle or epithelioid lesion of the breast if there has been a prior history of radiation treatment. These tumors may occur after radiation treatment or de novo. 159,160 Another significant malignant lesion with which metaplastic carcinoma can be confused is an angiosarcoma. However, CAM5.2 positivity alone is not enough to exclude a melanoma unless it is strong and diffuse.
157,158 Strong keratin reactivity or multiple keratin positivity would also exclude a melanoma. S100 is a very sensitive melanoma marker, but has been reported to stain between 20% and 50% of metaplastic breast carcinomas and therefore is not the best stain for this differential diagnosis. At least two melanoma markers should be performed. Although every effort should be made to prove an atypical/malignant-appearing spindle cell lesion to be a metaplastic carcinoma, the differential diagnosis also includes melanoma, angiosarcoma, and a stroma of phyllodes tumor. In many cases, an epithelial component is present only focally. 156 If all the keratins, EMA, and p63 fail to show any immunoreactivity on a core biopsy, complete excision of the lesion should be recommended. 151,154,155 Vimentin expression has been found in 50% of hormone-independent cell lines, and because metaplastic carcinomas are usually negative for receptors, vimentin expression is actually expected. 152,153 Vimentin expression in the tumor does not exclude a spindle cell carcinoma. 151 Another sensitive and specific marker for spindle cell metaplastic carcinoma is p63, and should always be included in the panel. 149 A panel composed of multiple keratin stains (CAM5.2, AE1/3, 34βE12, CK5, and CK7) and EMA is more useful than a single keratin. IHC stains can be helpful in this situation. This is usually the issue on a core biopsy rather than on an excision specimen. The most problematic cases are the ones that predominantly show spindle cell morphology without an obvious epithelial or DCIS component ( Fig. 149,150 Diagnosis is not problematic when there is a recognizable component of metaplastic carcinoma-that is, an obvious adenocarcinoma, adenosquamous or squamous cell carcinoma, or osseous or chondroid differentiation. Metaplastic carcinoma comprises a group of heterogeneous neoplasms that exhibit pure epithelial or a mixed epithelial and mesenchymal phenotypes. Dabbs MD, in Diagnostic Immunohistochemistry, 2019 Metaplastic Carcinoma-Use of Keratins, Melanoma, and Vascular Markers