The 3-layered Ductal Epithelium in Gynecomastia

Abstract

Gynecomastia is the most common abnormality in the male breast and has been associated with male breast cancer, but whether there is an etiological role remains unknown. In the present study we conducted an immunohistochemical investigation to further characterize gynecomastia. A total of 46 cases of gynecomastia were immunohistochemically stained on tissue microarrays for estrogen receptor (ER), progesterone receptor, HER2, androgen receptor, cytokeratins (CK5, CK14, CK7, and CK8/18), p63, E-cadherin, BRST2, cyclin D1, Bcl-2, p53, p16, p21, and Ki67. In addition, 8 cases of male ductal carcinoma in situ and normal breast tissue obtained from autopsies (n=10) and adjacent to male breast cancer (n=5) were studied. Normal ductal male breast epithelial cells were very often ER and Bcl-2 positive (>69%), and progesterone receptor and androgen receptor expression was also common (>39%). Gynecomastia showed a consistent 3-layered pattern: 1 myoepithelial and 2 epithelial cell layers with a distinctive immunohistochemical staining pattern. The intermediate luminal layer, consisting of vertically oriented cuboidal-to-columnar cells, is hormone receptor positive and expresses Bcl-2 and cyclin D1. The inner luminal layer is composed of smaller cells expressing CK5 and often CK14 but is usually negative for hormone receptors and Bcl-2. Male ductal carcinoma in situ was consistently ER positive and CK5/CK14 negative. In conclusion, for the first time we describe the 3-layered ductal epithelium in gynecomastia, which has a distinctive immunohistochemical profile. These results indicate that different cellular compartments exist in gynecomastia, and therefore gynecomastia does not seem to be an obligate precursor lesion of male breast cancer.

Columnar cell-like changes in the male breast

“…Gynaecomastoid hyperplasia was identified in 47.9% (34/71) of all the specimens. Morphologically it demonstrated ducts surrounded by an outer layer of myoepithelial cells with expression of CK5/6, an intermediate layer of cuboidal-to-columnar, vertically oriented cells expressing ER but not CK5/6, and an inner layer of slightly smaller luminal cells with or without micropapillae formation and these cells express CK5/6 consistently but ER only rarely 27. Thus this can be differentiated from the lesional foci basing on morphology and immune-phenotypic profile.…”

Do columnar cell lesions exist in the male breast?

“…However, such ducts were also seen in gynaecomastia (florid type), as has been recognized previously . Further, these ducts showed immunohistochemically the three layers that are typical of gynaecomastia: CK5/6‐ and CK14‐positive and ER‐negative outer myoepithelial and inner luminal layers, and an ER‐positive and CK5/6‐ and CK14‐negative intermediate layer …”

Differential Expression of Growth Factor Receptors and Membrane-Bound Tumor Markers for Imaging in Male and Female Breast Cancer

“…Since male breast cancer is often diagnosed together with gynecomastia, although gynecomastia is not an obligate precursor of male breast cancer [28], we examined whether the expression of the selected membrane markers was specific for male breast cancer. We found that expression patterns in gynecomastia were largely comparable with normal female breast tissue; i.e.…”

“…Original HE slides were reviewed by two observers (PJvD, RK) to confirm the diagnosis, and to subtype gynecomastia (florid, intermediate, fibrous) as described before [28]. Tissue microarrays were constructed as described by Kornegoor et al [7], [28].…”

“…Original HE slides were reviewed by two observers (PJvD, RK) to confirm the diagnosis, and to subtype gynecomastia (florid, intermediate, fibrous) as described before [28]. Tissue microarrays were constructed as described by Kornegoor et al [7], [28]. Since we are using archival pathology material which does not interfere with patient care and does not involve physical involvement of the patient, no ethical approval is required according to Dutch legislation [29].…”