Immunophenotypic alteration of the stromal component in minimal deviation adenocarcinoma ('adenoma malignum') and endocervical glandular hyperplasia:: a study using oestrogen receptor and α-smooth muscle actin double immunostaining

Aims: To define the phenotypic alteration of the stromal component in association with destructive invasion which is a crucial feature in distinguishing minimal deviation adenocarcinoma (MDA) from benign endocervical glandular lesions. Methods and results: We studied endocervical glandular hyperplasias including non-specific-type (NEGH) (n = 3) and lobular-type (LEGH) (n = 8), and minimal deviation adenocarcinoma (MDA) (n = 11), well-differentiated endocervical adenocarcinoma of usual-type (WDA) (n = 11), and adenocarcinoma in situ (AIS) (n = 6) of the cervix, by double immunostaining for oestrogen receptor (ER) and alpha-smooth muscle actin (alpha-SMA) using peroxidase- and alkaline phosphatase-polymer methods, respectively. Glands in NEGH invariably showed nuclear staining for ER, with surrounding ER+/alpha-SMA- stromal cells, whereas LEGH also harboured ER+/alpha-SMA- spindle cells, but lacked nuclear staining for ER in constituent glands. In contrast, both WDA and MDA displayed accompanying stroma rich in alpha-SMA+ spindle cells in close vicinity to the infiltrating neoplastic glands, with only occasional weakly ER+ stromal cells. WDA tended to contain more alpha-SMA+ cells. The distribution of alpha-SMA+ cells was periglandular (6/11), patchy (6/11), and/or diffuse (4/11) in WDA, whereas in MDA it was periglandular (11/11) and/or patchy (8/11). AIS was surrounded by ER+/alpha-SMA- stromal cells. All cases of WDA, MDA, and AIS lacked nuclear staining for ER. Conclusions: Both MDA and WDA can be distinguished from LEGH and NEGH by identifying surrounding alpha-SMA+ stromal cells and the absence or decreased number of ER+ cells, possibly as a result of the desmoplastic reaction with myofibroblasts replacing pre-existing ER+ stromal cells. In particular, the periglandular distribution of these alpha-SMA+ stromal cells can be a clue suggesting destructive stromal invasion in cases of MDA, although occasional glands may lack these cells.