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
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.
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.
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.
"Their findings suggested that MDA is characterized by positive immunoreactivity of stromal cells to alpha-smooth muscle actin and by weak or no response to estrogen receptor. Perhaps LEGH can be distinguished from MDA on the basis of these properties . "
[Show abstract][Hide abstract] ABSTRACT: Lobular endocervical glandular hyperplasia (LEGH) is usually assumed to be a benign tumor-like lesion of the glands of the uterine cervix. However, LEGH has been associated with obvious cervical adenocarcinoma. The clinicopathological significance of coexistence of LEGH with adenocarcinoma remains unclear. We microscopically examined the presence or absence of LEGH components in 95 stage Ib cervical adenocarcinomas. Gastric mucin was detected with the use of clone HIK1083. Associations of the coexistence of LEGH components with clinicopathological variables were analyzed. LEGH components were present in 16 cases (16.8%). Gastric mucin was positive in all 16 LEGH components, as compared with only 6 of the 95 adenocarcinoma components. Of the 16 adenocarcinomas with LEGH components, 15 were well-differentiated mucinous adenocarcinomas, and one was poorly differentiated adenocarcinoma. The mortality rate of tumor recurrence was 25% (4 of 16) in patients whose tumors had LEGH components, and 21.5% (17 of 79) in those whose tumors had no LEGH components. There was no significant difference in survival. Early cervical adenocarcinoma was relatively frequently associated with LEGH components. LEGH may be one of the factors related to the development of cervical adenocarcinoma, but adenocarcinoma with LEGH components does not necessarily develop into a highly aggressive "adenoma malignum."
Pathology - Research and Practice 02/2009; 205(5):331-7. DOI:10.1016/j.prp.2008.12.002 · 1.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report three cases of unusual tubal-type endocervical glandular proliferations simulating minimal deviation adenocarcinoma in women with a history of in utero diethylstilbestrol (DES) exposure. The lesions were characterized by haphazard glandular proliferations extending from 3.4 to 6.1 mm into the endocervical stroma and to the margins of excision in all cases. Most of the glands were small to medium-sized and round; some exhibited a moderate degree of cystic dilatation, and occasional glands had curvilinear profiles. The glandular epithelium displayed extensive tubal-type differentiation in all cases. In two cases, the glands lacked cytologic atypia and mitotic activity, and in one case, there was mild to moderate nuclear atypia with occasional mitotic activity. Immunohistochemical studies showed diffuse expression of estrogen and progesterone receptors and essentially no expression of p16 in two cases tested; there was no expression of CD10 in one case that was tested. The Ki-67 proliferation index was zero in one case and 25% in another. Human papillomavirus DNA was not detected by in situ hybridization in one case that was tested. The proliferations lacked features of mucinous and tubo-endometrioid types of minimal deviation adenocarcinoma. The clinicopathologic findings suggest the lesions are benign, and the association with in utero DES exposure raises the possibility that these could be a form of DES-related adenosis.
International Journal of Gynecological Pathology 11/2005; 24(4):391-8. DOI:10.1097/01.pgp.0000170064.95465.5c · 1.67 Impact Factor
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