Adenomyoepithelial tumours and myoepithelial carcinomas of the breast--a spectrum of monophasic and biphasic tumours dominated by immature myoepithelial cells

Abstract

Background: Adenomyoepithelial tumours and myoepithelial carcinomas of the breast are primarily defined by the presence of neoplastic cells with a myoepithelial immunophenotype. Current classification schemes are based on purely descriptive features and an assessment of individual prognosis is still problematic.

Methods: A series of 27 adenomyoepithelial tumours of the breast was analysed immunohistochemically with antibodies directed against various cytokeratins, p63, smooth muscle alpha-actin (SMA) and vimentin. Additionally, double immunofluorescence and comparative genomic hybridisation (CGH) was performed.

Results: Immunohistochemically, all the tumours showed a constant expression of high molecular weight cytokeratins (Ck) Ck5 and Ck14, p63, SMA and vimentin. With exception of one case diagnosed as myoepithelial carcinoma, all tested tumours expressed low molecular weight cytokeratin Ck18 in variable proportions of cells. Even in monophasic tumours lacking obvious glandular differentiation in conventional staining, a number of neoplastic cells still expressed those cytokeratins. Double immunofluorescence revealed tumour cells exclusively staining for Ck5/Ck14 in the presence of other cell populations that co-expressed high molecular weight Ck5/Ck14 as well as either low molecular weight Ck8/18 or SMA. Based on morphology, we assigned the series to three categories, benign, borderline and malignant. This classification was supported by a stepwise increase in cytogenetic alterations on CGH.

Conclusion: Adenomyoepithelial tumours comprise a spectrum of neoplasms consisting of an admixture of glandular and myoepithelial differentiation patterns. As a key component SMA-positive cells co-expressing cytokeratins could be identified. Although categorisation of adenomyoepithelial tumours in benign, borderline and malignant was supported by results of CGH, any assessment of prognosis requires to be firmly based on morphological grounds. At present it is not yet clear, if and to what extent proposed Ck5-positive progenitor cells contribute to the immunohistochemical and morphological heterogeneity of these neoplasms of the breast.

Figure 1

Conventional histology and immunostaining of two benign adenomyoepitheliomas of the breast (A,C,E,G: biphasic; B,D,F: monophasic). A shows a prominent tubular component, whereas in B a spindle-cell architecture predominates (A, H&E, magnification ×20, D, H&E, magnification ×20). C and D display distribution patterns of basal cytokeratin expression that are tantamount to the proportion of tumour cells (immunostaining for Ck5/6, magnification ×20) E and F show expression of sm α-actin (immunostaining for SMA, magnification ×20) with a distribution similar to normal breast tissue in biphasic benign adenomyoepithelioma. G shows double immunofluorescence staining (Ck5/6 green, Ck8/18 red, 40×) with prominent abluminal swarming of Ck5/6-positive cells. The proliferating glandular epithelium consists of differentiated (red signal) and less differentiated (hybrid signal) glandular cells. H shows double immunofluorescence staining (Ck5 red, SMA green, 63×) of a monophasic, malignant myoepithelial tumour with many cells coexpressing SMA and high molecular weigh Ck5. Note some less differentiated cells that express mainly Ck5 and some better differentiated cells with a predominance of SMA expression (green signal).

Figure 2

Conventional histology and immunostaining of two malignant adenomyoepitheliomas of the breast. A, C and E shows a biphasic malignant adenomyoepithelial tumour with distinct tubular formations, whereas B, D and F show a monophasic adenomyoepithelial carcinoma with diffuse infiltration of adipose tissue.(H&E, magnification ×20 C and D display distribution patterns of basal cytokeratin expression that are tantamount to the proportion of tumour cells (immunostaining for Ck5/6, magnification ×20). E and F show expression of SMA in a more irregular distribution compared to normal breast tissue in the malignant biphasic lesion and a rather diffuse pattern in monophasic lesions. A prominent mitotic figure is marked in F (arrow) (magnification ×20).

Figure 3

Summary of CGH profiles of 8 benign adenomyoepitheliomas (light blue), 5 adenomyoepitheliomas of borderline type (dark blue) and 14 adenomyoepithelial carcinomas (violet). A total of 131 gains and losses are distributed over 22 chromosomes with a preference of chromosomes 8, 17p and 13q.