Histology, Corpus Albicans

Structure

Ovarian structure:

To understand the structure of the corpus albicans, one must first understand the general structure of the ovary itself.  The structure of the ovary is made up of three different regions: the cortex, medulla, and hilum. The cortex of the ovary contains two major types of cells, follicular cells, and stromal cells. The cortex also contains the corpora lutea as well as the remnant corpora albicans. The medulla is made up of blood vessels and nerves, and the hilum contains major blood vessels to the ovary.[2]   

Corpus luteum structure:

When the formation of the corpus albicans begins, there is a tissue reorganization process that develops. The corpus albicans comes from a precursor endocrine organ called the corpus luteum. As the corpus luteum degenerates, there is an influx of matrix metalloproteinases, fibroblasts, and macrophages that take over the process of both organizations of dense connective tissue of the newly forming corpus albicans, as well as cellular cleanup needed after extensive apoptosis.[3] On histology, the freshly formed corpus luteum will appear as a nodule of dense connective tissue.[2]

Function

The ovulatory cycle:

Understanding the role of the corpus albicans requires first exploring the basics of the ovulatory cycle itself. The ovulatory cycle, or menstrual cycle, average 28 days in length and consists of two ovarian phases: the follicular phase and the luteal phase. The structure of the menstrual cycle (ranging from 26 to 35 days) begins with 5 days of menstruation followed by the remaining 9 days of the follicular phase, then followed by the 14 days of the luteal phase.[4]  This cycle begins at the onset of the reproductive years, termed menarche and continues until the end of the reproductive years, termed menopause.[5]

Follicular phase:

The follicular phase lasts fourteen days and starts on the first day of menses and continues until the day of ovulation. The luteal phase, which also lasts 14 days, then follows from ovulation until the day before the beginning of menses. These phases are responsible for producing a viable egg and preparing the endometrium for implantation, respectively. During the follicular phase, the follicle grows and develops under the influence of surrounding stromal cells called granulosa and thecal cells. As the luteinizing hormone (LH) surge reaches its peak, the follicle ruptures and releases a single developed oocyte. 

Luteal phase:

The portion of the follicle remaining in the ovary after ovulation will become the corpus luteum. This process is called luteinization. The cells making up the corpus luteum are granulosa cells, thecal cells, and contributing blood vessels. These granulosa cells go on to produce progesterone and estradiol, whereas thecal cells have the job of making androstenedione. The luteal phase will experience one of two outcomes; either an oocyte will be fertilized and implanted into the uterus, or menses will begin. If fertilization occurs, the corpus luteum is responsible for maintaining the endometrium with the production of progesterone and no corpus albicans will be formed. This maintenance of the corpus luteum initiates by the hormone human chorionic gonadotropin (HCG) produced by the implanting trophoblast which will begin production around day 8 after fertilization.[4] If fertilization does not take place, the corpus luteum will then undergo a process termed luteolysis around eight days after ovulation. 

Luteolysis:

The first sign of formation of the corpus albicans is with shrinkage of the granulosa cells within the corpus luteum, followed by apoptosis. This process gets explicitly triggered by uterine prostaglandin F2alpha, which ensures that both the corpus luteum will undergo both structural and hormonal degradation.[6] This tissue of the former corpus luteum has now termed the corpus albicans and is seen histologically as a dense connective tissue aggregate.[2] This degradation of the corpus luteum will, in turn, cause the onset of menstruation and the beginning of a new ovulatory cycle. This cycle will continue monthly until the decline of the female's reproductive years, ultimately ending with cessation of ovulatory function, termed menopause.[7]

Microscopy, Light

Under light microscopy, the corpus albicans will frequently be found in the post-menopausal ovary signifying prior ovulatory events.[8] The structure will appear as an aggregate of dense connective tissue.[2] This aspect is the remnant of that of the corpus luteum, which is about 2 cm of diameter, yellow and lobulated with a cystic center. 

Clinical Significance

Luteal phase deficiency:

Luteal phase deficiency is defined as a decreased lifespan of the corpus luteum and thus causes the premature formation of the corpus albicans. Normally the corpus luteum has a lifespan of eleven to fourteen days, but in a luteal phase defect the corpus luteum functions for less than nine days. Typically this deficiency is caused by a lack of the proper progesterone levels that are responsible for maintenance of the corpus luteum. Clinically, this deficiency can be a cause for recurrent early pregnancy loss. The past diagnostic gold standard for a luteal phase defect was a luteal phase biopsy; however, the medical community has decided its imprecision makes it no longer clinically relevant. Treatment can include progesterone supplementation.[9]

Corpus Albicans calcification:

The corpus albicans is infrequently visible on clinical imaging. However, in post-menopausal women, sometimes the corpus albicans can have an abnormal appearance due to the menopausal related hormonal changes. A decrease in estrogen and a decrease in both immune-mediated phagocytic and fibroblastic activity can lead to poor formation and regression of the corpus albicans; this can lead to ultrasound detection of these structures and possible confusion with ovarian neoplasms. Both hemosiderin and calcium deposition within the structure of the corpus albicans itself can lead to increased ultrasound detection. They appear as small echogenic foci without distal acoustic shadowing. In addition to ultrasound, these calcifications can also show up in plain film radiographs of the pelvis.[10]