Introduction

Apocrine glands are a subtype of exocrine secretory glands. They are found in many locations but are primarily in the axillae, areolae, and anogenital region. While in the past, certain glands, such as those in the areolae, were considered modified apocrine glands, it is now recognized that all of these glands are true apocrine glands. Apocrine glands release their products by “decapitation,” a process by which membrane-bound cytoplasm from the apical surface of the cells buds off into the lumen of the duct and is secreted. Histologically, apocrine glands can be viewed using light microscopy with hematoxylin and eosin staining. They can also be viewed using a variety of specific stains, including histochemical, enzymatic, and immunohistochemical stains. Apocrine glands are associated with multiple pathologies, including apocrine bromhidrosis, apocrine chromhidrosis, apocrine carcinoma of the breast, Fox-Fordyce disease, and hidradenitis suppurativa (acne inversa).[1][2][3]

Structure

Apocrine glands are larger than eccrine glands, with a 10-fold greater diameter. They are made up of 2 primary parts: a coiled secretory structure and an accompanying straight duct. The coiled secretory structure, which is the gland itself, is located in the lower dermis or the subcutaneous fat and is composed only of secretory cells. The gland contains multiple large granules. The accompanying straight duct enters the infundibulum. Apocrine glands originate from the hair germ and therefore generally enter the pilosebaceous follicle at its infundibulum; however, occasionally the duct will open directly on the skin surface in proximity to the pilosebaceous follicle.[4][5][6]

The gland, or coiled secretory structure, is made up of a single layer of cuboidal or columnar cells, which rest on a layer of myoepithelial cells. The ductal portion is made up of a double layer of basophilic cells, with a periluminal eosinophilic cuticle.

Function

There are 2 main types of secretory glands: exocrine glands and endocrine glands. Exocrine glands remain connected with the surface epithelium and secrete their products through ducts. They are subclassified as merocrine (or eccrine), apocrine, and holocrine. Apocrine glands are nonfunctional before puberty, at which time they grow and commence secretion. Various glands in the body practice apocrine secretion and are therefore considered apocrine glands, such as mammary glands. Apocrine glands are distributed in the axillae, anogenital region, periumbilical region, areolae, external auditory canals, and on the eyelids. Some apocrine glands have specific names, for example, those on the eyelids are referred to as Moll’s glands, and those on the external auditory meatus are termed ceruminous glands. While they can be found in many locations on the body, they secrete specific products at each distinct location. Although the exact function of apocrine glands varies depending on the gland's location, apocrine glands are believed to be an evolutionary remnant of an odorous organ of animals. For example, the scent glands of the skunk are modified apocrine-type structures.

The distinct characteristic of apocrine glands is that they secrete their product through decapitation, which entails membrane budding of the apical cytoplasm. This process involves 3 distinct phases. First, the apical cap is formed. This is followed by formation of a dividing membrane at the base of the apical cap. Finally, tubules form parallel to the dividing membrane, which creates both a base for the secreted apical cap, as well as a roof for the remaining secretory cell.

Tissue Preparation

Apocrine gland tissue for study can be obtained from patients with osmidrosis, and therefore the glands will be maintained in an active state. The tissue can be cut into small pieces (less than 1 mm^3) and fixed with 70% ethanol for 12 hours at 4 C, then embedded in paraffin. Alternatively, the tissue can be cut into small pieces (less than 1 mm^3) and stored in phosphate buffered saline (PBS) at 4 C. Staining can then be performed as desired. Apocrine secretion can be visualized with hematoxylin-eosin staining, in addition to other specific stains to identify structural components.

Histochemistry and Cytochemistry

Apocrine glands can be examined using a variety of histochemical and immunohistochemical stains. Hematoxylin and eosin staining reveal eosinophilic cytoplasm within the secretory cells of apocrine glands. Staining with Periodic Acid Schiff (PAS) allows for visualization of distinct PAS-positive, diastase-resistant mitochondria-like granules within the secretory portion of the gland. The granules also contain epidermal growth factor (EGF), which allows for an additional staining technique. These granules frequently also contain iron and can be visualized with acid-fast stains. Other targets for specific stains to visualize apocrine glands include luminal cell membranes with sialidase-sensitive anionic sites and antibodies that react with apocrine sweat glands but not with eccrine sweat glands (HMFG-1 1.10.F3 monoclonal antibody and antibody raised against purified 70 kD glycoprotein in human milk fat globule membranes). An additional marker for staining is Keratin AE1. Common markers of both eccrine and apocrine sweat glands include GCDFP-15, carcinoembryonic antigen, and epithelial membrane antigen (EMA) detected by anti-EMA monoclonal antibody (E29).

Microscopy, Electron

Observation of apocrine gland cells with light microscopy reveals the decapitation of the luminal portion of the secretory cells. The luminal portion of the cells is lined with microvilli. The ultrastructure reveals two types of cytoplasmic granules: small (approximately 50 nm) and large (variable in size). The small granules are round and elongated with a mitochondrial-like internal structure. The large granules are also round and contain fine electron-dense particles.

Clinical Significance

Apocrine glands can result in distinctive clinical pathology, dependent upon the location of the glands. Primary disorders of apocrine glands include apocrine bromhidrosis, which refers to excessive body odor arising from the secretions of the apocrine glands. This most commonly occurs in the axillae but may occur from secretions of the apocrine glands in the genitals or the plantar aspect of the feet. The second primary disorder of the apocrine glands, apocrine chromhidrosis, is a rare disorder in which the apocrine glands secrete colored apocrine sweat. This is generally found in the axillary and facial apocrine glands but can be seen in the areola apocrine glands. Two secondary disorders of the apocrine glands include Fox-Fordyce disease and hidradenitis suppurativa (acne inversa). In these disorders, apocrine glands are secondarily affected.[7][8]

Apocrine glands in the mammary region can also transform to apocrine carcinoma, a rare form of female breast cancer with an incidence of 0.5% to 4%.

Finally, apocrine metaplasia can occur, in which non-apocrine cells transform to apocrine phenotype. This is most commonly seen in the breast as fibrocystic change and is a benign lesion of the breast, with no increased risk for breast cancer.