Compiled and organized: HadronsDetailed description of the application of p63 in specific diseases of breast pathology (2).
Metaplastic breast cancer.
Metaplastic breast cancer includes a heterogeneous group of tumors with different directions of differentiation and varying degrees of expression of p63. The expression of p63 is more common and diffuse in fibromatosis-like spindle cell metaplasia, squamous cell metaplasia, other low- to medium-grade spindle cell metaplasia, and epithelial components in low-grade adenosquamous cell carcinoma. Interstitial spindle cells in low-grade adenosquamous cell carcinoma are p63-negative; In contrast, the spindle cell component in fibromatoid metaplastic carcinoma and other low- and intermediate-grade spindle cell metaplastic carcinomas is p63-positive because these cells are epithelial**. The probability and degree of p63 positivity in high-grade spindle cell metaplastic carcinoma gradually decreased, and p63 was not expressed in stromal-producing metaplastic carcinoma.
Figure 9Spindle cell components in metaplastic carcinoma express p63, such as low-grade metaplastic carcinoma (A) and high-grade metaplastic carcinoma (B); In panel B, there are myoepithelial cells around ductal carcinoma in situ and can be used as an internal control for p63.
Figure 10Low-grade fibromatosis-like metaplastic carcinoma, immunohistochemistry p63 is diffusely positive in spindle cell components, supporting the epithelial nature of these cells.
According to the authors of this paper, the expression of p63 in different types of metaplastic carcinoma is reflected in the relative proportion of squamous differentiation or myoepithelial differentiation, or in breast epithelial tumors with epithelial to mesenchymal spindle cell differentiation. Since p63 is also a squamous cell marker, it is also expressed in metaplastic carcinomas with morphological evidence of squamous differentiation. Expression of p63 in spindle cell metaplastic carcinoma** without squamous differentiation features. One possible explanation is that these spindle cells are epithelial in nature, but they have myoepithelial basal cell differentiation, and the expression of common basal CK and myogenic markers such as SMA, SMMHC, and CD10 is present. Ectoderm-mesenchymal interactions may also affect p63 expression.
As a marker of squamous differentiation, p63 can also be used for the diagnosis of mucinous epidermoid carcinoma (mainly expressed in squamous components) and metastatic squamous cell carcinoma in different sites (such as lung, cervix). It can also be expressed in benign and metaplastic squamous components of other breast lesions (eg, intraductal papillomas, pleomorphic adenomas). Low-differentiation metaplastic squamous cell carcinoma and high-grade basal-like breast cancer may overlap in morphology and immunophenotype, as both tumors express basal CK. In this case, p63 and p40 can be used to distinguish between these two markers in squamous cell carcinoma and negative in basal-like carcinoma.
Low-grade adenosquamous cell carcinoma.
The expression of p63 in low-grade adenosquamous cell carcinoma is unique, and its interpretation is often difficult. p63 is expressed in squamous cell nests and is generally diffusely colored. This staining may be focal and located around the nest and may also be seen in the outer layer of the glandular component. This peripheral pigmentation feature can resemble intrinsic myoepithelium and can lead to difficulty in sorting lesions.
Figure 11(a) Low-grade adenosquamous cell carcinoma, glandular and squamous components can be seen in the fibroproliferative interstitium; (b) peripheral p63 staining, resembling intrinsic myoepithelium around in situ lesions; (c) P63 stained in different areas of the same tumor, surrounding the nucleus of **, suggesting that the latter is not intrinsic myoepithelial cells. There is no expression of p63 in the interstitium.
The difference in p63 expression in low-grade adenosquamous cell carcinoma may be due to the different degrees of squamous differentiation in different tumor cell nests, resulting in medial epithelial and lateral myoepithelial manifestations similar to those in the normal milk ductal lobular system. The authors observed this peripheral P63-positive appearance in low-grade adenosquamous cell carcinoma with definite invasive growth and lymph node metastasis. Diagnosis of low-grade adenosquamous cell carcinoma with this immunohistochemical p63 presentation may be more difficult, as other myogenic myoepithelial markers and high-molecular-weight CK are similarly expressed. However, nests with typical morphology of well-defined invasive growth, hyperplasia that also express these markers, and peripheral p63-positive cells that are focal, and which are intermingled with nests that are mosaic or diffusely pigmented, can help identify these tumors as invasive carcinoma rather than in situ. Low-grade adenosquamous cell carcinoma with a low-grade nucleus and negative ER- and PR-negative is also helpful.
Salivary adenoid breast lesions.
Breast salivary adenocarcinoma is uncommon and difficult to diagnose. The histologic and molecular diagnostic features of these tumors are similar to those of the same name of the salivary gland. The authors also observed that most of the primary salivary adenoid tumors of the breast are heterozygous in nature, which may not be all the features reported in the literature on salivary gland tumors, but are genealogical in terms of phenotype and differentiation. For example, acinar cell carcinoma and adenoid cystic carcinoma may present as classical, with areas similar to high-grade, non-specific invasive breast cancer, and corresponding immunohistochemical phenotypic changes.
Some salivary gland tumors are predominantly epithelial components, such as acinar cell carcinoma, secretory carcinoma, and pleomorphic adenocarcinoma. Mucinous epidermoid carcinoma is also epithelial, but there will be heterologous differentiation with a squamous and glandular epithelial mixed phenotype. In contrast, some tumors are complex combinations of epithelial cells and myoepithelial cells, such as adenoid cystic carcinoma, adenomyoepitheloma, and pleomorphic adenoma. Immunohistochemistry p63 can show cells with myoepithelial differentiation or squamous epithelial differentiation in these tumors. For example, in adenoid cystic carcinoma and pleomorphic adenoma, most cells with a myoepithelial basal cell phenotype express p63.
Figure 12In adenoid cystic carcinoma with dual types of cells, immunohistochemical p63 was expressed positively in cells with myoepithelial basal differentiation and negative expression in luminal cells.
However, expression of p63 in adenoid cystic carcinoma varies from diffusely positive, to focal positive, or completely negative, and mosaic staining is most commonly found within hyperplastic cell clusters and cribriform cell islands. In general, p63 expression is reduced in adenoid cystic carcinoma of the high-grade solid subtype. P63 can also be used to distinguish adenoid cystic carcinoma from similar diseases such as collagen glomerular disease, particularly in rough needle aspiration biopsy, with the aid of careful morphological evaluation and other immunohistochemical markers (e.g., ER and high molecular weight CK).
P63 is not expressed in acinar cell carcinoma, secretory carcinoma, and pleomorphic adenocarcinoma because these tumors are not myoepithelially differentiated or squamous differentiated.
——To be continued——
Previous review: immunohistochemistry p63 in breast pathology (I).
Immunohistochemistry p63 in breast pathology (II).
Immunohistochemistry p63 in breast pathology (iii).